FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Shi, L
Oberdoerffer, P
AF Shi, Lei
Oberdoerffer, Philipp
TI Chromatin dynamics in DNA double-strand break repair
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE Chromatin; DNA repair; Nuclear reorganization; Histone modification
ID REMODELING FACTOR CHD4; DAMAGE RESPONSE; HISTONE H3; HOMOLOGOUS
RECOMBINATION; NUCLEAR-BODIES; IONIZING-RADIATION; REPLICATION STRESS;
GENOMIC STABILITY; TUMOR SUPPRESSION; MAMMALIAN-CELLS
AB DNA double-strand breaks (DSBs) occur in the context of a highly organized chromatin environment and are, thus, a significant threat to the epigenomic integrity of eukaryotic cells. Changes in break-proximal chromatin structure are thought to be a prerequisite for efficient DNA repair and may help protect the structural integrity of the nucleus. Unlike most bona fide DNA repair factors, chromatin influences the repair process at several levels: the existing chromatin context at the site of damage directly affects the access and kinetics of the repair machinery; DSB induced chromatin modifications influence the choice of repair factors, thereby modulating repair outcome; lastly, DNA damage can have a significant impact on chromatin beyond the site of damage. We will discuss recent findings that highlight both the complexity and importance of dynamic and tightly orchestrated chromatin reorganization to ensure efficient DSB repair and nuclear integrity. This article is part of a Special Issue entitled: Chromatin in time and space. Published by Elsevier B.V.
C1 [Shi, Lei; Oberdoerffer, Philipp] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
RP Oberdoerffer, P (reprint author), NCI, Mouse Canc Genet Program, 1050 Boyles St,Bldg 560,Room 32-40B, Frederick, MD 21702 USA.
EM Philipp.Oberdoerffer@nih.gov
FU Intramural Research Program of NIH; National Cancer Institute; Center
for Cancer Research
FX We apologize to authors who's original work we were unable to cite due
to space limitations. L.S. and P.O. were supported by the Intramural
Research Program of NIH, The National Cancer Institute, and The Center
for Cancer Research.
NR 109
TC 25
Z9 27
U1 2
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD JUL
PY 2012
VL 1819
IS 7
SI SI
BP 811
EP 819
DI 10.1016/j.bbagrm.2012.01.002
PG 9
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 972GK
UT WOS:000306265100026
PM 22285574
ER
PT J
AU McBride, AA
Sakakibara, N
Stepp, WH
Jang, MK
AF McBride, Alison A.
Sakakibara, Nozomi
Stepp, Wesley H.
Jang, Moon Kyoo
TI Hitchhiking on host chromatin: how papillomaviruses persist
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE Virus; HPV; Replication; Chromatin; DNA damage response; ND10
ID DNA-DAMAGE RESPONSE; E2 PROTEIN; MITOTIC CHROMOSOMES; CERVICAL-CANCER;
TRANSCRIPTIONAL ACTIVATION; EPISOMAL MAINTENANCE; NUCLEAR-BODIES; CAPSID
PROTEIN; BRD4; BOVINE
AB Persistent viruses need mechanisms to protect their genomes from cellular defenses and to ensure that they are efficiently propagated to daughter host cells. One mechanism by which papillomaviruses achieve this is through the association of viral genomes with host chromatin, mediated by the viral E2 tethering protein. Association of viral DNA with regions of active host chromatin ensures that the virus remains transcriptionally active and is not relegated to repressed heterochromatin. In addition, viral genomes are tethered to specific regions of host mitotic chromosomes to efficiently partition their DNA to daughter cells. Vegetative viral DNA replication also initiates at specific regions of host chromatin, where the viral El and E2 proteins initiate a DNA damage response that recruits cellular DNA damage and repair proteins to viral replication foci for efficient viral DNA synthesis. Thus, these small viruses have capitalized on interactions with chromatin to efficiently target their genomes to beneficial regions of the host nucleus. This article is part of a Special Issue entitled: Chromatin in time and space. Published by Elsevier B.V.
C1 [McBride, Alison A.; Sakakibara, Nozomi; Stepp, Wesley H.; Jang, Moon Kyoo] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, 33 N Dr MSC 3209, Bethesda, MD 20892 USA.
EM amcbride@nih.gov
OI McBride, Alison/0000-0001-5607-5157
FU Intramural Research Program of the NIAID, NIH
FX The work of the authors is funded by the Intramural Research Program of
the NIAID, NIH.
NR 44
TC 23
Z9 24
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD JUL
PY 2012
VL 1819
IS 7
SI SI
BP 820
EP 825
DI 10.1016/j.bbagrm.2012.01.011
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 972GK
UT WOS:000306265100027
PM 22306660
ER
PT J
AU Jha, JK
Baek, JH
Venkova-Canova, T
Chattoraj, DK
AF Jha, Jyoti K.
Baek, Jong Hwan
Venkova-Canova, Tatiana
Chattoraj, Dhruba K.
TI Chromosome dynamics in multichromosome bacteria
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE Divided genome; Genome evolution; Secondary chromosomes; Genome
maintenance; Communication between chromosome replication and
segregation; V. cholerae
ID VIBRIO-CHOLERAE CHROMOSOMES; REPLICATION INITIATION; BACILLUS-SUBTILIS;
ESCHERICHIA-COLI; CELL-CYCLE; SEGREGATION; GENOMES; ORGANIZATION;
RECRUITMENT; ORIGINS
AB On the basis of limited information, bacteria were once assumed to have no more than one chromosome. In the era of genomics, it has become clear that some, like eukaryotes, have more than one chromosome. Multichromosome bacteria provide opportunities to investigate how split genomes emerged, whether the individual chromosomes communicate to coordinate their replication and segregation, and what selective advantages split genomes might provide. Our current knowledge of these topics comes mostly from studies in Vibrio cholerae, which has two chromosomes, chr1 and chr2. Chr1 carries out most of the house-keeping functions and is considered the main chromosome, whereas chr2 appears to have originated from a plasmid and has acquired genes of mostly unknown origin and function. Nevertheless, unlike plasmids, chr2 replicates once and only once per cell cycle, like a bona fide chromosome. The two chromosomes replicate and segregate using separate programs, unlike eukaryotic chromosomes. They terminate replication synchronously, suggesting that there might be communication between them. Replication of the chromosomes is affected by segregation genes but in a chromosome specific fashion, a new development in the field of DNA replication control. The split genome allows genome duplication to complete in less time and with fewer replication forks, which could be beneficial for genome maintenance during rapid growth, which is the norm for V. cholerae in broth cultures and in the human host. In the latter, the expression of chr2 genes increases preferentially. Studies of chromosome maintenance in multichromosomal bacteria, although in their infancy, are already broadening our view of chromosome biology. This article is part of a Special Issue entitled: Chromatin in time and space. Published by Elsevier B.V.
C1 [Jha, Jyoti K.; Baek, Jong Hwan; Venkova-Canova, Tatiana; Chattoraj, Dhruba K.] NCI, Lab Mol Biol & Biochem, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Chattoraj, DK (reprint author), NCI, Lab Mol Biol & Biochem, Ctr Canc Res, NIH, 37 Convent Dr,Room 6044, Bethesda, MD 20892 USA.
EM chattoraj@nih.gov
FU Intramural NIH HHS [ZIA BC010277-12]
NR 36
TC 9
Z9 9
U1 6
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD JUL
PY 2012
VL 1819
IS 7
SI SI
BP 826
EP 829
DI 10.1016/j.bbagrm.2012.01.012
PG 4
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 972GK
UT WOS:000306265100028
PM 22306663
ER
PT J
AU Macvanin, M
Adhya, S
AF Macvanin, Mirjana
Adhya, Sankar
TI Architectural organization in E. coli nucleoid
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE Nucleoid; Histone-like protein; HU; Chromosome organization
ID HISTONE-LIKE PROTEIN; DNA-BINDING PROTEIN; LACKING HU PROTEIN; HOST
FACTOR IHF; ESCHERICHIA-COLI; BACTERIAL GENOME; ELECTRON-MICROSCOPY;
FOLDED CHROMOSOMES; GENE-REGULATION; CELL-DIVISION
AB In contrast to organized hierarchical structure of eukaryotic chromosome, bacterial chromosomes are believed not to have such structures. The genomes of bacteria are condensed into a compact structure called the nucleoid. Among many architectural, histone-like proteins which associate with the chromosomal DNA is HU which is implicated in folding DNA into a compact structure by bending and wrapping DNA. Unlike the majority of other histone-like proteins. HU is highly conserved in eubacteria and unique in its ability to bind RNA. Furthermore, an HU mutation profoundly alters the cellular transcription profile and consequently has global effects on physiology and the lifestyle of E. colt. Here we provide a short overview of the mechanisms by which the nucleoid is organized into different topological domains. We propose that HU is a major player in creating domain-specific superhelicities and thus influences the transcription profile from the constituent promoters. This article is part of a Special Issue entitled: Chromatin in time and space. Published by Elsevier B.V.
C1 [Macvanin, Mirjana; Adhya, Sankar] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Adhya, S (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM adhyas@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. We are grateful to our former and current colleagues
Rotem Edgar, Sudeshna Kar, Andrei Trostel and Victor Zhurkin for
experiments and discussions.
NR 74
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Z9 26
U1 2
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD JUL
PY 2012
VL 1819
IS 7
SI SI
BP 830
EP 835
DI 10.1016/j.bbagrm.2012.02.012
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 972GK
UT WOS:000306265100029
PM 22387214
ER
PT J
AU Schrump, DS
AF Schrump, David S.
TI Targeting epigenetic mediators of gene expression in thoracic
malignancies
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE Lung cancer; Esophageal cancer; Mesothelioma; Epigenetics; Prognosis;
Clinical trials
ID CELL LUNG-CANCER; DEACETYLASE INHIBITOR ROMIDEPSIN; CANCER/TESTIS
ANTIGEN-EXPRESSION; MODIFICATIONS PREDICT PROGNOSIS; GLOBAL HISTONE
MODIFICATIONS; PLEURAL MESOTHELIOMA CELLS; MESSENGER-RNA EXPRESSION;
POOR-PROGNOSIS; PROMOTER METHYLATION; DNA METHYLATION
AB Lung and esophageal cancers and malignant pleural mesotheliomas are highly lethal neoplasms that are leading causes of cancer-related deaths worldwide. Presently, limited information is available pertaining to epigenetic mechanisms mediating initiation and progression of these neoplasms. The following presentation will focus on the potential clinical relevance of epigenomic alterations in thoracic malignancies mediated by DNA methylation, perturbations in the histone code, and polycomb group proteins, as well as ongoing translational efforts to target epigenetic regulators of gene expression for treatment of these neoplasms. This article is part of a Special Issue entitled: Chromatin in time and space. (C) 2012 Elsevier B.V. All rights reserved.
C1 NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res, Rm 4-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM david_schrump@nih.gov
NR 191
TC 2
Z9 3
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
EI 0006-3002
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD JUL
PY 2012
VL 1819
IS 7
SI SI
BP 836
EP 845
DI 10.1016/j.bbagrm.2012.03.009
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 972GK
UT WOS:000306265100030
PM 22507242
ER
PT J
AU Bowen, JD
Kraft, GH
Wundes, A
Guan, Q
Maravilla, KR
Gooley, TA
McSweeney, PA
Pavletic, SZ
Openshaw, H
Storb, R
Wener, M
McLaughlin, BA
Henstorf, GR
Nash, RA
AF Bowen, J. D.
Kraft, G. H.
Wundes, A.
Guan, Q.
Maravilla, K. R.
Gooley, T. A.
McSweeney, P. A.
Pavletic, S. Z.
Openshaw, H.
Storb, R.
Wener, M.
McLaughlin, B. A.
Henstorf, G. R.
Nash, R. A.
TI Autologous hematopoietic cell transplantation following high-dose
immunosuppressive therapy for advanced multiple sclerosis: long-term
results
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE multiple sclerosis; TBI; CY; hematopoietic cell transplantation;
oligoclonal bands
ID BONE-MARROW-TRANSPLANTATION; SEVERE SYSTEMIC-SCLEROSIS;
AUTOIMMUNE-DISEASES; CEREBROSPINAL-FLUID; BLOOD; MS; NEURODEGENERATION;
IMMUNOABLATION; EXPERIENCE; ARTHRITIS
AB The purpose of the study was to determine the long-term safety and effectiveness of high-dose immunosuppressive therapy (HDIT) followed by autologous hematopoietic cell transplantation (AHCT) in advanced multiple sclerosis (MS). TBI, CY and antithymocyte globulin were followed by transplantation of autologous, CD34-selected PBSCs. Neurological examinations, brain magnetic resonance imaging and cerebrospinal fluid (CSF) for oligoclonal bands (OCB) were serially evaluated. Patients (n = 26, mean Expanded Disability Status Scale (EDSS) = 7.0, 17 secondary progressive, 8 primary progressive, 1 relapsing/remitting) were followed for a median of 48 months after HDIT followed by AHCT. The 72-month probability of worsening >= 1.0 EDSS point was 0.52 (95% confidence interval, 0.30-0.75). Five patients had an EDSS at baseline of <= 6.0; four of them had not failed treatment at last study visit. OCB in CSF persisted with minor changes in the banding pattern. Four new or enhancing lesions were seen on MRI, all within 13 months of treatment. In this population with high baseline EDSS, a significant proportion of patients with advanced MS remained stable for as long as 7 years after transplant. Non-inflammatory events may have contributed to neurological worsening after treatment. HDIT/AHCT may be more effective in patients with less advanced relapsing/remitting MS.
C1 [Nash, R. A.] Fred Hutchinson Canc Res Ctr, Clin Res Div D1 100, Seattle, WA 98109 USA.
[Bowen, J. D.] Swedish Neurosci Inst, Seattle, WA USA.
[Kraft, G. H.; Wener, M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Wundes, A.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Guan, Q.; Maravilla, K. R.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
[Gooley, T. A.; Storb, R.; Nash, R. A.] Univ Washington, Dept Med, Seattle, WA USA.
[McSweeney, P. A.] Colorado Blood & Canc Inst, Denver, CO USA.
[Pavletic, S. Z.] NCI, Bethesda, MD 20892 USA.
[Openshaw, H.] City Hope Natl Med Ctr, Duarte, CA USA.
RP Nash, RA (reprint author), Fred Hutchinson Canc Res Ctr, Clin Res Div D1 100, 1100 Fairview Ave N,POB 19024, Seattle, WA 98109 USA.
EM rnash@fhcrc.org
FU National Institute of Allergy and Infectious Diseases
[N01AI05419-16-0-1, N01-AI-05408]; National Heart, Lung and Blood
Institute [P01HL036444]; National Cancer Institute, National Institutes
of Health, Department of Health and Human Services [P30CA015704]; US
Department of Education's National Institute on Disability and
Rehabilitation Research [H133B980017]
FX We acknowledge the study coordinators and data technicians who
contributed to this study. We thank Helen Crawford, Bonnie Larson and
Sue Carbonneau for their excellent support in preparing this manuscript.
This work was supported by contract awards N01AI05419-16-0-1 (PI Keith
Sullivan) and N01-AI-05408 (PI Chris Bredeson) from the National
Institute of Allergy and Infectious Diseases, and grants numbered
P01HL036444 from the National Heart, Lung and Blood Institute,
P30CA015704 from the National Cancer Institute, National Institutes of
Health, Department of Health and Human Services; and H133B980017 from
the US Department of Education's National Institute on Disability and
Rehabilitation Research. We also thank Amgen for their generous gift of
filgrastim (G-CSF).
NR 44
TC 22
Z9 22
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JUL
PY 2012
VL 47
IS 7
BP 946
EP 951
DI 10.1038/bmt.2011.208
PG 6
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 970FI
UT WOS:000306113100007
PM 22056644
ER
PT J
AU Siegel, R
DeSantis, C
Virgo, K
Stein, K
Mariotto, A
Smith, T
Cooper, D
Gansler, T
Lerro, C
Fedewa, S
Lin, CC
Leach, C
Cannady, RS
Cho, HS
Scoppa, S
Hachey, M
Kirch, R
Jemal, A
Ward, E
AF Siegel, Rebecca
DeSantis, Carol
Virgo, Katherine
Stein, Kevin
Mariotto, Angela
Smith, Tenbroeck
Cooper, Dexter
Gansler, Ted
Lerro, Catherine
Fedewa, Stacey
Lin, Chunchieh
Leach, Corinne
Cannady, Rachel Spillers
Cho, Hyunsoon
Scoppa, Steve
Hachey, Mark
Kirch, Rebecca
Jemal, Ahmedin
Ward, Elizabeth
TI Cancer treatment and survivorship statistics, 2012
SO CA-A CANCER JOURNAL FOR CLINICIANS
LA English
DT Review
ID QUALITY-OF-LIFE; LONG-TERM SURVIVORS; ANDROGEN DEPRIVATION THERAPY;
ACUTE-LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; SUPERFICIAL
BLADDER-CANCER; LOCALIZED PROSTATE-CANCER; HEALTHY FOOD CHOICES;
BREAST-CANCER; CHILDHOOD-CANCER
AB Although there has been considerable progress in reducing cancer incidence in the United States, the number of cancer survivors continues to increase due to the aging and growth of the population and improvements in survival rates. As a result, it is increasingly important to understand the unique medical and psychosocial needs of survivors and be aware of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship. To highlight the challenges and opportunities to serve these survivors, the American Cancer Society and the National Cancer Institute estimated the prevalence of cancer survivors on January 1, 2012 and January 1, 2022, by cancer site. Data from Surveillance, Epidemiology, and End Results (SEER) registries were used to describe median age and stage at diagnosis and survival; data from the National Cancer Data Base and the SEER-Medicare Database were used to describe patterns of cancer treatment. An estimated 13.7 million Americans with a history of cancer were alive on January 1, 2012, and by January 1, 2022, that number will increase to nearly 18 million. The 3 most prevalent cancers among males are prostate (43%), colorectal (9%), and melanoma of the skin (7%), and those among females are breast (41%), uterine corpus (8%), and colorectal (8%). This article summarizes common cancer treatments, survival rates, and posttreatment concerns and introduces the new National Cancer Survivorship Resource Center, which has engaged more than 100 volunteer survivorship experts nationwide to develop tools for cancer survivors, caregivers, health care professionals, advocates, and policy makers. CA Cancer J Clin 2012. Published 2012 American Cancer Society.
C1 [Siegel, Rebecca; Stein, Kevin; Smith, Tenbroeck; Cooper, Dexter; Leach, Corinne; Cannady, Rachel Spillers] Amer Canc Soc, Behav Res Ctr, Atlanta, GA 30303 USA.
[Cho, Hyunsoon] NCI, Data Modeling Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Scoppa, Steve; Hachey, Mark] Informat Management Serv Inc, Silver Spring, MD USA.
RP Siegel, R (reprint author), Amer Canc Soc, Behav Res Ctr, 250 Williams St NW, Atlanta, GA 30303 USA.
EM rebecca.siegel@cancer.org
NR 194
TC 953
Z9 990
U1 48
U2 444
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-9235
EI 1542-4863
J9 CA-CANCER J CLIN
JI CA-Cancer J. Clin.
PD JUL-AUG
PY 2012
VL 62
IS 4
BP 220
EP 241
DI 10.3322/caac.21149
PG 22
WC Oncology
SC Oncology
GA 970JJ
UT WOS:000306123900004
ER
PT J
AU Khoury, MJ
Freedman, AN
Gillanders, EM
Harvey, CE
Kaefer, C
Reid, BC
Rogers, S
Schully, SD
Seminara, D
Verma, M
AF Khoury, Muin J.
Freedman, Andrew N.
Gillanders, Elizabeth M.
Harvey, Chinonye E.
Kaefer, Christie
Reid, Britt C.
Rogers, Scott
Schully, Sheri D.
Seminara, Daniela
Verma, Mukesh
TI Frontiers in Cancer Epidemiology: A Challenge to the Research Community
from the Epidemiology and Genomics Research Program at the National
Cancer Institute
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HEALTH
AB The Epidemiology and Genomics Research Program (EGRP) at the National Cancer Institute (NCI) is developing scientific priorities for cancer epidemiology research in the next decade. We would like to engage the research community and other stakeholders in a planning effort that will include a workshop in December 2012 to help shape new foci for cancer epidemiology research. To facilitate the process of defining the future of cancer epidemiology, we invite the research community to join in an ongoing web-based conversation at http://blog-epi.grants.cancer.gov/ to develop priorities and the next generation of high-impact studies. Cancer Epidemiol Biomarkers Prev; 21(7); 999-1001. (C)2012 AACR.
C1 [Khoury, Muin J.; Freedman, Andrew N.; Gillanders, Elizabeth M.; Harvey, Chinonye E.; Kaefer, Christie; Reid, Britt C.; Rogers, Scott; Schully, Sheri D.; Seminara, Daniela; Verma, Mukesh] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Khoury, MJ (reprint author), NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM muk1@cdc.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 10
TC 8
Z9 8
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 JUL
PY 2012
VL 21
IS 7
BP 999
EP 1001
DI 10.1158/1055-9965.EPI-12-0525
PG 3
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 971NH
UT WOS:000306210100001
PM 22665580
ER
PT J
AU Shearin, AL
Hedan, B
Cadieu, E
Erich, SA
Schmidt, EV
Faden, DL
Cullen, J
Abadie, J
Kwon, EM
Grone, A
Devauchelle, P
Rimbault, M
Karyadi, DM
Lynch, M
Galibert, F
Breen, M
Rutteman, GR
Andre, C
Parker, HG
Ostrander, EA
AF Shearin, Abigail L.
Hedan, Benoit
Cadieu, Edouard
Erich, Suzanne A.
Schmidt, Emmett V.
Faden, Daniel L.
Cullen, John
Abadie, Jerome
Kwon, Erika M.
Grone, Andrea
Devauchelle, Patrick
Rimbault, Maud
Karyadi, Danielle M.
Lynch, Mary
Galibert, Francis
Breen, Matthew
Rutteman, Gerard R.
Andre, Catherine
Parker, Heidi G.
Ostrander, Elaine A.
TI The MTAP-CDKN2A Locus Confers Susceptibility to a Naturally Occurring
Canine Cancer
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID WHOLE-GENOME ASSOCIATION; HISTIOCYTIC SARCOMA; WIDE ASSOCIATION;
POPULATION-STRUCTURE; P16(INK4A); MODEL; BREED; DOG; P16; DELETION
AB Background: Advantages offered by canine population substructure, combined with clinical presentations similar to human disorders, makes the dog an attractive system for studies of cancer genetics. Cancers that have been difficult to study in human families or populations are of particular interest. Histiocytic sarcoma is a rare and poorly understood neoplasm in humans that occurs in 15% to 25% of Bernese Mountain Dogs (BMD).
Methods: Genomic DNA was collected from affected and unaffected BMD in North America and Europe. Both independent and combined genome-wide association studies (GWAS) were used to identify cancer-associated loci. Fine mapping and sequencing narrowed the primary locus to a single gene region.
Results: Both populations shared the same primary locus, which features a single haplotype spanning MTAP and part of CDKN2A and is present in 96% of affected BMD. The haplotype is within the region homologous to human chromosome 9p21, which has been implicated in several types of cancer.
Conclusions: We present the first GWAS for histiocytic sarcoma in any species. The data identify an associated haplotype in the highly cited tumor suppressor locus near CDKN2A. These data show the power of studying distinctive malignancies in highly predisposed dog breeds.
Impact: Here, we establish a naturally occurring model of cancer susceptibility due to CDKN2 dysregulation, thus providing insight about this cancer-associated, complex, and poorly understood genomic region. Cancer Epidemiol Biomarkers Prey; 21(7); 1019-27. (C)2012 AACR.
C1 [Shearin, Abigail L.; Cadieu, Edouard; Schmidt, Emmett V.; Faden, Daniel L.; Kwon, Erika M.; Rimbault, Maud; Karyadi, Danielle M.; Parker, Heidi G.; Ostrander, Elaine A.] NHGRI, NIH, Canc Genet Branch, Bethesda, MD 20892 USA.
[Shearin, Abigail L.; Faden, Daniel L.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Hedan, Benoit; Galibert, Francis; Andre, Catherine] Univ Rennes 1, CNRS, UMR 6290, Rennes, France.
[Erich, Suzanne A.; Rutteman, Gerard R.] Univ Utrecht, Dept Clin Sci Compan Anim, Utrecht, Netherlands.
[Grone, Andrea] Univ Utrecht, Fac Vet Med, Dept Pathol, Utrecht, Netherlands.
[Schmidt, Emmett V.; Lynch, Mary] Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02114 USA.
[Schmidt, Emmett V.; Lynch, Mary] Harvard Univ, Boston, MA 02115 USA.
[Hedan, Benoit; Cullen, John; Breen, Matthew] N Carolina State Univ, Dept Populat Hlth, Raleigh, NC 27695 USA.
[Hedan, Benoit; Cullen, John] N Carolina State Univ, Dept Pathobiol, Raleigh, NC 27695 USA.
[Breen, Matthew] N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27695 USA.
[Breen, Matthew] N Carolina State Univ, Ctr Comparat Med & Translat Res, Raleigh, NC 27695 USA.
[Abadie, Jerome] ONIRIS, Ecole Natl Vet Agroalimentaire & Alimentation Nan, Nantes, France.
[Breen, Matthew] UNC Lineberger Comprehens Canc Ctr, Canc Genet Program, Chapel Hill, NC USA.
RP Ostrander, EA (reprint author), NHGRI, NIH, Canc Genet Branch, 50 S Dr,Bldg 50 Room,5351, Bethesda, MD 20892 USA.
EM eostrand@mail.nih.gov
OI Ostrander, Elaine/0000-0001-6075-9738
FU Intramural Program of the National Human Genome Research Institute at
NIH; AKC-Canine Health Foundation [2667, 760, 336, 935]; CNRS and French
Association for Swiss dogs; NIH NCI [R01 CA69069, NIH U01 AI07033];
Harvard Breast Cancer SPORE [P50 CA89393]; Alberto Vittoni Award;
Committee of Preventive Health Care of the Netherlands Royal Society of
Veterinary Medicine; breed societies for Bernese mountain dogs in the
Netherlands; breed societies for Bernese mountain dogs in the Germany;
breed societies for Bernese mountain dogs in the Austria; breed
societies for Bernese mountain dogs in the Belgium
FX This work was supported by the Intramural Program of the National Human
Genome Research Institute at NIH. Additional support was received from
the AKC-Canine Health Foundation grants 2667 and 760 (M. Breen), 336 and
935 (E.A. Ostrander and C. Andre); the CNRS and French Association for
Swiss dogs (C. Andre); NIH NCI R01 CA69069, NIH U01 AI07033, and the
Harvard Breast Cancer SPORE P50 CA89393 (E. V. Schmidt); the Alberto
Vittoni Award (B. Hedan, E. Cadieu, and G.R. Rutteman); the Committee of
Preventive Health Care of the Netherlands Royal Society of Veterinary
Medicine and the breed societies for Bernese mountain dogs in the
Netherlands, Belgium, Germany and Austria (CR. Rutteman).
NR 54
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U1 0
U2 14
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 JUL
PY 2012
VL 21
IS 7
BP 1019
EP 1027
DI 10.1158/1055-9965.EPI-12-0190-T
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 971NH
UT WOS:000306210100004
PM 22623710
ER
PT J
AU Doria-Rose, VP
White, MC
Klabunde, CN
Nadel, MR
Richards, TB
McNeel, TS
Rodriguez, JL
Marcus, PM
AF Doria-Rose, V. Paul
White, Mary C.
Klabunde, Carrie N.
Nadel, Marion R.
Richards, Thomas B.
McNeel, Timothy S.
Rodriguez, Juan L.
Marcus, Pamela M.
TI Use of Lung Cancer Screening Tests in the United States: Results from
the 2010 National Health Interview Survey
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID NEEDLE ASPIRATION BIOPSY; COMPUTED-TOMOGRAPHY; COST-EFFECTIVENESS;
FOLLOW-UP; PROJECT; PNEUMOTHORAX; MORTALITY; TRIAL; RISK; OVERDIAGNOSIS
AB Background: Before evidence of efficacy, lung cancer screening was being ordered by many physicians. The National Lung Screening Trial (NLST), which showed a 20% reduction in lung cancer mortality among those randomized to receive low-dose computed tomography (LDCT), will likely lead to increased screening use.
Methods: We estimated the prevalence of chest X-ray and CT use in the United States using data from the 2010 National Health Interview Survey (NHIS). Subjects included 15,537 NHIS respondents aged >= 40 years without prior diagnosis of lung cancer. Estimates of the size of the U. S. population by age and smoking status were calculated. Multivariate logistic regression examined predictors of test use adjusting for potential confounders.
Results: Twenty-three percent of adults reported chest X-ray in the previous year and 2.5% reported chest X-ray specifically to check for lung cancer; corresponding numbers for chest CT were 7.5% and 1.3%. Older age, black race, male gender, smoking, respiratory disease, personal history of cancer, and having health insurance were associated with test use. Approximately, 8.7 million adults in the United States would be eligible for LDCT screening according to NLST eligibility criteria.
Conclusions and Impact: Monitoring of trends in the use of lung screening tests will be vital to assess the impact of NLST and possible changes in lung cancer screening recommendations and insurance coverage in the future. Education of patients by their physicians, and of the general public, may help ensure that screening is used appropriately, in those most likely to benefit. Cancer Epidemiol Biomarkers Prev; 21(7); 1049-59. (C)2012 AACR.
C1 [Doria-Rose, V. Paul] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[White, Mary C.; Nadel, Marion R.; Richards, Thomas B.; Rodriguez, Juan L.] Ctr Dis Control & Prevent, Epidemiol & Appl Res Branch, Div Canc Prevent & Control, Atlanta, GA USA.
[McNeel, Timothy S.] Informat Management Serv Inc, Rockville, MD USA.
RP Doria-Rose, VP (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 4110,MSC 7344, Bethesda, MD 20892 USA.
EM doriarop@mail.nih.gov
RI White, Mary /C-9242-2012;
OI White, Mary /0000-0002-9826-3962; Doria-Rose,
Vincent/0000-0002-8802-5143
FU U. S. government
FX All authors are federal government employees or contractors, and the
National Health Interview Survey and preparation of the manuscript were
entirely funded by the U. S. government.
NR 37
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Z9 22
U1 0
U2 9
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 JUL
PY 2012
VL 21
IS 7
BP 1049
EP 1059
DI 10.1158/1055-9965.EPI-12-0343
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 971NH
UT WOS:000306210100007
PM 22573798
ER
PT J
AU van Bemmel, D
Lenz, P
Liao, LM
Baris, D
Sternberg, LR
Warner, A
Johnson, A
Jones, M
Kida, M
Schwenn, M
Schned, AR
Silverman, DT
Rothman, N
Moore, LE
AF van Bemmel, Dana
Lenz, Petra
Liao, Linda M.
Baris, Dalsu
Sternberg, Lawrence R.
Warner, Andrew
Johnson, Alison
Jones, Michael
Kida, Masatoshi
Schwenn, Molly
Schned, Alan R.
Silverman, Debra T.
Rothman, Nathaniel
Moore, Lee E.
TI Correlation of LINE-1 Methylation Levels in Patient-Matched Buffy Coat,
Serum, Buccal Cell, and Bladder Tumor Tissue DNA Samples
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GLOBAL METHYLATION; CANCER RISK; BLOOD; HYPOMETHYLATION; ASSOCIATION;
PATTERNS; DISEASE; GENE
AB Background: Evidence suggests that global methylation levels in blood cell DNA may be a biomarker for cancer risk. To date, most studies have used genomic DNA isolated from blood or urine as a surrogate marker of global DNA methylation levels in bladder tumor tissue.
Methods: A subset of 50 bladder cancer cases was selected from the New England Bladder Cancer Case Control Study. Genomic DNA was isolated from buffy coat, buccal cells, serum, and formalin-fixed, paraffin-embedded tissue for each participant. DNA methylalion at four CpG sites within the long interspersed nucleotide element (LINE-1) repetitive element was quantified using pyrosequencing and expressed as a mean methylation level across sites.
Results: Overall, the mean percent (%) LINE-1 5-methylcytosine (%5MeC) level was highest in serum (80.47% +/- 1.44%) and lowest in bladder tumor DNA (61.36% +/- 12.74%) and levels varied significantly across tissue types (P = 0.001). An inverse association between LINE-1 mean %5MeC and tumor stage (P = 0.001) and grade (P = 0.002) was observed. A moderate correlation between patient-matched serum and buffy coat DNA LINE-1 %5MeC levels was found (r = 0.32, P = 0.03) but levels were uncorrelated among other matched genomic DNA samples.
Conclusions: The mean promoter LINE-1 %5MeC measurements were correlated between buffy coat and serum DNA samples. No correlation was observed between genomic DNA sources and tumor tissues; however a significant inverse association between tumor percent LINE-1 methylation and tumor stage/grade was found.
Impact: LINE-1 methylation measured in case blood DNA did not reflect that observed in bladder tumor tissue but may represent other factors associated with carcinogenesis. Cancer Epiclemiol Biomarkers Prev; 21(7); 1143-8. (C)2012 AACR.
C1 [Moore, Lee E.] NCI, Occupat & Environm Epidemiol Branch, Epidemiol & Biostat Program, NIH,DHHS,Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA.
[Lenz, Petra] NCI, Div Canc Epidemiol & Genet, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
[Sternberg, Lawrence R.; Warner, Andrew] NCI, Pathol Histotechnol Lab, Lab Anim Sci Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
[Kida, Masatoshi] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Jones, Michael] Maine Med Ctr, Dept Pathol & Lab Med, Portland, ME USA.
[Schned, Alan R.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA.
[Schwenn, Molly] Maine Canc Registry, Augusta, ME USA.
RP Moore, LE (reprint author), NCI, Occupat & Environm Epidemiol Branch, Epidemiol & Biostat Program, NIH,DHHS,Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Rm 8102, Bethesda, MD 20852 USA.
EM moorele@mail.nih.gov
OI Liao, Linda/0000-0002-1923-5294
FU National Cancer Institute, NIH [HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, NIH, under contract no.
HHSN261200800001E. Mention of trade names, commercial products, or
organizations does not imply endorsement by the U.S. Government.
NR 30
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U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2012
VL 21
IS 7
BP 1143
EP 1148
DI 10.1158/1055-9965.EPI-11-1030
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 971NH
UT WOS:000306210100017
PM 22539607
ER
PT J
AU Vachon, CM
Scott, CG
Fasching, PA
Hall, P
Tamimi, RM
Li, JM
Stone, J
Apicella, C
Odefrey, F
Gierach, GL
Jud, SM
Heusinger, K
Beckmann, MW
Pollan, M
Fernandez-Navarro, P
Gonzalez-Neira, A
Benitez, J
van Gils, CH
Lokate, M
Onland-Moret, NC
Peeters, PHM
Brown, J
Leyland, J
Varghese, JS
Easton, DF
Thompson, DJ
Luben, RN
Warren, RML
Wareham, NJ
Loos, RJF
Khaw, KT
Ursin, G
Lee, E
Gayther, SA
Ramus, SJ
Eeles, RA
Leach, MO
Kwan-Lim, G
Couch, FJ
Giles, GG
Baglietto, L
Krishnan, K
Southey, MC
Le Marchand, L
Kolonel, LN
Woolcott, C
Maskarinec, G
Haiman, CA
Walker, K
Johnson, N
McCormack, VA
Biong, M
Alnaes, GIG
Gram, IT
Kristensen, VN
Borresen-Dale, AL
Lindstrom, S
Hankinson, SE
Hunter, DJ
Andrulis, IL
Knight, JA
Boyd, NF
Figuero, JD
Lissowska, J
Wesolowska, E
Peplonska, B
Bukowska, A
Reszka, E
Liu, JJ
Eriksson, L
Czene, K
Audley, T
Wu, AH
Pankratz, VS
Hopper, JL
dos-Santos-Silva, I
AF Vachon, Celine M.
Scott, Christopher G.
Fasching, Peter A.
Hall, Per
Tamimi, Rulla M.
Li, Jingmei
Stone, Jennifer
Apicella, Carmel
Odefrey, Fabrice
Gierach, Gretchen L.
Jud, Sebastian M.
Heusinger, Katharina
Beckmann, Matthias W.
Pollan, Marina
Fernandez-Navarro, Pablo
Gonzalez-Neira, Anna
Benitez, Javier
van Gils, Carla H.
Lokate, Mariette
Onland-Moret, N. Charlotte
Peeters, Petra H. M.
Brown, Judith
Leyland, Jean
Varghese, Jajini S.
Easton, Douglas F.
Thompson, Deborah J.
Luben, Robert N.
Warren, Ruth M. L.
Wareham, Nicholas J.
Loos, Ruth J. F.
Khaw, Kay-Tee
Ursin, Giske
Lee, Eunjung
Gayther, Simon A.
Ramus, Susan J.
Eeles, Rosalind A.
Leach, Martin O.
Kwan-Lim, Gek
Couch, Fergus J.
Giles, Graham G.
Baglietto, Laura
Krishnan, Kavitha
Southey, Melissa C.
Le Marchand, Loic
Kolonel, Laurence N.
Woolcott, Christy
Maskarinec, Gertraud
Haiman, Christopher A.
Walker, Kate
Johnson, Nichola
McCormack, Valeria A.
Biong, Margarethe
Alnaes, Grethe I. G.
Gram, Inger Torhild
Kristensen, Vessela N.
Borresen-Dale, Anne-Lise
Lindstroem, Sara
Hankinson, Susan E.
Hunter, David J.
Andrulis, Irene L.
Knight, Julia A.
Boyd, Norman F.
Figuero, Jonine D.
Lissowska, Jolanta
Wesolowska, Ewa
Peplonska, Beata
Bukowska, Agnieszka
Reszka, Edyta
Liu, JianJun
Eriksson, Louise
Czene, Kamila
Audley, Tina
Wu, Anna H.
Pankratz, V. Shane
Hopper, John L.
dos-Santos-Silva, Isabel
TI Common Breast Cancer Susceptibility Variants in LSP1 and RAD51L1 Are
Associated with Mammographic Density Measures that Predict Breast Cancer
Risk
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BRCA2 MUTATION CARRIERS; GENETIC POLYMORPHISMS;
LOCI; TISSUE; HERITABILITY; ESTROGEN; WOMEN
AB Background: Mammographic density adjusted for age and body mass index (BMI) is a heritable marker of breast cancer susceptibility. Little is known about the biologic mechanisms underlying the association between mammographic density and breast cancer risk. We examined whether common low-penetrance breast cancer susceptibility variants contribute to interindividual differences in mammographic density measures.
Methods: We established an international consortium (DENSNP) of 19 studies from 10 countries, comprising 16,895 Caucasian women, to conduct a pooled cross-sectional analysis of common breast cancer susceptibility variants in 14 independent loci and mammographic density measures. Dense and nondense areas, and percent density, were measured using interactive-thresholding techniques. Mixed linear models were used to assess the association between genetic variants and the square roots of mammographic density measures adjusted for study, age, case status, BMI, and menopausal status.
Results: Consistent with their breast cancer associations, the C-allele of rs3817198 in LSP1 was positively associated with both adjusted dense area (P = 0.00005) and adjusted percent density (P = 0.001), whereas the Aallele of rs10483813 in RAD51L1 was inversely associated with adjusted percent density (P = 0.003), but not with adjusted dense area (P = 0.07).
Conclusion: We identified two common breast cancer susceptibility variants associated with mammographic measures of radiodense tissue in the breast gland.
Impact: We examined the association of 14 established breast cancer susceptibility loci with mammographic density phenotypes within a large genetic consortium and identified two breast cancer susceptibility variants, LSP1-rs3817198 and RAD51L1-rs10483813, associated with mammographic measures and in the same direction as the breast cancer association. Cancer Epidemiol Biomarkers Prey; 21(7); 1156-66. (C)2012 AACR.
C1 [Vachon, Celine M.; Scott, Christopher G.; Pankratz, V. Shane] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Stone, Jennifer; Apicella, Carmel; Giles, Graham G.; Baglietto, Laura; Hopper, John L.] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Giles, Graham G.; Baglietto, Laura; Krishnan, Kavitha] Canc Council Victoda, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Odefrey, Fabrice; Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Ursin, Giske; Lee, Eunjung; Gayther, Simon A.; Ramus, Susan J.; Haiman, Christopher A.; Wu, Anna H.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA.
[Jud, Sebastian M.; Heusinger, Katharina; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Univ Breast Ctr Franconia, Dept Gynecol & Obstet, Univ Hosp Erlangen,Comprehens Canc Ctr Erlangen N, D-91054 Erlangen, Germany.
[Pollan, Marina; Fernandez-Navarro, Pablo] Inst Salud Carlos III, Area Epidemiol Ambiental & Canc, Ctr Nacl Epidemiol, Madrid, Spain.
[Pollan, Marina; Fernandez-Navarro, Pablo] CIBER Epidemiol & Salud Publ CIBERESP, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain.
[Gonzalez-Neira, Anna; Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid, Spain.
[Gonzalez-Neira, Anna; Benitez, Javier] CIBERER, Madrid, Spain.
[van Gils, Carla H.; Lokate, Mariette; Onland-Moret, N. Charlotte; Peeters, Petra H. M.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Brown, Judith; Easton, Douglas F.; Thompson, Deborah J.; Luben, Robert N.; Audley, Tina] Univ Cambridge, Dept Publ Hlth & Primary Care, Addenbrookes NHS Fdn Trust, Cambridge, England.
[Khaw, Kay-Tee] Univ Cambridge, MRC Ctr Nutr Epidemiol Canc Prevent & Survival CN, Addenbrookes NHS Fdn Trust, Cambridge, England.
[Leyland, Jean; Varghese, Jajini S.; Warren, Ruth M. L.] Univ Cambridge, Dept Radiol, Addenbrookes NHS Fdn Trust, Cambridge, England.
[Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England.
[Ursin, Giske] Univ Oslo, Dept Nutr, Inst Basic Med Sci, N-0316 Oslo, Norway.
[Biong, Margarethe; Alnaes, Grethe I. G.; Kristensen, Vessela N.; Borresen-Dale, Anne-Lise] Norwegian Radium Hosp, Dept Genet, Inst Canc Res, Oslo, Norway.
[Leach, Martin O.; Kwan-Lim, Gek] CR UK & EPSRC Canc Imaging Ctr, London, England.
[Eeles, Rosalind A.; Leach, Martin O.; Kwan-Lim, Gek] Royal Marsden NHS Fdn Trust, London, England.
[Walker, Kate; dos-Santos-Silva, Isabel] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1, England.
[Johnson, Nichola] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Le Marchand, Loic; Kolonel, Laurence N.; Woolcott, Christy; Maskarinec, Gertraud] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[McCormack, Valeria A.] Int Agcy Res Canc, Sect Environm & Radiat, F-69372 Lyon, France.
[Gram, Inger Torhild] Univ Tromso, Inst Community Med, Fac Hlth Sci, Tromso, Norway.
[Tamimi, Rulla M.; Hankinson, Susan E.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Lindstroem, Sara; Hunter, David J.] Program Mol & Genet Epidemiol, Boston, MA USA.
[Tamimi, Rulla M.; Lindstroem, Sara; Hankinson, Susan E.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Andrulis, Irene L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada.
[Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Knight, Julia A.; Boyd, Norman F.] Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Toronto, ON M4X 1K9, Canada.
[Gierach, Gretchen L.; Figuero, Jonine D.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Lissowska, Jolanta; Wesolowska, Ewa] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta; Wesolowska, Ewa] Inst Oncol, Warsaw, Poland.
[Peplonska, Beata; Bukowska, Agnieszka] Nofer Inst Occupat Med, Dept Environm Epidemiol, Lodz, Poland.
[Reszka, Edyta] Nofer Inst Occupat Med, Dept Toxicol & Carcinogenesis, Lodz, Poland.
[Hall, Per; Li, Jingmei; Eriksson, Louise; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Li, Jingmei; Liu, JianJun] Genome Inst Singapore, Singapore, Singapore.
[Hall, Per; Li, Jingmei; Liu, JianJun; Eriksson, Louise; Czene, Kamila] Singapore & Sweden Breast Canc Study SASBAC, Singapore, Singapore.
RP Vachon, CM (reprint author), Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
EM vachon@mayo.edu; isabel.silva@Ishtm.ac.uk
RI Knight, Julia/A-6843-2012; Pollan, Marina/M-3259-2014; Gonzalez-Neira,
Anna/C-5791-2015; Onland-Moret, N. Charlotte/G-9185-2011; leach,
martin/C-2248-2008; Gierach, Gretchen/E-1817-2016; Reszka,
Edyta/F-6008-2010; Li, Jingmei/I-2904-2012; Bukowska,
Agnieszka/G-4906-2010; Peplonska, Beata/F-6004-2010; Andrulis,
Irene/E-7267-2013;
OI leach, martin/0000-0002-0756-5368; Gierach,
Gretchen/0000-0002-0165-5522; Reszka, Edyta/0000-0003-2153-4864; Eeles,
Rosalind/0000-0002-3698-6241; Czene, Kamila/0000-0002-3233-5695; Li,
Jingmei/0000-0001-8587-7511; Ramus, Susan/0000-0003-0005-7798; Scott,
Christopher/0000-0003-1340-0647; Lissowska, Jolanta/0000-0003-2695-5799;
Luben, Robert/0000-0002-5088-6343; dos Santos Silva,
Isabel/0000-0002-6596-8798; Giles, Graham/0000-0003-4946-9099; Pollan,
Marina/0000-0002-4328-1565
FU NHS; National Health and Medical Research Council (NHMRC) [628911];
NHMRC; National Breast Cancer Foundation/Cancer Australia; ELAN-Program
of the University Hospital Erlangen (Erlangen, Germany); ELAN program of
the University Hospital Erlangen; Spain's Health Research Fund (Fond de
Investigacio'n Sanitaria) [FIS PI060386]; Collaboration Agreement
between Astra-Zeneca [EPY 1306/06]; Institut de Salud Carlos III;
Spanish Federation of Breast Cancer (FECMA); "Europe against Cancer"
Programme of the European Commission (SANCO); Dutch Ministry of Health;
Dutch Cancer Society; ZonMW the Netherlands Organisation for Health
Research and Development; World Cancer Research Fund (WCRF); Cancer
Research UK [C11518/A5644, C5047/A5830]; Medical Research Council;
Stroke Association; British Heart Foundation; UK Department of Health;
Research into Ageing and Academy of Medical Sciences; National Cancer
Institute, NIH (Bethesda, MD) [CA17054, CA74847]; California Breast
Cancer Research Program of the University of California [4PB-0092];
National Institute of Environmental Health Sciences, NIH [N01-PC-35139,
T32 ES-013678]; UK Medical Research Council [G9600413]; Mermaid arm of
the Eve Appeal; Public Health Service from the National Cancer
institute, NIH, Department of Health and Human Services [P50 CA 116201,
R01 CA 128931, R01 CA 128931-S01, R01 CA 122340, CA131332, CA087969,
CA089393, CA049449, CA98233]; Cancer Council of Victoria; Victorian
Breast Cancer Research Consortium; National Cancer Institute
[R37CA054281, R01CA063464, R01CA085265, R25CA090956, R01CA132839];
Cancer Research UK; Breast Cancer Campaign; Norwegian Research Council
[183621/S10, 175240/S10]; Norwegian Cancer Society [175240/S10,
PK80108002, PK60287003]; Radium Hospital Foundation; South Eastern
Norway Regional Health Authority [S-02036]; U.S. National Cancer
Institute, NIH under REA (Cancer Care Ontario) [CA-06-503, U01 CA69467];
Intramural Research Program of the U.S. National Cancer Institute,
Department of Health and Human Services; Norway through the Polish -
Norwegian Research Fund [PNRE-243-AI-1/07]; Marit and Hans Rausing's
Initiative against Breast Cancer; National Institutes of Health, Susan
Komen Foundation; Agency for Science, Technology and Research of
Singapore (A*STAR)
FX MOG: The authors acknowledge NHS funding to the NIHR Royal Marsden
Biomedical Research Centre.; AMDTSS: This research was facilitated
through access to the Australian Twin Registry, a national resource
supported by an Enabling grant (ID 628911) from the National Health and
Medical Research Council (NHMRC) and supported by grants from the NHMRC
and National Breast Cancer Foundation/Cancer Australia.; BBCC: This
study was funded, in part, by the ELAN-Program of the University
Hospital Erlangen (Erlangen, Germany); K. Heusinger was funded by the
ELAN program of the University Hospital Erlangen.; DDM-Spain: This study
was supported by Research Grant FIS PI060386 from Spain's Health
Research Fund (Fond de Investigacio'n Sanitaria); the EPY 1306/06
Collaboration Agreement between Astra-Zeneca and the Institut de Salud
Carlos III; and a grant from the Spanish Federation of Breast Cancer
(FECMA).; EPIC-NI: This study was funded by "Europe against Cancer"
Programme of the European Commission (SANCO), Dutch Ministry of Health,
Dutch Cancer Society, ZonMW the Netherlands Organisation for Health
Research and Development, and the World Cancer Research Fund (WCRF).;
EPIC-Norfolk I: This study was funded by research program grant funding
from Cancer Research UK and the Medical Research Council with additional
support from the Stroke Association, British Heart Foundation, UK
Department of Health, Research into Ageing and Academy of Medical
Sciences.; EPIC-Norfolk II: This study was funded by Cancer Research UK.
LIFE: This study was supported by grants CA17054 and CA74847 from the
National Cancer Institute, NIH (Bethesda, MD), 4PB-0092 from the
California Breast Cancer Research Program of the University of
California, and in part through contract no. N01-PC-35139, and T32
ES-013678 from the National Institute of Environmental Health Sciences,
NIH. The collection of cancer incidence data used in this publication
was supported by the California Department of Health Services as part of
the statewide cancer reporting program mandated by California Health and
Safety Code Section 103885.; MARIBS: This study was funded by a Cancer
Research UK project grant (C11518/A5644). The genetic studies were
funded by Cancer Research UK as a separate project grant (C5047/A5830).
The main MARIBS study was supported by a grant from the UK Medical
Research Council (G9600413). S.J. Ramus was funded by the Mermaid arm of
the Eve Appeal.; MCBCS: This study was supported by Public Health
Service Grants P50 CA 116201, R01 CA 128931, R01 CA 128931-S01, R01 CA
122340 from the National Cancer institute, NIH, Department of Health and
Human Services.; MCCS: The study was supported by the Cancer Council of
Victoria and by the Victorian Breast Cancer Research Consortium; MEC:
The study was supported by National Cancer Institute grants R37CA054281,
R01CA063464, R01CA085265 R25CA090956, and R01CA132839.; MOG: This study
was supported by program and project grants from Cancer Research UK and
Breast Cancer Campaign.; NBCS: This study has been supported with grants
to V.N. Kristensen and A.-L. Borresen-Dale from Norwegian Research
Council (#183621/S10 and #175240/S10), The Norwegian Cancer Society
(PK80108002, PK60287003), and The Radium Hospital Foundation as well as
S-02036 from South Eastern Norway Regional Health Authority.; NHS: This
study was supported by Public Health Service Grants CA131332, CA087969,
CA089393, CA049449, CA98233 from the National Cancer Institute, NIH,
Department of Health and Human Services.; OFBCR: This work was supported
by the U.S. National Cancer Institute, NIH under REA #CA-06-503 (Cancer
Care Ontario U01 CA69467) and through cooperative agreements with
members of the Breast Cancer Family Registry (BCFR) and Principal
Investigators.; PBCS: This study was supported by the Intramural
Research Program of the U.S. National Cancer Institute, Department of
Health and Human Services.; PNS: The project was supported by a grant
from Norway through the Polish - Norwegian Research Fund
(PNRE-243-AI-1/07).; SASBAC: The SASBAC study was supported by Marit and
Hans Rausing's Initiative against Breast Cancer, National Institutes of
Health, Susan Komen Foundation and Agency for Science, Technology and
Research of Singapore (A*STAR).
NR 35
TC 50
Z9 50
U1 0
U2 14
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 JUL
PY 2012
VL 21
IS 7
BP 1156
EP 1166
DI 10.1158/1055-9965.EPI-12-0066
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 971NH
UT WOS:000306210100019
PM 22454379
ER
PT J
AU Ma, XY
Beeghly-Fadiel, A
Lu, W
Shi, JJ
Xiang, YB
Cai, QY
Shen, HB
Shen, CY
Ren, ZF
Matsuo, K
Khoo, US
Iwasaki, M
Long, JR
Zhang, B
Ji, BT
Zheng, Y
Wang, WJ
Hu, ZB
Liu, Y
Wu, PE
Shieh, YL
Wang, SM
Xie, XM
Ito, H
Kasuga, Y
Chan, KYK
Iwata, H
Tsugane, S
Gao, YT
Shu, XO
Moses, HL
Zheng, W
AF Ma, Xiangyu
Beeghly-Fadiel, Alicia
Lu, Wei
Shi, Jiajun
Xiang, Yong-Bing
Cai, Qiuyin
Shen, Hongbing
Shen, Chen-Yang
Ren, Zefang
Matsuo, Keitaro
Khoo, Ui Soon
Iwasaki, Motoki
Long, Jirong
Zhang, Ben
Ji, Bu-Tian
Zheng, Ying
Wang, Wenjing
Hu, Zhibin
Liu, Yao
Wu, Pei-Ei
Shieh, Ya-Lan
Wang, Shenming
Xie, Xiaoming
Ito, Hidemi
Kasuga, Yoshio
Chan, Kelvin Y. K.
Iwata, Hiroji
Tsugane, Shoichiro
Gao, Yu-Tang
Shu, Xiao Ou
Moses, Harold L.
Zheng, Wei
TI Pathway Analyses Identify TGFBR2 as Potential Breast Cancer
Susceptibility Gene: Results from a Consortium Study among Asians
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID BETA SIGNALING PATHWAY; GROWTH-FACTOR-BETA; CHINESE WOMEN; HUMAN GENOME;
RISK; POLYMORPHISMS; ASSOCIATION; VARIANTS; IDENTIFICATION;
TRANSCRIPTION
AB Background: The TGF-beta signaling pathway plays a significant role in the carcinogenic process of breast cancer.
Methods: We systematically evaluated associations of common variants in TGF-beta signaling pathway genes with breast cancer risk using a multistage, case-control study among Asian women.
Results: In the first stage, 341 single-nucleotide polymorphisms with minor allele frequencies >= 0.05 across 11 genes were evaluated among 2,926 cases and 2,380 controls recruited as a part of the Shanghai Breast Cancer Genetics Study (SBCGS). In the second stage, 20 SNPs with promising associations were evaluated among an additional 1,890 cases and 2,000 controls from the SBCGS. One variant, TGFBR2 rs1078985, had highly consistent and significant associations with breast cancer risk among participants in both study stages, as well as promising results from in silica analysis. Additional genotyping was carried out among 2,475 cases and 2,343 controls from the SBCGS, as well as among 5,077 cases and 5,384 controls from six studies in the Asian Breast Cancer Consortium (stage III). Pooled analysis of all data indicated that minor allele homozygotes (GG) of TGFBR2 rs1078985 had a 24% reduced risk of breast cancer compared with major allele carriers (AG or AA; OR, 0.76; 95% CI, 0.65-0.89; P = 8.42 x 10(-4)).
Conclusion: These findings support a role for common genetic variation in TGF-beta signaling pathway genes, specifically in TGFBR2, in breast cancer susceptibility.
Impact: These findings may provide new insights into the etiology of breast cancer as well as future potential therapeutic targets. Cancer Epidemiol Biomarkers Prev; 21(7); 1176-84. (C)2012 AACR.
C1 [Beeghly-Fadiel, Alicia] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Med Ctr,Div Epidemiol,Dept Med,Sch Med, Nashville, TN 37203 USA.
[Lu, Wei; Zheng, Ying; Wang, Wenjing] Shanghai Ctr Dis Control & Prevent, Shanghai, Peoples R China.
[Xiang, Yong-Bing; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Shen, Hongbing; Hu, Zhibin; Liu, Yao] Nanjing Med Univ, Dept Epidemiol & Biostat, Nanjing, Peoples R China.
[Shen, Chen-Yang; Wu, Pei-Ei; Shieh, Ya-Lan] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
[Shen, Chen-Yang] China Med Univ, Coll Publ Hlth, Taichung, Taiwan.
[Ren, Zefang] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou 510275, Guangdong, Peoples R China.
[Matsuo, Keitaro; Ito, Hidemi] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan.
[Khoo, Ui Soon; Chan, Kelvin Y. K.] Univ Hong Kong, Dept Pathol, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Iwasaki, Motoki; Tsugane, Shoichiro] Natl Canc Ctr, Epidemiol & Prevent Div, Res Ctr Canc Prevent & Screening, Tokyo 104, Japan.
[Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Wang, Shenming] Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou 510275, Guangdong, Peoples R China.
[Xie, Xiaoming] Sun Yat Sen Univ, Ctr Canc, Guangzhou 510275, Guangdong, Peoples R China.
[Kasuga, Yoshio] Nagano Matsushiro Gen Hosp, Dept Surg, Nagano, Japan.
[Chan, Kelvin Y. K.] Univ Hong Kong, Dept Obstet & Gynecol, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Iwata, Hiroji] Aichi Canc Ctr, Dept Breast Oncol, Cent Hosp, Nagoya, Aichi 464, Japan.
[Moses, Harold L.] Vanderbilt Univ, Dept Canc Biol Med & Pathol, Sch Med, Nashville, TN 37203 USA.
RP Beeghly-Fadiel, A (reprint author), Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Med Ctr,Div Epidemiol,Dept Med,Sch Med, 2525 W End Ave,8th Floor, Nashville, TN 37203 USA.
EM alicia.beeghly@vanderbilt.edu
RI Shen, CY/F-6271-2010; Khoo, Ui Soon/C-1345-2014; Tsugane,
Shocichiro/A-2424-2015;
OI Khoo, Ui Soon/0000-0003-2200-7505; Matsuo, Keitaro/0000-0003-1761-6314
FU U.S. NIH USPHS [R01 CA124558, R01 CA148667, R01 CA064277, R01 CA090899,
R37 CA070867, R01 CA092585, R01 CA118229]; China Scholarship Council
(CSC)
FX This work was supported in part by U.S. NIH USPHS grants R01 CA124558,
R01 CA148667, R01 CA064277, R01 CA090899, and R37 CA070867 to W. Zheng,
and R01 CA092585 and R01 CA118229 to X. O. Shu. X. Ma (from the Third
Military Medical University in Chongqing, China) is supported by the
China Scholarship Council (CSC) while the author is visiting the
Vanderbilt Epidemiology Center in the United States.
NR 38
TC 9
Z9 9
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
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2012
VL 21
IS 7
BP 1176
EP 1184
DI 10.1158/1055-9965.EPI-12-0118
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 971NH
UT WOS:000306210100022
PM 22539603
ER
PT J
AU Spitz, MR
Gorlov, IP
Dong, Q
Wu, XF
Chen, W
Chang, DW
Etzel, CJ
Caporaso, NE
Zhao, Y
Christiani, DC
Brennan, P
Albanes, D
Shi, JX
Thun, M
Landi, MT
Amos, CI
AF Spitz, Margaret R.
Gorlov, Ivan P.
Dong, Qiong
Wu, Xifeng
Chen, Wei
Chang, David W.
Etzel, Carol J.
Caporaso, Neil E.
Zhao, Yang
Christiani, David C.
Brennan, Paul
Albanes, Demetrius
Shi, Jianxin
Thun, Michael
Landi, Maria Teresa
Amos, Christopher I.
TI Multistage Analysis of Variants in the Inflammation Pathway and Lung
Cancer Risk in Smokers
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID SUSCEPTIBILITY LOCUS; FORMER SMOKERS; ASSOCIATION; GENES; POLYMORPHISMS;
SMOKING; CELLS; MAPS; P53
AB Background: Tobacco-induced lung cancer is characterized by a deregulated inflammatory microenvironment. Variants in multiple genes in inflammation pathways may contribute to risk of lung cancer.
Methods: We therefore conducted a three-stage comprehensive pathway analysis (discovery, replication, and meta-analysis) of inflammation gene variants in ever-smoking lung cancer cases and controls. A discovery set (1,096 cases and 727 controls) and an independent and nonoverlapping internal replication set (1,154 cases and 1,137 controls) were derived from an ongoing case-control study. For discovery, we used an iSelect Bead Chip to interrogate a comprehensive panel of 11,737 inflammation pathway single-nucleotide polymorphisms (SNP) and selected nominally significant (P<0.05) SNPs for internal replication.
Results: There were six SNPs that achieved statistical significance (P<0.05) in the internal replication data set with concordant risk estimates for former smokers and five concordant and replicated SNPs in current smokers. Replicated hits were further tested in a subsequent meta-analysis using external data derived from two published genome-wide association studies (GWAS) and a case-control study. Two of these variants (a BCL2L14 SNP in former smokers and an SNP in IL2RB in current smokers) were further validated. In risk score analyses, there was a 26% increase in risk with each additional adverse allele when we combined the genotyped SNP and the most significant imputed SNP in IL2RB in current smokers and a 36% similar increase in risk for former smokers associated with genotyped and imputed BCL2L14 SNPs.
Conclusions/Impact: Before they can be applied for risk prediction efforts, these SNPs should be subject to further external replication and more extensive fine mapping studies. Cancer Epidemiol Biomarkers Prey; 21(7); 1213-21. (C) 2012 AACR.
C1 [Spitz, Margaret R.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Gorlov, Ivan P.] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA.
[Dong, Qiong; Wu, Xifeng; Chang, David W.; Etzel, Carol J.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Chen, Wei; Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
[Caporaso, Neil E.; Landi, Maria Teresa] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Shi, Jianxin] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Albanes, Demetrius] NIH, Nutr Epidemiol Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Zhao, Yang; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA.
[Brennan, Paul] IARC, Lyon, France.
[Thun, Michael] Amer Canc Soc, Atlanta, GA 30329 USA.
RP Spitz, MR (reprint author), Baylor Coll Med, Dan L Duncan Canc Ctr, 1 Baylor Plaza,MS BCM305,Ste 450A,Cullen Bldg, Houston, TX 77030 USA.
EM spitz@bcm.edu
RI Albanes, Demetrius/B-9749-2015
FU [RO1CA55769]; [RO1CA127219]; [RO1CA074386]; [P01CA090578]; [U19
CA148127]; [RP100443]; [CA121197]
FX The study was supported by RO1CA55769 and RO1CA127219 (to M.R. Spitz);
RO1CA074386 and P01CA090578 (to D.C. Christiani); U19 CA148127,
RP100443, and CA121197 (to C.I. Amos).
NR 38
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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 JUL
PY 2012
VL 21
IS 7
BP 1213
EP 1221
DI 10.1158/1055-9965.EPI-12-0352-T
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 971NH
UT WOS:000306210100026
PM 22573796
ER
PT J
AU Mondul, AM
Weinstein, SJ
Horst, RL
Purdue, M
Albanes, D
AF Mondul, Alison M.
Weinstein, Stephanie J.
Horst, Ronald L.
Purdue, Mark
Albanes, Demetrius
TI Serum Vitamin D and Risk of Bladder Cancer in the Prostate, Lung,
Colorectal, and Ovarian (PLCO) Cancer Screening Trial
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID D POOLING PROJECT; RARER CANCERS; DESIGN
AB Background: The one previous prospective study of vitamin D status and risk of urinary bladder cancer found that male smokers with low serum 25-hydroxy-vitamin D[25(OH)D] were at a nearly two-fold increased risk. We conducted an analysis of serum 25(OH)D and risk of bladder cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Study and examined whether serum vitamin D binding protein (DBP) concentration confounded or modified the association.
Methods: Three hundred and seventy-five cases of bladder cancer were matched 1:1 with controls based on age (+/- 5 years), race, sex, and date of blood collection (+/- 30 days). Conditional logistic regression was used to estimate ORs and 95% confidence intervals (Cl) of bladder cancer by prediagnosis levels of 25(OH)D.
Results: We found no strong or statistically significant association between serum 25(OH)D and bladder cancer risk (Q1 vs. Q4: OR, 0.84; 95% Cl, 0.52-1.36; P-trend = 0.56). Further adjustment for, or stratification by, serum DBP did not alter the findings, nor was there a main effect association between DBP and risk.
Conclusion: In contrast to an earlier report, we observed no association between vitamin D status and risk of bladder cancer; this difference could be due to the inclusion of women and nonsmokers in the current study population or due to the differences in the distribution of vitamin D concentrations between the two study populations.
Impact: These findings may contribute to future meta-analyses and help elucidate whether the vitamin D bladder cancer association varies across populations. Cancer Epidemiol Biomarkers Prey; 21(7); 1222-5. (C) 2012 AACR.
C1 [Mondul, Alison M.; Weinstein, Stephanie J.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Purdue, Mark] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA.
RP Mondul, AM (reprint author), NCI, NIH, 6120 Execut Blvd,Ste 320, Rockville, MD 21045 USA.
EM mondulam@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015;
OI Mondul, Alison/0000-0002-8843-1416
FU NIH Office of Dietary Supplements
FX This work was supported in part by intramural funding from the NIH
Office of Dietary Supplements.
NR 7
TC 18
Z9 18
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 JUL
PY 2012
VL 21
IS 7
BP 1222
EP 1225
DI 10.1158/1055-9965.EPI-12-0439
PG 4
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 971NH
UT WOS:000306210100027
PM 22623707
ER
PT J
AU Leung, JM
Udris, EM
Uman, J
Au, DH
AF Leung, Janice M.
Udris, Edmunds M.
Uman, Jane
Au, David H.
TI The Effect of End-of-Life Discussions on Perceived Quality of Care and
Health Status Among Patients With COPD
SO CHEST
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; LUNG-CANCER; COMMUNICATION; VENTILATION;
PREFERENCES; CLINICIAN; PROGNOSIS; INSIGHTS; BARRIERS; DEATH
AB Background: Despite strong preferences for discussions about end-of-life care, patients with COPD do not often have these discussions with their providers. Our objective was to determine whether patients who reported having end-of-life discussions also reported higher perceived markers of quality of care and health status.
Methods: A cross-sectional study of data collected at baseline for a trial to improve the occurrence and quality of end-of-life communication in patients with COPD was conducted. The primary exposure was self-reported acknowledgment of having discussions about end-of-life planning with their physicians. The primary outcome measures were patient-reported quality of care and satisfaction with care, which were dichotomized as best imaginable quality of care vs other ratings of quality and highest satisfaction vs other ratings of satisfaction. We adjusted for confounding factors, including patient and provider characteristics, using logistic regression clustered by provider.
Results: Three hundred seventy-six patients were enrolled, of whom 55 (14.6%) reported having end-of-life discussions. Individuals who reported having end-of-life discussions with their physicians were significantly more likely to rate their quality of care as the best imaginable (OR, 2.07; 95% CI, 1.05-4.09) and to be very satisfied with their medical care (OR, 1.98; 95% CI, 1.10-3.55). Discussions were more likely to have occurred among patients with worse health status as measured by St. George Respiratory Questionnaire total and impact scores.
Conclusions: Patients who reported having end-of-life care discussions with their physicians had higher perceived quality of care and satisfaction with their physicians. Discussing end-of-life care with patients who have COPD may improve their perceived overall quality of and satisfaction with care. CHEST 2012; 142(1):128-133
C1 [Leung, Janice M.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Leung, Janice M.; Au, David H.] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA USA.
[Udris, Edmunds M.; Uman, Jane; Au, David H.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA.
RP Leung, JM (reprint author), 10 Ctr Dr,2C145, Bethesda, MD 20892 USA.
EM Janice.Leung@nih.gov
FU Department of Veterans Affairs [IIR-0292]; Department of Veterans
Affairs; National Heart, Lung, and Blood Institute; Agency of Healthcare
Research and Quality; Gilead Sciences
FX This study was supported by the Department of Veterans Affairs
[IIR-0292].; Financial/nonfinancial disclosures: The authors have
reported to CHEST the following conflicts of interest: Dr Au is a
research advisor for Bosch. He receives research funding from the
Department of Veterans Affairs; the National Heart, Lung, and Blood
Institute; Agency of Healthcare Research and Quality; and Gilead
Sciences. Dr Leung, Mr Udris, and Ms Uman have reported that no
potential conflicts of interest exist with any companies/organizations
whose products or services may be discussed in this article.
NR 24
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U1 0
U2 13
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUL
PY 2012
VL 142
IS 1
BP 128
EP 133
DI 10.1378/chest.11-2222
PG 6
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 971NE
UT WOS:000306209800022
PM 22241761
ER
PT J
AU Haymond, S
Saenger, AK
Free, HM
Hicks, JM
Huestis, MA
Horvath, AR
Fantz, CR
AF Haymond, Shannon
Saenger, Amy K.
Free, Helen M.
Hicks, Jocelyn M.
Huestis, Marilyn A.
Horvath, Andrea Rita
Fantz, Corinne R.
TI Altering the Landscape for Women in Clinical Chemistry: Perspectives
from Multigenerational Leaders
SO CLINICAL CHEMISTRY
LA English
DT Editorial Material
C1 [Haymond, Shannon] NW Univ Feinberg, Sch Med, Childrens Mem Hosp, Dept Pathol & Lab Med, Chicago, IL 60614 USA.
[Saenger, Amy K.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Free, Helen M.] Bayer HealthCare, Elkhart, IN USA.
[Hicks, Jocelyn M.] George Washington Univ, Sch Med, Washington, DC USA.
[Huestis, Marilyn A.] Natl Inst Drug Abuse, Natl Inst Hlth, Baltimore, MD USA.
[Horvath, Andrea Rita] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Fantz, Corinne R.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
RP Haymond, S (reprint author), NW Univ Feinberg, Sch Med, Childrens Mem Hosp, Dept Pathol & Lab Med, 2300 Childrens Plaza,Box 17, Chicago, IL 60614 USA.
EM shaymond@childrensmemorial.org
FU Intramural NIH HHS [Z99 DA999999]
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD JUL
PY 2012
VL 58
IS 7
BP 1082
EP 1085
DI 10.1373/clinchem.2011.174284
PG 4
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 970AA
UT WOS:000306099300002
PM 22623746
ER
PT J
AU Lee, D
Milman, G
Schwope, DM
Barnes, AJ
Gorelick, DA
Huestis, MA
AF Lee, Dayong
Milman, Garry
Schwope, David M.
Barnes, Allan J.
Gorelick, David A.
Huestis, Marilyn A.
TI Cannabinoid Stability in Authentic Oral Fluid after Controlled Cannabis
Smoking
SO CLINICAL CHEMISTRY
LA English
DT Article
ID 11-NOR-DELTA(9)-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID; CYTOCHROME-P450
EXPRESSION; SMOKED CANNABIS; SATIVA L; DRUGS; SALIVA; ABUSE;
DELTA-9-TETRAHYDROCANNABINOL; CONSTITUENTS; DISPOSITION
AB BACKGROUND: Defining cannabinoid stability in authentic oral fluid (OF) is critically important for result interpretation. There are few published OF stability data, and of those available, all employed fortified synthetic OF solutions or elution buffers; none included authentic OF following controlled cannabis smoking.
METHODS: An expectorated OF pool and a pool of OF collected with Quantisal (TM) devices were prepared for each of 10 participants. Delta(9)-Tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), and cannabinol (CBN) stability in each of 10 authentic expectorated and Quantisal-collected OF pools were determined after storage at 4 degrees C for 1 and 4 weeks and at -20 degrees C for 4 and 24 weeks. Results within +/- 20% of baseline concentrations analyzed within 24 h of collection were considered stable.
RESULTS: All Quantisal OF cannabinoid concentrations were stable for 1 week at 4 degrees C. After 4 weeks at 4 degrees C, as well as 4 and 24 weeks at -20 degrees C, THC was stable in 90%, 80%, and 80% and THCCOOH in 89%, 40%, and 50% of Quantisal samples, respectively. Cannabinoids in expectorated OF were less stable than in Quantisal samples when refrigerated or frozen. After 4 weeks at 4 and -20 degrees C, CBD and CBN were stable in 33%-100% of Quantisal and expectorated samples; by 24 weeks at -20 degrees C, CBD and CBN were stable in <= 44%.
CONCLUSIONS: Cannabinoid OF stability varied by analyte, collection method, and storage duration and temperature, and across participants. OF collection with a device containing an elution/stabilization buffer, sample storage at 4 degrees C, and analysis within 4 weeks is preferred to maximize result accuracy. (c) 2012 American Association for Clinical Chemistry
C1 [Lee, Dayong; Milman, Garry; Schwope, David M.; Barnes, Allan J.; Gorelick, David A.; Huestis, Marilyn A.] Natl Inst Drug Abuse, NIH, IRP, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), Natl Inst Drug Abuse, NIH, IRP, Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Rm 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program, National Institute on Drug Abuse, NIH
FX M.A. Huestis, Intramural Research Program, National Institute on Drug
Abuse, NIH.; We acknowledge the contributions of the clinical staffs of
the National Institute on Drug Abuse, Intramural Research Program and
the Behavioral Pharmacology Research Unit. This research was funded by
the Intramural Research Program, National Institute on Drug Abuse, NIH.
NR 40
TC 29
Z9 29
U1 1
U2 11
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD JUL
PY 2012
VL 58
IS 7
BP 1101
EP 1109
DI 10.1373/clinchem.2012.184929
PG 9
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 970AA
UT WOS:000306099300009
PM 22532594
ER
PT J
AU Yenchek, RH
Ix, JH
Shlipak, MG
Bauer, DC
Rianon, NJ
Kritchevsky, SB
Harris, TB
Newman, AB
Cauley, JA
Fried, LF
AF Yenchek, Robert H.
Ix, Joachim H.
Shlipak, Michael G.
Bauer, Douglas C.
Rianon, Nahiof J.
Kritchevsky, Stephen B.
Harris, Tamara B.
Newman, Anne B.
Cauley, Jane A.
Fried, Linda F.
CA Hlth Aging & Body Composition Stud
TI Bone Mineral Density and Fracture Risk in Older Individuals with CKD
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE;
HEMODIALYSIS-PATIENTS; HIP FRACTURE; DIALYSIS PATIENTS; OSTEOPOROTIC
FRACTURE; RENAL OSTEODYSTROPHY; DIABETES-MELLITUS; HOMOCYSTEINE;
ULTRASOUND
AB Background and objectives Kidney Disease Improving Global Outcomes guidelines recommend against bone mineral density (BMD) screening in CKD patients with mineral bone disease, due to a lack of association of BMD with fractures in cross-sectional studies in CKD. We assessed whether BMD is associated with fractures in participants with and without CKD in the Health, Aging, and Body Composition study, a prospective study of well functioning older individuals.
Design, setting, participants, & measurements Hip BMD was measured by dual-energy x-ray absorptiometry. Osteoporosis was defined as a femoral neck BMD (FNBMD) T score below -2.5 and CKD as an estimated GFR <60 ml/min per 1.73 m(2). The association of BMD with incident nonspine, fragility fractures to study year 11 was analyzed using Cox proportional hazards analyses, adjusting for age, race, sex, body mass index, hyperparathyroidism, low vitamin D level, and CKD. Interaction terms were used to assess whether the association of BMD with fracture differed in those with and without CKD.
Results There were 384 incident fractures in 2754 individuals (mean age 73.6 years). Lower FNBMD was associated with greater fracture, regardless of CKD status. After adjustment, the hazard ratios (95% confidence intervals) were 2.74 (1.99, 3.77) and 2.15 (1.80, 2.57) per lower SD FNBMD for those with and without CKD, respectively (interaction P=0.68), and 2.10 (1.23, 3.59) and 1.63 (1.18, 2.23) among those with osteoporosis in patients with and without CKD, respectively (interaction P=0.75).
Conclusions BMD provides information on risk for fracture in older individuals with or without moderate CKD. Clin J Am Soc Nephrol 7: 1130-1136, 2012. doi: 10.2215/CJN.12871211
C1 [Yenchek, Robert H.] Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Sch Med, Pittsburgh, PA 15213 USA.
[Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA.
[Ix, Joachim H.] Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA 92103 USA.
[Ix, Joachim H.] Univ Calif San Diego, Sch Med, Dept Family & Prevent Med, San Diego, CA 92103 USA.
[Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Shlipak, Michael G.; Bauer, Douglas C.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA USA.
[Rianon, Nahiof J.] Univ Texas Houston, Sch Med, Dept Family & Community Med, Houston, TX USA.
[Kritchevsky, Stephen B.] Wake Forest Sch Med, Stricht Ctr Aging, Wake Forest, NC USA.
[Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA.
[Newman, Anne B.; Cauley, Jane A.; Fried, Linda F.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Fried, Linda F.] Vet Affairs Pittsburgh Hlth Care Syst, Renal Sect, Pittsburgh, PA USA.
RP Yenchek, RH (reprint author), Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Sch Med, 200 Lothrop St,C1100 PUH, Pittsburgh, PA 15213 USA.
EM yenchekrh@upmc.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Kritchevsky,
Stephen/0000-0003-3336-6781; Cauley, Jane A/0000-0003-0752-4408
FU Intramural Research Program of the National Institutes of Health;
National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG028050, R01-AG029364]; National Institute of
Nursing Research [R01-NR012459]; NIDDK [T32DK061296]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, as well as the National Institute
on Aging (Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; and
Grants R01-AG028050 and R01-AG029364) and the National Institute of
Nursing Research (Grant R01-NR012459). R.H.Y. is supported by NIDDK
Grant T32DK061296.
NR 32
TC 48
Z9 50
U1 1
U2 5
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 JUL
PY 2012
VL 7
IS 7
BP 1130
EP 1136
DI 10.2215/CJN.12871211
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 970QX
UT WOS:000306148500012
PM 22516286
ER
PT J
AU Malheiros, JM
Polli, RS
Paiva, FF
Longo, BM
Mello, LE
Silva, AC
Tannus, A
Covolan, L
AF Malheiros, Jackeline M.
Polli, Roberson S.
Paiva, Fernando F.
Longo, Beatriz M.
Mello, Luiz E.
Silva, Afonso C.
Tannus, Alberto
Covolan, Luciene
TI Manganese-enhanced magnetic resonance imaging detects mossy fiber
sprouting in the pilocarpine model of epilepsy
SO EPILEPSIA
LA English
DT Article
DE Mossy fiber sprouting; Epilepsy; Pilocarpine; Magnetic resonance
imaging; Manganese; Animal models
ID TEMPORAL-LOBE EPILEPSY; INDUCED STATUS EPILEPTICUS; SULFIDE-SILVER
METHOD; C-FOS EXPRESSION; KAINIC ACID; SYNAPTIC REORGANIZATION; DENTATE
GYRUS; RAT-BRAIN; CELL LOSS; HIPPOCAMPAL SCLEROSIS
AB Purpose: Mossy fiber sprouting (MFS) is a frequent finding following status epilepticus (SE). The present study aimed to test the feasibility of using manganese-enhanced magnetic resonance imaging (MEMRI) to detect MFS in the chronic phase of the well-established pilocarpine (Pilo) rat model of temporal lobe epilepsy (TLE). Methods: To modulate MFS, cycloheximide (CHX), a protein synthesis inhibitor, was coadministered with Pilo in a subgroup of animals. In vivo MEMRI was performed 3 months after induction of SE and compared to the neo-Timm histologic labeling of zinc mossy fiber terminals in the dentate gyrus (DG). Key Findings: Chronically epileptic rats displaying MFS as detected by neo-Timm histology had a hyperintense MEMRI signal in the DG, whereas chronically epileptic animals that did not display MFS had minimal MEMRI signal enhancement compared to nonepileptic control animals. A strong correlation (r = 0.81, p < 0.001) was found between MEMRI signal enhancement and MFS. Significance: This study shows that MEMRI is an attractive noninvasive method for detection of mossy fiber sprouting in vivo and can be used as an evaluation tool in testing therapeutic approaches to manage chronic epilepsy.
C1 [Malheiros, Jackeline M.; Polli, Roberson S.; Longo, Beatriz M.; Mello, Luiz E.; Covolan, Luciene] Univ Fed Sao Paulo, Dept Physiol, UNIFESP, BR-04023062 Sao Paulo, Brazil.
[Malheiros, Jackeline M.; Polli, Roberson S.; Paiva, Fernando F.] Univ Sao Paulo, CIERMag Sao Carlos Inst Phys, Sao Carlos, SP, Brazil.
[Silva, Afonso C.] Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA.
RP Covolan, L (reprint author), Univ Fed Sao Paulo, Dept Physiol, UNIFESP, Rua Botucatu 862,5 Andar, BR-04023062 Sao Paulo, Brazil.
EM lcovolan@unifesp.br
RI Mello, Luiz/B-4177-2009; Malheiros, Jackeline/F-3069-2014; Polli,
Roberson/I-5128-2015; Covolan, Luciene/C-5926-2012; Sao Carlos Institute
of Physics, IFSC/USP/M-2664-2016; Tannus, Alberto/B-9821-2012;
OI Mello, Luiz/0000-0002-6969-1108; Malheiros,
Jackeline/0000-0001-8512-3111; Polli, Roberson/0000-0002-5046-1732;
Covolan, Luciene/0000-0002-9751-6438; Tannus,
Alberto/0000-0002-1675-1971; Paiva, Fernando/0000-0002-8989-9707
FU FAPESP CInAPCe Program [2005/56663-1]; FAPESP [07/52911-6]; NIH, NINDS
FX FAPESP CInAPCe Program 2005/56663-1 (CIERMag). JMM was supported by an
FAPESP fellowship 07/52911-6. This research was supported in part by the
Intramural Research Program of the NIH, NINDS. We thank Vegeflora
Extracoes do Nordeste Ltd who kindly donated pilocarpine hydrochloride.
NR 44
TC 11
Z9 11
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JUL
PY 2012
VL 53
IS 7
BP 1225
EP 1232
DI 10.1111/j.1528-1167.2012.03521.x
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 967YR
UT WOS:000305944600019
PM 22642664
ER
PT J
AU Zhai, ZL
Gomez-Mejiba, SE
Gimenez, MS
Deterding, LJ
Tomer, KB
Mason, RP
Ashby, MT
Ramirez, DC
AF Zhai, Zili
Gomez-Mejiba, Sandra E.
Gimenez, Maria S.
Deterding, Leesa J.
Tomer, Kenneth B.
Mason, Ronald P.
Ashby, Michael T.
Ramirez, Dario C.
TI Free radical-operated proteotoxic stress in macrophages primed with
lipopolysaccharide
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Macrophage; Lipopolysaccharide; Reactive oxygen species; Protein
oxidation; Spin trapping; Antioxidant
ID ENDOPLASMIC-RETICULUM STRESS; NITRIC-OXIDE SYNTHASE; PROTEIN RADICALS;
OXIDATIVE STRESS; HYDROGEN-PEROXIDE; REACTIVE OXYGEN; AMINO-ACIDS; SPIN;
PEROXYNITRITE; DISEASE
AB The free-radical-operated mechanism of death of activated macrophages at sites of inflammation is unclear, but it is important to define it in order to find targets to prevent further tissue dysfunction. A well-defined model of macrophage activation at sites of inflammation is the treatment of RAW 264.7 cells with lipopolysaccharide (LPS), with the resulting production of reactive oxygen species (ROS). ROS and other free radicals can be trapped with the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), a cell-permeable probe with antioxidant properties, which thus interferes with free-radical-operated oxidation processes. Here we have used immuno-spin trapping to investigate the role of free-radical-operated protein oxidation in LPS-induced cytotoxicity in macrophages. Treatment of RAW 264.7 cells with LPS resulted in increased ROS production, oxidation of proteins, cell morphological changes and cytotoxicity. DMPO was found to trap protein radicals to form protein-DMPO nitrone adducts, to reduce protein carbonyls, and to block LPS-induced cell death. N-Acetylcysteine (a source of reduced glutathione), diphenyleneiodonium (an inhibitor of NADPH oxidase), and 2,2'-dipyridyl (a chelator of Fe2+) prevented LPS-induced oxidative stress and cell death and reduced DMPO-nitrone adduct formation, suggesting a critical role of ROS, metals, and protein-radical formation in LPS-induced cell cytotoxicity. We also determined the subcellular localization of protein-DMPO nitrone adducts and identified some candidate proteins for DMPO attachment by LC-MS/MS. The LC-MS/MS data are consistent with glyceraldehyde-3-phosphate dehydrogenase, one of the most abundant, sensitive, and ubiquitous proteins in the cell, becoming labeled with DMPO when the cell is primed with LPS. This information will help find strategies to treat inflammation-associated tissue dysfunction by focusing on preventing free radical-operated proteotoxic stress and death of macrophages. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Gomez-Mejiba, Sandra E.; Gimenez, Maria S.; Ramirez, Dario C.] Univ Nacl San Luis, Lab Expt & Therapeut Med, IMIBIO SL CONICET & Mol Genet, RA-5700 San Luis, Argentina.
[Zhai, Zili] Univ Chicago, Gastroenterol Sect, Dept Med, Chicago, IL 60637 USA.
[Deterding, Leesa J.; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Mason, Ronald P.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
[Ashby, Michael T.] Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73019 USA.
[Ramirez, Dario C.] Natl Univ San Luis, Sch Chem Biochem & Pharm, Dept Biochem & Biol Sci, RA-5700 San Luis, Argentina.
RP Ramirez, DC (reprint author), Univ Nacl San Luis, Lab Expt & Therapeut Med, IMIBIO SL CONICET & Mol Genet, Av Ejercito de los Andes 950, RA-5700 San Luis, Argentina.
EM ramirezlabimibiosl@ymail.com
RI Tomer, Kenneth/E-8018-2013; RAMIREZ, DARIO/K-3312-2013
OI RAMIREZ, DARIO/0000-0001-6725-3326
FU National Institute of Environmental Health Sciences [5R00ES015415-03];
Division of Intramural Research of the NIEHS/NIH [ES050171]
FX This work was supported by the National Institute of Environmental
Health Sciences (5R00ES015415-03 to DCR). KTB participation in this
project was supported by the Division of Intramural Research of the
NIEHS/NIH ES050171. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Institute of Environmental Health Sciences or the National
Institutes of Health. The authors thank Dr. Ann Motten and Mary Mason
for helping in the editing of this manuscript. The authors declare that
there are no conflicts of interest.
NR 55
TC 9
Z9 9
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUL 1
PY 2012
VL 53
IS 1
BP 172
EP 181
DI 10.1016/j.freeradbiomed.2012.04.023
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 966SJ
UT WOS:000305857400017
PM 22580125
ER
PT J
AU Craigie, R
AF Craigie, Robert
TI The molecular biology of HIV integrase
SO FUTURE VIROLOGY
LA English
DT Review
DE HIV-1; intasome; integrase; integration; retrovirus
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL DNA INTEGRATION; IN-VITRO;
CONCERTED INTEGRATION; VIRAL-DNA; PREINTEGRATION COMPLEXES; TYPE-1
INTEGRASE; STRAND TRANSFER; BINDING DOMAIN; NUCLEOPROTEIN COMPLEX
AB Integration of viral DNA into cellular DNA is an essential step in the replication cycle of HIV and other retroviruses. The first antiviral drugs that target integrase, the viral enzyme that catalyzes DNA integration, have recently been approved and more are in the pipeline. These drugs bind to an intermediate in DNA integration called the intasome, in which a pair of viral DNA ends are synapsed by a tetramer of integrase, rather than free integrase enzyme. We discuss the biochemical mechanism of integration, which is now quite well understood, and recent progress towards obtaining atomic-resolution structures of HIV intasomes in complex with inhibitors. Such structures are ultimately required to understand the detailed mechanism of inhibition and the mechanisms by which mutations in integrase confer resistance. The path from early biochemical studies to therapeutic inhibitors of integrase highlights the value of basic science in fighting human diseases.
C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Craigie, R (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM bobc@helix.nih.gov
FU NIDDK, NIH; AIDS Targeted Antiviral Program of the Office of the
Director of the NIH
FX This work was supported by the Intramural Program of NIDDK, NIH and by
the AIDS Targeted Antiviral Program of the Office of the Director of the
NIH. The author has no other relevant affiliations or financial
involvement with any organization or entity with a financial interest in
or financial conflict with the subject matter or materials discussed in
the manuscript apart from those disclosed.
NR 81
TC 12
Z9 13
U1 0
U2 18
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1746-0794
J9 FUTURE VIROL
JI Future Virol.
PD JUL
PY 2012
VL 7
IS 7
BP 679
EP 686
DI 10.2217/FVL.12.56
PG 8
WC Virology
SC Virology
GA 970RK
UT WOS:000306149800011
PM 23024700
ER
PT J
AU Goddard, KAB
Knaus, WA
Whitlock, E
Lyman, GH
Feigelson, HS
Schully, SD
Ramsey, S
Tunis, S
Freedman, AN
Khoury, MJ
Veenstra, DL
AF Goddard, Katrina A. B.
Knaus, William A.
Whitlock, Evelyn
Lyman, Gary H.
Feigelson, Heather Spencer
Schully, Sheri D.
Ramsey, Scott
Tunis, Sean
Freedman, Andrew N.
Khoury, Muin J.
Veenstra, David L.
TI Building the evidence base for decision making in cancer genomic
medicine using comparative effectiveness research
SO GENETICS IN MEDICINE
LA English
DT Review
DE clinical utility; evidence generation; evidence synthesis; stakeholder
ID CLUSTER RANDOMIZED-TRIALS; NEGATIVE BREAST-CANCER; TUMOR
GENE-EXPRESSION; PRIMARY-CARE; HEALTH-CARE; RISK; EXPERIENCE; DESIGN;
RECOMMENDATIONS; ASSOCIATIONS
AB The clinical utility is uncertain for many cancer genomic applications. Comparative effectiveness research (CER) can provide evidence to clarify this uncertainty. The aim of this study was to identify approaches to help stakeholders make evidence-based decisions and to describe potential challenges and opportunities in using CER to produce evidence-based guidance. We identified general CER approaches for genomic applications through literature review, the authors' experiences, and lessons learned from a recent, seven-site CER initiative in cancer genomic medicine. Case studies illustrate the use of CER approaches. Evidence generation and synthesis approaches used in CER include comparative observational and randomized trials, patient-reported outcomes, decision modeling, and economic analysis. Significant challenges to conducting CER in cancer genomics include the rapid pace of innovation, lack of regulation, and variable definitions and evidence thresholds for clinical and personal utility. Opportunities to capitalize on CER methods in cancer genomics include improvements in the conduct of evidence synthesis, stakeholder engagement, increasing the number of comparative studies, and developing approaches to inform clinical guidelines and research prioritization. CER offers a variety of methodological approaches that can address stakeholders' needs and help ensure an effective translation of genomic discoveries.
C1 [Goddard, Katrina A. B.; Whitlock, Evelyn] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA.
[Knaus, William A.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Lyman, Gary H.] Duke Univ, Durham, NC USA.
[Lyman, Gary H.] Duke Canc Inst, Durham, NC USA.
[Feigelson, Heather Spencer] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA.
[Schully, Sheri D.; Freedman, Andrew N.; Khoury, Muin J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Ramsey, Scott] Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA.
[Tunis, Sean] Ctr Med Technol Policy, Baltimore, MD USA.
[Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[Veenstra, David L.] Univ Washington, Dept Pharm, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA.
RP Goddard, KAB (reprint author), Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA.
EM katrina.ab.goddard@kpchr.org
FU National Institutes of Health [P50HG003374, RC2CA148570, UO1GM092676];
Centers for Disease Control and Prevention [U18GD000005,
5U18-GD000005-02]; American Recovery and Reinvestment Act from the
National Cancer Institute [UC2 CA148471, RC2 CA148570-01,
RC2CA148041-01, UC2CA150911]
FX D.L.V. reports serving as a consultant for Medco, Novartis Molecular
Diagnostics, and Genentech, and is supported by the following
genomics-related research grants: P50HG003374, RC2CA148570, and
UO1GM092676 from the National Institutes of Health and U18GD000005 from
the Centers for Disease Control and Prevention.; This study was
supported in part by cooperative agreements funded by the American
Recovery and Reinvestment Act from the National Cancer Institute
including the CERGEN study (UC2 CA148471 to K.A.B.G., E.W., and H.S.F.),
the CANCERGEN study (RC2 CA148570-01 to S.R. and D.L.V.), RC2CA148041-01
(to G. H. L.), Building a Genome Enabled Electronic Medical Record
(UC2CA150911 to W.A.K.), and a cooperative agreement funded by the
Centers for Disease Control and Prevention (5U18-GD000005-02 to D.L.V.).
NR 72
TC 19
Z9 20
U1 0
U2 2
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 JUL
PY 2012
VL 14
IS 7
BP 633
EP 642
DI 10.1038/gim.2012.16
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 971YB
UT WOS:000306241800001
PM 22516979
ER
PT J
AU Khoury, MJ
Gwinn, M
Dotson, WD
Schully, SD
AF Khoury, Muin J.
Gwinn, Marta
Dotson, W. David
Schully, Sheri D.
TI Knowledge integration at the center of genomic medicine
SO GENETICS IN MEDICINE
LA English
DT Article
DE evidence-based medicine; genomic medicine; knowledge integration;
management; synthesis; translation
ID PUBLIC-HEALTH GENOMICS; TRANSLATIONAL RESEARCH; PERSONALIZED MEDICINE;
CANCER; 21ST-CENTURY; EPIDEMIOLOGY; PREVENTION; CONTINUUM; BEDSIDE;
NETWORK
AB Three articles in this issue of Genetics in Medicine describe examples of "knowledge integration," involving methods for generating and synthesizing rapidly emerging information on health-related genomic technologies and engaging stakeholders around the evidence. Knowledge integration, the central process in translating genomic research, involves three closely related, iterative components: knowledge management, knowledge synthesis, and knowledge translation. Knowledge management is the ongoing process of obtaining, organizing, and displaying evolving evidence. For example, horizon scanning and "infoveillance" use emerging technologies to scan databases, registries, publications, and cyberspace for information on genomic applications. Knowledge synthesis is the process of conducting systematic reviews using a priori rules of evidence. For example, methods including meta-analysis, decision analysis, and modeling can be used to combine information from basic, clinical, and population research. Knowledge translation refers to stakeholder engagement and brokering to influence policy, guidelines and recommendations, as well as the research agenda to close knowledge gaps. The ultrarapid production of information requires adequate public and private resources for knowledge integration to support the evidence-based development of genomic medicine.
C1 [Khoury, Muin J.; Gwinn, Marta; Dotson, W. David] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA.
[Khoury, Muin J.; Schully, Sheri D.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Gwinn, Marta] McKing Consulting Corp, Atlanta, GA USA.
RP Khoury, MJ (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA.
EM muk1@cdc.gov
OI Dotson, William David/0000-0002-9606-6594
FU Intramural CDC HHS [CC999999]
NR 30
TC 12
Z9 13
U1 0
U2 10
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 JUL
PY 2012
VL 14
IS 7
BP 643
EP 647
DI 10.1038/gim.2012.43
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 971YB
UT WOS:000306241800002
PM 22555656
ER
PT J
AU Kaphingst, KA
McBride, CM
Wade, C
Alford, SH
Reid, R
Larson, E
Baxevanis, AD
Brody, LC
AF Kaphingst, Kimberly A.
McBride, Colleen M.
Wade, Christopher
Alford, Sharon Hensley
Reid, Robert
Larson, Eric
Baxevanis, Andreas D.
Brody, Lawrence C.
TI Patients' understanding of and responses to multiplex genetic
susceptibility test results
SO GENETICS IN MEDICINE
LA English
DT Article
DE direct-to-consumer genetic tests; genetic testing; provider-patient
communication; public health genomics; understanding
ID CONFOUNDER-SELECTION; HEALTH-PROMOTION; NEGATIVE AFFECT; PUBLIC-HEALTH;
PRIMARY-CARE; RISK; INFORMATION; GENOMICS; VALIDATION; PREVENTION
AB Purpose: Examination of patients' responses to direct-to-consumer genetic susceptibility tests is needed to inform clinical practice. This study examined patients' recall and interpretation of, and responses to, genetic susceptibility test results provided directly by mail.
Methods: This observational study had three prospective assessments (before testing, 10 days after receiving results, and 3 months later). Participants were 199 patients aged 25-40 years who received free genetic susceptibility testing for eight common health conditions.
Results: More than 80% of the patients correctly recalled their results for the eight health conditions. Patients were unlikely to interpret genetic results as deterministic of health outcomes (mean = 6.0, s.d. = 0.8 on a scale of 1-7, 1 indicating strongly deterministic). In multivariate analysis, patients with the least deterministic interpretations were white (P = 0.0098), more educated (P = 0.0093), and least confused by results (P = 0.001). Only 1% talked about their results with a provider.
Conclusion: Findings suggest that most patients will correctly recall their results and will not interpret genetics as the sole cause of diseases. The subset of those confused by results could benefit from consultation with a health-care provider, which could emphasize that health habits currently are the best predictors of risk. Providers could leverage patients' interest in genetic tests to encourage behavior changes to reduce disease risk.
C1 [Kaphingst, Kimberly A.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA.
[McBride, Colleen M.; Wade, Christopher] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[Wade, Christopher] Univ Washington, Dept Nursing, Bothell, WA USA.
[Alford, Sharon Hensley] Henry Ford Hosp, Detroit, MI 48202 USA.
[Reid, Robert; Larson, Eric] Grp Hlth Res Inst, Seattle, WA USA.
[Baxevanis, Andreas D.; Brody, Lawrence C.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
RP Kaphingst, KA (reprint author), Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA.
EM kkaphingst@gwbmail.wustl.edu
FU National Human Genome Research Institute, National Institutes of Health;
National Cancer Institute [U19 CA 079689]; Barnes-Jewish Hospital
Foundation; National Institutes of Health [HHSN268200782096C]
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
In addition, this research was made possible through a collaboration
with the Cancer Research Network, funded by the National Cancer
Institute (U19 CA 079689). Additional resources were provided by Group
Health Research Institute and Henry Ford Hospital. K.A.K. was supported
by funding from the Barnes-Jewish Hospital Foundation. Genotyping
services were provided by the Center for Inherited Disease Research
(CIDR). CIDR is fully funded through a federal contract from the
National Institutes of Health to The Johns Hopkins University
(HHSN268200782096C). We thank Cristofer Price and Yeqin He for their
assistance with statistical analysis, and the members of the Multiplex
Steering Committee who provided their critical review of this article.
We also thank Andrea Kalfoglou for her assistance. Our thanks also go to
the study participants who were all members of the Henry Ford Health
System.
NR 43
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Z9 38
U1 3
U2 12
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 JUL
PY 2012
VL 14
IS 7
BP 681
EP 687
DI 10.1038/gim.2012.22
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 971YB
UT WOS:000306241800007
PM 22481132
ER
PT J
AU Grady, PA
AF Grady, Patricia A.
TI "Vision and Innovation: The National Nursing Research Roundtable"
SO HEART & LUNG
LA English
DT Editorial Material
C1 NINR, NIH, Bethesda, MD 20892 USA.
RP Grady, PA (reprint author), NINR, NIH, Bethesda, MD 20892 USA.
EM info@ninr.nih.gov
NR 7
TC 2
Z9 2
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0147-9563
J9 HEART LUNG
JI Heart Lung
PD JUL-AUG
PY 2012
VL 41
IS 4
BP 319
EP 320
DI 10.1016/j.hrtlng.2012.05.003
PG 2
WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System
SC Cardiovascular System & Cardiology; Nursing; Respiratory System
GA 971LH
UT WOS:000306204900001
PM 22741537
ER
PT J
AU Vannucci, A
Tanofsky-Kraff, M
Shomaker, LB
Ranzenhofer, LM
Matheson, BE
Cassidy, OL
Zocca, JM
Kozlosky, M
Yanovski, SZ
Yanovski, JA
AF Vannucci, A.
Tanofsky-Kraff, M.
Shomaker, L. B.
Ranzenhofer, L. M.
Matheson, B. E.
Cassidy, O. L.
Zocca, J. M.
Kozlosky, M.
Yanovski, S. Z.
Yanovski, J. A.
TI Construct validity of the Emotional Eating Scale Adapted for Children
and Adolescents
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE emotional eating; pediatrics; negative affect; energy intake
ID INDIVIDUAL-DIFFERENCES; ENERGY-INTAKE; FOOD-INTAKE; BEHAVIOR;
VALIDATION; OVERWEIGHT; DISORDER; STRESS; STYLE; OBESE
AB BACKGROUND: Emotional eating, defined as eating in response to a range of negative emotions, is common in youths. Yet, there are few easily administered and well-validated methods to assess emotional eating in pediatric populations.
OBJECTIVE: The current study tested the construct validity of the Emotional Eating Scale (EES) Adapted for Children and Adolescents (EES-C) by examining its relationship to observed emotional eating at laboratory test meals.
METHOD: A total of 151 youths (8-18 years) participated in two multi-item lunch buffet meals on separate days. They ate ad libitum after being instructed to 'eat as much as you would at a normal meal' or to 'let yourself go and eat as much as you want'. State negative affect was assessed immediately before each meal. The EES-C was completed 3 months, on average, before the first test meal.
RESULTS: Among youths with high EES-C total scores, but not low EES-C scores, higher pre-meal state negative affect was related to greater total energy intake at both meals, with and without the inclusion of age, race, sex and body mass index (BMI) standard deviation as covariates (ps<0.03).
DISCUSSION: The EES-C demonstrates good construct validity for children and adolescents' observed energy intake across laboratory test meals designed to capture both normal and disinhibited eating. Future research is required to evaluate the construct validity of the EES-C in the natural environment and the predictive validity of the EES-C longitudinally.
C1 [Vannucci, A.; Tanofsky-Kraff, M.; Shomaker, L. B.; Ranzenhofer, L. M.; Matheson, B. E.; Cassidy, O. L.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Vannucci, A.; Tanofsky-Kraff, M.; Shomaker, L. B.; Ranzenhofer, L. M.; Matheson, B. E.; Cassidy, O. L.; Zocca, J. M.; Yanovski, J. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
[Kozlosky, M.] Ctr Clin, Dept Nutr, Bethesda, MD USA.
[Yanovski, S. Z.] NIDDKD, Div Digest Dis & Nutr, NIH, DHHS, Bethesda, MD 20892 USA.
RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM mtanofsky@usuhs.edu
OI Yanovski, Jack/0000-0001-8542-1637
FU NIH from the NICHD [1ZIAHD000641]; NIMHD
FX Research support: Intramural Research Program, NIH, grant 1ZIAHD000641
from the NICHD with supplemental funding from NIMHD.
NR 34
TC 9
Z9 9
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
J9 INT J OBESITY
JI Int. J. Obes.
PD JUL
PY 2012
VL 36
IS 7
BP 938
EP 943
DI 10.1038/ijo.2011.225
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 972JL
UT WOS:000306273300008
PM 22124451
ER
PT J
AU Tanofsky-Kraff, M
Shomaker, LB
Stern, EA
Miller, R
Sebring, N
DellaValle, D
Yanovski, SZ
Hubbard, VS
Yanovski, JA
AF Tanofsky-Kraff, M.
Shomaker, L. B.
Stern, E. A.
Miller, R.
Sebring, N.
DellaValle, D.
Yanovski, S. Z.
Hubbard, V. S.
Yanovski, J. A.
TI Children's binge eating and development of metabolic syndrome
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE binge eating; metabolic syndrome; children; adolescents; longitudinal
studies
ID RISK-FACTORS; ADOLESCENTS; WEIGHT; TRIGLYCERIDE; ADIPOSITY; INSULIN;
OBESITY; QUESTIONNAIRE; DISTRIBUTIONS; SENSITIVITY
AB BACKGROUND: Binge eating predisposes children to excessive weight gain. However, it is unknown if pediatric binge eating predicts other obesity-associated adverse health outcomes.
OBJECTIVE: The objective of this study was to investigate the relationship between binge eating and metabolic syndrome (MetS) in children.
METHOD: Children aged 5-12 years at high risk for adult obesity, either because they were overweight/obese when first examined or because their parents were overweight/obese, were recruited from Washington, DC and its suburbs. Children completed a questionnaire assessment of binge eating at baseline and underwent measurements of MetS components at baseline and at a follow-up visit approximately 5 years later. Magnetic resonance imaging was used to measure the visceral adipose tissue (VAT) in a subset.
RESULTS: In all, 180 children were studied between July 1996 and August 2010. Baseline self-reported binge eating presence was associated with a 5.33 greater odds of having MetS at follow-up (95% confidence interval (CI): 1.47, 19.27, P = 0.01). The association between binge eating and body mass index (BMI) only partially explained changes in MetS components: baseline binge eating predicted higher follow-up triglycerides, even after accounting for baseline triglycerides, baseline BMI, BMI change, sex, race, baseline age and time in study (P = 0.05). Also, adjusting for baseline VAT and demographics, baseline binge eating predicted greater follow-up L2-3 VAT (P = 0.01).
DISCUSSION: Children's reports of binge eating predicted development of MetS, worsening triglycerides and increased VAT. The excessive weight gain associated with children's binge eating partly explained its adverse metabolic health outcomes. Reported binge eating may represent an early behavioral marker upon which to focus interventions for obesity and MetS.
C1 [Tanofsky-Kraff, M.; Shomaker, L. B.; Stern, E. A.; Miller, R.; Yanovski, S. Z.; Yanovski, J. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Growth & Obes, NIH,DHHS,Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Tanofsky-Kraff, M.; Shomaker, L. B.; Miller, R.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Sebring, N.; DellaValle, D.] NIH, Ctr Clin, Dept Nutr, Bethesda, MD 20892 USA.
[Yanovski, S. Z.] NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA.
[Hubbard, V. S.] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA.
RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Growth & Obes, NIH,DHHS,Hatfield Clin Res Ctr, 10 Ctr Dr,Room 1E-3330,MSC 1103, Bethesda, MD 20892 USA.
EM jy15i@nih.gov
OI Yanovski, Jack/0000-0001-8542-1637
FU NICHD [1F32HD056762, 1ZIAHD000641]; NIMHD
FX The authors' responsibilities were as follows: MTK, LBS, SZY and JAY
designed the study; MTK, LBS, EAS, RM, NS, DD, SZY, VSH and JAY analyzed
and interpreted the data and drafted of the manuscript. All authors
contributed to the collection and assembly of data, provided critical
revision of the article for content and approved the final version of
the manuscript. We thank the volunteers who participated for their help
in completing these studies. The funding organization played no role in
design and conduct of the study; collection, management, analysis and
interpretation of the data; nor preparation or review of the manuscript.
None of the authors declare any conflict of interest. This work was
supported by National Research Service Award 1F32HD056762 from the NICHD
(to LBS) and Intramural Research Program Grant 1ZIAHD000641 from the
NICHD with supplemental funding from NIMHD (to JAY). ClinicalTrials.gov
IDs: NCT00001522, NCT00001195.
NR 44
TC 35
Z9 35
U1 2
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
J9 INT J OBESITY
JI Int. J. Obes.
PD JUL
PY 2012
VL 36
IS 7
BP 956
EP 962
DI 10.1038/ijo.2011.259
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 972JL
UT WOS:000306273300011
PM 22234282
ER
PT J
AU Campbell, KL
Foster-Schubert, KE
Alfano, CM
Wang, CC
Wang, CY
Duggan, CR
Mason, C
Imayama, I
Kong, A
Xiao, LR
Bain, CE
Blackburn, GL
Stanczyk, FZ
McTiernan, A
AF Campbell, Kristin L.
Foster-Schubert, Karen E.
Alfano, Catherine M.
Wang, Chia-Chi
Wang, Ching-Yun
Duggan, Catherine R.
Mason, Caitlin
Imayama, Ikuyo
Kong, Angela
Xiao, Liren
Bain, Carolyn E.
Blackburn, George L.
Stanczyk, Frank Z.
McTiernan, Anne
TI Reduced-Calorie Dietary Weight Loss, Exercise, and Sex Hormones in
Postmenopausal Women: Randomized Controlled Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID BREAST-CANCER RISK; DIABETES PREVENTION PROGRAM; LIFE-STYLE
INTERVENTION; BODY-MASS INDEX; SURGICAL ADJUVANT BREAST;
PHYSICAL-ACTIVITY; CLINICAL-TRIAL; CARDIOVASCULAR-DISEASE; EPIDEMIOLOGIC
EVIDENCE; CIRCULATING LEVELS
AB Purpose
Estrogens and androgens are elevated in obesity and associated with increased postmenopausal breast cancer risk, but the effect of weight loss on these biomarkers is unknown. We evaluated the individual and combined effects of a reduced-calorie weight loss diet and exercise on serum sex hormones in overweight and obese postmenopausal women.
Patients and Methods
We conducted a single-blind, 12-month, randomized controlled trial from 2005 to 2009. Participants (age 50 to 75 years; body mass index > 25.0 kg/m(2), exercising < 100 minutes/wk) were randomly assigned using a computer-generated sequence to (1) reduced-calorie weight loss diet ("diet"; n = 118), (2) moderate-to vigorous-intensity aerobic exercise ("exercise"; n = 117), (3) combined reduced-calorie weight loss diet and moderate-to vigorous-intensity aerobic exercise ("diet + exercise"; n = 117), or (4) control (n = 87). Outcomes were estrone concentration (primary) and estradiol, free estradiol, total testosterone, free testosterone, androstenedione, and sex hormone-binding globulin (SHBG) concentrations (secondary).
Results
Mean age and body mass index were 58 years and 30.9 kg/m(2), respectively. Compared with controls, estrone decreased 9.6% (P = .001) with diet, 5.5% (P = .01) with exercise, and 11.1% (P < .001) with diet + exercise. Estradiol decreased 16.2% (P < .001) with diet, 4.9% (P = .10) with exercise, and 20.3% (P < .001) with diet + exercise. SHBG increased 22.4% (P < .001) with diet and 25.8% (P < .001) with diet + exercise. Free estradiol decreased 21.4% (P < .001) with diet and 26.0% (P < .001) with diet + exercise. Free testosterone decreased 10.0% (P < .001) with diet and 15.6% (P < .001) with diet + exercise. Greater weight loss produced stronger effects on estrogens and SHBG.
Conclusion
Weight loss significantly lowered serum estrogens and free testosterone, supporting weight loss for risk reduction through lowering exposure to breast cancer biomarkers.
C1 [Campbell, Kristin L.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Foster-Schubert, Karen E.; McTiernan, Anne] Univ Washington, Seattle, WA 98195 USA.
[Wang, Chia-Chi; Wang, Ching-Yun; Duggan, Catherine R.; Mason, Caitlin; Imayama, Ikuyo; Xiao, Liren; Bain, Carolyn E.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA USA.
[Alfano, Catherine M.] NCI, Bethesda, MD 20892 USA.
[Kong, Angela] Univ Illinois, Chicago, IL USA.
[Blackburn, George L.] Harvard Univ, Sch Med, Boston, MA USA.
[Stanczyk, Frank Z.] Univ So Calif, Los Angeles, CA USA.
RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N, Seattle, WA USA.
EM amctiern@fhcrc.org
RI Duggan, Catherine/F-9414-2015
OI Duggan, Catherine/0000-0001-7369-4021
FU National Cancer Institute at the National Institutes of Health [R01
CA102504, 5KL2RR025015-03, R25 CA94880, 2R25CA057699]; Canadian
Institutes of Health Research; Wyeth
FX Supported by National Cancer Institute at the National Institutes of
Health (Grants No. R01 CA102504; 5KL2RR025015-03 to K. F. S.; R25
CA94880 and 2R25CA057699 to A. K.); and Canadian Institutes of Health
Research (Fellowships to K. L. C. and C. M.). None of the funding
agencies were involved in the trial design or conduct.; Employment or
Leadership Position: None Consultant or Advisory Role: Anne McTiernan,
Merck (C), Metagenics (C), Novartis (C), Proctor & Gamble (C),
ZymoGenetics (C) Stock Ownership: Anne McTiernan, Merck Honoraria: Anne
McTiernan, Novartis, Wyeth Research Funding: Anne McTiernan, Wyeth
Expert Testimony: None Other Remuneration: None
NR 84
TC 57
Z9 58
U1 2
U2 25
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 1
PY 2012
VL 30
IS 19
BP 2314
EP 2326
DI 10.1200/JCO.2011.37.9792
PG 13
WC Oncology
SC Oncology
GA 971CW
UT WOS:000306182300008
PM 22614972
ER
PT J
AU Smalley, SR
Benedetti, JK
Haller, DG
Hundahl, SA
Estes, NC
Ajani, JA
Gunderson, LL
Goldman, B
Martenson, JA
Jessup, JM
Stemmermann, GN
Blanke, CD
Macdonald, JS
AF Smalley, Stephen R.
Benedetti, Jacqueline K.
Haller, Daniel G.
Hundahl, Scott A.
Estes, Norman C.
Ajani, Jaffer A.
Gunderson, Leonard L.
Goldman, Bryan
Martenson, James A.
Jessup, J. Milburn
Stemmermann, Grant N.
Blanke, Charles D.
Macdonald, John S.
TI Updated Analysis of SWOG-Directed Intergroup Study 0116: A Phase III
Trial of Adjuvant Radiochemotherapy Versus Observation After Curative
Gastric Cancer Resection
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RANDOMIZED CLINICAL-TRIAL; LYMPH-NODE DISSECTION; DATA-BASE REPORT;
NEOADJUVANT CHEMOTHERAPY; CARCINOMA PATIENTS; SURGICAL-TREATMENT;
STOMACH-CANCER; ADENOCARCINOMA; SURGERY; SURVIVAL
AB Purpose
Surgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up. This update, with a more than 10-year median follow-up, presents data on failure patterns and second malignancies and explores selected subset analyses.
Patients and Methods
In all, 559 patients with primaries >= T3 and/or node-positive gastric cancer were randomly assigned to observation versus radiochemotherapy after R0 resection. Fluorouracil and leucovorin were administered before, during, and after radiotherapy. Radiotherapy was given to all LRF sites to a dose of 45 Gy.
Results
Overall survival (OS) and relapse-free survival (RFS) data demonstrate continued strong benefit from postoperative radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse. Second malignancies were observed in 21 patients with radiotherapy versus eight with observation (P = .21). Subset analyses show robust treatment benefit in most subsets, with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect.
Conclusion
Intergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant radiochemotherapy. Toxicities, including second malignancies, appear acceptable, given the magnitude of RFS and OS improvement. LRF reduction may account for the majority of overall relapse reduction. Adjuvant radiochemotherapy remains a rational standard therapy for curatively resected gastric cancer with primaries T3 or greater and/or positive nodes.
C1 [Smalley, Stephen R.] Radiat Oncol Ctr Olathe, Olathe, KS 66061 USA.
[Goldman, Bryan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Haller, Daniel G.] Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA.
[Hundahl, Scott A.] Univ Calif Davis, Davis, CA 95616 USA.
[Macdonald, John S.] Aptium Oncol, Los Angeles, CA USA.
[Estes, Norman C.] Univ Illinois, Coll Med, Peoria, IL 61656 USA.
[Ajani, Jaffer A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Gunderson, Leonard L.] Mayo Clin Arizona, Scottsdale, AZ USA.
[Martenson, James A.] Mayo Clin, Rochester, MN USA.
[Jessup, J. Milburn] NCI, Diagnost Evaluat Branch, Rockville, MD USA.
[Stemmermann, Grant N.] Univ Cincinnati, Cincinnati, OH USA.
[Blanke, Charles D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Blanke, Charles D.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
RP Smalley, SR (reprint author), Radiat Oncol Ctr Olathe, 20375 W 151st St,Suite 180, Olathe, KS 66061 USA.
EM s_smalley@msn.com
FU Stewart Fund; Pathfinder Fund
FX Employment or Leadership Position: None Consultant or Advisory Role:
None Stock Ownership: None Honoraria: None Research Funding: Scott A.
Hundahl, Stewart Fund, Pathfinder Fund Expert Testimony: None Other
Remuneration: Scott A. Hundahl, National Cancer Institute
NR 49
TC 223
Z9 245
U1 1
U2 21
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 1
PY 2012
VL 30
IS 19
BP 2327
EP 2333
DI 10.1200/JCO.2011.36.7136
PG 7
WC Oncology
SC Oncology
GA 971CW
UT WOS:000306182300009
PM 22585691
ER
PT J
AU Demark-Wahnefried, W
Morey, MC
Sloane, R
Snyder, DC
Miller, PE
Hartman, TJ
Cohen, HJ
AF Demark-Wahnefried, Wendy
Morey, Miriam C.
Sloane, Richard
Snyder, Denise C.
Miller, Paige E.
Hartman, Terryl J.
Cohen, Harvey J.
TI Reach Out to Enhance Wellness Home-Based Diet-Exercise Intervention
Promotes Reproducible and Sustainable Long-Term Improvements in Health
Behaviors, Body Weight, and Physical Functioning in Older,
Overweight/Obese Cancer Survivors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIALS; LIFE-STYLE INTERVENTIONS; BREAST-CANCER;
SURVEY SF-36; DISABILITY INSTRUMENT; EATING INDEX-2005; MEDICAL
OUTCOMES; ADULTS; MAINTENANCE; NUTRITION
AB Purpose
Diet and exercise interventions have been tested in cancer survivors as a means to reduce late effects and comorbidity, but few have assessed adherence and health outcomes long term.
Methods
Between July 2005 and May 2007, the Reach Out to Enhance Wellness (RENEW) trial accrued 641 locoregionally staged, long-term (>= 5 years from diagnosis) colorectal, breast, and prostate cancer survivors in the United States (21 states), Canada, and the United Kingdom. All participants were sedentary (< 150 minutes of physical activity [PA] a week), overweight or obese (body mass index, 25 to 40 kg/m(2)), and over age 65 years. The trial tested a diet-exercise intervention delivered via mailed print materials and telephone counseling. RENEW used a wait-list control, cross-over design (ie, participants received the year-long intervention immediately or after a 1-year delay), which allowed the opportunity to assess program efficacy (previously reported primary outcome), durability, and reproducibility (reported herein). Measures included diet quality (DQ), PA, BMI, and physical function (PF).
Results
No significant relapse was observed in the immediate-intervention arm for DQ, PA, and BMI; however, rates of functional decline increased when the intervention ceased. From year 1 to year 2, significant improvements were observed in the delayed-intervention arm; mean change scores in behaviors and BMI and PF slopes were as follows: DQ score, 5.2 (95% CI, 3.4 to 7.0); PA, 45.8 min/wk (95% CI, 26.9 to 64.6 min/wk); BMI, -0.56 (95% CI, -0.75 to -0.36); and Short Form-36 PF, -1.02 versus -5.52 (P < .001 for all measures). Overall, both arms experienced significant improvements in DQ, PA, and BMI from baseline to 2-year follow-up (P < .001).
Conclusion
Older cancer survivors respond favorably to lifestyle interventions and make durable changes in DQ and PA that contribute to sustained weight loss. These changes positively reorient functional decline trajectories during intervention delivery.
C1 [Demark-Wahnefried, Wendy] UAB, Ctr Comprehens Canc, Birmingham, AL USA.
[Demark-Wahnefried, Wendy] UAB, Ctr Aging, Birmingham, AL USA.
[Demark-Wahnefried, Wendy; Sloane, Richard; Snyder, Denise C.; Cohen, Harvey J.] Duke Univ, Sch Nursing, Durham, NC 27706 USA.
[Morey, Miriam C.; Sloane, Richard; Cohen, Harvey J.] Duke Univ, Med Ctr, Durham, NC 27706 USA.
[Morey, Miriam C.; Cohen, Harvey J.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA.
[Miller, Paige E.] NCI, Bethesda, MD 20892 USA.
[Hartman, Terryl J.] Penn State Univ, University Pk, PA 16802 USA.
RP Demark-Wahnefried, W (reprint author), 1675 Univ Blvd 346, Birmingham, AL 35294 USA.
EM demark@uab.edu
FU National Institutes of Health, Bethesda, MD [R01CA106919, P30AG028716,
UL1 RR024128]
FX Supported by Grants No. R01CA106919, P30AG028716, and UL1 RR024128 from
the National Institutes of Health, Bethesda, MD.
NR 66
TC 57
Z9 57
U1 4
U2 32
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 1
PY 2012
VL 30
IS 19
BP 2354
EP 2361
DI 10.1200/JCO.2011.40.0895
PG 8
WC Oncology
SC Oncology
GA 971CW
UT WOS:000306182300013
PM 22614994
ER
PT J
AU Parsons, HM
Harlan, LC
Lynch, CF
Hamilton, AS
Wu, XC
Kato, I
Schwartz, SM
Smith, AW
Keel, G
Keegan, THM
AF Parsons, Helen M.
Harlan, Linda C.
Lynch, Charles F.
Hamilton, Ann S.
Wu, Xiao-Cheng
Kato, Ikuko
Schwartz, Stephen M.
Smith, Ashley W.
Keel, Gretchen
Keegan, Theresa H. M.
TI Impact of Cancer on Work and Education Among Adolescent and Young Adult
Cancer Survivors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID GENERIC CORE SCALES; CHILDHOOD-CANCER; BREAST-CANCER; NEUROCOGNITIVE
STATUS; EMPLOYMENT; RETURN; INSURANCE; REHABILITATION; PATTERNS;
OUTCOMES
AB Purpose
To examine the impact of cancer on work and education in a sample of adolescent and young adult (AYA) patients with cancer.
Patients and Methods
By using the Adolescent and Young Adult Health Outcomes and Patient Experience Study (AYA HOPE)-a cohort of 463 recently diagnosed patients age 15 to 39 years with germ cell cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, sarcoma, and acute lymphocytic leukemia from participating Surveillance, Epidemiology, and End Results (SEER) cancer registries-we evaluated factors associated with return to work/school after cancer diagnosis, a belief that cancer had a negative impact on plans for work/school, and reported problems with work/school after diagnosis by using descriptive statistics, chi(2) tests, and multivariate logistic regression.
Results
More than 72% (282 of 388) of patients working or in school full-time before diagnosis had returned to full-time work or school 15 to 35 months postdiagnosis compared with 34% (14 of 41) of previously part-time workers/students, 7% (one of 14) of homemakers, and 25% (five of 20) of unemployed/disabled patients (P < .001). Among full-time workers/students before diagnosis, patients who were uninsured (odds ratio [OR], 0.21; 95% CI, 0.07 to 0.67; no insurance v employer-/school-sponsored insurance) or quit working directly after diagnosis (OR, 0.15; 95% CI, 0.06 to 0.37; quit v no change) were least likely to return. Very intensive cancer treatment and quitting work/school were associated with a belief that cancer negatively influenced plans for work/school. Finally, more than 50% of full-time workers/students reported problems with work/studies after diagnosis.
Conclusion
Although most AYA patients with cancer return to work after cancer, treatment intensity, not having insurance, and quitting work/school directly after diagnosis can influence work/educational outcomes. Future research should investigate underlying causes for these differences and best practices for effective transition of these cancer survivors to the workplace/school after treatment.
C1 [Parsons, Helen M.; Harlan, Linda C.; Smith, Ashley W.] NCI, Appl Res Program, Bethesda, MD 20892 USA.
[Keel, Gretchen] Informat Management Serv Inc, Silver Spring, MD USA.
[Lynch, Charles F.] Univ Iowa, Iowa City, IA USA.
[Hamilton, Ann S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Keegan, Theresa H. M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Keegan, Theresa H. M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Wu, Xiao-Cheng] Louisiana State Univ, Program Epidemiol, Louisiana Tumor Registry, Sch Publ Hlth,Hlth Sci Ctr, New Orleans, LA USA.
[Kato, Ikuko] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA.
[Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Parsons, HM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, 7703 Floyd Curl Dr,Mail Code 7933, San Antonio, TX 78229 USA.
EM parsonsh@uthscsa.edu
OI Schwartz, Stephen/0000-0001-7499-8502
FU National Cancer Institute [N01-PC-35136, N01-PC-35139, N01-PC-35142,
N01-PC-35143, N01-PC-35145, N01-PC-54402, N01-PC-54404]
FX Supported by Contracts No. N01-PC-35136, N01-PC-35139, N01-PC-35142,
N01-PC-35143, N01-PC-35145, N01-PC-54402, and N01-PC-54404 from the
National Cancer Institute.
NR 42
TC 41
Z9 41
U1 2
U2 14
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 1
PY 2012
VL 30
IS 19
BP 2393
EP 2400
DI 10.1200/JCO.2011.39.6333
PG 8
WC Oncology
SC Oncology
GA 971CW
UT WOS:000306182300018
PM 22614977
ER
PT J
AU Arnold, MM
Brownback, CS
Taraporewala, ZF
Patton, JT
AF Arnold, Michelle M.
Brownback, Catie Small
Taraporewala, Zenobia F.
Patton, John T.
TI Rotavirus variant replicates efficiently although encoding an aberrant
NSP3 that fails to induce nuclear localization of poly(A)-binding
protein
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID SEGMENTED DSRNA VIRUSES; NONSTRUCTURAL PROTEIN; BOVINE ROTAVIRUS;
RNA-BINDING; NUCLEOTIDE-SEQUENCES; BIOCHEMICAL-EVIDENCE; CONSENSUS
SEQUENCE; LOOP MODEL; REARRANGEMENT; GENE
AB The rotavirus (RV) non-structural protein NSP3 forms a dimer that has binding domains for the translation initiation factor elF4G and for a conserved 3'-terminal sequence of viral mRNAs. Through these activities, NSP3 has been proposed to promote viral mRNA translation by directing circularization of viral polysomes. In addition, by disrupting interactions between elF4G and the poly(A)-binding protein (PABP), NSP3 has been suggested to inhibit translation of host polyadenylated mRNAs and to stimulate relocalization of PABP from the cytoplasm to the nucleus. Herein, we report the isolation and characterization of SA11-4Fg7re, an SA11-4F RV derivative that contains a large sequence duplication initiating within the genome segment (gene 7) encoding NSP3. Our analysis showed that mutant NSP3 (NSP3m) encoded by SA11-4Fg7re is almost twice the size of the wild-type protein and retains the capacity to dimerize. However, in comparison to wild-type NSP3, NSP3m has a decreased capacity to interact with elF4G and to suppress the translation of polyadenylated mRNAs. In addition, NSP3m fails to induce the nuclear accumulation of PABP in infected cells. Despite the defective activities of NSP3m, the levels of viral protein and progeny virus produced in SA11-4Fg7re- and SA11-4F-infected cells were indistinguishable. Collectively, these data are consistent with a role for NSP3 in suppressing host protein synthesis through antagonism of PABP activity, but also suggest that NSP3 functions may have little or no impact on the efficiency of virus replication in widely used RV-permissive cell lines.
C1 [Arnold, Michelle M.; Brownback, Catie Small; Taraporewala, Zenobia F.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 50 South Dr,MSC 8026,Room 6314, Bethesda, MD 20892 USA.
EM jpatton@niaid.nih.gov
RI Patton, John/P-1390-2014
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, NIH
FX We thank Sarah McDonald and Mario Barro for their help on the project.
This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, NIH.
NR 55
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U1 0
U2 1
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 JUL
PY 2012
VL 93
BP 1483
EP 1494
DI 10.1099/vir.0.041830-0
PN 7
PG 12
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 973GT
UT WOS:000306348900010
PM 22442114
ER
PT J
AU Trinca, CS
de Thoisy, B
Rosas, FCW
Waldemarin, HF
Koepfli, KP
Vianna, JA
Eizirik, E
AF Trinca, Cristine S.
de Thoisy, Benoit
Rosas, Fernando C. W.
Waldemarin, Helen F.
Koepfli, Klaus-Peter
Vianna, Juliana A.
Eizirik, Eduardo
TI Phylogeography and Demographic History of the Neotropical Otter (Lontra
longicaudis)
SO JOURNAL OF HEREDITY
LA English
DT Article
DE Bayesian skyline plot; biogeography; conservation; divergence time;
population structure; taxonomy
ID EVOLUTIONARILY-SIGNIFICANT-UNITS; MITOCHONDRIAL-DNA VARIATION;
LUTRA-LUTRA; CONSERVATION GENETICS; POPULATION HISTORY; STATISTICAL
TESTS; IBERIAN PENINSULA; SOUTHERN BRAZIL; CONTROL-REGION; SOFTWARE
AB The Neotropical otter (Lontra longicaudis) is a medium-sized semiaquatic carnivore with a broad distribution in the Neotropical region. Despite being apparently common in many areas, it is one of the least known otters, and genetic studies on this species are scarce. Here, we have investigated its genetic diversity, population structure, and demographic history across a large portion of its geographic range by analyzing 1471 base pairs (bp) of mitochondrial DNA from 52 individuals. Our results indicate that L. longicaudis presents high levels of genetic diversity and a consistent phylogeographic pattern, suggesting the existence of at least 4 distinct evolutionary lineages in South America. The observed phylogeographic partitions are partially congruent with the subspecies classification previously proposed for this species. Coalescence-based analyses indicate that Neotropical otter mitochondrial DNA lineages have shared a rather recent common ancestor, approximately 0.5 Ma, and have subsequently diversified into the observed phylogroups. A consistent scenario of recent population expansion was identified in Eastern South America based on several complementary analyses of historical demography. The results obtained here provide novel insights on the evolutionary history of this largely unknown Neotropical mustelid and should be useful to design conservation and management policies on behalf of this species and its habitats.
C1 [Trinca, Cristine S.; Eizirik, Eduardo] Pontificia Univ Catolica Rio Grande do Sul, Fac Biociencias, Porto Alegre, RS, Brazil.
[Trinca, Cristine S.] Univ Fed Rio Grande do Sul, Dept Genet, Porto Alegre, RS, Brazil.
[de Thoisy, Benoit] Kwata NGO, F-97300 Cayenne, French Guiana.
[de Thoisy, Benoit] Inst Pasteur, Lab Interact Virus Hotes, F-97300 Cayenne, French Guiana.
[Rosas, Fernando C. W.] INPA, Manaus, Amazonas, Brazil.
[Waldemarin, Helen F.] Assoc Ecol Ecomarapendi, Projeto Ecolontras, Rio De Janeiro, Brazil.
[Koepfli, Klaus-Peter] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
[Vianna, Juliana A.] Pontificia Univ Catolica Chile, Dept Ecosistemas & Medio Ambiente, Santiago, Chile.
[Eizirik, Eduardo] Inst Procarnivoros, Sao Paulo, Brazil.
RP Eizirik, E (reprint author), Pontificia Univ Catolica Rio Grande do Sul, Fac Biociencias, Ave Ipiranga 6681,Predio 12C,Sala 172, Porto Alegre, RS, Brazil.
EM eduardo.eizirik@pucrs.br
RI Eizirik, Eduardo/K-8034-2012; Adapta, Inct/J-8371-2013; Trinca,
Cristine/G-9507-2012; Vianna, Juliana/E-9847-2015
OI Eizirik, Eduardo/0000-0002-9658-0999; Vianna,
Juliana/0000-0003-2330-7825
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq,
Brazil [478385/2007-2]; WWF Network; European Funds (FEDER); Fonds
Francais pour l'Environnement Mondial (FFEM); French Ministry of Higher
Education and Research
FX Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq,
Brazil (grant number 478385/2007-2). Data collection from French Guiana
samples was performed in the context of the SPECIES project, which was
funded by WWF Network, European Funds (FEDER), Fonds Francais pour
l'Environnement Mondial (FFEM), and the French Ministry of Higher
Education and Research.
NR 55
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U1 2
U2 49
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1503
J9 J HERED
JI J. Hered.
PD JUL
PY 2012
VL 103
IS 4
BP 479
EP 492
DI 10.1093/jhered/ess001
PG 14
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA 973NN
UT WOS:000306367000002
PM 22589556
ER
PT J
AU Chou, DB
Sworder, B
Bouladoux, N
Roy, CN
Uchida, AM
Grigg, M
Robey, PG
Belkaid, Y
AF Chou, David B.
Sworder, Brian
Bouladoux, Nicolas
Roy, Cindy N.
Uchida, Amiko M.
Grigg, Michael
Robey, Pamela G.
Belkaid, Yasmine
TI Stromal-derived IL-6 alters the balance of myeloerythroid progenitors
during Toxoplasma gondii infection
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE Hematopoiesis; bone marrow stromal cell; inflammation
ID BONE-MARROW; MESENCHYMAL STEM; CELLS; INFLAMMATION; HEPCIDIN; ANEMIA;
INTERLEUKIN-6; RESISTANCE; MICE; MONOCYTES
AB Inflammation alters hematopoiesis, often by decreasing erythropoiesis and enhancing myeloid output. The mechanisms behind these changes and how the BM stroma contributes to this process are active areas of research. In this study, we examine these questions in the setting of murine Toxoplasma gondii infection. Our data reveal that infection alters early myeloerythroid differentiation, blocking erythroid development beyond the Pre MegE stage, while expanding the GMP population. IL-6 was found to be a critical mediator of these differences, independent of hepcidin-induced iron restriction. Comparing the BM with the spleen showed that the hematopoietic response was driven by the local microenvironment, and BM chimeras demonstrated that radioresistant cells were the relevant source of IL-6 in vivo. Finally, direct ex vivo sorting revealed that VCAM(+)CD146(lo) BM stromal fibroblasts significantly increase IL-6 secretion after infection. These data suggest that BMSCs regulate the hematopoietic changes during inflammation via IL-6. J. Leukoc. Biol. 92: 123-131; 2012.
C1 [Chou, David B.; Bouladoux, Nicolas; Uchida, Amiko M.; Belkaid, Yasmine] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Grigg, Michael] NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Sworder, Brian; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
[Chou, David B.] Univ Paris 07, Ecole Doctorale B3MI, Paris, France.
[Sworder, Brian] Boston Univ, Sch Med, Grad Program Mol Med, Boston, MA 02118 USA.
[Roy, Cindy N.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA.
[Uchida, Amiko M.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA.
EM ybelkaid@niaid.nih.gov
RI Robey, Pamela/H-1429-2011;
OI Robey, Pamela/0000-0002-5316-5576; Sworder, Brian/0000-0002-5902-5507
FU DIR, NIAID; DIR, NIDCR, of the Intramural Research Program, NIH, U.S.
Department of Health and Human Services; Howard Hughes Medical
Institute-NIH Research Scholars Program
FX This study was supported by the DIR, NIAID, and the DIR, NIDCR, of the
Intramural Research Program, NIH, U.S. Department of Health and Human
Services. Kevin Holmes, Calvin Eigsti, Thomas Moyer, and Elina
Stregevsky of the NIAID sorting facility were an essential help in
performing these studies. D. B. C. thanks Gerard Eberl and Michael T.
Lotze for their invaluable support and advice. D. B. C., B. S., and A.
M. U. also acknowledge the Howard Hughes Medical Institute-NIH Research
Scholars Program for funding and support.
NR 40
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Z9 21
U1 0
U2 4
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 JUL
PY 2012
VL 92
IS 1
BP 123
EP 131
DI 10.1189/jlb.1011527
PG 9
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 966KS
UT WOS:000305837100015
PM 22493080
ER
PT J
AU Reich, W
AF Reich, Walter
TI THE SCHIZOPHRENIA SPECTRUM: A GENETIC CONCEPT
SO JOURNAL OF NERVOUS AND MENTAL DISEASE
LA English
DT Article
ID TRANSMISSION; ENVIRONMENT; DISEASE; FAMILY
AB A spectrum concept of schizophrenia is described which hypothesizes that classical schizophrenia results at least in part from a genetic diathesis; that certain other, usually milder, psychopathological states, which do not satisfy the classical criteria for the diagnosis of schizophrenia, represent varying clinical expressions of the same diathesis; and that all of these states can therefore, be said to constitute a genetically based spectrum of schizophrenic disorders. This concept is, in its broad outlines, not new, but it has had an increasing impact within psychiatry in recent years. Most importantly, it provides a conceptual framework for a variety of schizophrenia studies, particularly those dealing with biological markers, genetic vulnerability clinical phenomenology, and modes of inheritance. A program of research which has attempted to test the concept, and to identify, describe, and classify the components of the genetic spectrum, is reviewed. Its methodology makes possible an approach to schizophrenia which simultaneously takes into account its two most vexing problems-nosology and etiology.
C1 NIH, Psychol & Psychopathol Lab, Bethesda, MD 20014 USA.
RP Reich, W (reprint author), NIH, Psychol & Psychopathol Lab, Bldg 10,Rm 2N 222,9000 Rockville Pike, Bethesda, MD 20014 USA.
NR 57
TC 0
Z9 0
U1 0
U2 0
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 JUL
PY 2012
VL 200
IS 7
BP 554
EP 563
DI 10.1097/NMD.0b013e3182532326
PG 10
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 970GD
UT WOS:000306115200002
PM 22759929
ER
PT J
AU Zheng, F
Wess, J
Alzheimer, C
AF Zheng, Fang
Wess, Juergen
Alzheimer, Christian
TI M-2 muscarinic acetylcholine receptors regulate long-term potentiation
at hippocampal CA3 pyramidal cell synapses in an input-specific fashion
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE muscarinic receptors; hippocampus
ID MOSSY FIBER SYNAPSES; KNOCK-OUT MICE; SYNAPTIC-TRANSMISSION; RAT
HIPPOCAMPUS; CHOLINERGIC INNERVATION; MUTANT MICE; SK CHANNELS; REGION
CA3; MODULATION; PLASTICITY
AB Zheng F, Wess J, Alzheimer C. M-2 muscarinic acetylcholine receptors regulate long-term potentiation at hippocampal CA3 pyramidal cell synapses in an input-specific fashion. J Neurophysiol 108: 91-100, 2012. First published April 4, 2012; doi:10.1152/jn.00740.2011.-Muscarinic receptors have long been known as crucial players in hippocampus-dependent learning and memory, but our understanding of the cellular underpinnings and the receptor subtypes involved lags well behind. This holds in particular for the hippocampal CA3 region, where the mechanisms of synaptic plasticity depend on the type of afferent input. Williams and Johnston (Williams S, Johnston D. Science 242: 84-87, 1988; Williams S, Johnston D. J Neurophysiol 64: 1089-1097, 1990) demonstrated muscarinic depression of mossy fiber (MF) long-term potentiation (LTP) through a presynaptic site of action and Maeda et al. (Maeda T, Kaneko S, Satoh M. Brain Res 619: 324-330, 1993) proposed a bidirectional modulation of MF LTP by muscarinic receptor subtypes. Since then, this issue, as well as muscarinic regulation of plasticity at associational/commissural (A/C) fiber-CA3 synapses has remained largely neglected, not least because of the lack of highly selective ligands for the different muscarinic receptor subtypes. In the present study, we performed field potential and whole cell recordings from the hippocampal CA3 region of M-2 receptor knockout mice to determine the role of M-2 receptors in short-term and long-term plasticity at A/C and MF inputs to CA3 pyramidal cells. At the A/C synapse, M-2 receptors promoted short-term facilitation and LTP. Unexpectedly, M-2 receptors mediated the opposite effect on LTP at the MF synapse, which was significantly reduced, most likely involving a depressant effect of M-2 receptors on adenylyl cyclase activity in MF terminals. Our data demonstrate that cholinergic projections recruit M-2 receptors to redistribute the gain of LTP in CA3 pyramidal cells in an input-specific manner.
C1 [Zheng, Fang; Alzheimer, Christian] Univ Erlangen Nurnberg, Inst Physiol & Pathophysiol, D-91054 Erlangen, Germany.
[Zheng, Fang; Alzheimer, Christian] Univ Kiel, Inst Physiol, D-2300 Kiel, Germany.
[Wess, Juergen] NIDDK, Mol Signaling Sect, Bethesda, MD USA.
RP Alzheimer, C (reprint author), Univ Erlangen Nurnberg, Inst Physiol & Pathophysiol, Univ Str 17, D-91054 Erlangen, Germany.
EM Christian.Alzheimer@physiologie1.med.uni-erlangen.de
FU Deutsche Forschungsgemeinschaft [AL 294/9-1]
FX This work was supported by Deutsche Forschungsgemeinschaft Grant AL
294/9-1 (to C. Alzheimer).
NR 40
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U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD JUL
PY 2012
VL 108
IS 1
BP 91
EP 100
DI 10.1152/jn.00740.2011
PG 10
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 971GM
UT WOS:000306191800010
PM 22490561
ER
PT J
AU Wakabayashi, KT
Kiyatkin, EA
AF Wakabayashi, Ken T.
Kiyatkin, Eugene A.
TI Rapid changes in extracellular glutamate induced by natural arousing
stimuli and intravenous cocaine in the nucleus accumbens shell and core
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE amperometry; stress; enzyme-based sensors; neural activation; glutamate
release; brain temperature; metabolism
ID CENTRAL-NERVOUS-SYSTEM; FREELY MOVING RATS; DOPAMINE RELEASE; STRIATAL
NEURONS; LIMBIC SYSTEM; BRAIN; ADDICTION; TRANSMISSION; DYNAMICS;
BEHAVIOR
AB Wakabayashi KT, Kiyatkin EA. Rapid changes in extracellular glutamate induced by natural arousing stimuli and intravenous cocaine in the nucleus accumbens shell and core. J Neurophysiol 108: 285-299, 2012. First published April 11, 2012; doi:10.1152/jn.01167.2011.-Glutamate (Glu) is a major excitatory neurotransmitter, playing a crucial role in the functioning of the nucleus accumbens (NAc), a critical area implicated in somatosensory integration and regulation of motivated behavior. In this study, high-speed amperometry with enzyme-based biosensors was used in freely moving rats to examine changes in extracellular Glu in the NAc shell and core induced by a tone, tail pinch (TP), social interaction with a male conspecific (SI), and intravenous (iv) cocaine (1 mg/kg). To establish the contribution of Glu to electrochemical signal changes, similar recordings were conducted with null (Glu(0)) sensors, which were exposed to the same chemical and physical environment but were insensitive to Glu. TP, SI, and cocaine, but not a tone, induced relatively large and prolonged current increases detected by both Glu and Glu(0) sensors. However, current differentials revealed very rapid, much smaller, and transient increases in extracellular Glu levels, more predominantly in the NAc shell than core. In contrast to monophasic responses with natural stimuli, cocaine induced a biphasic Glu increase in the shell, with a transient peak during the injection and a slower postinjection peak. Therefore, Glu is phasically released in the NAc after exposure to natural arousing stimuli and cocaine; this release is rapid, stimulus dependent, and structure specific, suggesting its role in triggering neural and behavioral activation induced by these stimuli. This study also demonstrates the need for multiple in vitro and in vivo controls to reveal relatively small, highly phasic, and transient fluctuations in Glu levels occurring under behaviorally relevant conditions.
C1 [Kiyatkin, Eugene A.] NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA.
RP Kiyatkin, EA (reprint author), NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM ekiyatki@intra.nida.nih.gov
RI Reis, Aline/G-9573-2012
FU National Institute on Drug Abuse
FX This study was supported by the Intramural Research Program of the
National Institute on Drug Abuse.
NR 69
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U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD JUL
PY 2012
VL 108
IS 1
BP 285
EP 299
DI 10.1152/jn.01167.2011
PG 15
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 971GM
UT WOS:000306191800025
PM 22496525
ER
PT J
AU Dawson, DA
Goldstein, RB
Grant, BF
AF Dawson, Deborah A.
Goldstein, Rise B.
Grant, Bridget F.
TI Factors Associated With First Utilization of Different Types of Care for
Alcohol Problems
SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS
LA English
DT Article
ID NATIONAL EPIDEMIOLOGIC SURVEY; SUBSTANCE USE DISORDERS; DRUG-USE
DISORDERS; DSM-IV ALCOHOL; UNITED-STATES; HELP-SEEKING;
GENERAL-POPULATION; UNTREATED INDIVIDUALS; GENDER-DIFFERENCES;
BEHAVIORAL-MODEL
AB Objective: The purpose of this research was to investigate whether factors associated with first obtaining care for alcohol problems vary by source of care. Method: This study used data from the National Epidemiologic Survey on Alcohol and Related Conditions to examine initiation of different types of care over a 3-year follow-up interval among individuals with baseline alcohol use disorders who had not previously obtained any care (n = 2,170). Three hierarchical, mutually exclusive types of care were compared: substance use disorder (SUD) specialty sources, general medical but no SUD specialty sources, and nonmedical sources only. Results: Having injured oneself or someone else because of drinking was associated with initiating all three types of care. Additional factors associated with initiating care from SUD specialty treatment sources (vs. no care) comprised male sex, alcohol use disorder severity, major financial problems, and nondependent tobacco/drug use. Factors associated with initiating care from general medical but not SUD specialty sources (vs. no care) comprised marriage/cohabitation, college student status, number of medical conditions, and other substance dependence. Factors associated with obtaining care only from nonmedical sources (vs. no care) comprised low income and anxiety disorder. When direct comparisons were made among types of care, factors drawing individuals into general medical care for reasons not necessarily related to alcohol problems were those that primarily distinguished utilization of general medical sources from the other two types of care. Conclusions: Results support the importance of screening in general medical practice and student health services as an important means of identifying individuals in need of brief intervention or more intensive SUD treatment and reiterate the importance of nonmedical sources for individuals whose alcohol problems might never be addressed in routine medical visits. (1 Stud. Alcohol Drugs, 73, 647-656, 2012)
C1 [Dawson, Deborah A.] Kelly Govt Serv, Bethesda, MD USA.
[Dawson, Deborah A.; Goldstein, Rise B.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA.
RP Dawson, DA (reprint author), 5111 Duvall Dr, Bethesda, MD 20816 USA.
EM deborah.anne.dawson@gmail.com
OI Goldstein, Rise/0000-0002-9603-9473
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health, U.S. Department of Health and Human Services; National
Institutes of Health, National Institute on Alcohol Abuse and Alcoholism
FX The study on which this article is based, the National Epidemiologic
Survey on Alcohol and Related Conditions, is sponsored by the National
Institute on Alcohol Abuse and Alcoholism, National Institutes of
Health, U.S. Department of Health and Human Services, with supplemental
support from the National Institute on Drug Abuse. This research was
supported in part by the Intramural Program of the National Institutes
of Health, National Institute on Alcohol Abuse and Alcoholism. The views
and opinions expressed in this article are those of the authors and
should not be construed to represent the views of any of the sponsoring
organizations, the sponsoring agencies, or the U.S. government.
NR 52
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U1 0
U2 7
PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV
PI PISCATAWAY
PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA
SN 1937-1888
J9 J STUD ALCOHOL DRUGS
JI J. Stud. Alcohol Drugs
PD JUL
PY 2012
VL 73
IS 4
BP 647
EP 656
PG 10
WC Substance Abuse; Psychology
SC Substance Abuse; Psychology
GA 971KJ
UT WOS:000306202500015
PM 22630803
ER
PT J
AU Wu, SH
Shu, XO
Chow, WH
Xiang, YB
Zhang, XL
Li, HL
Cai, QY
Ji, BT
Cai, H
Rothman, N
Gao, YT
Zheng, W
Yang, G
AF Wu, Sheng Hui
Shu, Xiao Ou
Chow, Wong-Ho
Xiang, Yong-Bing
Zhang, Xianglan
Li, Hong-Lan
Cai, Qiuyin
Ji, Bu-Tian
Cai, Hui
Rothman, Nathaniel
Gao, Yu-Tang
Zheng, Wei
Yang, Gong
TI Soy Food Intake and Circulating Levels of Inflammatory Markers in
Chinese Women
SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
LA English
DT Article
DE Soy; Inflammation; Interleukin-1 beta; Interleukin-6; Tumor necrosis
factor-alpha
ID C-REACTIVE PROTEIN; NECROSIS-FACTOR-ALPHA; CORONARY-HEART-DISEASE;
ENDOTHELIAL FUNCTION; POSTMENOPAUSAL WOMEN; PLATELET-AGGREGATION;
COLORECTAL-CANCER; OXIDATIVE STRESS; BLOOD-PRESSURE; RISK
AB Background Soy and some of its constituents, such as isoflavones, have been shown to affect the inflammatory process in animal studies. The association between soy food intake and inflammatory markers has not been evaluated adequately in humans.
Objective Our aim was to evaluate whether higher intake of soy foods was inversely associated with inflammatory markers in 1,005 middle-aged Chinese women.
Design In this cross-sectional study, dietary intake of soy foods was assessed by a validated food frequency questionnaire and by a 24-hour recall when biospecimens were procured. A general linear model was used to estimate the geometric means of selected inflammatory, markers, including interleukin-6 (IL-6), IL-1 beta, tumor necrosis factor-alpha (TNF alpha), soluble IL-6 receptor, soluble GP130, soluble TNF receptors 1 and 2, and C-reactive protein, across categories of soy food intake after adjusting for age, lifestyle and dietary factors, and history of infectious or inflammation-related diseases.
Results We found that multivariable-adjusted geometric mean concentrations of IL-6 and TNF alpha were inversely associated with quintiles of soy food intake, with a difference between the highest and lowest quintiles of 25.5% for IL-6 (P for trend=0.008) and 14% for TNF alpha (P for trend=0.04). Similar inverse associations were found for TNF alpha (P for trend=0.003), soluble TNF receptor 1 (P for trend=0.01), soluble TNF receptor 2 (P for trend=0.02), IL-1 beta (P for trend=0.05), and IL-6 (P for trend=0.04) when soy food consumption was assessed by the frequency of consumption in the preceding 24 hours. No significant associations were found for other markers studied.
Conclusions This study suggests that soy food consumption is related to lower circulating levels of IL-6, TNF alpha, and soluble TNF receptors 1 and 2 in Chinese women. J Acad Nutr Diet. 2012;112:996-1004.
C1 [Wu, Sheng Hui; Shu, Xiao Ou; Zhang, Xianglan; Cai, Qiuyin; Cai, Hui; Zheng, Wei; Yang, Gong] Vanderbilt Univ, Div Epidemiol, Dept Med, Med Ctr, Nashville, TN 37203 USA.
[Chow, Wong-Ho; Ji, Bu-Tian; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Xiang, Yong-Bing; Li, Hong-Lan; Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China.
RP Yang, G (reprint author), Vanderbilt Univ, Div Epidemiol, Dept Med, Med Ctr, 2525 W End Ave,Suite 600 IMPH, Nashville, TN 37203 USA.
EM Gong.Yang@Vanderbilt.edu
FU US Public Health Service [R01CA122364, R37CA070867, R01HL095931];
National Institutes of Health intramural program [N02 CP1101066];
Vanderbilt-Ingram Cancer Center [P30 CA68485]
FX This study was supported by US Public Health Service grants R01CA122364
and R37CA070867 and, in part, by R01HL095931, the National Institutes of
Health intramural program (N02 CP1101066), and the Vanderbilt-Ingram
Cancer Center (P30 CA68485).
NR 50
TC 13
Z9 13
U1 1
U2 8
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 JUL
PY 2012
VL 112
IS 7
BP 996
EP 1004
DI 10.1016/j.jand.2012.04.001
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 972RE
UT WOS:000306296800005
PM 22889631
ER
PT J
AU Baxi, S
Fury, M
Ganly, I
Rao, S
Pfister, DG
AF Baxi, Shrujal
Fury, Matthew
Ganly, Ian
Rao, Shyam
Pfister, David G.
TI Ten Years of Progress in Head and Neck Cancers
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Editorial Material
ID LOCALLY ADVANCED HEAD; TRANSORAL ROBOTIC SURGERY; SQUAMOUS-CELL
CARCINOMA; HUMAN-PAPILLOMAVIRUS; INDUCTION CHEMOTHERAPY; OROPHARYNGEAL
CANCER; PLUS CETUXIMAB; PHASE-III; CISPLATIN; FLUOROURACIL
C1 [Ganly, Ian] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland.
[Pfister, David G.] Mem Sloan Kettering Canc Ctr, Head & Neck Canc Dis Management Team, New York, NY USA.
[Pfister, David G.] Mem Sloan Kettering Canc Ctr, Head & Neck Oncol Serv, Dept Med, New York, NY USA.
[Pfister, David G.] Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA.
[Pfister, David G.] NCI, Bethesda, MD 20892 USA.
FU NCATS NIH HHS [UL1 TR000457]; NCI NIH HHS [P30 CA008748]
NR 32
TC 13
Z9 13
U1 0
U2 1
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD JUL
PY 2012
VL 10
IS 7
BP 806
EP 810
PG 5
WC Oncology
SC Oncology
GA 972TR
UT WOS:000306303900004
PM 22773796
ER
PT J
AU Lynch, RM
Tran, L
Louder, MK
Schmidt, SD
Cohen, M
DerSimonian, R
Euler, Z
Gray, ES
Karim, SA
Kirchherr, J
Montefiori, DC
Sibeko, S
Soderberg, K
Tomaras, G
Yang, ZY
Nabel, GJ
Schuitemaker, H
Morris, L
Haynes, BF
Mascola, JR
AF Lynch, Rebecca M.
Tran, Lillian
Louder, Mark K.
Schmidt, Stephen D.
Cohen, Myron
DerSimonian, Rebecca
Euler, Zelda
Gray, Elin S.
Karim, Salim Abdool
Kirchherr, Jennifer
Montefiori, David C.
Sibeko, Sengeziwe
Soderberg, Kelly
Tomaras, Georgia
Yang, Zhi-Yong
Nabel, Gary J.
Schuitemaker, Hanneke
Morris, Lynn
Haynes, Barton F.
Mascola, John R.
TI The Development of CD4 Binding Site Antibodies during HIV-1 Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; B-CELL
RESPONSES; NEUTRALIZING ANTIBODIES; HIV-1-INFECTED INDIVIDUALS; DISEASE
PROGRESSION; GP120 GLYCOPROTEIN; RATIONAL DESIGN; BROAD; EPITOPE
AB Broadly neutralizing antibodies to the CD4 binding site (CD4bs) of gp120 are generated by some HIV-1-infected individuals, but little is known about the prevalence and evolution of this antibody response during the course of HIV-1 infection. We analyzed the sera of 113 HIV-1 seroconverters from three cohorts for binding to a panel of gp120 core proteins and their corresponding CD4bs knockout mutants. Among sera collected between 99 and 258 weeks post-HIV-1 infection, 88% contained antibodies to the CD4bs and 47% contained antibodies to resurfaced stabilized core (RSC) probes that react preferentially with broadly neutralizing CD4bs antibodies (BNCD4), such as monoclonal antibodies (MAbs) VRC01 and VRC-CH31. Analysis of longitudinal serum samples from a subset of 18 subjects revealed that CD4bs antibodies to gp120 arose within the first 4 to 16 weeks of infection, while the development of RSC-reactive antibodies was more varied, occurring between 10 and 152 weeks post-HIV-1 infection. Despite the presence of these antibodies, serum neutralization mediated by RSC-reactive antibodies was detected in sera from only a few donors infected for more than 3 years. Thus, CD4bs antibodies that bind a VRC01-like epitope are often induced during HIV-1 infection, but the level and potency required to mediate serum neutralization may take years to develop. An improved understanding of the immunological factors associated with the development and maturation of neutralizing CD4bs antibodies during HIV-1 infection may provide insights into the requirements for eliciting this response by vaccination.
C1 [Lynch, Rebecca M.; Tran, Lillian; Louder, Mark K.; Schmidt, Stephen D.; Yang, Zhi-Yong; Nabel, Gary J.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[DerSimonian, Rebecca; Tomaras, Georgia] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Kirchherr, Jennifer; Montefiori, David C.; Soderberg, Kelly; Haynes, Barton F.] Duke Univ, Med Ctr, Durham, NC USA.
[Cohen, Myron] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Gray, Elin S.; Morris, Lynn] Natl Inst Communicable Dis, Johannesburg, South Africa.
[Gray, Elin S.; Morris, Lynn] Univ Witwatersrand, Johannesburg, South Africa.
[Karim, Salim Abdool; Sibeko, Sengeziwe] Univ KwaZulu Natal, CAPRISA, Durban, South Africa.
[Gray, Elin S.; Schuitemaker, Hanneke] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jmascola@mail.nih.gov
RI Abdool Karim, Salim Safurdeen/N-5947-2013; Schmidt, Stephen/B-5398-2012;
Tomaras, Georgia/J-5041-2016;
OI Abdool Karim, Salim Safurdeen/0000-0002-4986-2133; Gray,
Elin/0000-0002-8613-3570
FU Vaccine Research Center,NIAID,NIH; U.S. National Institutes of Health
Comprehensive International Program of Research on AIDS (CIPRA)
[AI51794]; Columbia University-Southern African Fogarty AIDS
International Training and Research Programme (AITRP) [D43TW00231];
Center for Infectious Disease Control of theNetherlands National
Institute for Public Health and the Environment; Netherlands
Organization for Scientific research [918.66.628]; European Community
[037611, 201433]; Division of AIDS, NIAID, NIH [AI067854]
FX This research was supported by CHAVI grant AI067854 from the Division of
AIDS, NIAID, NIH, and by the intramural research program of the Vaccine
Research Center, NIAID, NIH. We thank the U.S. National Institutes of
Health Comprehensive International Program of Research on AIDS (CIPRA)
(grant AI51794) and the Columbia University-Southern African Fogarty
AIDS International Training and Research Programme (AITRP) (grant
D43TW00231) for the research infrastructure and training that made the
CAPRISA 002 Acute Infection study possible. The Amsterdam Cohort Studies
on HIV infection and AIDS, a collaboration between the Amsterdam Health
Service, the Academic Medical Center of the University of Amsterdam,
Sanquin Blood Supply Foundation, the University Medical Center Utrecht,
and the Jan van Goyen Clinic, are part of the Netherlands HIV Monitoring
Foundation and are financially supported by the Center for Infectious
Disease Control of the Netherlands National Institute for Public Health
and the Environment. This study was financially supported by the
Netherlands Organization for Scientific research (grant 918.66.628), the
European Community's Six Framework Program European HIV Enterprise
(EUROPRISE; FP6/2007-2012) under grant agreement 037611, and the
European Community's Seventh Framework Program Next Generation HIV-1
Immunogens Inducing Broadly Reactive Neutralizing Antibodies (NGIN)
(FP7/2007-2013) under grant agreement 201433.
NR 45
TC 55
Z9 55
U1 0
U2 5
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 JUL
PY 2012
VL 86
IS 14
BP 7588
EP 7595
DI 10.1128/JVI.00734-12
PG 8
WC Virology
SC Virology
GA 969ZO
UT WOS:000306098100012
PM 22573869
ER
PT J
AU Budde, ML
Greene, JM
Chin, EN
Ericsen, AJ
Scarlotta, M
Cain, BT
Pham, NH
Becker, EA
Harris, M
Weinfurter, JT
O'Connor, SL
Piatak, M
Lifson, JD
Gostick, E
Price, DA
Friedrich, TC
O'Connor, DH
AF Budde, Melisa L.
Greene, Justin M.
Chin, Emily N.
Ericsen, Adam J.
Scarlotta, Matthew
Cain, Brian T.
Pham, Ngoc H.
Becker, Ericka A.
Harris, Max
Weinfurter, Jason T.
O'Connor, Shelby L.
Piatak, Michael, Jr.
Lifson, Jeffrey D.
Gostick, Emma
Price, David A.
Friedrich, Thomas C.
O'Connor, David H.
TI Specific CD8(+) T Cell Responses Correlate with Control of Simian
Immunodeficiency Virus Replication in Mauritian Cynomolgus Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRAL LOAD; DISEASE PROGRESSION; HIV-1 VACCINE; INFECTION; HLA; TYPE-1;
GALAXY; BROAD; AIDS; DNA
AB Specific major histocompatibility complex (MHC) class I alleles are associated with an increased frequency of spontaneous control of human and simian immunodeficiency viruses (HIV and SIV). The mechanism of control is thought to involve MHC class I-restricted CD8(+) T cells, but it is not clear whether particular CD8(+) T cell responses or a broad repertoire of epitope-specific CD8(+) T cell populations (termed T cell breadth) are principally responsible for mediating immunologic control. To test the hypothesis that heterozygous macaques control SIV replication as a function of superior T cell breadth, we infected MHC-homozygous and MHC-heterozygous cynomolgus macaques with the pathogenic virus SIVmac239. As measured by a gamma interferon enzyme-linked immunosorbent spot assay (IFN-gamma ELISPOT) using blood, T cell breadth did not differ significantly between homozygotes and heterozygotes. Surprisingly, macaques that controlled Sly replication, regardless of their MHC zygosity, shared durable T cell responses against similar regions of Nef. While the limited genetic variability in these animals prevents us from making generalizations about the importance of Nef-specific T cell responses in controlling HIV, these results suggest that the T cell-mediated control of virus replication that we observed is more likely the consequence of targeting specificity rather than T cell breadth.
C1 [Greene, Justin M.; Scarlotta, Matthew; Cain, Brian T.; Pham, Ngoc H.; Harris, Max; O'Connor, Shelby L.; O'Connor, David H.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.
[Budde, Melisa L.; Ericsen, Adam J.; Becker, Ericka A.; Weinfurter, Jason T.; O'Connor, Shelby L.; Friedrich, Thomas C.; O'Connor, David H.] Wisconsin Natl Primate Res Ctr, Madison, WI USA.
[Weinfurter, Jason T.; Friedrich, Thomas C.] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA.
[Chin, Emily N.] Univ Wisconsin, Dept Cellular & Mol Biol, Madison, WI USA.
[Piatak, Michael, Jr.; Lifson, Jeffrey D.] Sci Applicat Int Corp Frederick Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
[Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Univ Hosp, Cardiff, S Glam, Wales.
RP O'Connor, DH (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.
EM doconnor@primate.wisc.edu
RI Price, David/C-7876-2013;
OI Price, David/0000-0001-9416-2737; Weinfurter, Jason/0000-0001-8076-2598;
o'connor, david/0000-0003-2139-470X; Friedrich,
Thomas/0000-0001-9831-6895; Ericsen, Adam/0000-0003-4176-8270
FU National Institutes of Health [R01 AI077376, R01 AI08747]; National
Cancer Institute, National Institutes of Health [HHSN261200800001E];
National Center for Research Resources [P51 RR000167]; Research
Facilities Improvement Program [RR15459-01, RR020141-01]
FX This research was supported by National Institutes of Health grants R01
AI077376, awarded to David H. O'Connor, and R01 AI08747, awarded to
Thomas C. Friedrich and David H. O'Connor. This research was also
supported in part with federal funds from the National Cancer Institute,
National Institutes of Health, under contract no. HHSN261200800001E
(Michael Piatak, Jr., and Jeffrey D. Lifson). This work was conducted at
facilities supported in part by grant number P51 RR000167 from the
National Center for Research Resources, a component of the National
Institutes of Health. Additionally, work for the manuscript was
conducted in a facility constructed with support from Research
Facilities Improvement Program grant numbers RR15459-01 and RR020141-01.
NR 31
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U1 1
U2 8
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 JUL
PY 2012
VL 86
IS 14
BP 7596
EP 7604
DI 10.1128/JVI.00716-12
PG 9
WC Virology
SC Virology
GA 969ZO
UT WOS:000306098100013
PM 22573864
ER
PT J
AU Mir, KD
Bosinger, SE
Gasper, M
Ho, O
Else, JG
Brenchley, JM
Kelvin, DJ
Silvestri, G
Hu, SI
Sodora, DL
AF Mir, Kiran D.
Bosinger, Steven E.
Gasper, Melanie
Ho, On
Else, James G.
Brenchley, Jason M.
Kelvin, David J.
Silvestri, Guido
Hu, Shiu-Iok
Sodora, Donald L.
TI Simian Immunodeficiency Virus-Induced Alterations in Monocyte Production
of Tumor Necrosis Factor Alpha Contribute to Reduced Immune Activation
in Sooty Mangabeys
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NONPATHOGENIC SIV INFECTION; T-CELL DEPLETION; HIV-1 INFECTION; RHESUS
MACAQUES; ANTI-TNF; MICROBIAL TRANSLOCATION; INTERFERON RESPONSES;
PATHOGENIC INFECTION; DOWN-REGULATION; NATURAL HOSTS
AB Human immunodeficiency virus type 1 (HIV-1) infection is characterized by persistent viral replication in the context of CD4(+) T cell depletion and elevated immune activation associated with disease progression. In contrast, simian immunodeficiency virus (SIV) infection of African-origin sooty mangabeys (SM) generally does not result in simian AIDS despite high viral loads and therefore affords a unique model in which to study the immunologic contributions to a nonpathogenic lentiviral disease outcome. A key feature of these natural SLY infections is the maintenance of low levels of immune activation during chronic infection. Our goal was to delineate the contribution of monocytes to maintaining low levels of immune activation in Sly-infected SM. Utilizing an ex vivo whole-blood assay, proinflammatory cytokine production was quantified in monocytes in response to multiple Toll-like receptor (TLR) ligands and a specific, significant reduction in the tumor necrosis factor alpha (TNF-alpha) response to lipopolysaccharide (LPS) was observed in SIV-infected SM. In contrast, monocytes from hosts of pathogenic infections (HIV-infected humans and SIV-infected Asian macaques) maintained a robust TNF-alpha response. In Sly-infected SM, monocyte TNF-alpha responses to low levels of LPS could be augmented by the presence of plasma from uninfected control animals. The impact of LPS-induced TNF-alpha production on immune activation was demonstrated in vitro, as TNF-alpha blocking antibodies inhibited downstream CD8(+) T cell activation in a dose-dependent manner. These data demonstrate an association between nonpathogenic SIV infection of SM and a reduced monocyte TNF-alpha response to LPS, and they identify a role for monocytes in contributing to the suppressed chronic immune activation observed in these natural hosts.
C1 [Mir, Kiran D.; Gasper, Melanie; Sodora, Donald L.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Bosinger, Steven E.; Else, James G.; Silvestri, Guido] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Ho, On; Hu, Shiu-Iok] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA.
[Else, James G.; Silvestri, Guido] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Brenchley, Jason M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Kelvin, David J.] Univ Toronto, Dept Immunol, Toronto, ON, Canada.
[Hu, Shiu-Iok] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.
RP Sodora, DL (reprint author), Seattle Biomed Res Inst, 4 Nickerson St, Seattle, WA 98109 USA.
EM don.sodora@seattlebiomed.org
FU NIH [P51-RR00165]; University of Washington Center for AIDS Research
(CFAR) [P30 AI027757, T32AI083203, R56 AI087468, R01 DE017541];
Pendleton Trust
FX Work was supported by the NIH, including grants to the Yerkes Primate
Center (P51-RR00165), the University of Washington Center for AIDS
Research (CFAR) (P30 AI027757), M. Gasper (T32AI083203), and D. Sodora
(R56 AI087468 and R01 DE017541), and by the Pendleton Trust.
NR 53
TC 9
Z9 9
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 JUL
PY 2012
VL 86
IS 14
BP 7605
EP 7615
DI 10.1128/JVI.06813-11
PG 11
WC Virology
SC Virology
GA 969ZO
UT WOS:000306098100014
PM 22553338
ER
PT J
AU Cui, J
Holmes, EC
AF Cui, Jie
Holmes, Edward C.
TI Endogenous Hepadnaviruses in the Genome of the Budgerigar (Melopsittacus
undulatus) and the Evolution of Avian Hepadnaviruses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PHYLOGENIES
AB Endogenous hepadnaviruses (hepatitis B viruses [HBVs]) were recently discovered in the genomes of passerine birds. We mined six additional avian genomes and discovered multiple copies of endogenous HBVs in the budgerigar (order Psittaciformes), designated eBHBV. A phylogenetic analysis reveals that the endogenous hepadnaviruses are more diverse than their exogenous counterparts and that the endogenous and exogenous hepadnaviruses form distinct lineages even when sampled from the same avian order, indicative of multiple genomic integration events.
C1 [Cui, Jie; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM ech15@psu.edu
OI Cui, Jie/0000-0001-8176-9951; Holmes, Edward/0000-0001-9596-3552
NR 13
TC 13
Z9 13
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 JUL
PY 2012
VL 86
IS 14
BP 7688
EP 7691
DI 10.1128/JNI.00769-12
PG 4
WC Virology
SC Virology
GA 969ZO
UT WOS:000306098100021
PM 22553337
ER
PT J
AU Wagster, MV
King, JW
Resnick, SM
Rapp, PR
AF Wagster, Molly V.
King, Jonathan W.
Resnick, Susan M.
Rapp, Peter R.
TI The 87%
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Editorial Material
C1 [Wagster, Molly V.] NIA, Div Neurosci, Bethesda, MD 20892 USA.
[Resnick, Susan M.; Rapp, Peter R.] NIA, Baltimore, MD 21224 USA.
RP Wagster, MV (reprint author), NIA, Div Neurosci, Gateway Bldg,Suite 350,7201 Wisconsin Ave, Bethesda, MD 20892 USA.
EM wagsterm@nia.nih.gov
FU Intramural NIH HHS [ZIA AG000191-16, ZIA AG000198-01]
NR 0
TC 7
Z9 7
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUL
PY 2012
VL 67
IS 7
BP 739
EP 740
DI 10.1093/gerona/gls140
PG 2
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 970PD
UT WOS:000306143700005
PM 22773154
ER
PT J
AU Kosik, KS
Rapp, PR
Raz, N
Small, SA
Sweatt, JD
Tsai, LH
AF Kosik, Kenneth S.
Rapp, Peter R.
Raz, Naftali
Small, Scott A.
Sweatt, J. David
Tsai, Li-Huei
TI Mechanisms of Age-Related Cognitive Change and Targets for Intervention:
Epigenetics
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Cognitive changes; Epigenetics
ID HISTONE DEACETYLASE INHIBITORS; REGULATES MEMORY FORMATION; LONG-TERM
POTENTIATION; EARLY GENE-EXPRESSION; SYNAPTIC PLASTICITY; TRANSGENIC
MICE; IN-VIVO; ACETYLATION; HIPPOCAMPUS; DISEASE
AB Epigenetic regulation of gene expression plays an important role in learning and memory, mediating the influence of experience on critical mechanisms of plasticity. Speakers in the opening session of the Summit reviewed research on epigenetic contributions to age-related cognitive decline and discussed strategies for the development of interventions targeting epigenetic mechanisms. The presentations focused on experience-dependent DNA methylation, the regulatory role of microRNAs, histone deacetylases as potential therapeutic targets, and strategies for exploring epigenetic contributions to the aging of brain and cognition. This session established useful mileposts for gaging progress in this rapidly advancing area of research.
C1 [Rapp, Peter R.] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
[Kosik, Kenneth S.] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
[Kosik, Kenneth S.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
[Raz, Naftali] Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA.
[Raz, Naftali] Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA.
[Small, Scott A.] Columbia Univ, Coll Phys & Surg, Dept Neurol, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA.
[Sweatt, J. David] Univ Alabama Birmingham, Evelyn F McKnight Brain Inst, Dept Neurobiol, Birmingham, W Midlands, England.
[Tsai, Li-Huei] Harvard Univ, Stanley Ctr Psychiat Res, Broad Inst, Cambridge, MA 02138 USA.
[Tsai, Li-Huei] MIT, Howard Hughes Med Inst, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
RP Rapp, PR (reprint author), NIA, Lab Expt Gerontol, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM rappp@mail.nih.gov
OI Sweatt, J. David/0000-0003-3567-485X
FU NIA NIH HHS [P50 AG008702]
NR 48
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U1 1
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUL
PY 2012
VL 67
IS 7
BP 741
EP 746
DI 10.1093/gerona/gls110
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 970PD
UT WOS:000306143700006
PM 22522509
ER
PT J
AU Craft, S
Foster, TC
Landfield, PW
Maier, SF
Resnick, SM
Yaffe, K
AF Craft, Suzanne
Foster, Thomas C.
Landfield, Philip W.
Maier, Steven F.
Resnick, Susan M.
Yaffe, Kristine
TI Session III: Mechanisms of Age-Related Cognitive Change and Targets for
Intervention: Inflammatory, Oxidative, and Metabolic Processes
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Aging; Cognition; Inflammation; Oxidative stress; Metabolism
ID ALZHEIMER-DISEASE; IMPAIRMENT; DECLINE; MEMORY; RISK; HIPPOCAMPUS;
PREVALENCE; DEMENTIA; LATINOS; PROTEIN
AB There is increasing evidence from basic science and human epidemiological studies that inflammation, oxidative stress, and metabolic abnormalities are associated with age-related cognitive decline and impairment. This article summarizes selected research on these topics presented at the Cognitive Aging Summit II. Speakers in this session presented evidence highlighting the roles of these processes and pathways on age-related cognitive decline, pointing to possible targets for intervention in nondemented older adults. Specific areas discussed included age differences in the production of cytokines following injury or infection, mechanisms underlying oxidative stress-induced changes in memory consolidation, insulin effects on brain signaling and memory, and the association between metabolic syndrome and cognitive decline in older adults. These presentations emphasize advances in our understanding of mechanisms and modifiers of age-related cognitive decline and provide insights into potential targets to promote cognitive health in older adults.
C1 [Resnick, Susan M.] NIA, Lab Behav Neurosci, BRC, Baltimore, MD 21224 USA.
[Craft, Suzanne] Univ Washington, Dept Psychiat & Behav Sci, Geriatr Res Educ & Clin Ctr, Seattle, WA 98195 USA.
[Foster, Thomas C.] Univ Florida, Dept Neurosci, Evelyn F & William L McKnight Brain Inst, Gainesville, FL 32610 USA.
[Landfield, Philip W.] Univ Kentucky, Dept Mol & Biomed Pharmacol, Coll Med, Lexington, KY 40506 USA.
[Maier, Steven F.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA.
[Maier, Steven F.] Univ Colorado, Dept Neurosci, Boulder, CO 80309 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Resnick, SM (reprint author), NIA, Lab Behav Neurosci, BRC, Room 4B335,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM susan.resnick@nih.gov
FU Intramural NIH HHS [ZIA AG000191-15]; NCATS NIH HHS [UL1 TR000064]; NIA
NIH HHS [R01 AG014979, R01 AG034605, R37 AG036800]
NR 26
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U1 1
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUL
PY 2012
VL 67
IS 7
BP 754
EP 759
DI 10.1093/gerona/gls112
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 970PD
UT WOS:000306143700008
PM 22570133
ER
PT J
AU Galpern, WR
Corrigan-Curay, J
Lang, AE
Kahn, J
Tagle, D
Barker, RA
Freeman, TB
Goetz, CG
Kieburtz, K
Kim, SYH
Piantadosi, S
Rick, AC
Federoff, HJ
AF Galpern, Wendy R.
Corrigan-Curay, Jacqueline
Lang, Anthony E.
Kahn, Jeffrey
Tagle, Danilo
Barker, Roger A.
Freeman, Thomas B.
Goetz, Christopher G.
Kieburtz, Karl
Kim, Scott Y. H.
Piantadosi, Steven
Rick, Amy Comstock
Federoff, Howard J.
TI Sham neurosurgical procedures in clinical trials for neurodegenerative
diseases: scientific and ethical considerations
SO LANCET NEUROLOGY
LA English
DT Article
ID FETAL NIGRAL TRANSPLANTATION; ADVANCED PARKINSONS-DISEASE; PIGMENT
EPITHELIAL-CELLS; LONG-TERM SURVIVAL; DOUBLE-BLIND; DOPAMINE NEURONS;
NEUROTROPHIC FACTOR; INTRASTRIATAL TRANSPLANTATION; PUTAMINAL IMPLANTS;
PLACEBO SURGERY
AB There have been several recent scientific advances in gene-based and cell-based therapies that might translate into novel therapeutic approaches for neurodegenerative disorders. Such therapies might need to be directly delivered into the CNS, and complex scientific and ethical assessment will be needed to determine whether a sham neurosurgical arm should be included in clinical trials assessing these agents. We have developed a framework of points for investigators to consider when designing trials that involve direct delivery of a therapeutic agent to the CNS. The inclusion of a sham neurosurgical arm will be guided in part by the objectives of the clinical study (preliminary safety, optimisation, and feasibility vs preliminary efficacy vs confirmatory efficacy) and the need to minimise bias and confounds. Throughout the clinical development process, the perspectives of researchers, ethicists, and patients must be considered, and risks should be minimised whenever possible in a manner that is consistent with good trial design.
C1 [Galpern, Wendy R.] NINDS, Off Clin Res, NIH, Bethesda, MD 20892 USA.
[Corrigan-Curay, Jacqueline] NIH, Off Biotechnol Act, Bethesda, MD 20892 USA.
[Lang, Anthony E.] Toronto Western Hosp, Movement Disorders Ctr, Toronto, ON M5T 2S8, Canada.
[Lang, Anthony E.] Edmond J Safra Program Parkinsons Dis, Toronto, ON, Canada.
[Kahn, Jeffrey] Johns Hopkins Univ, Berman Inst Bioeth, Baltimore, MD USA.
[Barker, Roger A.] Univ Cambridge, Dept Neurol, Cambridge, England.
[Freeman, Thomas B.] Univ S Florida, Dept Neurosurg & Brain Repair, Tampa, FL USA.
[Goetz, Christopher G.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Kieburtz, Karl] Univ Rochester, Med Ctr, Ctr Human Expt Therapeut, Rochester, NY 14642 USA.
[Kim, Scott Y. H.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Kim, Scott Y. H.] Univ Michigan, Ctr Bioeth & Social Sci Med, Ann Arbor, MI 48109 USA.
[Piantadosi, Steven] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Rick, Amy Comstock] Parkinsons Act Network, Washington, DC USA.
[Federoff, Howard J.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA.
RP Galpern, WR (reprint author), NINDS, Off Clin Res, NIH, 6001 Execut Blvd,2225, Bethesda, MD 20892 USA.
EM galpernw@ninds.nih.gov
FU Canadian Institutes of Health Research; Dystonia Medical Research
Foundation; Michael J Fox Foundation; National Parkinson Foundation;
Ontario Problem Gambling Research Centre; National Institutes of Health
(NIH); Parkinson's Disease Foundation; Movement Disorder Society;
Medivation; National Eye Institute; NINDS; National Institute on Aging
(NIA); National Institute of Child Health and Human Development;
Neurosearch; Pfizer; NIA; Department of Defense
FX AEL is an adviser for Abbott, Anon Therapeutics, AstraZeneca, Avanir
Pharmaceuticals, Biovail, Boehringer-Ingelheim, Cephalon, Ceregene,
Eisai, GlaxoSmithKline, Lundbeck, Medtronic, Merck Serono, Novartis,
Santhera, Solvay, and Teva; has received grants from Canadian Institutes
of Health Research, Dystonia Medical Research Foundation, Michael J Fox
Foundation, National Parkinson Foundation, and Ontario Problem Gambling
Research Centre; has received publishing royalties from Saunders,
Wiley-Blackwell, Johns Hopkins Press, and Cambridge University Press;
and has served as an expert witness in cases related to the welding
industry. TBF is a consultant for SanBio, Spine Guard, Synthes Spine,
Medtronic, Alnylam Pharmaceuticals, and Signus; Medical Director for
Saneron CCEL Therapeutics; scientific advisory board member for Neural
Stem; Founding Scientist, President, Chairman of the Board for Ciracell;
receives fees for consulting for all the aforementioned companies; holds
stock options for NeuralStem, Saneron, and Ciracell; has a licensing
agreement with Medtronic Neuromodulation; and holds patents and
provisional patents, numbers 7896889,7981120,7963980,8012159
B2,7699854,7416885, and 6528245. CGG receives honoraria for consulting
and advisory board membership from Addex Pharma, Asubio, Biovail
Technologies, Boston Scientific, Cleveland Medical Devices, Decision
Resources, Dixon Group, ICON Clinical Research, Impax Pharmaceuticals,
Ingenix (i3 Research), Intec Pharmaceuticals, Kenes International, Motac
Neurosciences, Oxford Biomedica, United Bioscience Corporation, and UCB;
grants or research funding from the National Institutes of Health (NIH)
and Michael J Fox Foundation; honoraria from the Movement Disorder
Society, American Academy of Neurology, University of Pennsylvania,
Washington University, and University of Michigan; and royalties from
Oxford University Press, Elsevier Publishers, Wolters Kluwer Health, and
Lippincott, Wilkins and Williams. CGG directs the Rush Parkinson's
Disease Research Center, which receives support from the Parkinson's
Disease Foundation, and directs the translation programme for the
MDS-UPDRS (Movement Disorder Society unified Parkinson's disease rating
scale) and UDysRS (unified dyskinesia rating scale), for which he
receives funds from the Movement Disorder Society. KK is a consultant
for the National Institute of Neurological Disorders and Stroke (NINDS),
The US Food and Drug Administration, The US Veteran's Administration,
Abbott, Acorda, Aptiv, Biogen Idec, Biotie, Biovail, Boehringer
Ingelheim, Ceregene, Civitas, Clintrex, Cynapsus, EMD Merck Serono,
Genzyme, Impax, Intec, Ipsen, Isis, Knopp, Lilly, Link Medicine,
Lundbeck, LZ Therapeutics, Merz, Novartis, Orion, Otsuka, Pharm2B,
Phytopharm, Schering-Plough, Siena Biotech, Synosia, Solvay, Synagile,
Teva, UCB Pharma, Vaccinex, Vectura, and Xenoport; receives grants or
research support from Medivation, Michael J Fox Foundation, National Eye
Institute, NINDS, National Institute on Aging (NIA), National Institute
of Child Health and Human Development, Neurosearch, and Pfizer; and does
legal consulting for Pfizer, Thompson Hine, and welding rod litigation
defendants. HJF is founder, equity participant, and scientific advisor
for MedGenesis; founder and equity participant of Socratec; board member
for the American Federation for Aging Research and Biomedical Research
and Education Foundation; adviser for Oxford University Parkinson's
Disease Center; and has received grants from NINDS, NIA, and the
Department of Defense.; All other authors declare that they have no
conflicts of interest.; The National Institutes of Health (NIH) convened
a meeting of international experts to discuss the complex issues
surrounding the decision to include sham neurosurgical procedures in
clinical trials at a workshop entitled Sham Neurological Procedures in
Clinical Trials for Neurodegenerative Diseases: Scientific and Ethical
Considerations (June 30 July 1,2010). The deliberations at this meeting
were used in the development of this manuscript, and the authors
acknowledge the contributions of the meeting participants. Authors were
selected by the Organising Committee (WRG, JC-C, AEL, DT, and HJF) to
represent the areas of expertise and opinions represented at the
meeting. Authors include the members of the Organising Committee and a
subset of meeting participants with expertise in clinical trials,
neurology, neurosurgery, basic science research, ethics, and patient
advocacy. A participant roster, slide presentations, written public
comments, and a webcast are available online. The meeting was funded by
the NIH. We also thank the following staff from the Office of
Biotechnology Activities, NIH, for their contributions in bringing
together this symposium: R Jambou, E Rosenthal, M O'Reilly, M
Montgomery, and L Gargiulo. We also thank Perry Cohen for his
contributions in the development of this symposium. The points described
should not be interpreted to represent a consensus statement or the
opinions of any individual or the NIH.
NR 54
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U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
EI 1474-4465
J9 LANCET NEUROL
JI Lancet Neurol.
PD JUL
PY 2012
VL 11
IS 7
BP 643
EP 650
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 969YN
UT WOS:000306095400011
PM 22710757
ER
PT J
AU Malhotra, SV
Brown, HC
AF Malhotra, Sanjay V.
Brown, Herbert C.
TI Highly Efficient One Step Synthesis of Primary Amines from
B-Chlorodialkylboranes
SO LETTERS IN ORGANIC CHEMISTRY
LA English
DT Article
DE Amination; B-Chlorodialkylboranes; chiral amine; organoborane
ID CONVENIENT SYNTHESIS; ORGANOBORANES; HYDROBORATION; OLEFINS; ACID
AB A convenient and simple method for synthesis of primary amines has been developed by direct amination of B-Chlorodialkylboranes. This general procedure has been applied to synthesize acyclic, cyclic, hindered and chiral amines in very high yields using both hydroxylamine-O-sulfonic acid and monochloroamine as reagents.
C1 Purdue Univ, HC Brown Lab Chem, W Lafayette, IN 47906 USA.
Purdue Univ, RW Wetherill Lab Chem, W Lafayette, IN 47906 USA.
RP Malhotra, SV (reprint author), SAIC Frederick Inc, NCI, Lab Synthet Chem, 1050 Boyles St, Frederick, MD 21702 USA.
EM malhotrasa@mail.nih.gov
FU United States Army Research office
FX Financial support from the United States Army Research office is
gratefully acknowledged.
NR 10
TC 0
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U1 2
U2 21
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-1786
J9 LETT ORG CHEM
JI Lett. Org. Chem.
PD JUL
PY 2012
VL 9
IS 6
BP 383
EP 385
PG 3
WC Chemistry, Organic
SC Chemistry
GA 970ZS
UT WOS:000306171900001
ER
PT J
AU Consonni, D
Sindaco, R
Agnello, L
Caporaso, NE
Landi, MT
Pesatori, AC
Bertazzi, PA
AF Consonni, D.
Sindaco, Raffaella
Agnello, L.
Caporaso, N. E.
Landi, Maria Teresa
Pesatori, Angela Cecilia
Bertazzi, P. A.
TI Plasma levels of dioxins, furans, non-ortho-PCBs, and TEQs in the Seveso
population 17 years after the accident
SO MEDICINA DEL LAVORO
LA English
DT Article
DE Environmental pollution; dioxin; PCDD; PCDF; PCB; TEQ
ID TOXIC EQUIVALENCY FACTORS; DIBENZO-P-DIOXIN; OCCUPATIONALLY EXPOSED
PERSONS; MUNICIPAL WASTE INCINERATORS; SERUM SAMPLES; US POPULATION;
HUMAN BLOOD; FOLLOW-UP; PCDD/F; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN
AB Background: The Seveso accident (Italy) in 1976 caused the contamination of a large population by 2,3,7,8-tetrachlorodibenzo-para-dioxin (2,3,7,8-TCDD). The contaminated territory was divided into three zones: A (very high contamination), B (high contamination), and R (low contamination). We report here the plasma concentrations of seven polychlorinated dibenzo-para-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), four non-ortho-polychlorinated biphenyls PCBs (nPCBs), and Toxic Equivalencies (TEQs) in a sample of residents in the most polluted zones A and B and in a reference non-contaminated zone. Methods: From December 1992 to March 1994, 62 individuals were randomly selected from the population living in zone A (No. =7) and B (No. =55). A sample of 59 subjects living in a surrounding non-contaminated area (non-ABR), frequency-matched by gender, age, and smoking history, was used as reference. All subjects were administered a questionnaire surveying demographic, lifestyle, medical history, and accident-related factors. We assayed plasma PCDD, PCDF, and nPCB concentrations by high-resolution gas chromatography/high resolution mass spectrometric (HRGC/HRMS) analysis, with results reported as pg/g of lipid, or parts per trillion (ppt). We calculated TEQs using the WHO 2005 Toxic Equivalency Factors (TEFs). Results: We found elevated median levels of 2,3,7,8-TCDD in plasma samples of subjects living in zone A (73.3 ppt) and zone B (12.4 ppt), compared with residents in the reference zone (5.5 ppt). In analyses adjusted for gender, age, smoking, and body mass index (BMI), none of the other congeners showed levels higher than reference in the contaminated zones. Compared with men, women showed higher levels (113%) of 2,3,7,8-TCDD and a slight elevation (17%) of TEQ for the other congeners. Age was strongly positively associated with most congener levels; TEQs for PCDDs, PCDFs, and nPCBs showed respectively 12%, 24%, and 41% increases for every 10 years of age. Current smokers had lower (from -37% to -67%) TEQ levels than subjects who had never smoked. BMI was negatively associated with levels of a few congeners, but with no impact on TEQ values. Conclusions: The Seveso accident caused a severe exposure of the population to 2,3,7,8- TCDD only. None of the other congeners analyzed showed variation across zones. Age showed a strong positive association with TEQs for all classes of compounds ( PCDDs, PCDFs, and nPCBs).
C1 [Consonni, D.; Sindaco, Raffaella] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Epidemiol Unit, Dept Prevent Med, I-20122 Milan, Italy.
[Agnello, L.; Pesatori, Angela Cecilia; Bertazzi, P. A.] Univ Milan, Dept Occupat & Environm Med, Milan, Italy.
[Caporaso, N. E.; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Consonni, D (reprint author), Fdn IRCCS Ca Granda Osped Maggiore Policlin, Epidemiol Unit, Dept Prevent Med, Via San Barnaba 8, I-20122 Milan, Italy.
EM dario.consonni@unimi.it
RI bertazzi, pietro alberto/D-5039-2017;
OI bertazzi, pietro alberto/0000-0003-3475-2449; pesatori,
angela/0000-0002-0261-3252
FU Lombardy Region (Environmental Epidemiology Program)
FX This work was partially funded by the Lombardy Region (Environmental
Epidemiology Program).
NR 32
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U1 3
U2 17
PU MATTIOLI 1885
PI FIDENZA
PA VIA CODURO 1-B, FIDENZA, 43046 PR, ITALY
SN 0025-7818
J9 MED LAV
JI Med. Lav.
PD JUL-AUG
PY 2012
VL 103
IS 4
BP 259
EP 267
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 971SI
UT WOS:000306223700003
PM 22880488
ER
PT J
AU Kortum, RL
Sommers, CL
Pinski, JM
Alexander, CP
Merrill, RK
Li, WM
Love, PE
Samelson, LE
AF Kortum, Robert L.
Sommers, Connie L.
Pinski, John M.
Alexander, Clayton P.
Merrill, Robert K.
Li, Wenmei
Love, Paul E.
Samelson, Lawrence E.
TI Deconstructing Ras Signaling in the Thymus
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID T-CELL DEVELOPMENT; NEGATIVE SELECTION; THYMOCYTE DEVELOPMENT; DELETION
REVEALS; TRANSGENIC MICE; ACTIVATION; DIFFERENTIATION; RECEPTOR; LAT;
TOLERANCE
AB Thymocytes must transit at least two distinct developmental checkpoints, governed by signals that emanate from either the pre-T cell receptor (pre-TCR) or the TCR to the small G protein Ras before emerging as functional T lymphocytes. Recent studies have shown a role for the Ras guanine exchange factor (RasGEF) Sos1 at the pre-TCR checkpoint. At the second checkpoint, the quality of signaling through the TCR is interrogated to ensure the production of an appropriate T cell repertoire. Although Ras-GRP1 is the only confirmed RasGEF required at the TCR checkpoint, current models suggest that the intensity and character of Ras activation, facilitated by both Sos and RasGRP1, will govern the boundary between survival (positive selection) and death (negative selection) at this stage. Using mouse models, we have assessed the independent and combined roles for the RasGEFs Sos1, Sos2, and RasGRP1 during thymocyte development. Although Sos1 was the dominant RasGEF at the pre-TCR checkpoint, combined Sos1/RasGRP1 deletion was required to effectively block development at this stage. Conversely, while RasGRP1 deletion efficiently blocked positive selection, combined RasGRP1/Sosl deletion was required to block negative selection. This functional redundancy in RasGEFs during negative selection may act as a failsafe mechanism ensuring appropriate central tolerance.
C1 [Kortum, Robert L.; Sommers, Connie L.; Pinski, John M.; Alexander, Clayton P.; Merrill, Robert K.; Li, Wenmei; Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
[Love, Paul E.] NIH, Lab Mammalian Genes & Dev, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA.
EM samelson@helix.nih.gov
FU NIH, CCR, NCI; Eunice Kennedy Shriver National Institute of Child Health
and Human Development; PRAT, NIGMS, NIH
FX This research was supported by the Intramural Research Program of the
NIH, CCR, NCI, and the Eunice Kennedy Shriver National Institute of
Child Health and Human Development. R.L.K. received additional support
from a PRAT Research Fellowship, NIGMS, NIH.
NR 26
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U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUL
PY 2012
VL 32
IS 14
BP 2748
EP 2759
DI 10.1128/MCB.00317-12
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 972AR
UT WOS:000306249400010
PM 22586275
ER
PT J
AU Reis, J
Cohen, LG
Pearl, PL
Fritsch, B
Jung, NH
Dustin, I
Theodore, WH
AF Reis, Janine
Cohen, Leonardo G.
Pearl, Phillip L.
Fritsch, Brita
Jung, Nikolai H.
Dustin, Irene
Theodore, William H.
TI GABA(B)-ergic motor cortex dysfunction in SSADH deficiency
SO NEUROLOGY
LA English
DT Article
ID TRANSCRANIAL MAGNETIC STIMULATION; SEMIALDEHYDE
DEHYDROGENASE-DEFICIENCY; GAMMA-HYDROXYBUTYRIC ACID; GABA(A) RECEPTOR
MUTATION; CEREBRAL-CORTEX; SILENT PERIOD; 4-HYDROXYBUTYRIC ACIDURIA;
CONSCIOUS HUMANS; INHIBITION; BINDING
AB Objective: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder of GABA degradation leading to elevations in brain GABA and gamma-hydroxybutyric acid (GHB). The effect of chronically elevated GABA and GHB on cortical excitability is unknown. We hypothesized that use-dependent downregulation of GABA receptor expression would promote cortical disinhibition rather than inhibition, predominantly via presynaptic GABAergic mechanisms.
Methods: We quantified the magnitude of excitation and inhibition in primary motor cortex (M1) in patients with SSADH deficiency, their parents (obligate heterozygotes), age-matched healthy young controls, and healthy adults using single and paired pulse transcranial magnetic stimulation (TMS).
Results: Long interval intracortical inhibition was significantly reduced and the cortical silent period was significantly shortened in patients with SSADH deficiency compared to heterozygous parents and control groups.
Conclusions: Since long interval intracortical inhibition and cortical silent period are thought to reflect GABA(B) receptor-mediated inhibitory circuits, our results point to a particularly GABA(B) ergic motor cortex dysfunction in patients with SSADH deficiency. This human phenotype is consistent with the proposed mechanism of use-dependent downregulation of postsynaptic GABA(B) receptors in SSADH deficiency animal models. Additionally, the results suggest autoinhibition of GABAergic neurons. This first demonstration of altered GABA(B)-ergic function in patients with SSADH deficiency may help to explain clinical features of the disease, and suggest pathophysiologic mechanisms in other neurotransmitter-related disorders. Neurology (R) 2012; 79:47-54
C1 [Reis, Janine; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
[Dustin, Irene; Theodore, William H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
[Reis, Janine; Fritsch, Brita] Univ Freiburg, Dept Neurol, Freiburg, Germany.
[Jung, Nikolai H.] Univ Freiburg, Dept Pediat, Freiburg, Germany.
[Pearl, Phillip L.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
RP Reis, J (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM janine.reis@uniklinik-freiburg.de
OI Fritsch, Brita/0000-0003-4884-9049
FU Alexander von Humboldt Foundation Germany; Intramural Research Program,
NINDS, NIH
FX J. Reis received personal funding (postdoctoral fellowship) from the
Alexander von Humboldt Foundation Germany and the Intramural Research
Program, NINDS, NIH. L. Cohen received funding from the Intramural
Research Program, NINDS, NIH. P. Pearl, B. Fritsch, and N. Jung report
no disclosures. I. Dustin received funding from the Intramural Research
Program, NINDS, NIH. W. Theodore received funding from the Intramural
Research Program, NINDS, NIH, serves as the Co-Editor in Chief of
Epilepsy Research, and holds stock in General Electric. Go to
Neurology.org for full disclosures.
NR 40
TC 11
Z9 11
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUL
PY 2012
VL 79
IS 1
BP 47
EP 54
DI 10.1212/WNL.0b013e31825dcf71
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 971BE
UT WOS:000306176000013
PM 22722631
ER
PT J
AU Weaver, FM
Follett, KA
Stern, M
Luo, P
Harris, CL
Hur, K
Marks, WJ
Rothlind, J
Sagher, O
Moy, C
Pahwa, R
Burchiel, K
Hogarth, P
Lai, EC
Duda, JE
Holloway, K
Samii, A
Horn, S
Bronstein, JM
Stoner, G
Starr, PA
Simpson, R
Baltuch, G
De Salles, A
Huang, GD
Reda, DJ
AF Weaver, Frances M.
Follett, Kenneth A.
Stern, Matthew
Luo, Ping
Harris, Crystal L.
Hur, Kwan
Marks, William J., Jr.
Rothlind, Johannes
Sagher, Oren
Moy, Claudia
Pahwa, Rajesh
Burchiel, Kim
Hogarth, Penelope
Lai, Eugene C.
Duda, John E.
Holloway, Kathryn
Samii, Ali
Horn, Stacy
Bronstein, Jeff M.
Stoner, Gatana
Starr, Philip A.
Simpson, Richard
Baltuch, Gordon
De Salles, Antonio
Huang, Grant D.
Reda, Domenic J.
CA CSP 468 Study Grp
TI Randomized trial of deep brain stimulation for Parkinson disease
Thirty-six-month outcomes
SO NEUROLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; 5-YEAR FOLLOW-UP; PALLIDAL STIMULATION;
GLOBUS-PALLIDUS; SUBTHALAMIC NUCLEUS; MOTOR FLUCTUATIONS; MEDICAL
THERAPY; MULTICENTER; VALIDATION; EFFICACY
AB Objectives: Our objective was to compare long-term outcomes of deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) for patients with Parkinson disease (PD) in a multicenter randomized controlled trial.
Methods: Patients randomly assigned to GPi (n = 89) or STN DBS (n = 70) were followed for 36 months. The primary outcome was motor function on stimulation/off medication using the Unified Parkinson's Disease Rating Scale motor subscale. Secondary outcomes included quality of life and neurocognitive function.
Results: Motor function improved between baseline and 36 months for GPi (41.1 to 27.1; 95% confidence interval [CI] -16.4 to -10.8; p < 0.001) and STN (42.5 to 29.7; 95% CI -15.8 to -9.4; p < 0.001); improvements were similar between targets and stable over time (p = 0.59). Health-related quality of life improved at 6 months on all subscales (all p values significant), but improvement diminished over time. Mattis Dementia Rating Scale scores declined faster for STN than GPi patients (p = 0.01); other neurocognitive measures showed gradual decline overall.
Conclusions: The beneficial effect of DBS on motor function was stable and comparable by target over 36 months. Slight declines in quality of life following initial gains and gradual decline in neurocognitive function likely reflect underlying disease progression and highlight the importance of nonmotor symptoms in determining quality of life.
Classification of Evidence: This study provides Class III evidence that improvement of motor symptoms of PD by DBS remains stable over 3 years and does not differ by surgical target. Neurology (R) 2012; 79:55-65
C1 [Weaver, Frances M.] Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA.
[Weaver, Frances M.] Loyola Univ Stritch Sch Med, Maywood, IL USA.
[Follett, Kenneth A.] Iowa City VA Med Ctr, Iowa City, IA USA.
[Follett, Kenneth A.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Stern, Matthew; Horn, Stacy; Baltuch, Gordon] Univ Penn Hlth Syst, Philadelphia, PA USA.
[Luo, Ping; Hur, Kwan; Reda, Domenic J.] Hines VA Hosp, Cooperat Studies Coordinating Ctr, Hines, IL USA.
[Harris, Crystal L.] VA Cooperat Studies Program, Albuquerque, NM USA.
[Marks, William J., Jr.; Rothlind, Johannes; Starr, Philip A.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Marks, William J., Jr.; Rothlind, Johannes; Starr, Philip A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Sagher, Oren] Univ Michigan Med Ctr, Ann Arbor, MI USA.
[Moy, Claudia] NINDS, Rockville, MD USA.
[Pahwa, Rajesh] Univ Kansas Med Ctr, Kansas City, KS USA.
[Burchiel, Kim] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Burchiel, Kim; Hogarth, Penelope] Portland VA Med Ctr, Portland, OR USA.
[Lai, Eugene C.; Simpson, Richard] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Lai, Eugene C.; Simpson, Richard] Methodist Neurol Inst, Houston, TX USA.
[Stern, Matthew; Duda, John E.; Baltuch, Gordon] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Holloway, Kathryn] Richmond VA Med Ctr, Richmond, VA USA.
[Samii, Ali] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Bronstein, Jeff M.; De Salles, Antonio] W Los Angeles VA Med Ctr, Los Angeles, CA USA.
[Bronstein, Jeff M.; De Salles, Antonio] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Stoner, Gatana] Univ Iowa Hlth Care, Iowa City, IA USA.
[Huang, Grant D.] US Dept Vet Affairs, Cooperat Studies Program, Cent Off, Washington, DC USA.
RP Weaver, FM (reprint author), Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA.
EM Frances.Weaver@va.gov
FU Medtronic Neurological, Inc.; Cooperative Studies Program, Department of
Veterans Affairs Office of Research and Development; NINDS; Teva; Ipsen;
Medtronic; Adamas Pharma; Schering-Plough; GSK; GE Healthcare; EMD
Serono; Boehringer Ingelheim; St Jude Medical; Impax Pharma; Novartis;
Biogen; Xenoport; Solvay; Eisai; NIH/NINDS; NPF; Allon; Acadia; Valeant;
Kyowa; Johnson Johnson; Schering; Santhera
FX Medtronic Neurological, Inc. provided financial support. The Cooperative
Studies Program, Department of Veterans Affairs Office of Research and
Development, provided financial support and contributed to the study
design. NINDS provided financial support and contributed to the design
of the study.; F. Weaver reports no disclosures relevant to the
manuscript. K. Follett reports serving as a consultant for Medtronic
Neurological (safety monitoring panel). M. Stern reports receiving
consulting fees from Teva, Ipsen, Medtronic, Adamas Pharma,
Schering-Plough, payment for speakers bureaus from Teva, Novartis, and
the Movement Disorder Society, payment for development of educational
presentations from Teva and Medtronic. P. Luo, C. Harris, and K. Hur
report no disclosures relevant to the manuscript. W. Marks reports
receiving consulting fees from Medtronic and lecture fees from
Medtronic. J. Rothlind, O. Sagher, and C. Moy report no disclosures
relevant to the manuscript. R. Pahwa reports receiving consulting fees
from Teva, GSK, GE Healthcare, EMD Serono, Boehringer Ingelheim,
Medtronic, St Jude Medical, Impax Pharma, Novartis, Adamas Pharma, and
Biogen, providing expert testimony, grants/grants pending from Teva,
Novartis, Xenoport, Impax Pharma, Boehringer Ingelheim, Solvay, EMD
Serono, Eisai, NIH/NINDS, NPF, Allon, Acadia, GSK, Valeant, Kyowa,
Johnson & Johnson, Santhera, and Schering, payment for lectures from
Teva, GSK, and Medtronic, royalties from Oxford Press and Informa
Healthcare, payment for development of educational presentations from
Medscape, Co-Editor in Chief International Journal of Neuroscience, and
DSMB member (Ceregene). K. Burchiel reports grants/grants pending from
Medtronic, and owning stock/stock options in Medtronic. P. Hogarth, E.
Lai, and J. Duda report no disclosures relevant to the manuscript. K.
Holloway reports receiving consulting fees and grant/grants pending from
Medtronic. A. Samii reports receiving payment for lectures from Teva,
Ipsen, and Boehringer Ingelheim. S. Horn, J. Bronstein, and G. Stoner
report no disclosures relevant to the manuscript. P. Starr reports
receiving consulting fees from Medtronic. R. Simpson reports
participating on advisory board and receiving consulting fees from
Medtronic, and providing expert testimony. G. Baltuch, A. DeSalles, G.
Huang, and D. Reda report no disclosures relevant to the manuscript. Go
to Neurology.org for full disclosures.
NR 30
TC 114
Z9 118
U1 4
U2 24
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUL
PY 2012
VL 79
IS 1
BP 55
EP 65
DI 10.1212/WNL.0b013e31825dcdc1
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA 971BE
UT WOS:000306176000014
PM 22722632
ER
PT J
AU Pierson, TM
Adams, DA
Markello, T
Golas, G
Yang, S
Sincan, M
Simeonov, DR
Fajardo, KF
Hansen, NF
Cherukuri, PF
Cruz, P
Teer, JK
Mullikin, JC
Gahl, WA
Tifft, CJ
AF Pierson, Tyler Mark
Adams, David A.
Markello, Thomas
Golas, Gretchen
Yang, Sandra
Sincan, Murat
Simeonov, Dimitre R.
Fajardo, Karin Fuentes
Hansen, Nancy F.
Cherukuri, Praveen F.
Cruz, Pedro
Teer, Jamie K.
Mullikin, James C.
Gahl, William A.
Tifft, Cynthia J.
CA NISC Comparative Sequencing Progra
Boerkoel, CF
TI Exome sequencing as a diagnostic tool in a case of undiagnosed
juvenile-onset GM(1)-angliosidosis
SO NEUROLOGY
LA English
DT Article
ID BETA-GALACTOSIDASE DEFICIENCY; GENE-MUTATIONS; GANGLIOSIDOSIS
AB Objective: To utilize high-throughput sequencing to determine the etiology of juvenile-onset neurodegeneration in a 19-year-old woman with progressive motor and cognitive decline.
Methods: Exome sequencing identified an initial list of 133,555 variants in the proband's family, which were filtered using segregation analysis, presence in dbSNP, and an empirically derived gene exclusion list. The filtered list comprised 52 genes: 21 homozygous variants and 31 compound heterozygous variants. These variants were subsequently scrutinized with predicted pathogenicity programs and for association with appropriate clinical syndromes.
Results: Exome sequencing data identified 2 GLB1 variants (c. 602G>A, p. R201H; c. 785G>T, p. G262V). beta-Galactosidase enzyme analysis prior to our evaluation was reported as normal; however, subsequent testing was consistent with juvenile-onset GM(1)-gangliosidosis. Urine oligosaccharide analysis was positive for multiple oligosaccharides with terminal galactose residues.
Conclusions: We describe a patient with juvenile-onset neurodegeneration that had eluded diagnosis for over a decade. GM(1)-gangliosidosis had previously been excluded from consideration, but was subsequently identified as the correct diagnosis using exome sequencing. Exome sequencing can evaluate genes not previously associated with neurodegeneration, as well as most known neurodegeneration-associated genes. Our results demonstrate the utility of "agnostic" exome sequencing to evaluate patients with undiagnosed disorders, without prejudice from prior testing results. Neurology (R) 2012;79:123-126
C1 [Pierson, Tyler Mark; Adams, David A.; Markello, Thomas; Fajardo, Karin Fuentes; Gahl, William A.; Tifft, Cynthia J.; Boerkoel, CF] NIH Off Rare Dis Res, NIH Undiagnosed Dis Program, Bethesda, MD USA.
[Pierson, Tyler Mark] NINDS, Neurogenet Branch, NIH, Bethesda, MD USA.
[Adams, David A.; Sincan, Murat; Simeonov, Dimitre R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD USA.
[Markello, Thomas; Golas, Gretchen; Yang, Sandra; Gahl, William A.; Tifft, Cynthia J.] NHGRI, Off Clin Director, NIH, Bethesda, MD USA.
[Mullikin, James C.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD USA.
[Hansen, Nancy F.; Cherukuri, Praveen F.; Cruz, Pedro; Mullikin, James C.] NHGRI, Comparat Genom Unit, Genome Technol Branch, NIH, Bethesda, MD USA.
[Teer, Jamie K.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD USA.
[Golas, Gretchen] NIH, Intramural Program, Off Rare Dis Res, Off Director, Bethesda, MD 20892 USA.
RP Pierson, TM (reprint author), NIH Off Rare Dis Res, NIH Undiagnosed Dis Program, Bethesda, MD USA.
EM Tyler.Pierson@cshs.org
FU NIH Undiagnosed Diseases Program; Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health
FX T.M.P., D.A., T.M., K.F.F., C.F.B., and C.T. were supported by the NIH
Undiagnosed Diseases Program and T.M., G.G., S.Y., M.S., D.R.S., N.F.H.,
P.F.C., P.C., J.K.T., J.C.M., and W.A.G. were supported by the
Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health.
NR 10
TC 13
Z9 15
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 JUL
PY 2012
VL 79
IS 2
BP 123
EP 126
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 971XV
UT WOS:000306241000008
PM 22675082
ER
PT J
AU Sailer, A
Scholz, SW
Gibbs, JR
Tucci, A
Johnson, JO
Wood, NW
Plagnol, V
Hummerich, H
Ding, JH
Hernandez, D
Hardy, J
Federoff, HJ
Traynor, BJ
Singleton, AB
Houlden, H
AF Sailer, Anna
Scholz, Sonja W.
Gibbs, J. Raphael
Tucci, Arianna
Johnson, Janel O.
Wood, Nicholas W.
Plagnol, Vincent
Hummerich, Holger
Ding, Jinhui
Hernandez, Dena
Hardy, John
Federoff, Howard J.
Traynor, Bryan J.
Singleton, Andrew B.
Houlden, Henry
TI Exome sequencing in an SCA14 family demonstrates its utility in
diagnosing heterogeneous diseases
SO NEUROLOGY
LA English
DT Article
ID DOMINANT CEREBELLAR ATAXIAS; CAG REPEAT; POLYGLUTAMINE EXPANSIONS;
TRINUCLEOTIDE REPEAT; MUTATIONS; REVEALS; PROTEIN; REGION; GENE
AB Objective: Genetic heterogeneity is common in many neurologic disorders. This is particularly true for the hereditary ataxias where at least 36 disease genes or loci have been described for spinocerebellar ataxia and over 100 genes for neurologic disorders that present primarily with ataxia. Traditional genetic testing of a large number of candidate genes delays diagnosis and is expensive. In contrast, recently developed genomic techniques, such as exome sequencing that targets only the coding portion of the genome, offer an alternative strategy to rapidly sequence all genes in a comprehensive manner. Here we describe the use of exome sequencing to investigate a large, 5-generational British kindred with an autosomal dominant, progressive cerebellar ataxia in which conventional genetic testing had not revealed a causal etiology.
Methods: Twenty family members were seen and examined; 2 affected individuals were clinically investigated in detail without a genetic or acquired cause being identified. Exome sequencing was performed in one patient where coverage was comprehensive across the known ataxia genes, excluding the known repeat loci which should be examined using conventional analysis.
Results: A novel p.Arg26Gly change in the PRKCG gene, mutated in SCA14, was identified. This variant was confirmed using Sanger sequencing and showed segregation with disease in the entire family.
Conclusions: This work demonstrates the utility of exome sequencing to rapidly screen heterogeneous genetic disorders such as the ataxias. Exome sequencing is more comprehensive, faster, and significantly cheaper than conventional Sanger sequencing, and thus represents a superior diagnostic screening tool in clinical practice. Neurology (R) 2012;79:127-131
C1 [Sailer, Anna; Gibbs, J. Raphael; Wood, Nicholas W.; Plagnol, Vincent; Hernandez, Dena; Hardy, John; Houlden, Henry] UCL, Inst Neurol, Dept Mol Neurosci, London, England.
[Sailer, Anna; Gibbs, J. Raphael; Wood, Nicholas W.; Plagnol, Vincent; Hernandez, Dena; Hardy, John; Houlden, Henry] UCL, Inst Neurol, Reta Lila Weston Labs, London, England.
[Scholz, Sonja W.; Federoff, Howard J.] Georgetown Univ, Dept Neurol, Washington, DC USA.
[Scholz, Sonja W.; Gibbs, J. Raphael; Tucci, Arianna; Johnson, Janel O.; Ding, Jinhui; Hernandez, Dena; Traynor, Bryan J.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Houlden, Henry] UCL, MRC, Prion Unit, Dept Neurodegenerat Dis,Inst Neurol, London, England.
[Traynor, Bryan J.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA.
RP Houlden, H (reprint author), UCL, Inst Neurol, Dept Mol Neurosci, London, England.
EM h.houlden@ion.ucl.ac.uk
RI Hardy, John/C-2451-2009; Plagnol, Vincent/A-5667-2011; Traynor,
Bryan/G-5690-2010; Houlden, Henry/C-1532-2008; Singleton,
Andrew/C-3010-2009; Wood, Nicholas/C-2505-2009
OI Houlden, Henry/0000-0002-2866-7777; Wood, Nicholas/0000-0002-9500-3348
FU Medical Research Council; MSA Trust; Ataxia UK; Wellcome Trust;
Department of Health's NIHR Biomedical Research Centres; Intramural
Research Program of the National Institute on Aging, NIH; Department of
Health and Human Services [Z01 AG000958-08]
FX Supported in part by the Intramural Research Program of the National
Institute on Aging, NIH, Department of Health and Human Services;
project number: Z01 AG000958-08.; The authors thank the patients and
family who supported this work. They also thank the following for grant
support: The Medical Research Council (H.H. and N.W.), The MSA Trust
(A.S.), Ataxia UK (H.H.), and The Wellcome Trust. This work was
undertaken at UCLH/UCL, which received a proportion of funding from the
Department of Health's NIHR Biomedical Research Centres funding scheme.
NR 20
TC 23
Z9 24
U1 0
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 JUL
PY 2012
VL 79
IS 2
BP 127
EP 131
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 971XV
UT WOS:000306241000009
PM 22675081
ER
PT J
AU Landoure, G
Sullivan, JM
Johnson, JO
Munns, CH
Shi, YJ
Diallo, O
Gibbs, JR
Gaudet, R
Ludlow, CL
Fischbeck, KH
Traynor, BJ
Burnett, BG
Sumner, CJ
AF Landoure, Guida
Sullivan, Jeremy M.
Johnson, Janel O.
Munns, Clare H.
Shi, Yijun
Diallo, Oumarou
Gibbs, J. Raphael
Gaudet, Rachelle
Ludlow, Christy L.
Fischbeck, Kenneth H.
Traynor, Bryan J.
Burnett, Barrington G.
Sumner, Charlotte J.
TI EXOME SEQUENCING IDENTIFIES A NOVEL TRPV4 MUTATION IN A CMT2C FAMILY
SO NEUROLOGY
LA English
DT Editorial Material
ID GENE
C1 [Sullivan, Jeremy M.; Sumner, Charlotte J.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Landoure, Guida; Shi, Yijun; Diallo, Oumarou; Fischbeck, Kenneth H.; Burnett, Barrington G.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Johnson, Janel O.; Gibbs, J. Raphael; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Landoure, Guida] UCL, Dept Med, London, England.
[Landoure, Guida] UCL, Dept Neurosci, London, England.
[Johnson, Janel O.; Gibbs, J. Raphael] UCL, Dept Mol Neurosci, London, England.
[Johnson, Janel O.; Gibbs, J. Raphael] UCL, Reta Lila Weston Labs, Inst Neurol, London, England.
[Landoure, Guida] Univ Bamako, Ctr Hosp Univ Point G, Serv Neurol, Bamako, Mali.
[Munns, Clare H.; Sumner, Charlotte J.] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD 21218 USA.
[Munns, Clare H.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21218 USA.
[Munns, Clare H.] Johns Hopkins Univ, Ctr Sensory Biol, Baltimore, MD 21218 USA.
[Gaudet, Rachelle] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Ludlow, Christy L.] James Madison Univ, Lab Neural Bases Commun & Swallowing, Harrisonburg, VA 22807 USA.
RP Sumner, CJ (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
EM csumner1@jhmi.edu
RI Traynor, Bryan/G-5690-2010; Gaudet, Rachelle/I-4133-2014;
OI Gaudet, Rachelle/0000-0002-9177-054X; Ludlow,
Christy/0000-0002-2015-6171
FU NIA NIH HHS [Z01-AG000949-02]; NIGMS NIH HHS [R01GM081340]; NINDS NIH
HHS [R01NS062869]
NR 7
TC 13
Z9 14
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUL
PY 2012
VL 79
IS 2
BP 192
EP 194
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 971XV
UT WOS:000306241000019
PM 22675077
ER
PT J
AU Bian, Y
Hall, B
Sun, ZJ
Molinolo, A
Chen, W
Gutkind, JS
Waes, CV
Kulkarni, AB
AF Bian, Y.
Hall, B.
Sun, Z-J
Molinolo, A.
Chen, W.
Gutkind, J. S.
Waes, C. V.
Kulkarni, A. B.
TI Loss of TGF-beta signaling and PTEN promotes head and neck squamous cell
carcinoma through cellular senescence evasion and cancer-related
inflammation
SO ONCOGENE
LA English
DT Article
DE TGF-beta; PI3K/Akt; head and neck squamous cell carcinoma; conditional
knockout; cancer mouse model
ID GROWTH-FACTOR-BETA; FACTOR-KAPPA-B; MAMMARY-CARCINOMA; TUMOR-SUPPRESSOR;
COLON-CANCER; TUMORIGENESIS; ACTIVATION; PATHWAYS; APOPTOSIS; MODEL
AB The molecular mechanisms that contribute to the initiation and progression of head and neck squamous cell carcinoma (HNSCC) have not been completely delineated. Our observations indicate that defects in the transforming growth factor-beta and PI3K/Akt signaling pathways are common in human HNSCCs. Conditional activation of the PI3K/Akt pathway due to Pten deletion in the mouse head and neck epithelia gives rise to hyperproliferation, but only a few lesions progress to HNSCC. However, Pten-deficient mice developed full-penetrance HNSCC in combination with type I TGF-beta receptor (Tgfbr1) deletion. Molecular analysis revealed enhanced cell proliferation, decreased apoptosis, and increased expression of CCND1 in the basal layer of the head and neck epithelia, as well as in the tumors of Tgfbr1/Pten double conditional knockout (2cKO) mice. Furthermore, neoplastic transformation involves senescence evasion, and is associated with an increased number of putative cancer stem cells. In addition, the nuclear factor-kappa B pathway activation, myeloid-derived suppressor cell infiltration, angiogenesis and immune suppression in the tumor microenvironment, all of which are characteristics of human HNSCCs, contribute significantly to head and neck carcinogenesis in 2cKO mice. These tumors display pathology and multiple molecular alterations resembling human HNSCCs. This suggests that the Tgfbr1/Pten 2cKO mouse model is suitable for preclinical intervention, and that it has significant implications in the development of diagnostic cancer biomarkers and effective strategies for prevention and treatment of HNSCCs. Oncogene (2012) 31, 3322-3332; doi: 10.1038/onc.2011.494; published online 31 October 2011
C1 [Kulkarni, A. B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Molinolo, A.; Gutkind, J. S.] Oral & Pharyngeal Canc Branch, Bethesda, MD USA.
[Chen, W.] Natl Inst Dent & Craniofacial Res, Mucosal Immun Sect, Oral Immun & Infect Branch, Bethesda, MD 20892 USA.
[Bian, Y.; Waes, C. V.] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, 30 Convent Dr,Bldg 30,Room 130, Bethesda, MD 20892 USA.
EM ak40m@nih.gov
FU Divisions of Intramural Research, National Institute of Dental and
Craniofacial Research [Z01-DE-000698]; National Institute on Deafness
and Communication Disorders, NIH [ZIA-DC-000073]
FX We would like to thank Dr Stefan Karlsson for providing us with the
Tgfbr1 flox mice, Drs Raj Puri and Lalage Wakefield for critical reading
of the manuscript, Drs Juan Du, Ping Zhang, Zhong Chen and Anita Terse
for technical help, and Shelagh Johnson for the expert editorial
assistance. This work was supported by the Divisions of Intramural
Research, National Institute of Dental and Craniofacial Research
(Z01-DE-000698), and National Institute on Deafness and Communication
Disorders (ZIA-DC-000073), NIH.
NR 51
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U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUL
PY 2012
VL 31
IS 28
BP 3322
EP 3332
DI 10.1038/onc.2011.494
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 973NT
UT WOS:000306367600002
PM 22037217
ER
PT J
AU Cannon, C
AF Cannon, Carol
TI New Oncology Nurse Encouraged by Editorial
SO ONCOLOGY NURSING FORUM
LA English
DT Letter
C1 NIH, Bethesda, MD 20892 USA.
RP Cannon, C (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD JUL
PY 2012
VL 39
IS 4
BP 344
EP 344
DI 10.1188/12.ONF.344
PG 1
WC Oncology; Nursing
SC Oncology; Nursing
GA 970QI
UT WOS:000306147000004
ER
PT J
AU Nussenblatt, RB
Calogero, D
Buchen, SY
Leder, HA
Goodkin, M
Eydelman, MB
AF Nussenblatt, Robert B.
Calogero, Don
Buchen, Shelley Y.
Leder, Henry A.
Goodkin, Margot
Eydelman, Malvina B.
TI Rabbit Intraocular Reactivity to Endotoxin Measured by Slit-Lamp
Biomicroscopy and Laser Flare Photometry
SO OPHTHALMOLOGY
LA English
DT Article
ID OCULAR INFLAMMATORY RESPONSE; ANTERIOR SEGMENT; INHIBITION; UVEITIS;
ALPHA
AB Objective: To evaluate the ocular reactivity of the rabbit to an intracameral injection of a dispersive ophthalmic viscosurgical device (OVD) containing various levels of bacterial endotoxin using slit-lamp biomicroscopy and laser flare photometry.
Design: Experimental, randomized, masked animal study.
Participants: Thirty Dutch-Belted rabbits.
Methods: The rabbits were randomized into 6 groups to receive 0.05 ml of a hydroxypropyl methylcellulose-based dispersive OVD to which had been added one of 5 different doses of bacterial endotoxin ranging from 0.02 to 1.4 endotoxin units (EUs) or a vehicle control to both eyes. The eyes were evaluated for anterior segment inflammation at baseline and 3, 6, 9, 24, 48, and 72 hours after injection using slit-lamp biomicroscopy and laser flare photometry.
Main Outcome Measures: Corneal clarity and anterior chamber (AC) inflammation.
Results: All the corneas remained clear throughout the study. Anterior chamber cells were seen at 6, 9, and 24 hours in 60% to 100% of the eyes intracamerally injected with endotoxin-containing OVD, and the response declined rapidly after 24 hours. A dose-response effect was seen between the concentration of endotoxin and the AC cell response. The aqueous flare response in eyes injected with the 2 highest doses of endotoxin was significantly greater (P<0.05) than that of controls. The amounts of fibrin observed in the AC were random, with no apparent dose-response effect seen. The flare values as obtained by laser flare photometry were consistent with the slit-lamp biomicroscopy flare findings up to grade 3+. However, the increase in laser flare value seemed to level off in eyes with more than 3+ flare. Neither measure of flare correlated with endotoxin level.
Conclusions: Among the parameters evaluated in this study, the AC cell response, evaluated by slit-lamp biomicroscopy and graded using a standard grading system, was found to be the most reliable indicator of the amount of endotoxin in the dispersive OVD. The use of laser flare photometry alone does not seem to be useful in detecting an ocular response to endotoxin contamination in OVDs.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:e19-e23 (C) 2012 by the American Academy of Ophthalmology.
C1 [Calogero, Don; Goodkin, Margot; Eydelman, Malvina B.] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, Silver Spring, MD 20993 USA.
[Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA.
[Buchen, Shelley Y.; Leder, Henry A.] US FDA, ORISE, Silver Spring, MD 20993 USA.
RP Eydelman, MB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, 10903 New Hampshire Ave,WO 66-2410, Silver Spring, MD 20993 USA.
EM malvina.eydelman@fda.hhs.gov
FU Food and Drug Administration, Silver Spring, Maryland
FX Supported by the Food and Drug Administration, Silver Spring, Maryland.
The Food and Drug Administration personnel participated in the design of
the study, conducting the study, data collection, data management, data
analyses, data interpretation, and manuscript preparation and review.
The mention of commercial products, their sources, or their use in
connection with material reported herein is not to be construed as
either an actual or implied endorsement of such products by the
Department of Health and Human Services (DHHS).
NR 17
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Z9 4
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2012
VL 119
IS 7
BP E19
EP E23
DI 10.1016/j.ophtha.2012.04.004
PG 5
WC Ophthalmology
SC Ophthalmology
GA 968UQ
UT WOS:000306011000003
PM 22578448
ER
PT J
AU Martin, DF
Maguire, MG
Fine, SL
Ying, GS
Jaffe, GJ
Grunwald, JE
Toth, C
Redford, M
Ferris, FL
AF Martin, Daniel F.
Maguire, Maureen G.
Fine, Stuart L.
Ying, Gui-shuang
Jaffe, Glenn J.
Grunwald, Juan E.
Toth, Cynthia
Redford, Maryann
Ferris, Frederick L., III
CA Comparison Age-related Macular
TI Ranibizumab and Bevacizumab for Treatment of Neovascular Age-Related
Macular Degeneration
SO OPHTHALMOLOGY
LA English
DT Article
ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; PHOTODYNAMIC THERAPY;
CLINICAL-TRIALS; VERTEPORFIN; LESIONS
AB Objective: To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment.
Design: Multicenter, randomized clinical trial.
Participants: Patients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial.
Interventions: At enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment.
Main Outcome Measures: Mean change in visual acuity.
Results: Among patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (-2.2 letters; P = 0.03) and a lower proportion without fluid (-19%; P < 0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P > 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF).
Conclusions: Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;xx:xxx (C) 2012 by the American Academy of Ophthalmology.
C1 [Maguire, Maureen G.; Ying, Gui-shuang; Grunwald, Juan E.] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Martin, Daniel F.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA.
[Fine, Stuart L.] Univ Colorado, Dept Ophthalmol, Denver, CO 80202 USA.
[Jaffe, Glenn J.; Toth, Cynthia] Duke Univ, Dept Ophthalmol, Durham, NC USA.
[Redford, Maryann; Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA.
RP Maguire, MG (reprint author), Univ Penn, Dept Ophthalmol, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM maguirem@mail.med.upenn.edu
FU Regeneron; Genentech; Bioptigen; Physical Sciences Incorporated;
National Eye Institute, National Institutes of Health, Department of
Health and Human Services [U10 EY017823, U10 EY017825, U10 EY017826, U10
EY017828]
FX Glenn J. Jaffe - Consultant - Heidelberg Engineering; Financial support
- Regeneron; Cynthia Toth - Consultant - Physical Sciences Incorporated;
Financial support - Genentech, Bioptigen, and Physical Sciences
Incorporated; Patents pending - OCT analysis technology related to
analysis for age-related macular degeneration; Royalties - Alcon
Laboratories for ophthalmic surgical technologies; Supported by
cooperative agreements U10 EY017823, U10 EY017825, U10 EY017826, and U10
EY017828 from the National Eye Institute, National Institutes of Health,
Department of Health and Human Services. The funding organization
participated in the design and conduct of the study, data analysis and
interpretation, and review of the manuscript.
NR 16
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Z9 561
U1 6
U2 55
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 JUL
PY 2012
VL 119
IS 7
DI 10.1016/j.ophtha.2012.03.053
PG 11
WC Ophthalmology
SC Ophthalmology
GA 968UQ
UT WOS:000306011000021
ER
PT J
AU Ramulu, PY
van Landingham, SW
Massof, RW
Chan, ES
Ferrucci, L
Friedman, DS
AF Ramulu, Pradeep Y.
van Landingham, Suzanne W.
Massof, Robert W.
Chan, Emilie S.
Ferrucci, Luigi
Friedman, David S.
TI Fear of Falling and Visual Field Loss from Glaucoma
SO OPHTHALMOLOGY
LA English
DT Article
ID SALISBURY EYE EVALUATION; QUALITY-OF-LIFE; OLDER-ADULTS; MOBILITY
PERFORMANCE; LENS OPACITIES; RISK-FACTORS; COMMUNITY; EFFICACY;
CONSEQUENCES; IMPAIRMENT
AB Objective: To determine if visual field (VF) loss resulting from glaucoma is associated with greater fear of falling.
Design: Prospective, observational study.
Participants: Fear of falling was compared between 83 glaucoma subjects with bilateral VF loss and 60 control subjects with good visual acuity and without significant VF loss recruited from patients followed up for suspicion of glaucoma.
Methods: Participants completed the University of Illinois at Chicago Fear of Falling Questionnaire. The extent of fear of falling was assessed using Rasch analysis.
Main Outcome Measures: Subject ability to perform tasks without fear of falling was expressed in logits, with lower scores implying less ability and greater fear of falling.
Results: Glaucoma subjects had greater VF loss than control subjects (median better-eye mean deviation [MD] of -8.0 decibels [dB] vs. +0.2 dB; P<0.001), but did not differ with regard to age, race, gender, employment status, the presence of other adults in the home, body mass index (BMI), grip strength, cognitive ability, mood, or comorbid illness (P >= 0.1 for all). In multivariate models, glaucoma subjects reported greater fear of falling as compared with controls (beta= -1.20 logits; 95% confidence interval [CI], -1.87 to -0.53; P = 0.001), and fear of falling increased with greater VF loss severity (beta = -0.52 logits per 5-dB decrement in the better eye VF MD; 95% CI, -0.72 to -0.33; P<0.001). Other variables predicting greater fear of falling included female gender (beta = -0.55 logits; 95% CI, -1.03 to -0.06; P = 0.03), higher BMI (beta = -0.07 logits per 1-unit increase in BMI; 95% CI, -0.13 to -0.01; P = 0.02), living with another adult (beta = -1.16 logits; 95% CI, -0.34 to -1.99 logits; P = 0.006), and greater comorbid illness (beta = -0.53 logits/1 additional illness; 95% CI, -0.74 to -0.32; P< 0.001).
Conclusions: Bilateral VF loss resulting from glaucoma is associated with greater fear of falling, with an impact that exceeds numerous other risk factors. Given the physical and psychological repercussions associated with fear of falling, significant quality-of-life improvements may be achievable in patients with VF loss by screening for, and developing interventions to minimize, fear of falling.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;xx:xxx (C) 2012 by the American Academy of Ophthalmology.
C1 [Ramulu, Pradeep Y.; van Landingham, Suzanne W.; Massof, Robert W.; Chan, Emilie S.; Friedman, David S.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Bethesda, MD 20892 USA.
RP Ramulu, PY (reprint author), 600 N Wolfe St,Maumenee B-110, Baltimore, MD 21287 USA.
EM pramulu1@jhmi.edu
FU American Geriatrics Society, New York, New York; National Institutes of
Health, Bethesda, Maryland [EY018595]; Robert and Helen Schaub Special
Scholar Award, Research to Prevent Blindness, Inc., New York, New York;
National Institutes of Health, National Institute on Aging, Bethesda,
Maryland
FX Supported by the American Geriatrics Society, Dennis W. Jahnigen
Memorial Award, New York, New York; the National Institutes of Health,
Bethesda, Maryland (grant no.: EY018595); the Robert and Helen Schaub
Special Scholar Award, Research to Prevent Blindness, Inc., New York,
New York; and the Intramural Research Program of the National Institutes
of Health, National Institute on Aging, Bethesda, Maryland. All funding
organizations had no role in the design or conduct of this research.
NR 36
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U1 0
U2 8
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 JUL
PY 2012
VL 119
IS 7
DI 10.1016/j.ophtha.2012.01.037
PG 7
WC Ophthalmology
SC Ophthalmology
GA 968UQ
UT WOS:000306011000016
PM 22480738
ER
PT J
AU Davis, JL
Pandalai, PK
Ripley, RT
Langan, RC
Avital, I
AF Davis, Jeremy L.
Pandalai, Prakash K.
Ripley, R. Taylor
Langan, Russell C.
Avital, Itzhak
TI Expanding Surgical Treatment of Pancreatic Cancer The Role of Regional
Chemotherapy
SO PANCREAS
LA English
DT Review
DE pancreatic cancer; chemotherapy; cancer; regional perfusion; infusion;
intra-arterial
ID PERIOPERATIVE INTRAPERITONEAL CHEMOTHERAPY; INTRAARTERIAL INFUSION
CHEMOTHERAPY; COOPERATIVE-ONCOLOGY-GROUP; CELIAC AXIS INFUSION;
LONG-TERM SURVIVAL; PHASE-III TRIAL; MITOMYCIN-C; ARTERIAL INFUSION;
ANGIOTENSIN-II; GEMCITABINE
AB Objectives: Pancreatic cancer is a lethal disease that offers little chance of long-term survival for patients with unresectable tumors. Surgery remains the most effective means of attaining prolonged survival, yet its role remains limited. Regional chemotherapy has been described for patients with pancreatic cancer, including reports of objective tumor regression allowing for tumor resection in previously unresectable cases. However, comprehensive data have not been reviewed to date.
Methods: A review of the literature from 1995 to 2010 was performed to analyze the results of regional chemotherapy administered to patients with advanced pancreatic cancer. Reports of individual cases, postoperative regional therapy, and treatment of mixed tumor types were excluded.
Results: Twenty-one reports of 895 total patients with pancreatic cancer were reviewed. Greater than 95% of the patients had stage III or IV adenocarcinoma. Objective response rates ranged from nil to 58%, with associated median survivals of 4 to 22 months. Low-grade gastrointestinal and hematologic toxicities were not uncommon.
Conclusions: Regional chemotherapy can be administered safely to patients with pancreatic cancer but with unclear benefit. Advanced pancreatic tumors converted to resectable status by the use of regional chemotherapy may improve patient survival.
C1 [Davis, Jeremy L.; Pandalai, Prakash K.; Ripley, R. Taylor; Langan, Russell C.; Avital, Itzhak] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Avital, I (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 10 Ctr Dr,CRC Room 4-3961, Bethesda, MD 20892 USA.
EM itzhakavital@gmail.com
FU Center for Cancer Research, National Cancer Institute, NIH
FX Conflicts of Interest and Source of Funding: No conflicting interests to
report. Intramural funding was through the Center for Cancer Research,
National Cancer Institute, NIH.
NR 49
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Z9 6
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD JUL
PY 2012
VL 41
IS 5
BP 678
EP 684
DI 10.1097/MPA.0b013e318249955a
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 969NH
UT WOS:000306061900003
PM 22695088
ER
PT J
AU Bratton, SL
Newth, CJL
Zuppa, AF
Moler, FW
Meert, KL
Berg, RA
Berger, J
Wessel, D
Pollack, M
Harrison, R
Carcillo, JA
Shanley, TP
Liu, T
Holubkov, R
Dean, JM
Nicholson, CE
AF Bratton, Susan L.
Newth, Christopher J. L.
Zuppa, Athena F.
Moler, Frank W.
Meert, Kathleen L.
Berg, Robert A.
Berger, John
Wessel, David
Pollack, Murray
Harrison, Rick
Carcillo, Joseph A.
Shanley, Thomas P.
Liu, Teresa
Holubkov, Richard
Dean, J. Michael
Nicholson, Carol E.
CA Eunice Kennedy Shriver Natl Inst C
TI Critical care for pediatric asthma: Wide care variability and challenges
for study
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Article
DE asthma; heliox; magnesium sulfate; mechanical ventilation;
methylxanthines; noninvasive ventilation; pediatric; terbutaline;
variation
ID INTRAVENOUS TERBUTALINE; CHILDREN; VENTILATION; MANAGEMENT
AB Objectives: To describe pediatric severe asthma care, complications, and outcomes to plan for future prospective studies by the Collaborative Pediatric Critical Care Research Network.
Design: Retrospective cohort study.
Setting: Pediatric intensive care units in the United States that submit administrative data to the Pediatric Health Information System.
Patients: Children 1-18 yrs old treated in a Pediatric Health Information System pediatric intensive care unit for asthma during 2004-2008.
Interventions: None.
Measurements and Main Results: Thirteen-thousand five-hundred fifty-two children were studied; 2,812 (21%) were treated in a Collaborative Pediatric Critical Care Research Network and 10,740 (79%) were treated in a non-Collaborative Pediatric Critical Care Research Network pediatric intensive care unit. Medication use in individual Collaborative Pediatric Critical Care Research Network centers differed widely: ipratropium bromide (41%-84%), terbutaline (11%-74%), magnesium sulfate (23%-64%), and methylxanthines (0%-46%). Complications including pneumothorax (0%-0.6%), cardiac arrest (0.2%-2%), and aspiration (0.2%-2%) were rare. Overall use of medical therapies and complications at Collaborative Pediatric Critical Care Research Network centers were representative of pediatric asthma care at non-Collaborative Pediatric Critical Care Research Network pediatric intensive care units. Median length of pediatric intensive care unit stay at Collaborative Pediatric Critical Care Research Network centers was 1 to 2 days and death was rare (0.1%-3%). Ten percent of children treated at Collaborative Pediatric Critical Care Research Network centers received invasive mechanical ventilation compared to 12% at non-Collaborative Pediatric Critical Care Research Network centers. Overall 44% of patients who received invasive mechanical ventilation were intubated in the pediatric intensive care unit. Children intubated outside the pediatric intensive care unit had significantly shorter median ventilation days (1 vs. 3), pediatric intensive care unit days (2 vs. 4), and hospital days (4 vs. 7) compared to those intubated in the pediatric intensive care unit. Among children who received mechanical respiratory support, significantly more (41% vs. 25%) were treated with noninvasive ventilation and significantly fewer (41% vs. 58%) were intubated before pediatric intensive care unit care when treated in a Pediatric Health Information System hospital emergency department.
Conclusions: Marked variations in medication therapies and mechanical support exist. Death and other complications were rare. More than half of patients treated with mechanical ventilation were intubated before pediatric intensive care unit care. Site of respiratory mechanical support initiation was associated with length of stay. (Pediatr Crit Care Med 2012; 13:407-414)
C1 [Bratton, Susan L.; Harrison, Rick; Liu, Teresa; Dean, J. Michael] Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA.
[Newth, Christopher J. L.] Childrens Hosp Los Angeles, Dept Anesthesiol Crit Care Medinein, Los Angeles, CA 90027 USA.
[Zuppa, Athena F.; Berg, Robert A.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Moler, Frank W.; Shanley, Thomas P.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Meert, Kathleen L.] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Berger, John; Wessel, David] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
[Pollack, Murray] Phoenix Childrens Hosp, Dept Pediat, Phoenix, AZ USA.
[Holubkov, Richard] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA.
[Nicholson, Carol E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Washington, DC USA.
RP Bratton, SL (reprint author), Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA.
EM Susan.Bratton@hsc.utah.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, Department of Health and Human Services [U10HD500009,
U10HD050096, U10HD049981, U10HD049945, U10HD049983, U10HD050012,
U01HD049934]
FX Supported, in part, by cooperative agreements (U10HD500009, U10HD050096,
U10HD049981, U10HD049945, U10HD049983, U10HD050012, and U01HD049934)
from the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, Department of Health and Human Services.
NR 25
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U1 0
U2 4
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 JUL
PY 2012
VL 13
IS 4
BP 407
EP 414
DI 10.1097/PCC.0b013e318238b428
PG 8
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA 970FU
UT WOS:000306114300015
PM 22067984
ER
PT J
AU Shen, DW
Pouliot, LM
Hall, MD
Gottesman, MM
AF Shen, Ding-Wu
Pouliot, Lynn M.
Hall, Matthew D.
Gottesman, Michael M.
TI Cisplatin Resistance: A Cellular Self-Defense Mechanism Resulting from
Multiple Epigenetic and Genetic Changes
SO PHARMACOLOGICAL REVIEWS
LA English
DT Review
ID EPITHELIAL-MESENCHYMAL TRANSITION; BREAST-CANCER CELLS; MODULATES
MULTIDRUG-RESISTANCE; FINGER TRANSCRIPTION FACTOR; NUCLEOTIDE
EXCISION-REPAIR; COPPER TRANSPORTER CTR1; WNT SIGNALING PATHWAY;
PLATINUM-DNA ADDUCT; HEAT-SHOCK-PROTEIN; DRUG-RESISTANCE
AB Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its effectiveness seems to be due to the unique properties of cisplatin, which enters cells via multiple pathways and forms multiple different DNA-platinum adducts while initiating a cellular self-defense system by activating or silencing a variety of different genes, resulting in dramatic epigenetic and/or genetic alternations. As a result, the development of cisplatin resistance in human cancer cells in vivo and in vitro by necessity stems from bewilderingly complex genetic and epigenetic changes in gene expression and alterations in protein localization. Extensive published evidence has demonstrated that pleiotropic alterations are frequently detected during development of resistance to this toxic metal compound. Changes occur in almost every mechanism supporting cell survival, including cell growth-promoting pathways, apoptosis, developmental pathways, DNA damage repair, and endocytosis. In general, dozens of genes are affected in cisplatin-resistant cells, including pathways involved in copper metabolism as well as transcription pathways that alter the cytoskeleton, change cell surface presentation of proteins, and regulate epithelial-to-mesenchymal transition. Decreased accumulation is one of the most common features resulting in cisplatin resistance. This seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisplatin, and decreased fluid phase endocytosis.
C1 [Shen, Ding-Wu; Pouliot, Lynn M.; Hall, Matthew D.; Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 2108, Bethesda, MD 20892 USA.
EM mgottesman@nih.gov
FU National Institutes of Health, Center for Cancer Research, National
Cancer Institute
FX This research was funded by the Intramural Research Program of the
National Institutes of Health, Center for Cancer Research, National
Cancer Institute. We thank George Leiman for editorial assistance.
NR 143
TC 166
Z9 176
U1 18
U2 72
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0031-6997
EI 1521-0081
J9 PHARMACOL REV
JI Pharmacol. Rev.
PD JUL
PY 2012
VL 64
IS 3
BP 706
EP 721
DI 10.1124/pr.111.005637
PG 16
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 971CT
UT WOS:000306182000011
PM 22659329
ER
PT J
AU Ell, K
Katon, W
Lee, PJ
Kapetanovic, S
Guterman, J
Xie, B
Chou, CP
AF Ell, Kathleen
Katon, Wayne
Lee, Pey-Jiuan
Kapetanovic, Suad
Guterman, Jeffrey
Xie, Bin
Chou, Chih-Ping
TI Depressive Symptom Deterioration among Predominantly Hispanic Diabetes
Patients in Safety Net Care
SO PSYCHOSOMATICS
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; MAJOR DEPRESSION; COLLABORATIVE CARE;
COGNITIVE THERAPY; LOW-INCOME; RECURRENCE; RELAPSE; PREVENTION; HEALTH;
COMPLICATIONS
AB Objective: This study examines clinical predictors of symptom deterioration (relapse/recurrence) at the completion of a clinical intervention trial of depressed, low-income, predominantly Hispanic diabetes patients who were randomized to socio-culturally adapted collaborative depression treatment or usual care and who no longer met clinically significant depression criteria at 12 months post-trial baseline. Methods: A sub-cohort of 193 diabetes patients with major depression symptoms at baseline, who were randomized to a 12-month collaborative care intervention (INT) (problem-solving therapy and/or pharmacotherapy, telephone symptom monitoring/relapse prevention, behavioral activation and patient navigation support) or enhanced usual care (EUC), and who did not meet major depression criteria at 12 months were subsequently observed over 18 to 24 months. Results: Post-trial depression symptom deterioration was similar between INT (35.2%) and EUC (35.3%) groups. Among the combined groups, significant predictors of symptom deterioration were baseline history of previous depression and/or dysthymia (odds ratio [OR] = 2.66), 12-month PHQ-9 score (OR = 1.22), antidepressant treatment receipt during the initial 12-months (OR = 2.38), 12-month diabetes symptoms (OR = 2.27), and new ICD-9 medical diagnoses in the initial 12 months (OR = 1.11) (R-2 = 27%; max-rescaled R-2 = 37%; likelihood ratio test, chi(2) = 59.79, 4f = 5, P < 0.0001). Conclusions: Among predominantly Hispanic diabetes patients in community safety net primary care clinics whose depression had improved over 1 year, more than one-third experienced symptom deterioration over the following year. A primary care management depression care protocol that includes ongoing depression symptom monitoring, antidepressant adherence, and diabetes and co-morbid illness monitoring plus depression medication adjustment and behavioral activation may reduce and/or effectively treat depression symptom deterioration. (Psychosomatics 2012; 53:347-355)
C1 [Ell, Kathleen; Lee, Pey-Jiuan] Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA.
[Katon, Wayne] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Kapetanovic, Suad] NIMH, NIH, Bethesda, MD USA.
[Guterman, Jeffrey] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Guterman, Jeffrey] Los Angeles Cty Dept Hlth Serv, Los Angeles, CA USA.
[Xie, Bin] Claremont Grad Univ, Sch Community & Global Hlth, Claremont, CA 91711 USA.
[Chou, Chih-Ping] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.
RP Ell, K (reprint author), Univ So Calif, Sch Social Work, MRF 102R,MC 0411, Los Angeles, CA 90089 USA.
EM ell@usc.edu
FU National Institute of Mental Health [R01 MH068468, K-24 MH069741]
FX The study is supported by R01 MH068468 from the National Institute of
Mental Health (PI, Dr. Ell) and K-24 MH069741 (Katon) from the National
Institute of Mental Health.
NR 36
TC 5
Z9 5
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD JUL-AUG
PY 2012
VL 53
IS 4
BP 347
EP 355
PG 9
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 970XD
UT WOS:000306164700006
PM 22458987
ER
PT J
AU Koh, SH
Huh, YM
Noh, MY
Kim, HY
Kim, KS
Lee, ES
Ko, HJ
Cho, GW
Yoo, AR
Song, HT
Hwang, S
Lee, K
Haam, S
Frank, JA
Suh, JS
Kim, SH
AF Koh, Seong-Ho
Huh, Yong-Min
Noh, Min Young
Kim, Hyun Young
Kim, Kyung Suk
Lee, Eun-Sook
Ko, Hyun-Ju
Cho, Goang Won
Yoo, A. Rum
Song, Ho-taek
Hwang, Sejin
Lee, Kwangyeol
Haam, Seungjoo
Frank, Joseph A.
Suh, Jin-Suck
Kim, Seung Hyun
TI beta-PIX Is Critical for Transplanted Mesenchymal Stromal Cell Migration
SO STEM CELLS AND DEVELOPMENT
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; PROGENITOR CELLS; ISCHEMIC-STROKE;
EXCHANGE FACTOR; STEM-CELLS; PHOSPHORYLATION; CAPACITY; PATHWAY;
DISEASE; BINDING
AB Bone marrow-derived mesenchymal stromal cells (MSCs) have been used successfully as a source of stem cells for treating neurodegenerative diseases. However, for reasons that are not clear, autologous MSC transplants have not yielded successful results in human trials. To test one possible reason, we compared the migratory ability of MSCs from amyotrophic lateral sclerosis (ALS) patients with those of healthy controls. We found that MSCs derived from ALS patients (ALS-MSCs) had a reduced ability to migrate, which may explain why autologous transplantation is not successful. We also found that expression of one of the intracellular factors implicated in migration, beta-PIX, was significantly reduced in ALS-MSCs compared with healthy stem cells. Restoration of beta-PIX expression by genetic manipulation restored the migratory ability of ALS-MSCs, and inhibition of beta-PIX expression with shRNA reduced the migration of healthy MSCs. We suggest that transplantation of allogeneic or genetically modified autologous stem cells might be a more promising strategy for ALS patients than transplantation of autologous stem cells.
C1 [Koh, Seong-Ho; Noh, Min Young; Kim, Hyun Young; Cho, Goang Won; Yoo, A. Rum; Kim, Seung Hyun] Hanyang Univ, Coll Med, Dept Neurol, Seoul 133791, South Korea.
[Huh, Yong-Min; Lee, Eun-Sook; Ko, Hyun-Ju; Song, Ho-taek; Suh, Jin-Suck] Yonsei Univ, Coll Med, Dept Radiol, Seoul 120752, South Korea.
[Kim, Kyung Suk] CoreStem Inc, Bioengn Inst, Seoul, South Korea.
[Cho, Goang Won] Chosun Univ, Coll Nat Sci, Dept Biol, Kwangju, South Korea.
[Hwang, Sejin] Hanyang Univ, Coll Med, Dept Anat, Seoul 133791, South Korea.
[Lee, Kwangyeol] Korea Univ, Dept Chem, Seoul 136701, South Korea.
[Haam, Seungjoo] Yonsei Univ, Dept Chem & Biomol Engn, Seoul 120749, South Korea.
[Frank, Joseph A.] Ctr Clin, Frank Lab, Bethesda, MD USA.
[Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
RP Kim, SH (reprint author), Hanyang Univ, Coll Med, Dept Neurol, 17 Haengdang Dong Dong, Seoul 133791, South Korea.
EM jss@yuhs.ac; kimsh1@hanyang.ac.kr
RI Haam, Seungjoo/G-8042-2012; Lee, Kwangyeol /A-9269-2010
FU NanoBio R&D Program of the Korea Science and Engineering Foundation;
Ministry of Education, Science and Technology [2007-04717]; Korea
Healthcare Technology R&D Project, Ministry for Health, Welfare & Family
Affairs, Republic of Korea [A101712]
FX This work was supported by the NanoBio R&D Program of the Korea Science
and Engineering Foundation, funded by the Ministry of Education, Science
and Technology (2007-04717), and a grant from the Korea Healthcare
Technology R&D Project, Ministry for Health, Welfare & Family Affairs,
Republic of Korea (A101712).
NR 32
TC 3
Z9 3
U1 0
U2 6
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1547-3287
J9 STEM CELLS DEV
JI Stem Cells Dev.
PD JUL
PY 2012
VL 21
IS 11
BP 1989
EP 1999
DI 10.1089/scd.2011.0430
PG 11
WC Cell & Tissue Engineering; Hematology; Medicine, Research &
Experimental; Transplantation
SC Cell Biology; Hematology; Research & Experimental Medicine;
Transplantation
GA 973NB
UT WOS:000306365700015
PM 22087847
ER
PT J
AU Bryant, BJ
Yau, YY
Arceo, SM
Daniel-Johnson, J
Hopkins, JA
Leitman, SF
AF Bryant, Barbara J.
Yau, Yu Ying
Arceo, Sarah M.
Daniel-Johnson, Jennifer
Hopkins, Julie A.
Leitman, Susan F.
TI Iron replacement therapy in the routine management of blood donors
SO TRANSFUSION
LA English
DT Article
ID CORONARY-HEART-DISEASE; SERUM FERRITIN; CARBONYL IRON; CAROTID
ATHEROSCLEROSIS; DEFICIENCY; RISK; SUPPLEMENTATION; ASSOCIATION;
ANGIOGRAPHY; STORES
AB BACKGROUND: Iron depletion or deficiency in blood donors frequently results in deferrals for low hemoglobin (Hb), yet blood centers remain reluctant to dispense iron replacement therapy to donors. STUDY DESIGN AND METHODS: During a 39-month period, 1236 blood donors deferred for a Hb level of less than 12.5 g/dL and 400 nondeferred control donors underwent health history screening and laboratory testing (complete blood counts, iron studies). Iron depletion and deficiency were defined as a ferritin level of 9 to 19 and less than 9 mu g/L in females and 18 to 29 and less than 18 mu g/L in males. Deferred donors and iron-deficient control donors were given a 60-pack of 325-mg ferrous sulfate tablets and instructed to take one tablet daily. Another 60-pack was dispensed at all subsequent visits. RESULTS: In the low-Hb group, 30 and 23% of females and 8 and 53% of males had iron depletion or deficiency, respectively, compared with 29 and 10% of females and 18 and 21% of males in the control group. Iron-depleted or -deficient donors taking iron showed normalization of iron-related laboratory parameters, even as they continued to donate. Compliance with oral iron was 68%. Adverse gastrointestinal effects occurred in 21% of donors. The study identified 13 donors with serious medical conditions, including eight with gastrointestinal bleeding. No donors had malignancies or hemochromatosis. CONCLUSION: Iron depletion or deficiency was found in 53% of female and 61% of male low-Hb donors and in 39% of female and male control donors. Routine administration of iron replacement therapy is safe and effective and prevents the development of iron depletion and deficiency in blood donors.
C1 [Bryant, Barbara J.] Univ Texas Galveston, Med Branch, Dept Pathol, Blood Bank Div, Galveston, TX 77555 USA.
NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Bryant, BJ (reprint author), Univ Texas Galveston, Med Branch, Dept Pathol, Blood Bank Div, 301 Univ Blvd, Galveston, TX 77555 USA.
EM bbryant@utmb.edu
FU Intramural NIH HHS [Z99 CL999999]
NR 36
TC 25
Z9 26
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD JUL
PY 2012
VL 52
IS 7
BP 1566
EP 1575
DI 10.1111/j.1537-2995.2011.03488.x
PG 10
WC Hematology
SC Hematology
GA 972PO
UT WOS:000306289500025
PM 22211316
ER
PT J
AU Carty, NC
Xu, J
Kurup, P
Brouillette, J
Goebel-Goody, SM
Austin, DR
Yuan, P
Chen, G
Correa, PR
Haroutunian, V
Pittenger, C
Lombroso, PJ
AF Carty, N. C.
Xu, J.
Kurup, P.
Brouillette, J.
Goebel-Goody, S. M.
Austin, D. R.
Yuan, P.
Chen, G.
Correa, P. R.
Haroutunian, V.
Pittenger, C.
Lombroso, P. J.
TI The tyrosine phosphatase STEP: implications in schizophrenia and the
molecular mechanism underlying antipsychotic medications
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE glutamate hypothesis; neuroleptics; NMDA receptor trafficking;
schizophrenia; STEP; tyrosine phosphatase
ID D-ASPARTATE RECEPTOR; LONG-TERM CHANGES; NMDA ANTAGONIST; PREPULSE
INHIBITION; HIPPOCAMPAL-NEURONS; COGNITIVE DEFICITS; SURFACE EXPRESSION;
ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; KNOCKOUT MICE
AB Glutamatergic signaling through N-methyl-D-aspartate receptors (NMDARs) is required for synaptic plasticity. Disruptions in glutamatergic signaling are proposed to contribute to the behavioral and cognitive deficits observed in schizophrenia (SZ). One possible source of compromised glutamatergic function in SZ is decreased surface expression of GluN2B-containing NMDARs. STEP61 is a brain-enriched protein tyrosine phosphatase that dephosphorylates a regulatory tyrosine on GluN2B, thereby promoting its internalization. Here, we report that STEP61 levels are significantly higher in the postmortem anterior cingulate cortex and dorsolateral prefrontal cortex of SZ patients, as well as in mice treated with the psychotomimetics MK-801 and phencyclidine (PCP). Accumulation of STEP61 after MK-801 treatment is due to a disruption in the ubiquitin proteasome system that normally degrades STEP61. STEP knockout mice are less sensitive to both the locomotor and cognitive effects of acute and chronic administration of PCP, supporting the functional relevance of increased STEP61 levels in SZ. In addition, chronic treatment of mice with both typical and atypical antipsychotic medications results in a protein kinase A-mediated phosphorylation and inactivation of STEP61 and, consequently, increased surface expression of GluN1/GluN2B receptors. Taken together, our findings suggest that STEP61 accumulation may contribute to the pathophysiology of SZ. Moreover, we show a mechanistic link between neuroleptic treatment, STEP61 inactivation and increased surface expression of NMDARs, consistent with the glutamate hypothesis of SZ. Translational Psychiatry (2012) 2, e137; doi:10.1038/tp.2012.63; published online 10 July 2012
C1 [Carty, N. C.; Xu, J.; Kurup, P.; Brouillette, J.; Goebel-Goody, S. M.; Pittenger, C.; Lombroso, P. J.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06520 USA.
[Austin, D. R.; Yuan, P.; Chen, G.] NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Res Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Correa, P. R.; Pittenger, C.; Lombroso, P. J.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Haroutunian, V.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Pittenger, C.] Yale Univ, Sch Med, Dept Psychol, New Haven, CT USA.
[Lombroso, P. J.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA.
RP Lombroso, PJ (reprint author), Yale Univ, Sch Med, Ctr Child Study, POB 207900, New Haven, CT 06520 USA.
EM paul.lombroso@yale.edu
RI Pittenger, Christopher/G-8402-2012; XU, JIAN/E-6915-2010; Kurup,
Pradeep/F-1291-2010; Chen, Guang/A-2570-2017;
OI Carty, Nikisha/0000-0002-0824-3897
FU NIH grants [MH091037, MH052711]; Intramural Research Program of the
National Institute of Mental Health; National Institutes of Health
(IRP-NIMH-NIH)
FX We thank Ms Veronica Galvin and Mr Evan Wilson-Wallis for technical
assistance, as well as laboratory members for helpful discussions and
critical reading of the manuscript. The work was funded by NIH grants
MH091037 and MH052711 (PJL). Postmortem brain study was supported by the
Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH).
NR 79
TC 25
Z9 26
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD JUL
PY 2012
VL 2
AR e137
DI 10.1038/tp.2012.63
PG 11
WC Psychiatry
SC Psychiatry
GA 971RK
UT WOS:000306221300009
PM 22781170
ER
PT J
AU Du, X
Leang, L
Mustafa, T
Renoir, T
Pang, TY
Hannan, AJ
AF Du, X.
Leang, L.
Mustafa, T.
Renoir, T.
Pang, T. Y.
Hannan, A. J.
TI Environmental enrichment rescues female-specific hyperactivity of the
hypothalamic-pituitary-adrenal axis in a model of Huntington's disease
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE acute stress; adrenal gland; environmental enrichment; glucocorticoid
receptor; HPA axis; Huntington's disease
ID DEXAMETHASONE SUPPRESSION TEST; TRANSGENIC MOUSE MODEL;
GLUCOCORTICOID-RECEPTOR; POLYGLUTAMINE INCLUSIONS; PLASMA TESTOSTERONE;
MOOD DISORDERS; HPA AXIS; MICE; STRESS; EXPRESSION
AB Huntington's disease (HD) has long been regarded as a disease of the central nervous system, partly due to typical disease symptoms that include loss of motor control, cognitive deficits and neuropsychiatric disturbances. However, the huntingtin gene is ubiquitously expressed throughout the body. We had previously reported a female-specific depression-related behavioural phenotype in the R6/1 transgenic mouse model of HD. One hypothesis suggests that pathology of the hypothalamic-pituitary-adrenal (HPA) axis, the key physiological stress-response system that links central and peripheral organs, is a cause of depression. There is evidence of HPA axis pathology in HD, but whether it contributes to the female R6/1 behavioural phenotype is unclear. We have examined HPA axis response of R6/1 mice following acute stress and found evidence of a female-specific dysregulation of the HPA axis in R6/1 mice, which we further isolated to a hyper-response of adrenal cortical cells to stimulation by adrenocorticotrophin hormone. Interestingly, the adrenal pathophysiology was not detected in mice that had been housed in environmentally enriching conditions, an effect of enrichment that was also reproduced in vitro. This constitutes the first evidence that environmental enrichment can in fact exert a lasting influence on peripheral organ function. Cognitive stimulation may therefore not only have benefits for mental function, but also for overall physiological wellbeing. Translational Psychiatry (2012) 2, e133; doi:10.1038/tp.2012.58; published online 3 July 2012
C1 [Pang, T. Y.] Univ Melbourne, Melbourne Brain Ctr, Neural Plast Lab, Behav Neurosci Div,Florey Neurosci Inst, Parkville, Vic 2010, Australia.
[Du, X.; Hannan, A. J.] Univ Melbourne, Dept Anat & Cell Biol, Parkville, Vic 2010, Australia.
[Mustafa, T.] NIMH, Sect Mol Neurosci, Bethesda, MD 20892 USA.
RP Pang, TY (reprint author), Univ Melbourne, Melbourne Brain Ctr, Neural Plast Lab, Behav Neurosci Div,Florey Neurosci Inst, Parkville, Vic 2010, Australia.
EM terence.pang@unimelb.edu.au
FU NHMRC; ARC Future Fellowship; Melbourne Research Scholarship (University
of Melbourne)
FX This work was supported by Project Grant funding (AJH) from the NHMRC
and an ARC Future Fellowship (AJH). XD is supported by a Melbourne
Research Scholarship (University of Melbourne).
NR 47
TC 31
Z9 31
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD JUL
PY 2012
VL 2
AR e133
DI 10.1038/tp.2012.58
PG 8
WC Psychiatry
SC Psychiatry
GA 971RK
UT WOS:000306221300005
PM 22760557
ER
PT J
AU Rao, JS
Keleshian, VL
Klein, S
Rapoport, SI
AF Rao, J. S.
Keleshian, V. L.
Klein, S.
Rapoport, S. I.
TI Epigenetic modifications in frontal cortex from Alzheimer's disease and
bipolar disorder patients
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE Alzheimer's disease; arachidonic acid cascade; bipolar disorder; DNA
methylation; drebrin; synaptophysin
ID POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; NF-KAPPA-B; DNA
METHYLATION; GENE-EXPRESSION; PSYCHIATRIC-DISORDERS; HISTONE
ACETYLATION; PHOSPHOLIPASE A(2); ARACHIDONIC-ACID; BLOOD-VESSELS
AB Alzheimer's disease (AD) and bipolar disorder (BD) are progressive brain disorders. Upregulated mRNA and protein levels of neuroinflammatory and arachidonic acid (AA) markers with loss of synaptic markers (synaptophysin and drebrin) have been reported in brain tissue from AD and BD patients. We hypothesized that some of these changes are associated with epigenetic modifications of relevant genes. To test this, we measured gene-specific CpG methylation, global DNA methylation and histone modifications in postmortem frontal cortex from BD (n = 10) and AD (n = 10) patients and respective age-matched controls (10 per group). AD and BD brains showed several epigenetic similarities, including global DNA hypermethylation, and histone H3 phosphorylation. These changes were associated with hypo- and hypermethylation of CpG islands in cyclooxygenase-2 and brain-derived neurotrophic factor promoter regions, respectively. Only the AD brain showed hyper- and hypomethylated CpG islands in promoter regions for cAMP response element-binding protein and nuclear transcription factor kappa B genes, respectively. Only the BD brain demonstrated increased global histone H3 acetylation and hypermethylation of the promotor region for the drebrin-like protein gene. There was no significant epigenetic modification for 12-lipooxygenase or p450 epoxygenase in either illness. Many observed epigenetic changes were inversely related to respective changes in mRNA and protein levels. These epigenetic modifications involving neuroinflammatory, AA cascade and synaptic markers may contribute to progression in AD and BD and identify new targets for drug development. Translational Psychiatry (2012) 2, e132; doi:10.1038/tp.2012.55; published online 3 July 2012
C1 [Rao, J. S.; Keleshian, V. L.; Klein, S.; Rapoport, S. I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,Room 1S-126, Bethesda, MD 20892 USA.
EM jrao@mail.nih.gov
FU Harvard Brain Bank, Boston, MA [R24MH068855]; Intramural Research
Program of the National Institute on Aging; National Institutes of
Health, Bethesda, MD, USA
FX We thank the NIH Fellows Editorial Board for editorial assistance. We
thank the Harvard Brain Bank, Boston, MA for providing the postmortem
brain samples under PHS grant number R24MH068855. This research was
entirely supported by the Intramural Research Program of the National
Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
NR 67
TC 84
Z9 90
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD JUL
PY 2012
VL 2
AR e132
DI 10.1038/tp.2012.55
PG 7
WC Psychiatry
SC Psychiatry
GA 971RK
UT WOS:000306221300004
PM 22760556
ER
PT J
AU Andersen, DK
AF Andersen, Dana K.
TI How Can Educators Use Simulation Applications to Teach and Assess
Surgical Judgment?
SO ACADEMIC MEDICINE
LA English
DT Article
ID RANDOMIZED-CONTROLLED-TRIAL; RELIABILITY ASSESSMENT OCHRA;
OPERATING-ROOM PERFORMANCE; COGNITIVE TASK-ANALYSIS; INGUINAL-HERNIA
REPAIR; SITUATION AWARENESS; TECHNICAL SKILLS; LAPAROSCOPIC PERFORMANCE;
ENDOSCOPIC SURGERY; DECISION-MAKING
AB Surgical simulation applications have been largely limited to the acquisition and assessment of technical skills. Current teaching and assessment of surgical judgment is nonsystematic and prone to error. Interest in methods to enhance the acquisition and assessment of knowledge-based (judgment) skills for intraoperative decision making has led to the application of cognitive task analysis (CTA) and human error assessment to facilitate this process. CTA-based delineation of the steps and hazards of a surgical procedure creates a structured process to teach and assess expert surgical judgment and improves trainees' operative planning, hazard recognition, error prevention, and error recovery when coupled with low-fidelity, synthesized simulation models for open and laparoscopic surgery. Web-based simulation applications facilitate curricular learning (rules-guided skills), allow cognitive rehearsal of procedures, and are accessible independent of location and time. Simulation applications that facilitate the assessment and learning of expert intraoperative judgment should include a consensus-derived outline based on CTA of the operative steps and potential points of risk for each surgical procedure; the ability to detect the situational awareness of the performer and the options considered to avoid error at critical steps; an assessment (scoring) of options considered or attempted; immediate evaluation feedback to inform improved performance; and a program of deliberate practice in which progressively more challenging scenarios can be introduced, based on the trainee's demonstrated skills. High-fidelity simulators currently lack these essential components, and future simulation-assisted teaching and assessment of surgical judgment skills are likely to employ low-fidelity simulators coupled to Web-based instruction.
C1 [Andersen, Dana K.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
[Andersen, Dana K.] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA.
RP Andersen, DK (reprint author), NIDDK, Div Digest Dis & Nutr, NIH, 6707 Democracy Blvd,Rm 659, Bethesda, MD 20892 USA.
EM danakandersen@yahoo.com
NR 69
TC 27
Z9 27
U1 3
U2 7
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 JUL
PY 2012
VL 87
IS 7
BP 934
EP 941
DI 10.1097/ACM.0b013e3182583248
PG 8
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 967HL
UT WOS:000305897400023
PM 22622214
ER
PT J
AU Galiwango, RM
Lamers, SL
Redd, AD
Manucci, J
Tobian, AAR
Sewankambo, N
Kigozi, G
Nakigozi, G
Serwadda, D
Boaz, I
Nalugoda, F
Sullivan, DJ
Kong, XR
Wawer, MJ
Gray, RH
Quinn, TC
Laeyendecker, O
AF Galiwango, Ronald M.
Lamers, Susanna L.
Redd, Andrew D.
Manucci, Jordyn
Tobian, Aaron A. R.
Sewankambo, Nelson
Kigozi, Godfrey
Nakigozi, Gertrude
Serwadda, David
Boaz, Iga
Nalugoda, Fred
Sullivan, David J.
Kong, Xiangrong
Wawer, Maria J.
Gray, Ronald H.
Quinn, Thomas C.
Laeyendecker, Oliver
CA Rakai Hlth Sci Program
TI HIV Type 1 Genetic Variation in Foreskin and Blood from Subjects in
Rakai, Uganda
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; SEXUALLY-TRANSMITTED INFECTIONS;
RESERVOIRS; RECOMBINATION; TRANSMISSION; CELLS; MEN
AB The foreskin contains a subset of dendritic cells, macrophages, and CD4(+) and CD8(+) T cells that may be targets for initial HIV infection in female-to-male sexual transmission of HIV-1. We present analyses comparing HIV-1 sequences isolated from foreskin DNA and serum RNA in 12 heterosexual men enrolled in an adult male circumcision trial performed in Rakai, Uganda. Phylogenetic analysis demonstrated three topologies: (1) little divergence between foreskin and serum, (2) multiple genetic bottlenecks occurring in both foreskin and serum, and (3) complete separation of foreskin and serum populations. The latter tree topology provided evidence that foreskin may serve as a reservoir for distinct HIV-1 strains. Distance and recombination analysis also demonstrated that viral genotypes in the foreskin might segregate independently from the circulating pool of viruses.
C1 [Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Galiwango, Ronald M.; Sewankambo, Nelson; Kigozi, Godfrey; Nakigozi, Gertrude; Serwadda, David; Boaz, Iga; Nalugoda, Fred; Kong, Xiangrong; Wawer, Maria J.; Gray, Ronald H.] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Lamers, Susanna L.] BioInfoExperts Inc, Thibodaux, LA USA.
[Redd, Andrew D.; Quinn, Thomas C.; Laeyendecker, Oliver] NIAID, Immunoregulat Lab, DIR, NIH, Baltimore, MD USA.
[Tobian, Aaron A. R.; Sullivan, David J.; Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Sewankambo, Nelson] Makerere Univ, Sch Med, Kampala, Uganda.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
RP Quinn, TC (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Rangos Bldg,Room 530,855 N Wolfe St, Baltimore, MD 21205 USA.
EM tquinn2@jhmi.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Sewankambo, Nelson/0000-0001-9362-053X; Laeyendecker,
Oliver/0000-0002-6429-4760
FU Bill and Melinda Gates Foundation [22006.02, 22006.03]; Fogarty
International Center [3D43TW000010-21S2]; Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX This work was supported by the Bill and Melinda Gates Foundation Grants
22006.02 and 22006.03, the Fogarty International Center Grant
3D43TW000010-21S2, and the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 15
TC 4
Z9 4
U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD JUL
PY 2012
VL 28
IS 7
BP 729
EP 733
DI 10.1089/aid.2011.0176
PG 5
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 966BF
UT WOS:000305810900013
PM 21902587
ER
PT J
AU Stuebe, AM
Landon, MB
Lai, YL
Spong, CY
Carpenter, MW
Ramin, SM
Casey, B
Wapner, RJ
Varner, MW
Rouse, DJ
Sciscione, A
Catalano, P
Harper, M
Saade, G
Sorokin, Y
Peaceman, AM
Tolosa, JE
AF Stuebe, Alison M.
Landon, Mark B.
Lai, Yinglei
Spong, Catherine Y.
Carpenter, Marshall W.
Ramin, Susan M.
Casey, Brian
Wapner, Ronald J.
Varner, Michael W.
Rouse, Dwight J.
Sciscione, Anthony
Catalano, Patrick
Harper, Margaret
Saade, George
Sorokin, Yoram
Peaceman, Alan M.
Tolosa, Jorge E.
CA Eunice Kennedy Shriver Natl Inst C
TI Maternal BMI, glucose tolerance, and adverse pregnancy outcomes
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE body mass index; gestational diabetes mellitus (GDM); glycemia; obesity
ID BODY-MASS INDEX; GESTATIONAL WEIGHT-GAIN; RANDOMIZED CONTROLLED-TRIAL;
DIABETES-MELLITUS; WOMEN; OBESITY; HYPERGLYCEMIA; OVERWEIGHT;
INTERVENTIONS; DIETARY
AB OBJECTIVE: The purpose of this study was to estimate the association of pregravid body mass index (BMI), independent of 3-hour oral glucose tolerance test (OGTT) results, with pregnancy outcome.
STUDY DESIGN: In this secondary analysis of a cohort of women with untreated mild gestational glucose intolerance, which was defined as a 50-g glucose loading test between 135 and 199 mg/dL and fasting glucose level of <95 mg/dL, we modeled the association between pregravid BMI, OGTT results, and both pregnancy complications and neonatal adiposity.
RESULTS: Among 1250 participants, both pregravid BMI and glucose at hour 3 of the OGTT were associated with increased risk of gestational hypertension. Maternal pregravid BMI also was associated positively with large-for-gestational-age infants; both maternal BMI and fasting glucose were associated with birthweight z-score and neonatal fat mass.
CONCLUSION: Among women with untreated mild gestational glucose intolerance, pregravid BMI is associated with increased gestational hypertension, birthweight, and neonatal fat mass, independent of OGTT values.
C1 [Stuebe, Alison M.] Univ N Carolina, Sch Med, Div Maternal Fetal Med, Dept Obstet & Gynecol, Chapel Hill, NC 27599 USA.
[Landon, Mark B.] Ohio State Univ, Ohio State Coll Med, Columbus, OH 43210 USA.
[Carpenter, Marshall W.] Brown Univ, Sch Med, Providence, RI 02912 USA.
[Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Casey, Brian] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Wapner, Ronald J.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Varner, Michael W.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Rouse, Dwight J.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA.
[Sciscione, Anthony] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Catalano, Patrick] Case Western Reserve Univ, Metrohlth Med Ctr, Sch Med, Cleveland, OH USA.
[Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Saade, George] Univ Texas Med Branch, Galveston, TX USA.
[Sorokin, Yoram] Wayne State Univ, Sch Med, Detroit, MI USA.
[Peaceman, Alan M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Portland, OR 97201 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 Stuebe, AM (reprint author), Univ N Carolina, Sch Med, Div Maternal Fetal Med, Dept Obstet & Gynecol, 3010 Old Clin Bldg,CB 7516, Chapel Hill, NC 27599 USA.
EM astuebe@med.unc.edu
RI Varner, Michael/K-9890-2013
OI Peaceman, Alan/0000-0002-4515-4850; Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD27915, HD34116, HD40485, HD34208, HD27869,
HD40500, HD40560, HD34136, HD40544, HD27860, HD40545, HD53097, HD21410,
HD27917, HD40512, HD53118, HD36801]; General Clinical Research Centers
[M01-RR00034]; National Center for Research Resources [UL1-RR024989,
M01-RR00080, UL1-RR025764, C06-RR11234]; Women's Reproductive Health
Research Career Development Center at the University of North Carolina
[5K12HD050113-04]
FX Supported by the following grants from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD): nos.
HD27915, HD34116, HD40485, HD34208, HD27869, HD40500, HD40560, HD34136,
HD40544, HD27860, HD40545, HD53097, HD21410, HD27917, HD40512, HD53118,
and HD36801; General Clinical Research Centers grant no. M01-RR00034;
and National Center for Research Resources grant nos. UL1-RR024989,
M01-RR00080, UL1-RR025764, and C06-RR11234. A. M. S. receives support
from the Women's Reproductive Health Research Career Development Center
at the University of North Carolina (grant no. 5K12HD050113-04).
NR 34
TC 5
Z9 6
U1 0
U2 9
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 JUL
PY 2012
VL 207
IS 1
AR 62.e1
DI 10.1016/j.ajog.2012.04.035
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 965GJ
UT WOS:000305755000024
PM 22609018
ER
PT J
AU Padmakumar, VC
Speer, K
Pal-Ghosh, S
Masiuk, KE
Ryscavage, A
Dengler, SL
Hwang, S
Edwards, JC
Coppola, V
Tessarollo, L
Stepp, MA
Yuspa, SH
AF Padmakumar, V. C.
Speer, Kelsey
Pal-Ghosh, Sonali
Masiuk, Katelyn E.
Ryscavage, Andrew
Dengler, Samuel L.
Hwang, Shelly
Edwards, John C.
Coppola, Vincenzo
Tessarollo, Lino
Stepp, Mary Ann
Yuspa, Stuart H.
TI Spontaneous Skin Erosions and Reduced Skin and Corneal Wound Healing
Characterize CLIC4(NULL) Mice
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID CHLORIDE CHANNEL PROTEIN; CELL-MIGRATION; TRANSFORMING
GROWTH-FACTOR-BETA-1; PROTEOMIC ANALYSIS; MOUSE; KERATINOCYTES; CLIC4;
EXPRESSION; CANCER; HEMIDESMOSOMES
AB Cutaneous wound healing is a complex process involving blood clotting, inflammation, migration of keratinocytes, angiogenesis, and, ultimately, tissue remodeling and wound closure. Many of these processes involve transforming growth factor-beta (TGF-beta) signaling, and mice lacking components of the TGF-beta signaling pathway are defective in wound healing. We show herein that CLIC4, an integral component of the TGF-beta pathway, is highly up-regulated in skin wounds. We genetically deleted murine CLIC4 and generated a colony on a C57Bl/6 background. CLIC4(NULL) mice were viable and fertile but had smaller litters than did wild-type mice. After 6 months of age, up to 40% of null mice developed spontaneous skin erosions. Reepithelialization of induced full-thickness skin wounds and superficial corneal wounds was delayed in CLIC4(NULL) mice, resolution of inflammation was delayed, and expression of beta 4 integrin and p21 was reduced in lysates of constitutive and wounded CLIC4(NULL) skin. The induced level of phosphorylated Smad2 in response to TGF-beta was reduced in cultured CLIC4(NULL) keratinocytes relative to in wild-type cells, and CLIC4(NULL) keratinocytes migrated slower than did wild-type keratinocytes and did not increase migration in response to TGF-beta. CLIC4(NULL) keratinocytes were also less adherent on plates coated with matrix secreted by wild-type keratinocytes. These results indicate that CLIC4 participates in skin healing and corneal wound reepithelialization through enhancement of epithelial migration by a mechanism that may involve a compromised TGF-beta pathway. (Am J Pathol 2012, 181:74-84; http://dx.doi.org/10.1016/j.ajpath.2012.03.025)
C1 [Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Pal-Ghosh, Sonali; Stepp, Mary Ann] George Washington Univ, Sch Med, Dept Anat & Regenerat Biol, Washington, DC USA.
[Edwards, John C.] St Louis Univ, Sch Med, Dept Med, Div Renal, St Louis, MO 63104 USA.
[Coppola, Vincenzo; Tessarollo, Lino] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bldg 37,Room 4068A1,37 Convent Dr, Bethesda, MD 20892 USA.
EM yuspas@mail.nih.gov
RI Coppola, Vincenzo/E-2917-2011
OI Coppola, Vincenzo/0000-0001-6163-1779
FU Center for Cancer Research, National Cancer Institute; NIH [EY08512,
5R01HL092131]
FX Supported by the Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, and by NIH grants EY08512 (S.P.-G.
and M.A.S.) and 5R01HL092131 (J.C.E.).
NR 44
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 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUL
PY 2012
VL 181
IS 1
BP 74
EP 84
DI 10.1016/j.ajpath.2012.03.025
PG 11
WC Pathology
SC Pathology
GA 966PY
UT WOS:000305851100009
PM 22613027
ER
PT J
AU Blair, RJR
AF Blair, R. J. R.
TI Cortical Thinning and Functional Connectivity in Psychopathy
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
ID VENTROMEDIAL PREFRONTAL CORTEX; DYSFUNCTION; ATTENTION; AMYGDALA; AUTISM
C1 NIMH, Unit Affect Cognit Neurosci, Bethesda, MD 20892 USA.
RP Blair, RJR (reprint author), NIMH, Unit Affect Cognit Neurosci, Bethesda, MD 20892 USA.
EM JamesBlair@mail.nih.gov
NR 12
TC 5
Z9 5
U1 0
U2 4
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUL
PY 2012
VL 169
IS 7
BP 684
EP 687
DI 10.1176/appi.ajp.12030396
PG 4
WC Psychiatry
SC Psychiatry
GA 966QV
UT WOS:000305853400004
PM 22760187
ER
PT J
AU Apud, JA
Zhang, FY
Decot, H
Bigos, KL
Weinberger, DR
AF Apud, Jose A.
Zhang, Fengyu
Decot, Heather
Bigos, Kristin L.
Weinberger, Daniel R.
TI Genetic Variation in KCNH2 Associated With Expression in the Brain of a
Unique hERG Isoform Modulates Treatment Response in Patients With
Schizophrenia
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID POTASSIUM CHANNEL; ATYPICAL ANTIPSYCHOTICS; DOPAMINE TRANSMISSION;
BLOCKADE; TARGET; DRUGS
AB Objective: Antidopaminergic drugs bind to hERG1 potassium channels encoded by the gene KCNH2, which accounts for the side effect of QT interval prolongation. KCNH2 has also been associated with schizophrenia risk, and risk alleles predict increased expression of a brain-selective isoform, KCNH2 3.1, that has unique physiological properties. The authors assessed whether genetic variation associated with KCNH2 3.1 expression influences the therapeutic effects of antipsychotic drugs.
Method: The authors performed a pharmacogenetic analysis of antipsychotic treatment response in patients with schizophrenia using data from two independent studies: a National Institute of Mental Health (NIMH) double-blind, placebo-controlled inpatient crossover trial (N=54) and the multicenter outpatient Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) study (N=364). The KCNH2 genotype that was previously associated with increased expression of KCNH2 3.1 in the brain was treated as a predictor variable. Treatment-associated changes in symptoms were evaluated in both groups with the Positive and Negative Syndrome Scale. The authors also analyzed time to discontinuation in the olanzapine arm of the CATIE study.
Results: In the NIMH study, individuals who were homozygous for the KCNH2 3.1 increased expression-associated T allele of rs1036145 showed significant improvement in positive symptoms, general psychopathology, and thought disturbance, while patients with other genotypes showed little change. In the CATIE study, analogous significant genotypic effects were observed. Moreover, individuals who were homozygous for the T allele at rs1036145 were one-fifth as likely to discontinue olanzapine.
Conclusions: These consistent findings in two markedly different treatment studies support the hypothesis that hERG1-mediated effects of antipsychotics may not be limited to their potential cardiovascular side effects but may also involve therapeutic actions related to the brainspecific 3.1 isoform of KCNH2. (Am J Psychiatry 2012; 169:725-734)
C1 [Weinberger, Daniel R.] NIMH, Intramural Res Program, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
Lieber Inst Brain Dev, Baltimore, MD USA.
RP Weinberger, DR (reprint author), NIMH, Intramural Res Program, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
EM drweinberger@libd.org
NR 27
TC 21
Z9 22
U1 1
U2 6
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUL
PY 2012
VL 169
IS 7
BP 725
EP 734
DI 10.1176/appi.ajp.2012.11081214
PG 10
WC Psychiatry
SC Psychiatry
GA 966QV
UT WOS:000305853400011
PM 22706279
ER
PT J
AU White, SF
Marsh, AA
Fowler, KA
Schechter, JC
Adalio, C
Pope, K
Sinclair, S
Pine, DS
Blair, RJR
AF White, Stuart F.
Marsh, Abigail A.
Fowler, Katherine A.
Schechter, Julia C.
Adalio, Christopher
Pope, Kayla
Sinclair, Stephen
Pine, Daniel S.
Blair, R. James R.
TI Reduced Amygdala Response in Youths With Disruptive Behavior Disorders
and Psychopathic Traits: Decreased Emotional Response Versus Increased
Top-Down Attention to Nonemotional Features
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID CALLOUS-UNEMOTIONAL TRAITS; VENTROMEDIAL PREFRONTAL CORTEX; COMMON
STEREOTACTIC SPACE; CONDUCT PROBLEMS; VISUAL-ATTENTION; CHILDREN;
ADOLESCENTS; MODULATION; DELINQUENCY; ACTIVATION
AB Objective: Amygdala dysfunction has been reported to exist in youths and adults with psychopathic traits. However, there has been disagreement as to whether this dysfunction reflects a primary emotional deficit or is secondary to atypical attentional control. The authors examined the validity of the contrasting predictions.
Method: Participants were 15 children and adolescents (ages 10-17 years) with both disruptive behavior disorders and psychopathic traits and 17 healthy comparison youths. Functional MRI was used to assess the response of the amygdala and regions implicated in top-down attentional control (the dorsomedial and lateral frontal cortices) to emotional expression under conditions of high and low attentional load.
Results: Relative to youths with disruptive behavior disorders and psychopathic traits, healthy comparison subjects showed a significantly greater increase in the typical amygdala response to fearful expressions under low relative to high attentional load conditions. There was also a selective inverse relationship between the response to fearful expressions under low attentional load and the callous-unemotional component (but not the narcissism or impulsivity component) of psychopathic traits. In contrast, the two groups did not differ in the significant recruitment of the dorsomedial and lateral frontal cortices as a function of attentional load.
Conclusions: Youths with disruptive behavior disorders and psychopathic traits showed reduced amygdala responses to fearful expressions under low attentional load but no indications of increased recruitment of regions implicated in top-down attentional control. These findings suggest that the emotional deficit observed in youths with disruptive behavior disorders and psychopathic traits is primary and not secondary to increased top-down attention to nonemotional stimulus features. (Am J Psychiatry 2012; 169:750-758)
C1 [White, Stuart F.] NIMH, Bethesda, MD 20892 USA.
Georgetown Univ, Dept Psychol, Washington, DC 20057 USA.
Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
RP White, SF (reprint author), NIMH, Bethesda, MD 20892 USA.
EM whitesf@mail.nih.gov
FU NIMH
FX Supported by the Intramural Research Program of NIMH.
NR 40
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Z9 41
U1 3
U2 24
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUL
PY 2012
VL 169
IS 7
BP 750
EP 758
DI 10.1176/appi.ajp.2012.11081270
PG 9
WC Psychiatry
SC Psychiatry
GA 966QV
UT WOS:000305853400014
PM 22456823
ER
PT J
AU Mattson, MP
AF Mattson, Mark P.
TI An ECSIT-centric view of Alzheimer's disease (Comment on DOI
10.1002/bies.201100193)
SO BIOESSAYS
LA English
DT Editorial Material
ID OXIDATIVE STRESS
C1 NIA, Neurosci Lab, Intramural Res Program, Bethesda, MD 20892 USA.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Bethesda, MD 20892 USA.
EM mattsonm@grc.nia.nih.gov
FU National Institute on Aging
FX This work was supported by the intramural research program of the
National Institute on Aging.
NR 15
TC 4
Z9 4
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0265-9247
J9 BIOESSAYS
JI Bioessays
PD JUL
PY 2012
VL 34
IS 7
BP 526
EP 527
DI 10.1002/bies.201200058
PG 2
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 958KG
UT WOS:000305234800005
PM 22641226
ER
PT J
AU Jiao, XL
Sherman, BT
Huang, DW
Stephens, R
Baseler, MW
Lane, HC
Lempicki, RA
AF Jiao, Xiaoli
Sherman, Brad T.
Huang, Da Wei
Stephens, Robert
Baseler, Michael W.
Lane, H. Clifford
Lempicki, Richard A.
TI DAVID-WS: a stateful web service to facilitate gene/protein list
analysis
SO BIOINFORMATICS
LA English
DT Article
ID LARGE GENE LISTS; BIOINFORMATICS RESOURCES; DATABASE
AB The database for annotation, visualization and integrated discovery (DAVID), which can be freely accessed at http://david.abcc.ncifcrf.gov/, is a web-based online bioinformatics resource that aims to provide tools for the functional interpretation of large lists of genes/proteins. It has been used by researchers from more than 5000 institutes worldwide, with a daily submission rate of similar to 1200 gene lists from similar to 400 unique researchers, and has been cited by more than 6000 scientific publications. However, the current web interface does not support programmatic access to DAVID, and the uniform resource locator (URL)-based application programming interface (API) has a limit on URL size and is stateless in nature as it uses URL request and response messages to communicate with the server, without keeping any state-related details. DAVID-WS (web service) has been developed to automate user tasks by providing stateful web services to access DAVID programmatically without the need for human interactions.
C1 [Jiao, Xiaoli; Sherman, Brad T.; Huang, Da Wei; Lempicki, Richard A.] NCI, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21702 USA.
[Stephens, Robert] NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
[Baseler, Michael W.] NCI, SAIC Frederick Inc, Clin Serv Program, Frederick, MD 21702 USA.
[Lane, H. Clifford] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Lempicki, RA (reprint author), NCI, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21702 USA.
EM xiaoli.jiao@nih.gov; rlempicki@nih.gov
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
FU National Institute of Allergy and Infectious Diseases (NIAID), National
institutes of Health (NIH) [NOI-CO-56000]
FX Funding: This project has been funded by the National Institute of
Allergy and Infectious Diseases (NIAID), National institutes of Health
(NIH), under Contract No. NOI-CO-56000. The contents do not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products or
organizations imply endorsement by the US Government.
NR 7
TC 119
Z9 121
U1 2
U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD JUL 1
PY 2012
VL 28
IS 13
BP 1805
EP 1806
DI 10.1093/bioinformatics/bts251
PG 2
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 966GJ
UT WOS:000305825600023
PM 22543366
ER
PT J
AU Troendle, JF
Zhang, ZW
Mathews, ME
Guo, JC
AF Troendle, James F.
Zhang, Zhiwei
Mathews, Megan E.
Guo, Junchi
TI Methods of adjusted comparison of medians
SO BIOMETRICAL JOURNAL
LA English
DT Article
DE Box-Cox transformation; Mean squared error; Predicted values; Reference
population
ID REGRESSION-MODELS
AB Consider the problem of making an adjusted comparison of the medians of two populations on an interval type outcome variable. A common method of doing this is through the use of a linear model requiring the residuals to be normally distributed. We describe here two methods based on a linear model after BoxCox transformation of the outcome variable. The methods require a reference population, which could be either of the populations under study or their aggregate. We compare the new procedures with the comparison of normal means procedure and other procedures proposed for this problem by simulation. It is found that the procedure based on comparison of the predicted values obtained from the observed covariates of the reference population has higher power for testing and smaller mean square error of estimation than the other methods, while maintaining reasonable control of the type I error rate. We illustrate the methods by analyzing the duration of the second stage of labor for women in two large observation studies (Collaborative Perinatal Project and Consortium on Safe Labor) separated by 50 years. We recommend the method based on comparison of the predicted values of the transformed outcomes, with careful attention to how close the resulting residual distribution is to normal.
C1 [Troendle, James F.] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH,DHHS, Bethesda, MD 20892 USA.
[Zhang, Zhiwei] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Mathews, Megan E.] Penn State Univ, Dept Stat, University Pk, PA 16802 USA.
[Guo, Junchi] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
RP Troendle, JF (reprint author), NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH,DHHS, Bld RLK2,Room 9195, Bethesda, MD 20892 USA.
EM jt3t@nih.gov
FU Intramural Research Program of the NICHD, National Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the NICHD, National Institutes of Health.
NR 16
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0323-3847
J9 BIOMETRICAL J
JI Biom. J.
PD JUL
PY 2012
VL 54
IS 4
BP 481
EP 493
DI 10.1002/bimj.201100220
PG 13
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 968MG
UT WOS:000305985000003
PM 22622655
ER
PT J
AU Liu, ZH
Lenardo, MJ
AF Liu, Zhihua
Lenardo, Michael J.
TI The role of LRRK2 in inflammatory bowel disease
SO CELL RESEARCH
LA English
DT Editorial Material
ID CROHNS-DISEASE; TRANSCRIPTION FACTOR; SUSCEPTIBILITY LOCI;
ULCERATIVE-COLITIS; NUCLEAR FACTOR; NFAT; ACTIVATION; NUMBER; CELLS
AB LRRK2 was recently identified as a major susceptibility gene for Crohn's disease (CD) by genome-wide association studies (GWAS). LRRK2 deficiency in mice confers enhanced susceptibility to experimental colitis. In this research highlight, we discuss the current understanding of LRRK2 in the context of colitis, and postulate the future directions.
C1 [Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Liu, Zhihua] Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China.
RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM lenardo@nih.gov
FU Intramural NIH HHS
NR 15
TC 6
Z9 6
U1 0
U2 6
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 JUL
PY 2012
VL 22
IS 7
BP 1092
EP 1094
DI 10.1038/cr.2012.42
PG 3
WC Cell Biology
SC Cell Biology
GA 968SF
UT WOS:000306004200002
PM 22430149
ER
PT J
AU Chen, GB
Weng, NP
AF Chen, Guobing
Weng, Nan-ping
TI Analyzing the phenotypic and functional complexity of lymphocytes using
CyTOF (cytometry by time-of-flight)
SO CELLULAR & MOLECULAR IMMUNOLOGY
LA English
DT Editorial Material
ID CONTINUUM
C1 [Chen, Guobing; Weng, Nan-ping] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
RP Weng, NP (reprint author), 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM wengn@mail.nih.gov
RI Chen, Guobing/D-9572-2012
OI Chen, Guobing/0000-0002-2401-6168
FU Intramural NIH HHS [ZIA AG000756-19, ZIA AG000757-19, ZIA AG000757-18]
NR 3
TC 6
Z9 6
U1 1
U2 12
PU CHIN SOCIETY IMMUNOLOGY
PI BEING
PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA
SN 1672-7681
J9 CELL MOL IMMUNOL
JI Cell. Mol. Immunol.
PD JUL
PY 2012
VL 9
IS 4
BP 322
EP 323
DI 10.1038/cmi.2012.16
PG 2
WC Immunology
SC Immunology
GA 968QZ
UT WOS:000306000800006
PM 22635255
ER
PT J
AU Chetty, M
Mattison, D
Rostami-Hodjegan, A
AF Chetty, Manoranjenni
Mattison, Donald
Rostami-Hodjegan, Amin
TI Sex Differences in the Clearance of CYP3A4 Substrates: Exploring
Possible Reasons for the Substrate Dependency and Lack of Consensus
SO CURRENT DRUG METABOLISM
LA English
DT Review
DE Sex differences; clearance differences; CYP3A4 substrates; study power;
benzodiazepines
ID CYTOCHROME-P450 3A ACTIVITY; IN-VITRO DATA; INTERINDIVIDUAL VARIABILITY;
PHARMACOKINETIC PROPERTIES; COMPARATIVE KINETICS; HUMAN-POPULATIONS;
DRUG-METABOLISM; ORAL NIFEDIPINE; ANGIOTENSIN-II; PHARMACODYNAMICS
AB Sex differences in the clearance of substrates of Cytochrome P4503A (CYP3A4) have been reported frequently although there has been no consensus on reasons for variation in observations amongst drugs which are seemingly all dependent on this enzyme for their metabolism. Moreover, these observations could not be replicated in all studies even when investigating the same drugs. Differing study designs and inadequate power to identify the sex differences may explain the conflicting reports. The aim of the current study was to use in vitro data on a number of CYP3A4 substrates to develop mechanistic population pharmacokinetic models which are capable of integrating various attributes of drugs and estimating the statistical power of in vivo studies designed to discern sex differences in the clearance of CYP3A4 substrates. Midazolam, triazolam, alprazolam, nifedipine and zolpidem were selected as test substrates. These compounds are predominantly metabolized by CYP3A4, unaffected by p-glycoprotein and have abundant clinical studies which can be used for validation purposes. Simulated apparent clearance, obtained by use of the Simcyp (R) Population-based Simulator and in vitro in vivo extrapolation (IVIVE) techniques, was compared in males and females after correcting for weight (CL/wt) in 1560 trials. Results suggested that about 105 subjects per study are required for an 80% probability of identifying a higher CL/wt in females with alprazolam, while the corresponding numbers for a similar power were 120, about 150 and 300 for nifedipine, triazolam and oral midazolam, respectively. The results were consistent with outcomes in published clinical studies and support the view that many of the published studies have inadequate power to detect these sex differences in drug clearance, thereby contributing to the lack of consensus on this subject.
C1 [Chetty, Manoranjenni; Rostami-Hodjegan, Amin] Simcyp Ltd, Blades Enterprise Ctr, Sheffield S2 4SU, S Yorkshire, England.
[Mattison, Donald] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Rostami-Hodjegan, Amin] Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PT, Lancs, England.
RP Chetty, M (reprint author), Simcyp Ltd, Blades Enterprise Ctr, John St, Sheffield S2 4SU, S Yorkshire, England.
EM m.chetty@simcyp.com
RI Mattison, Donald/L-4661-2013
OI Mattison, Donald/0000-0001-5623-0874
FU Simcyp Limited; Eunice Kennedy Shriver National, Institute of Child
Health and Human Development, National Institute of Health
FX This work was partly funded by Simcyp Limited. AR-H is seconded
part-time to Simcyp by the University of Manchester and is a shareholder
in the company. MC is an employee of Simcyp. Funding was also provided
in part by the intramural program of the Eunice Kennedy Shriver
National, Institute of Child Health and Human Development, National
Institute of Health to DRM. This paper was prepared in part by DRM as an
employee of the US Government making this a "work of the US, Government"
and therefore copyright is non-transferrable.
NR 69
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U1 1
U2 6
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-2002
J9 CURR DRUG METAB
JI Curr. Drug Metab.
PD JUL
PY 2012
VL 13
IS 6
BP 778
EP 786
PG 9
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 965VY
UT WOS:000305796700008
PM 22452452
ER
PT J
AU Telford, WG
AF Telford, William G.
TI Detecting apoptosis by flow cytometry: a practical guide
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 2nd Bi-Annual International Practical Cytometry Workshop
CY AUG 26-30, 2011
CL Moscow, RUSSIA
C1 [Telford, William G.] Natl Canc Inst, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD JUL
PY 2012
VL 82B
IS 4
BP O8
EP O8
PG 1
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 962PH
UT WOS:000305556900019
ER
PT J
AU Telford, WG
AF Telford, William G.
TI Analysis of stem cells by side-population evaluation
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 2nd Bi-Annual International Practical Cytometry Workshop
CY AUG 26-30, 2011
CL Moscow, RUSSIA
C1 [Telford, William G.] Natl Canc Inst, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD JUL
PY 2012
VL 82B
IS 4
BP O8
EP O8
PG 1
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 962PH
UT WOS:000305556900018
ER
PT J
AU Barzilay, JI
Howard, AG
Evans, GW
Fleg, JL
Cohen, RM
Booth, GL
Kimel, AR
Pedley, CF
Cushman, WC
AF Barzilay, Joshua I.
Howard, Annie G.
Evans, Gregory W.
Fleg, Jerome L.
Cohen, Robert M.
Booth, Gillian L.
Kimel, Angela R.
Pedley, Carolyn F.
Cushman, William C.
TI Intensive Blood Pressure Treatment Does Not Improve Cardiovascular
Outcomes in Centrally Obese Hypertensive Individuals With Diabetes The
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood
Pressure Trial
SO DIABETES CARE
LA English
DT Article
ID TO-HEIGHT RATIO; DISEASE; MELLITUS; COHORT
AB OBJECTIVE-The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial reported no differences in most cardiovascular disease (CVD) outcomes between intensive and standard blood pressure therapy in individuals with diabetes mellitus (DM) and hypertension. Many such individuals are centrally obese. Here we evaluate whether the trial outcomes varied by the level of central obesity.
RESEARCH DESIGN AND METHODS-The cohort included 4,687 people (47.7% women) with DM and hypertension. Mean age was 62.2, and mean follow-up was 4.7 years. Participants were randomly assigned to one of two blood pressure treatment strategies: intensive (systolic <120 mmHg) or standard (systolic <140 mmHg). Sex-specific quartiles of waist-to-height ratio were used as the measure of central obesity. The primary ACCORD outcome (a composite of nonfatal myocardial infarction [MI], nonfatal stroke, or CVD death) and three secondary outcomes (nonfatal MI, fatal or nonfatal stroke, and CVD death) were examined using proportional hazard models.
RESULTS-There was no evidence that the effect of intensively lowering blood pressure differed by quartile of waist-to-height ratio for any of the four outcomes (P > 0.25 in all cases). Controlling for waist-to-height quartile had no significant impact on previously published results for intensive blood pressure therapy. Waist-to-height ratio was significantly related to CVD mortality (hazard ratio 2.32 [95% CI 1.40-3.83], P = 0.0009 comparing the heaviest to lightest quartiles), but not to the other outcomes (P > 0.09 in all cases).
CONCLUSIONS-Intensive lowering of blood pressure versus standard treatment does not ameliorate CVD risk in individuals with DM and hypertension. These results did not vary by quartile of waist-to-height ratio.
C1 [Barzilay, Joshua I.] Emory Univ, Div Endocrinol, Sch Med, Kaiser Permanente Georgia, Atlanta, GA 30322 USA.
[Howard, Annie G.; Evans, Gregory W.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Neurol, Winston Salem, NC USA.
[Howard, Annie G.; Evans, Gregory W.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA.
[Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Cohen, Robert M.] Univ Cincinnati, Div Endocrinol Diabet & Metab, Coll Med, Cincinnati, OH USA.
[Booth, Gillian L.] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Kimel, Angela R.] Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Pedley, Carolyn F.] Wake Forest Sch Med, Dept Med, Winston Salem, NC USA.
[Cushman, William C.] Vet Affairs Med Ctr, Dept Med, Memphis, TN USA.
RP Barzilay, JI (reprint author), Emory Univ, Div Endocrinol, Sch Med, Kaiser Permanente Georgia, Atlanta, GA 30322 USA.
EM joshua.barzilay@kp.org
FU National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179,
N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184,
IAA Y1-HC-9035, IAA Y1-HC-1010]; National Institutes of Health; National
Institute of Diabetes and Digestive and Kidney Diseases; National
Institute on Aging; National Eye Institute; Centers for Disease Control
and Prevention within ACCORD on cost-effectiveness and health-related
quality of life
FX This study was supported by contracts from the National Heart, Lung, and
Blood Institute (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181,
N01-HC-95182, N01-HC-95183, N01-HC-95184 and IAA#Y1-HC-9035 and
IAA#Y1-HC-1010). Other components of the National Institutes of Health,
including the National Institute of Diabetes and Digestive and Kidney
Diseases, the National Institute on Aging, and the National Eye
Institute, contributed funding. The Centers for Disease Control and
Prevention funded substudies within ACCORD on cost-effectiveness and
health-related quality of life. General Clinical Research Centers
provide support at many sites. The following companies provided study
medications, equipment, or supplies: Abbott Laboratories, Arnylin
Pharmaceutical, AstraZeneca Pharmaceuticals, Bayer Health Care, Closer
Healthcare, GlaxoSmitliKline Pharmaceuticals, King Pharmaceuticals,
Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare,
sanofi-aventis U.S., and Takecla. No other potential conflicts of
interest relevant to this article were reported.
NR 16
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PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2012
VL 35
IS 7
BP 1401
EP 1405
DI 10.2337/dc11-1827
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 962MJ
UT WOS:000305548900003
PM 22723577
ER
PT J
AU O'Connor, PJ
Narayan, KMV
Anderson, R
Feeney, P
Fine, L
Ali, MK
Simmons, DL
Hire, DG
Sperl-Hillen, JM
Katz, LA
Margolis, KL
Sullivan, MD
AF O'Connor, Patrick J.
Narayan, K. M. Venkat
Anderson, Roger
Feeney, Patricia
Fine, Larry
Ali, Mohammed K.
Simmons, Debra L.
Hire, Don G.
Sperl-Hillen, JoAnn M.
Katz, Lois Anne
Margolis, Karen L.
Sullivan, Mark D.
TI Effect of Intensive Versus Standard Blood Pressure Control on Depression
and Health-Related Quality of Life in Type 2 Diabetes The ACCORD trial
SO DIABETES CARE
LA English
DT Article
ID MELLITUS; HYPERTENSION
AB OBJECTIVE-We tested the hypothesis that intensive (systolic blood pressure [SBP] <120 mmHg) rather than standard (SBP 130-139 mmHg) blood pressure (BP) control improves health-related quality of life (HRQL) in those with type 2 diabetes.
RESEARCH DESIGN AND METHODS-Subjects were 1,028 ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial HRQL substudy participants who completed baseline and one or more 12-, 36-, or 48-month HRQL evaluations. Multivariable linear regression assessed impact of BP treatment assignment on change in HRQL.
RESULTS-Over 4.0 years of follow-up, no significant differences occurred in five of six HRQL measures. Those assigned to intensive (vs. standard) BP control had statistically significant worsening of the Medical Outcomes Study 36-item short-form health survey (SF36) physical component scores (-0.8 vs. -0.2; P = 0.02), but magnitude of change was not clinically significant. Findings persisted across all prespecified subgroups.
CONCLUSIONS-Intensive BP control in the ACCORD trial did not have a clinically significant impact, either positive or negative, on depression or patient-reported HRQL.
C1 [O'Connor, Patrick J.; Sperl-Hillen, JoAnn M.; Margolis, Karen L.] HealthPartners Res Fdn, Minneapolis, MN USA.
[Narayan, K. M. Venkat; Ali, Mohammed K.] Emory Univ, Hubert Dept Global Hlth, Atlanta, GA 30322 USA.
[Anderson, Roger] Penn State Univ, Coll Med, Dept Publ Hlth Sci, Hershey, PA USA.
[Feeney, Patricia; Hire, Don G.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Fine, Larry] NHLBI, NIH, Bethesda, MD 20892 USA.
[Simmons, Debra L.] Univ Arkansas Med Sci, Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA.
[Katz, Lois Anne] VA New York Harbor Healthcare Syst, New York, NY USA.
[Sullivan, Mark D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
RP O'Connor, PJ (reprint author), HealthPartners Res Fdn, Minneapolis, MN USA.
EM patrick.j.oconnor@healthpartners.com
RI Narayan, K.M. Venkat /J-9819-2012
OI Narayan, K.M. Venkat /0000-0001-8621-5405
FU National Heart, Lung, and Blood Institute [N01-HC-095183]; National
Institute of Diabetes and Digestive and Kidney Diseases; Centers for
Disease Control and Prevention
FX This study was funded by the National Heart, Lung, and Blood Institute
(N01-HC-095183 and other contracts), National Institute of Diabetes and
Digestive and Kidney Diseases, and Centers for Disease Control and
Prevention.
NR 15
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U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2012
VL 35
IS 7
BP 1479
EP 1481
DI 10.2337/dc11-1868
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 962MJ
UT WOS:000305548900014
PM 22584134
ER
PT J
AU Schwartz, AV
Margolis, KL
Sellmeyer, DE
Vittinghoff, E
Ambrosius, WT
Bonds, DE
Josse, RG
Schnall, AM
Simmons, DL
Hue, TF
Palermo, L
Hamilton, BP
Green, JB
Atkinson, HH
O'Connor, PJ
Force, RW
Bauer, DC
AF Schwartz, Ann V.
Margolis, Karen L.
Sellmeyer, Deborah E.
Vittinghoff, Eric
Ambrosius, Walter T.
Bonds, Denise E.
Josse, Robert G.
Schnall, Adrian M.
Simmons, Debra L.
Hue, Trisha F.
Palermo, Lisa
Hamilton, Bruce P.
Green, Jennifer B.
Atkinson, Hal H.
O'Connor, Patrick J.
Force, Rex W.
Bauer, Douglas C.
TI Intensive Glycemic Control Is Not Associated With Fractures or Falls in
the ACCORD Randomized Trial
SO DIABETES CARE
LA English
DT Article
ID BLOOD-GLUCOSE CONTROL; DIABETES-MELLITUS; OLDER WOMEN; EPIDEMIOLOGIC
ANALYSIS; POSTMENOPAUSAL WOMEN; VERTEBRAL FRACTURES; SEVERE
HYPOGLYCEMIA; PRACTICE GUIDELINES; INCREASED RISK; HIP FRACTURE
AB OBJECTIVE-Older adults with type 2 diabetes are at high risk of fractures and falls, but the effect of glycemic control on these outcomes is unknown. To determine the effect of intensive versus standard glycemic control, we assessed fractures and falls as outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) randomized trial.
RESEARCH DESIGN AND METHODS ACCORD-participants were randomized to intensive or standard glycemia strategies, with an achieved median A1C of 6.4 and 7.5%, respectively. In the ACCORD BONE ancillary study, fractures were assessed at 54 of the 77 ACCORD clinical sites that included 7,287 of the 10,251 ACCORD participants. At annual visits, 6,782 participants were asked about falls in the previous year.
RESULTS-During an average follow-up of 3.8 (SD 1.3) years, 198 of 3,655 participants in the intensive glycemia and 189 of 3,632 participants in the standard glycemia group experienced at least one nonspine fracture. The average rate of first nonspine fracture was 13.9 and 13.3 per 1,000 person-years in the intensive and standard groups, respectively (hazard ratio 1.04 [95% CI 0.86-1.27]). During an average follow-up of 2.0 years, 1,122 of 3,364 intensive- and 1,133 of 3,418 standard-therapy participants reported at least one fall. The average rate of falls was 60.8 and 55.3 per 100 person-years in the intensive and standard glycemia groups, respectively (1.10 [0.84-1.43]).
CONCLUSIONS-Compared with standard glycemia, intensive glycemia did not increase or decrease fracture or fall risk in ACCORD.
C1 [Schwartz, Ann V.; Vittinghoff, Eric; Hue, Trisha F.; Palermo, Lisa; Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Margolis, Karen L.; O'Connor, Patrick J.] HealthPartners Res Fdn, Minneapolis, MN USA.
[Sellmeyer, Deborah E.] Johns Hopkins Sch Med, Div Endocrinol, Baltimore, MD USA.
[Ambrosius, Walter T.; Atkinson, Hal H.] Wake Forest Sch Med, Dept Biostat, Winston Salem, NC USA.
[Bonds, Denise E.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA.
[Josse, Robert G.] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Schnall, Adrian M.] Case Western Reserve Sch Med, Dept Med, Cleveland, OH USA.
[Simmons, Debra L.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Simmons, Debra L.] Cent Arkansas Vet Healthcare Syst, Dept Endocrinol & Metab, Little Rock, AR USA.
[Hamilton, Bruce P.] Univ Maryland, Sch Med, Dept Med, Baltimore VA Med Ctr, Baltimore, MD 21201 USA.
[Green, Jennifer B.] Duke Univ, Med Ctr, Dept Med Endocrinol & Metab, Durham, NC USA.
[Force, Rex W.] Idaho State Univ, Coll Pharm, Pocatello, ID 83209 USA.
RP Schwartz, AV (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
EM aschwanz@psg.ucsf.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[R01DK069514]; National Heart, Lung, and Blood Institute [N01-HC-95178,
N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183,
N01-HC-95184, IAA-Y1-HC-9035, IAA-Y1-HC-1010]; National Institutes of
Health; NIDDK; National Institute on Aging; National Eye Institute;
Centers for Disease Control and Prevention; General Clinical Research
Centers; Medtronic; Merck; Amylin; Takeda; Taking Control of Your
Diabetes; American Association of Clinical Endocrinology
FX The ACCORD BONE ancillary study was funded by a grant (R01DK069514) from
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK). The ACCORD study was supported by grants (N01-HC-95178,
N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183,
N01-HC-95184, IAA-Y1-HC-9035, and IAA-Y1-HC-1010) from the National
Heart, Lung, and Blood Institute; by other components of the National
Institutes of Health, including the NIDDK, the National Institute on
Aging, and the National Eye Institute; by the Centers for Disease
Control and Prevention; and by General Clinical Research Centers. The
following companies provided study medications, equipment, or supplies:
Abbott Laboratories, Amyl in Pharmaceutical, AstraZeneca, Bayer
HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals,
Merck, Novartis, Novo Nordisk, Omron Healthcare, sanofi-aventis, and
Schering-Plough. J.B.G. has been a paid consultant for Medtronic;
received grant funding from Medtronic, Merck, and Amylin; received
speaking fees from Merck and Takeda; and received payment for
educational presentations from Taking Control of Your Diabetes and the
American Association of Clinical Endocrinology. No other potential
conflicts of interest relevant to this article were reported.
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PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2012
VL 35
IS 7
BP 1525
EP 1531
DI 10.2337/dc11-2184
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 962MJ
UT WOS:000305548900022
PM 22723583
ER
PT J
AU Sosenko, JM
Skyler, JS
Mahon, J
Krischer, JP
Beam, CA
Boulware, DC
Greenbaum, CJ
Rafkin, LE
Cowie, C
Cuthbertson, D
Palmer, JP
AF Sosenko, Jay M.
Skyler, Jay S.
Mahon, Jeffrey
Krischer, Jeffrey P.
Beam, Craig A.
Boulware, David C.
Greenbaum, Carla J.
Rafkin, Lisa E.
Cowie, Catherine
Cuthbertson, David
Palmer, Jerry P.
CA Type 1 Diabet TrialNet & Diabet Pr
TI The Application of the Diabetes Prevention Trial-Type 1 Risk Score for
Identifying a Preclinical State of Type 1 Diabetes
SO DIABETES CARE
LA English
DT Article
ID BETA-CELL FUNCTION; GLUCOSE-TOLERANCE; INSULIN; ONSET; TRIAL-TYPE-1;
MELLITUS; PARTICIPANTS; PROGRESSION; ANTIBODIES
AB OBJECTIVE-We assessed the utility of the Diabetes Prevention Trial Type 1 Risk Score (DPTRS) for identifying individuals who are highly likely to progress to type 1 diabetes (T ID) within 2 years.
RESEARCH DESIGN AND METHODS-The DPTRS was previously developed from Diabetes Prevention Trial Type 1 (DPT-1) data and was subsequently validated in the TrialNet Natural History Study (TNNHS). DPTRS components included C-peptide and glucose indexes from oral glucose tolerance testing, along with age and BM1. The cumulative incidence of T ID was determined after DPTRS thresholds were first exceeded and after the first occurrences of glucose abnormalities.
RESULTS-The 2-year risks after the 9.00 DPTRS threshold was exceeded were 0.88 and 0.77 in DPT-1 (n = 90) and the TNNHS (n = 69), respectively. In DPT-1, the 2-year risks were much lower after dysglycemia first occurred (0.37; n = 306) and after a 2-h glucose value between 190 and 199 mg/dL was first reached (0.64; n = 59). Among those who developed T1D in DPT-1, the 9.00 threshold was exceeded 0.81 +/- 0.53 years prior to the conventional diagnosis. Post-challenge C-peptide levels were substantially higher (P = 0.001 for 30 min; P < 0.001 for other time points) when the 9.00 threshold was first exceeded compared with the levels at diagnosis.
CONCLUSIONS-A DPTRS threshold of 9.00 identifies individuals who are very highly likely to progress to the conventional diagnosis of T ID within 2 years and, thus, are essentially in a preclinical diabetic state. The 9.00 threshold is exceeded well before diagnosis, when stimulated C-peptide levels are substantially higher. Diabetes Care 35:1552-1555,2012
C1 [Sosenko, Jay M.; Skyler, Jay S.; Rafkin, Lisa E.] Univ Miami, Div Endocrinol, Miami, FL 33136 USA.
[Mahon, Jeffrey] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada.
[Krischer, Jeffrey P.; Beam, Craig A.; Boulware, David C.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA.
[Greenbaum, Carla J.] Benaroya Res Inst Virginia Mason, Seattle, WA USA.
[Cowie, Catherine] NIDDK, NIH, Bethesda, MD USA.
[Cuthbertson, David] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA.
[Palmer, Jerry P.] Univ Washington, VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA.
RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL 33136 USA.
EM jsosenko@med.miami.edu
RI Skyler, Jay/F-4211-2016
FU National Institutes of Health through the National Institute of Diabetes
and Digestive and Kidney Diseases; National Institute of Allergy and
Infectious Diseases; Eunice Kennedy Shriver National Institute for Child
Health and Human Development; National Center for Research Resources;
Juvenile Diabetes Research Foundation International; American Diabetes
Association
FX This work was funded by the National Institutes of Health through the
National Institute of Diabetes and Digestive and Kidney Diseases, the
National Institute of Allergy and Infectious Diseases, the Eunice
Kennedy Shriver National Institute for Child Health and Human
Development, and the National Center for Research Resources; by the
Juvenile Diabetes Research Foundation International; and by the American
Diabetes Association.
NR 20
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PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2012
VL 35
IS 7
BP 1552
EP 1555
DI 10.2337/dc12-0011
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 962MJ
UT WOS:000305548900026
PM 22547092
ER
PT J
AU Casagrande, SS
Burrows, NR
Geiss, LS
Bainbridge, KE
Fradkin, JE
Cowie, CC
AF Casagrande, Sarah Stark
Burrows, Nilka Rios
Geiss, Linda S.
Bainbridge, Kathleen E.
Fradkin, Judith E.
Cowie, Catherine C.
TI Diabetes Knowledge and Its Relationship With Achieving Treatment
Recommendations in a National Sample of People With Type 2 Diabetes
SO DIABETES CARE
LA English
DT Article
ID GLYCEMIC CONTROL; SELF-MANAGEMENT; RISK-FACTORS; DISEASE; EDUCATION;
TARGETS; ADULTS
AB OBJECTIVE-We examined the prevalence of knowledge of A1C, blood pressure, and LDL cholesterol (ABC) levels and goals among people with diabetes, its variation by patient characteristics, and whether knowledge was associated with achieving levels of ABC control recommended for the general diabetic population.
RESEARCH DESIGN AND METHODS-Data came from 1,233 adults who self-reported diabetes in the 2005-2008 National Health and Nutrition Examination Survey. Participants reported their last ABC level and goals specified by their physician (not validated by medical record data). Analysis included descriptive statistics and logistic regression.
RESULTS-Among participants tested in the past year, 48% stated their last A1C level. Overall, 63% stated their last blood pressure level and 22% stated their last LDL cholesterol level. Knowledge of ABC levels was greatest in non-Hispanic whites, lowest in Mexican Americans, and higher with more education and income (all P <= 0.02). Demographic associations were similar for those reporting physician-specified ABC goals at the American Diabetes Association recommended levels (A1C <7%, blood pressure <130/80 mmHg, and LDL cholesterol <100 mg/dL). Nineteen percent of participants stated that their provider did not specify an A1C goal compared with 47% and 41% for blood pressure and LDL cholesterol goals, respectively. For people who self-reported A1C <7.0%, 83% had an actual A1C <7.0%. Otherwise, participant knowledge was not significantly associated with risk factor control, except for in those who knew their last LDL cholesterol level (P = 0.046 for A1C <7.0%). Results from logistic regression corroborated these findings.
CONCLUSIONS-Ample opportunity exists to improve ABC knowledge. Diabetes education should include behavior change components in addition to information on ABC clinical measures. Diabetes Care 35:1556-1565,2012
C1 [Casagrande, Sarah Stark] Social & Sci Syst, Silver Spring, MD USA.
[Burrows, Nilka Rios; Geiss, Linda S.] Natl Ctr Chron Dis Prevent & Hlth Promot, Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA.
[Bainbridge, Kathleen E.] Natl Inst Deafness & Other Commun Disorders, Div Sci Programs, Bethesda, MD USA.
[Fradkin, Judith E.; Cowie, Catherine C.] NIDDK, Div Endocrinol Diabet & Metab, Bethesda, MD USA.
RP Casagrande, SS (reprint author), Social & Sci Syst, Silver Spring, MD USA.
EM scasagrande@s-3.com
FU National Institute of Diabetes and Digestive and Kidney Diseases
[HHSN267200700001G]
FX This work was financially supported by the National Institute of
Diabetes and Digestive and Kidney Diseases (HHSN267200700001G).
NR 24
TC 9
Z9 9
U1 1
U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2012
VL 35
IS 7
BP 1556
EP 1565
DI 10.2337/dc11-1943
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 962MJ
UT WOS:000305548900027
ER
PT J
AU Romero, OA
Setien, F
John, S
Gimenez-Xavier, P
Gomez-Lopez, G
Pisano, D
Condom, E
Villanueva, A
Hager, GL
Sanchez-Cespedes, M
AF Romero, Octavio A.
Setien, Fernando
John, Sam
Gimenez-Xavier, Pol
Gomez-Lopez, Gonzalo
Pisano, David
Condom, Enric
Villanueva, Alberto
Hager, Gordon L.
Sanchez-Cespedes, Montse
TI The tumour suppressor and chromatin-remodelling factor BRG1 antagonizes
Myc activity and promotes cell differentiation in human cancer
SO EMBO MOLECULAR MEDICINE
LA English
DT Article
DE BRG1; lung cancer; MYC; retinoic acid; SWI; SNF
ID RETINOIC ACID RECEPTOR; LUNG-CANCER; GLUCOCORTICOID-RECEPTOR; ACTIN
CYTOSKELETON; SWI/SNF COMPLEX; NUCLEOSOME DISRUPTION; LINES; GENE;
EXPRESSION; TRANSACTIVATION
AB BRG1, a member of the SWI/SNF complex, is mutated in cancer, but it is unclear how it promotes tumourigenesis. We report that re-expression of BRG1 in lung cancer cells up-regulates lung-specific transcripts, restoring the gene expression signature of normal lung. Using cell lines from several cancer types we found that those lacking BRG1 do not respond to retinoic acid (RA) or glucocorticoids (GC), while restoration of BRG1 restores sensitivity. Conversely, in SH-SY5Y cells, a paradigm of RA-dependent differentiation, abrogation of BRG1 prevented the response to RA. Further, our data suggest an antagonistic functional connection between BRG1 and MYC, whereby, refractoriness to RA and GC by BRG1 inactivation involves deregulation of MYC activity. Mechanistically, some of these effects are mediated by BRG1 binding to MYC and MYC-target promoters. The BRG1-MYC antagonism was also evident in primary tumours. Finally, BRG1 restoration significantly dampened invasion and progression and decreased MYC in lung cancer cells orthotopically implanted in nude mice. Thus, BRG1 inactivation enables cancer cells to sustain undifferentiated gene expression programs and prevent its response to environmental stimuli.
C1 [Romero, Octavio A.; Setien, Fernando; Gimenez-Xavier, Pol; Sanchez-Cespedes, Montse] Bellvitge Biomed Res Inst IDIBELL, Genes & Canc Grp, Canc Epigenet & Biol Program PEBC, Barcelona, Spain.
[John, Sam; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Gomez-Lopez, Gonzalo; Pisano, David] Spanish Natl Canc Ctr CNIO, Bioinformat Unit, Struct Biol & BioComp Programme, Madrid, Spain.
[Condom, Enric] Bellvitge Hosp, Dept Pathol, Barcelona, Spain.
[Villanueva, Alberto] Catalan Inst Oncol ICO, Translat Res Lab, Barcelona, Spain.
RP Sanchez-Cespedes, M (reprint author), Bellvitge Biomed Res Inst IDIBELL, Genes & Canc Grp, Canc Epigenet & Biol Program PEBC, Barcelona, Spain.
EM mscespedes@idibell.cat
RI Sanchez-Cespedes, Montse/H-8485-2012; Pisano, David/N-5817-2014;
Gomez-Lopez, Gonzalo/D-9123-2016;
OI Sanchez-Cespedes, Montse/0000-0002-6045-5627; Pisano,
David/0000-0002-4895-4124; Gomez-Lopez, Gonzalo/0000-0002-4146-0551;
Gimenez Xavier, Pol/0000-0003-1611-5083
FU Spanish Grants [SAF2008-02698, RTICCs (RD06/0020/0062)]; Fundacion
Sandra Ibarra; FPI from the Ministerio de Ciencia e Innovacion, Spain
FX We acknowledge the technical assistance of Albert Coll (Genes and Cancer
Group) Daniel Cuadras (IDIBELL) for bioinformatic support and Orlando
Dominguez (CNIO). This work has been supported by Spanish Grants
SAF2008-02698, RTICCs (RD06/0020/0062) and the Fundacion Sandra Ibarra.
OAR is in receipt of a fellowship (FPI) from the Ministerio de Ciencia e
Innovacion, Spain.
NR 54
TC 30
Z9 31
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1757-4676
J9 EMBO MOL MED
JI EMBO Mol. Med.
PD JUL
PY 2012
VL 4
IS 7
BP 603
EP 616
DI 10.1002/emmm.201200236
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 967YH
UT WOS:000305943600010
PM 22407764
ER
PT J
AU Meissner, EG
Bennett, JE
Qvarnstrom, Y
da Silva, A
Chu, EY
Tsokos, M
Gea-Banacloche, J
AF Meissner, Eric G.
Bennett, John E.
Qvarnstrom, Yvonne
da Silva, Alexandre
Chu, Emily Y.
Tsokos, Maria
Gea-Banacloche, Juan
TI Disseminated Microsporidiosis in an Immunosuppressed Patient
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID NODULAR CUTANEOUS MICROSPORIDIOSIS; ACUTE MYELOGENOUS LEUKEMIA; AIDS
AB We report a case of disseminated microsporidiosis in a patient with multiple myeloma who had received an allogeneic stem cell transplant requiring substantial immunosuppression. The causative organism was identified as Tubulinosema acridophagus, confirming this genus of microsporidia as a novel human pathogen.
C1 [Meissner, Eric G.; Bennett, John E.; Chu, Emily Y.; Tsokos, Maria; Gea-Banacloche, Juan] NIAID, NIH, Bethesda, MD 20892 USA.
[Qvarnstrom, Yvonne; da Silva, Alexandre] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Meissner, EG (reprint author), NIAID, NIH, 10 Ctr Dr,Room 11N204, Bethesda, MD 20892 USA.
EM eric.meissner@nih.gov
FU National Institutes of Health (National Institute of Allergy and
Infectious Diseases and National Cancer Institute)
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (National Institute of Allergy and
Infectious Diseases and National Cancer Institute).
NR 8
TC 17
Z9 19
U1 0
U2 1
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD JUL
PY 2012
VL 18
IS 7
BP 1155
EP 1158
DI 10.3201/eid1807.120047
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 969CZ
UT WOS:000306034600021
PM 22709509
ER
PT J
AU Li, Y
Burns, KA
Arao, Y
Luh, CJ
Korach, KS
AF Li, Yin
Burns, Katherine A.
Arao, Yukitomo
Luh, Colin J.
Korach, Kenneth S.
TI Differential Estrogenic Actions of Endocrine-Disrupting Chemicals
Bisphenol A, Bisphenol AF, and Zearalenone through Estrogen Receptor
alpha and beta in Vitro
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE BPA; BPAF; ER alpha; ER alpha mutants; ER beta; ERE; estrogen;
zearalenone
ID GENE-EXPRESSION; BINDING DOMAIN; ER-ALPHA; MECHANISMS; ESTRADIOL;
NUCLEAR; VIVO; TRANSCRIPTION; ANTAGONIST; ELEMENTS
AB BACKGROUND: Endocrine-disrupting chemicals (EDCs) are widely found in the environment. Estrogen-like activity is attributed to EDCs, such as bisphenol A (BPA), bisphenol AF (BPAF), and zearalenone (Zea), but mechanisms of action and diversity of effects are poorly understood.
OBJECTIVES: We used in vitro models to evaluate the mechanistic actions of BPA, BPAF, and Zea on estrogen receptor (ER) alpha and ER beta.
METHODS: We used three human cell lines (Ishikawa, He La, and HepG2) representing three cell types to evaluate the estrogen promoter activity of BPA, BPAF, and Zea on ER alpha and ER beta. Ishikawa/ER alpha stable cells were used to determine changes in estrogen response element (ERE)-mediated target gene expression or rapid action-mediated effects.
RESULTS: The three EDCs showed strong estrogenic activity as agonists for ER alpha in a dose-dependent manner. At lower concentrations, BPA acted as an antagonist for ER alpha in Ishikawa cells and BPAF acted as an antagonist for ER beta in He La cells, whereas Zea was only a partial antagonist for ER alpha. ERE-mediated activation by BPA and BPAF was via the AF-2 function of ER alpha, but Zea activated via both the AF-1 and AF-2 functions. Endogenous ER alpha target genes and rapid signaling via the p44/42 MAPK pathway were activated by BPA, BPAF, and Zea.
CONCLUSION: BPA and BPAF can function as EDCs by acting as cell type specific agonists (>= 10 nM) or antagonists (<= 10 nM) for ER alpha and ER beta. Zea had strong estrogenic activity and activated both the AF-1 and AF-2 functions of ER alpha. In addition, all three compounds induced the rapid action-mediated response for ER alpha.
C1 [Li, Yin; Burns, Katherine A.; Arao, Yukitomo; Luh, Colin J.; Korach, Kenneth S.] NIEHS, Receptor Biol Sect, LRDT, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, LRDT, NIH,Dept Hlth & Human Serv, MD B3-02,POB 12233, Res Triangle Pk, NC 27709 USA.
EM korach@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU Division of Intramural Research, National Institute of Environmetal
Health Sciences [Z01 ES70065]
FX This research was supported by the Division of Intramural Research,
National Institute of Environmetal Health Sciences through Z01 ES70065
to K.S.K.
NR 35
TC 57
Z9 60
U1 5
U2 61
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUL
PY 2012
VL 120
IS 7
BP 1029
EP 1035
DI 10.1289/ehp.1104689
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 969DG
UT WOS:000306035300030
PM 22494775
ER
PT J
AU Drew, CH
Pettibone, KG
O'Fallon, LR
Collman, GW
Birnbaum, LS
AF Drew, Christina H.
Pettibone, Kristianna G.
O'Fallon, Liam R.
Collman, Gwen W.
Birnbaum, Linda S.
TI Measuring Partnership Activities: Partnerships in Environmental Public
Health Evaluation Metrics Manual
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
C1 [Drew, Christina H.; Pettibone, Kristianna G.; O'Fallon, Liam R.; Collman, Gwen W.] Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Natl Inst Hlth, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Birnbaum, Linda S.] Natl Toxicol Program, Natl Inst Hlth, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Birnbaum, Linda S.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
RP Drew, CH (reprint author), Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Natl Inst Hlth, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
EM drewc@niehs.nih.gov; birnbaumls@niehs.nih.gov
NR 3
TC 1
Z9 1
U1 0
U2 2
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUL
PY 2012
VL 120
IS 7
BP A261
EP A262
DI 10.1289/ehp.1205512
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 969DG
UT WOS:000306035300002
PM 22759358
ER
PT J
AU Landrigan, PJ
Lambertini, L
Birnbaum, LS
AF Landrigan, Philip J.
Lambertini, Luca
Birnbaum, Linda S.
TI A Research Strategy to Discover the Environmental Causes of Autism and
Neurodevelopmental Disabilities
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
ID SPECTRUM DISORDERS; DEVELOPING BRAIN; EXPOSURE; CHILDREN; CHEMICALS;
AGE; BEHAVIOR; LEAD; BANGLADESH; GENES
C1 [Landrigan, Philip J.; Lambertini, Luca] Mt Sinai Sch Med, Childrens Environm Hlth Ctr, New York, NY USA.
[Birnbaum, Linda S.] NTP, Natl Inst Hlth, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Birnbaum, Linda S.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Landrigan, PJ (reprint author), Mt Sinai Sch Med, Childrens Environm Hlth Ctr, New York, NY USA.
EM phil.landrigan@mssm.edu; birnbaumls@niehs.nih.gov
NR 36
TC 54
Z9 56
U1 7
U2 30
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUL
PY 2012
VL 120
IS 7
BP A258
EP A260
DI 10.1289/ehp.1104285
PG 3
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 969DG
UT WOS:000306035300001
PM 22543002
ER
PT J
AU Opsenica, I
Filipovic, V
Nuss, JE
Gomba, LM
Opsenica, D
Burnett, JC
Gussio, R
Solaja, BA
Bavari, S
AF Opsenica, Igor
Filipovic, Vuk
Nuss, Jon E.
Gomba, Laura M.
Opsenica, Dejan
Burnett, James C.
Gussio, Rick
Solaja, Bogdan A.
Bavari, Sina
TI The synthesis of 2,5-bis(4-amidinophenyl)thiophene derivatives providing
submicromolar-range inhibition of the botulinum neurotoxin serotype A
metalloprotease
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Bioterrorism; Botulinum neurotoxin; Inhibition
ID PROTEOLYTIC ACTIVITY; TOXIN; PHARMACOPHORE
AB Botulinum neurotoxins (BoNTs), composed of a family of seven serotypes (categorized A-G), are the deadliest of known biological toxins. The activity of the metalloprotease, light chain (LC) component of the toxins is responsible for causing the life-threatening paralysis associated with the disease botulism. Herein we report significantly more potent analogs of novel, lead BoNT serotype A LC inhibitor 2,5-bis(4-amidinophenyl)thiophene (K-i = 10.881 mu M +/- 0.90 mu M). Specifically, synthetic modifications involved simultaneously replacing the lead inhibitor's terminal bis-amidines with secondary amines and the systematic tethering of 4-amino-7-chloroquinoline substituents to provide derivatives with K-i values ranging from 0.302 mu M (+/- 0.03 mu M) to 0.889 mu M (+/- 0.11 mu M). (C) 2012 Elsevier Masson SAS. All rights reserved.
C1 [Opsenica, Igor; Filipovic, Vuk; Solaja, Bogdan A.] Univ Belgrade, Fac Chem, Belgrade, Serbia.
[Nuss, Jon E.; Gomba, Laura M.] USA, Med Res Inst Infect Dis, Dept Bacteriol, Frederick, MD 21702 USA.
[Opsenica, Dejan] Univ Belgrade, Inst Chem Technol & Met, Belgrade 11001, Serbia.
[Burnett, James C.] SAIC Frederick Inc, Natl Canc Inst Frederick, Target Struct Based Drug Discovery Grp, Frederick, MD 21702 USA.
[Gussio, Rick] NCI, Dev Therapeut Program, Frederick, MD 21702 USA.
RP Solaja, BA (reprint author), Univ Belgrade, Fac Chem, Studentski Trg 16,POB 51, Belgrade, Serbia.
EM burnettjames@mail.nih.gov; bsolaja@chem.bg.ac.rs;
sina.bavari@us.army.mil
RI Opsenica, Igor/P-5308-2016;
OI Opsenica, Igor/0000-0003-4942-4042; Solaja, Bogdan/0000-0002-9975-2725
FU NATO's Public Diplomacy Division; National Institute of Allergy and
Infectious Diseases (USA) [5-U01 AI082051-02]; National Cancer
Institute; National Institutes of Health (USA) [HHSN261200800001E]
FX This research was supported by NATO's Public Diplomacy Division in the
framework of Science for Peace project SfP983638 and by National
Institute of Allergy and Infectious Diseases (USA) grant 5-U01
AI082051-02.; Furthermore, for J.C.B., in compliance with
SAIC-Frederick, Inc. contractual requirements: this project has been
funded in whole or in part with federal funds from the National Cancer
Institute, National Institutes of Health (USA), under Contract No.
HHSN261200800001E.
NR 29
TC 12
Z9 12
U1 0
U2 4
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD JUL
PY 2012
VL 53
BP 374
EP 379
DI 10.1016/j.ejmech.2012.03.043
PG 6
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 966UO
UT WOS:000305863100040
PM 22516424
ER
PT J
AU Naude, PJW
Csaba, N
Eiden, LE
Ait-Ali, D
van der Heide, R
Engelborghs, S
Luiten, PGM
De Deyn, PP
den Boer, JA
Eisel, ULM
AF Naude, Petrus J. W.
Csaba Nyakas
Eiden, Lee E.
Ait-Ali, Djida
van der Heide, Ragna
Engelborghs, Sebastiaan
Luiten, Paul G. M.
De Deyn, Peter P.
den Boer, Johan A.
Eisel, Ulrich L. M.
TI Lipocalin 2: Novel component of proinflammatory signaling in Alzheimer's
disease
SO FASEB JOURNAL
LA English
DT Article
DE mild cognitive impairment; TNF-alpha; neurodegeneration
ID TUMOR-NECROSIS-FACTOR; GELATINASE-ASSOCIATED LIPOCALIN; MILD COGNITIVE
IMPAIRMENT; ACUTE-PHASE PROTEIN; KAPPA-B PATHWAY; TNF-ALPHA;
AMYLOID-BETA; NEUTROPHIL-GELATINASE; APOLIPOPROTEIN J; GENE-EXPRESSION
AB Alzheimer's disease (AD) is associated with an altered immune response, resulting in chronic increased inflammatory cytokine production with a prominent role of TNF-alpha. TNF-alpha signals are mediated by two receptors: TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). Signaling through TNFR2 is associated with neuroprotection, whereas signaling through TNFR1 is generally proinflammatory and proapoptotic. Here, we have identified a TNF-alpha-induced proinflammatory agent, lipocalin 2 (Lcn2) via gene array in murine primary cortical neurons. Further investigation showed that Lcn2 protein production and secretion were activated solely upon TNFR1 stimulation when primary murine neurons, astrocytes, and microglia were treated with TNFR1 and TNFR2 agonistic antibodies. Lcn2 was found to be significantly decreased in CSF of human patients with mild cognitive impairment and AD and increased in brain regions associated with AD pathology in human postmortem brain tissue. Mechanistic studies in cultures of primary cortical neurons showed that Lcn2 sensitizes nerve cells to beta-amyloid toxicity. Moreover, Lcn2 silences a TNFR2-mediated protective neuronal signaling cascade in neurons, pivotal for TNF-alpha-mediated neuroprotection. The present study introduces Lcn2 as a molecular actor in neuroinflammation in early clinical stages of AD.-Naud, P.J.W., Nyakas, C., Eiden, L. E., Ait-Ali, D., van der Heide, R., Engelborghs, S., Luiten, P. G. M., De Deyn, P. P., den Boer, J.A., Eisel, U. L. M. Lipocalin 2: Novel component of proinflammatory signaling in Alzheimer's disease. FASEB J. 26, 2811-2823 (2012). www.fasebj.org
C1 [Naude, Petrus J. W.; van der Heide, Ragna; Luiten, Paul G. M.; Eisel, Ulrich L. M.] Univ Groningen, Dept Mol Neurobiol, NL-9747 AG Groningen, Netherlands.
[Naude, Petrus J. W.; Luiten, Paul G. M.; den Boer, Johan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Biol Psychiat, NL-9747 AG Groningen, Netherlands.
[De Deyn, Peter P.] Univ Groningen, Univ Med Ctr Groningen, Dept Neurol, NL-9747 AG Groningen, Netherlands.
[De Deyn, Peter P.] Univ Groningen, Univ Med Ctr Groningen, Alzheimer Res Ctr, NL-9747 AG Groningen, Netherlands.
[Csaba Nyakas] Semmelweis Univ, Neuropsychopharmacol Res Grp, H-1085 Budapest, Hungary.
[Csaba Nyakas] Hungarian Acad Sci, Budapest, Hungary.
[Eiden, Lee E.; Ait-Ali, Djida] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
[Engelborghs, Sebastiaan; De Deyn, Peter P.] Ziekenhuis Netwerk Antwerpen, Dept Neurol, Antwerp, Belgium.
[Engelborghs, Sebastiaan; De Deyn, Peter P.] Ziekenhuis Netwerk Antwerpen, Memory Clin, Antwerp, Belgium.
[Engelborghs, Sebastiaan; De Deyn, Peter P.] Univ Antwerp, Inst Born Bunge, Lab Neurochem & Behav, B-2020 Antwerp, Belgium.
[Engelborghs, Sebastiaan; De Deyn, Peter P.] Univ Antwerp, Inst Born Bunge, Reference Ctr Biol Markers Dementia, B-2020 Antwerp, Belgium.
[Engelborghs, Sebastiaan; De Deyn, Peter P.] Univ Antwerp, Inst Born Bunge, Biobank Antwerp, B-2020 Antwerp, Belgium.
RP Eisel, ULM (reprint author), Univ Groningen, Dept Mol Neurobiol, Nijenborgh 7, NL-9747 AG Groningen, Netherlands.
EM u.l.m.eisel@rug.nl
OI Eiden, Lee/0000-0001-7524-944X; Eisel, Ulrich/0000-0003-4178-0384
FU De Cock Stichting [635155]; European Union [LSHM-CT-2005-018637]; School
of Behavioral and Cognitive Neurosciences; NIMH-IRP [Z01-MH002386-23];
Research Foundation Flanders (FWO); Inter-university Poles of Attraction
(IAP Network) of the Belgian Federal Science Policy Office [P6/43];
Flemish Government
FX The authors thank Dr. Abdel Elkahloun [Manager, National Human Genome
Research Institute/National Institute of Mental Health (NIMH)/National
Institute of Neurological Disorders and Stroke, U. S. National
Institutes of Health (NIH) Microarray Core] for invaluable assistance
with microarray analysis and data capture; Babru Samal [NIMH-Intramural
Research Program (IRP) Bioinformatics Core Specialist] for help with
statistical analysis; David Huddleston (Biologist, Section on Molecular
Neuroscience, NIMH-IRP) for processing of RNAs for microarray analysis;
Dennis van der Meer and Erin van Buel for helping with cell culture and
Western blotting; Dr. Amalia Dolga for assisting with cell culture,
treatment, and mRNA isolation; and the Antwerp Biobank at the Institute
Born-Bunge of the University of Antwerp for providing the biosamples of
control subjects, patients with MCI, and patients with AD. This study
was funded by De Cock Stichting (project 635155 to P.J.W.N.) and the
European Union (grant FP6 NeuropromMiSe LSHM-CT-2005-018637 to U. L. M.
E.) and by a stipend from the School of Behavioral and Cognitive
Neurosciences to P.J.W.N. The authors acknowledge the support of
NIMH-IRP (project Z01-MH002386-23). In addition, this work was supported
by the Research Foundation Flanders (FWO), Inter-university Poles of
Attraction (IAP Network P6/43) of the Belgian Federal Science Policy
Office, Methusalem excellence grant of the Flemish Government, agreement
between Institute Born-Bunge and University of Antwerp, the Medical
Research Foundation Antwerp, the Thomas Riellaerts research fund, and
Neurosearch Antwerp.
NR 58
TC 43
Z9 43
U1 1
U2 11
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 JUL
PY 2012
VL 26
IS 7
BP 2811
EP 2823
DI 10.1096/fj.11-202457
PG 13
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 967MP
UT WOS:000305912500010
PM 22441986
ER
PT J
AU Li, GH
Li, WX
Mumper, RJ
Nath, A
AF Li, Guan-Han
Li, Wenxue
Mumper, Russell J.
Nath, Avindra
TI Molecular mechanisms in the dramatic enhancement of HIV-1 Tat
transduction by cationic liposomes
SO FASEB JOURNAL
LA English
DT Article
DE transactivation; uptake; endocytosis; intracellular delivery;
hydrophobic peptide
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELL-PENETRATING PEPTIDES; HEPARAN-SULFATE
PROTEOGLYCANS; FUSION INHIBITOR T-20; DRUG-DELIVERY; LIPID RAFTS;
DEPENDENT ENDOCYTOSIS; FUNCTIONAL DOMAINS; PLASMA-MEMBRANE; PROTEIN TAT
AB Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription (Tat) protein possesses a unique membrane-transduction property. Interestingly, Tat transduction could be dramatically increased 1000-fold based on LTR-transactivation assay when complexed with cationic liposomes (lipo-Tat), compared with Tat alone. Therefore, underlining mechanisms were explored further. Microscopy and flow cytometry showed that this effect was associated with enhanced membrane binding, large particle formation (1-2 mu m) and increased intracellular uptake of Tat fluorescent proteins. Using pharmacological assays and immune colocalizations, it was found that lipid raft-dependent endocytosis and macropinocytosis were major pathways involved in lipo-Tat uptake, and actinfilaments played a major role in intracellular trafficking of lipo-Tat to the nucleus. Furthermore, we found that the Tat hydrophobic domain (aa 36-47) mediated formation of two positively charged molecules into lipo-Tat complexes via hydrophobic bonds, based on LTR-transactivation inhibition assay. Thus, the hydrophobic domain may play an important role in Tat protein uptake and be useful for intracellular delivery of biomacromolecules if coupled together with Tat basic peptide, a cell-penetrating peptide.-Li, G.-H., Li, W., Mumper, R. J., Nath, A. Molecular mechanisms in the dramatic enhancement of HIV-1 Tat transduction by cationic liposomes. FASEB J. 26, 2824-2834 (2012). www.fasebj.org
C1 [Li, Guan-Han; Li, Wenxue; Nath, Avindra] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Li, Guan-Han; Li, Wenxue; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
[Mumper, Russell J.] Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Ctr Nanotechnol Drug Delivery, Chapel Hill, NC USA.
RP Nath, A (reprint author), NINDS, Sect Infect Nervous Syst, NIH, Bldg 10,7C-103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM natha@ninds.nih.gov
RI Li, Guanhan/E-3497-2012
FU U.S. National Insitutes of Health [R01NS039253, R01AI058842]
FX This study was supported by U.S. National Insitutes of Health grants
R01NS039253 (A.N.) and R01AI058842 (R.J.M.). The authors thank Yan Huang
(A.N. laboratory) and Michael Delannoy (Johns Hopkins Medical
Institutions-Microscope Facility, Baltimore, MD, USA) for technical
assistance.
NR 73
TC 11
Z9 11
U1 2
U2 8
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 JUL
PY 2012
VL 26
IS 7
BP 2824
EP 2834
DI 10.1096/fj.11-203315
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 967MP
UT WOS:000305912500011
PM 22447980
ER
PT J
AU Jia, Y
Suzuki, N
Yamamoto, M
Gassmann, M
Noguchi, CT
AF Jia, Yi
Suzuki, Norio
Yamamoto, Masayuki
Gassmann, Max
Noguchi, Constance Tom
TI Endogenous erythropoietin signaling facilitates skeletal muscle repair
and recovery following pharmacologically induced damage
SO FASEB JOURNAL
LA English
DT Article
DE PI3K/Akt; myoblast; wound healing; transgenic mice
ID MICE OVEREXPRESSING ERYTHROPOIETIN; STEM-CELLS; EXCESSIVE
ERYTHROCYTOSIS; RECEPTOR; ACTIVATION; ANGIOGENESIS; EXPRESSION; GATA-1;
DIFFERENTIATION; PROLIFERATION
AB Erythropoietin acts by binding to its cell surface receptor on erythroid progenitor cells to stimulate erythrocyte production. Erythropoietin receptor expression in nonhematopoietic tissue, including skeletal muscle progenitor cells, raises the possibility of a role for erythropoietin beyond erythropoiesis. Mice with erythropoietin receptor restricted to hematopoietic tissue were used to assess contributions of endogenous erythropoietin to promote skeletal myoblast proliferation and survival and wound healing in a mouse model of cardiotoxin induced muscle injury. Compared with wild-type controls, these mice had fewer skeletal muscle Pax-7(+) satellite cells and myoblasts that do not proliferate in culture, were more susceptible to skeletal muscle injury and reduced maximum load tolerated by isolated muscle. In contrast, mice with chronic elevated circulating erythropoietin had more Pax-7(+) satellite cells and myoblasts with increased proliferation and survival in culture, decreased muscle injury, and accelerated recovery of maximum load tolerated by isolated muscle. Skeletal muscle myoblasts also produced endogenous erythropoietin that increased at low O-2. Erythropoietin promoted proliferation, survival, and wound recovery in myoblasts via the phosphoinositide 3-kinase/AKT pathway. Therefore, endogenous and exogenous erythropoietin contribute to increasing satellite cell number following muscle injury, improve myoblast proliferation and survival, and promote repair and regeneration in this mouse induced muscle injury model independent of its effect on erythrocyte production.-Jia, Y., Suzuki, N., Yamamoto, M., Gassmann, M., Noguchi, C. T. Endogenous erythropoietin signaling facilitates skeletal muscle repair and recovery following pharmacologically induced damage. FASEB J. 26, 2847-2858 (2012). www.fasebj.org
C1 [Jia, Yi; Noguchi, Constance Tom] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
[Suzuki, Norio; Yamamoto, Masayuki] Tohoku Univ, Grad Sch Med, Dept Med Biochem, Sendai, Miyagi 980, Japan.
[Gassmann, Max] Univ Zurich, Inst Vet Physiol, Vetsuisse Fac, Zurich, Switzerland.
[Gassmann, Max] Univ Zurich, Zurich Ctr Integrat Human Physiol ZIHP, Zurich, Switzerland.
[Gassmann, Max] UPCH, Lima, Peru.
RP Noguchi, CT (reprint author), NIDDK, Mol Med Branch, NIH, Bldg 10,Rm 9N319,10 Ctr Dr,MSC 1822, Bethesda, MD 20892 USA.
EM connien@mail.nih.gov
RI Yamamoto, Masayuki/A-4873-2010; Suzuki, Norio/F-3456-2010
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX The authors thank Li Wang, Heather Rogers, Susan E. Ivie, and Xiaobing
Yu for their contributions in studies on transcription regulation and
position-holding time. Funding is provided by the Intramural Research
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases. Author contributions: Y.J. performed conception and design,
collection and/or assembly of data, data analysis and interpretation,
manuscript writing, and final approval of manuscript; N.S. provided
study material and data analysis and interpretation; M.Y. provided study
material and data analysis and interpretation; M. G. provided study
material and data analysis and interpretation; and C.T.N. provided
conception and design, financial support, data analysis and
interpretation, manuscript writing, and final approval of manuscript.
NR 44
TC 15
Z9 15
U1 0
U2 6
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 JUL
PY 2012
VL 26
IS 7
BP 2847
EP 2858
DI 10.1096/fj.11-196618
PG 12
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 967MP
UT WOS:000305912500013
PM 22490927
ER
PT J
AU Tota, B
Gentile, S
Pasqua, T
Bassino, E
Koshimizu, H
Cawley, NX
Cerra, MC
Loh, YP
Angelone, T
AF Tota, Bruno
Gentile, Stefano
Pasqua, Teresa
Bassino, Eleonora
Koshimizu, Hisatsugu
Cawley, Niamh X.
Cerra, Maria C.
Loh, Y. Peng
Angelone, Tommaso
TI The novel chromogranin A-derived serpinin and pyroglutaminated serpinin
peptides are positive cardiac beta-adrenergic-like inotropes
SO FASEB JOURNAL
LA English
DT Article
DE heart; adenylate cyclase; PKA
ID RAT-HEART; NATRIURETIC PEPTIDES; MYOCARDIAL PRODUCTION; TARGETED
ABLATION; PROGNOSTIC VALUE; NITRIC-OXIDE; RECEPTOR; FAILURE; CELLS;
PHEOCHROMOCYTOMA
AB Three forms of serpinin peptides, serpinin (Ala26Leu), pyroglutaminated (pGlu)-serpinin (pGlu23Leu), and serpinin-Arg-Arg-Gly (Ala29Gly), are derived from cleavage at pairs of basic residues in the highly conserved C terminus of chromogranin A (CgA). Serpinin induces PN-1 expression in neuroendocrine cells to up-regulate granule biogenesis via a cAMP-protein kinase A-Sp1 pathway, while pGlu-serpinin inhibits cell death. The aim of this study was to test the hypothesis that serpinin peptides are produced in the heart and act as novel beta-adrenergic-like cardiac modulators. We detected serpinin peptides in the rat heart by HPLC and ELISA methods. The peptides included predominantly Ala29Gly and pGlu-serpinin and a small amount of serpinin. Using the Langendorff perfused rat heart to evaluate the hemodynamic changes, we found that serpinin and pGlu-serpinin exert dose-dependent positive inotropic and lusitropic effects at 11-165 nM, within the first 5 min after administration. The pGlu-serpinin-induced contractility is more potent than that of serpinin, starting from 1 nM. Using the isolated rat papillary muscle preparation to measure contractility in terms of tension development and muscle length, we further corroborated the pGlu-serpinin-induced positive inotropism. Ala29Gly was unable to affect myocardial performance. Both pGlu-serpinin and serpinin act through a beta 1-adrenergic receptor/adenylate cyclase/cAMP/PKA pathway, indicating that, contrary to the beta-blocking profile of the other CgA-derived cardiosuppressive peptides, vasostatin-1 and catestatin, these two C-terminal peptides act as beta-adrenergic-like agonists. In cardiac tissue extracts, pGlu-serpinin increased intracellular cAMP levels and phosphorylation of phospholamban (PLN) Ser16, ERK1/2, and GSK-3 beta. Serpinin and pGlu-serpinin peptides emerge as novel beta-adrenergic inotropic and lusitropic modulators, suggesting that CgA and the other derived cardioactive peptides can play a key role in how the myocardium orchestrates its complex response to sympathochromaffin stimulation.-Tota, B., Gentile, S., Pasqua, T., Bassino, E., Koshimizu, H., Cawley, N. X., Cerra, M. C., Loh, Y. P., Angelone, T. The novel chromogranin A-derived serpinin and pyroglutaminated serpinin peptides are positive cardiac beta-adrenergic-like inotropes. FASEB J. 26, 2888-2898 (2012). www.fasebj.org
C1 [Tota, Bruno; Gentile, Stefano; Pasqua, Teresa; Cerra, Maria C.; Angelone, Tommaso] Univ Calabria, Dept Cell Biol, Arcavacata Di Rende, Italy.
[Cerra, Maria C.] Univ Calabria, Dept Pharmacobiol, Arcavacata Di Rende, Italy.
[Bassino, Eleonora] Univ Turin, Dept Anim & Human Biol, Turin, Italy.
[Koshimizu, Hisatsugu; Cawley, Niamh X.; Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, NIH, Bethesda, MD USA.
RP Loh, YP (reprint author), NICHD, NIH, Bldg 49,Rm 5A2249,Convent Dr, Bethesda, MD 20892 USA.
EM lohp@mail.nih.gov; t.angelone@unical.it
OI Angelone, Tommaso/0000-0001-7797-7862
FU Ministero dell'Universita e Ricerca Scientifica e Tecnologica; Italian
National Institute of Cardiovascular Research (INRC); Eunice Kennedy
Shriver National Institute of Child Health and Human Development (U.S.
National Institutes of Health)
FX The authors thank Dr. G. Mengozzi and M. Lucchiari (Dipartimento di
Diagnostica di Laboratorio, Azienda Ospedaliera Universitaria San
Giovanni Battista di Torino, Turin, Italy) for their precious support in
NE detection. The authors also thank Prof. Alan Kopin and Mr. Benjamin
Harwood (Molecular Pharmacology Research Center, Tufts Medical Center,
Boston, MA, USA) for their help with the GPCR signaling assays. This
research was supported by grants from Ministero dell'Universita e
Ricerca Scientifica e Tecnologica (ex60%), the Italian National
Institute of Cardiovascular Research (INRC), and the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development (U.S. National Institutes of Health). The authors
declare no conflicts of interest.
NR 40
TC 14
Z9 17
U1 0
U2 3
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 JUL
PY 2012
VL 26
IS 7
BP 2888
EP 2898
DI 10.1096/fj.11-201111
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 967MP
UT WOS:000305912500017
PM 22459152
ER
PT J
AU Hill, MJ
Levens, ED
Whitcomb, BW
AF Hill, Micah J.
Levens, Eric D.
Whitcomb, Brian W.
TI Recombinant LH supplementation in women of 35 years and older undergoing
IVF? REPLY
SO FERTILITY AND STERILITY
LA English
DT Letter
ID ADVANCED REPRODUCTIVE AGE; LUTEINIZING-HORMONE; TRIAL
C1 [Hill, Micah J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20814 USA.
[Levens, Eric D.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
[Whitcomb, Brian W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
RP Hill, MJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20814 USA.
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 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUL
PY 2012
VL 98
IS 1
DI 10.1016/j.fertnstert.2012.04.049
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 968AU
UT WOS:000305950200005
ER
PT J
AU Meisel, RP
Malone, JH
Clark, AG
AF Meisel, Richard P.
Malone, John H.
Clark, Andrew G.
TI Disentangling the relationship between sex-biased gene expression and
X-linkage
SO GENOME RESEARCH
LA English
DT Article
ID DROSOPHILA-MELANOGASTER; CHROMOSOME INACTIVATION; REPRODUCTIVE PROTEINS;
ONTOGENIC CONFLICT; LINKED GENES; RNA-SEQ; EVOLUTION; TRANSCRIPTOME;
DIFFERENTIATION; ENCYCLOPEDIA
AB X chromosomes are preferentially transmitted through females, which may favor the accumulation of X-linked alleles/genes with female-beneficial effects. Numerous studies have shown that genes with sex-biased expression are under- or over-represented on the X chromosomes of a wide variety of organisms. The patterns, however, vary between different animal species, and the causes of these differences are unresolved. Additionally, genes with sex-biased expression tend to be narrowly expressed in a limited number of tissues, and narrowly expressed genes are also non-randomly X-linked in a taxon-specific manner. It is therefore unclear whether the unique gene content of the X chromosome is the result of selection on genes with sex-biased expression, narrowly expressed genes, or some combination of the two. To address this problem, we measured sex-biased expression in multiple Drosophila species and at different developmental time points. These data were combined with available expression measurements from Drosophila melanogaster and mouse to reconcile the inconsistencies in X-chromosome content among taxa. Our results suggest that most of the differences between Drosophila and mammals are confounded by disparate data collection/analysis approaches as well as the correlation between sex bias and expression breadth. Both the Drosophila and mouse X chromosomes harbor an excess of genes with female-biased expression after controlling for the confounding factors, suggesting that the asymmetrical transmission of the X chromosome favors the accumulation of female-beneficial mutations in X-linked genes. However, some taxon-specific patterns remain, and we provide evidence that these are in part a consequence of constraints imposed by the dosage compensation mechanism in Drosophila.
C1 [Meisel, Richard P.; Clark, Andrew G.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.
[Malone, John H.] NIDDKD, Cellular & Dev Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Meisel, RP (reprint author), Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.
EM meisel@cornell.edu
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; National Institutes of Health fellowship
[F32GM087611]
FX This work was supported in part by the Intramural Research Program of
the National Institute of Diabetes and Digestive and Kidney Diseases.
R.P.M. was supported by National Institutes of Health fellowship
F32GM087611, and J.H.M. completed this work while in the laboratory of
Brian Oliver. We would like to thank Caroline Sartain for assisting in
the sexing of larvae, Amanda Manfredo for preparing RNA-seq libraries,
and the Cornell University Genomics Core Laboratory for running RNA-seq
and microarray samples. This manuscript benefited from discussions with
Brian Oliver, Colin Meiklejohn, and members of the Clark laboratory, as
well as comments from three anonymous reviewers.
NR 77
TC 53
Z9 53
U1 1
U2 43
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
EI 1549-5469
J9 GENOME RES
JI Genome Res.
PD JUL
PY 2012
VL 22
IS 7
BP 1255
EP 1265
DI 10.1101/gr.132100.111
PG 11
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 969BF
UT WOS:000306030000006
PM 22499666
ER
PT J
AU Jacques, BE
Dabdoub, A
Kelley, MW
AF Jacques, Bonnie E.
Dabdoub, Alain
Kelley, Matthew W.
TI Fgf signaling regulates development and transdifferentiation of hair
cells and supporting cells in the basilar papilla
SO HEARING RESEARCH
LA English
DT Article
ID CHICK INNER-EAR; AUDITORY SENSORY EPITHELIUM; GROWTH-FACTOR RECEPTOR;
MAMMALIAN COCHLEA; ACOUSTIC TRAUMA; CELLULAR-DIFFERENTIATION; EXPRESSION
PATTERNS; PROSENSORY PATCHES; NONSENSORY REGIONS; NOTCH LIGANDS
AB The avian basilar papilla (BP) is a likely homolog of the auditory sensory epithelium of the mammalian cochlea, the organ of Corti. During mammalian development Fibroblast growth factor receptor-3 (Fgfr3) is known to regulate the differentiation of auditory mechanosensory hair cells (HCs) and supporting cells (SCs), both of which are required for sound detection. Fgfr3 is expressed in developing progenitor cells (PCs) and SCs of both the BP and the organ of Corti; however its role in BP development is unknown. Here we utilized an in vitro whole organ embryonic culture system to examine the role of Fgf signaling in the developing avian cochlea. SU5402 (an antagonist of Fgf signaling) was applied to developing BP cultures at different stages to assay the role of Fgf signaling during HC formation. Similar to the observed effects of inhibition of Fgfr3 in the mammalian cochlea, Fgfr inhibition in the developing BP increased the number of HCs that formed. This increase was not associated with increased proliferation, suggesting that inhibition of the Fgf pathway leads to the direct conversion of PCs or supporting cells into HCs, a process known as transdifferentiation. This also implies that Fgf signaling is required to prevent the conversion of PCs and SCs into HCs. The ability of Fgf signaling to inhibit transdifferentiation suggests that its down-regulation may be essential for the initial steps of HC formation, as well as for the maintenance of SC phenotypes. (C) 2012 Published by Elsevier B.V.
C1 [Jacques, Bonnie E.; Kelley, Matthew W.] NIDCD, Lab Cochlear Dev, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
[Jacques, Bonnie E.; Dabdoub, Alain] UCSD Sch Med, Dept Surg, Div Otolaryngol, La Jolla, CA 92093 USA.
[Jacques, Bonnie E.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA.
RP Kelley, MW (reprint author), NIDCD, Lab Cochlear Dev, NIH, Porter Neurosci Res Ctr, 35 Convent Dr,Room 2A-100, Bethesda, MD 20892 USA.
EM bjacques@ucsd.edu; adabdoub@ucsd.edu; kelleymt@nidcd.nih.gov
FU National Institute on Deafness and other Communication Disorders; [P30
CA23100]
FX We would like to thank Drs. Douglas Cotanche and Jennifer Stone for
reading an earlier version of the manuscript and providing very helpful
comments. We would like to thank Dr. Guy Richardson at the University of
Sussex for kindly providing the HCA antibody. Some of the images were
generated at the UCSD Shared Microscopy Facility, Cancer Center
specialized support grant P30 CA23100. This research was supported by
funds from the intramural program at the National Institute on Deafness
and other Communication Disorders (M.W.K.).
NR 76
TC 16
Z9 16
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
J9 HEARING RES
JI Hear. Res.
PD JUL
PY 2012
VL 289
IS 1-2
BP 27
EP 39
DI 10.1016/j.heares.2012.04.018
PG 13
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA 967UL
UT WOS:000305933200003
PM 22575790
ER
PT J
AU Uccellini, L
Tseng, FC
Monaco, A
Shebl, FM
Pfeiffer, R
Dotrang, M
Buckett, D
Busch, MP
Wang, E
Edlin, BR
Marincola, FM
O'Brien, TR
AF Uccellini, Lorenzo
Tseng, Fan-Chen
Monaco, Alessandro
Shebl, Fatma M.
Pfeiffer, Ruth
Dotrang, Myhanh
Buckett, Dianna
Busch, Michael P.
Wang, Ena
Edlin, Brian R.
Marincola, Francesco M.
O'Brien, Thomas R.
TI HCV RNA levels in a multiethnic cohort of injection drug users: Human
genetic, viral and demographic associations
SO HEPATOLOGY
LA English
DT Article
ID HEPATITIS-C VIRUS; HIV-INFECTED PATIENTS; SPONTANEOUS CLEARANCE;
LIVER-DISEASE; SAN-FRANCISCO; IL28B; GENOTYPE; LOAD; SEROPREVALENCE;
PEGINTERFERON
AB In patients with chronic hepatitis C, the hepatitis C virus (HCV) RNA level is an important predictor of treatment response. To explore the relationship of HCV RNA with viral and demographic factors, as well as IL28B genotype, we examined viral levels in an ethnically diverse group of injection drug users (IDUs). Between 1998 and 2000, the Urban Health Study (UHS) recruited IDUs from street settings in San Francisco Bay area neighborhoods. Participants who were positive by HCV enzyme immunoassay were tested for HCV viremia by a branched-chain DNA assay. HCV genotype was determined by sequencing the HCV nonstructural 5B protein region. For a subset of participants, IL28B rs12979860 genotype was determined by Taqman. Among 1,701 participants with HCV viremia, median age was 46 years and median duration of injection drug use was 26 years; 56.0% were African American and 34.0% were of European ancestry (non-Hispanic). Human immunodeficiency virus type 1 (HIV-1) prevalence was 13.9%. The overall median HCV RNA level was 6.45 log10 copies/mL. In unadjusted analyses, higher levels were found with older age, male gender, African-American ancestry, hepatitis B virus infection, HIV-1 infection, and IL28B rs12979860-CC genotype; compared to participants infected with HCV genotype 1, HCV RNA was lower in participants with genotypes 3 or 4. In an adjusted analysis, age, gender, racial ancestry, HIV-1 infection, HCV genotype, and IL28B rs12979860 genotype were all independently associated with HCV RNA. Conclusion: The level of HCV viremia is influenced by a large number of demographic, viral, and human genetic factors. (HEPATOLOGY 2012;56:8694)
C1 [Tseng, Fan-Chen; Shebl, Fatma M.; Pfeiffer, Ruth; Buckett, Dianna; O'Brien, Thomas R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Uccellini, Lorenzo; Monaco, Alessandro; Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Uccellini, Lorenzo; Monaco, Alessandro; Wang, Ena; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol, Bethesda, MD 20892 USA.
[Uccellini, Lorenzo] Univ Milan, Inst Infect & Trop Dis, L Sacco Hosp, Milan, Italy.
[Dotrang, Myhanh] Comp Sci Corp, Rockville, MD USA.
[Busch, Michael P.; Edlin, Brian R.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA.
[Edlin, Brian R.] SUNY Downstate Coll Med, Brooklyn, NY USA.
[Edlin, Brian R.] Cornell Univ, Ctr Study Hepatitis C, Weill Med Coll, New York, NY 10021 USA.
RP O'Brien, TR (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5052, Bethesda, MD 20892 USA.
EM obrient@mail.nih.gov
RI Monaco, Alessandro/O-5338-2015;
OI Monaco, Alessandro/0000-0002-9941-7003; Edlin, Brian/0000-0001-8172-8797
FU National Institutes of Health (National Cancer Institute, Division of
Cancer Epidemiology and Genetics); National Institutes of Health [NIH]
Clinical Center; National Cancer Institute [NO1-CO-12400, N02-CP-91027];
NIH [R01-DA09532, R01-DA12109, R01-DA13245, R01-DA16159]; Substance
Abuse and Mental Health Services Administration [H79-TI12103]; City and
County of San Francisco Department of Public Health; CaridanBCT;
Chiron/Novartis
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (National Cancer Institute, Division of
Cancer Epidemiology and Genetics; National Institutes of Health [NIH]
Clinical Center) and by federal funds from the National Cancer Institute
(contracts NO1-CO-12400 and N02-CP-91027). This work was also supported
by NIH grants (R01-DA09532, R01-DA12109, R01-DA13245, and R01-DA16159),
a grant from the Substance Abuse and Mental Health Services
Administration (H79-TI12103; Center for Substance Abuse Treatment), and
the City and County of San Francisco Department of Public Health.; Dr.
Busch consults for, advises, is on the speakers' bureau for, and
received compensation from Gen-Probe. He consults for, advises, is on
the speakers' bureau of, and received grants from CaridanBCT and
Chiron/Novartis. He consults for, advises, and is on the speakers'
bureau of Abbott. He advises and is on the speakers' bureau of Merck and
Ortho Diagnostics.
NR 41
TC 15
Z9 15
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUL
PY 2012
VL 56
IS 1
BP 86
EP 94
DI 10.1002/hep.25652
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 967ZQ
UT WOS:000305947200012
PM 22331649
ER
PT J
AU Tanaka, N
Matsubara, T
Krausz, KW
Patterson, AD
Gonzalez, FJ
AF Tanaka, Naoki
Matsubara, Tsutomu
Krausz, Kristopher W.
Patterson, Andrew D.
Gonzalez, Frank J.
TI Disruption of phospholipid and bile acid homeostasis in mice with
nonalcoholic steatohepatitis
SO HEPATOLOGY
LA English
DT Article
ID FATTY LIVER-DISEASE; PPAR-ALPHA ACTIVATION; HEPATIC STEATOSIS;
NATURAL-HISTORY; HEPATOCELLULAR-CARCINOMA; FOLLOW-UP;
LYSOPHOSPHATIDYLCHOLINE; METABOLOMICS; CHOLINE; PHOSPHATIDYLCHOLINE
AB Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease that can develop into cirrhosis, hepatic failure, and hepatocellular carcinoma. Although several metabolic pathways are disrupted and endogenous metabolites may change in NASH, the alterations in serum metabolites during NASH development remain unclear. To gain insight into the disease mechanism, serum metabolite changes were assessed using metabolomics with ultraperformance liquid chromatographyelectrospray ionizationquadrupole time-of-flight mass spectrometry and a conventional mouse NASH model induced by a methionine- and choline-deficient (MCD) diet. Significant decreases in serum palmitoyl-, stearoyl-, and oleoyl-lysophosphatidylcholine (LPC) and marked increases in tauro-beta-muricholate, taurocholate and 12-hydroxyeicosatetraenoic acid (12-HETE) were detected in mice with NASH. In agreement with these metabolite changes, hepatic mRNAs encoding enzymes and proteins involved in LPC degradation (lysophosphatidylcholine acyltransferase [Lpcat] 1-4), basolateral bile acid excretion (ATP-binding cassette subfamily C member [Abcc] 1/4/5 and organic solute transporter beta), and 12-HETE synthesis (arachidonate 12-lipoxygenase) were significantly up-regulated. In contrast, the expression of solute carrier family 10 member 1 (Slc10a1) and solute carrier organic anion transporter family member (Slco) 1a1 and 1b2, responsible for transporting bile acids into hepatocytes, were markedly suppressed. Supplementation of the MCD diet with methionine revealed that the changes in serum metabolites and the related gene expression were derived from steatohepatitis, but not dietary choline deficiency or steatosis. Furthermore, tumor necrosis factor-a and transforming growth factor-beta 1 induced the expression of Lpcat2/4 and Abcc1/4 and down-regulated Slc10a1 and Slco1a1 in primary hepatocytes, suggesting an association between the changes in serum LPC and bile acids and proinflammatory cytokines. Finally, induction of hepatitis in ob/ob mice by D-galactosamine injection led to similar changes in serum metabolites and related gene expression. Conclusion: Phospholipid and bile acid metabolism is disrupted in NASH, likely due to enhanced hepatic inflammatory signaling. (HEPATOLOGY 2012;56:118129)
C1 [Tanaka, Naoki; Matsubara, Tsutomu; Krausz, Kristopher W.; Patterson, Andrew D.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Patterson, Andrew D.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Patterson, Andrew D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
RI Patterson, Andrew/G-3852-2012
OI Patterson, Andrew/0000-0003-2073-0070
FU National Cancer Institute Intramural Research Program [U54 ES16015];
Japanese Society for the Promotion of Science
FX Supported by the National Cancer Institute Intramural Research Program
and U54 ES16015 (F.J.G) and a fellowship from the Japanese Society for
the Promotion of Science (T.M.).
NR 38
TC 64
Z9 65
U1 2
U2 33
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUL
PY 2012
VL 56
IS 1
BP 118
EP 129
DI 10.1002/hep.25630
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 967ZQ
UT WOS:000305947200015
PM 22290395
ER
PT J
AU Patterson, AD
Shah, YM
Matsubara, T
Krausz, KW
Gonzalez, FJ
AF Patterson, Andrew D.
Shah, Yatrik M.
Matsubara, Tsutomu
Krausz, Kristopher W.
Gonzalez, Frank J.
TI Peroxisome proliferator-activated receptor alpha induction of uncoupling
protein 2 protects against acetaminophen-induced liver toxicity
SO HEPATOLOGY
LA English
DT Article
ID PPAR-ALPHA; SPECIES-DIFFERENCES; TERMINAL KINASE; NULL MICE; UCP2;
HEPATOTOXICITY; CLOFIBRATE; MECHANISM; INJURY; PARACETAMOL
AB Acetaminophen (APAP) overdose causes acute liver failure in humans and rodents due in part to the destruction of mitochondria as a result of increased oxidative stress followed by hepatocellular necrosis. Activation of the peroxisome proliferator-activated receptor alpha (PPARa), a member of the nuclear receptor superfamily that controls the expression of genes encoding peroxisomal and mitochondrial fatty acid beta-oxidation enzymes, with the experimental ligand Wy-14,643 or the clinically used fibrate drug fenofibrate, fully protects mice from APAP-induced hepatotoxicity. PPARa-humanized mice were also protected, whereas Ppara-null mice were not, thus indicating that the protection extends to human PPARa and is PPARa-dependent. This protection is due in part to induction of the PPARa target gene encoding mitochondrial uncoupling protein 2 (UCP2). Forced overexpression of UCP2 protected wildtype mice against APAP-induced hepatotoxicity in the absence of PPARa activation. Ucp2-null mice, however, were sensitive to APAP-induced hepatotoxicity despite activation of PPARa with Wy-14,643. Protection against hepatotoxicity by UCP2-induction through activation of PPARa is associated with decreased APAP-induced c-jun and c-fos expression, decreased phosphorylation of JNK and c-jun, lower mitochondrial H2O2 levels, increased mitochondrial glutathione in liver, and decreased levels of circulating fatty acyl-carnitines. These studies indicate that the PPARa target gene UCP2 protects against elevated reactive oxygen species generated during drug-induced hepatotoxicity and suggest that induction of UCP2 may also be a general mechanism for protection of mitochondria during fatty acid beta-oxidation. (HEPATOLOGY 2012;56:281290)
C1 [Patterson, Andrew D.; Shah, Yatrik M.; Matsubara, Tsutomu; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20814 USA.
[Patterson, Andrew D.] Penn State Univ, Dept Vet & Biomed Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Shah, Yatrik M.] Univ Michigan, Sch Med, Div Gastroenterol, Dept Mol & Integrat Physiol, Ann Arbor, MI USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20814 USA.
EM gonzalef@mail.nih.gov
RI Patterson, Andrew/G-3852-2012
OI Patterson, Andrew/0000-0003-2073-0070
FU Intramural NIH HHS [ZIA BC005561-23]; NCI NIH HHS [R01 CA148828]
NR 31
TC 41
Z9 45
U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUL
PY 2012
VL 56
IS 1
BP 281
EP 290
DI 10.1002/hep.25645
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 967ZQ
UT WOS:000305947200031
PM 22318764
ER
PT J
AU Wang, SJ
Petrick, N
Van Uitert, RL
Periaswamy, S
Wei, ZS
Summers, RM
AF Wang, Shijun
Petrick, Nicholas
Van Uitert, Robert L.
Periaswamy, Senthil
Wei, Zhuoshi
Summers, Ronald M.
TI Matching 3-D Prone and Supine CT Colonography Scans Using Graphs
SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE
LA English
DT Article
DE Computed tomographic colonography; colon registration; graph matching;
mean field theory
ID COMPUTER-AIDED DETECTION; COLON CENTERLINE; REGISTRATION; TRIAL;
COLONOSCOPY; REDUCTION; POLYPS
AB In this paper, we propose a new registration method for prone and supine computed tomographic colonography scans using graph matching. We formulate 3-D colon registration as a graph matching problem and propose a new graph matching algorithm based on mean field theory. In the proposed algorithm, we solve the matching problem in an iterative way. In each step, we use mean field theory to find the matched pair of nodes with highest probability. During iterative optimization, one-to-one matching constraints are added to the system in a step-by-step approach. Prominent matching pairs found in previous iterations are used to guide subsequent mean field calculations. The proposed method was found to have the best performance with smallest standard deviation compared with two other baseline algorithms called the normalized distance along the colon centerline (NDACC) (p = 0.17) with manual colon centerline correction and spectral matching (p < 1e-5). A major advantage of the proposed method is that it is fully automatic and does not require defining a colon centerline for registration. For the latter NDACC method, user interaction is almost always needed for identifying the colon centerlines.
C1 [Wang, Shijun; Wei, Zhuoshi; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
[Petrick, Nicholas] US FDA, Silver Spring, MD 20993 USA.
[Van Uitert, Robert L.; Periaswamy, Senthil] iCAD Inc, Nashua, NH 03062 USA.
RP Wang, SJ (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
EM wangshi@cc.nih.gov; nicholas.petrick@fda.hhs.gov;
rvanuitert@icadmed.com; speriaswamy@icadmed.com; weiz@cc.nih.gov;
rms@nih.gov
FU U.S. NIH Clinical Center; Food and Drug Administration
FX This research was supported by the Intramural Research Programs of the
U.S. NIH Clinical Center and the Food and Drug Administration.
NR 26
TC 3
Z9 3
U1 1
U2 7
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1089-7771
J9 IEEE T INF TECHNOL B
JI IEEE T. Inf. Technol. Biomed.
PD JUL
PY 2012
VL 16
IS 4
BP 676
EP 682
DI 10.1109/TITB.2012.2194297
PG 7
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Mathematical & Computational Biology;
Medical Informatics
SC Computer Science; Mathematical & Computational Biology; Medical
Informatics
GA 968KK
UT WOS:000305979500017
PM 22552585
ER
PT J
AU High, KP
Brennan-Ing, M
Clifford, DB
Cohen, MH
Currier, J
Deeks, SG
Deren, S
Effros, RB
Gebo, K
Goronzy, JJ
Justice, AC
Landay, A
Levin, J
Miotti, PG
Munk, RJ
Nass, H
Rinaldo, CR
Shlipak, MG
Tracy, R
Valcour, V
Vance, DE
Walston, JD
Volberding, P
AF High, Kevin P.
Brennan-Ing, Mark
Clifford, David B.
Cohen, Mardge H.
Currier, Judith
Deeks, Steven G.
Deren, Sherry
Effros, Rita B.
Gebo, Kelly
Goronzy, Joerg J.
Justice, Amy C.
Landay, Alan
Levin, Jules
Miotti, Paolo G.
Munk, Robert J.
Nass, Heidi
Rinaldo, Charles R., Jr.
Shlipak, Michael G.
Tracy, Russell
Valcour, Victor
Vance, David E.
Walston, Jeremy D.
Volberding, Paul
CA OAR Working Grp HIV Aging
TI HIV and Aging: State of Knowledge and Areas of Critical Need for
Research. A Report to the NIH Office of AIDS Research by the HIV and
Aging Working Group
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE aging; HIV/AIDS; co-morbidity; research priorities
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC KIDNEY-DISEASE; OLDER-ADULTS;
CARDIOVASCULAR-DISEASE; INFECTED PATIENTS; IMMUNE-SYSTEM; COHORT;
BIOMARKERS; RISK; INFLAMMATION
AB HIV risk behaviors, susceptibility to HIV acquisition, progression of disease after infection, and response to antiretroviral therapy all vary by age. In those living with HIV, current effective treatment has increased the median life expectancy to >70 years of age. Biologic, medical, individual, social, and societal issues change as one ages with HIV infection, but there has been only a small amount of research in this field. Therefore, the Office of AIDS Research of the National Institutes of Health commissioned a working group to develop an outline of the current state of knowledge and areas of critical need for research in HIV and Aging; the working groups' findings and recommendations are summarized in this report. Key overarching themes identified by the group included the following: multimorbidity, polypharmacy, and the need to emphasize maintenance of function; the complexity of assessing HIV versus treatment effects versus aging versus concurrent disease; the inter-related mechanisms of immune senescence, inflammation, and hypercoagulability; the utility of multivariable indices for predicting outcomes; a need to emphasize human studies to account for complexity; and a required focus on issues of community support, caregivers, and systems infrastructure. Critical resources are needed to enact this research agenda and include expanded review panel expertise in aging, functional measures, and multimorbidity, and facilitated use and continued funding to allow long-term follow-up of cohorts aging with HIV.
C1 [High, Kevin P.] Wake Forest Univ, Baptist Med Ctr, Infect Dis Sect, Dept Internal Med,Wake Forest Sch Med, Winston Salem, NC 27157 USA.
[Brennan-Ing, Mark] ACRIA Ctr HIV & Aging, New York, NY USA.
[Clifford, David B.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Cohen, Mardge H.] Rush Univ, Dept Internal Med, WIHS, Chicago, IL 60612 USA.
[Currier, Judith; Effros, Rita B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Currier, Judith; Effros, Rita B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Deren, Sherry] NYU, Coll Nursing, New York, NY USA.
[Gebo, Kelly] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
[Goronzy, Joerg J.] Stanford Univ, Sch Med, Dept Immunol & Rheumatol, Stanford, CA 94305 USA.
[Justice, Amy C.] Yale Univ, Dept Med, Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA.
[Landay, Alan] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA.
[Levin, Jules] Natl AIDS Treatment Advocacy Project, Off AIDS Res, New York, NY USA.
[Miotti, Paolo G.] NIH, Off AIDS Res, DHHS, Rockville, MD USA.
[Munk, Robert J.] AIDS InfoNet, Arroyo Seco, NM USA.
[Rinaldo, Charles R., Jr.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, Vet Affairs Med Ctr, San Francisco, CA USA.
[Tracy, Russell] Univ Vermont, Coll Med, Dept Pathol & Biochem, Colchester, VT USA.
[Valcour, Victor] Univ Calif San Francisco, Dept Neurol, Div Geriatr Med, Memory & Aging Ctr, San Francisco, CA USA.
[Vance, David E.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA.
[Volberding, Paul] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA.
[Walston, Jeremy D.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA.
RP High, KP (reprint author), Wake Forest Univ, Baptist Med Ctr, Infect Dis Sect, Dept Internal Med,Wake Forest Sch Med, 100 Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM khigh@wakehealth.edu
FU Office of AIDS Research, National Institutes of Health
FX Supported by the Office of AIDS Research, National Institutes of Health.
NR 88
TC 157
Z9 159
U1 5
U2 23
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUL 1
PY 2012
VL 60
SU 1
BP S1
EP S18
PG 18
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 968ZH
UT WOS:000306024400001
PM 22688010
ER
PT J
AU Paulson, OB
Kanno, I
Reivich, M
Sokoloff, L
AF Paulson, Olaf B.
Kanno, Iwao
Reivich, Martin
Sokoloff, Louis
TI History of International Society for Cerebral Blood Flow and Metabolism
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Review
DE cerebral blood flow; cerebral hemodynamics; cerebral ischemia; cerebral
metabolism; magnetic resonance; positron emission tomography
ID GLUCOSE-UTILIZATION; BRAIN-FUNCTION; CIRCULATION; ISCHEMIA; RAT
AB Interest in the brain's circulation dates back more than a century and has been steadily growing. Quantitative methods for measurements of cerebral blood flow (CBF) and energy metabolism became available in the middle of the 20th century and gave a new boost to the research. Scientific meetings dealing with CBF and metabolism were arranged, and the fast growing research led to a demand for a specialized journal. In this scientific environment, the International Society for Cerebral Blood Flow and Metabolism (ISCBFM) and its official Journal of Cerebral Metabolism were established in 1981 and has since then been a major success. The development of new brain imaging methods has had a major impact. Regulation of CBF and ischemia has been the main topics at the meetings. A new field of brain mapping research emerged and has now its own society and meetings. Brain emission tomography research has grown within the society and is now an integrated part. The ISCBFM is a sound society, and support of young scientists is among its goals. Several awards have been established. Other activities including summer schools, courses, satellite meetings, and Gordon conferences have contributed to the success of the society and strengthened the research. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1099-1106; doi: 10.1038/ jcbfm. 2011.183; published online 21 December 2011
C1 [Paulson, Olaf B.] Rigshosp, Copenhagen Univ Hosp, Neurobiol Res Unit, DK-2100 Copenhagen, Denmark.
[Paulson, Olaf B.] Univ Copenhagen, Hvidovre Hosp, Danish Res Ctr Magnet Resonance, Copenhagen, Denmark.
[Kanno, Iwao] Natl Inst Radiol Sci, Mol Imaging Ctr, Chiba 260, Japan.
[Reivich, Martin] Univ Penn, Dept Neurol, Cerebrovasc Res Ctr, Philadelphia, PA 19104 USA.
[Sokoloff, Louis] NIH, Bethesda, MD 20892 USA.
RP Paulson, OB (reprint author), Rigshosp, Copenhagen Univ Hosp, Neurobiol Res Unit, Build 9201,9 Blegdamsvej, DK-2100 Copenhagen, Denmark.
EM olaf.paulson@nru.dk
RI Paulson, Olaf/N-6924-2016
OI Paulson, Olaf/0000-0001-7712-8596
NR 27
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 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUL
PY 2012
VL 32
IS 7
BP 1099
EP 1106
DI 10.1038/jcbfm.2011.183
PG 8
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 968IH
UT WOS:000305970800002
PM 22186671
ER
PT J
AU Mittelstadt, PR
Monteiro, JP
Ashwell, JD
AF Mittelstadt, Paul R.
Monteiro, Joao P.
Ashwell, Jonathan D.
TI Thymocyte responsiveness to endogenous glucocorticoids is required for
immunological fitness
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID CELL ANTIGEN RECEPTOR; LCK PROXIMAL PROMOTER; PERIPHERAL T-CELLS;
NF-KAPPA-B; NEGATIVE SELECTION; THYMIC SELECTION; TRANSGENIC MICE;
IN-VIVO; AUTOREACTIVE THYMOCYTES; POSITIVE SELECTION
AB Generation of a self-tolerant but antigen-responsive T cell repertoire occurs in the thymus. Although glucocorticoids are usually considered immunosuppressive, there is also evidence that they play a positive role in thymocyte selection. To address the question of how endogenous glucocorticoids might influence the adaptive immune response, we generated GR(lck-Cre) mice, in which the glucocorticoid receptor gene (GR) is deleted in thymocytes prior to selection. These mice were immunocompromised, with reduced polyclonal T cell proliferative responses to alloantigen, defined peptide antigens, and viral infection. This was not due to an intrinsic proliferation defect, because GR-deficient T cells responded normally when the TCR was cross-linked with antibodies or when the T cell repertoire was "fixed" with alpha beta TCR transgenes. Varying the affinity of self ligands in alpha beta TCR transgenic mice showed that affinities that would normally lead to thymocyte-positive selection caused negative selection, and alterations in the TCR repertoire of polyclonal T cells were confirmed by analysis of TCR V beta CDR3 regions. Thus, endogenous glucocorticoids are required for a robust adaptive immune response because of their promotion of the selection of T cells that have sufficient affinity for self, and the absence of thymocyte glucocorticoid signaling results in an immunocompromised state.
C1 [Mittelstadt, Paul R.; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
[Monteiro, Joao P.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Ashwell, JD (reprint author), Bldg 37,Room 3002,37 Convent Dr, Bethesda, MD 20892 USA.
EM jda@pop.nci.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, NIH
FX We thank Ivana Munitic, Remy Bosselut, Paul Love, and Ronald Germain for
critical reading of the manuscript; and Kathryn Sun and Eric Stahlberg
of the NCI Center for Cancer Research Bioinformatics Core, Advanced
Biomedical Computing Center (ABCC) and SAIC-Frederick, for statistical
analysis of the TCR sequencing data and bioinformatics support. We also
thank Subhadra Banerjee and Barbara Taylor for assistance with cell
sorting, Ehydel Castro for performing cell transfers, and Bei Dong for
assistance with cloning. This work was supported by the Intramural
Research Program of the Center for Cancer Research, National Cancer
Institute, NIH. J.P. Monteiro is a Pew Fellow in the Biomedical
Sciences.
NR 70
TC 31
Z9 31
U1 0
U2 10
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUL
PY 2012
VL 122
IS 7
BP 2384
EP 2394
DI 10.1172/JCI63067
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 969GV
UT WOS:000306044600012
PM 22653054
ER
PT J
AU Sinha, RA
You, SH
Zhou, J
Siddique, MM
Bay, BH
Zhu, XG
Privalsky, ML
Cheng, SY
Stevens, RD
Summers, SA
Newgard, CB
Lazar, MA
Yen, PM
AF Sinha, Rohit Anthony
You, Seo-Hee
Zhou, Jin
Siddique, Mobin M.
Bay, Boon-Huat
Zhu, Xuguang
Privalsky, Martin L.
Cheng, Sheue-Yann
Stevens, Robert D.
Summers, Scott A.
Newgard, Christopher B.
Lazar, Mitchell A.
Yen, Paul M.
TI Thyroid hormone stimulates hepatic lipid catabolism via activation of
autophagy
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID ACTION IN-VIVO; INSULIN-RESISTANCE; NUCLEAR RECEPTOR; MONITORING
AUTOPHAGY; NONALCOHOLIC STEATOHEPATITIS; GENE-EXPRESSION; RAT-LIVER;
COREPRESSOR; BETA; PROTEIN
AB For more than a century, thyroid hormones (THs) have been known to exert powerful catabolic effects, leading to weight loss. Although much has been learned about the molecular mechanisms used by TH receptors (TRs) to regulate gene expression, little is known about the mechanisms by which THs increase oxidative metabolism. Here, we report that TH stimulation of fatty acid beta-oxidation is coupled with induction of hepatic autophagy to deliver fatty acids to mitochondria in cell culture and in vivo. Furthermore, blockade of autophagy by autophagy-related 5 (ATG5) siRNA markedly decreased TH-mediated fatty acid beta-oxidation in cell culture and in vivo. Consistent with this model, autophagy was altered in livers of mice expressing a mutant TR that causes resistance to the actions of TH as well as in mice with mutant nuclear receptor corepressor (NCoR). These results demonstrate that THs can regulate lipid homeostasis via autophagy and help to explain how THs increase oxidative metabolism.
C1 [Sinha, Rohit Anthony; Zhou, Jin; Siddique, Mobin M.; Summers, Scott A.; Yen, Paul M.] Duke NUS Grad Med Sch, Cardiovasc & Metab Disorders Program, Singapore 018987, Singapore.
[Lazar, Mitchell A.] Univ Penn, Sch Med, Perelman Sch Med,Translat Res Ctr, Div Endocrinol Diabet & Metab,Dept Med,Inst Diabe, Philadelphia, PA 19104 USA.
[Bay, Boon-Huat] Natl Univ Singapore, Dept Anat, Yong Loo Lin Sch Med, Singapore 117548, Singapore.
[Zhu, Xuguang; Cheng, Sheue-Yann] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Privalsky, Martin L.] UCD, Dept Microbiol, Davis, CA USA.
[Newgard, Christopher B.] Duke Univ, Med Ctr, Dept Med, Sarah W Stedman Nutr & Metab Ctr,Duke Independenc, Durham, NC 27704 USA.
[Stevens, Robert D.; Summers, Scott A.; Newgard, Christopher B.; Yen, Paul M.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27704 USA.
RP Yen, PM (reprint author), Duke NUS Grad Med Sch, Lab Hormonal Regulat, CVMD Program, 8 Coll Rd, Singapore 018987, Singapore.
EM newga002@mc.duke.edu; lazar@mail.med.upenn.edu; paul.yen@duke-nus.edu.sg
FU NIH [DK 43806]; Nuclear Receptor Signaling Atlas grant [NIH U19DK/HL/ES
62434]; American Diabetes Association (ADA) mentored research
fellowship; Duke-NUS Graduate Medical School Faculty Funds; Ministry of
Health; Ministry of Trade, Singapore; A*StaR; Ministry of Education
FX The authors would like to thank Benjamin A. Bikman, Chui Sun Yap,
Brijesh Singh, Guan Yuguang and Sherwin Ying Xie (Cardiovascular and
Metabolic Disorders Program, Duke-NUS Graduate Medical School), and Mei
Wang (Cancer Stem Cell Program, Duke-NUS Graduate Medical School) for
their helpful advice and constructive criticism. This work was supported
by grant NIH DK 43806 (to M.A. Lazar), the Nuclear Receptor Signaling
Atlas grant NIH U19DK/HL/ES 62434 (to C.B. Newgard and M.A. Lazar), and
an American Diabetes Association (ADA) mentored research fellowship (to
S.H. You and M.A. Lazar). This work also was supported by Duke-NUS
Graduate Medical School Faculty Funds (to P.M. Yen and S.A. Summers)
sponsored by the Ministry of Health, Ministry of Education, and Ministry
of Trade, Singapore, and A*StaR.
NR 63
TC 57
Z9 58
U1 3
U2 11
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 JUL
PY 2012
VL 122
IS 7
BP 2428
EP 2438
DI 10.1172/JCI60580
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 969GV
UT WOS:000306044600016
PM 22684107
ER
PT J
AU Li, WJ
Nava, RG
Bribriesco, AC
Zinselmeyer, BH
Spahn, JH
Gelman, AE
Krupnick, AS
Miller, MJ
Kreisel, D
AF Li, Wenjun
Nava, Ruben G.
Bribriesco, Alejandro C.
Zinselmeyer, Bernd H.
Spahn, Jessica H.
Gelman, Andrew E.
Krupnick, Alexander S.
Miller, Mark J.
Kreisel, Daniel
TI Intravital 2-photon imaging of leukocyte trafficking in beating heart
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID INTERCELLULAR-ADHESION MOLECULE-1; MYOCARDIAL REPERFUSION INJURY;
ISCHEMIA-REPERFUSION; TNF-ALPHA; NEUTROPHIL DEPLETION; VASCULAR
ENDOTHELIUM; INFARCT SIZE; MIGRATION; ICAM-1; INFLAMMATION
AB Two-photon intravital microscopy has substantially broadened our understanding of tissue- and organ-specific differences in the regulation of inflammatory responses. However, little is known about the dynamic regulation of leukocyte recruitment into inflamed heart tissue, largely due to technical difficulties inherent in imaging moving tissue. Here, we report a method for imaging beating murine hearts using intravital 2-photon microscopy. Using this method, we visualized neutrophil trafficking at baseline and during inflammation. Ischemia reperfusion injury induced by transplantation or transient coronary artery ligation led to recruitment of neutrophils to the heart, their extravasation from coronary veins, and infiltration of the myocardium where they formed large clusters. Grafting hearts containing mutant ICAM-1, a ligand important for neutrophil recruitment, reduced the crawling velocities of neutrophils within vessels, and markedly inhibited their extravasation. Similar impairment was seen with the inhibition of Mac-1, a receptor for ICAM-1. Blockade of LFA-1, another ICAM-1 receptor, prevented neutrophil adherence to endothelium and extravasation in heart grafts. As inflammatory responses in the heart are of great relevance to public health, this imaging approach holds promise for studying cardiac-specific mechanisms of leukocyte recruitment and identifying novel therapeutic targets for treating heart disease.
C1 [Li, Wenjun; Nava, Ruben G.; Bribriesco, Alejandro C.; Spahn, Jessica H.; Gelman, Andrew E.; Krupnick, Alexander S.; Kreisel, Daniel] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Zinselmeyer, Bernd H.] NINDS, NIH, Bethesda, MD 20892 USA.
[Gelman, Andrew E.; Miller, Mark J.; Kreisel, Daniel] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
RP Kreisel, D (reprint author), Washington Univ, Sch Med, Dept Surg, Campus Box 8234,660 S Euclid Ave, St Louis, MO 63110 USA.
EM miller@pathology.wustl.edu; kreiseld@wudosis.wustl.edu
FU National Heart, Lung and Blood Institute [1R01HL094601]; National
Institute of Allergy and Infectious Diseases [AI077600]
FX D. Kreisel and A.E. Gelman are supported by the National Heart, Lung and
Blood Institute (1R01HL094601), and M.J. Miller is supported by the
National Institute of Allergy and Infectious Diseases (AI077600) We
thank Arlene Ligori for medical illustration.
NR 37
TC 46
Z9 49
U1 0
U2 9
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUL
PY 2012
VL 122
IS 7
BP 2499
EP 2508
DI 10.1172/JCI62970
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 969GV
UT WOS:000306044600022
PM 22706307
ER
PT J
AU Rodrigues, TL
Foster, BL
Silverio, KG
Martins, L
Casati, MZ
Sallum, EA
Somerman, MJ
Nociti, FH
AF Rodrigues, Thaisangela L.
Foster, Brian L.
Silverio, Karina G.
Martins, Luciane
Casati, Marcio Z.
Sallum, Enilson A.
Somerman, Martha J.
Nociti, Francisco H., Jr.
TI Hypophosphatasia-associated Deficiencies in Mineralization and Gene
Expression in Cultured Dental Pulp Cells Obtained from Human Teeth
SO JOURNAL OF ENDODONTICS
LA English
DT Article
DE Alkaline phosphatase; dental pulp cells; dentin; hypophosphatasia;
pyrophosphate
ID NONSPECIFIC ALKALINE-PHOSPHATASE; DOMINANT HYPOPHOSPHATASIA; FAMILY;
PYROPHOSPHATE; OSTEOPONTIN; CEMENTUM; TISSUE; BINDING; MICE
AB Introduction: Mutations in the gene ALPL in hypophosphatasia (HPP) reduce the function of tissue nonspecific alkaline phosphatase, and the resulting increase in pyrophosphate (PPi) contributes to bone and tooth mineralization defects by inhibiting physiologic calcium-phosphate (P-i) precipitation. Although periodontal phenotypes are well documented, pulp/dentin abnormalities have been suggested in the clinical literature although reports are variable and underlying mechanisms remains unclear. in vitro analyses were used to identify mechanisms involved in HPP-associated pulp/dentin phenotypes. Methods: Primary pulp cells cultured from HPP subjects were established to assay alkaline phosphatase (ALP) activity, mineralization, and gene expression compared with cells from healthy controls. Exogenous P-i was provided to the correct P-i/PPi ratio in cell culture. Results: HPP cells exhibited significantly reduced ALP activity (by 50%) and mineral nodule formation (by 60%) compared with the controls. The expression of PP; regulatory genes was altered in HPP pulp cells, including reduction in the progressive ankylosis gene (ANKH) and increased ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Odontoblast marker gene expression was disrupted in HPP cells, including reduced osteopontin (OPN), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoprotein (MEPE). The addition of P-i provided a corrective measure for mineralization and partially rescued the expression of some genes although cells retained altered messenger RNA levels for PPi-associated genes. Conclusions: These studies suggest that under HPP conditions pulp cells have the compromised ability to mineralize and feature a disrupted odontoblast profile, providing a first step toward understanding the molecular mechanisms for dentin phenotypes observed in HPP. (J Endod 2012;38:907-912)
C1 [Rodrigues, Thaisangela L.; Silverio, Karina G.; Martins, Luciane; Casati, Marcio Z.; Sallum, Enilson A.; Nociti, Francisco H., Jr.] Univ Estadual Campinas, Sch Dent, Div Periodont, Dept Prosthodont & Periodont, Sao Paulo, Brazil.
[Foster, Brian L.; Somerman, Martha J.; Nociti, Francisco H., Jr.] NIAMSD, Natl Inst Hlth NIAMSNIH, Bethesda, MD 20892 USA.
RP Nociti, FH (reprint author), Univ Estadual Campinas, Sch Dent, Div Periodont, Dept Prosthodont & Periodont, Piracicaba, SP, Brazil.
EM nociti@fop.unicamp.br
RI Silverio, Karina/E-9424-2013; Rodrigues, Thaisangela/C-2293-2014;
Nociti, Francisco/G-4907-2015; Foster, Brian/H-8375-2015; Martins,
Luciane/C-9010-2016; Sallum, Enilson/G-2097-2016; casati, marcio
/G-7475-2012
OI Foster, Brian/0000-0003-3444-0576; Martins, Luciane/0000-0003-3635-7928;
FU Sao Paulo State Research Foundation (FAPESP, Brazil) [07/08192-5,
08/00534-7]; National Institutes of Health (NIH)/National Institute of
Dental and Craniofacial Research (NIDCR) [DE15109]; NIH Fogarty
International Research Collaboration Award (FIRCA) [5R03TW007590-03]
FX Supported by Sao Paulo State Research Foundation (FAPESP, Brazil, grant
#07/08192-5 and 08/00534-7 (FHNJ), National Institutes of Health
(NIH)/National Institute of Dental and Craniofacial Research (NIDCR)
DE15109 (M.J.S.), and NIH Fogarty International Research Collaboration
Award (FIRCA) grant 5R03TW007590-03 (M.J.S. and F.H.N.).
NR 34
TC 5
Z9 6
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0099-2399
J9 J ENDODONT
JI J. Endod.
PD JUL
PY 2012
VL 38
IS 7
BP 907
EP 912
DI 10.1016/j.joen.2012.02.008
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 966PR
UT WOS:000305850400007
PM 22703652
ER
PT J
AU Guedez, L
Jensen-Taubman, S
Bourboulia, D
Kwityn, CJ
Wei, BY
Caterina, J
Stetler-Stevenson, WG
AF Guedez, Liliana
Jensen-Taubman, Sandra
Bourboulia, Dimitra
Kwityn, Clifford J.
Wei, Beiyang
Caterina, John
Stetler-Stevenson, William G.
TI TIMP-2 Targets Tumor-associated Myeloid Suppressor Cells With Effects in
Cancer Immune Dysfunction and Angiogenesis
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE tumor immunotherapy; myeloid-derived suppressor cells (MDSC); tumor
inflammation; angiogenesis; tumor immunosuppression; matrix
metalloproteinases; tissue inhibitor of metalloproteases; non-small cell
lung cancer (NSCLC); VEGF-A; VEGF-R1
ID BONE-MARROW MICROENVIRONMENT; MEDIATED UP-REGULATION; NF-KAPPA-B;
ANNEXIN A1; ENDOTHELIAL-CELLS; MATRIX METALLOPROTEINASES; METASTASIS
FORMATION; PREMETASTATIC LUNG; COLORECTAL-CANCER; STEM-CELLS
AB Angiogenesis and inflammation are important therapeutic targets in non-small cell lung cancer (NSCLC). It is well known that proteolysis mediated by matrix metalloproteinases (MMPs) promotes angiogenesis and inflammation in the tumor microenvironment. Here, the effects of the MMP inhibitor TIMP-2 on NSCLC inflammation and angiogenesis were evaluated in TIMP-2-deficient (timp2(-/-)) mice injected subcutaneously (SC) with Lewis lung carcinoma cells and compared with the effects on tumors in wild-type mice. TIMP-2-deficient mice demonstrated increased tumor growth, enhanced expression of angiogenic marker alpha(v)beta(3) in tumor and endothelial cells, and significantly higher serum vascular endothelial growth factor-A levels. Tumor-bearing timp2(-/-) mice showed a significant number of inflammatory cells in their tumors, upregulation of inflammation mediators, nuclear factor-kappaB, and Annexin A1, as well as higher levels of serum interleukin (IL)-6. Phenotypic analysis revealed an increase in myeloid-derived suppressor cell (MDSC) cells (CD11b(+) and Gr-1(+)) that coexpressed vascular-endothelial-growth factor receptor 1 (VEGF-R1) and elevated MMP activation present in tumors and spleens from timp2(-/-) mice. Furthermore, TIMP-2-deficient tumors upregulated expression of the immunosuppressing genes controlling MDSC growth, IL-10, IL-13, IL-11, and chemokine ligand (CCL-5/RANTES), and decreased interferon-gamma and increased CD40L. Moreover, forced TIMP-2 expression in human lung adenocarcinoma A-549 resulted in a significant reduction of MDSCs recruited into tumors, as well as suppression of angiogenesis and tumor growth. The increase in MDSCs has been linked to cancer immunosuppression and angiogenesis. Therefore, this study supports TIMP-2 as a negative regulator of MDSCs with important implications for the immunotherapy and/or antiangiogenic treatment of NSCLC.
C1 [Guedez, Liliana; Jensen-Taubman, Sandra; Bourboulia, Dimitra; Wei, Beiyang; Stetler-Stevenson, William G.] NCI, Radiat Oncol Branch, Extracellular Matrix Pathol Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kwityn, Clifford J.] Baylor Coll Med, Dept Trop Med, Houston, TX 77030 USA.
[Caterina, John] Bethel Univ, Div Sci & Math, Mckenzie, TN USA.
RP Guedez, L (reprint author), NCI, Adv Technol Ctr, Radiat Oncol Branch, Room 115,8717 Grovemont Circle, Bethesda, MD 20892 USA.
EM guedezl@mail.nih.gov
RI Stetler-Stevenson, William/H-6956-2012; Guedez, Liliana/H-4951-2012
OI Stetler-Stevenson, William/0000-0002-5500-5808;
FU Center for Cancer Research, NCI [Z01 SC009179-20]
FX This work was supported by funds from the Center for Cancer Research,
NCI intramural project number Z01 SC009179-20.
NR 55
TC 19
Z9 23
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD JUL-AUG
PY 2012
VL 35
IS 6
BP 502
EP 512
DI 10.1097/CJI.0b013e3182619c8e
PG 11
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 967GY
UT WOS:000305896000006
PM 22735808
ER
PT J
AU Saslow, D
Solomon, D
Lawson, HW
Killackey, M
Kulasingam, SL
Cain, JM
Garcia, FAR
Moriarty, AT
Waxman, AG
Wilbur, DC
Wentzensen, N
Downs, LS
Spitzer, M
Moscicki, AB
Franco, EL
Stoler, MH
Schiffman, M
Castle, PE
Myers, ER
AF Saslow, Debbie
Solomon, Diane
Lawson, Herschel W.
Killackey, Maureen
Kulasingam, Shalini L.
Cain, Joanna M.
Garcia, Francisco A. R.
Moriarty, Ann T.
Waxman, Alan G.
Wilbur, David C.
Wentzensen, Nicolas
Downs, Levi S., Jr.
Spitzer, Mark
Moscicki, Anna-Barbara
Franco, Eduardo L.
Stoler, Mark H.
Schiffman, Mark
Castle, Philip E.
Myers, Evan R.
TI American Cancer Society, American Society for Colposcopy and Cervical
Pathology, and American Society for Clinical Pathology Screening
Guidelines for the Prevention and Early Detection of Cervical Cancer
SO JOURNAL OF LOWER GENITAL TRACT DISEASE
LA English
DT Article
DE adult HPV; cervical intraepithelial neoplasia/epidemiology/prevention;
female cervical cancer
ID HUMAN-PAPILLOMAVIRUS DNA; RANDOMIZED CONTROLLED-TRIAL; ATYPICAL
SQUAMOUS-CELLS; INTRAEPITHELIAL NEOPLASIA GRADE-2; INTERNATIONAL
INCIDENCE RATES; ADENOCARCINOMA IN-SITU; LIQUID-BASED CYTOLOGY;
LONG-TERM RISK; COST-EFFECTIVENESS; UNITED-STATES
AB An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium co-sponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16/18 infections.
C1 [Saslow, Debbie] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30303 USA.
[Solomon, Diane] NCI, Canc Prevent Div, NIH, Rockville, MD USA.
[Lawson, Herschel W.] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA.
[Killackey, Maureen] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, Mem Sloan Kettering Canc Ctr Reg Network, New York, NY 10021 USA.
[Kulasingam, Shalini L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Cain, Joanna M.] Univ Massachusetts, Sch Med, Dept Obstet & Gynecol, Worcester, MA USA.
[Garcia, Francisco A. R.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Ctr Excellence Womens Hlth, Tucson, AZ USA.
[Moriarty, Ann T.] AmeriPath Indiana, Dept Esoter Testing, Indianapolis, IN USA.
[Moriarty, Ann T.] Univ New Mexico, Sch Med, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA.
[Wilbur, David C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Downs, Levi S., Jr.] Univ Minnesota, Sch Med, Div Gynecol Oncol, Dept Obstet Gynecol & Womens Hlth,Mason Canc Ctr, Minneapolis, MN 55455 USA.
[Spitzer, Mark] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
[Moscicki, Anna-Barbara] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Franco, Eduardo L.] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
[Franco, Eduardo L.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada.
[Stoler, Mark H.] Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA.
[Schiffman, Mark] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Castle, Philip E.] Amer Chem Soc, Clin Pathol Inst, Washington, DC 20036 USA.
[Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
RP Saslow, D (reprint author), Amer Canc Soc, Canc Control Sci Dept, 250 Williams St NW,Suite 600, Atlanta, GA 30303 USA.
EM debbie.saslow@cancer.org
OI Franco, Eduardo/0000-0002-4409-8084
FU Merck Sharp Dohme; Merck, Inc.; Roche Pharmaceutical/Roche Molecular;
Hologic; Third Wave; MTM; Qiagen; Becton Dickinson; Medispectra/Luma;
Roche; Gen-Probe; Abbott; Gen-Probe, Inc.; GSK, Inc.; Precision
Therapeutics; National Surgical Adjuvant Breast and Bowel Project; Merck
Research Laboratories; Ventana Medical Systems; IKONOBGYN; Hatt, Co.;
Merck, Inc; National Institute of Allergy and Infectious Diseases; Gen
Probe
FX Philip E. Castle, PhD, MPH, receives payment for service on the Data
Monitoring and Safety Board for Merck Sharp & Dohme. Carmel Cohen, MD,
serves as a speaker for Merck, Inc. and receives honoraria. The spouse
of Mitchell Edelson, MD, is employed and receives salary from Merck,
Inc. Francisco Garcia, MD, MPH, is employed by the University of
Arizona, which holds contracts for the performance of research with
Roche Pharmaceutical/Roche Molecular, Hologic, Third Wave, MTM, Qiagen,
Becton Dickinson, and Medispectra/Luma. Dr Garcia also serves on the
speakers' list for Qiagen and receives honoraria. Jack Cuzick, MD,
serves on advisory boards and as an ad hoc consultant for Qiagen, Roche,
Gen-Probe, Becton Dickinson, and Abbott, with research fund provided to
his institution from Qiagen, Roche, Gen-Probe, Becton Dickinson, and
Abbott. Patti Gravitt, MD, provides service on the scientific advisory
board from Qiagen and for which she received honoraria. Evan R. Myers,
MD, MPH, received research support for investigations for Gen-Probe,
Inc. and from GSK, Inc. He served as a speaker for and received
honoraria from Gen-Probe, Inc. and has served as a consultant for Merck,
Inc., for which he received an honorarium. Mark Schiffman, MD, MPH,
holds a research agreement to serve as a medical monitor in the National
Cancer Institute vaccine trial through GlaxoSmithKline; Dr Schiffman
also receives research support from Qiagen for CareHPV research in
Nigeria. Carolyn Runowicz, MD, serves on the board of directors for the
American Society for Clinical Oncology and provides service on the
scientific advisory board from Bayer for which she receives honoraria.
Dr Runowicz has provided scientific review for and received payment from
Precision Therapeutics, as well as served on the advisory board for
Ovarian Cancer Research Fund (no payments received). Dr Runowicz is a
paid reviewer for Champions Oncology, and she has received research
funding from National Surgical Adjuvant Breast and Bowel Project. Diane
Solomon, MD, serves as a medical monitor for the National Cancer
Institute's HPV Vaccine Trial in Costa Rica: the trial receives vaccine
from GlaxoSmithKline. Mark H. Stoler, MD, received fees for serving as a
consultant to Merck Research Laboratories, Roche, Ventana Medical
Systems, Becton Dickinson, Hologic, MTM, and Gen-Probe. Richard S.
Guido, MD, received research funds for services as the primary
investigator on a multicenter study (contracted research and serves
local PI) for IKONOBGYN. Dr Guido also received research funds to be a
primary investigator on a multicenter study (local PI) for Hatt, Co.
Dina R. Mody, MD, conducted lectures/workshops for both CAP and the
American Society for Clinical Pathology and from which she received
honoraria. Dr Mody received reimbursement for her travel expenses for
conducting an ASC lecture/workshop. Jeffrey Waldman, MD, attended a
consultants meeting for Graceway Pharmaceuticals and received an
honorarium. The employer of George Birdsong, MD, receives funding for
contracted research performed by Dr Birdsong for Becton Dickinson
Diagnostics. Cosette Wheeler, PhD, is an employee of University of New
Mexico, which is contracted by GlaxoSmithKline for its vaccine trials
and for which Dr Wheeler serves as a principal investigator. Dr Wheeler
also serves as a principal investigator employee of the University of
New Mexico, which receives equipment/reagents from Roche Molecular
Systems for human papillomavirus genotyping. J.; Thomas Cox, MD, serves
on the scientific advisory boards for Gen-Probe, Graceway, and Bradley
Pharmaceuticals and receives honoraria for these services. Dr Cox also
serves on the Data and Safety Monitoring Board and receives a fee from
Merck, Inc; he was reimbursed for travel expenses for meetings of the
Roche Data and Steering Committee. Dr Cox serves on the speakers' bureau
for Bradley Pharmaceuticals and has served to both speak and moderate at
a symposium for Becton Dickinson Diagnostics; honoraria were received
for these activities. David Wilbur, MD, serves on the scientific
advisory board for Corista, LLC. Teresa M. Darragh, MD, received Thin
Prep supplies for research from Ho logic. She serves on an advisory
board from OncoHealth and has received stock options as payment. Dr
Darragh also serves on an advisory board for Arbor Vita Corporation and
receives honoraria. Edward J. Mayeaux, Jr., MD, serves on the speakers'
advisory board for both Merck, Inc. and PharmaDerm, and he receives
honoraria from both companies for his service. Mark Spitzer, MD, serves
as a speaker for both Merck, Inc. and Qiagen and receives honoraria. He
received an honorarium and royalties from Elsevier for book editorship;
Dr Spitzer also received royalties as an author for the Colposcopy Image
Library CD-ROM produced by SABK, Inc. Kevin A. Ault, MD, received
clinical research grants from National Institute of Allergy and
Infectious Diseases, Gen Probe, Merck, Inc., and Roche and served as a
site principal investigator for the research. All grants were provided
to his employer, Emory University. Eduardo Franco, MD, received
honorarium as a study steering committee member for GlaxoSmithKline; Dr
Franco serves on the advisory boards of Merck, Inc., Roche, and GenProbe
and from which he receives honoraria. Michael A. Gold, MD, received
honorarium for serving as a speaker and consultant for Hologic. Warner
K. Huh, MD, serves as a consultant to Roche, Qiagen, Merck, Inc., and
Inovio and receives honoraria from all four companies. Anna-Barbara
Moscicki, MD, received honorarium for serving as a consultant to an
advisory board for Merck, Inc. Mark E. Einstein, MD, has advised or
participated in educational speaking activities but does not receive an
honorarium from any companies. His employer, Montefiore Medical Center,
has received payment for his time spent on activities for Merck, Inc.,
GlaxoSmithKline, Roche, Bristol-Myers Squibb, Hologic, Advaxis, Aura
Biosciences, Inovio, Photocure, Neodiagnostix, and PDS Biotechnologies.
Montefiore Medical Center has received grant funding for research
related to the costs of those Merck, GlaxoSmithKline, Roche, Advaxis,
and Hologic clinical trials for which Dr Einstein served as the
principal investigator of Montefiore Medical Center's. Ann T. Moriarty,
MD, received honorarium as a speaker for the American Society of
Cytopathology; Dr Moriarty also receives a salary as compensation for
her employment with AmeriPath.
NR 156
TC 92
Z9 97
U1 3
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1089-2591
J9 J LOW GENIT TRACT DI
JI J. Low. Genit. Tract. Dis.
PD JUL
PY 2012
VL 16
IS 3
BP 175
EP 204
PG 30
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 966OC
UT WOS:000305846300004
PM 22418039
ER
PT J
AU Widiapradja, A
Vegh, V
Lok, KZ
Manzanero, S
Thundyil, J
Gelderblom, M
Cheng, YL
Pavlovski, D
Tang, SC
Jo, DG
Magnus, T
Chan, SL
Sobey, CG
Reutens, D
Basta, M
Mattson, MP
Arumugam, TV
AF Widiapradja, Alexander
Vegh, Viktor
Lok, Ker Zhing
Manzanero, Silvia
Thundyil, John
Gelderblom, Mathias
Cheng, Yi-Lin
Pavlovski, Dale
Tang, Sung-Chun
Jo, Dong-Gyu
Magnus, Tim
Chan, Sic L.
Sobey, Christopher G.
Reutens, David
Basta, Milan
Mattson, Mark P.
Arumugam, Thiruma V.
TI Intravenous immunoglobulin protects neurons against amyloid beta-peptide
toxicity and ischemic stroke by attenuating multiple cell death pathways
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE A ss; Alzheimer's disease; apoptosis; IVIg; neurons; stroke
ID CEREBRAL-ARTERY OCCLUSION; ALZHEIMERS-DISEASE; BRAIN-INJURY;
LIPID-PEROXIDATION; ANTIINFLAMMATORY ACTIVITY; INDUCED APOPTOSIS;
KAPPA-B; MECHANISMS; EXPRESSION; MODEL
AB J. Neurochem. (2012) 122, 321332. Abstract Intravenous immunoglobulin (IVIg) preparations obtained by fractionating blood plasma, are increasingly being used increasingly as an effective therapeutic agent in treatment of several inflammatory diseases. Its use as a potential therapeutic agent for treatment of stroke and Alzheimers disease has been proposed, but little is known about the neuroprotective mechanisms of IVIg. In this study, we investigated the effect of IVIg on downstream signaling pathways that are involved in neuronal cell death in experimental models of stroke and Alzheimers disease. Treatment of cultured neurons with IVIg reduced simulated ischemia- and amyloid beta peptide (A beta)-induced caspase 3 cleavage, and phosphorylation of the cell death-associated kinases p38MAPK, c-Jun NH2-terminal kinase and p65, in vitro. Additionally, A beta-induced accumulation of the lipid peroxidation product 4-hydroxynonenal was attenuated in neurons treated with IVIg. IVIg treatment also up-regulated the anti-apoptotic protein, Bcl2 in cortical neurons under ischemia-like conditions and exposure to A beta. Treatment of mice with IVIg reduced neuronal cell loss, apoptosis and infarct size, and improved functional outcome in a model of focal ischemic stroke. Together, these results indicate that IVIg acts directly on neurons to protect them against ischemic stroke and A beta-induced neuronal apoptosis by inhibiting cell death pathways and by elevating levels of the anti-apoptotic protein Bcl2.
C1 [Widiapradja, Alexander; Lok, Ker Zhing; Manzanero, Silvia; Thundyil, John; Cheng, Yi-Lin; Pavlovski, Dale; Arumugam, Thiruma V.] Univ Queensland, Sch Biomed Sci, St Lucia, Qld, Australia.
[Vegh, Viktor; Reutens, David] Univ Queensland, Ctr Adv Imaging, St Lucia, Qld, Australia.
[Gelderblom, Mathias; Magnus, Tim] Univ Clin Hamburg Eppendorf, Dept Neurol, Hamburg, Germany.
[Tang, Sung-Chun] Natl Taiwan Univ Hosp, Dept Neurol, Stroke Ctr, Taipei, Taiwan.
[Jo, Dong-Gyu] Sungkyunkwan Univ, Sch Pharm, Suwon, South Korea.
[Chan, Sic L.] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32816 USA.
[Sobey, Christopher G.] Monash Univ, Dept Pharmacol, Clayton, Vic 3168, Australia.
[Basta, Milan] Biovisions Inc, Potomac, MD USA.
[Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Arumugam, TV (reprint author), Univ Queensland, Sch Biomed Sci, St Lucia, Qld, Australia.
EM t.arumugam@uq.edu.au
RI Arumugam, Thiruma/B-4898-2011;
OI Basta, Milan/0000-0001-5958-9241; Tang, Sung-Chun/0000-0003-3731-5973;
Manzanero, Silvia/0000-0002-5294-7082
FU National Heart Foundation of Australia [G 09B 4272]; Australian National
Health and Medical Research Council [NHMRC APP1008048]; ARC Future
Fellowship [FT100100427]; National Institute on Aging
FX This work was supported by the National Heart Foundation of Australia
for a Grant-In-Aid (G 09B 4272), the Australian National Health and
Medical Research Council grant (NHMRC APP1008048), ARC Future Fellowship
(FT100100427) awarded to TVA, and the National Institute on Aging
Intramural Research Program. The authors declare no conflict of
interest.
NR 47
TC 16
Z9 16
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JUL
PY 2012
VL 122
IS 2
BP 321
EP 332
DI 10.1111/j.1471-4159.2012.07754.x
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 967HH
UT WOS:000305897000010
PM 22494053
ER
PT J
AU Lee, JK
Chung, J
Druey, KM
Tansey, MG
AF Lee, Jae-Kyung
Chung, Jaegwon
Druey, Kirk M.
Tansey, Malu G.
TI RGS10 exerts a neuroprotective role through the PKA/c-AMP
response-element (CREB) pathway in dopaminergic neuron-like cells
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE CREB; dopaminergic; MN9D; neuroinflammation; RGS10; TNF
ID NECROSIS-FACTOR-ALPHA; GTPASE-ACTIVATING PROTEINS; MESSENGER-RNA
EXPRESSION; PARKINSONS-DISEASE; SUSCEPTIBILITY GENE;
SUBCELLULAR-LOCALIZATION; HEMIPARKINSONIAN RATS; ALZHEIMERS-DISEASE;
SIGNALING RGS; SCHIZOPHRENIA
AB J. Neurochem. (2012) 122, 333343. Abstract Regulator of G-protein signaling-10 (RGS10) is a GTPase activating protein for Gai/q/z subunits that is highly expressed in the immune system and in a broad range of brain regions including the hippocampus, striatum, dorsal raphe, and ventral midbrain. Previously, we reported that RGS10-null mice display increased vulnerability to chronic systemic inflammation-induced degeneration of nigral dopaminergic (DA) neurons. Given that RGS10 is expressed in DA neurons, we investigated the extent to which RGS10 regulates cell survival under conditions of inflammatory stress. Because of the inherent limitations associated with use of primary DA neurons for biochemical analyses, we employed a well-characterized ventral mesencephalon DA neuroblastoma cell line (MN9D) for our studies. We found that stable over-expression of RGS10 rendered them resistant to TNF-induced cytotoxicity; whereas MN9D cells expressing mutant RGS10-S168A (which is resistant to phosphorylation by protein kinase A at a serine residue that promotes its nuclear translocation) showed similar sensitivity to TNF as the parental MN9D cells. Using biochemical and pharmacologic approaches, we identified protein kinase A and the downstream phospho-cAMP response element-binding signaling pathway (and ruled out ERK 1/2, JNK, and NFkB) as key mediators of the neuroprotective effect of RGS10 against inflammatory stress.
C1 [Lee, Jae-Kyung; Chung, Jaegwon; Tansey, Malu G.] Emory Univ, Sch Med, Dept Physiol, Atlanta, GA 30322 USA.
[Druey, Kirk M.] NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Tansey, MG (reprint author), Emory Univ, Sch Med, Dept Physiol, 615 Michael St,605L Whitehead Biomed Res Bldg, Atlanta, GA 30322 USA.
EM jaekyung.lee@emory.edu; malu.tansey@emory.edu
FU Michael J. Fox Foundation for Parkinson's Research; Emory University
Parkinson's Disease Collaborative Environmental Research Center
Development Program; NINDS at National Institutes of Health
[R01NS072467-02]
FX This work was supported by a Target Validation grant from the Michael J.
Fox Foundation for Parkinson's Research (M. G. T.), a pilot grant from
Emory University Parkinson's Disease Collaborative Environmental
Research Center Development Program (J.-K.L.), and Grant R01NS072467-02
(M. G. T.) from the NINDS at the National Institutes of Health. We thank
Patrick Burgon at The University of Ottawa for kindly providing the
RGS10-SA mutant cDNA, Lynn Malone for technical help with cell culture,
and members of the Tansey Lab for useful discussions.
NR 50
TC 10
Z9 11
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JUL
PY 2012
VL 122
IS 2
BP 333
EP 343
DI 10.1111/j.1471-4159.2012.07780.x
PG 11
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 967HH
UT WOS:000305897000011
PM 22564151
ER
PT J
AU Conforto, AB
Anjos, SM
Saposnik, G
Mello, EA
Nagaya, EM
Santos, W
Ferreiro, KN
Melo, ES
Reis, FI
Scaff, M
Cohen, LG
AF Conforto, Adriana B.
Anjos, Sarah M.
Saposnik, Gustavo
Mello, Eduardo A.
Nagaya, Erina M.
Santos, Waldyr, Jr.
Ferreiro, Karina N.
Melo, Eduardo S.
Reis, Felipe I.
Scaff, Milberto
Cohen, Leonardo G.
TI Transcranial magnetic stimulation in mild to severe hemiparesis early
after stroke: a proof of principle and novel approach to improve motor
function
SO JOURNAL OF NEUROLOGY
LA English
DT Article
DE Stroke; Transcranial magnetic stimulation; Rehabilitation; Hemiparesis;
Neuromodulation
ID UPPER EXTREMITY FUNCTION; CONSTRAINT-INDUCED MOVEMENT; ACUTE
ISCHEMIC-STROKE; BRAIN-STIMULATION; UPPER-LIMB; RECOVERY; THERAPY;
CORTEX; TRIAL; HAND
AB Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can enhance function of the paretic hand in patients with mild motor impairment. Effects of low-frequency rTMS to the contralesional motor cortex at an early stage of mild to severe hemiparesis after stroke are unknown. In this pilot, randomized, double-blind clinical trial we compared the effects of low-frequency rTMS or sham rTMS as add-on therapies to outpatient customary rehabilitation, in 30 patients within 5-45 days after ischemic stroke, and mild to severe hand paresis. The primary feasibility outcome was compliance with the interventions. The primary safety outcome was the proportion of intervention-related adverse events. Performance of the paretic hand in the Jebsen-Taylor test and pinch strength were secondary outcomes. Outcomes were assessed at baseline, after ten sessions of treatment administered over 2 weeks and at 1 month after end of treatment. Baseline clinical features were comparable across groups. For the primary feasibility outcome, compliance with treatment was 100% in the active group and 94% in the sham group. There were no serious intervention-related adverse events. There were significant improvements in performance in the Jebsen-Taylor test (mean, 12.3% 1 month after treatment) and pinch force (mean, 0.5 Newtons) in the active group, but not in the sham group. Low-frequency rTMS to the contralesional motor cortex early after stroke is feasible, safe and potentially effective to improve function of the paretic hand, in patients with mild to severe hemiparesis. These promising results will be valuable to design larger randomized clinical trials.
C1 [Conforto, Adriana B.; Anjos, Sarah M.; Mello, Eduardo A.; Nagaya, Erina M.; Santos, Waldyr, Jr.; Ferreiro, Karina N.; Melo, Eduardo S.; Reis, Felipe I.; Scaff, Milberto] Univ Sao Paulo, Div Clin Neurol, Hosp Clin, BR-05403010 Sao Paulo, Brazil.
[Conforto, Adriana B.] Inst Israelita Ensino & Pesquisa Albert Einstein, Sao Paulo, Brazil.
[Saposnik, Gustavo] Univ Toronto, St Michaels Hosp, Stroke Outcomes Res Unit, Toronto, ON M5B 1W8, Canada.
[Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Rehabil Sect, Bethesda, MD 20892 USA.
RP Conforto, AB (reprint author), Univ Sao Paulo, Div Clin Neurol, Hosp Clin, Av Dr Eneas C Aguiar 255-5084, BR-05403010 Sao Paulo, Brazil.
EM adriana.conforto@gmail.com
RI DOS ANJOS, SARAH/G-9277-2015;
OI DOS ANJOS, SARAH/0000-0002-7792-862X; Saposnik,
Gustavo/0000-0002-5950-9886
FU Sao Paulo State's Foundation for Research Support (FAPESP), a Brazilian
governmental agency [2006/55504-0]; FAPESP [2009/51641-0, 2010/12696-1];
Sarah dos Anjos [2010/15660-8]
FX This work was funded by grant 2006/55504-0 from Sao Paulo State's
Foundation for Research Support (FAPESP), a Brazilian governmental
agency. The authors have no financial relationships with FAPESP.
Scholarships from FAPESP were funded to Erina Nagaya (2009/51641-0 and
2010/12696-1) and Sarah dos Anjos (2010/15660-8). FAPESP had no roles in
the design and conduct of the study; collection, management, analysis,
and interpretation of the data; and preparation, review, or approval of
the manuscript. We thank David Luckenbaugh for helpful discussions about
statistical analysis of the data.
NR 41
TC 31
Z9 38
U1 1
U2 6
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
J9 J NEUROL
JI J. Neurol.
PD JUL
PY 2012
VL 259
IS 7
BP 1399
EP 1405
DI 10.1007/s00415-011-6364-7
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 970JZ
UT WOS:000306125700020
PM 22173953
ER
PT J
AU Kao, PF
Banigan, MG
Vanderburg, CR
McKee, AC
Polgar, PR
Seshadri, S
Delalle, I
AF Kao, Patricia F.
Banigan, Meredith G.
Vanderburg, Charles R.
McKee, Ann C.
Polgar, Peter R.
Seshadri, Sudha
Delalle, Ivana
TI Increased Expression of TrkB and Capzb2 Accompanies Preserved Cognitive
Status in Early Alzheimer Disease Pathology
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Alzheimer disease; Brain-derived neurotrophic factor; Brain reserve;
Capzb2; TrkB
ID NEUROTROPHIC FACTOR BDNF; DATA SET UDS; MESSENGER-RNA; ASSOCIATION
WORKGROUPS; DIAGNOSTIC GUIDELINES; VAL66MET POLYMORPHISM;
HIPPOCAMPAL-NEURONS; NATIONAL INSTITUTE; NEURITE OUTGROWTH; LIFETIME
RISK
AB Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) may influence brain reserve, the ability of the brain to tolerate pathological changes without significant decline in function. Here, we explore whether a specifically vulnerable population of human neurons shows a compensatory response to the neuropathological changes of Alzheimer disease (AD) and whether that response depends on an upregulation of the BDNF pathway. We observed increased neuronal TrkB expression associated with early-stage AD pathology (Braak and Braak stages I-II) in hippocampal CA1 region samples from cognitively intact Framingham Heart Study subjects (n = 5) when compared with cognitively intact individuals with no neurofibrillary tangles (n = 4). Because BDNF/TrkB signaling affects memory formation and retention through modification of the actin cytoskeleton, we examined the expression of actin capping protein beta 2 (Capzb2), a marker of actin cytoskeleton reorganization. Capzb2 expression was also significantly increased in CA1 hippocampal neurons of cognitively intact subjects with early-stage AD pathology. Our data suggest that increased expression of TrkB and Capzb2 accompanies adequate brain reserve in the initial stages of AD pathology. In subsequent stages of AD, the higher levels of TrkB and Capzb2 expression achieved may not be sufficient to prevent cognitive decline.
C1 [Kao, Patricia F.; Delalle, Ivana] Boston Univ, Dept Pathol & Lab Med, Sch Med, Boston, MA 02118 USA.
[McKee, Ann C.; Seshadri, Sudha; Delalle, Ivana] Boston Univ, Dept Neurol, Sch Med, Boston, MA 02118 USA.
[Polgar, Peter R.] Boston Univ, Dept Biochem, Sch Med, Boston, MA 02118 USA.
[Banigan, Meredith G.; Vanderburg, Charles R.] Harvard NeuroDiscovery Ctr, Adv Tissue Resource Ctr, Charlestown, MA USA.
[McKee, Ann C.; Seshadri, Sudha; Delalle, Ivana] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
RP Delalle, I (reprint author), Boston Univ, Dept Pathol, Boston Med Ctr, Sch Med, Housman Med Re Bldg R097, Boston, MA 02118 USA.
EM idelalle@bu.edu
OI Polgar, Peter/0000-0002-9112-1101; Seshadri, Sudha/0000-0001-6135-2622
FU National Institutes of Health [5T32AG000115-25, R01AG031287, R01AG08122,
R01AG033193, R01AG16495, P30AG013846]; Mallory funds at Boston
University School of Medicine Pathology Department
FX This work was supported by National Institutes of Health Grants
5T32AG000115-25 (PFK, PRP), R01AG031287, R01AG08122, R01AG033193,
R01AG16495, and P30AG013846 (SS) and by Mallory funds at Boston
University School of Medicine Pathology Department (ID).
NR 53
TC 9
Z9 10
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUL
PY 2012
VL 71
IS 7
BP 654
EP 664
DI 10.1097/NEN.0b013e31825d06b7
PG 11
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 968FS
UT WOS:000305963300006
PM 22710966
ER
PT J
AU Kim, YS
Farrar, W
Colburn, NH
Milner, JA
AF Kim, Young S.
Farrar, William
Colburn, Nancy H.
Milner, John A.
TI Cancer stem cells: potential target for bioactive food components
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Review
DE Cancer stem cells; Vitamins A and D; Sulforaphane; Genistein; EGCG;
Theanine; Curcumin; Piperine
ID HEDGEHOG SIGNALING PATHWAY; HUMAN-COLON-CANCER; TO-MESENCHYMAL
TRANSITION; BREAST-CANCER; SELF-RENEWAL; PANCREATIC-CANCER; VITAMIN-D;
MYELOID-LEUKEMIA; INITIATING CELLS; EPITHELIAL-CELLS
AB Cancer stem cells often have phenotypic and functional characteristics similar to normal stem cells including the properties of self-renewal and differentiation. Recent findings suggest that uncontrolled self-renewal may explain cancer relapses and may represent a critical target for cancer prevention. It is conceivable that the loss of regulatory molecules resulting from inappropriate consumption of specific foods and their constituents may foster the aberrant self-renewal of cancer stem cells. In fact, increasing evidence points to the network delivering signals for self-renewal from extracellular compartments to the nucleus including changes in stem cell environments, inducible expression of microRNAs, hyperplastic nuclear chromatin structures, and the on/off of differentiation process as possible sites of action for bioactive food components. Diverse dietary constituents such as vitamins A and D, genistein, (-)-epigallocatechin-3-gallate (EGCG), sulforaphane, curcumin, piperine, theanine and choline have been shown to modify self-renewal properties of cancer stem cells. The ability of these bioactive food components to influence the balance between proliferative and quiescent cells by regulating critical feedback molecules in the network including dickkopf 1 (DKK-1), secreted frizzled-related protein 2 (sFRP2), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and cyclin-dependent kinase 6 (CDK6) may account for their biological response. Overall, the response to food components does not appear to be tissue or organ specific, suggesting there may be common cellular mechanisms. Unquestionably, additional studies are needed to clarify the physiological role of these dietary components in preventing the resistance of tumor cells to traditional drugs and cancer recurrence. Published by Elsevier Inc.
C1 [Kim, Young S.; Milner, John A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Farrar, William; Colburn, Nancy H.] NCI Frederick, Lab Canc Prevent, Ctr Canc Res, NCI, Ft Detrick, MD 21702 USA.
RP Kim, YS (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
EM yk47s@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 98
TC 22
Z9 23
U1 0
U2 40
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD JUL
PY 2012
VL 23
IS 7
BP 691
EP 698
DI 10.1016/j.jnutbio.2012.03.002
PG 8
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 962KM
UT WOS:000305544000001
PM 22704055
ER
PT J
AU George, SM
Smith, AW
AF George, Stephanie M.
Smith, Ashley Wilder
TI Commentary: Understanding Risk Behavior Among Adolescent Cancer
Survivors-Are They More Like Healthy Adolescents or is Cancer a
Teachable Moment? A Commentary on Klosky and Colleagues' Article on
Health Behaviors in Survivors of Childhood Cancer and Their Siblings
SO JOURNAL OF PEDIATRIC PSYCHOLOGY
LA English
DT Editorial Material
ID INTERVENTIONS; SMOKING
C1 [George, Stephanie M.; Smith, Ashley Wilder] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP George, SM (reprint author), 6130 Execut Blvd,EPN 4017A, Bethesda, MD 20892 USA.
EM stephanie.george@nih.gov
NR 11
TC 1
Z9 1
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0146-8693
J9 J PEDIATR PSYCHOL
JI J. Pediatr. Psychol.
PD JUL
PY 2012
VL 37
IS 6
BP 647
EP 649
DI 10.1093/jpepsy/jss064
PG 3
WC Psychology, Developmental
SC Psychology
GA 966HD
UT WOS:000305827600006
PM 22586152
ER
PT J
AU Bornstein, MH
Scrimin, S
Putnick, DL
Capello, F
Haynes, OM
de Falco, S
Carli, M
Pillon, M
AF Bornstein, Marc H.
Scrimin, Sara
Putnick, Diane L.
Capello, Fabia
Haynes, O. Maurice
de Falco, Simona
Carli, Modesto
Pillon, Marta
TI Neurodevelopmental Functioning in Very Young Children Undergoing
Treatment for Non-CNS Cancers
SO JOURNAL OF PEDIATRIC PSYCHOLOGY
LA English
DT Article
DE childhood cancer; cognitive behavior; growth and development; pediatric
psychology; social behavior
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LONG-TERM SURVIVORS; SYSTEM PROPHYLACTIC
CHEMOTHERAPY; ACUTE LYMPHOCYTIC-LEUKEMIA; CHILDHOOD LEUKEMIA;
MAGNETIC-RESONANCE; WHITE-MATTER; NEUROPSYCHOLOGICAL SEQUELAE;
INTRATHECAL CHEMOTHERAPY; BRAIN
AB Objective We initiated a prospective study of very young children with cancer, in comparison with matched healthy children, to investigate neurodevelopmental consequences of non-CNS cancers and treatment. Methods A total of 61 children (42 months) with non-CNS cancers and 61 matched controls underwent an identical age-appropriate neuropsychological test battery. Results Children with cancer manifested deficits compared to healthy controls in motor, mental, and language development, but were similar to controls in cognitive representational abilities and emotional relationships in interaction with their mothers. Better physician-rated health status at diagnosis and mother-rated behavioral status 1 month prior to assessment were associated with better motor and mental performance in the cancer group. Conclusions This study identifies deficits as well as spared functions in children with non-CNS cancers; the results suggest ways parents and healthcare professionals may plan specific remediations to enhance quality of life in young cancer survivors.
C1 [Bornstein, Marc H.; Putnick, Diane L.; Haynes, O. Maurice] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Scrimin, Sara; Capello, Fabia] Univ Padua, Dept Dev & Social Psychol, I-35100 Padua, Italy.
[de Falco, Simona] Univ Trento, Dept Cognit Sci & Educ, Trento, Italy.
[Carli, Modesto; Pillon, Marta] Univ Padua, Dept Pediat, I-35100 Padua, Italy.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM Marc_H_Bornstein@nih.gov
OI Putnick, Diane/0000-0002-6323-749X
FU Intramural NIH HHS
NR 63
TC 2
Z9 2
U1 0
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0146-8693
J9 J PEDIATR PSYCHOL
JI J. Pediatr. Psychol.
PD JUL
PY 2012
VL 37
IS 6
BP 660
EP 673
DI 10.1093/jpepsy/jss003
PG 14
WC Psychology, Developmental
SC Psychology
GA 966HD
UT WOS:000305827600008
PM 22300666
ER
PT J
AU Seto, B
Friedman, C
AF Seto, Belinda
Friedman, Charles
TI Moving toward multimedia electronic health records: how do we get there?
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
AB This report, based on a workshop jointly sponsored the National Institute of Biomedical Imaging and Biomedical Engineering and the Office of the National Coordinator for Health Information Technology, examines the role and value of images as multimedia data in electronic health records (EHRs). The workshop, attended by a wide range of stakeholders, was motivated in part by the absence of image data from discussions of meaningful use of health information technology. Collectively, the workshop presenters and participants argued that images are not ancillary data and should be central to health information systems to facilitate clinical decisions and higher quality, efficiency, and safety of care. They emphasized that the imaging community has already developed standards that form the basis of interoperability. Despite the apparent value of images, workshop participants also identified challenges and barriers to their implementation within EHRs. Weighing the opportunities and challenges, workshop participants provided their perspectives on possible paths forward toward fully multimedia EHRs.
C1 [Seto, Belinda] NIBIB, NIH, Bethesda, MD 20892 USA.
[Friedman, Charles] Univ Michigan, Sch Informat, Ann Arbor, MI 48109 USA.
RP Seto, B (reprint author), NIBIB, NIH, 6707 Democracy Blvd,Suite 202,MSC 5477, Bethesda, MD 20892 USA.
EM setob@mail.nih.gov
NR 6
TC 6
Z9 6
U1 0
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1067-5027
EI 1527-974X
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD JUL
PY 2012
VL 19
IS 4
BP 503
EP 505
DI 10.1136/amiajnl-2011-000660
PG 3
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 968ZG
UT WOS:000306024100003
PM 22306113
ER
PT J
AU Estabrooks, PA
Boyle, M
Emmons, KM
Glasgow, RE
Hesse, BW
Kaplan, RM
Krist, AH
Moser, RP
Taylor, MV
AF Estabrooks, Paul A.
Boyle, Maureen
Emmons, Karen M.
Glasgow, Russell E.
Hesse, Bradford W.
Kaplan, Robert M.
Krist, Alexander H.
Moser, Richard P.
Taylor, Martina V.
TI Harmonized patient-reported data elements in the electronic health
record: supporting meaningful use by primary care action on health
behaviors and key psychosocial factors
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; SELF-MANAGEMENT; SCREENING-TEST;
UNITED-STATES; LIFE; DEPRESSION; INTERVENTION; METFORMIN; SYMPTOMS;
SCIENCE
AB Background Electronic health records (EHR) have the potential to improve patient care through efficient access to complete patient health information. This potential may not be reached because many of the most important determinants of health outcome are rarely included. Successful health promotion and disease prevention requires patient-reported data reflecting health behaviors and psychosocial issues. Furthermore, there is a need to harmonize this information across different EHR systems.
Methods To fill this gap a three-phased process was used to conceptualize, identify and recommend patient-reported data elements on health behaviors and psychosocial factors for the EHR. Expert panels (n=13) identified candidate measures (phase 11 that were reviewed and rated by a wide range of health professionals (n=93) using the grid-enabled measures wiki social media platform (phase 2). Recommendations were finalized through a town hall meeting with key stakeholders including patients, providers, researchers, policy makers, and representatives from healthcare settings (phase 3).
Results Nine key elements from three areas emerged as the initial critical patient-reported elements to incorporate systematically into EHR health behaviors (eg, exercise), psychosocial issues (eg, distress), and patient-centered factors (eg, demographics). Recommendations were also made regarding the frequency of collection ranging from a single assessment leg, demographic characteristics), to annual assessment (eg, health behaviors), or more frequent (eg, patient goals).
Conclusions There was strong stakeholder support for this initiative reflecting the perceived value of incorporating patient-reported elements into EHR. The next steps will include testing the feasibility of incorporating these elements into the EHR across diverse primary care settings.
C1 [Estabrooks, Paul A.] Virginia Tech, Dept Human Nutr Foods & Exercise, Blacksburg, VA 24016 USA.
[Boyle, Maureen; Kaplan, Robert M.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Emmons, Karen M.] Harvard, Dept Soc Human Dev & Hlth, Boston, MA USA.
[Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Hesse, Bradford W.; Moser, Richard P.] NCI, Behav Res Program, Bethesda, MD 20892 USA.
[Krist, Alexander H.] Virginia Commonwealth Univ, Dept Family Med, Richmond, VA USA.
[Taylor, Martina V.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Estabrooks, PA (reprint author), Virginia Tech, Dept Human Nutr Foods & Exercise, 1 Riverside Circle, Blacksburg, VA 24016 USA.
EM estabrkp@vt.edu
OI Hesse, Bradford/0000-0003-1142-1161
FU NIH Office of Behavioral and Social Sciences Research; National Cancer
Institute; Society for Behavioral Medicine; National Institute of
Nursing Research; Preventive Cardiovascular Nurses Association; American
College of Sports Medicine
FX Funding for the activities described in this paper was provided by the
NIH Office of Behavioral and Social Sciences Research, the National
Cancer Institute, the Society for Behavioral Medicine, the National
Institute of Nursing Research, the Preventive Cardiovascular Nurses
Association, and the American College of Sports Medicine. The opinions
expressed are those of the authors and do not necessarily represent
those of any of these organizations.
NR 36
TC 50
Z9 50
U1 5
U2 28
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 JUL
PY 2012
VL 19
IS 4
BP 575
EP 582
DI 10.1136/amiajnl-2011-000576
PG 8
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 968ZG
UT WOS:000306024100016
PM 22511015
ER
PT J
AU Matsusaka, T
Niimura, F
Shimizu, A
Pastan, I
Saito, A
Kobori, H
Nishiyama, A
Ichikawa, I
AF Matsusaka, Taiji
Niimura, Fumio
Shimizu, Akihiro
Pastan, Ira
Saito, Akihiko
Kobori, Hiroyuki
Nishiyama, Akira
Ichikawa, Iekuni
TI Liver Angiotensinogen Is the Primary Source of Renal Angiotensin II
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID SALT-SENSITIVE RATS; CONVERTING-ENZYME; INTRARENAL ANGIOTENSINOGEN;
GLOMERULAR SCLEROSIS; DIABETIC-NEPHROPATHY; TYPE-2 DIABETES/;
KIDNEY-DISEASE; SYSTEM; HYPERTENSION; PROTEINURIA
AB Angiotensin II content in the kidney is much higher than in the plasma, and it increases more in kidney diseases through an uncertain mechanism. Because the kidney abundantly expresses angiotensinogen mRNA, transcriptional dysregulation of angiotensinogen within the kidney is one potential cause of increased renal angiotensin II in the setting of disease. Here, we observed that kidney-specific angiotensinogen knockout mice had levels of renal angiotensinogen protein and angiotensin II that were similar to those levels of control mice. In contrast, liver-specific knockout of angiotensinogen nearly abolished plasma and renal angiotensinogen protein and renal tissue angiotensin II. Immunohistochemical analysis in mosaic proximal tubules of megalin knockout mice revealed that angiotensinogen protein was incorporated selectively in megalin-intact cells of the proximal tubule, indicating that the proximal tubule reabsorbs filtered angiotensinogen through megalin. Disruption of the filtration barrier in a transgenic mouse model of podocyte-selective injury increased renal angiotensin II content and markedly increased both tubular and urinary angiotensinogen protein without an increase in renal renin activity, supporting the dependency of renal angiotensin II generation on filtered angiotensinogen. Taken together, these data suggest that liver-derived angiotensinogen is the primary source of renal angiotensinogen protein and angiotensin II. Furthermore, an abnormal increase in the permeability of the glomerular capillary wall to angiotensinogen, which characterizes proteinuric kidney diseases, enhances the synthesis of renal angiotensin II.
C1 [Matsusaka, Taiji] Tokai Univ, Dept Internal Med, Sch Med, Isehara, Kanagawa 2591193, Japan.
[Niimura, Fumio] Tokai Univ, Dept Pediat, Sch Med, Isehara, Kanagawa 2591193, Japan.
[Ichikawa, Iekuni] Tokai Univ, Dept Bioeth, Sch Med, Isehara, Kanagawa 2591193, Japan.
[Matsusaka, Taiji] Tokai Univ, Inst Med Sci, Sch Med, Isehara, Kanagawa 2591193, Japan.
[Shimizu, Akihiro] Jikei Univ, Sch Med, Dept Internal Med, Div Kidney & Hypertens, Tokyo, Japan.
[Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Saito, Akihiko] Niigata Univ, Dept Appl Mol Med, Grad Sch Med & Dent Sci, Niigata, Japan.
[Kobori, Hiroyuki] Tulane Univ, Hlth Sci Ctr, Dept Med & Physiol, Renal Ctr Excellence, New Orleans, LA 70118 USA.
[Kobori, Hiroyuki] Tulane Univ, Hlth Sci Ctr, Dept Hypertens, Renal Ctr Excellence, New Orleans, LA 70118 USA.
[Nishiyama, Akira] Kagawa Univ, Dept Pharmacol, Sch Med, Miki, Kagawa, Japan.
[Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
[Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
RP Matsusaka, T (reprint author), Tokai Univ, Dept Internal Med, Sch Med, 143 Shimokasuya, Isehara, Kanagawa 2591193, Japan.
EM taijim@is.icc.u-tokai.ac.jp
RI Kobori, Hiroyuki/F-1994-2014
OI Kobori, Hiroyuki/0000-0001-5128-5059
FU Japan Society for the Promotion of Science; Ministry of Education,
Culture, Sports, Science and Technology in Japan; High-Tech Research
Center Project of the Ministry of Education, Culture, Sports, Science
and Technology in Japan; Tokai University School of Medicine; Project
Research; National Institute of Diabetes and Digestive and Kidney
Disease; National Institutes of Health [DK037868, DK44757]; National
Institutes of Health, National Cancer Institute; Center for Cancer
Research
FX This study was supported by a Grant-in Aid for Scientific Research of
Japan Society for the Promotion of Science, the Ministry of Education,
Culture, Sports, Science and Technology in Japan, High-Tech Research
Center Project of the Ministry of Education, Culture, Sports, Science
and Technology in Japan, Tokai University School of Medicine, Project
Research (2010-2011), the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Disease, and National
Institutes of Health Grants DK037868 and DK44757 and in part by the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute, and Center for Cancer Research.
NR 45
TC 79
Z9 79
U1 1
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUL
PY 2012
VL 23
IS 7
BP 1181
EP 1189
DI 10.1681/ASN.2011121159
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 968ZZ
UT WOS:000306026800011
PM 22518004
ER
PT J
AU Singh, SP
Gierada, DS
Pinsky, P
Sanders, C
Fineberg, N
Sun, YH
Lynch, D
Nath, H
AF Singh, Satinder P.
Gierada, David S.
Pinsky, Paul
Sanders, Colleen
Fineberg, Naomi
Sun, Yanhui
Lynch, David
Nath, Hrudaya
TI Reader Variability in Identifying Pulmonary Nodules on Chest Radiographs
From the National Lung Screening Trial
SO JOURNAL OF THORACIC IMAGING
LA English
DT Article
DE lung cancer; chest radiograph; reader variability; screening
ID CANCER MORTALITY; AGREEMENT; SYSTEM
AB Purpose: To measure reader variability related to the evaluation of screening chest radiographs (CXRs) for findings of primary lung cancer.
Materials and Methods: From the National Lung Screening Trial (NLST), 100 cases were randomly selected from baseline CXR examinations for retrospective interpretation by 9 NLST radiologists; images with noncalcified lung nodules (NCNs) or other abnormalities suspicious for lung cancer as determined by the original NLST reader were oversampled. Agreement on the presence of pulmonary nodules and abnormalities suspicious for cancer and recommendations for follow-up were assessed by the multi-rater kappa statistic.
Results: The multirater kappa statistic for interreader agreement on the presence of at least 1 NCN was 0.38. Rates at which readers reported the presence of at least 1 NCN ranged from 32% to 63% (mean, 41%); among 16 subjects with NCN and a cancer diagnosis within 1 year of the CXR examination, an average of 87% (range, 81% to 94%) of cases were classified as suspicious for cancer across all readers. The multirater kappa for agreement on follow-up recommendations was 0.34; pairwise kappa values ranged from 0.15 to 0.64 (mean, 0.36). For all subjects, readers recommended a follow-up procedure classified as high level (computed tomography, fluorodeoxyglucose-positron emission tomography, or biopsy) 42% of the time on average (range, 30% to 67%); this increased to 84% (range, 52% to 100%) when readers reported an NCN and 88% (range, 82% to 94%) for subjects with cancer.
Conclusion: Reader agreement for screening CXR interpretation and follow-up recommendations is fair overall but is high for malignant lesions.
C1 [Singh, Satinder P.; Sanders, Colleen; Nath, Hrudaya] Univ Alabama Hosp Birmingham, Dept Radiol, Birmingham, AL 35233 USA.
[Fineberg, Naomi; Sun, Yanhui] Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA.
[Pinsky, Paul] NCI, Canc Prevent Div, NIH, Rockville, MD USA.
[Gierada, David S.] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, Dept Radiol, St Louis, MO 63110 USA.
[Lynch, David] Natl Jewish Hlth Hosp, Div Radiol, Denver, CO USA.
RP Nath, H (reprint author), Univ Alabama Hosp Birmingham, Dept Radiol, JT N370,619 S 19th St, Birmingham, AL 35233 USA.
EM hnath@uabmc.edu
FU Division of Cancer Prevention, National Cancer Institute, NIH; DHHS;
National Lung Screening Trail (NLST)
FX Supported by grants from the Division of Cancer Prevention, National
Cancer Institute, NIH, DHHS, and National Lung Screening Trail (NLST)
(http://www.cancer.gov/nlst, clinicaltrials.gov identifier NCT00047385).
NR 19
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0883-5993
J9 J THORAC IMAG
JI J. Thorac. Imaging
PD JUL
PY 2012
VL 27
IS 4
BP 249
EP 254
DI 10.1097/RTI.0b013e318256951e
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 967GW
UT WOS:000305895800018
PM 22627615
ER
PT J
AU Meller, J
Malinin, NL
Panigrahi, S
Kerr, BA
Patil, A
Ma, Y
Venkateswaran, L
Rogozin, IB
Mohandas, N
Ehlayel, MS
Podrez, EA
Chinen, J
Byzova, TV
AF Meller, J.
Malinin, N. L.
Panigrahi, S.
Kerr, B. A.
Patil, A.
Ma, Y.
Venkateswaran, L.
Rogozin, I. B.
Mohandas, N.
Ehlayel, M. S.
Podrez, E. A.
Chinen, J.
Byzova, T. V.
TI Novel aspects of Kindlin-3 function in humans based on a new case of
leukocyte adhesion deficiency III
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE integrins; kindlins; leukocyte adhesion deficiency; platelets; red blood
cells; white blood cells
ID INTEGRIN ACTIVATION; PLATELET; CELL
AB . Background: Kindlin-3 is a novel integrin activator in hematopoietic cells, and its deficiency leads to immune problems and severe bleeding, known as leukocyte adhesion deficiency III (LAD-III). Our current understanding of Kindlin-3 function primarily relies on analysis of animal models or cell lines. Objectives: To understand the functions of Kindlin-3 in human primary blood cells. Patients/Methods: We analyzed primary and immortalized hematopoietic cells obtained from a new LAD-III patient with immune problems, bleeding, a history of anemia, and abnormally shaped red blood cells. Results: The patients white blood cells (WBCs) and platelets showed defects in agonist-induced integrin activation and botrocetin-induced platelet agglutination. Primary leukocytes from this patient exhibited abnormal activation of beta 1 integrin. Integrin activation defects were responsible for the observed deficiency in the botrocetin-induced platelet response. Analysis of patient genomic DNA revealed a novel mutation in the Kindlin3 gene. The mutation abolished Kindlin-3 expression in primary WBCs and platelets, owing to abnormal splicing. Kindlin-3 is expressed in red blood cells (RBCs), and its deficiency is proposed to lead to abnormally shaped RBCs. Immortalized patient WBCs expressed a truncated form of Kindlin-3 that was not sufficient to support integrin activation. Expression of Kindlin-3 cDNA in immortalized patient WBCs rescued integrin activation defects, whereas overexpression of the truncated form did not. Conclusions: Kindlin-3 deficiency impairs integrin function, including activation of beta 1 integrin. Abnormalities in glycoprotein IbIX function in Kindlin-3-deficient platelets are secondary to integrin defects. The region of Kindlin-3 encoded by exon 11 is crucial for its ability to activate integrins in humans.
C1 [Meller, J.; Malinin, N. L.; Panigrahi, S.; Kerr, B. A.; Patil, A.; Ma, Y.; Podrez, E. A.; Byzova, T. V.] Cleveland Clin, Dept Mol Cardiol, Lerner Res Inst, Joseph J Jacobs Ctr Thrombosis & Vasc Biol, Cleveland, OH 44195 USA.
[Venkateswaran, L.] Baylor Coll Med, Dept Pediat, Hematol Oncol Sect, Houston, TX 77030 USA.
[Rogozin, I. B.] NIH, Natl Ctr Biotechnol Informat NLM, Bethesda, MD 20892 USA.
[Mohandas, N.] New York Blood Ctr, New York, NY 10021 USA.
[Ehlayel, M. S.] Weill Cornell Med Coll Qatar, Hamad Med Corp, Dept Pediat, Sect Pediat Allergy Immunol, Doha, Qatar.
[Chinen, J.] Baylor Coll Med, Dept Pediat, Allergy & Immunol Sect, Hematol Sect, Houston, TX 77030 USA.
RP Byzova, TV (reprint author), Cleveland Clin, Dept Mol Cardiol, Lerner Res Inst, Joseph J Jacobs Ctr Thrombosis & Vasc Biol, NB50,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM byzovat@ccf.org
RI Kerr, Bethany/D-1644-2012; Malinin, Nikolay/J-4271-2012;
OI Kerr, Bethany/0000-0002-2995-7549; Malinin, Nikolay/0000-0002-2654-1783
FU US National Institutes of Health [HL073311, HL071625]; NRSA postdoctoral
fellowship of the Health/National Heart, Lung, and Blood Institute
[HL104920-02]
FX This study was supported by HL073311 and HL071625 US National Institutes
of Health grants. J. Meller is supported by NRSA postdoctoral fellowship
HL104920-02 of the Health/National Heart, Lung, and Blood Institute.
NR 18
TC 11
Z9 11
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD JUL
PY 2012
VL 10
IS 7
BP 1397
EP 1408
DI 10.1111/j.1538-7836.2012.04768.x
PG 12
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 968KI
UT WOS:000305979300024
PM 22564402
ER
PT J
AU Abi-Jaoudeh, N
Pritchard, WF
Amalou, H
Linguraru, M
Chiesa, OA
Adams, JD
Gacchina, C
Wesley, R
Maruvada, S
McDowell, B
Frenkel, V
Karanian, JW
Wood, BJ
AF Abi-Jaoudeh, Nadine
Pritchard, William F.
Amalou, Hayet
Linguraru, Marius
Chiesa, Oscar A.
Adams, Joshua D.
Gacchina, Carmen
Wesley, Robert
Maruvada, Subha
McDowell, Briana
Frenkel, Victor
Karanian, John W.
Wood, Bradford J.
TI Pulsed High-Intensity-focused US and Tissue Plasminogen Activator (TPA)
Versus TPA Alone for Thrombolysis of Occluded Bypass Graft in Swine
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID ULTRASOUND-ACCELERATED THROMBOLYSIS; IN-VITRO; ENHANCED THROMBOLYSIS;
MEDIATED THROMBOLYSIS; ARTERIAL OCCLUSIONS; RANDOMIZED-TRIAL; MODEL;
THERAPY; VIVO; ANGIOPLASTY
AB Purpose: Prosthetic arteriovenous or arterial-arterial bypass grafts can thrombose and be resistant to revascularization. A thrombosed bypass graft model was created to evaluate the potential therapeutic enhancement and safety profile of pulsed high intensity-focused ultrasound (pHIFU) on pharmaceutical thrombolysis.
Materials and Methods: In swine, a right carotid-carotid expanded polytetrafluoroethylene bypass graft was surgically constructed, containing a 40% stenosis at its distal end to induce graft thrombosis. The revascularization procedure was performed 7 days after surgery. After model development and dose response experiments (n = 11), two cohorts were studied: pHIFU with tissue plasminogen activator (TPA; n = 4) and sham pHIFU with TPA (n = 3). The experiments were identical in both groups except no energy was delivered in the sham pHIFU group. Serial angiograms were obtained in all cases. The area of graft opacified by contrast medium on angiograms was quantified with digital image processing software. A blinded reviewer calculated the change in the graft area pacified by contrast medium and expressed it as a percentage, representing percentage of thrombolysis.
Results: Combining pHIFU with 0.5 mg of TPA resulted in a 52% +/- 4% increase in thrombolysis on angiograms obtained at 30 minutes, compared with a 9% +/- 14% increase with sham pHIFU and 0.5 mg TPA (P = .003). Histopathologic examination demonstrated no differences between the groups.
Conclusions: Thrombolysis of occluded bypass grafts was significantly increased when combining pHIFU and TPA versus sham pHIFU and TPA. These results suggest that application of pHIFU may augment thrombolysis with a reduced time and dose.
C1 [Abi-Jaoudeh, Nadine; Amalou, Hayet; Gacchina, Carmen; Wood, Bradford J.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Wesley, Robert] NIH, Off Director, Ctr Clin, Bethesda, MD 20892 USA.
[Pritchard, William F.; Chiesa, Oscar A.; McDowell, Briana; Karanian, John W.] US FDA, Lab Cardiovasc & Intervent Therapeut, Ctr Devices & Radiol Hlth, Laurel, MD USA.
[Maruvada, Subha] US FDA, Off Sci, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Maruvada, Subha] US FDA, Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Adams, Joshua D.] Univ Virginia, Dept Vasc Surg, Charlottesville, VA USA.
[Adams, Joshua D.] Univ Virginia, Dept Radiol, Charlottesville, VA USA.
[Frenkel, Victor] Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA.
[Linguraru, Marius] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
RP Abi-Jaoudeh, N (reprint author), NIH, Dept Radiol & Imaging Sci, Room 1C365,Bldg 10,MSC 1182,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM naj@mail.nih.gov
FU National Institutes of Health (NIH) [1Z01CL046011-01]
FX This work was supported in part by the National Institutes of Health
(NIH) Intramural Research Program Grant 1Z01CL046011-01. This project is
a collaboration between the NIH and the Food and Drug Administration as
part of an Interagency Agreement.
NR 36
TC 1
Z9 1
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD JUL
PY 2012
VL 23
IS 7
BP 953
EP 961
DI 10.1016/j.jvir.2012.04.001
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 967TI
UT WOS:000305930300016
PM 22609287
ER
PT J
AU Yeh, WW
Brassard, LM
Miller, CA
Basavapathruni, A
Zhang, JR
Rao, SS
Nabel, GJ
Mascola, JR
Letvin, NL
Seaman, MS
AF Yeh, Wendy W.
Brassard, Laura M.
Miller, Caroline A.
Basavapathruni, Aravind
Zhang, Jinrong
Rao, Srinivas S.
Nabel, Gary J.
Mascola, John R.
Letvin, Norman L.
Seaman, Michael S.
TI Envelope Variable Region 4 Is the First Target of Neutralizing
Antibodies in Early Simian Immunodeficiency Virus mac251 Infection of
Rhesus Monkeys
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIV-1/SIV CHIMERIC VIRUS; MONOCLONAL-ANTIBODIES; GLYCOPROTEIN; MACAQUES;
TYPE-1; VARIANTS; CHALLENGE; RECOGNITION; PROTECTION; EPITOPE
AB A major goal of AIDS vaccine development is to design vaccination strategies that can elicit broad and potent protective antibodies. The initial viral targets of neutralizing antibodies (NAbs) early after human or simian immunodeficiency virus (HIV/SIV) infection are not known. The identification of early NAb epitopes that induce protective immunity or retard the progression of disease is important for AIDS vaccine development. The aim of this study was to determine the Env residues targeted by early SIV NAbs and to assess the influence of prior vaccination on neutralizing antibody kinetics and specificity during early infection. We previously described stereotypic env sequence variations in SIVmac251-infected rhesus monkeys that resulted in viral escape from NAbs. Here, we defined the early viral targets of neutralization and determined whether the ability of serum antibody from infected monkeys to neutralize SIV was altered in the setting of prior vaccination. To localize the viral determinants recognized by early NAbs, a panel of mutant pseudoviruses was assessed in a TZM-bl reporter gene neutralization assay to define the precise changes that eliminate recognition by SIV Env-specific NAbs in 16 rhesus monkeys. Changing R420 to G or R424 to Q in V4 of Env resulted in the loss of recognition by NAbs in vaccinated monkeys. In contrast, mutations in the VI region of Env did not alter the NAb profile. These findings indicate that early NAbs are directed toward SIVmac251 Env V4 but not the V1 region, and that this env vaccination regimen did not alter the kinetics or the breadth of NAbs during early infection.
C1 [Yeh, Wendy W.; Brassard, Laura M.; Miller, Caroline A.; Basavapathruni, Aravind; Zhang, Jinrong; Letvin, Norman L.; Seaman, Michael S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis,Dept Med, Boston, MA 02215 USA.
[Rao, Srinivas S.; Nabel, Gary J.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Yeh, WW (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis,Dept Med, Boston, MA 02215 USA.
EM wyeh@partners.org
FU Harvard CFAR [P30 060354-07]; NIAID [K08 AI069995]; Shore Fellowship
from Harvard Medical School; Pfizer Young Investigator Award in Vaccine
Development from Infectious Disease Society of America; intramural
research program of the Vaccine Research Center, NIAID, NIH; NIH NIAID
Center for HIV/AIDS Vaccine Immunology [AI067854]; Bill and Melinda
Gates Collaboration for AIDS Vaccine Discovery Vaccine Immune Monitoring
Consortium [38619]
FX We thank Rebecca Gelman (supported by Harvard CFAR P30 060354-07) for
helpful discussions on statistics.; This work was supported by NIAID K08
AI069995 (W.W.Y.), the Shore Fellowship from Harvard Medical School
(W.W.Y.), and the Pfizer Young Investigator Award in Vaccine Development
from Infectious Disease Society of America (W.W.Y.); the intramural
research program of the Vaccine Research Center, NIAID, NIH; NIH NIAID
Center for HIV/AIDS Vaccine Immunology AI067854 (N.L.L.); and the Bill
and Melinda Gates Collaboration for AIDS Vaccine Discovery Vaccine
Immune Monitoring Consortium Grant 38619 (M.S.S.).
NR 45
TC 5
Z9 5
U1 0
U2 4
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 JUL
PY 2012
VL 86
IS 13
BP 7052
EP 7059
DI 10.1128/JVI.00107-12
PG 8
WC Virology
SC Virology
GA 961XA
UT WOS:000305501600004
PM 22532675
ER
PT J
AU Garidou, L
Heydari, S
Gossa, S
McGavern, DB
AF Garidou, Lucile
Heydari, Sara
Gossa, Selamawit
McGavern, Dorian B.
TI Therapeutic Blockade of Transforming Growth Factor Beta Fails To Promote
Clearance of a Persistent Viral Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; T-CELL EXHAUSTION; REVERSIBLE IMMUNE
DYSFUNCTION; TGF-BETA; PD-1 EXPRESSION; IN-VIVO; IMMUNOLOGICAL
TOLERANCE; DISEASE PROGRESSION; AUTOIMMUNE-DISEASE; STENT PLACEMENT
AB Persistent viral infections often overburden the immune system and are a major cause of disease in humans. During many persistent infections, antiviral T cells are maintained in a state of immune exhaustion characterized by diminished effector and helper functions. In mammalian systems, an extensive immune regulatory network exists to limit unwanted, potentially fatal immunopathology by inducing T cell exhaustion. However, this regulatory network at times overprotects the host and fosters viral persistence by severely dampening adaptive immune responsiveness. Importantly, recent studies have shown that T cell exhaustion is mediated in part by host immunoregulatory pathways (e.g., programmed death 1 [PD-1], interleukin 10 [IL-10]) and that therapeutic blockade of these pathways either before or during persistent infection can promote viral clearance. Transforming growth factor beta (TGF-beta) is another immunosuppressive cytokine known to impede both self-and tumor-specific T cells, but its role in regulating antiviral immunity is not entirely understood. In this study, we inhibited TGF-beta with three potent antagonists to determine whether neutralization of this regulatory molecule is a viable approach to control a persistent viral infection. Our results revealed that these inhibitors modestly elevate the number of antiviral T cells following infection with a persistent variant of lymphocytic choriomeningitis virus (LCMV) but have no impact on viral clearance. These data suggest that therapeutic neutralization of TGF-beta is not an efficacious means to promote clearance of a persistent viral infection.
C1 [Heydari, Sara; Gossa, Selamawit; McGavern, Dorian B.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Garidou, Lucile] Inst Metab & Cardiovasc Dis I2MC, INSERM, U1048, Obes Res Lab, Toulouse, France.
RP McGavern, DB (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
EM mcgavernd@mail.nih.gov
OI McGavern, Dorian/0000-0001-9568-545X
FU National Institutes of Health; Ray Thomas Edwards Foundation;
Association pour la Recherche sur la Sclerose en Plaques
FX This work was supported by the National Institutes of Health Intramural
Program as well as a grant from the Ray Thomas Edwards Foundation (to D.
B. McGavern). L. Garidou was supported by a fellowship from Association
pour la Recherche sur la Sclerose en Plaques.
NR 76
TC 18
Z9 19
U1 0
U2 1
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 JUL
PY 2012
VL 86
IS 13
BP 7060
EP 7071
DI 10.1128/JVI.00164-12
PG 12
WC Virology
SC Virology
GA 961XA
UT WOS:000305501600005
PM 22553324
ER
PT J
AU Mitsuki, YY
Terahara, K
Shibusawa, K
Yamamoto, T
Tsuchiya, T
Mizukoshi, F
Ishige, M
Okada, S
Kobayashi, K
Morikawa, Y
Nakayama, T
Takeda, M
Yanagi, Y
Tsunetsugu-Yokota, Y
AF Mitsuki, Yu-ya
Terahara, Kazutaka
Shibusawa, Kentaro
Yamamoto, Takuya
Tsuchiya, Takatsugu
Mizukoshi, Fuminori
Ishige, Masayuki
Okada, Seiji
Kobayashi, Kazuo
Morikawa, Yuko
Nakayama, Tetsuo
Takeda, Makoto
Yanagi, Yusuke
Tsunetsugu-Yokota, Yasuko
TI HIV-1 Infection Ex Vivo Accelerates Measles Virus Infection by
Upregulating Signaling Lymphocytic Activation Molecule (SLAM) in CD4(+)
T Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CELLULAR RECEPTOR; ZAMBIAN CHILDREN; DENDRITIC CELLS; REPLICATION;
PROTEIN; EXPRESSION; APOPTOSIS; VACCINE; INHIBITION; CONTACT
AB Measles virus (MV) infection in children harboring human immunodeficiency virus type 1 (HIV-1) is often fatal, even in the presence of neutralizing antibodies; however, the underlying mechanisms are unclear. Therefore, the aim of the present study was to examine the interaction between HIV-1 and wild-type MV (MVwt) or an MV vaccine strain (MVvac) during dual infection. The results showed that the frequencies of MVwt- and MVvac-infected CD4(+) T cells within the resting peripheral blood mononuclear cells (PBMCs) were increased 3- to 4-fold after HIV-1 infection, and this was associated with a marked upregulation of signaling lymphocytic activation molecule (SLAM) expression on CD4(+) T cells but not on CD8(+) T cells. SLAM upregulation was induced by infection with a replication-competent HIV-1 isolate comprising both the X4 and R5 types and to a lesser extent by a pseudotyped HIV-1 infection. Notably, SLAM upregulation was observed in HIV-infected as well as -uninfected CD4(+) T cells and was abrogated by the removal of HLA-DR+ cells from the PBMC culture. Furthermore, SLAM upregulation did not occur in uninfected PBMCs cultured together with HIV-infected PBMCs in compartments separated by a permeable membrane, indicating that no soluble factors were involved. Rather, CD4(+) T cell activation mediated through direct contact with dendritic cells via leukocyte function-associated molecule 1 (LFA-1)/intercellular adhesion molecule 1 (ICAM-1) and LFA-3/CD2 was critical. Thus, HIV-1 infection induces a high level of SLAM expression on CD4(+) T cells, which may enhance their susceptibility to MV and exacerbate measles in coinfected individuals.
C1 [Mitsuki, Yu-ya; Terahara, Kazutaka; Shibusawa, Kentaro; Tsuchiya, Takatsugu; Mizukoshi, Fuminori; Ishige, Masayuki; Kobayashi, Kazuo; Tsunetsugu-Yokota, Yasuko] Natl Inst Infect Dis, Dept Immunol, Shinjuku Ku, Tokyo 1628640, Japan.
[Yamamoto, Takuya] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Ishige, Masayuki; Okada, Seiji] Kumamoto Univ, Ctr AIDS Res, Kumamoto, Japan.
[Morikawa, Yuko] Kitasato Univ, Kitasato Inst Life Sci, Lab Viral Infect 2, Tokyo, Japan.
[Nakayama, Tetsuo] Kitasato Univ, Kitasato Inst Life Sci, Lab Viral Infect 1, Tokyo, Japan.
[Takeda, Makoto] Natl Inst Infect Dis, Dept Virol 3, Tokyo, Japan.
[Yanagi, Yusuke] Kyushu Univ, Fac Med, Dept Virol, Fukuoka 812, Japan.
RP Tsunetsugu-Yokota, Y (reprint author), Natl Inst Infect Dis, Dept Immunol, Shinjuku Ku, Tokyo 1628640, Japan.
EM yyokota@nih.go.jp
RI Okada, Seiji/F-5785-2013; Kumamoto University, CAIDS/G-8446-2013;
Yamamoto, Takuya/L-2642-2013
OI Yamamoto, Takuya/0000-0003-3753-1211
FU Ministry of Health, Labor, and Welfare of Japan; Japanese Foundation for
AIDS Prevention
FX This work was supported by a grant from the Ministry of Health, Labor,
and Welfare of Japan. Y.-Y. Mitsuki receives support from the Japanese
Foundation for AIDS Prevention.
NR 29
TC 0
Z9 0
U1 0
U2 4
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 JUL
PY 2012
VL 86
IS 13
BP 7227
EP 7234
DI 10.1128/JVI.06681-11
PG 8
WC Virology
SC Virology
GA 961XA
UT WOS:000305501600020
PM 22532682
ER
PT J
AU Rosenke, K
Lavignon, M
Malik, F
Kolokithas, A
Hendrick, D
Virtaneva, K
Peterson, K
Evans, LH
AF Rosenke, Kyle
Lavignon, Marc
Malik, Frank
Kolokithas, Angelo
Hendrick, Duncan
Virtaneva, Kimmo
Peterson, Karin
Evans, Leonard H.
TI Profound Amplification of Pathogenic Murine Polytropic Retrovirus
Release from Coinfected Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID FOCUS-FORMING VIRUSES; LEUKEMIA VIRUSES; HOST RANGE; HETERODUPLEX
ANALYSIS; THYMIC LYMPHOMAS; SURFACE RECEPTOR; MOLONEY-MULV; AKR/J MICE;
ENV GENE; FRIEND
AB Previous studies indicate that mice infected with mixtures of mouse retroviruses (murine leukemia viruses [MuLVs]) exhibit dramatically altered pathology compared to mice infected with individual viruses of the mixture. Coinoculation of the ecotropic virus Friend MuLV (F-MuLV) with Fr98, a polytropic MuLV, induced a rapidly fatal neurological disease that was not observed in infections with either virus alone. The polytropic virus load in coinoculated mice was markedly enhanced, while the ecotropic F-MuLV load was unchanged. Furthermore, pseudotyping of the polytropic MuLV genome within ecotropic virions was nearly complete in coinoculated mice. In an effort to better understand these phenomena, we examined mixed retrovirus infections by utilizing in vitro cell lines. Similar to in vivo mixed infections, the polytropic MuLV genome was extensively pseudotyped within ecotropic virions; polytropic virus release was profoundly elevated in coinfected cells, and the ecotropic virus release was unchanged. A reduced level of polytropic SU protein on the surfaces of coinfected cells was observed and correlated with a reduced level of nonpseudotyped polytropic virion release. Marked amplification and pseudotyping of the polytropic MuLV were also observed in mixed Fr98-F-MuLV infections of cell lines derived from the central nervous system (CNS), the target for Fr98 pathogenesis. Additional experiments indicated that pseudotyping contributed to the elevated polytropic virus titer by increasing the efficiency of packaging and release of the polytropic genomes within ecotropic virions. Mixed infections are the rule rather than the exception in retroviral infection, and the ability to examine them in vitro should facilitate a more thorough understanding of retroviral interactions in general.
C1 [Rosenke, Kyle; Lavignon, Marc; Malik, Frank; Kolokithas, Angelo; Hendrick, Duncan; Virtaneva, Kimmo; Peterson, Karin; Evans, Leonard H.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
RP Evans, LH (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
EM levans@niaid.nih.gov
RI Peterson, Karin/D-1492-2016
OI Peterson, Karin/0000-0003-4177-7249
FU NIAID, NIH
FX This research was supported by the intramural research program of the
NIAID, NIH.
NR 46
TC 5
Z9 5
U1 0
U2 0
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 JUL
PY 2012
VL 86
IS 13
BP 7241
EP 7248
DI 10.1128/JVI.00225-12
PG 8
WC Virology
SC Virology
GA 961XA
UT WOS:000305501600022
PM 22514353
ER
PT J
AU Parra, GI
Abente, EJ
Sandoval-Jaime, C
Sosnovtsev, SV
Bok, K
Green, KY
AF Parra, Gabriel I.
Abente, Eugenio J.
Sandoval-Jaime, Carlos
Sosnovtsev, Stanislav V.
Bok, Karin
Green, Kim Y.
TI Multiple Antigenic Sites Are Involved in Blocking the Interaction of
GII.4 Norovirus Capsid with ABH Histo-Blood Group Antigens
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRUS-LIKE PARTICLES; REACTIVE MONOCLONAL-ANTIBODY; NORWALK-LIKE
VIRUSES; GENOGROUP-II; P2 DOMAIN; MURINE NOROVIRUS; STRUCTURAL BASIS;
UNITED-STATES; PROTEIN; GASTROENTERITIS
AB Noroviruses are major etiological agents of acute viral gastroenteritis. In 2002, a GII.4 variant (Farmington Hills cluster) spread so rapidly in the human population that it predominated worldwide and displaced previous GII.4 strains. We developed and characterized a panel of six monoclonal antibodies (MAbs) directed against the capsid protein of a Farmington Hills-like GII.4 norovirus strain that was associated with a large hospital outbreak in Maryland in 2004. The six MAbs reacted with high titers against homologous virus-like particles (VLPs) by enzyme-linked immunoassay but did not react with denatured capsid protein in immunoblots. The expression and self-assembly of newly developed genogroup I/II chimeric VLPs showed that five MAbs bound to the GII.4 protruding (P) domain of the capsid protein, while one recognized the GII.4 shell (S) domain. Cross-competition assays and mutational analyses showed evidence for at least three distinct antigenic sites in the P domain and one in the S domain. MAbs that mapped to the P domain but not the S domain were able to block the interaction of VLPs with ABH histo-blood group antigens (HBGA), suggesting that multiple antigenic sites of the P domain are involved in HBGA blocking. Further analysis showed that two MAbs mapped to regions of the capsid that had been associated with the emergence of new GII.4 variants. Taken together, our data map antibody and HBGA carbohydrate binding to proximal regions of the norovirus capsid, showing that evolutionary pressures on the norovirus capsid protein may affect both antigenic and carbohydrate recognition phenotypes.
C1 [Parra, Gabriel I.; Abente, Eugenio J.; Sandoval-Jaime, Carlos; Sosnovtsev, Stanislav V.; Bok, Karin; Green, Kim Y.] NIAID, Caliciviruses Sect, Infect Dis Lab, NIH,DHHS, Bethesda, MD 20892 USA.
RP Green, KY (reprint author), NIAID, Caliciviruses Sect, Infect Dis Lab, NIH,DHHS, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kgreen@niaid.nih.gov
OI Abente, Eugenio/0000-0002-3390-2786; Parra, Gabriel/0000-0002-1102-4740
FU NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID.
NR 69
TC 20
Z9 22
U1 0
U2 5
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 JUL
PY 2012
VL 86
IS 13
BP 7414
EP 7426
DI 10.1128/JVI.06729-11
PG 13
WC Virology
SC Virology
GA 961XA
UT WOS:000305501600038
PM 22532688
ER
PT J
AU Levy, BR
Zonderman, AB
Slade, MD
Ferrucci, L
AF Levy, Becca R.
Zonderman, Alan B.
Slade, Martin D.
Ferrucci, Luigi
TI Memory Shaped by Age Stereotypes over Time
SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL
SCIENCES
LA English
DT Article
DE Ageism; Aging; Memory; Self-perception; Stereotypes
ID COGNITIVE DECLINE; PERFORMANCE; PREDICTORS; MECHANISMS; IDENTITY;
DISEASE; THREAT; LIFE
AB Objectives. Previous studies showed that negative self-stereotypes detrimentally affect the cognitive performance of marginalized group members; however, these findings were confined to short-term experiments. In the present study, we considered whether stereotypes predicted memory over time, which had not been previously examined. We also considered whether self-relevance increased the influence of stereotypes on memory over time.
Method. Multiple waves of memory performance were analyzed using individual growth models. The sample consisted of 395 participants in the Baltimore Longitudinal Study of Aging.
Results. Those with more negative age stereotypes demonstrated significantly worse memory performance over 38 years than those with less negative age stereotypes, after adjusting for relevant covariates. The decline in memory performance for those aged 60 and above was 30.2% greater for the more negative age stereotype group than for the less negative age stereotype group. Also, the impact of age stereotypes on memory was significantly greater among those for whom the age stereotypes were self-relevant.
Discussion. This study shows that the adverse influence of negative self-stereotypes on cognitive performance is not limited to a short-term laboratory effect. Rather, the findings demonstrate, for the first time, that stereotypes also predict memory performance over an extended period in the community.
C1 [Levy, Becca R.; Slade, Martin D.] Yale Univ, Yale Sch Publ Hlth, New Haven, CT 06520 USA.
[Zonderman, Alan B.; Ferrucci, Luigi] Natl Inst Aging, Baltimore, MD USA.
RP Levy, BR (reprint author), Yale Univ, Yale Sch Publ Hlth, 60 Coll St,POB 208034, New Haven, CT 06520 USA.
EM Becca.Levy@yale.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institute on Aging Intramural Research Program; Patrick and
Catherine Weldon Donaghue Medical Research Foundation; National Heart,
Lung, and Blood Institute [R01HL089314]; National Institute on Aging
[R01AG032284]
FX This research was supported by the National Institute on Aging
Intramural Research Program and grants from the Patrick and Catherine
Weldon Donaghue Medical Research Foundation, National Heart, Lung, and
Blood Institute (R01HL089314), and National Institute on Aging
(R01AG032284) to the first author.
NR 29
TC 28
Z9 30
U1 3
U2 24
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5014
J9 J GERONTOL B-PSYCHOL
JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci.
PD JUL
PY 2012
VL 67
IS 4
BP 432
EP 436
DI 10.1093/geronb/gbr120
PG 5
WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology,
Multidisciplinary
SC Geriatrics & Gerontology; Psychology
GA 966FZ
UT WOS:000305824500005
PM 22056832
ER
PT J
AU Robb, ML
Rerks-Ngarm, S
Nitayaphon, S
Pitisuttithum, P
Kaewkungwal, J
Kunasol, P
Khamboonruang, C
Thongcharoen, P
Morgan, P
Benenson, M
Paris, RM
Chiu, J
Adams, E
Francis, D
Gurunathan, S
Tartaglia, J
Gilbert, P
Stablein, D
Michael, NL
Kim, JH
AF Robb, Merlin L.
Rerks-Ngarm, Supachai
Nitayaphon, Sorachai
Pitisuttithum, Punnee
Kaewkungwal, Jaranit
Kunasol, Prayura
Khamboonruang, Chirasak
Thongcharoen, Prasert
Morgan, Patricia
Benenson, Michael
Paris, Robert M.
Chiu, Joseph
Adams, Elizabeth
Francis, Donald
Gurunathan, Sanjay
Tartaglia, Jim
Gilbert, Peter
Stablein, Don
Michael, Nelson L.
Kim, Jerome H.
TI Risk behaviour and time as covariates for efficacy of the HIV vaccine
regimen ALVAC-HIV (vCP1521) and AIDSVAX B/E: a post-hoc analysis of the
Thai phase 3 efficacy trial RV 144
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS; RHESUS-MONKEYS; INFECTION; MACAQUES; SIV;
METAANALYSIS; REPLICATION; ACQUISITION; CHALLENGES; PREVENTION
AB Background The Thai phase 3 HIV vaccine trial RV 144 showed modest efficacy of a vaccine against HIV acquisition. Baseline variables of age, sex, marital status, and risk did not modify vaccine efficacy. We did a post-hoc analysis of the trial's data to investigate behavioural risk and efficacy every 6 months after vaccination.
Methods RV 144 was a randomised, multicentre, double-blind, placebo-controlled efficacy trial testing the combination of the HIV vaccines ALVAC-HIV (vCP1521) and AIDSVAX B/E to prevent HIV infection or reduce setpoint viral load. Male and female volunteers aged 18-30 years were recruited from the community. In this post-hoc analysis of the modified intention-to-treat population (16395 participants), HIV risk behaviour was assessed with a self-administered questionnaire at the time of initial vaccination in the trial and every 6 months thereafter for 3 years. We classified participants' behaviour as low, medium, or high risk. Both the acquisition endpoint and the early viral-load endpoint were examined for interactions with risk status over time and temporal effects after vaccination. Multiple proportional hazards regression models with treatment and time-varying risk covariates were analysed.
Findings Risk of acquisition of HIV was low in each risk group, but 9187 (58.2%) participants reported higher-risk behaviour at least once during the study. Participants classified as high or increasing risk at least once during follow-up were compared with those who maintained low-risk or medium-risk behaviour as a time-varying covariate, and the interaction of risk status and acquisition efficacy was significant (p=0.01), with greater benefit in low-risk individuals. Vaccine efficacy seemed to peak early-cumulative vaccine efficacy was estimated to be 60.5% (95% CI 22-80) through the 12 months after initial vaccination-and declined quickly. Vaccination did not seem to affect viral load in either early or late infections.
Interpretation Future HIV vaccine trials should recognise potential interactions between challenge intensity and risk heterogeneity in both population and treatment effects. The regimen tested in the RV 144 phase 3 trial might benefit from extended immunisation schedules.
C1 [Robb, Merlin L.; Michael, Nelson L.; Kim, Jerome H.] Walter Reed Army Inst Res, Div Retrovirol, US Mil HIV Res Program, Rockville, MD USA.
[Rerks-Ngarm, Supachai; Kunasol, Prayura; Khamboonruang, Chirasak; Thongcharoen, Prasert] Minist Publ Hlth, Dept Dis Control, Nonthaburi, Thailand.
[Nitayaphon, Sorachai; Morgan, Patricia; Benenson, Michael] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand.
[Pitisuttithum, Punnee] Mahidol Univ, Vaccine Trials Ctr, Fac Trop Med, Bangkok 10700, Thailand.
[Kaewkungwal, Jaranit] Mahidol Univ, Data Management Unit, Fac Trop Med, Bangkok 10700, Thailand.
[Kaewkungwal, Jaranit] Henry Jackson Fdn, Rockville, MD USA.
[Morgan, Patricia; Benenson, Michael] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Paris, Robert M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Adams, Elizabeth] Global Solut Infect Dis, San Francisco, CA USA.
[Francis, Donald] Sanofi Pasteur, Swiftwater, PA USA.
[Gurunathan, Sanjay; Tartaglia, Jim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Gilbert, Peter] EMMES Corp, Rockville, MD USA.
[Stablein, Don; Kim, Jerome H.] USA, Med Mat Dev Act, Ft Detrick, MD USA.
RP Kim, JH (reprint author), 1600 E Gude Dr, Rockville, MD 20850 USA.
EM jkim@hivresearch.org
FU US National Institutes of Health, Division of AIDS; US Army Medical
Research and Materiel Command; Division of AIDS, National Institute of
Allergy and Infectious Disease, National Institutes of Health
FX The study was funded by the US National Institutes of Health, Division
of AIDS and the US Army Medical Research and Materiel Command. We
recognise the crucial support and commitment of the volunteers, research
staff, and communities of Chonburi and Rayong where the study was done.
The opinions in this paper are those of the authors and are not to be
construed as official and do not reflect the views of the Department of
Army or the Department of Defense.; Funding US Army Medical Research and
Materiel Command and Division of AIDS, National Institute of Allergy and
Infectious Disease, National Institutes of Health.
NR 27
TC 74
Z9 75
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUL
PY 2012
VL 12
IS 7
BP 531
EP 537
DI 10.1016/S1473-3099(12)70088-9
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA 969HC
UT WOS:000306045300026
PM 22652344
ER
PT J
AU Patel, MM
Glass, R
Desai, R
Tate, JE
Parashar, UD
AF Patel, Manish M.
Glass, Roger
Desai, Rishi
Tate, Jacqueline E.
Parashar, Umesh D.
TI Fulfilling the promise of rotavirus vaccines: how far have we come since
licensure?
SO LANCET INFECTIOUS DISEASES
LA English
DT Review
ID ORAL POLIOVIRUS VACCINE; DIARRHEA-ASSOCIATED HOSPITALIZATIONS; 1ST 2
YEARS; UNITED-STATES; DEVELOPING-COUNTRIES; DOUBLE-BLIND;
GASTROENTERITIS HOSPITALIZATIONS; CHILDHOOD DIARRHEA; SUSTAINED DECLINE;
LESS-THAN-5 YEARS
AB Rotavirus is the most common cause of fatal and severe childhood diarrhoea worldwide. Two new rotavirus vaccines have shown efficacy against severe rotavirus disease in large clinical trials. Between 2006 and 2010, 27 countries introduced rotavirus vaccination into national immunisation programmes and, subsequently, the burden of severe rotavirus disease in these countries has decreased substantially in both vaccinated and unvaccinated children. Rotavirus vaccination has led to large, sustained declines in childhood deaths from diarrhoea in Brazil and Mexico, which supports estimates that rotavirus was the leading cause of diarrhoeal deaths in these countries. Studies after licensing have provided new insights into these vaccines, such as the duration of protection, relative effectiveness in poor populations, and strain evolution after vaccine introduction. The challenge for policy makers worldwide is to analyse the effect of vaccination in early adopter countries and to assess whether the benefits outweigh the costs and encourage wider dissemination of these vaccines.
C1 [Patel, Manish M.; Glass, Roger; Desai, Rishi; Tate, Jacqueline E.; Parashar, Umesh D.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA.
[Glass, Roger] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Patel, MM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, 1600 Clifton Rd NE,Mail Stop A-34, Atlanta, GA 30333 USA.
EM aul3@cdc.gov
NR 116
TC 64
Z9 65
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUL
PY 2012
VL 12
IS 7
BP 561
EP 570
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA 969HC
UT WOS:000306045300029
PM 22742639
ER
PT J
AU Thomas, A
Hassan, RT
AF Thomas, Anish
Hassan, Raffi T.
TI Immunotherapies for non-small-cell lung cancer and mesothelioma
SO LANCET ONCOLOGY
LA English
DT Review
ID BLP25 LIPOSOME VACCINE; GROWTH-FACTOR-BETA; REFRACTORY SOLID TUMORS;
RANDOMIZED PHASE-II; T-REGULATORY CELLS; MALIGNANT MESOTHELIOMA;
MYCOBACTERIUM-VACCAE; PLEURAL MESOTHELIOMA; ORAL TALACTOFERRIN;
BELAGENPUMATUCEL-L
AB Non-small-cell lung cancer and mesothelioma are thoracic malignancies, which in their advanced stages are incurable and have poor prognosis. Advances in our understanding of immune responses to tumours, tumour immunosuppression mechanisms, and tumour-specific shared antigens enabled successful early clinical trials of several specific and non-specific immuno therapies. For non-small-cell lung cancer, phase 3 clinical trial results of Toll-like receptor agonists show little promise. However, ongoing phase 3 trials are assessing melanoma-associated antigen A3 vaccine, liposomal BLP25, belagenpumatucel-L, and talactoferrin. In mesothelioma, immunotherapies being investigated include dendritic cell-based and Listeria-based vaccines, and allogeneic tumour cell and WT1 analogue peptide vaccines. Selection of appropriate patients and disease stages for immunotherapy, measurement of tumour-specific immune responses, and understanding the association between immune and clinical responses are some of the major challenges for the development of immunotherapies for these malignancies.
C1 [Hassan, Raffi T.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Thomas, Anish] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hassan, RT (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM hassanr@mail.nih.gov
OI Thomas, Anish/0000-0003-3293-3115
FU Intramural NIH HHS
NR 95
TC 42
Z9 45
U1 0
U2 29
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD JUL
PY 2012
VL 13
IS 7
BP E301
EP E310
PG 10
WC Oncology
SC Oncology
GA 968CX
UT WOS:000305955700026
PM 22748269
ER
PT J
AU Degese, MS
Mendizabal, JE
Gandini, NA
Gutkind, JS
Molinolo, A
Hewitt, SM
Curino, AC
Coso, OA
Facchinetti, MM
AF Degese, Maria S.
Mendizabal, Javier E.
Gandini, Norberto A.
Gutkind, J. Silvio
Molinolo, Alfredo
Hewitt, Stephen M.
Curino, Alejandro C.
Coso, Omar A.
Facchinetti, Maria M.
TI Expression of heme oxygenase-1 in non-small cell lung cancer (NSCLC) and
its correlation with clinical data
SO LUNG CANCER
LA English
DT Article
DE Heme-oxygenase-1; Lung cancer; NSCLC; Tissue microarray;
Immunohistochemistry
ID LYMPH-NODE METASTASIS; NITRIC-OXIDE SYNTHASE; PULMONARY-DISEASE;
OXIDATIVE STRESS; INHIBITION; OVEREXPRESSION; SUSCEPTIBILITY;
MACROPHAGES; CARCINOMA; SURVIVAL
AB While changes in heme oxygenase (HO-1) in lung cancer have already been reported, conflicting results were obtained for enzyme expression in human lung cancer specimens. Therefore, the aim of this work was to study HO-1 expression in a large collection of human lung cancer samples. For this purpose, we analyzed the expression of HO-1 in an organized tissue microarray (TMA) and investigated its correlation with clinicopathological data. Ninety-six percent of tumor samples were positive for HO-1, and the expression of HO-1 was significantly higher in cancerous than in non-cancerous tissues. Importantly, HO-1 expression correlated with advanced stages and lymph node involvement. Additionally, quantitative RT-PCR in 18 pairs of human lung carcinomas and their adjacent non-malignant tissues was performed. Our results demonstrate that HO-1 protein is upregulated in epithelial malignant cells in NSCLC and its expression is associated with higher stages of the disease. Additionally, different subcellular localization is observed between tumor and adjacent non-malignant tissues. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Degese, Maria S.; Mendizabal, Javier E.; Coso, Omar A.] Univ Buenos Aires, Fac Ciencias Exactas & Nat, IFIBYNE CONICET, Lab Fisiol & Biol Mol, RA-1053 Buenos Aires, DF, Argentina.
[Gandini, Norberto A.; Curino, Alejandro C.; Facchinetti, Maria M.] CCT Bahia Blanca CONICET, INIBIBB, Lab Biol Canc, RA-8000 Bahia Blanca, Buenos Aires, Argentina.
[Gutkind, J. Silvio; Molinolo, Alfredo] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Hewitt, Stephen M.] Tarp AMPL NCI Adv Technol Ctr, Bethesda, MD USA.
RP Facchinetti, MM (reprint author), Camino Carrindanga Km 7, Bahia Blanca, Buenos Aires, Argentina.
EM facchinm@criba.edu.ar
OI Hewitt, Stephen/0000-0001-8283-1788
FU CONICET; ANPCyT, Argentina
FX This work was supported by grants and fellowships awarded by CONICET and
ANPCyT, Argentina.
NR 37
TC 27
Z9 28
U1 1
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
J9 LUNG CANCER
JI Lung Cancer
PD JUL
PY 2012
VL 77
IS 1
BP 168
EP 175
DI 10.1016/j.lungcan.2012.02.016
PG 8
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 966MO
UT WOS:000305842200028
PM 22418244
ER
PT J
AU Gehlsen, KR
Gong, R
Bramhill, D
Wiersma, DA
Kirkpatrick, SA
Wang, YP
Feng, Y
Dimitrov, DS
AF Gehlsen, Kurt R.
Gong, Rui
Bramhill, Dave
Wiersma, David A.
Kirkpatrick, Shaun A.
Wang, Yangping
Feng, Yang
Dimitrov, Dimiter S.
TI Pharmacokinetics of engineered human monomeric and dimeric CH2 domains
SO MABS
LA English
DT Article
DE serum half-life; CH2 domain; IgG(1); protein scaffolds; FcRn
ID NEONATAL-FC-RECEPTOR; SERUM HALF-LIFE; THERAPEUTIC ANTIBODIES;
INCREASED-STABILITY; MOLECULAR-SIZE; HUMAN IGG1; FRAGMENTS; PROTEINS;
AFFINITY; DRUGS
AB Therapeutic monoclonal antibodies have several advantages over small molecule drugs and small proteins and peptides, including a long serum half-life. The long serum half-life of IgG is due, in part, to its molecular weight (150 kDa) and its ability to bind FcRn. Both the CH2 and CH3 domains of Fc are involved in FcRn binding. Antibody fragments and antibody-like scaffolds have improved penetration into tissues due to their small size, but they commonly have serum half-lifes of less than one hour. The human CH2 domain (CH2D) of IgG1 retains a portion of the FcRn binding site, is amenable to modification for target binding, and may represent the smallest antibody-like scaffold retaining a relatively long serum half-life. We describe here the generation of a dimeric CH2D (dCH2D) and determination of its pharmacokinetics (PK), as well as the PK of wild-type monomeric CH2D (mCH2D) and a short stabilized CH2D variant (ssCH2D) in normal B6 mice, human FcRn transgenic mice and cynomolgus macaques. The elimination half-life of dCH2D was 9.9, 10.4 and 11.2 h, and that of ssCH2D was 13.1, 9.9 and 11.4 h, in B6 mice, hFcRn mice and cynomolgus macaques, respectively. These half-lives were slightly longer than that of mCH2D (6.9 and 8.8 h) in B6 and hFcRn mice, respectively. These data demonstrate that engineered CH2D-based variants have relatively long serum half-lives, making them a unique scaffold suitable for development of targeted therapeutics.
C1 [Gehlsen, Kurt R.; Bramhill, Dave; Wiersma, David A.; Kirkpatrick, Shaun A.] Res Corp Technol Inc, Tucson, AZ USA.
[Gong, Rui; Wang, Yangping; Feng, Yang; Dimitrov, Dimiter S.] NIH, Prot Interact Grp, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Wang, Yangping] NCI, Basic Res Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
RP Gehlsen, KR (reprint author), Res Corp Technol Inc, Tucson, AZ USA.
EM kgehlsen@rctech.com
FU Research Corporation Technologies; CRADA; NCI; RCT; Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research
FX K.R.G., D.B., D.A.W. and S.A.K. are employed at Research Corporation
Technologies, which provided financial support for this study.; This
project was supported by a CRADA between NCI and RCT, and the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 32
TC 13
Z9 13
U1 1
U2 6
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1942-0862
J9 MABS-AUSTIN
JI mAbs
PD JUL-AUG
PY 2012
VL 4
IS 4
BP 466
EP 474
DI 10.4161/mabs.20652
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 968FD
UT WOS:000305961800004
PM 22699277
ER
PT J
AU Jukic, AMZ
Evenson, KR
Daniels, JL
Herring, AH
Wilcox, AJ
Hartmann, KE
AF Jukic, Anne Marie Z.
Evenson, Kelly R.
Daniels, Julie L.
Herring, Amy H.
Wilcox, Allen J.
Hartmann, Katherine E.
TI A Prospective Study of the Association Between Vigorous Physical
Activity During Pregnancy and Length of Gestation and Birthweight
SO MATERNAL AND CHILD HEALTH JOURNAL
LA English
DT Article
DE Gestational age; Preterm birth; Exercise; Frequency; Duration
ID IMPACT AEROBIC DANCE; UTERINE BLOOD-FLOW; PRETERM BIRTH; FETAL-GROWTH;
MATERNAL EXERCISE; ENDURANCE EXERCISE; HORMONAL RESPONSES;
REGRESSION-MODELS; UNITED-STATES; WAVE-FORMS
AB Current US pregnancy-related physical activity recommendations do not provide specific guidance for vigorous intensity activity. We examined the associations between vigorous physical activity during pregnancy and length of gestation and birthweight. Methods: Women were recruited before 10 weeks gestation. At 13-16 weeks gestation, participants reported the type, frequency, and duration of their typical weekly vigorous physical activities. Activity domains included recreational, occupational, household, and child/adult care. Infant birth date was obtained from medical or vital records; if unavailable, self-report was used. Birthweight (from vital records) was studied among term births. We analyzed gestational age among 1,647 births using discrete-time survival analysis. We used logistic and linear regression to analyze preterm birth (birth at < 37 weeks) and birthweight, respectively. Vigorous recreational activity was associated with longer gestation (any vs. none, hazard ratio (HR) [95% CI]: 0.85 [0.70, 1.05]) and we did not detect any dose-response association. Higher frequency of vigorous recreational activity sessions (adjusted for total volume of activity) was associated with a decreased odds of preterm birth (a parts per thousand yen4 sessions/week vs. 0 or 1, OR [95% CI]: 0.08 (0.006, 1.0). Birthweight was not associated with physical activity measures. In summary, vigorous physical activity does not appear to be detrimental to the timing of birth or birthweight. Our data support a reduced risk of preterm birth with vigorous recreational activity, particularly with increased frequency of recreational activity sessions. Future studies should investigate the components of physical activity (i.e., intensity, duration, and frequency) in relation to birth outcomes.
C1 [Jukic, Anne Marie Z.; Wilcox, Allen J.] NIEHS, Epidemiol Branch, Durham, NC 27709 USA.
[Jukic, Anne Marie Z.; Evenson, Kelly R.; Daniels, Julie L.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Daniels, Julie L.] Univ N Carolina, Dept Maternal & Child Hlth, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Herring, Amy H.] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Herring, Amy H.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Hartmann, Katherine E.] Vanderbilt Univ, Inst Med & Publ Hlth, Nashville, TN USA.
RP Jukic, AMZ (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Durham, NC 27709 USA.
EM jukica@niehs.nih.gov
OI Wilcox, Allen/0000-0002-3376-1311
FU Intramural NIH HHS [Z01 ES044003-30, Z99 ES999999]; NCI NIH HHS [R01
CA109804, R01 CA109804-06]; NICHD NIH HHS [R01 HD043883, R01
HD043883-01A1, R01 HD049675, R01 HD049675-01A1, R01HD043883,
R01HD049675, R24 HD050924]; NIEHS NIH HHS [T32 ES007018-30, P30
ES010126, P30ES10126, T32 ES007018, T32ES007018]
NR 78
TC 18
Z9 18
U1 0
U2 25
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1092-7875
EI 1573-6628
J9 MATERN CHILD HLTH J
JI Matern. Child Health J.
PD JUL
PY 2012
VL 16
IS 5
BP 1031
EP 1044
DI 10.1007/s10995-011-0831-8
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 965ZA
UT WOS:000305805100013
PM 21674218
ER
PT J
AU Anderson, G
LaCroix, A
Limacher, M
Prentice, R
Stefanick, M
Wassertheil-Smoller, S
Rossouw, J
AF Anderson, Garnet
LaCroix, Andrea
Limacher, Marian
Prentice, Ross
Stefanick, Marcia
Wassertheil-Smoller, Sylvia
Rossouw, Jacques
TI The 2010 North American Menopause Society position statement on hormone
therapy goes beyond the available evidence
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Letter
ID RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; ESTROGEN;
HYSTERECTOMY; BENEFITS; RISKS
C1 [Anderson, Garnet; LaCroix, Andrea; Prentice, Ross] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Limacher, Marian] Univ Florida, Gainesville, FL USA.
[Stefanick, Marcia] Stanford Univ, Stanford, CA 94305 USA.
[Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Rossouw, Jacques] NHLBI, Bethesda, MD 20892 USA.
RP Anderson, G (reprint author), Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
OI Anderson, Garnet/0000-0001-5087-7837
NR 9
TC 1
Z9 1
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD JUL
PY 2012
VL 19
IS 7
BP 835
EP 836
DI 10.1097/gme.0b013e3182594f76
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 967II
UT WOS:000305900100019
PM 22668818
ER
PT J
AU Gass, MLS
Manson, J
Stuenkel, C
Cosman, F
Grodstein, F
Jordan, VC
Karas, R
Kaunitz, AM
Maki, P
Schmidt, PJ
Shifren, J
Utian, WH
AF Gass, Margery L. S.
Manson, JoAnn
Stuenkel, Cynthia
Cosman, Felicia
Grodstein, Francine
Jordan, V. Craig
Karas, Richard
Kaunitz, Andrew M.
Maki, Pauline
Schmidt, Peter J.
Shifren, Jan
Utian, Wulf H.
TI The 2010 North American Menopause Society position statement on hormone
therapy goes beyond the available evidence Response
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Letter
ID POSTMENOPAUSAL WOMEN
C1 [Gass, Margery L. S.] N Amer Menopause Soc, Mayfield Hts, OH 44124 USA.
[Manson, JoAnn; Grodstein, Francine; Shifren, Jan] Harvard Univ, Sch Med, Boston, MA USA.
[Stuenkel, Cynthia] Univ Calif San Diego, San Diego, CA 92103 USA.
[Cosman, Felicia] Columbia Univ, New York, NY USA.
[Jordan, V. Craig] Georgetown Univ, Washington, DC USA.
[Karas, Richard] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Kaunitz, Andrew M.] Univ Florida, Coll Med, Jacksonville, FL USA.
[Maki, Pauline] Univ Illinois, Coll Med, Chicago, IL USA.
[Schmidt, Peter J.] NIMH, Bethesda, MD 20892 USA.
[Utian, Wulf H.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
RP Gass, MLS (reprint author), N Amer Menopause Soc, Mayfield Hts, OH 44124 USA.
RI Jordan, V. Craig/H-4491-2011
NR 6
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD JUL
PY 2012
VL 19
IS 7
BP 836
EP 837
DI 10.1097/gme.0b013e31825b32ea
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 967II
UT WOS:000305900100020
ER
PT J
AU Chocron, ES
Sayre, NL
Holstein, D
Saelim, N
Ibdah, JA
Dong, LQ
Zhu, XG
Cheng, SY
Lechleiter, JD
AF Chocron, E. Sandra
Sayre, Naomi L.
Holstein, Deborah
Saelim, Nuttawut
Ibdah, Jamal A.
Dong, Lily Q.
Zhu, Xuguang
Cheng, Sheue-Yann
Lechleiter, James D.
TI The Trifunctional Protein Mediates Thyroid Hormone Receptor-Dependent
Stimulation of Mitochondria Metabolism
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID FATTY-ACID OXIDATION; ADENINE-NUCLEOTIDE TRANSLOCASE; ACETYL-COA
CARBOXYLASE; MALONYL-COA; RAT-LIVER; TRIIODOTHYRONINE T3;
ENERGY-EXPENDITURE; KINASE; INHIBITION; BETA
AB We previously demonstrated that the thyroid hormone, T-3, acutely stimulates mitochondrial metabolism in a thyroid hormone receptor (TR)-dependent manner. T-3 has also recently been shown to stimulate mitochondrial fatty acid oxidation (FAO). Here we report that TR-dependent stimulation of metabolism is mediated by the mitochondrial trifunctional protein (MTP), the enzyme responsible for long-chain FAO. Stimulation of FAO was significant in cells that expressed a nonnuclear amino terminus shortened TR isoform (sTR(43)) but not in adult fibroblasts cultured from mice deficient in both TR alpha and TR beta isoforms (TR alpha(-/-)beta(-/-)). Mouse embryonic fibroblasts deficient in MTP (MTP-/-) did not support T-3-stimulated FAO. Inhibition of fatty-acid trafficking into mitochondria using the AMP-activated protein kinase inhibitor 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine (compound C) or the carnitine palmitoyltransferase 1 inhibitor etomoxir prevented T-3-stimulated FAO. However, T-3 treatment could increase FAO when AMP-activated protein kinase was maximally activated, indicating an alternate mechanism of T-3-stimulated FAO exists, even when trafficking is presumably high. MTP alpha protein levels and higher molecular weight complexes of MTP subunits were increased by T-3 treatment. We suggest that T-3-induced increases in mitochondrial metabolism are at least in part mediated by a T-3-shortened TR isoform-dependent stabilization of the MTP complex, which appears to lower MTP subunit turnover. (Molecular Endocrinology 26: 1117-1128, 2012)
C1 [Sayre, Naomi L.; Holstein, Deborah; Dong, Lily Q.; Lechleiter, James D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Chocron, E. Sandra] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Saelim, Nuttawut] Naresuan Univ, Fac Pharmaceut Sci, Dept Pharm Practice, Phitsanulok 65000, Thailand.
[Ibdah, Jamal A.] Univ Missouri Columbia, Div Gastroenterol & Hepatol, Columbia, MO 65212 USA.
[Zhu, Xuguang; Cheng, Sheue-Yann] NCI, Gene Regulat Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Lechleiter, JD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM lechleiter@uthscsa.edu
FU National Institutes of Health [RO1 AG29461]
FX This work was supported by the National Institutes of Health Grant RO1
AG29461 (to J.D.L.).
NR 49
TC 6
Z9 8
U1 1
U2 10
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD JUL
PY 2012
VL 26
IS 7
BP 1117
EP 1128
DI 10.1210/me.2011-1348
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 968FK
UT WOS:000305962500005
PM 22570332
ER
PT J
AU Mingozzi, F
Chen, YF
Murphy, SL
Edmonson, SC
Tai, A
Price, SD
Metzger, ME
Zhou, SZ
Wright, JF
Donahue, RE
Dunbar, CE
High, KA
AF Mingozzi, Federico
Chen, Yifeng
Murphy, Samuel L.
Edmonson, Shyrie C.
Tai, Alex
Price, Sandra D.
Metzger, Mark E.
Zhou, Shangzhen
Wright, J. Fraser
Donahue, Robert E.
Dunbar, Cynthia E.
High, Katherine A.
TI Pharmacological Modulation of Humoral Immunity in a Nonhuman Primate
Model of AAV Gene Transfer for Hemophilia B
SO MOLECULAR THERAPY
LA English
DT Article
ID ADENOASSOCIATED VIRAL VECTORS; DEFICIENT MOUSE MODEL; T-CELL RESPONSES;
FACTOR-IX; TRANSGENE PRODUCT; FACTOR-VIII; THERAPY; LIVER; RITUXIMAB;
INHIBITORS
AB Liver gene transfer for hemophilia B has shown very promising results in recent clinical studies. A potential complication of gene-based treatments for hemophilia and other inherited disorders, however, is the development of neutralizing antibodies (NAb) against the therapeutic transgene. The risk of developing NAb to the coagulation factor IX (F.IX) transgene product following adeno-associated virus (AAV)-mediated hepatic gene transfer for hemophilia is small but not absent, as formation of inhibitory antibodies to F.IX is observed in experimental animals following liver gene transfer. Thus, strategies to modulate antitransgene NAb responses are needed. Here, we used the anti-B cell monoclonal antibody rituximab (rtx) in combination with cyclosporine A (CsA) to eradicate anti-human FIX NAb in rhesus macaques previously injected intravenously with AAV8 vectors expressing human F.IX. A short course of immunosuppression (IS) resulted in eradication of anti-F.IX NAb with restoration of plasma F.IX transgene product detection. In one animal, following IS anti-AAV6 antibodies also dropped below detection, allowing for successful AAV vector readministration and resulting in high levels (60% or normal) of F.IX transgene product in plasma. Though the number of animals is small, this study supports for the safety and efficacy of B cell-targeting therapies to eradicate NAb developed following MV-mediated gene transfer. Received 6 January 2012; accepted 5 April 2012; advance online publication 8 May 2012. doi:10.1038/mt.2012.84
C1 [Mingozzi, Federico; Chen, Yifeng; Murphy, Samuel L.; Edmonson, Shyrie C.; Tai, Alex; Zhou, Shangzhen; Wright, J. Fraser; High, Katherine A.] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA.
[Chen, Yifeng; Edmonson, Shyrie C.; High, Katherine A.] Howard Hughes Med Inst, Philadelphia, PA USA.
[Price, Sandra D.; Metzger, Mark E.; Donahue, Robert E.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Wright, J. Fraser] Univ Penn, Sch Med, Dept Pathol, Philadelphia, PA 19104 USA.
[High, Katherine A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
RP Mingozzi, F (reprint author), Childrens Hosp Philadelphia, Div Hematol, CTRB Room 5064,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM mingozzi@email.chop.edu
FU Howard Hughes Medical Institute; National Heart, Lung, and Blood
Institute [P01 HL078810]
FX This work was supported by the Howard Hughes Medical Institute (to
K.A.H.) and by the National Heart, Lung, and Blood Institute (grant P01
HL078810 to K.A.H. and intramural funding to M.E.M., S.D.P., RED., and
C.E.D.). We thank the staff at 5 Research Court for their excellent care
and handling of the rhesus macaques. F.M., J.F.W., and K.A.H. are
inventors on patents related to AAV gene therapy and have consulted for
companies developing gene therapeutics. The other authors declared no
conflict of interest.
NR 50
TC 28
Z9 30
U1 1
U2 7
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 JUL
PY 2012
VL 20
IS 7
BP 1410
EP 1416
DI 10.1038/mt.2012.84
PG 7
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 969CW
UT WOS:000306034300016
PM 22565846
ER
PT J
AU Hurley, JH
Odorizzi, G
AF Hurley, James H.
Odorizzi, Greg
TI Get on the exosome bus with ALIX
SO NATURE CELL BIOLOGY
LA English
DT Editorial Material
ID UBIQUITINATION; MEMBRANE; VESICLES; PROTEIN
AB Exosomes have a growing inventory of functions, but the mechanism of protein sorting into exosomes has been unclear. Now, a signal sequence first described in viral budding provides just such a cargo sorting mechanism, revealing closer-than-expected parallelism between exosome biogenesis and the ESCRT-dependent endolysdsomal pathway.
C1 [Hurley, James H.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Odorizzi, Greg] Univ Colorado, Dept Mol Cell & Dev Biol, Boulder, CO 80309 USA.
RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM James.hurley@nih.gov; Odorizzi@colorado.edu
NR 15
TC 55
Z9 55
U1 3
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD JUL
PY 2012
VL 14
IS 7
BP 654
EP 655
PG 2
WC Cell Biology
SC Cell Biology
GA 967PV
UT WOS:000305921200003
PM 22743708
ER
PT J
AU Gan, XQ
Wang, JY
Wang, C
Sommer, E
Kozasa, T
Srinivasula, S
Alessi, D
Offermanns, S
Simon, MI
Wu, DQ
AF Gan, Xiaoqing
Wang, Jiyong
Wang, Chen
Sommer, Eeva
Kozasa, Tohru
Srinivasula, Srinivasa
Alessi, Dario
Offermanns, Stefan
Simon, Melvin I.
Wu, Dianqing
TI PRR5L degradation promotes mTORC2-mediated PKC-delta phosphorylation and
cell migration downstream of G alpha(12)
SO NATURE CELL BIOLOGY
LA English
DT Article
ID PROTEIN-KINASE-C; RICTOR-MTOR COMPLEX; MAMMALIAN TARGET; BINDING
PARTNER; MOTIF PHOSPHORYLATION; ACTIN CYTOSKELETON; G(12) FAMILY;
MUSCLE-CELLS; GROWTH; ACTIVATION
AB Mammalian target of rapamycin complex 2 (mTORC2) phosphorylates AGC protein kinases including protein kinase C (PKC) and regulates cellular functions such as cell migration. However, its regulation remains poorly understood. Here we show that lysophosphatidic acid (LPA) induces two phases of PKC-delta hydrophobic motif phosphorylation. The late phase is mediated by G alpha(12), which specifically activates ARAF, leading to upregulation of the RFFL E3 ubiquitin ligase and subsequent ubiquitylation and degradation of the PRR5L subunit of mTORC2. Destabilization of PRR5L, a suppressor of mTORC2-mediated hydrophobic motif phosphorylation of PKC-delta, but not AKT, results in PKC-delta hydrophobic motif phosphorylation and activation. This G alpha(12)-mediated signalling pathway for mTORC2 regulation is critically important for fibroblast migration and pulmonary fibrosis development.
C1 [Gan, Xiaoqing; Wang, Jiyong; Wang, Chen; Wu, Dianqing] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA.
[Gan, Xiaoqing; Wang, Jiyong; Wang, Chen; Wu, Dianqing] Yale Univ, Sch Med, Program Vasc Biol & Therapeut, New Haven, CT 06520 USA.
[Sommer, Eeva; Alessi, Dario] Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland.
[Kozasa, Tohru] Univ Illinois, Dept Pharmacol, Chicago, IL 60612 USA.
[Kozasa, Tohru] Univ Tokyo, Res Ctr Adv Sci & Technol, Tokyo 153, Japan.
[Srinivasula, Srinivasa] NCI, NIH, Bethesda, MD 20892 USA.
[Offermanns, Stefan] Max Planck Inst Heart & Lung Res, Dept Pharmacol, D-61231 Bad Nauheim, Germany.
[Simon, Melvin I.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
RP Wu, DQ (reprint author), Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA.
EM dan.wu@yale.edu
OI Alessi, Dario/0000-0002-2140-9185
FU National Institutes of Health [HL070694, HL080706, CA139395, GM61454,
GM074001]; Ellison Medical Foundation [AG-SS-2190-08]
FX We thank B. Su for discussion and the anti-MAPKAP1 antibody, and M.
Orsulak for technical help. This work is supported by National
Institutes of Health grants (HL070694, HL080706 and CA139395 to D.W. and
GM61454 and GM074001 to T.K.) and an Ellison Medical Foundation grant
(AG-SS-2190-08 to M.I.S.).
NR 56
TC 32
Z9 40
U1 1
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD JUL
PY 2012
VL 14
IS 7
BP 686
EP 696
DI 10.1038/ncb2507
PG 11
WC Cell Biology
SC Cell Biology
GA 967PV
UT WOS:000305921200008
PM 22609986
ER
PT J
AU Wynn, TA
Ramalingam, TR
AF Wynn, Thomas A.
Ramalingam, Thirumalai R.
TI Mechanisms of fibrosis: therapeutic translation for fibrotic disease
SO NATURE MEDICINE
LA English
DT Review
ID IDIOPATHIC PULMONARY-FIBROSIS; TUMOR-NECROSIS-FACTOR; REGULATORY
T-CELLS; RENAL INTERSTITIAL FIBROSIS; PLACEBO-CONTROLLED TRIAL; HEPATIC
STELLATE-CELLS; TISSUE GROWTH-FACTOR; ENDOPLASMIC-RETICULUM STRESS;
MESSENGER-RNA EXPRESSION; ACTIVATED RECEPTOR-GAMMA
AB Fibrosis is a pathological feature of most chronic inflammatory diseases. Fibrosis, or scarring, is defined by the accumulation of excess extracellular matrix components. If highly progressive, the fibrotic process eventually leads to organ malfunction and death. Fibrosis affects nearly every tissue in the body. Here we discuss how key components of the innate and adaptive immune response contribute to the pathogenesis of fibrosis. We also describe how cell-intrinsic changes in important structural cells can perpetuate the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix-producing myofibroblasts. Finally, we highlight some of the key mechanisms and pathways of fibrosis that are being targeted as potential therapies for a variety of important human diseases.
C1 [Wynn, Thomas A.; Ramalingam, Thirumalai R.] NIAID, Immunopathogenesis Sect, Program Barrier Immun & Repair, Parasit Dis Lab,NIH, Bethesda, MD 20892 USA.
RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Program Barrier Immun & Repair, Parasit Dis Lab,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twynn@niaid.nih.gov
FU US National Institutes of Health; National Institute of Allergy and
Infectious Diseases; Pfizer; MedImmune; Amgen; Regeneron; Centocor;
Genentech
FX We would like to sincerely thank the past and present members of our
laboratory for their guidance, comments and support. The Wynn laboratory
is supported by the intramural research program of the US National
Institutes of Health, National Institute of Allergy and Infectious
Diseases and has benefited from cooperative research-and-development
agreements with Pfizer, MedImmune, Amgen, Regeneron, Centocor and
Genentech.
NR 181
TC 568
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U1 34
U2 177
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 JUL
PY 2012
VL 18
IS 7
BP 1028
EP 1040
DI 10.1038/nm.2807
PG 13
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 970IM
UT WOS:000306121600032
PM 22772564
ER
PT J
AU Zeissig, S
Murata, K
Sweet, L
Publicover, J
Hu, ZY
Kaser, A
Bosse, E
Iqbal, J
Hussain, MM
Balschun, K
Rocken, C
Arlt, A
Gunther, R
Hampe, J
Schreiber, S
Baron, JL
Moody, DB
Liang, TJ
Blumberg, RS
AF Zeissig, Sebastian
Murata, Kazumoto
Sweet, Lindsay
Publicover, Jean
Hu, Zongyi
Kaser, Arthur
Bosse, Esther
Iqbal, Jahangir
Hussain, M. Mahmood
Balschun, Katharina
Roecken, Christoph
Arlt, Alexander
Guenther, Rainer
Hampe, Jochen
Schreiber, Stefan
Baron, Jody L.
Moody, D. Branch
Liang, T. Jake
Blumberg, Richard S.
TI Hepatitis B virus-induced lipid alterations contribute to natural killer
T cell-dependent protective immunity
SO NATURE MEDICINE
LA English
DT Article
ID TRIGLYCERIDE TRANSFER PROTEIN; NKT CELLS; IN-VIVO; ANTIGEN PRESENTATION;
PHOSPHOLIPASE A(2); MICROBIAL INFECTION; VIRAL CLEARANCE;
SURFACE-ANTIGEN; MOUSE MODEL; INNATE
AB In most adult humans, hepatitis B is a self-limiting disease leading to life-long protective immunity, which is the consequence of a robust adaptive immune response occurring weeks after hepatitis B virus (HBV) infection. Notably, HBV-specific T cells can be detected shortly after infection, but the mechanisms underlying this early immune priming and its consequences for subsequent control of viral replication are poorly understood. Using primary human and mouse hepatocytes and mouse models of transgenic and adenoviral HBV expression, we show that HBV-expressing hepatocytes produce endoplasmic reticulum (ER)-associated endogenous antigenic lipids including lysophospholipids that are generated by HBV-induced secretory phospholipases and that lead to activation of natural killer T (NKT) cells. The absence of NKT cells or CD1d or a defect in ER-associated transfer of lipids onto CD1d results in diminished HBV-specific T and B cell responses and delayed viral control in mice. NKT cells may therefore contribute to control of HBV infection through sensing of HBV-induced modified self-lipids.
C1 [Zeissig, Sebastian; Kaser, Arthur; Blumberg, Richard S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA.
[Zeissig, Sebastian; Bosse, Esther; Arlt, Alexander; Guenther, Rainer; Hampe, Jochen; Schreiber, Stefan] Univ Kiel, Univ Med Ctr Schleswig Holstein, Dept Internal Med 1, Kiel, Germany.
[Murata, Kazumoto; Hu, Zongyi; Liang, T. Jake] NIDDK, Liver Dis Branch, US Natl Inst Hlth, Bethesda, MD USA.
[Sweet, Lindsay; Moody, D. Branch] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Publicover, Jean; Baron, Jody L.] Univ Calif San Francisco, Ctr Liver, Dept Med, San Francisco, CA 94143 USA.
[Iqbal, Jahangir; Hussain, M. Mahmood] SUNY Hlth Sci Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA.
[Hussain, M. Mahmood] SUNY Hlth Sci Ctr, Dept Pediat, Brooklyn, NY 11203 USA.
[Balschun, Katharina; Roecken, Christoph] Univ Kiel, Univ Med Ctr Schleswig Holstein, Dept Pathol, Kiel, Germany.
RP Blumberg, RS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA.
EM jliang@nih.gov; rblumberg@partners.org
RI Schreiber, Stefan/B-6748-2008; Zeissig, Sebastian/B-6297-2012; Rocken,
Christoph/A-9239-2010; Hampe, Jochen/A-2555-2010;
OI Schreiber, Stefan/0000-0003-2254-7771; Rocken,
Christoph/0000-0002-6989-8002; Hampe, Jochen/0000-0002-2421-6127; Arlt,
Alexander/0000-0002-6160-1059
FU US National Institutes of Health (NIH) [DK51362, DK44319, DK53056,
DK88199]; Harvard Digestive Diseases Center [DK034854]; Deutsche
Forschungsgemeinschaft [Ze 814/1-1, Ze 814/4-1]; Marie Curie
International Reintegration Grant within the 7th European Community
Framework Programme [256363]; Crohn's and Colitis Foundation of America;
Austrian Science Fund; Max Kade Foundation; NIH [AR048632, AI049313];
Burroughs Wellcome Fund for Translational Research; NIH Intramural
Research Program; Burroughs Wellcome Fund [AI068090, DK026743]; A.P.
Gianinni Foundation; [DK46900]
FX This work was supported by US National Institutes of Health (NIH) grants
DK51362, DK44319, DK53056, DK88199, the Harvard Digestive Diseases
Center DK034854 (to R.S.B.); the Deutsche Forschungsgemeinschaft (Ze
814/1-1, Ze 814/4-1), a Marie Curie International Reintegration Grant
within the 7th European Community Framework Programme (256363) and the
Crohn's and Colitis Foundation of America (to S.Z.); the Crohn's and
Colitis Foundation of America, Austrian Science Fund, and Max Kade
Foundation (to A.K.); NIH AR048632, AI049313 and the Burroughs Wellcome
Fund for Translational Research (to D.B.M.); DK46900 (to M.M.H.); the
NIH Intramural Research Program (K.M., Z.H. and T.J.L.); NIH grants
AI068090, DK026743 and the Burroughs Wellcome Fund (to J.L.B.); and the
A.P. Gianinni Foundation (to J.P.). We thank D.E. Cohen, E. Scapa and
S.K. Dougan for insightful discussions.
NR 55
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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 JUL
PY 2012
VL 18
IS 7
BP 1060
EP +
DI 10.1038/nm.2811
PG 11
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 970IM
UT WOS:000306121600035
PM 22706385
ER
PT J
AU Kentsis, A
Reed, C
Rice, KL
Sanda, T
Rodig, SJ
Tholouli, E
Christie, A
Valk, PJM
Delwel, R
Ngo, V
Kutok, JL
Dahlberg, SE
Moreau, LA
Byers, RJ
Christensen, JG
Woude, GV
Licht, JD
Kung, AL
Staudt, LM
Look, AT
AF Kentsis, Alex
Reed, Casie
Rice, Kim L.
Sanda, Takaomi
Rodig, Scott J.
Tholouli, Eleni
Christie, Amanda
Valk, Peter J. M.
Delwel, Ruud
Vu Ngo
Kutok, Jeffery L.
Dahlberg, Suzanne E.
Moreau, Lisa A.
Byers, Richard J.
Christensen, James G.
Woude, George Vande
Licht, Jonathan D.
Kung, Andrew L.
Staudt, Louis M.
Look, A. Thomas
TI Autocrine activation of the MET receptor tyrosine kinase in acute
myeloid leukemia
SO NATURE MEDICINE
LA English
DT Article
ID CANCER-CELLS; INHIBITOR; SCREEN; AML; CLASSIFICATION; PATHWAYS; TARGETS;
FLT3
AB Although the treatment of acute myeloid leukemia (AML) has improved substantially in the past three decades, more than half of all patients develop disease that is refractory to intensive chemotherapy(1,2). Functional genomics approaches offer a means to discover specific molecules mediating the aberrant growth and survival of cancer cells(3-8). Thus, using a loss-of-function RNA interference genomic screen, we identified the aberrant expression of hepatocyte growth factor (HGF) as a crucial element in AML pathogenesis. We found HGF expression leading to autocrine activation of its receptor tyrosine kinase, MET, in nearly half of the AML cell lines and clinical samples we studied. Genetic depletion of HGF or MET potently inhibited the growth and survival of HGF-expressing AML cells. However, leukemic cells treated with the specific MET kinase inhibitor crizotinib developed resistance resulting from compensatory upregulation of HGF expression, leading to the restoration of MET signaling. In cases of AML where MET is coactivated with other tyrosine kinases, such as fibroblast growth factor receptor 1 (FGFR1)(9), concomitant inhibition of FGFR1 and MET blocked this compensatory HGF upregulation, resulting in sustained logarithmic cell killing both in vitro and in xenograft models in vivo. Our results show a widespread dependence of AML cells on autocrine activation of MET, as well as the key role of compensatory upregulation of HGF expression in maintaining leukemogenic signaling by this receptor. We anticipate that these findings will lead to the design of additional strategies to block adaptive cellular responses that drive compensatory ligand expression as an essential component of the targeted inhibition of oncogenic receptors in human cancers.
C1 [Kentsis, Alex; Reed, Casie; Sanda, Takaomi; Christie, Amanda; Moreau, Lisa A.; Kung, Andrew L.; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Kentsis, Alex; Reed, Casie; Sanda, Takaomi; Christie, Amanda; Moreau, Lisa A.; Kung, Andrew L.; Look, A. Thomas] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol & Oncol, Boston, MA USA.
[Rice, Kim L.; Licht, Jonathan D.] Northwestern Univ, Feinberg Sch Med, Div Hematol & Oncol, Chicago, IL 60611 USA.
[Rodig, Scott J.; Kutok, Jeffery L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Tholouli, Eleni; Byers, Richard J.] Cent Manchester Univ Hosp Natl Hlth Serv Fdn Trus, Manchester Royal Infirm, Dept Haematol, Manchester, Lancs, England.
[Tholouli, Eleni; Byers, Richard J.] Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Christie, Amanda; Kung, Andrew L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA.
[Valk, Peter J. M.; Delwel, Ruud] Erasmus MC, Dept Hematol, Rotterdam, Netherlands.
[Vu Ngo] City Hope Natl Med Ctr, Div Hematopoiet Stem Cell & Leukemia Res, Duarte, CA 91010 USA.
[Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Byers, Richard J.] Univ Manchester, Fac Med & Human Sci, Sch Canc & Enabling Sci, Manchester, Lancs, England.
[Christensen, James G.] Pfizer Global Res & Dev, Dept Res Pharmacol, La Jolla, CA USA.
[Woude, George Vande] Van Andel Res Inst, Dept Mol Oncol, Grand Rapids, MI USA.
[Staudt, Louis M.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM thomas_look@dfci.harvard.edu
OI Kentsis, Alex/0000-0002-8063-9191; Byers, Richard/0000-0003-0796-0365;
Kung, Andrew/0000-0002-9091-488X
FU US National Institutes of Health grant [K08CA160660]; William Lawrence
and Blanche Hughes Foundation; Samuel Waxman Cancer Research Foundation;
V Foundation; Intramural Research Program of the National Cancer
Institute, Center for Cancer Research
FX We thank A. Gutierrez, M. Mansour and E. Gjini for critical discussions
and J. Gilbert for editorial advice. This research was supported by the
US National Institutes of Health grant K08CA160660 (A.K.), the William
Lawrence and Blanche Hughes Foundation (T.S.), the Samuel Waxman Cancer
Research Foundation (J.D.L.), the V Foundation (A.T.L.) and the
Intramural Research Program of the National Cancer Institute, Center for
Cancer Research (L.M.S.).
NR 25
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U1 2
U2 17
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 JUL
PY 2012
VL 18
IS 7
BP 1118
EP +
DI 10.1038/nm.2819
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 970IM
UT WOS:000306121600042
PM 22683780
ER
PT J
AU Eliceiri, KW
Berthold, MR
Goldberg, IG
Ibanez, L
Manjunath, BS
Martone, ME
Murphy, RF
Peng, HC
Plant, AL
Roysam, B
Stuurmann, N
Swedlow, JR
Tomancak, P
Carpenter, AE
AF Eliceiri, Kevin W.
Berthold, Michael R.
Goldberg, Ilya G.
Ibanez, Luis
Manjunath, B. S.
Martone, Maryann E.
Murphy, Robert F.
Peng, Hanchuan
Plant, Anne L.
Roysam, Badrinath
Stuurmann, Nico
Swedlow, Jason R.
Tomancak, Pavel
Carpenter, Anne E.
TI Biological imaging software tools
SO NATURE METHODS
LA English
DT Review
ID SUBCELLULAR LOCATION PATTERNS; ILLUMINATION MICROSCOPY; PLANE
ILLUMINATION; CELLS; VISUALIZATION; MACHINE; CLASSIFICATION; MANAGEMENT;
RESOLUTION; ELEGANS
AB Few technologies are more widespread in modern biological laboratories than imaging. Recent advances in optical technologies and instrumentation are providing hitherto unimagined capabilities. Almost all these advances have required the development of software to enable the acquisition, management, analysis and visualization of the imaging data. We review each computational step that biologists encounter when dealing with digital images, the inherent challenges and the overall status of available software for bioimage informatics, focusing on open-source options.
C1 [Eliceiri, Kevin W.] Univ Wisconsin, Lab Opt & Computat Instrumentat, Madison, WI 53706 USA.
[Berthold, Michael R.] Univ Konstanz, Dept Comp & Informat Sci, Constance, Germany.
[Goldberg, Ilya G.] NIA, NIH, Baltimore, MD 21224 USA.
[Ibanez, Luis] Kitware Inc, New York, NY USA.
[Manjunath, B. S.] Univ Calif Santa Barbara, Dept Elect & Comp Engn, Ctr Bioimage Informat, Santa Barbara, CA 93106 USA.
[Martone, Maryann E.] Univ Calif San Diego, Natl Ctr Microscopy & Imaging Res, La Jolla, CA 92093 USA.
[Murphy, Robert F.] Carnegie Mellon Univ, Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA.
[Peng, Hanchuan] Howard Hughes Med Inst, Ashburn, VA USA.
[Plant, Anne L.] Natl Inst Stand & Technol, Div Biochem Sci, Gaithersburg, MD 20899 USA.
[Roysam, Badrinath] Univ Houston, Dept Elect & Comp Engn, Houston, TX USA.
[Stuurmann, Nico] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
[Swedlow, Jason R.] Univ Dundee, Wellcome Trust Ctr Gene Regulat & Express, Dundee, Scotland.
[Tomancak, Pavel] Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany.
[Carpenter, Anne E.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA.
RP Eliceiri, KW (reprint author), Univ Wisconsin, Lab Opt & Computat Instrumentat, Madison, WI 53706 USA.
EM eliceiri@wisc.edu; anne@broadinstitute.org
RI Goldberg, Ilya/H-5307-2011; Tomancak, Pavel/C-2109-2009; Carpenter,
Anne/C-4982-2008;
OI Goldberg, Ilya/0000-0001-8514-6110; Martone,
Maryann/0000-0002-8406-3871; Tomancak, Pavel/0000-0002-2222-9370;
Carpenter, Anne/0000-0003-1555-8261; Eliceiri,
Kevin/0000-0001-8678-670X; Swedlow, Jason/0000-0002-2198-1958
FU US National Institutes of Health [R01 GM089652, RC2 GM092519]
FX We acknowledge our respective funding sources and members of our
laboratories for feedback and useful comments, in particular A. Merouane
and A. Narayanswamy of the Roysam lab for their assistance in preparing
figures, and L. Kamentsky and M. Bray of the Carpenter lab for useful
input and edits on the manuscript. A.E.C. and K.W.E. were supported by
US National Institutes of Health grants R01 GM089652 (to A.E.C.) and RC2
GM092519 (to K.W.E.).
NR 60
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U1 2
U2 74
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 JUL
PY 2012
VL 9
IS 7
BP 697
EP 710
DI 10.1038/NMETH.2084
PG 14
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 967XT
UT WOS:000305942200024
PM 22743775
ER
PT J
AU York, AG
Parekh, SH
Nogare, DD
Fischer, RS
Temprine, K
Mione, M
Chitnis, AB
Combs, CA
Shroff, H
AF York, Andrew G.
Parekh, Sapun H.
Nogare, Damian Dalle
Fischer, Robert S.
Temprine, Kelsey
Mione, Marina
Chitnis, Ajay B.
Combs, Christian A.
Shroff, Hari
TI Resolution doubling in live, multicellular organisms via multifocal
structured illumination microscopy
SO NATURE METHODS
LA English
DT Article
ID GENETICALLY EXPRESSED PROBES; FLUORESCENCE MICROSCOPY; LOCALIZATION
MICROSCOPY; SCALE RESOLUTION; CELLS; NANOSCOPY; DYNAMICS; LIMIT;
ARCHITECTURE; HOMEOSTASIS
AB We demonstrate three-dimensional (3D) super-resolution in live multicellular organisms using structured illumination microscopy (SIM). Sparse multifocal illumination patterns generated by a digital micromirror device (DMD) allowed us to physically reject out-of-focus light, enabling 3D subdiffractive imaging in samples eightfold thicker than had been previously imaged with SIM. We imaged samples at one 2D image per second, at resolutions as low as 145 nm laterally and 400 nm axially. In addition to dual-labeled, whole fixed cells, we imaged GFP-labeled microtubules in live transgenic zebrafish embryos at depths >45 mu m. We captured dynamic changes in the zebrafish lateral line primordium and observed interactions between myosin IIA and F-actin in cells encapsulated in collagen gels, obtaining two-color 4D super-resolution data sets spanning tens of time points and minutes without apparent phototoxicity. Our method uses commercially available parts and open-source software and is simpler than existing SIM implementations, allowing easy integration with wide-field microscopes.
C1 [York, Andrew G.; Parekh, Sapun H.; Temprine, Kelsey; Shroff, Hari] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut, US Natl Inst Hlth NIH, Bethesda, MD USA.
[Nogare, Damian Dalle; Chitnis, Ajay B.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Fischer, Robert S.; Combs, Christian A.] NHLBI, Light Microscopy Facil, NIH, Bethesda, MD 20892 USA.
[Mione, Marina] Karlsruhe Inst Technol, Inst Toxicol & Genet, Karlsruhe, Germany.
RP York, AG (reprint author), Natl Inst Biomed Imaging & Bioengn, Sect High Resolut, US Natl Inst Hlth NIH, Bethesda, MD USA.
EM andrew.g.york+naturemethods@gmail.com
RI Mione, Maria Caterina /I-3073-2013; Shroff, Hari/E-7247-2016
OI Shroff, Hari/0000-0003-3613-8215
FU American Association for the Advancement of Science; Intramural Research
Program of the NIH National Institute of Biomedical Imaging and
Bioengineering; National Institute of Heart, Lung, and Blood; National
Institute of Child Health and Development
FX We thank M. Davidson (Florida State University) for the U2OS cells, Z.
Bao (Sloan-Kettering Institute) for the BV24 nematode strain, K.
Hazelwood for assistance with cell culture, G. Patterson for the use of
his cell culture facilities, and H. Eden, P. Winter, Y. Wu and C.
Waterman for feedback and suggestions on the manuscript. S. H. P.
acknowledges financial support from the American Association for the
Advancement of Science. This work was supported by the Intramural
Research Program of the NIH National Institute of Biomedical Imaging and
Bioengineering, the National Institute of Heart, Lung, and Blood and the
National Institute of Child Health and Development.
NR 36
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD JUL
PY 2012
VL 9
IS 7
BP 749
EP U167
DI 10.1038/NMETH.2025
PG 8
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 967XT
UT WOS:000305942200034
PM 22581372
ER
PT J
AU Chen, S
Li, W
AF Chen, Shan
Li, Wei
TI A color-coding amacrine cell may provide a blue-Off signal in a
mammalian retina
SO NATURE NEUROSCIENCE
LA English
DT Article
ID GANGLION-CELLS; PRIMATE RETINA; OPPONENT PATHWAY; MACAQUE RETINA;
BIPOLAR CELLS; VISION; CONES
AB Retinal amacrine cells are thought to lack chromatic or color-selective light responses and have only a minor role in color processing. We found that a type of mammalian (Ictidomys tridecemlineatus) amacrine cell selectively carries a blue-On signal, which is received from a blue or short wavelength sensitive (S) cone On bipolar cell. This glycinergic inhibitory S-cone amacrine cell is ideally placed for driving blue-Off responses in downstream ganglion cells.
C1 [Chen, Shan; Li, Wei] NEI, Unit Retinal Neurophysiol, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Li, W (reprint author), NEI, Unit Retinal Neurophysiol, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM liwei2@nei.nih.gov
FU Intramural Research Program of the National Eye Institute [ZIA
EY000508-01]
FX We thank D. Merriman and T. Rosenberg for editing and S. DeVries and B.
Szmajda for critically reading the manuscript. This work was supported
by the Intramural Research Program of the National Eye Institute (ZIA
EY000508-01).
NR 15
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U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD JUL
PY 2012
VL 15
IS 7
BP 954
EP 956
DI 10.1038/nn.3128
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 966EE
UT WOS:000305819600011
PM 22634731
ER
PT J
AU Sheng, JS
He, LM
Zheng, HW
Xue, L
Luo, FJ
Shin, W
Sun, T
Kuner, T
Yue, DT
Wu, LG
AF Sheng, Jiansong
He, Liming
Zheng, Hongwei
Xue, Lei
Luo, Fujun
Shin, Wonchul
Sun, Tao
Kuner, Thomas
Yue, David T.
Wu, Ling-Gang
TI Calcium-channel number critically influences synaptic strength and
plasticity at the active zone
SO NATURE NEUROSCIENCE
LA English
DT Article
ID READILY RELEASABLE POOL; CALYX-TYPE SYNAPSE; FAST CNS SYNAPSE;
TRANSMITTER RELEASE; CA2+ CHANNELS; NEUROTRANSMITTER RELEASE;
PRESYNAPTIC CAPACITANCE; DETERMINES FAST; TRAPEZOID BODY; MEDIAL NUCLEUS
AB How synaptic-vesicle release is controlled at the basic release structure, the active zone, is poorly understood. By performing cell-attached current and capacitance recordings predominantly at single active zones in rat calyces, we found that single active zones contained 5-218 (mean, 42) calcium channels and 1-10 (mean, 5) readily releasable vesicles (RRVs) and released 0-5 vesicles during a 2-ms depolarization. Large variation in the number of calcium channels caused wide variation in release strength (measured during a 2-ms depolarization) by regulating the RRV release probability (P-RRV) and the RRV number. Consequently, an action potential opened similar to 1-35 (mean, similar to 7) channels, resulting in different release probabilities at different active zones. As the number of calcium-channels determined P-RRV, it critically influenced whether subsequent release would be facilitated or depressed. Regulating calcium channel density at active zones may thus be a major mechanism to yield synapses with different release properties and plasticity. These findings may explain large differences reported at synapses regarding release strength (release of 0,1 or multiple vesicles), P-RRV, short-term plasticity, calcium transients and the requisite calcium-channel number for triggering release.
C1 [Sheng, Jiansong; He, Liming; Xue, Lei; Luo, Fujun; Shin, Wonchul; Sun, Tao; Wu, Ling-Gang] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[Zheng, Hongwei] Heidelberg Univ, Interdisciplinary Ctr Sci Comp, Inst Pharmacol, Heidelberg, Germany.
[Zheng, Hongwei; Kuner, Thomas] Heidelberg Univ, Inst Anat & Cell Biol, Heidelberg, Germany.
[Yue, David T.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
[Yue, David T.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Wu, LG (reprint author), Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
EM wul@ninds.nih.gov
RI Luo, Fujun/I-1016-2013; SHENG, JIANSONG/K-1914-2013
FU US National Institute of Neurological Disorders and Stroke Intramural
Research Program
FX We thank K. Ritzier and J. Lubke for providing the electron microscopy
data for analysis, and J. Diamond, J. Xu and M. Baydyuk for comments on
the manuscript. This work was supported by the US National Institute of
Neurological Disorders and Stroke Intramural Research Program.
NR 50
TC 52
Z9 52
U1 4
U2 14
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 JUL
PY 2012
VL 15
IS 7
BP 998
EP 1006
DI 10.1038/nn.3129
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 966EE
UT WOS:000305819600018
PM 22683682
ER
PT J
AU Rapisarda, A
Melillo, G
AF Rapisarda, Annamaria
Melillo, Giovanni
TI Overcoming disappointing results with antiangiogenic therapy by
targeting hypoxia
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Review
ID PHASE-III TRIAL; METASTATIC COLORECTAL-CANCER; RENAL-CELL CARCINOMA;
BEVACIZUMAB PLUS IRINOTECAN; UNFOLDED PROTEIN RESPONSE; ANTI-ANGIOGENIC
THERAPY; DNA-DAMAGE RESPONSE; BREAST-CANCER; GROWTH-FACTOR; TUMOR-GROWTH
AB Cancer cells rely on angiogenesis to fulfil their need for oxygen and nutrients; hence, agents targeting angiogenic pathways and mediators have been investigated as potential cancer drugs. Although this strategy has demonstrated delayed tumour progression-leading to progression-free survival and overall survival benefits compared with standard therapy-in some patients, the results are more modest than predicted. A significant number of patients either do not respond to antiangiogenic agents or fairly rapidly develop resistance to them, which raises questions about how resistance develops and how it can be overcome. Furthermore, whether cancers, once they develop resistance, become more invasive or lead to metastatic disease remains unclear. Several mechanisms of resistance have been recently proposed and emerging evidence indicates that, under certain experimental conditions, antiangiogenic agents increase intratumour hypoxia by promoting vessel pruning and inhibiting neoangiogenesis. Indeed, several studies have highlighted the possibility that inhibitors of VEGF (and its receptors) can promote an invasive metastatic switch, in part by creating an increasingly hypoxic tumour microenvironment. As a potential remedy, a number of therapeutic approaches have been investigated that target the hypoxic tumour compartment to improve the clinical outcome of antiangiogenic therapy.
C1 [Melillo, Giovanni] Bristol Myers Squibb Co, Discovery Med Oncol, Princeton, NJ 08540 USA.
[Rapisarda, Annamaria] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Melillo, G (reprint author), Bristol Myers Squibb Co, Discovery Med Oncol, Rt 206 & Prov Line Rd, Princeton, NJ 08540 USA.
EM giovanni.melillo@bms.com
FU National Cancer Institute, NIH [N01-CO12400]; Developmental Therapeutics
Program, DCTD, of the National Cancer Institute, NIH
FX The authors would like to thank Nicole Fer and Monica Mancini for their
helpful discussions. This study was supported in part with federal funds
from the National Cancer Institute, NIH, under Contract No. N01-CO12400.
The content of this publication does not necessarily reflect the views
or policies of the US Department of Health and Human Services. Any
mention of trade names, commercial products or specific organizations
does not imply endorsement by the US Government. This research was
supported (in part) by the Developmental Therapeutics Program, DCTD, of
the National Cancer Institute, NIH.
NR 151
TC 71
Z9 72
U1 0
U2 33
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 JUL
PY 2012
VL 9
IS 7
BP 378
EP 390
DI 10.1038/nrclinonc.2012.64
PG 13
WC Oncology
SC Oncology
GA 967MF
UT WOS:000305911400005
PM 22525710
ER
PT J
AU Hurley, JH
Bonifacino, JS
AF Hurley, James H.
Bonifacino, Juan S.
TI Nef-arious goings-on at the Golgi
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Editorial Material
AB HIV-1 avoids the immune detection of infected cells by preventing class I molecules of the major histocompatibility complex (MHC-I) bound to viral peptides from reaching the cell surface. A new structure shows how Nef turns MHC-I from a noncargo into a cargo for the clathrin adaptor AP-1, thus directing MHC-I to the lysosome instead of the plasma membrane.
C1 [Hurley, James H.] NIDDK, Mol Biol Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, US Natl Inst Hlth, Bethesda, MD USA.
RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM james.hurley@nih.gov; juan@helix.nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370
NR 7
TC 1
Z9 1
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD JUL
PY 2012
VL 19
IS 7
BP 661
EP 662
DI 10.1038/nsmb.2304
PG 3
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 970DA
UT WOS:000306107100003
PM 22767237
ER
PT J
AU Gamaldo, AA
An, Y
Allaire, JC
Triolo, MHK
Zonderman, AB
AF Gamaldo, Alyssa A.
An, Yang
Allaire, Jason C.
Triolo, Melissa H. Kitner
Zonderman, Alan B.
TI Variability in Performance: Identifying Early Signs of Future Cognitive
Impairment
SO NEUROPSYCHOLOGY
LA English
DT Article
DE cognitive impairment; dementia; neuropsychological tests; cognition;
variability
ID WITHIN-PERSON VARIABILITY; ALZHEIMERS-DISEASE; INTRAINDIVIDUAL
VARIABILITY; NEUROPSYCHOLOGICAL TESTS; DEMENTIA; ADULTS; DIAGNOSIS; TASK
AB Objective: The current study examined whether year-to-year variability in cognitive performance differ between individuals cognitively unimpaired and individuals who subsequently develop dementia. Method: Analyses included a case-control sample of Baltimore Longitudinal Study of Aging (BLSA; mean [M] age = 69.90, standard deviation [SD] = 8.92) participants. One hundred and 35 clinically diagnosed demented participants were matched with 135 nondemented participants based on age at initial testing and sex. Cognitive performance was examined using measures of memory, executive function, attention, language, and global mental status performance. Cognitive performance was examined from baseline to 5 years before cognitive impairment (M, assessments = 3.03, SD = 2.80). Results: As compared with unimpaired individuals, individuals diagnosed with dementia had greater variability on measures of attention, executive function, language, and semantic memory at least 5 years before the estimated onset of cognitive impairment, which may be indicative of maladaptive cognitive functioning. The dementia cases, however, had less variability on visual memory than the unimpaired group, which may suggest that these cases had more difficulty learning. Conclusions: These results demonstrate that performance variability indexed over annual or biennial visits may be useful in identifying early signs of subsequent cognitive impairment.
C1 [Gamaldo, Alyssa A.; An, Yang; Triolo, Melissa H. Kitner; Zonderman, Alan B.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA.
[Allaire, Jason C.] N Carolina State Univ, Dept Psychol, Raleigh, NC 27695 USA.
RP Gamaldo, AA (reprint author), NIA, Lab Behav Neurosci, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM Alyssa.Gamaldo@nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU Intramural NIH HHS [Z01 AG000185-18]
NR 33
TC 9
Z9 9
U1 1
U2 19
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0894-4105
J9 NEUROPSYCHOLOGY
JI Neuropsychology
PD JUL
PY 2012
VL 26
IS 4
BP 534
EP 540
DI 10.1037/a0028686
PG 7
WC Psychology, Clinical; Neurosciences; Psychology
SC Psychology; Neurosciences & Neurology
GA 969DQ
UT WOS:000306036300014
PM 22746310
ER
PT J
AU Basuli, F
Wu, HT
Shi, ZD
Teng, B
Li, C
Sulima, A
Bate, A
Young, P
McMillan, M
Griffiths, GL
AF Basuli, Falguni
Wu, Haitao
Shi, Zhen-Dan
Teng, Bao
Li, Changhui
Sulima, Agnieszka
Bate, Aaron
Young, Philip
McMillan, Mathew
Griffiths, Gary L.
TI Synthesis of ApoSense compound [F-18]2-(5-(dimethylamino)
naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid ([F-18] NST732)
by nucleophilic ring opening of an aziridine precursor
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
ID EXPERIMENTAL CEREBRAL STROKE; PROGRAMMED CELL-DEATH; ALPHA-AMINO-ACIDS;
IN-VIVO DETECTION; ANNEXIN-V; PHOSPHATIDYLSERINE EXPOSURE; INDUCED
APOPTOSIS; IMAGING AGENT; CANCER; PET
AB Introduction: The small molecule 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid (NST732) is a member of the ApoSense family of compounds, capable of selective targeting, binding and accumulation within cells undergoing apoptotic cell death. It has application in molecular imaging and blood clotting particularly for monitoring antiapoptotic drug treatments. We are investigating a fluorine-18-radiolabeled analog of this compound for positron emission tomography studies.
Methods: We prepared the tosylate precursor methyl 2-(5-(dimethylamino)naphthalene-l-sulfonamido)-2-(tosyloxymethyl)butanoate (4) to synthesize fluorine-18-labeled NST732. Fluorination reaction of the tosylate precursor in 1:1 acetonitrile:dimethylsulfoxide with tetrabutyl ammonium fluoride proceeds through an aziridine intermediate (4A) to afford two regioisomers: 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-fluorcbutanoate (5) and methyl 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoate (6). Acid hydrolysis of the fluoromethylbutanoate (6) isomer produced NST732. As the fluorination reaction of the tosylate precursor proceeds through an aziridine intermediate (4A) and the fluorination conceivably could be done directly on the aziridine, we have separately prepared an aziridine precursor (4A). Fluorine-18 labeling of the aziridine precursor (4A) was performed with [F-18]tetrabutyl ammonium fluoride to afford the same two regioisomers (5 and 6). The [F-18]2((5-dimethylamino)naphthalene-1-sulfonamidolmethyl)-2-fluorobutanoic acid (NST732) was then obtained by the hydrolysis of corresponding [F-18]-labeled ester (6) with 6 N hydrochloric acid.
Results: Two regioisomers obtained from the fluorination reaction of aziridine were easily separated by high-performance liquid chromatography. The total radiochemical yield was 15%+/-3% (uncorrected, n=18) from the aziridine precursor in a 70-min synthesis time with a radiochemical purity >99%.
Conclusion: Fluorine-18-labeled ApoSense compound [F-18]NST732 is prepared in moderate yield by direct fluorination of an aziridine precursor. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Basuli, Falguni; Wu, Haitao; Shi, Zhen-Dan; Teng, Bao; Li, Changhui; Sulima, Agnieszka; Bate, Aaron; Young, Philip; McMillan, Mathew; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA.
RP Basuli, F (reprint author), NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA.
EM bhattacharyyaf@mail.nih.gov
FU National Institutes of Health through Roadmap for Medical Research
initiative
FX The authors would like to thank Christine Enders for her excellent
technical assistance. This study was funded by National Institutes of
Health through its 2004 Roadmap for Medical Research initiative.
NR 51
TC 4
Z9 4
U1 1
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD JUL
PY 2012
VL 39
IS 5
BP 687
EP 696
DI 10.1016/j.nucmedbio.2011.12.008
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 969BZ
UT WOS:000306032000012
PM 22336374
ER
PT J
AU Bhattacharjee, S
Chatterjee, S
Jiang, JJ
Sinha, BK
Mason, RP
AF Bhattacharjee, Suchandra
Chatterjee, Saurabh
Jiang, JinJie
Sinha, Birandra Kumar
Mason, Ronald P.
TI Detection and imaging of the free radical DNA in cells-Site-specific
radical formation induced by Fenton chemistry and its repair in cellular
DNA as seen by electron spin resonance, immuno-spin trapping and
confocal microscopy
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID UNIMOLECULAR TRANSFORMATION REACTIONS; AQUEOUS-SOLUTION;
HYDROGEN-PEROXIDE; CHARGE-TRANSPORT; EXCISION-REPAIR; OH ADDUCTS;
ADENINE; CARCINOGENESIS; INHIBITION; DAMAGE
AB Oxidative stress-related damage to the DNA macromolecule produces lesions that are implicated in various diseases. To understand damage to DNA, it is important to study the free radical reactions causing the damage. Measurement of DNA damage has been a matter of debate as most of the available methods measure the end product of a sequence of events and provide limited information on the initial free radical formation. We report a measurement of free radical damage in DNA induced by a Cu(II)-H2O2 oxidizing system using immuno-spin trapping supplemented with electron paramagnetic resonance. In this investigation, the short-lived radical generated is trapped by the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) immediately upon formation. The DMPO adduct formed is initially electron paramagnetic resonance active, but is subsequently oxidized to the stable nitrone adduct, which can be detected and visualized by immuno-spin trapping and has the potential to be further characterized by other analytical techniques. The radical was found to be located on the 2'-deoxyadenosine (dAdo) moiety of DNA. The nitrone adduct was repaired on a time scale consistent with DNA repair. In vivo experiments for the purpose of detecting DMPO-DNA nitrone adducts should be conducted over a range of time in order to avoid missing adducts due to the repair processes.
C1 [Bhattacharjee, Suchandra; Chatterjee, Saurabh; Jiang, JinJie; Sinha, Birandra Kumar; Mason, Ronald P.] NIEHS, Lab Toxicol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
RP Bhattacharjee, S (reprint author), NIEHS, Lab Toxicol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM bhattac1@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences
FX Funding for open access charge: Intramural Research Program of the
National Institutes of Health and the National Institute of
Environmental Health Sciences.
NR 48
TC 8
Z9 8
U1 0
U2 19
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL
PY 2012
VL 40
IS 12
BP 5477
EP 5486
DI 10.1093/nar/gks180
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 966HR
UT WOS:000305829000032
PM 22387463
ER
PT J
AU Kumar, KG
Zhang, JY
Gao, S
Rossi, J
McGuinness, OP
Halem, HH
Culler, MD
Mynatt, RL
Butler, AA
AF Kumar, K. Ganesh
Zhang, Jingying
Gao, Su
Rossi, Jari
McGuinness, Owen P.
Halem, Heather H.
Culler, Michael D.
Mynatt, Randall L.
Butler, Andrew A.
TI Adropin Deficiency Is Associated With Increased Adiposity and Insulin
Resistance
SO OBESITY
LA English
DT Article
ID LIPID-METABOLISM; FATTY LIVER; PPAR-ALPHA; IN-VIVO; MOUSE; MICE;
FIBROBLAST-GROWTH-FACTOR-21; INDUCTION; SECRETION; DISEASE
AB Adropin is a secreted peptide that improves hepatic steatosis and glucose homeostasis when administered to diet-induced obese mice. It is not clear if adropin is a peptide hormone regulated by signals of metabolic state. Moreover, the significance of a decline in adropin expression with obesity with respect to metabolic disease is also not clear. We investigated the regulation of serum adropin by metabolic status and diet. Serum adropin levels were high in chow-fed conditions and were suppressed by fasting and diet-induced obesity (DIO). High adropin levels were observed in mice fed a high-fat low carbohydrate diet, whereas lower levels were observed in mice fed a low-fat high carbohydrate diet. To investigate the role of adropin deficiency in metabolic homeostasis, we generated adropin knockout mice (AdrKO) on the C57BL/6J background. AdrKO displayed a 50%-increase in increase in adiposity, although food intake and energy expenditure were normal. AdrKO also exhibited dyslipidemia and impaired suppression of endogenous glucose production (EndoR(a)) in hyperinsulinemic-euglycemic clamp conditions, suggesting insulin resistance. While homo-and heterozygous carriers of the null adropin allele exhibited normal DIO relative to controls, impaired glucose tolerance associated with weight gain was more severe in both groups. In summary, adropin is a peptide hormone regulated by fasting and feeding. In fed conditions, adropin levels are regulated dietary macronutrients, and increase with dietary fat content. Adropin is not required for regulating food intake, however, its functions impact on adiposity and are involved in preventing insulin resistance, dyslipidemia, and impaired glucose tolerance.
C1 [Kumar, K. Ganesh; Gao, Su; Rossi, Jari; Butler, Andrew A.] Scripps Res Inst, Dept Metab & Aging, Jupiter, FL USA.
[Zhang, Jingying; Mynatt, Randall L.] Louisiana State Univ Syst, Transgen Core Lab, Pennington Biomed Res Ctr, Baton Rouge, LA USA.
[McGuinness, Owen P.] Vanderbilt Univ, Sch Med, Vanderbilt NIDDK Mouse Metab Phenotyping Ctr, Nashville, TN 37212 USA.
[Halem, Heather H.; Culler, Michael D.] Biomeasure Inc, IPSEN, Milford, MA USA.
RP Butler, AA (reprint author), Scripps Res Inst, Dept Metab & Aging, Jupiter, FL USA.
EM AButler@scripps.edu
RI Gao, Su/E-6864-2016;
OI Gao, Su/0000-0002-0403-5783; Rossi, Jari/0000-0002-3728-9800
FU American Diabetes Association [1-04-JF09, 07-08-RA-16]; Pennington
Biomedical Research Foundation; Biomeasure, Inc. IPSEN; State of
Florida; Vanderbilt MMPC [DK59637]; Vanderbilt Diabetes Research and
Training Center [DK020693]; Clinical Nutrition Research Unit Center
[1P30 DK072476]; National Institute of Diabetes and Digestive and Kidney
Diseases
FX We thank Dr Danielle Skorupa for assistance with manuscript production.
This work was supported provided by grants from the American Diabetes
Association (1-04-JF09 and 07-08-RA-16), The Pennington Biomedical
Research Foundation, a sponsored research agreement from Biomeasure,
Inc. IPSEN, and the State of Florida to A.A.B.; Vanderbilt MMPC DK59637
and Vanderbilt Diabetes Research and Training Center DK020693. A.A.B.
and R.L.M. were partially supported provided by the Clinical Nutrition
Research Unit Center Grant (1P30 DK072476) entitled "Nutritional
Programming: Environmental and Molecular Interactions" sponsored by
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 28
TC 38
Z9 38
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD JUL
PY 2012
VL 20
IS 7
BP 1394
EP 1402
DI 10.1038/oby.2012.31
PG 9
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 966LW
UT WOS:000305840200010
ER
PT J
AU Lipsky, LM
Strawderman, MS
Olson, CM
AF Lipsky, Leah M.
Strawderman, Myla S.
Olson, Christine M.
TI Maternal Weight Change Between 1 and 2 Years Postpartum: The Importance
of 1 Year Weight Retention
SO OBESITY
LA English
DT Article
ID BODY-WEIGHT; PSYCHOSOCIAL FACTORS; RELATIVE IMPORTANCE; EARLY-PREGNANCY;
BIRTH-WEIGHT; GAIN; WOMEN; OBESITY; OVERWEIGHT; RISK
AB Pregnancy weight gain may lead to long-term increases in maternal BMI for some women. The objective of this study was to examine maternal body weight change 1y-2y postpartum, and to compare classifications of 2y weight retention with and without accounting for 1y-2y weight gain. Early pregnancy body weight (EPW, first trimester) was measured or imputed, and follow-up measures obtained before delivery, 1 year postpartum (1y) and 2 years postpartum (2y) in an observational cohort study of women seeking prenatal care in several counties in upstate New York (n = 413). Baseline height was measured; demographic and behavioral data were obtained from questionnaires and medical records. Associations of 1y-2y weight change (kg) and 1y-2y weight gain (>= 2.25 kg) with anthropometric, socioeconomic, and behavioral variables were evaluated using linear and logistic regressions. While mean +/- SE 1y-2y weight change was 0.009 +/- 4.6 kg, 1y-2y weight gain (>= 2.25 kg) was common (n = 108, 26%). Odds of weight gain 1y-2y were higher for overweight (ORadj = 2.63, CI95% = 1.43-4.82) and obese (ORadj = 2.93, CI95% = 1.62-5.27) women than for women with BMI <25. Two year weight retention (2y-EPW >= 2.25 kg) was misclassified in 38% (n = 37) of women when 1y-2y weight gain was ignored. One year weight retention (1YWR) (1y-EPW) was negatively related to 1y-2y weight change (beta(adj) +/- SE = -0.28 +/- 0.04, P < 0.001) and weight gain (>= 2.25 kg) (ORadj = 0.91, CI95% = 0.87-0.95). Relations between 1y weight retention and 1y-2y weight change were attenuated for women with higher early pregnancy BMI. Weight change 1y-2y was predicted primarily by an inverse relation with 1y weight retention. The high frequency of weight gain has important implications for classification of postpartum weight retention.
C1 [Lipsky, Leah M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Strawderman, Myla S.; Olson, Christine M.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
RP Lipsky, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
EM lipskylm@mail.nih.gov
OI Lipsky, Leah/0000-0003-2645-4388
FU NIH [HD29549]; Cornell University; Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX The authors thank Dr Kathleen Rasmussen, Dr Jeffery Sobal, Dr David Just
and Dr Tonja Nansel for their helpful comments. This research was funded
by NIH grant # HD29549, Cornell University and the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development.
NR 41
TC 13
Z9 16
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD JUL
PY 2012
VL 20
IS 7
BP 1496
EP 1502
DI 10.1038/oby.2012.41
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 966LW
UT WOS:000305840200024
PM 22334257
ER
PT J
AU Ambalavanan, N
Carlo, WA
Tyson, JE
Langer, JC
Walsh, MC
Parikh, NA
Das, A
Van Meurs, KP
Shankaran, S
Stoll, BJ
Higgins, RD
AF Ambalavanan, Namasivayam
Carlo, Waldemar A.
Tyson, Jon E.
Langer, John C.
Walsh, Michele C.
Parikh, Nehal A.
Das, Abhik
Van Meurs, Krisa P.
Shankaran, Seetha
Stoll, Barbara J.
Higgins, Rosemary D.
CA Generic Database Follow-Up Subcomm
TI Outcome Trajectories in Extremely Preterm Infants
SO PEDIATRICS
LA English
DT Article
DE logistic models; premature infant; predictive value of tests; prognosis
ID BIRTH-WEIGHT INFANTS; EXTREMELY PREMATURE-INFANTS; WEEKS GESTATION;
NEURODEVELOPMENTAL OUTCOMES; INTRAVENTRICULAR HEMORRHAGE;
BRONCHOPULMONARY DYSPLASIA; CRANIAL ULTRASOUND; CEREBRAL-PALSY;
INTENSIVE-CARE; DEATH
AB OBJECTIVE: Methods are required to predict prognosis with changes in clinical course. Death or neurodevelopmental impairment in extremely premature neonates can be predicted at birth/admission to the ICU by considering gender, antenatal steroids, multiple birth, birth weight, and gestational age. Predictions may be improved by using additional information available later during the clinical course. Our objective was to develop serial predictions of outcome by using prognostic factors available over the course of NICU hospitalization.
METHODS: Data on infants with birth weight <= 1.0 kg admitted to 18 large academic tertiary NICUs during 1998-2005 were used to develop multivariable regression models following stepwise variable selection. Models were developed by using all survivors at specific times during hospitalization (in delivery room [n = 8713], 7-day [n = 6996], 28-day [n = 6241], and 36-week postmenstrual age [n = 5118]) to predict death or death/neurodevelopmental impairment at 18 to 22 months.
RESULTS: Prediction of death or neurodevelopmental impairment in extremely premature infants is improved by using information available later during the clinical course. The importance of birth weight declines, whereas the importance of respiratory illness severity increases with advancing postnatal age. The c-statistic in validation models ranged from 0.74 to 0.80 with misclassification rates ranging from 0.28 to 0.30.
CONCLUSIONS: Dynamic models of the changing probability of individual outcome can improve outcome predictions in preterm infants. Various current and future scenarios can be modeled by input of different clinical possibilities to develop individual "outcome trajectories" and evaluate impact of possible morbidities on outcome. Pediatrics 2012;130:e115-e125
C1 [Ambalavanan, Namasivayam] Univ Alabama Birmingham, Women & Infants Ctr, Dept Pediat, Birmingham, AL 35249 USA.
[Tyson, Jon E.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
[Langer, John C.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Parikh, Nehal A.] Nationwide Childrens Hosp, Ctr Perinatal Res, Columbus, OH USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA.
[Van Meurs, Krisa P.] Lucile Packard Childrens Hosp, Palo Alto, CA USA.
[Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30303 USA.
[Stoll, Barbara J.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Ambalavanan, N (reprint author), Univ Alabama Birmingham, Women & Infants Ctr, Dept Pediat, 176F Suite 9380,619 S 20th St, Birmingham, AL 35249 USA.
EM ambal@uab.edu
OI Ambalavanan, Namasivayam/0000-0003-0731-9092
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Child Health and Human Development;
Department of Health and Human Services [U10 HD21364, U10 HD21373, U10
HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10
HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10
HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10 HD40498, U10
HD40521, U10 HD40689]; National Institutes of Health [UL1 RR24139, UL1
RR24160, UL1 RR25008, M01 RR30, M01 RR32, M01 RR39, M01 RR44, M01 RR70,
M01 RR80, M01 RR125, M01 RR633, M01 RR750, M01 RR997, M01 RR6022, M01
RR7122, M01 RR8084, M01 RR16587]; National Institutes of Health (NIH)
FX The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development provided grant
support for the Neonatal Research Network's Generic Database Study and
Follow-up Study. The authors were supported by grants from the National
Institute of Child Health and Human Development and the Department of
Health and Human Services (U10 HD21364, U10 HD21373, U10 HD21385, U10
HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10
HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34216, U10
HD36790, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40521, and U10
HD40689) and from the National Institutes of Health (UL1 RR24139, UL1
RR24160, UL1 RR25008, M01 RR30, M01 RR32, M01 RR39, M01 RR44, M01 RR70,
M01 RR80, M01 RR125, M01 RR633, M01 RR750, M01 RR997, M01 RR6022, M01
RR7122, M01 RR8084, and M01 RR16587). Funded by the National Institutes
of Health (NIH).
NR 29
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Z9 23
U1 2
U2 8
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD JUL
PY 2012
VL 130
IS 1
BP E115
EP E125
DI 10.1542/peds.2011-3693
PG 11
WC Pediatrics
SC Pediatrics
GA 967KH
UT WOS:000305905900016
PM 22689874
ER
PT J
AU Wendler, D
AF Wendler, David
TI The ethics of studying subjects in non-ideal circumstances
SO TOBACCO CONTROL
LA English
DT Editorial Material
C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Wendler, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM dwendler@nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0964-4563
J9 TOB CONTROL
JI Tob. Control
PD JUL
PY 2012
VL 21
IS 4
BP 385
EP 386
DI 10.1136/tobaccocontrol-2012-050620
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 965WZ
UT WOS:000305799600005
PM 22730459
ER
PT J
AU Sarsour, K
Johnston, JA
Milton, DR
Duhig, A
Melfi, C
Moss, HB
AF Sarsour, Khaled
Johnston, Joseph A.
Milton, Denai R.
Duhig, Amy
Melfi, Catherine
Moss, Howard B.
TI Factors Predicting Change in Frequency of Heavy Drinking Days among
Alcohol-Dependent Participants in the National Epidemiologic Survey on
Alcohol and Related Conditions (NESARC)
SO ALCOHOL AND ALCOHOLISM
LA English
DT Article
ID UNITED-STATES; MAJOR DEPRESSION; NICOTINE DEPENDENCE; USE DISORDERS;
TOBACCO SMOKING; BINGE DRINKING; OLDER-ADULTS; CONSUMPTION; ABUSE;
PREVALENCE
AB Aims: To discover the predictors of change in the frequency of heavy drinking (HD) over a 4-year period in alcohol dependent (AD)-individuals identified in the general population, namely, among participants of the US National Epidemiologic Survey on Alcohol and Related Conditions interviewed at Wave 1 (2001-2002) and at Wave 2 (2004-2005). Methods: The study cohort included subjects meeting DSM-IV criteria for AD in the past year at Wave 1 (n = 1484), who were present at Wave 2 (n = 1172) and had complete data on factors of interest (n = 1123). Frequency of HD was defined as the number of HD days (HDD) (>= 5 drinks per day for men and >= 4 for women). Change in frequency of HDD from baseline (Wave 1) to similar to 3 years later (Wave 2) was determined. An analysis of covariance model (ANCOVA), adjusting for baseline HDD, was used to examine individual factors associated with change in frequency of HDD, while a multivariable regression model was employed to assess factors associated with change in frequency of HDD simultaneously. Results: Overall, there was a decrease in mean (SE) HDD [from 119.4 (1.8) at Wave 1 to 82.5 (2.1) at Wave 2, P < 0.0001]. Compared with smokers, non-smokers had a mean (SE) HDD reduction of 13.4 (6.7), P < 0.05. AD criteria of tolerance was significantly associated (P < 0.05) with less reduction in HDD. Change in depression/dysthymia status was associated with greater reduction in HDD in the ANCOVA model, but not the fully adjusted multivariable model. Conclusion: Findings from this study suggest that smoking and AD criteria of tolerance are important factors for long-term follow-up of AD patients and they should influence the selection of the kinds of interventions required for AD patients to achieve maximal therapeutic benefit.
C1 [Sarsour, Khaled; Johnston, Joseph A.; Milton, Denai R.; Melfi, Catherine] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA.
[Duhig, Amy] Abbott Labs, N Chicago, IL 60064 USA.
[Moss, Howard B.] NIAAA, Bethesda, MD USA.
RP Sarsour, K (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, DC 1833, Indianapolis, IN 46285 USA.
EM sarsour_khaled@lilly.com
NR 46
TC 4
Z9 4
U1 4
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0735-0414
J9 ALCOHOL ALCOHOLISM
JI Alcohol Alcohol.
PD JUL-AUG
PY 2012
VL 47
IS 4
BP 443
EP 450
DI 10.1093/alcalc/ags036
PG 8
WC Substance Abuse
SC Substance Abuse
GA 963NX
UT WOS:000305629400014
PM 22493046
ER
PT J
AU Fung, GJ
Steffen, LM
Zhou, X
Harnack, L
Tang, WH
Lutsey, PL
Loria, CM
Reis, JP
Van Horn, LV
AF Fung, Grace J.
Steffen, Lyn M.
Zhou, Xia
Harnack, Lisa
Tang, Weihong
Lutsey, Pamela L.
Loria, Catherine M.
Reis, Jared P.
Van Horn, Linda V.
TI Vitamin D intake is inversely related to risk of developing metabolic
syndrome in African American and white men and women over 20 y: the
Coronary Artery Risk Development in Young Adults study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR-DISEASE RISK; D
SUPPLEMENTATION; PARATHYROID-HORMONE; 25-HYDROXYVITAMIN D;
INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; BLOOD-PRESSURE; D DEFICIENCY; US
ADULTS
AB Background: Vitamin D intake may play a key role in the prevention of cardiovascular disease.
Objective: We evaluated associations of dietary and supplemental vitamin D intake with the 20-y incidence of metabolic syndrome.
Design: Data from 4727 black and white young men and women from the Coronary Artery Risk Development in Young Adults study were used to examine relations of dietary plus supplemental vitamin D intake with the incidence of metabolic syndrome (as defined by Adult Treatment Panel, third report, guidelines) and the prevalence of its components, including abdominal obesity, elevated blood pressure, and high glucose, low HDL, and high:triglyceride concentrations.
Results: The intake of vitamin D from dietary and supplemental sources was inversely related to the 20-y cumulative prevalence of abdominal obesity (P = 0.05) and high glucose (P = 0.02) and low HDL (P = 0.004) concentrations after adjustment for age, sex, race, education, center, and energy intake. In comparison with the lowest intake quintile (quintile 1), HRs (95% CIs) of developing incident metabolic syndrome for quintiles 2-5 of vitamin D intake were 0.82 (0.67, 1.00), 0.84 (0.68, 1.03), 0.70 (0.56, 0.88), and 0.82 (95% CI: 0.65, 1.02), respectively (P-trend = 0.03) after adjustment for demographic and lifestyle factors.
Conclusions: In young adults, the dietary plus supplemental vitamin D intake was inversely related to the development of incident metabolic syndrome over 20 y of follow-up. These findings support the recommendations of the Dietary Guidelines for Americans to increase intakes of vitamin D rich foods, such as milk and fish. Am J Clin Alum 2012;96:24-9.
C1 [Steffen, Lyn M.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Loria, Catherine M.; Reis, Jared P.] Natl Heart Lung Blood Inst, Div Prevent & Populat Sci, Bethesda, MD USA.
[Van Horn, Linda V.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
RP Steffen, LM (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA.
EM steffen@umn.edu
FU National Heart, Lung, and Blood Institute [N01-HC-48047, N01-HC-48048,
N01-HC-48049, N01-HC-48050, N01-HC-95095, N01-HC-45134]
FX The Coronary Artery Risk Development in Young Adults Study was supported
by the National Heart, Lung, and Blood Institute (contracts
N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095,
and N01-HC-45134).
NR 41
TC 24
Z9 25
U1 1
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 JUL
PY 2012
VL 96
IS 1
BP 24
EP 29
DI 10.3945/ajcn.112.036863
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 964CA
UT WOS:000305670100005
PM 22648727
ER
PT J
AU Fischer, MJ
Xie, DW
Jordan, N
Kop, WJ
Krousel-Wood, M
Tamura, MK
Kusek, JW
Ford, V
Rosen, LK
Strauss, L
Teal, VL
Yaffe, K
Powe, NR
Lash, JP
AF Fischer, Michael J.
Xie, Dawei
Jordan, Neil
Kop, Willem J.
Krousel-Wood, Marie
Tamura, Manjula Kurella
Kusek, John W.
Ford, Virginia
Rosen, Leigh K.
Strauss, Louise
Teal, Valerie L.
Yaffe, Kristine
Powe, Neil R.
Lash, James P.
CA CRIC Study Grp Investigators
TI Factors Associated With Depressive Symptoms and Use of Antidepressant
Medications Among Participants in the Chronic Renal Insufficiency Cohort
(CRIC) and Hispanic-CRIC Studies
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Depression; chronic kidney disease; disparities; antidepressants
ID CHRONIC KIDNEY-DISEASE; QUALITY-OF-LIFE; NATIONAL COMORBIDITY SURVEY;
BASE-LINE CHARACTERISTICS; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS;
PRIMARY-CARE; AFRICAN-AMERICANS; MAJOR DEPRESSION; COMMUNITY SAMPLE
AB Background: Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied.
Study Design: Cross-sectional analysis.
Settings & Participants: Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008.
Measurement: Depressive symptoms measured by Beck Depression Inventory (BDI).
Predictors: Demographic and clinical factors.
Outcomes: Elevated depressive symptoms (BDI score >= 11) and antidepressant medication use.
Results: Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73 m(2) and 33.8% of those with eGFR <30 mL/min/1.73 m(2). Lower eGFR (OR per 10-mL/min/1.73 m(2) decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each).
Limitations: Absence of clinical diagnosis of depression and use of nonpharmacologic treatments.
Conclusions: Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a greater burden of elevated depressive symptoms and lower use of antidepressant medications. Am J Kidney Dis. 60(1): 27-38. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.
C1 [Fischer, Michael J.; Lash, James P.] Univ Illinois, Med Ctr, Chicago, IL USA.
[Fischer, Michael J.; Lash, James P.] Jesse Brown VA Med Ctr, Chicago, IL USA.
[Xie, Dawei; Ford, Virginia; Rosen, Leigh K.; Teal, Valerie L.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Jordan, Neil] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Kop, Willem J.] Univ Maryland, Baltimore, MD 21201 USA.
[Kop, Willem J.] Tilburg Univ, NL-5000 LE Tilburg, Netherlands.
[Krousel-Wood, Marie] Tulane Univ, New Orleans, LA 70118 USA.
[Krousel-Wood, Marie] Ochsner Clin Fdn, Ctr Hlth Res, New Orleans, LA USA.
[Tamura, Manjula Kurella] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[Kusek, John W.] NIDDK, NIH, Bethesda, MD USA.
[Strauss, Louise] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA.
[Yaffe, Kristine; Powe, Neil R.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
[Powe, Neil R.] San Francisco Gen Hosp, San Francisco, CA 94110 USA.
[Fischer, Michael J.; Jordan, Neil] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA.
RP Fischer, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, 5000 S 5th Ave 151H, Hines, IL 60141 USA.
EM fischerm@uic.edu
RI Krousel-Wood, Marie Antoinette/D-4718-2011; Kurella Tamura,
Manjula/C-8284-2014
OI Kurella Tamura, Manjula/0000-0001-5227-2479
FU National Institute of Diabetes and Digestive and Kidney Diseases
[5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028,
5U01DK60980, 5U01DK060963, 5U01DK060902, R01 DK072231]; Clinical
Translational Science Awards (CTSA); National Institutes of Health (NIH)
Johns Hopkins University [UL1 RR-025005]; National Institutes of Health
(NIH) University of Maryland GRCR [M01 RR-16500]; National Institutes of
Health (NIH) Case Western Reserve University Clinical and Translational
Science Collaborative (University Hospitals of Cleveland, Cleveland
Clinic Foundation, and MetroHealth) [UL1 RR-024989]; National Institutes
of Health (NIH) University of Michigan GCRC [M01 RR-000042, CTSA UL1
RR-024986]; National Institutes of Health (NIH) University of Illinois
at Chicago Clinical Research Center [M01 RR-013987-06]; National
Institutes of Health (NIH) Tulane/LSU/Charity Hospital General Clinical
Research Center [RR-05096]; National Institutes of Health (NIH) Kaiser
NIH/National Center for Research Resources UCSF-CTSI [UL1 RR-024131,
5K24DK002651]
FX In addition to funding under a cooperative agreement from the National
Institute of Diabetes and Digestive and Kidney Diseases (5U01DK060990,
5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980,
5U01DK060963, and 5U01DK060902) and R01 DK072231 (H-CRIC), this work was
supported in part by the following institutional Clinical Translational
Science Awards (CTSA) and other National Institutes of Health (NIH)
grants: Johns Hopkins University UL1 RR-025005, University of Maryland
GRCR M01 RR-16500, Case Western Reserve University Clinical and
Translational Science Collaborative (University Hospitals of Cleveland,
Cleveland Clinic Foundation, and MetroHealth) UL1 RR-024989, University
of Michigan GCRC M01 RR-000042, CTSA UL1 RR-024986, University of
Illinois at Chicago Clinical Research Center, M01 RR-013987-06,
Tulane/LSU/Charity Hospital General Clinical Research Center RR-05096,
and Kaiser NIH/National Center for Research Resources UCSF-CTSI UL1
RR-024131, 5K24DK002651. Additional support provided by the National
Center for Minority Health and Health Disparities, NIH, and Department
of Veterans Affairs Health Services Research and Development Service
(Career Development Award to Dr Fischer).
NR 49
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U1 1
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JUL
PY 2012
VL 60
IS 1
BP 27
EP 38
DI 10.1053/j.ajkd.2011.12.033
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA 960RJ
UT WOS:000305406200007
PM 22497791
ER
PT J
AU Davis, DA
Soule, EE
Davidoff, KS
Daniels, SI
Naiman, NE
Yarchoan, R
AF Davis, David A.
Soule, Erin E.
Davidoff, Katharine S.
Daniels, Sarah I.
Naiman, Nicole E.
Yarchoan, Robert
TI Activity of Human Immunodeficiency Virus Type 1 Protease Inhibitors
against the Initial Autocleavage in Gag-Pol Polyprotein Processing
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID NAIVE HIV-1-INFECTED PATIENTS; HIV-1 PROTEASE; DRUG-RESISTANCE;
PHARMACOKINETICS; SAQUINAVIR; MUTATIONS; RITONAVIR; CLEAVAGE;
DIMERIZATION; REPLICATION
AB Inhibitors of HIV protease have proven to be important drugs in combination anti-HIV therapy. These inhibitors were designed to target mature protease and prevent viral particle maturation by blocking Gag and Gag-Pol processing by mature protease. Currently there are few data assessing the ability of these protease inhibitors to block the initial step in autoproteolytic processing of Gag-Pol. This unique step involves the dimerization of two Gag-Pol polyproteins and autocleavage of the Gag-Pol polyprotein by the embedded dimeric protease. We developed a plasmid encoding a modified form of Gag-Pol that can undergo autoprocessing only at the initial cleavage site between p2 and nucleocapsid. Using an in vitro transcription/translation system, we assessed the ability of six different approved protease inhibitors (darunavir, indinavir, nelfinavir, ritonavir, saquinavir, and tipranavir) to block this initial autocleavage step. Of these inhibitors, darunavir and saquinavir were the most effective. Darunavir and saquinavir were also the most effective at blocking the initial autoprocessing of full-length Gag-Pol in HIV-1-infected T cells. Thus, we have identified at least two HIV-1 protease inhibitors that have activity against the primary autocatalytic step of the embedded HIV-1 protease in Gag-Pol at concentrations that may be attained in HIV-1-infected patients. Due to unique aspects of the initial processing step, it may be possible to develop inhibitors with greater potency against this step, thus halting viral maturation at the earliest stages. The transcription/translation assay could be used to develop more potent inhibitors of this essential first step in viral maturation.
C1 [Davis, David A.; Soule, Erin E.; Davidoff, Katharine S.; Daniels, Sarah I.; Naiman, Nicole E.; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Davis, DA (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM dadavis@helix.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 27
TC 10
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U1 1
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 JUL
PY 2012
VL 56
IS 7
BP 3620
EP 3628
DI 10.1128/AAC.00055-12
PG 9
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 964DD
UT WOS:000305673000023
PM 22508308
ER
PT J
AU Hayashi, K
Hooper, LC
Okuno, T
Takada, Y
Hooks, JJ
AF Hayashi, Kozaburo
Hooper, Laura C.
Okuno, Toshiomi
Takada, Yuichiro
Hooks, John J.
TI Inhibition of HSV-1 by chemoattracted neutrophils: supernatants of
corneal epithelial cells (HCE) and macrophages (THP-1) treated with
virus components chemoattract neutrophils (PMN), and supernatants of PMN
treated with these conditioned media inhibit viral growth
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID INFECTION; DIFFERENTIATION; INVOLVEMENT; KERATITIS; DISEASE
AB The role of PMNs (neutrophils) in corneal herpes was studied using an in vitro system. Human corneal cells (HCE) and macrophages (THP-1) infected with HSV-1 or treated with virus components (DNA or virus immune complexes) released chemokines, which attracted PMNs. Highly reactive oxygen species were detected in PMNs. PMNs inhibited HSV when overlaid onto infected HCE cells (50:1). PMNs incubated with the supernatants of HCE cells treated with virus components released H2O2 and myeloperoxidase. These inhibited virus growth. PMNs released NO and MIG, which may differentiate CD4 T cells to Th1. PMNs participate in innate immune responses, limit virus growth, and initiate immunopathology.
C1 [Hayashi, Kozaburo; Hooper, Laura C.; Hooks, John J.] NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Okuno, Toshiomi] Hyogo Coll Med, Dept Microbiol, Nishinomiya, Hyogo, Japan.
RP Hayashi, K (reprint author), NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM kozaburo@yc4.so-net.ne.jp
FU NEI, NIH
FX This was supported (in part) by the Intramural Research Program of NEI,
NIH.
NR 16
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U1 0
U2 0
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
J9 ARCH VIROL
JI Arch. Virol.
PD JUL
PY 2012
VL 157
IS 7
BP 1377
EP 1381
DI 10.1007/s00705-012-1306-y
PG 5
WC Virology
SC Virology
GA 965VL
UT WOS:000305795300019
PM 22527863
ER
PT J
AU Satoh, M
Chan, EKL
Ho, LA
Rose, KM
Parks, CG
Cohn, RD
Jusko, TA
Walker, NJ
Germolec, DR
Whitt, IZ
Crockett, PW
Pauley, BA
Chan, JYF
Ross, SJ
Birnbaum, LS
Zeldin, DC
Miller, FW
AF Satoh, Minoru
Chan, Edward K. L.
Ho, Lindsey A.
Rose, Kathryn M.
Parks, Christine G.
Cohn, Richard D.
Jusko, Todd A.
Walker, Nigel J.
Germolec, Dori R.
Whitt, Irene Z.
Crockett, Patrick W.
Pauley, Brad A.
Chan, Jason Y. F.
Ross, Steven J.
Birnbaum, Linda S.
Zeldin, Darryl C.
Miller, Frederick W.
TI Prevalence and sociodemographic correlates of antinuclear antibodies in
the United States
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; AUTOIMMUNE RHEUMATIC-DISEASES; C-REACTIVE
PROTEIN; HEALTHY-INDIVIDUALS; BLOOD-DONORS; GENERAL-POPULATION;
AUTOANTIBODIES; OBESITY; ASSOCIATION; ANTIGEN
AB Objective To estimate the prevalence, types, and sociodemographic and biobehavioral correlates of antinuclear antibodies (ANAs) in the US. Methods We conducted a cross-sectional analysis of 4,754 individuals from the National Health and Nutrition Examination Survey 19992004. ANAs were assessed by indirect immunofluorescence. In ANA-positive individuals, cellular staining patterns were determined, and specific autoantibody reactivities were assessed by immunoprecipitation. Results The ANA prevalence in the US population of individuals ages 12 years and older was 13.8% (95% confidence interval [95% CI] 12.215.5%). ANA prevalence increased with age (P = 0.01), and ANAs were more prevalent among females than males (17.8% versus 9.6%; P < 0.001), with the female-to-male ratio peaking at 4049 years of age. ANA prevalence was modestly higher in African Americans compared with whites (age-adjusted prevalence odds ratio [POR] 1.30, 95% CI 1.001.70). Remarkably, ANAs were less common in overweight and obese individuals (age-adjusted POR 0.74) than in persons of normal weight. No significant associations of ANA with education, family income, alcohol use, smoking history, serum levels of cotinine, or C-reactive protein were observed. In ANA-positive individuals, nuclear patterns were seen in 84.6%, cytoplasmic patterns were seen in 21.8%, and nucleolar patterns were seen in 6.1%; the most common specific autoantibodies were anti-Ro (3.9%) and anti-Su (2.4%). Conclusion These findings suggest that more than 32 million persons in the US have ANAs, and that the prevalence is higher among females, older individuals, African Americans, and those with a normal body weight. These data will serve as a useful baseline for future investigations of predictors and changes in ANA prevalence over time.
C1 [Miller, Frederick W.] NIEHS, Environm Autoimmun Grp, Program Clin Res, NIH, Bethesda, MD 20892 USA.
[Chan, Edward K. L.; Pauley, Brad A.; Ross, Steven J.] Univ Florida, Hlth Sci Ctr, Gainesville, FL USA.
[Ho, Lindsey A.; Rose, Kathryn M.; Cohn, Richard D.] SRA Int, Durham, NC USA.
[Parks, Christine G.; Jusko, Todd A.; Walker, Nigel J.; Germolec, Dori R.; Zeldin, Darryl C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda S.] NCI, NIH, Res Triangle Pk, NC USA.
RP Miller, FW (reprint author), NIEHS, Environm Autoimmun Grp, Program Clin Res, NIH, NIH 10,Room 4-2352,10 Ctr Dr,MSC 1301, Bethesda, MD 20892 USA.
EM millerf@mail.nih.gov
RI Chan, Edward/B-5671-2009; Walker, Nigel/D-6583-2012;
OI Chan, Edward/0000-0003-3938-9503; Walker, Nigel/0000-0002-9111-6855;
Miller, Frederick/0000-0003-2831-9593; Parks,
Christine/0000-0002-5734-3456
FU National Institute of Environmental Health Sciences, NIH [Z01ES101074];
[GS-23F-9806H]
FX Supported in part by the Intramural Program of the National Institute of
Environmental Health Sciences, NIH (grant Z01ES101074) and contract
GS-23F-9806H to SRA International.
NR 50
TC 81
Z9 85
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
EI 1529-0131
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD JUL
PY 2012
VL 64
IS 7
BP 2319
EP 2327
DI 10.1002/art.34380
PG 9
WC Rheumatology
SC Rheumatology
GA 965CD
UT WOS:000305742800028
PM 22237992
ER
PT J
AU Sibley, CH
Plass, N
Snow, J
Wiggs, EA
Brewer, CC
King, KA
Zalewski, C
Kim, HJ
Bishop, R
Hill, S
Paul, SM
Kicker, P
Phillips, Z
Dolan, JG
Widemann, B
Jayaprakash, N
Pucino, F
Stone, DL
Chapelle, D
Snyder, C
Butman, JA
Wesley, R
Goldbach-Mansky, R
AF Sibley, Cailin H.
Plass, Nikki
Snow, Joseph
Wiggs, Edythe A.
Brewer, Carmen C.
King, Kelly A.
Zalewski, Christopher
Kim, H. Jeffrey
Bishop, Rachel
Hill, Suvimol
Paul, Scott M.
Kicker, Patrick
Phillips, Zachary
Dolan, Joseph G.
Widemann, Brigitte
Jayaprakash, Nalini
Pucino, Frank
Stone, Deborah L.
Chapelle, Dawn
Snyder, Christopher
Butman, John A.
Wesley, Robert
Goldbach-Mansky, Raphaela
TI Sustained response and prevention of damage progression in patients with
neonatal-onset multisystem inflammatory disease treated with anakinra: A
cohort study to determine three- and five-year outcomes
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; COLD AUTOINFLAMMATORY SYNDROME;
JUVENILE IDIOPATHIC ARTHRITIS; ARTICULAR SYNDROME; NALP3 INFLAMMASOME;
EFFICACY; INHIBITION; MUTATIONS; CRYSTALS; SAFETY
AB Objective Blocking interleukin-1 with anakinra in patients with the autoinflammatory syndrome neonatal-onset multisystem inflammatory disease (NOMID) reduces systemic and organ-specific inflammation. However, the impact of long-term treatment has not been established. This study was undertaken to evaluate the long-term effect of anakinra on clinical and laboratory outcomes and safety in patients with NOMID. Methods We conducted a cohort study of 26 NOMID patients ages 0.8042.17 years who were followed up at the NIH and treated with anakinra 15 mg/kg/day for at least 36 months. Disease activity was assessed using daily diaries, questionnaires, and C-reactive protein level. Central nervous system (CNS) inflammation, hearing, vision, and safety were evaluated. Results Sustained improvements in diary scores, parent's/patient's and physician's global scores of disease activity, parent's/patient's pain scores, and inflammatory markers were observed (all P < 0.001 at 36 and 60 months). At 36 and 60 months, CNS inflammation was suppressed, with decreased cerebrospinal fluid white blood cell counts (P = 0.0026 and P = 0.0076, respectively), albumin levels, and opening pressures (P = 0.0012 and P < 0.001, respectively). Most patients showed stable or improved hearing. Cochlear enhancement on magnetic resonance imaging correlated with continued hearing loss. Visual acuity and peripheral vision were stable. Low optic nerve size correlated with poor visual field. Bony lesions progressed. Adverse events other than viral infections were rare, and all patients continued to receive the medication. Conclusion These findings indicate that anakinra provides sustained efficacy in the treatment of NOMID for up to 5 years, with the requirement of dose escalation. Damage progression in the CNS, ear, and eye, but not bone, is preventable. Anakinra is well tolerated overall.
C1 [Goldbach-Mansky, Raphaela] NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
[Snow, Joseph] NIMH, Bethesda, MD 20892 USA.
[Wiggs, Edythe A.] NINDS, Bethesda, MD 20892 USA.
[Brewer, Carmen C.; King, Kelly A.; Zalewski, Christopher; Kim, H. Jeffrey] NIDCD, Bethesda, MD USA.
[Bishop, Rachel] NEI, Bethesda, MD 20892 USA.
[Hill, Suvimol; Paul, Scott M.; Butman, John A.; Wesley, Robert] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Widemann, Brigitte; Jayaprakash, Nalini] NCI, NIH, Bethesda, MD 20892 USA.
RP Goldbach-Mansky, R (reprint author), NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bldg 10,Room 6D47-B,10 Ctr Dr, Bethesda, MD 20892 USA.
EM goldbacr@mail.nih.gov
RI Butman, John/J-2780-2013;
OI Butman, John/0000-0002-1547-9195; Paul, Scott/0000-0003-1274-6670
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases,
NIH; National Cancer Institute; National Institute on Deafness and Other
Communication Disorders; National Eye Institute; National Institute of
Mental Health; National Institute of Neurological Disorders and Stroke;
NIH Clinical Center; Regeneron; Novartis; Swedish Orphan Biovitrum AB
FX Supported by the Intramural Research Program of the National Institute
of Arthritis and Musculoskeletal and Skin Diseases, NIH. Portions of the
work were supported in part by the Intramural Research Programs of the
National Cancer Institute, the National Institute on Deafness and Other
Communication Disorders, the National Eye Institute, the National
Institute of Mental Health, the National Institute of Neurological
Disorders and Stroke, and the NIH Clinical Center.; Dr. Goldbach-Mansky
has received grant support from Regeneron, Novartis, and Swedish Orphan
Biovitrum AB.
NR 31
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U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD JUL
PY 2012
VL 64
IS 7
BP 2375
EP 2386
DI 10.1002/art.34409
PG 12
WC Rheumatology
SC Rheumatology
GA 965CD
UT WOS:000305742800034
PM 22294344
ER
PT J
AU Mendoza, FA
Keyes-Elstein, LL
Jimenez, SA
AF Mendoza, Fabian A.
Keyes-Elstein, Lynette L.
Jimenez, Sergio A.
TI Systemic sclerosis disease modification clinical trials design: Quo
vadis?
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID PLACEBO-CONTROLLED TRIAL; INTERSTITIAL LUNG-DISEASE; DOSE
D-PENICILLAMINE; MYCOPHENOLATE-MOFETIL; DOUBLE-BLIND; DIFFUSE
SCLERODERMA; SKIN THICKNESS; OPEN-LABEL; FIBROSIS; METHOTREXATE
C1 [Mendoza, Fabian A.; Jimenez, Sergio A.] Thomas Jefferson Univ, Jefferson Inst Mol Med, Philadelphia, PA 19107 USA.
[Mendoza, Fabian A.; Jimenez, Sergio A.] Thomas Jefferson Univ, Scleroderma Ctr, Philadelphia, PA 19107 USA.
[Keyes-Elstein, Lynette L.] NIAID, Stat & Clin Coordinating Ctr Autoimmune Dis Clin, NIH, Bethesda, MD 20892 USA.
RP Jimenez, SA (reprint author), Thomas Jefferson Univ, Jefferson Inst Mol Med, 233 S 10th St,Suite 509 BLSB, Philadelphia, PA 19107 USA.
EM sergio.jimenez@jefferson.edu
FU NIH [AR-19616]
FX Dr. Jimenez's work was supported in part by NIH grant AR-19616.
NR 43
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Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2151-464X
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD JUL
PY 2012
VL 64
IS 7
BP 945
EP 954
DI 10.1002/acr.21667
PG 10
WC Rheumatology
SC Rheumatology
GA 965BL
UT WOS:000305741000001
PM 22422541
ER
PT J
AU Deakin, IH
Nissen, W
Law, AJ
Lane, T
Kanso, R
Schwab, MH
Nave, KA
Lamsa, KP
Paulsen, O
Bannerman, DM
Harrison, PJ
AF Deakin, Inga H.
Nissen, Wiebke
Law, Amanda J.
Lane, Tracy
Kanso, Riam
Schwab, Markus H.
Nave, Klaus-Armin
Lamsa, Karri P.
Paulsen, Ole
Bannerman, David M.
Harrison, Paul J.
TI Transgenic Overexpression of the Type I Isoform of Neuregulin 1 Affects
Working Memory and Hippocampal Oscillations but not Long-term
Potentiation
SO CEREBRAL CORTEX
LA English
DT Article
DE gamma oscillation; hippocampus; neuregulin; schizophrenia; synaptic
plasticity
ID PARVALBUMIN-POSITIVE INTERNEURONS; GAMMA-OSCILLATIONS; NETWORK
OSCILLATIONS; MUTANT MICE; SCHIZOPHRENIA RISK; NERVOUS-SYSTEM; SPATIAL
WORKING; GENE-EXPRESSION; ERBB4; NRG1
AB Neuregulin 1 (NRG1) is a growth factor involved in neurodevelopment and plasticity. It is a schizophrenia candidate gene, and hippocampal expression of the NRG1 type I isoform is increased in the disorder. We have studied transgenic mice overexpressing NRG1 type I (NRG1(tg-type I)) and their wild-type littermates and measured hippocampal electrophysiological and behavioral phenotypes. Young NRG1(tg-type I) mice showed normal memory performance, but in older NRG1(tg-type I) mice, hippocampus-dependent spatial working memory was selectively impaired. Hippocampal slice preparations from NRG1(tg-type I) mice exhibited a reduced frequency of carbachol-induced gamma oscillations and an increased tendency to epileptiform activity. Long-term potentiation in NRG1(tg-type I) mice was normal. The results provide evidence that NRG1 type I impacts on hippocampal function and circuitry. The effects are likely mediated via inhibitory interneurons and may be relevant to the involvement of NRG1 in schizophrenia. However, the findings, in concert with those from other genetic and pharmacological manipulations of NRG1, emphasize the complex and pleiotropic nature of the gene, even with regard to a single isoform.
C1 [Deakin, Inga H.; Law, Amanda J.; Lane, Tracy; Harrison, Paul J.] Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England.
[Nissen, Wiebke; Kanso, Riam; Lamsa, Karri P.] Univ Oxford, Dept Pharmacol, Oxford OX3 7JX, England.
[Law, Amanda J.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
[Schwab, Markus H.; Nave, Klaus-Armin] Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany.
[Paulsen, Ole] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX3 7JX, England.
[Bannerman, David M.] Univ Oxford, Dept Expt Psychol, Oxford OX3 7JX, England.
RP Harrison, PJ (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Neurosci Bldg, Oxford OX3 7JX, England.
EM paul.harrison@psych.ox.ac.uk
RI Law, Amanda/G-6372-2012;
OI Law, Amanda/0000-0002-2574-1564
FU Wellcome Trust; Department of Pharmacology; UK Medical Research Council;
Stanley Medical Research Institute; Medical Research Council
FX Wellcome Trust studentship to I. H. D.; Department of Pharmacology
studentship to W.N.; UK Medical Research Council Career Development
Fellowship to A.J.L.; Wellcome Trust Career Development Fellowship to K.
P. L.; Wellcome Trust Senior Research Fellowship to D. M. B.; Stanley
Medical Research Institute and Medical Research Council grants to P.J.H.
NR 94
TC 28
Z9 30
U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD JUL
PY 2012
VL 22
IS 7
BP 1520
EP 1529
DI 10.1093/cercor/bhr223
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 963HJ
UT WOS:000305610700005
PM 21878485
ER
PT J
AU Song, SB
Sharma, N
Buch, ER
Cohen, LG
AF Song, Sunbin
Sharma, Nikhil
Buch, Ethan R.
Cohen, Leonardo G.
TI White Matter Microstructural Correlates of Superior Long-term Skill
Gained Implicitly under Randomized Practice
SO CEREBRAL CORTEX
LA English
DT Article
DE consolidation; contextual interference; diffusion tensor imaging;
magnetic resonance imaging; motor learning; motor sequence; online
learning
ID DORSOLATERAL PREFRONTAL CORTEX; SUPPLEMENTARY MOTOR AREA; CONTEXTUAL
INTERFERENCE; VISUOMOTOR ADAPTATION; INTERMANUAL TRANSFER; VOLLEYBALL
SKILLS; CORPUS-CALLOSUM; MEMORY-SYSTEMS; HUMAN BRAIN; ACQUISITION
AB We value skills we have learned intentionally, but equally important are skills acquired incidentally without ability to describe how or what is learned, referred to as implicit. Randomized practice schedules are superior to grouped schedules for long-term skill gained intentionally, but its relevance for implicit learning is not known. In a parallel design, we studied healthy subjects who learned a motor sequence implicitly under randomized or grouped practice schedule and obtained diffusion-weighted images to identify white matter microstructural correlates of long-term skill. Randomized practice led to superior long-term skill compared with grouped practice. Whole-brain analyses relating interindividual variability in fractional anisotropy (FA) to long-term skill demonstrated that 1) skill in randomized learners correlated with FA within the corticostriatal tract connecting left sensorimotor cortex to posterior putamen, while 2) skill in grouped learners correlated with FA within the right forceps minor connecting homologous regions of the prefrontal cortex (PFC) and the corticostriatal tract connecting lateral PFC to anterior putamen. These results demonstrate first that randomized practice schedules improve long-term implicit skill more than grouped practice schedules and, second, that the superior skill acquired through randomized practice can be related to white matter microstructure in the sensorimotor corticostriatal network.
C1 [Song, Sunbin; Sharma, Nikhil; Buch, Ethan R.; Cohen, Leonardo G.] Natl Inst Neurol Disorders & Stroke, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20814 USA.
[Buch, Ethan R.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England.
RP Cohen, LG (reprint author), Natl Inst Neurol Disorders & Stroke, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bldg 10,Room 7D54, Bethesda, MD 20892 USA.
EM cohenl@mail.nih.gov
OI Sharma, Nikhil/0000-0001-8903-2938
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke at the National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke at the National
Institutes of Health and utilized the high-performance computational
capabilities of the Biowulf Linux cluster at the National Institutes of
Health (http://biowulf.nih.gov).
NR 71
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U1 1
U2 18
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD JUL
PY 2012
VL 22
IS 7
BP 1671
EP 1677
DI 10.1093/cercor/bhr247
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 963HJ
UT WOS:000305610700019
PM 21914632
ER
PT J
AU Marcus, PM
Childs, J
Gahagan, B
Gren, LH
AF Marcus, Pamela M.
Childs, Jeffery
Gahagan, Betsy
Gren, Lisa H.
TI Tracking and tracing of participants in two large cancer screening
trials
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Randomized controlled trial as topic; Cancer; Mass screening; Lost to
follow-up
AB Background: Many clinical trials rely on participant report to first learn about study events. It is therefore important to have current contact information and the ability to locate participants should information become outdated. The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) and the Lung Screening Study (LSS) component of the National Lung Screening Trial, two large randomized cancer screening trials, enrolled almost 190,000 participants on whom annual contact was necessary. Ten screening centers participated in both trials. Centers developed methods to track participants and trace them when necessary. We describe the methods used to keep track of participants and trace them when lost, and the extent to which each method was used.
Methods: Screening center coordinators were asked, using a self-administered paper questionnaire, to rate the extent to which specific tracking and tracing methods were used.
Results: Many methods were used by the screening centers, including telephone calls, mail, and internet searches. The most extensively used methods involved telephoning the participant on his or her home or cell phone, or telephoning a person identified by the participant as someone who would know about the participant's whereabouts. Internet searches were used extensively as well; these included searches on names, reverse-lookup searches (on addresses or telephone numbers) and searches of the Social Security Death Index. Over time, the percentage of participants requiting tracing decreased.
Conclusions: Telephone communication and internet services were useful in keeping track of PLCO and LSS participants and tracing them when contact information was no longer valid. Published by Elsevier Inc.
C1 [Marcus, Pamela M.] NCI, Bethesda, MD 20892 USA.
[Childs, Jeffery; Gren, Lisa H.] Univ Utah, Salt Lake City, UT 84108 USA.
[Gahagan, Betsy] Univ Pittsburgh, Pittsburgh, PA 15232 USA.
RP Marcus, PM (reprint author), NCI, 6130 Execut Blvd,Room 4106, Bethesda, MD 20892 USA.
EM marcusp@mail.nih.gov; gahagan@pitt.edu; lisa.gren@hsc.utah.edu
FU Division of Cancer Prevention, National Cancer Institute, NIH, DHHS
FX This research was supported by contracts from the Division of Cancer
Prevention, National Cancer Institute, NIH, DHHS. The authors thank Drs.
Christine Berg and Richard Fagerstrom, Division of Cancer Prevention,
National Cancer Institute, the Screening Center investigators and staff
of the PLCO Trial and the LSS component of the NIST, Mr. Tom Riley and
staff, Information Management Services, Inc., Ms. Brenda Brewer and
staff, Westat Most importantly, we acknowledge the study participants,
whose contributions made this study possible.
NR 6
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD JUL
PY 2012
VL 33
IS 4
BP 601
EP 605
DI 10.1016/j.cct.2012.04.006
PG 5
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 964QL
UT WOS:000305711700007
PM 22561392
ER
PT J
AU Jacob, ST
Banura, P
Baeten, JM
Moore, CC
Meya, D
Nakiyingi, L
Burke, R
Horton, CL
Iga, B
Wald, A
Reynolds, SJ
Mayanja-Kizza, H
Scheid, WM
AF Jacob, Shevin T.
Banura, Patrick
Baeten, Jared M.
Moore, Christopher C.
Meya, David
Nakiyingi, Lydia
Burke, Rebecca
Horton, Cheryl Lynn
Iga, Boaz
Wald, Anna
Reynolds, Steven J.
Mayanja-Kizza, Harriet
Scheid, W. Michael
CA Promoting Resource-Ltd
TI The impact of early monitored management on survival in hospitalized
adult Ugandan patients with severe sepsis: A prospective intervention
study
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE Africa; fluid therapy; management bundle; mortality; pulmonary edema;
sepsis; Uganda
ID GOAL-DIRECTED THERAPY; SEPTIC SHOCK; INCOME COUNTRIES; CARE;
METAANALYSIS; POPULATION; MORTALITY; CAMPAIGN; PROGRAM
AB In sub-Saharan Africa, sepsis is an important cause of mortality. Optimal sepsis management including fluid resuscitation, early antibiotic administration, and patient monitoring is limited by lack of supplies and skilled health workers.
Objective: To evaluate whether early, monitored sepsis management provided by a study medical officer can improve survival among patients with severe sepsis admitted to two public hospitals in Uganda.
Design, Setting, and Patients: A prospective before and after study of an intervention cohort (n = 426) with severe sepsis receiving early, monitored sepsis management compared to an observation cohort (n = 245) of similarly ill patients with severe sepsis receiving standard management after admission to the medical wards of two Ugandan hospitals.
Intervention: Early sepsis management provided by a dedicated study medical officer comprising fluid resuscitation, early antibiotics, and regular monitoring in the first 6 hrs of hospitalization.
Measurements: Kaplan-Meier survival and unadjusted and adjusted Cox proportional hazards analysis were used to compare the effect of early, monitored sepsis management on 30-day mortality between the intervention cohort (enrolled May 2008 to May 2009) and observation cohort (enrolled July 2006 to November 2006).
Results:The majority (86%) of patients in both cohorts were human immuno-deficiency virus-infected. Median fluid volume provided in the first 6 hrs of hospitalization was higher in intervention than observation cohort patients (3000 mL vs. 500 mL, p < .001) and a greater proportion of intervention cohort patients received antibacterial therapy in <1 hr (67% vs. 30.4%, p < .001). Mortality at 30 days was significantly lower in the intervention cohort compared to the observation cohort (33.0% vs. 45.7%, log-rank p = .005). After adjustment for potential confounders, the hazard of 30-day mortality was 26% less in the intervention cohort compared to the observation cohort (adjusted hazards ratio 0.74, 95% confidence interval 0.55-0.98). Mortality among the 13% of intervention patients who developed signs of respiratory distress was associated with baseline illness severity rather than fluid volume administered.
Conclusion: Early, monitored management of severely septic patients in Uganda improves survival and is feasible and safe even in a busy public referral hospital. (Crit Care Med 2012; 40:2050-2058)
C1 [Jacob, Shevin T.; Baeten, Jared M.; Wald, Anna] Univ Washington, Div Allergy & Infect Dis, Dept Med, Seattle, WA 98105 USA.
[Jacob, Shevin T.] Univ Washington, Dept Med, Int Resp & Severe Illness Ctr INTERSECT, Seattle, WA USA.
[Banura, Patrick] Masaka Reg Referral Hosp, Masaka, Uganda.
[Baeten, Jared M.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Baeten, Jared M.; Wald, Anna] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Moore, Christopher C.; Scheid, W. Michael] Univ Virginia, Dept Med, Charlottesville, VA USA.
[Meya, David; Nakiyingi, Lydia; Mayanja-Kizza, Harriet] Makerere Univ, Sch Med, Coll Hlth Sci, Kampala, Uganda.
[Meya, David; Nakiyingi, Lydia] Makerere Univ, Infect Dis Inst, Kampala, Uganda.
[Burke, Rebecca] Duke Univ, Dept Med, Durham, NC USA.
[Horton, Cheryl Lynn] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA.
[Wald, Anna] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Wald, Anna] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Iga, Boaz; Reynolds, Steven J.] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Reynolds, Steven J.] NIAID, NIH, Bethesda, MD 20892 USA.
[Reynolds, Steven J.] Johns Hopkins Sch Med, Baltimore, MD USA.
RP Jacob, ST (reprint author), Univ Washington, Div Allergy & Infect Dis, Dept Med, Seattle, WA 98105 USA.
EM sjacob2@uw.edu
RI Wald, Anna/B-6272-2012;
OI Wald, Anna/0000-0003-3486-6438; Meya, David/0000-0002-4138-240X;
Mayanja-Kizza, Harriet/0000-0002-9297-6208
FU Investigator-Initiated Award; Pfizer, Inc.; National Institutes of
Health K24 [Al 071113]
FX Primary funding for the study was from an Investigator-Initiated Award
provided by Pfizer, Inc. Pfizer, Inc. had no role in the design and
conduct of the study; the collection, management analysis, and
interpretation of the data; or the preparation, review or approval of
the manuscript.; Additional non-grant support was provided by the Rakai
Health Sciences Program through the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. In addition, Dr. Wald is supported by a National
Institutes of Health K24 (Al 071113).
NR 18
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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 JUL
PY 2012
VL 40
IS 7
BP 2050
EP 2058
DI 10.1097/CCM.0b013e31824e65d7
PG 9
WC Critical Care Medicine
SC General & Internal Medicine
GA 965KX
UT WOS:000305767800006
PM 22564958
ER
PT J
AU Natarajan, G
Pappas, A
Shankaran, S
Kendrick, DE
Das, A
Higgins, RD
Laptook, AR
Bell, EF
Stoll, BJ
Newman, N
Hale, EC
Bara, R
Walsh, MC
AF Natarajan, Girija
Pappas, Athina
Shankaran, Seetha
Kendrick, Douglas E.
Das, Abhik
Higgins, Rosemary D.
Laptook, Abbot R.
Bell, Edward F.
Stoll, Barbara J.
Newman, Nancy
Hale, Ellen C.
Bara, Rebecca
Walsh, Michele C.
TI Outcomes of extremely low birth weight infants with bronchopulmonary
dysplasia: Impact of the physiologic definition
SO EARLY HUMAN DEVELOPMENT
LA English
DT Article
DE Outcome; Preterm; Bronchopulmonary dysplasia; Physiologic definition
ID EXTREMELY PRETERM INFANTS; NEONATAL RESEARCH NETWORK; BORN; AGE;
GESTATION; CHILDREN; HEALTH
AB Aims: We compared neurodevelopmental outcomes of extremely low birth weight (ELBW) infants with and without bronchopulmonary dysplasia (BPD), using the physiologic definition.
Study design: ELBW (birth weights<1000 g) infants admitted to the Neonatal Research Network centers and hospitalized at 36 weeks postmenstrual age (n=1189) were classified using the physiologic definition of BPD. Infants underwent Bayley III assessment at 18-22 months corrected age. Multivariable logistic regression was used to determine the association between physiologic BPD and cognitive impairment (score<70).
Results: BPD by the physiologic definition was diagnosed in 603 (52%) infants, 537 of whom were mechanically ventilated or on FiO(2)>30% and 66 who failed the room air challenge. Infants on room air (n=505) and those who passed the room air challenge (n=51) were classified as "no BPD" (n=556). At follow up, infants with BPD had significantly lower mean weight and head circumference. Moderate to severe cerebral palsy (7 vs. 2.1%) and spastic diplegia (7.8 vs. 4.1%) and quadriplegia (3.9 vs. 0.9%) phenotypes as well as cognitive (12.8 vs. 4.6%) and language scores<70 (242 vs. 12.3%) were significantly more frequent in those with BPD compared to those without BPD. BPD was independently associated (adjusted OR 2.4; 95% CI 1.40-4.13) with cognitive impairment.
Conclusions: Rates of adverse neurodevelopmental outcomes in early childhood were significantly higher in those with BPD. BPD by the physiologic definition was independently associated with cognitive impairment using Bayley Scales III. These findings have implications for targeted post-discharge surveillance and early intervention. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Natarajan, Girija; Pappas, Athina; Shankaran, Seetha; Bara, Rebecca] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Kendrick, Douglas E.; Das, Abhik] Res Triangle Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Stoll, Barbara J.; Hale, Ellen C.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Stoll, Barbara J.; Hale, Ellen C.] Emory Univ, Sch Med, Atlanta, GA USA.
[Newman, Nancy; Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
RP Natarajan, G (reprint author), Childrens Hosp Michigan, Div Neonatol, 3901 Beaubien Blvd, Detroit, MI 48201 USA.
EM gnatara@med.wayne.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD)
FX The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD)
provided grant support for the Neonatal Research Network's Generic
Database and Follow-up Studies.
NR 23
TC 48
Z9 55
U1 0
U2 11
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-3782
J9 EARLY HUM DEV
JI Early Hum. Dev.
PD JUL
PY 2012
VL 88
IS 7
BP 509
EP 515
DI 10.1016/j.earlhumdev.2011.12.013
PG 7
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 964CW
UT WOS:000305672300010
PM 22236557
ER
PT J
AU Parham, F
Wise, A
Axelrad, DA
Guyton, KZ
Portier, C
Zeise, L
Zoeller, RT
Woodruff, TJ
AF Parham, Fred
Wise, Amber
Axelrad, Daniel A.
Guyton, Kathryn Z.
Portier, Christopher
Zeise, Lauren
Zoeller, R. Thomas
Woodruff, Tracey J.
TI Adverse effects in risk assessment: Modeling polychlorinated biphenyls
and thyroid hormone disruption outcomes in animals and humans
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE (5-10):polychlorinated biphenyls; Thyroid hormones; Adverse health
outcomes; Biological perturbations; Risk assessment
ID CONGENITAL HYPOTHYROIDISM; ORGANOCHLORINE PESTICIDES; DEVELOPMENTAL
EXPOSURE; PCB CONGENERS; YOUNG-ADULTS; SERUM; THYROXINE; RATS;
ASSOCIATION; METABOLISM
AB There is a growing need for quantitative approaches to extrapolate relationships between chemical exposures and early biological perturbations from animals to humans given increasing use of biological assays to evaluate toxicity pathways. We have developed such an approach using polychlorinated biphenyls (PCBs) and thyroid hormone (TH) disruption as a case study. We reviewed and identified experimental animal literature from which we developed a low-dose, linear model of PCB body burdens and decrements in free thyroxine (FT4) and total thyroxine (TT4), accounting for 33 PCB congeners; extrapolated the dose-response from animals to humans; and compared the animal dose-response to the dose-response of PCB body burdens and TH changes from eleven human epidemiological studies. We estimated a range of potencies for PCB congeners (over 4 orders of magnitude), with the strongest for PCB 126. Our approach to developing toxic equivalency models produced relative potencies similar to the toxicity equivalency factors (TEFs) from the World Health Organization (WHO). We generally found that the dose-response extrapolated from the animal studies tends to under-predict the dose-response estimated from human epidemiological studies. A quantitative approach to evaluating the relationship between chemical exposures and TH perturbations, based on animal data can be used to assess human health consequences of thyroid toxicity and inform decision-making. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Parham, Fred] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Wise, Amber; Woodruff, Tracey J.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Program Reprod Hlth & Environm, San Francisco, CA USA.
[Axelrad, Daniel A.] US EPA, Off Policy, Washington, DC 20460 USA.
[Guyton, Kathryn Z.] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA.
[Portier, Christopher] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Zeise, Lauren] Calif Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Oakland, CA USA.
[Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA.
RP Woodruff, TJ (reprint author), 1330 Broadway St,Suite 1100, Oakland, CA 94612 USA.
EM woodrufft@obgyn.ucsf.edu
RI Portier, Christopher/A-3160-2010
OI Portier, Christopher/0000-0002-0954-0279
FU USEPA [EP08h001138]; Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences
FX This project was supported under USEPA contract #EP08h001138 and by the
Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences. This paper does not reflect the views of
any of the affiliated agencies, including the USEPA, California EPA, or
National Institute of Environmental Health Sciences. The findings and
conclusions in this report are those of the author(s) and do not
necessarily represent the official position of the Centers for Disease
Control and Prevention/the Agency for Toxic Substances and Disease
Registry.
NR 51
TC 5
Z9 5
U1 4
U2 29
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
J9 ENVIRON RES
JI Environ. Res.
PD JUL
PY 2012
VL 116
BP 74
EP 84
DI 10.1016/j.envres.2012.04.003
PG 11
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 959IR
UT WOS:000305306600010
PM 22575326
ER
PT J
AU Eisenhofer, G
Lenders, JWM
Siegert, G
Bornstein, SR
Friberg, P
Milosevic, D
Mannelli, M
Linehan, WM
Adams, K
Timmers, HJ
Pacak, K
AF Eisenhofer, Graeme
Lenders, Jacques W. M.
Siegert, Gabriele
Bornstein, Stefan R.
Friberg, Peter
Milosevic, Dragana
Mannelli, Massimo
Linehan, W. Marston
Adams, Karen
Timmers, Henri J.
Pacak, Karel
TI Plasma methoxytyramine: A novel biomarker of metastatic pheochromocytoma
and paraganglioma in relation to established risk factors of tumour
size, location and SDHB mutation status
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Pheochromocytoma; Paraganglioma; Metastases; Methoxytyramine; Dopamine;
Metanephrines; Catecholamines; Succinate dehydrogenase type B
ID MALIGNANT PHEOCHROMOCYTOMA; CLINICAL-EXPERIENCE; BENIGN; EXPRESSION;
MANAGEMENT; EXCRETION; DOPAMINE; GENE; DIAGNOSIS
AB Background: There are currently no reliable biomarkers for malignant pheochromocytomas and paragangliomas (PPGLs). This study examined whether measurements of catecholamines and their metabolites might offer utility for this purpose.
Methods: Subjects included 365 patients with PPGLs, including 105 with metastases, and a reference population of 846 without the tumour. Eighteen catecholamine-related analytes were examined in relation to tumour location, size and mutations of succinate dehydrogenase subunit B (SDHB).
Results: Receiver-operating characteristic curves indicated that plasma methoxytyramine, the O-methylated metabolite of dopamine, provided the most accurate biomarker for discriminating patients with and without metastases. Plasma methoxytyramine was 4.7-fold higher in patients with than without metastases, a difference independent of tumour burden and the associated 1.6- to 1.8-fold higher concentrations of norepinephrine and normetanephrine. Increased plasma methoxytyramine was associated with SDHB mutations and extra-adrenal disease, but was also present in patients with metastases without SDHB mutations or those with metastases secondary to adrenal tumours. High risk of malignancy associated with SDHB mutations reflected large size and extra-adrenal locations of tumours, both independent predictors of metastatic disease. A plasma methoxytyramine above 0.2 nmol/L or a tumour diameter above 5 cm indicated increased likelihood of metastatic spread, particularly when associated with an extra-adrenal location.
Conclusion: Plasma methoxytyramine is a novel biomarker for metastatic PPGLs that together with SDHB mutation status, tumour size and location provide useful information to assess the likelihood of malignancy and manage affected patients. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Eisenhofer, Graeme; Siegert, Gabriele] Univ Dresden, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany.
[Eisenhofer, Graeme; Lenders, Jacques W. M.; Bornstein, Stefan R.] Univ Dresden, Dept Med, D-01307 Dresden, Germany.
[Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands.
[Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[Friberg, Peter] Univ Gothenburg, Univ Hosp, Gothenburg, Sweden.
[Friberg, Peter] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Milosevic, Dragana] Univ Florence, Dept Clin Pathophysiol, Florence, Italy.
[Mannelli, Massimo] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Linehan, W. Marston] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Eisenhofer, G (reprint author), Univ Dresden, Inst Clin Chem & Lab Med, Fetscherstr 74, D-01307 Dresden, Germany.
EM Graeme.Eisenhofer@uniklinikum-dresden.de
RI Lenders, J.W.M./L-4487-2015;
OI Mannelli, Massimo/0000-0002-8001-9857
FU Intramural programmes of the Eunice Kennedy Shriver National Institute
of Child Health and Human Development; Center for Cancer Research,
National Cancer Institute, NIH; European Union [HEALTH-F2-2010-259735];
Deutsche Forschungsgesellschaft; Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research
FX This work was supported by Intramural programmes of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development and the
Center for Cancer Research, National Cancer Institute, NIH. Other
funding was from the European Union 7th Framework Program (ENS@T-CANCER;
HEALTH-F2-2010-259735) and the Deutsche Forschungsgesellschaft. Thanks
are extended to Thanh-Truc Huynh, Nan Qin, Stephanie Fliedner, Kathryn
King and Tamara Prodanov for technical help or assistance with
collections of patient materials and data. This research was supported
by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 33
TC 83
Z9 86
U1 0
U2 11
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD JUL
PY 2012
VL 48
IS 11
BP 1739
EP 1749
DI 10.1016/j.ejca.2011.07.016
PG 11
WC Oncology
SC Oncology
GA 965QC
UT WOS:000305781300019
PM 22036874
ER
PT J
AU de Bartolomeis, A
Tomasetti, C
Cicale, M
Yuan, PX
Manji, HK
AF de Bartolomeis, Andrea
Tomasetti, Carmine
Cicale, Maria
Yuan, Pei-Xiong
Manji, Husseini K.
TI Chronic treatment with lithium or valproate modulates the expression of
Homer1b/c and its related genes Shank and Inositol 1,4,5-trisphosphate
receptor
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Bipolar disorder; Gene expression; Glutamate; Postsynaptic density;
Schizophrenia; Striatum
ID GLYCOGEN-SYNTHASE KINASE-3; RAT-BRAIN; METABOTROPIC
GLUTAMATE-RECEPTOR-5; POSTSYNAPTIC DENSITY; GLUTAMATE RECEPTORS;
UNANESTHETIZED RATS; SCAFFOLD PROTEINS; MOOD STABILIZERS; BIPOLAR
DISORDER; ARACHIDONIC-ACID
AB Homer proteins are associated with both dopaminergic and glutamatergic function. In addition, these proteins are implicated in many signal transduction pathways that are also putative targets of the mood stabilizers lithium and valproate (VPA). This study investigated the effect of in vivo chronic administration of therapeutically-relevant doses of lithium and VPA on the expression of the inducible (Homer 1a and ania-3) and constitutive (Homer1b/c) isoforms of the Homer1 gene in rat brain, and of two other Homer-related genes: Inositol 1,4,5 trisphosphate receptor (IP3R) and Shank. Homer1b/c was significantly decreased in cortex by VPA, and in striatal and accumbal subregions by both lithium and VPA. Both mood stabilizers reduced Homer1b/c expression in the dorsolateral caudate-putamen, white only VPA decreased gene expression in all other striatal subregions. Shank and IP3R were downregulated by both mood stabilizers in the cortex. Neither chronic lithium nor VPA affected Homer immediate-early genes. These results suggest that lithium and VPA similarly modulate the expression of structural postsynaptic genes with topographic specificity in cortical and subcortical regions. Thus, Homer may represent an additional molecular substrate for mood stabilizers, and a potential link with dopaminergic function. (C) 2011 Elsevier B.V. and ECNP. All rights reserved.
C1 [de Bartolomeis, Andrea; Tomasetti, Carmine; Cicale, Maria] Univ Sch Med Federico II, Sect Psychiat, Dept Neurosci, Lab Mol Psychiat & Psychopharmacotherapeut, I-80131 Naples, Italy.
[Yuan, Pei-Xiong; Manji, Husseini K.] NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA.
[Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
RP de Bartolomeis, A (reprint author), Univ Sch Med Federico II, Sect Psychiat, Dept Neurosci, Lab Mol Psychiat & Psychopharmacotherapeut, Via Pansini 5, I-80131 Naples, Italy.
EM adebarto@unina.it
OI de Bartolomeis, Andrea/0000-0002-3188-5652
FU Intramural Research Program of National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH); Astra Zeneca;
Janssen-Cilag; Lundbeck; Astra-Zeneca Italia; Janssen-Cilag Italy; Eli
Lilly; Bristol-Myers Squibb
FX Funding for this study was provided by unrestricted grants supplied to
the Department of Neuroscience, University Medical School of Naples
"Federico II" and by the Intramural Research Program of the National
Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH). Neither the University Medical School of Naples nor the
NIMH played a further role in study design; in the collection, analysis,
and interpretation of data; in the writing of the report; or in the
decision to submit the paper for publication.; Dr. Manji is a full-time
employee of Johnson and Johnson Pharmaceutical Research and Development.
Andrea de Bartolomeis has received unrestricted research funding from
Astra Zeneca, Janssen-Cilag, and Lundbeck. The funding was made
available to the Department of Neuroscience, University of Naples
Federico II. He has received honoraria as speaker at educational
activity sponsored by Astra-Zeneca Italia, Janssen-Cilag Italy, Eli
Lilly, Bristol-Myers Squibb.
NR 42
TC 19
Z9 19
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD JUL
PY 2012
VL 22
IS 7
BP 527
EP 535
DI 10.1016/j.euroneuro.2011.11.006
PG 9
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 964CT
UT WOS:000305672000008
PM 22245542
ER
PT J
AU Mathews, CE
Moore, SC
George, SM
Sampson, J
Bowles, HR
AF Mathews, Charles E.
Moore, Steven C.
George, Stephanie M.
Sampson, Joshua
Bowles, Heather R.
TI Improving Self-Reports of Active and Sedentary Behaviors in Large
Epidemiologic Studies
SO EXERCISE AND SPORT SCIENCES REVIEWS
LA English
DT Review
DE exposure assessment; exercise; sitting; measurement error; disease
prevention
ID PHYSICAL-ACTIVITY QUESTIONNAIRES; ACTIVITY ENERGY-EXPENDITURE;
ARTIFICIAL NEURAL-NETWORK; MEASUREMENT ERROR; OLDER-ADULTS; VALIDATION;
ACCELEROMETER; HEALTH; RECALL; RELIABILITY
AB MATTHEWS, C.E., S.C. MOORE, S.M. GEORGE, J. SAMPSON, and H.R. BOWLES. Improving self-reports of active and sedentary behaviors in large epidemiologic studies. Exerc. Sport Sci. Rev., Vol. 40, No. 3, pp. 118-126, 2012. Questionnaires that assess active and sedentary behaviors in large-scale epidemiologic studies are known to contain substantial errors. We present three options for improving measures of physical activity behaviors in large-scale epidemiologic studies, discuss the problems and prospects for each of these options, and highlight a new direction for measuring these behaviors in such studies.
C1 [Mathews, Charles E.; Moore, Steven C.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[George, Stephanie M.; Bowles, Heather R.] NCI, Appl Reseach Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Sampson, Joshua] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Mathews, CE (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 3028, Bethesda, MD 20892 USA.
EM charles.matthews2@nih.gov
RI matthews, Charles/E-8073-2015; Moore, Steven/D-8760-2016
OI matthews, Charles/0000-0001-8037-3103; Moore, Steven/0000-0002-8169-1661
NR 46
TC 11
Z9 11
U1 3
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0091-6331
J9 EXERC SPORT SCI REV
JI Exerc. Sport Sci. Rev.
PD JUL
PY 2012
VL 40
IS 3
BP 118
EP 126
PG 9
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 965MA
UT WOS:000305770700002
ER
PT J
AU Hoenen, T
Groseth, A
Feldmann, H
AF Hoenen, Thomas
Groseth, Allison
Feldmann, Heinz
TI Current ebola vaccines
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Review
DE ebolavirus; filoviruses; hemorrhagic fever; intervention; vaccine
ID PROTECTS NONHUMAN-PRIMATES; VIRUS-LIKE PARTICLES; ADENOVIRUS-BASED
VACCINE; ATTENUATED RECOMBINANT VACCINE; EQUINE ENCEPHALITIS-VIRUS;
HEMORRHAGIC-FEVER; GUINEA-PIGS; POSTEXPOSURE PROTECTION; MARBURG VIRUS;
FILOVIRUS INFECTION
AB Introduction: Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates (NHPs), with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in NHPs, the gold standard animal model for ebola hemorrhagic fever.
Areas covered: This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios and describes current ebolavirus vaccines. Among these vaccines are recombinant adenoviruses, recombinant vesicular stomatitis viruses (VSVs), recombinant human parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant VSVs, has also demonstrated post-exposure protection in NHPs.
Expert opinion: The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and toward licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible.
C1 [Hoenen, Thomas] NIAID, NIH, Div Intramural Res,Lab Virol, Rocky Mt Labs,Dis Modelling & Transmiss Unit, Hamilton, MT USA.
[Groseth, Allison] NIAID, NIH, Div Intramural Res,Lab Virol, Rocky Mt Labs,Mol Virol & Host Pathogen Interact, Hamilton, MT USA.
RP Hoenen, T (reprint author), NIAID, NIH, Div Intramural Res,Lab Virol, Rocky Mt Labs,Dis Modelling & Transmiss Unit, 2A120A,903 S 4th St, Hamilton, MT USA.
EM thomas.hoenen@nih.gov
OI Hoenen, Thomas/0000-0002-5829-6305
FU NIH, NIAID
FX Research on filoviruses by the authors was supported in part by the
Intramural Research Program of the NIH, NIAID. H Feldman also claims
intellectual property regarding vesicular stomatitis virus-based
vaccines for ebola and Marburg infections. The other authors have no
other competing interests to declare.
NR 91
TC 35
Z9 41
U1 1
U2 60
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1471-2598
J9 EXPERT OPIN BIOL TH
JI Expert Opin. Biol. Ther.
PD JUL
PY 2012
VL 12
IS 7
BP 859
EP 872
DI 10.1517/14712598.2012.685152
PG 14
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA 956LV
UT WOS:000305092000005
PM 22559078
ER
PT J
AU Radoshitzky, SR
Kuhn, JH
de Kok-Mercado, F
Jahrling, PB
Bavari, S
AF Radoshitzky, Sheli R.
Kuhn, Jens H.
de Kok-Mercado, Fabian
Jahrling, Peter B.
Bavari, Sina
TI Drug discovery technologies and strategies for Machupo virus and other
New World arenaviruses
SO EXPERT OPINION ON DRUG DISCOVERY
LA English
DT Review
DE antivirals; arenavirus; Machupo; therapeutics; viral hemorrhagic fever
ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; ARGENTINE HEMORRHAGIC-FEVER;
FINGER-Z-PROTEIN; STABLE SIGNAL PEPTIDE; VIRAL-RNA SYNTHESIS; REVERSE
GENETICS GENERATION; I INTERFERON INDUCTION; PH-INDUCED ACTIVATION;
ZINC-BINDING PROTEIN; GLYCOPROTEIN GP-C
AB Introduction: Seven arenaviruses cause viral hemorrhagic fever in humans: the Old World arenaviruses Lassa and Lujo, and the New World Clade B arenaviruses Machupo (MACV), Junin (JUNV), Guanarito (GTOV), Sabia (SABV), and Chapare (CHPV). All of these viruses are Risk Group 4 biosafety pathogens. MACV causes human disease outbreak with high case-fatality rates. To date, at least 1,200 cases with approximate to 200 fatalities have been recorded.
Areas covered: This review summarizes available systems and technologies for the identification of antivirals against MACV. Furthermore, the article summarizes animal models that have been used for the in vivo evaluation of novel inhibitors. The article highlights present treatments for arenaviral diseases and provides an overview of efficacious small molecules and other therapeutics reported to date. Finally, the article summarizes strategies to identify novel inhibitors for anti-arenaviral therapy.
Expert opinion: New high-throughput approaches to quantitate infection rates of arenaviruses, as well as viruses modified to carry reporter genes, will accelerate compound screens and drug discovery efforts. RNAi, gene expression profiling and proteomics studies will identify host targets for therapeutic intervention. New discoveries in the cell entry mechanism of MACV and other arenaviruses as well as extensive structural studies of arenaviral L and NP could facilitate the rational design of antivirals effective against all pathogenic New World arenaviruses.
C1 [Radoshitzky, Sheli R.; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
[Kuhn, Jens H.; de Kok-Mercado, Fabian; Jahrling, Peter B.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD 21702 USA.
RP Bavari, S (reprint author), USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
EM sina.bavari@us.army.mil
RI Kuhn, Jens H./B-7615-2011
OI Kuhn, Jens H./0000-0002-7800-6045
FU Joint Science and Technology Office Transformational Medical
Technologies [TMTI0048_09_RDE_T]; NIAID [HHSN272200200016I]
FX `SR Radoshitzky and S Bavari's research is supported by the Joint
Science and Technology Office Transformational Medical Technologies
(proposal #TMTI0048_09_RDE_T). F de Kok-Mercado performed this work as
an employee of Battelle-Memorial Institute under its prime contract with
NIAID (Contract No. HHSN272200200016I). JH Kuhn performed this work as
an employee of Tunnell Consulting, Inc., a subcontractor to Battelle
Memorial Institute under its prime contract with NIAID (Contract No.
HHSN272200200016I).
NR 207
TC 8
Z9 8
U1 2
U2 12
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1746-0441
J9 EXPERT OPIN DRUG DIS
JI Expert. Opin. Drug Discov.
PD JUL
PY 2012
VL 7
IS 7
BP 613
EP 632
DI 10.1517/17460441.2012.687719
PG 20
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 963WB
UT WOS:000305654600007
PM 22607481
ER
PT J
AU Feng, DC
Kong, XN
Weng, HL
Park, O
Wang, H
Dooley, S
Gershwin, ME
Gao, B
AF Feng, Dechun
Kong, Xiaoni
Weng, Honglei
Park, Ogyi
Wang, Hua
Dooley, Steven
Gershwin, M. Eric
Gao, Bin
TI Interleukin-22 Promotes Proliferation of Liver Stem/Progenitor Cells in
Mice and Patients With Chronic Hepatitis B Virus Infection
SO GASTROENTEROLOGY
LA English
DT Article
DE Immune Regulation; Viral Hepatitis; Oval Cells; Signal Transduction
ID ETHIONINE-SUPPLEMENTED DIET; OVAL CELLS; SIGNAL TRANSDUCER; PROGENITOR
CELLS; TRANSCRIPTION 3; STEM-CELLS; CHOLINE-DEFICIENT; DISEASE SEVERITY;
KNOCKOUT MICE; MOUSE-LIVER
AB BACKGROUND & AIMS: Proliferation of liver stem/progenitor cells (LPCs), which can differentiate into hepatocytes or biliary epithelial cells, is often observed in chronically inflamed regions of liver in patients. We investigated how inflammation might promote proliferation of LPCs. METHODS: We examined the role of interleukin (IL)-22, a survival factor for hepatocytes, on proliferation of LPCs in patients with chronic hepatitis B virus (HBV) infection and in mice. Proliferation of LPCs in mice was induced by feeding a diet that contained 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). RESULTS: Hepatic expression of IL-22 was increased in patients with HBV and correlated with the grade of inflammation and proliferation of LPCs. Mice on the DDC diet that overexpressed an IL-22 transgene specifically in liver (IL-22TG), or that were infected with an IL-22-expressing adenovirus, had increased proliferation of LPCs. Signal transducer and activator of transcription (STAT) 3, a component of the IL-22 signaling pathway, was activated in LPCs isolated from DDC-fed IL-22TG mice. Deletion of STAT3 from livers of IL-22TG mice reduced proliferation of LPCs. In addition, the receptors IL-22R1 and IL-10R2 were detected on epithelial cell adhesion molecule(+)CD45(-) LPCs isolated from DDC-fed wild-type mice. Culture of these cells with IL-22 activated STAT3 and led to cell proliferation, but IL-22 had no effect on proliferation of STAT3-deficient EpCAM(+)CD45(-) LPCs. IL-22 also activated STAT3 and promoted proliferation of cultured BMOL cells (a mouse LPC line). CONCLUSIONS: In livers of mice and patients with chronic HBV infection, inflammatory cells produce IL-22, which promotes proliferation of LPCs via STAT3. These findings link inflammation with proliferation of LPCs in patients with HBV infection.
C1 [Feng, Dechun; Kong, Xiaoni; Park, Ogyi; Wang, Hua; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
[Weng, Honglei; Dooley, Steven] Univ Heidelberg, Fac Med Mannheim, Med Clin 2, D-6900 Heidelberg, Germany.
[Gershwin, M. Eric] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Sch Med, Davis, CA 95616 USA.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
RI Feng, Dechun/Q-5962-2016
FU National Institute on Alcohol Abuse and Alcoholism/National Institutes
of Health; German Research Foundation [SFB TRR77, Do373/8-1]; Federal
Ministry of Education and Research
FX This work was supported by the intramural program of National Institute
on Alcohol Abuse and Alcoholism/National Institutes of Health (BG), the
German Research Foundation programs "SFB TRR77 Liver Cancer" and
"Do373/8-1" (SD) and the Federal Ministry of Education and Research
grants "The Virtual Liver" (SD) and "Cell Therapy in Liver Regeneration"
(SD and H Weng).
NR 43
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U2 14
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 JUL
PY 2012
VL 143
IS 1
BP 188
EP U375
DI 10.1053/j.gastro.2012.03.044
PG 18
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 965QE
UT WOS:000305781500041
PM 22484119
ER
PT J
AU Deng, ZH
Gao, XJ
Kirk, GD
Wolinsky, S
Carrington, M
AF Deng, Zhihui
Gao, Xiaojiang
Kirk, Gregory D.
Wolinsky, Steven
Carrington, Mary
TI Characterization of the HLA-C*07:01:01G allele group in European and
African-American cohorts
SO HUMAN IMMUNOLOGY
LA English
DT Article
ID HLA CLASS-I; MARROW-TRANSPLANTATION; C ALLELES; DIVERSITY; HAPLOTYPES;
ASSOCIATION; POPULATION; MOLECULES; LIGATION; HIV
AB The HLA-C*07:01:01G allele group consists of three nonsynonymous alleles, C*07:01:01, C*07:06 and C*07:18, plus C*07:01:02, which is synonymous to C*07:01:01. All of these alleles have identical exons 2, 3 and 4, but differ in exons 5 or 6. Therefore routine sequence-based typing (SBT) of exons 2 and 3 is unable to resolve these subtypes, resulting in ambiguous typing results in population and disease cohort studies. In the present study, we fully characterized C*07:01:01G subtypes in European and African Americans and examined their relative frequency distributions. In European Americans C*07:01:01G is predominantly represented by C*07:01:01 (94.4%), whereas C*07:01:02 (1.1%) and C*07:18 (4.5%) were detected relatively infrequently. In African Americans C*07:18 (42.4%) showed a high frequency similar to that of C*07:01:01 (44.7%) whereas C*07:06 was detected at a low frequency (4.7%). C*07:06 was found exclusively on B*44:03 carrying haplotypes in both ethnic groups, but C*07:18 showed multiple linkage relationships with HLA-B. These results demonstrate that C*07:01:01G as defined by routine SBT is a heterogeneous group of alleles, especially among individuals of African origin. If C*07:01:01G subtypes prove to bear divergent functional significance, it would be necessary to include these subtypes in routine HLA-C typing for clinical transplantation and disease association studies. (c) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
C1 [Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Frederick, MD 21702 USA.
[Deng, Zhihui] Shenzhen Blood Ctr, Immunogenet Lab, Shenzhen 518035, Guangdong, Peoples R China.
[Gao, Xiaojiang; Carrington, Mary] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA.
[Kirk, Gregory D.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Wolinsky, Steven] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA.
RP Carrington, M (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, POB B,Bldg 560,Rm 21-89, Frederick, MD 21702 USA.
EM carringm@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research; Guangdong Science &
Technology Department [2008B030301277]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This Research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. This
study was supported by the research fund of Guangdong Science &
Technology Department (Research Project number: 2008B030301277).
NR 23
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
J9 HUM IMMUNOL
JI Hum. Immunol.
PD JUL
PY 2012
VL 73
IS 7
BP 715
EP 719
DI 10.1016/j.humimm.2012.04.021
PG 5
WC Immunology
SC Immunology
GA 965NZ
UT WOS:000305775800005
PM 22548719
ER
PT J
AU Song, SE
Cho, NB
Iordachita, II
Guion, P
Fichtinger, G
Kaushal, A
Camphausen, K
Whitcomb, LL
AF Song, Sang-Eun
Cho, Nathan Bongjoon
Iordachita, Iulian I.
Guion, Peter
Fichtinger, Gabor
Kaushal, Aradhana
Camphausen, Kevin
Whitcomb, Louis L.
TI Biopsy Needle Artifact Localization in MRI-Guided Robotic Transrectal
Prostate Intervention
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Needle artifact; prostate intervention; robotic intervention;
transrectal biopsy
ID TRANSGLUTEAL BIOPSIES; PNEUMATIC ROBOT; FIELD SYSTEM; CANCER;
BRACHYTHERAPY; MANIPULATOR; PLACEMENT; FEASIBILITY; ACCURACY; GUIDANCE
AB Recently a number of robotic intervention systems for magnetic resonance image (MRI)-guided needle placement in the prostate have been reported. In MRI-guided needle interventions, after a needle is inserted, the needle position is often confirmed with a volumetric MRI scan. Commonly used titanium needles are not directly visible in an MRI, but they generate a susceptibility artifact in the immediate neighborhood of the needle. This paper reports the results of a quantitative study of the relationship between the true position of titanium biopsy needle and the corresponding needle artifact position in MRI, thereby providing a better understanding of the influence of needle artifact on targeting errors. The titanium needle tip artifact extended 9 mm beyond the actual needle tip location with tendency to bend toward the scanner's B-0 magnetic field direction, and axially displaced 0.38 and 0.32 mm (mean) in scanner's frequency and phase encoding direction, respectively.
C1 [Song, Sang-Eun; Cho, Nathan Bongjoon; Iordachita, Iulian I.; Whitcomb, Louis L.] Johns Hopkins Univ, Lab Computat Sensing & Robot, Baltimore, MD 21202 USA.
[Cho, Nathan Bongjoon; Iordachita, Iulian I.; Whitcomb, Louis L.] Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21202 USA.
[Guion, Peter; Kaushal, Aradhana; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Fichtinger, Gabor] Queens Univ, Dept Mech & Mat Engn, Kingston, ON K7L 3N6, Canada.
[Fichtinger, Gabor] Queens Univ, Dept Elect & Comp Engn, Kingston, ON K7L 3N6, Canada.
[Fichtinger, Gabor] Queens Univ, Sch Comp, Kingston, ON K7L 3N6, Canada.
RP Song, SE (reprint author), Harvard Univ, Surg Nav & Robot Lab, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
EM sam0song@gmail.com; cho591@gmail.com; iordachita@jhu.edu;
guionp@mail.nih.gov; gabor@cs.queensu.ca; kaushala@mail.nih.gov;
camphauk@mail.nih.gov; llw@jhu.edu
RI Iordachita, Iulian/A-3507-2010
OI Iordachita, Iulian/0000-0002-2510-9008
FU National Institutes of Health (NIH) [RO1-EB02963]
FX This work was supported by the National Institutes of Health (NIH) under
Grant RO1-EB02963. The work of G. Fichtinger was supported as Cancer
Care Ontario Research Chair. A preliminary version of this paper was
presented at the Proceedings of the 2011 IEEE International Conference
on Robotics and Automation [1].
NR 46
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U2 4
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD JUL
PY 2012
VL 59
IS 7
BP 1902
EP 1911
DI 10.1109/TBME.2012.2192118
PG 10
WC Engineering, Biomedical
SC Engineering
GA 963LL
UT WOS:000305622100012
PM 22481805
ER
PT J
AU Traore, B
Diarra, B
Dembele, BPP
Somboro, AM
Hammond, AS
Siddiqui, S
Maiga, M
Kone, B
Sarro, YS
Washington, J
Parta, M
Coulibaly, N
M'Baye, O
Diallo, S
Koita, O
Tounkara, A
Polis, MA
AF Traore, B.
Diarra, B.
Dembele, B. P. P.
Somboro, A. M.
Hammond, A. S.
Siddiqui, S.
Maiga, M.
Kone, B.
Sarro, Y. S.
Washington, J.
Parta, M.
Coulibaly, N.
M'Baye, O.
Diallo, S.
Koita, O.
Tounkara, A.
Polis, M. A.
TI Molecular strain typing of Mycobacterium tuberculosis complex in Bamako,
Mali
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Article
DE Bamako; MDR; spoligotyping
ID GENETIC DIVERSITY; RESISTANT TUBERCULOSIS; CENTRAL-ASIA; AFRICANUM;
EPIDEMIOLOGY
AB OBJECTIVE: To identify strains of Mycobacterium tuberculosis complex (MTC) circulating in Bamako and to examine the relationship between the strains and their drug susceptibility profiles.
METHODS: Between 2006 and 2010, we conducted a cross-sectional study using spoligotyping to identify strains of MTC recovered from 126 tuberculosis (TB) patients under treatment in Bamako, Mali.
RESULT: Three members of the MTC were isolated: M. tuberculosis (71.4%), M. africanum (27.8%) and M. bovis (0.8%). Of these, three strains were found to be the most prevalent: M. tuberculosis T1 (MTB T1; 38.9%), M. africanum F2 (MAF2; 26.2%) and M. tuberculosis Latin American and Mediterranean 10 (MTB LAM 10; 10.3%). MAF2 and MTB LAM 10 strains have a lower risk of multidrug resistance (MDR) than MTB T1 (respectively OR 0.1, 95%CI 0.03-0.4 and OR 0.1, 95%CI 0.01-0.8). Age >= 32 years (OR 1.4, 95%CI 0.4-3.9), negative human immunodeficiency virus status (OR 0.4, 95%CI 0.1-2.5) and male sex (OR 4, 95%CI 0.9-16.5) were not associated with MDR. The prevalence of MDR among treatment and retreatment failure patients was respectively 25% and 81.8% compared to new patients (2.9%).
CONCLUSION: This study indicates a low level of primary drug resistance in Bamako, affirms the importance of using correct drug regimens, and suggests that the MTB T1 strain may be associated with the development of resistance.
C1 [Traore, B.; Diarra, B.; Dembele, B. P. P.; Somboro, A. M.; Hammond, A. S.; Maiga, M.; Kone, B.; Sarro, Y. S.; Coulibaly, N.; M'Baye, O.; Diallo, S.; Koita, O.; Tounkara, A.] Univ Bamako Res Collaborat HIV TB, Project SEREFO NIAID, Ctr Rech & Format VIH, Sida & TB Inst Natl Malad Infectieuses & Allergiq, Bamako, Mali.
[Siddiqui, S.; Washington, J.; Parta, M.; Polis, M. A.] Natl Inst Allergy & Infect Dis, Div Clin Res, Collaborat Clin Res Branch, Bethesda, MD USA.
RP Diarra, B (reprint author), Univ Bamako, SEREFO, BP 1805, Bamako, Mali.
EM bdiarra@icermali.org
OI Traore, Brehima/0000-0001-9075-9157; Polis, Michael/0000-0002-9151-2268
FU intramural program of the US National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX The authors express special thanks to D Dabitao, S Dao, S Diop, D Goita,
H Kassambara, B Baya, O Guindo, H Diallo, M Tall, Sogoba, M Sanogo and M
H Diallo for their assistance either in the recruitment of patients or
in performing laboratory testing. They also thank all the study
volunteers for participating in this study. This work was supported by
the intramural program of the US National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
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U2 2
PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
PI PARIS
PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE
SN 1027-3719
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD JUL
PY 2012
VL 16
IS 7
BP 911
EP 916
DI 10.5588/ijtld.11.0397
PG 6
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA 964AQ
UT WOS:000305666500012
PM 22508197
ER
PT J
AU Carroll, MW
Lee, M
Cai, Y
Hallahan, CW
Shaw, PA
Min, JH
Goldfeder, LC
Alekseyev, V
Grinkrug, S
Kang, HS
Hwang, S
Park, HM
Kang, E
Lee, SY
Jin, B
Park, HE
Min, S
Park, SK
Jeon, DS
Via, LE
Barry, CE
AF Carroll, M. W.
Lee, M.
Cai, Y.
Hallahan, C. W.
Shaw, P. A.
Min, J. H.
Goldfeder, L. C.
Alekseyev, V.
Grinkrug, S.
Kang, H. S.
Hwang, S.
Park, H-M.
Kang, E.
Lee, S-Y.
Jin, B.
Park, H-E.
Min, S.
Park, S. K.
Jeon, D. S.
Via, L. E.
Barry, C. E., III
TI Frequency of adverse reactions to first- and second-line
anti-tuberculosis chemotherapy in a Korean cohort
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Article
DE drug-resistant tuberculosis; drug toxicity; linezolid
ID DRUG-RESISTANT TUBERCULOSIS; INTRACTABLE MULTIDRUG-RESISTANT;
HIV-INFECTED PATIENTS; TREATMENT OUTCOMES; MDR-TB; SURVIVAL; 1ST-LINE;
IMPACT
AB OBJECTIVE: To determine the frequency of and risk factors for major adverse drug reactions (MADRs) associated with anti-tuberculosis treatment at a tuberculosis (TB) referral hospital in the Republic of Korea.
METHODS: Data from an ongoing natural history cohort study were analyzed for permanent regimen changes due to adverse drug reactions and confirmed by chart review.
RESULTS: Among 655 subjects, there were 132 MADRs in 112 (17%) subjects. The most common MADRs were gastrointestinal (n = 53), musculoskeletal (n = 22), psychiatric (n = 10), visual (n = 9) and peripheral neuropathic (n = 8). MADRs were more frequent in subjects being treated with second-line regimens (16%) compared to first-line regimens (2.5%). Drugs frequently associated with MADRs were amikacin (3/10, 30%), linezolid (8/29, 28%), para-aminosalicylic acid (47/192, 24%), pyrazinamide (31/528, 5.8%), macrolides (2/44, 4.5%) and cycloserine (12/272, 4.4%). Fluoroquinolones accounted for a single MADR (1/377, 0.003%), despite widespread usage. In multivariate analysis, infection with multi- or extensively drug-resistant disease and previous history of anti-tuberculosis treatment were risk factors for MADR, with adjusted hazard ratios of respectively 2.2 (P = 0.02) and 1.6 (P = 0.04).
CONCLUSION: MADRs are common during anti-tuberculosis chemotherapy in this population, occurring in more than one in six subjects. New and less toxic agents to treat drug-resistant TB are urgently needed.
C1 [Barry, C. E., III] NIAID, TB Res Sect, NIH, Biostat Res Branch, Bethesda, MD 20892 USA.
[Carroll, M. W.; Lee, M.; Park, H-M.; Kang, E.; Lee, S-Y.; Jin, B.; Park, H-E.; Min, S.; Park, S. K.] Int TB Res Ctr, Masan, South Korea.
[Carroll, M. W.; Cai, Y.; Goldfeder, L. C.; Via, L. E.] TB Res Sect, Lab Clin Infect Dis, Bethesda, MD USA.
[Min, J. H.; Kang, H. S.; Hwang, S.; Park, S. K.; Jeon, D. S.] Natl Masan TB Hosp, Masan, South Korea.
[Alekseyev, V.; Grinkrug, S.] NIAID, Off Cyber Infrastruct & Comp Biol, NIH, Bethesda, MD USA.
RP Barry, CE (reprint author), NIAID, TB Res Sect, NIH, Biostat Res Branch, Room 2W20D,Bldg 33,33 N Dr, Bethesda, MD 20892 USA.
EM cbarry@mail.niaid.gov
RI Barry, III, Clifton/H-3839-2012;
OI Via, Laura/0000-0001-6074-9521
FU Intramural Research Program of the National Institutes of Health, NIAID;
Korean Ministry of Health and Welfare
FX The authors sincerely thank the many subjects who have been willing to
sacrifice their time and energy to contribute to this study, and the
doctors and nurses of the National Masan Tuberculosis Hospital for their
continued support. They also thank the National Institute of Allergy and
Infectious Diseases (NIAID) Office of Cyber Infrastructure and
Computational Biology for supporting the development of the database
that made this study possible. This research was funded (in part) by the
Intramural Research Program of the National Institutes of Health, NIAID
and (in part) by on-going support from the Korean Ministry of Health and
Welfare.
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U2 4
PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
PI PARIS
PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE
SN 1027-3719
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD JUL
PY 2012
VL 16
IS 7
BP 961
EP 966
DI 10.5588/ijtld.11.0574
PG 6
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA 964AQ
UT WOS:000305666500021
PM 22584241
ER
PT J
AU Watts, DH
AF Watts, D. Heather
TI Mother to Child Transmission of HIV-Another Complication of Bacterial
Vaginosis?
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Editorial Material
ID IMMUNODEFICIENCY-VIRUS TYPE-1; PELVIC-INFLAMMATORY-DISEASE; SPONTANEOUS
PRETERM BIRTH; ABNORMAL VAGINAL FLORA; FEMALE GENITAL-TRACT;
RISK-FACTORS; GRAM STAIN; INFECTION; ASSOCIATION; WOMEN
C1 NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD 20852 USA.
RP Watts, DH (reprint author), NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD 20852 USA.
NR 46
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U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUL 1
PY 2012
VL 60
IS 3
BP 221
EP 224
DI 10.1097/QAI.0b013e318256941c
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 965YT
UT WOS:000305804400011
PM 22481604
ER
PT J
AU Rasimas, J
Katsounas, A
Raza, H
Murphy, AA
Yang, J
Lempicki, RA
Osinusi, A
Masur, H
Polis, M
Kottilil, S
Rosenstein, D
AF Rasimas, Joseph
Katsounas, Antonios
Raza, Haniya
Murphy, Alison A.
Yang, Jun
Lempicki, Richard A.
Osinusi, Anu
Masur, Henry
Polis, Michael
Kottilil, Shyam
Rosenstein, Donald
TI Gene Expression Profiles Predict Emergence of Psychiatric Adverse Events
in HIV/HCV-Coinfected Patients on Interferon-Based HCV Therapy
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV/HCV; peg-interferon; psychiatric toxicities; gene expression;
prediction
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC HEPATITIS-C; HIV-INFECTED
PATIENTS; PLUS RIBAVIRIN; PEGYLATED INTERFERON-ALPHA-2B;
GLUTAMINE-SYNTHETASE; HUMAN-BRAIN; ALPHA; ACTIVATION; DEPRESSION
AB Background: The efficacy of pegylated interferon-alpha and ribavirin (pegIFN/RBV) in the treatment of Hepatitis C infection is limited by psychiatric adverse effects (IFN-PE). Our study examined the ability of differential gene expression patterns before therapy to predict emergent IFN-PE among 28 HIV/HCV-coinfected patients treated with pegIFN-alpha 2b/RBV.
Methods: Patients dually infected with HIV and HCV were evaluated at baseline and during treatment by board-certified psychiatrists who classified patients into 2 groups: those who developed IFN-PE and those who did not (IFN-NPE). Gene expression analysis (Affymetrix HG-U133A) was performed using peripheral blood mononuclear cells before and after initiation of treatment. Analysis of Variance, post hoc analysis based on pair-wise comparisons, and functional annotation analysis identified differentially expressed genes within and between groups. Prediction analysis for microarrays was used to test the predictive ability of selected genes.
Results: Twenty-four genes (16 upregulated and 8 downregulated) that were differentially expressed at baseline in patients who subsequently developed IFN-PE compared with the IFN-NPE group showed the ability to predict IFN-PE with an accuracy of 82%. In 16 patients with IFN-PE, 135 genes (117 upregulated; 18 downregulated) were significantly modulated after treatment. Of these, 10 genes have already been shown to be associated with neuropsychiatric illnesses and were significantly modulated only in patients who experienced IFN-PE.
Conclusions: We describe a novel molecular diagnostic biomarker panel to predict emergent IFN-PE in HIV/HCV-coinfected patients undergoing pegIFN/RBV treatment, which may improve the identification of patients at greatest risk for IFN-PE and suggest candidate therapeutic targets for preventing or treating IFN-PE.
C1 [Murphy, Alison A.; Osinusi, Anu; Polis, Michael; Kottilil, Shyam] NIAID, Sect Immunopathogenesis, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Rasimas, Joseph; Rosenstein, Donald] NIMH, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Rasimas, Joseph] Penn State Coll Med, Dept Psychiat, Hershey, PA USA.
[Katsounas, Antonios; Yang, Jun; Lempicki, Richard A.] NCI, Lab Immunopathogenesis & Bioinformat, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Katsounas, Antonios] Dept Gastroenterol & Hepatol, D Essen, Germany.
[Raza, Haniya] Childrens Natl Med Ctr, Dept Psychiat & Behav Sci, Washington, DC 20010 USA.
[Osinusi, Anu] NCI, Clin Res Directorate, Clin Monitoring Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Masur, Henry] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Rosenstein, Donald] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
RP Kottilil, S (reprint author), NIAID, Sect Immunopathogenesis, Immunoregulat Lab, NIH, Bldg 10,Room 11N204,10 Ctr Dr, Bethesda, MD 20892 USA.
EM skotti-lil@niaid.nih.gov
RI Lempicki, Richard/E-1844-2012;
OI Lempicki, Richard/0000-0002-7059-409X; Polis,
Michael/0000-0002-9151-2268
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH (National Institute of Allergy and Infectious
Diseases)
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. This research was supported in whole or
in part by the Intramural Research Program of the NIH (National
Institute of Allergy and Infectious Diseases).
NR 31
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUL 1
PY 2012
VL 60
IS 3
BP 273
EP 281
DI 10.1097/QAI.0b013e31824c17c4
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 965YT
UT WOS:000305804400018
PM 22728749
ER
PT J
AU Faussone-Pellegrini, MS
Grover, M
Pasricha, PJ
Bernard, CE
Lurken, MS
Smyrk, TC
Parkman, HP
Abell, TL
Snape, WJ
Hasler, WL
Unalp-Arida, A
Nguyen, L
Koch, KL
Calles, J
Lee, LD
Tonascia, J
Hamilton, FA
Farrugia, G
AF Faussone-Pellegrini, Maria Simonetta
Grover, Madhusudan
Pasricha, Pankaj J.
Bernard, Cheryl E.
Lurken, Matthew S.
Smyrk, Thomas C.
Parkman, Henry P.
Abell, Thomas L.
Snape, William J.
Hasler, William L.
Uenalp-Arida, Aynur
Linda Nguyen
Koch, Kenneth L.
Calles, Jorges
Lee, Linda
Tonascia, James
Hamilton, Frank A.
Farrugia, Gianrico
CA NIDDK Gastroparesis Clinical Res
TI Ultrastructural differences between diabetic and idiopathic
gastroparesis
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE electron microscopy; smooth muscle; enteric nerves; interstitial cells
of Cajal
ID NITRIC-OXIDE SYNTHASE; INTERSTITIAL-CELLS; PATHOLOGICAL FINDINGS;
MYENTERIC PLEXUS; HUMAN STOMACH; ANIMAL-MODEL; CAJAL; EXPRESSION;
INNERVATION; NETWORK
AB The ultrastructural changes in diabetic and idiopathic gastroparesis are not well studied and it is not known whether there are different defects in the two disorders. As part of the Gastroparesis Clinical Research Consortium, full thickness gastric body biopsies from 20 diabetic and 20 idiopathic gastroparetics were studied by light microscopy. Abnormalities were found in many (83%) but not all patients. Among the common defects were loss of interstitial cells of Cajal (ICC) and neural abnormalities. No distinguishing features were seen between diabetic and idiopathic gastroparesis. Our aim was to provide a detailed description of the ultrastructural abnormalities, compare findings between diabetic and idiopathic gastroparesis and determine if patients with apparently normal immunohistological features have ultrastructural abnormalities. Tissues from 40 gastroparetic patients and 24 age- and sex-matched controls were examined by transmission electron microscopy (TEM). Interstitial cells of Cajal showing changes suggestive of injury, large and empty nerve endings, presence of lipofuscin and lamellar bodies in the smooth muscle cells were found in all patients. However, the ultrastructural changes in ICC and nerves differed between diabetic and idiopathic gastroparesis and were more severe in idiopathic gastroparesis. A thickened basal lamina around smooth muscle cells and nerves was characteristic of diabetic gastroparesis whereas idiopathic gastroparetics had fibrosis, especially around the nerves. In conclusion, in all the patients TEM showed abnormalities in ICC, nerves and smooth muscle consistent with the delay in gastric emptying. The significant differences found between diabetic and idiopathic gastroparesis offers insight into pathophysiology as well as into potential targeted therapies.
C1 [Grover, Madhusudan; Bernard, Cheryl E.; Lurken, Matthew S.; Smyrk, Thomas C.; Farrugia, Gianrico] Mayo Clin, Rochester, MN 55905 USA.
[Faussone-Pellegrini, Maria Simonetta] Univ Florence, Florence, Italy.
[Pasricha, Pankaj J.; Linda Nguyen] Stanford Univ, Palo Alto, CA 94304 USA.
[Parkman, Henry P.] Temple Univ, Philadelphia, PA 19122 USA.
[Smyrk, Thomas C.] Univ Mississippi, Jackson, MS 39216 USA.
[Snape, William J.] Calif Pacific Med Ctr, San Francisco, CA USA.
[Abell, Thomas L.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Uenalp-Arida, Aynur; Lee, Linda; Tonascia, James] Johns Hopkins Univ, Baltimore, MD USA.
[Koch, Kenneth L.; Calles, Jorges] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Hamilton, Frank A.] NIDDK, Bethesda, MD USA.
RP Farrugia, G (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA.
EM farrugia.gianrico@mayo.edu
RI Vaughn, Ivana/B-6138-2016
OI Vaughn, Ivana/0000-0002-7201-0289
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[U01DK073983, U01DK073975, U01DK073985, U01DK074007, U01DK073974,
U01DK074008]; [DK57061]; [DK84567]; [PO1 DK68055]
FX We give thanks to Dr. Sean Harbison, Megan Garrity-Park, Shelly Gray,
Valerie McNair, Gary Stoltz, Peter Strege and Kristy Zodrow for
excellent technical and secretarial assistance, and to Daniele Guasti
for his precious and excellent technical support for the electron
microscope study. The Gastroparesis Clinical Research Consortium (GpCRC)
is supported by the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) (grants U01DK073983, U01DK073975, U01DK073985,
U01DK074007, U01DK073974, U01DK074008). This work was also supported by
DK57061, DK84567 and PO1 DK68055.
NR 33
TC 28
Z9 34
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1582-1838
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD JUL
PY 2012
VL 16
IS 7
BP 1573
EP 1581
DI 10.1111/j.1582-4934.2011.01451.x
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 965UA
UT WOS:000305791600021
PM 21914127
ER
PT J
AU Giannobile, WV
Joskow, RW
AF Giannobile, W. V.
Joskow, R. W.
TI Clinical and Translational Oral Health Research: Prospects for the
Future
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Editorial Material
DE clinical research; translational research; personalized medicine;
biomedical research; comparative effectiveness research; dental devices
ID MEDICINE
C1 [Giannobile, W. V.] Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Michigan Ctr Oral Hlth Res, Ann Arbor, MI 48109 USA.
[Giannobile, W. V.] Univ Michigan, Coll Engn, Dept Biomed Engn, Ann Arbor, MI 48109 USA.
[Joskow, R. W.] NIH, US Dept Hlth & Human Serv, Natl Ctr Adv Translat Sci, Div Clin Innovat, Bethesda, MD 20892 USA.
[Joskow, R. W.] US Hlth Resources & Serv Adm, US Dept Hlth & Human Serv, Off Special Hlth Affairs, Rockville, MD 20857 USA.
RP Giannobile, WV (reprint author), Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Michigan Ctr Oral Hlth Res, 1011 N Univ Ave, Ann Arbor, MI 48109 USA.
EM wgiannob@umich.edu
OI Giannobile, William/0000-0002-7102-9746
NR 31
TC 2
Z9 2
U1 0
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD JUL
PY 2012
VL 91
IS 7
BP 633
EP 636
DI 10.1177/0022034512450711
PG 4
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 964PM
UT WOS:000305708600001
PM 22736671
ER
PT J
AU Zsengeller, ZK
Ellezian, L
Brown, D
Horvath, B
Mukhopadhyay, P
Kalyanaraman, B
Parikh, SM
Karumanchi, SA
Stillman, IE
Pacher, P
AF Zsengeller, Zsuzsanna K.
Ellezian, Lena
Brown, Dan
Horvath, Bela
Mukhopadhyay, Partha
Kalyanaraman, Balaraman
Parikh, Samir M.
Karumanchi, S. Ananth
Stillman, Isaac E.
Pacher, Pal
TI Cisplatin Nephrotoxicity Involves Mitochondrial Injury with Impaired
Tubular Mitochondrial Enzyme Activity
SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
LA English
DT Article
DE cisplatin; nephrotoxicity; mitochondria; cytochrome c oxidase;
functional electron microscopy
ID ACUTE-RENAL-FAILURE; RESPIRATORY-CHAIN; ALPHA; CELLS; RATS; DYSFUNCTION;
INHIBITION; EXPRESSION; DECREASES; MECHANISM
AB Cisplatin is a widely used antineoplastic agent. However, its major limitation is dose-dependent nephrotoxicity whose precise mechanism is poorly understood. Recent studies have suggested that mitochondrial dysfunction in tubular epithelium contributes to cisplatin-induced nephrotoxicity. Here the authors extend those findings by describing the role of an important electron transport chain enzyme, cytochrome c oxidase (COX). Immunohistochemistry for COX 1 protein demonstrated that, in response to cisplatin, expression was mostly maintained in focally damaged tubular epithelium. In contrast, COX enzyme activity in proximal tubules (by light microscopy) was decreased. Ultrastructural analysis of the cortex and outer stripe of the outer medulla showed decreased mitochondrial mass, disruption of cristae, and extensive mitochondrial swelling in proximal tubular epithelium. Functional electron microscopy showed that COX enzyme activity was decreased in the remaining mitochondria in the proximal tubules but maintained in distal tubules. In summary, cisplatin-induced nephrotoxicity is associated with structural and functional damage to the mitochondria. More broadly, using functional electron microscopy to measure mitochondrial enzyme activity may generate mechanistic insights across a spectrum of renal disorders. (J Histochem Cytochem 60:521-529, 2012)
C1 [Zsengeller, Zsuzsanna K.; Ellezian, Lena; Brown, Dan; Stillman, Isaac E.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
[Parikh, Samir M.; Karumanchi, S. Ananth; Stillman, Isaac E.] Beth Israel Deaconess Med Ctr, Div Renal, Dept Med, Boston, MA 02215 USA.
[Parikh, Samir M.; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02215 USA.
[Horvath, Bela; Mukhopadhyay, Partha; Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA.
[Kalyanaraman, Balaraman] Med Coll Wisconsin, Free Rad Res Ctr, Dept Biophys, Milwaukee, WI 53226 USA.
RP Zsengeller, ZK (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA.
EM zzsengel@bidmc.harvard.edu
RI MUKHOPADHYAY, PARTHA/G-3890-2010; Horvath, Bela/A-7368-2009; Pacher,
Pal/B-6378-2008
OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher,
Pal/0000-0001-7036-8108
FU NIH/NIAAA
FX The authors disclosed receipt of the following financial support for the
research and/or authorship of this article: This study was supported by
the Intramural Program of NIH/NIAAA to PP.
NR 42
TC 30
Z9 31
U1 0
U2 5
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0022-1554
J9 J HISTOCHEM CYTOCHEM
JI J. Histochem. Cytochem.
PD JUL
PY 2012
VL 60
IS 7
BP 521
EP 529
DI 10.1369/0022155412446227
PG 9
WC Cell Biology
SC Cell Biology
GA 964PO
UT WOS:000305709000004
PM 22511597
ER
PT J
AU Savasan, ZA
Chaiworapongsa, T
Romero, R
Hussein, Y
Kusanovic, JP
Xu, Y
Dong, Z
Kim, CJ
Hassan, SS
AF Savasan, Zeynep Alpay
Chaiworapongsa, Tinnakorn
Romero, Roberto
Hussein, Youssef
Kusanovic, Juan Pedro
Xu, Yi
Dong, Zhong
Kim, Chong Jai
Hassan, Sonia S.
TI Interleukin-19 in fetal systemic inflammation
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Fetal inflammatory response syndrome (FIRS); chorioamnionitis;
funisitis; anti-inflammatory limb; IL-10; preterm repture of membranes
(PROM); childhood asthma; SIDS; prematurity; preterm labor; immune
programming
ID PRETERM PREMATURE RUPTURE; NECROSIS-FACTOR-ALPHA; INFANT-DEATH-SYNDROME;
AMNIOTIC-FLUID INTERLEUKIN-6; WHITE-MATTER LESIONS; EXPERIMENTAL
INTRAUTERINE INFECTION; ANTIINFLAMMATORY RESPONSE SYNDROME; IMPAIRED
NEUROLOGIC OUTCOMES; HERPES-SIMPLEX INFECTION; PREGNANT RHESUS-MONKEYS
AB Objective: The fetal inflammatory response syndrome (FIRS) is considered the fetal counterpart of the systemic inflammatory response syndrome (SIRS), which can be caused by infection and non-infection-related insults. Although the initial response is mediated by pro-inflammatory signals, the control of this response is achieved by anti-inflammatory mediators which are essential for the successful outcome of the affected individual. Interleukin (IL)-19 is capable of stimulating the production of IL-10, a major anti-inflammatory cytokine, and is a potent inducer of the T-helper 2 (Th2) response. The aim of this study was to determine if there is a change in umbilical cord plasma IL-19 and IL-10 concentrations in preterm neonates with and without acute funisitis, the histologic counterpart of FIRS. Methods: A case-control study was conducted including 80 preterm neonates born after spontaneous labor. Neonates were classified according to the presence (n = 40) or absence of funisitis (n = 40), which is the pathologic hallmark of FIRS. Neonates in each group were also matched for gestational age. Umbilical cord plasma IL-19 and IL-10 concentrations were determined by ELISA. Results: 1) The median umbilical cord plasma IL-19 concentration was 2.5-fold higher in neonates with funisitis than in those without funisitis (median 87 pg/mL; range 20.6-412.6 pg/mL vs. median 37 pg/mL; range 0-101.7 pg/mL; p < 0.001); 2) newborns with funisitis had a significantly higher median umbilical cord plasma IL-10 concentration than those without funisitis (median 4 pg/mL; range 0-33.5 pg/mL vs. median 2 pg/mL; range 0-13.8 pg/mL; p < 0.001); and 3) the results were similar when we included only patients with funisitis who met the definition of FIRS by umbilical cord plasma IL-6 concentrations >= 17.5 pg/mL (p < 0.001). Conclusion: IL-19 and IL-10 are parts of the immunologic response of FIRS. A subset of fetuses with FIRS had high umbilical cord plasma IL-19 concentrations. In utero exposure to high systemic concentrations of IL-19 may reprogram the immune response.
C1 [Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, NICHD NIH DHHS, Perinatol Res Branch, Detroit, MI 48201 USA.
[Savasan, Zeynep Alpay; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Kusanovic, Juan Pedro] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile.
[Kusanovic, Juan Pedro] Hosp Dr Sotero del Rio, Ctr Perinatal Res, Santiago, Chile.
[Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD NIH DHHS, Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported, in part, by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS. Presented at
the 56th Annual Meeting of the Society for Gynecologic Investigation,
March 16-19, 2011, Miami, FL
NR 248
TC 11
Z9 11
U1 1
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD JUL
PY 2012
VL 25
IS 7
BP 995
EP 1005
DI 10.3109/14767058.2011.605917
PG 11
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 964NZ
UT WOS:000305704000026
PM 21767236
ER
PT J
AU Romero, R
Soto, E
Berry, SM
Hassan, SS
Kusanovic, JP
Yoon, BH
Edwin, S
Mazor, M
Chaiworapongsa, T
AF Romero, Roberto
Soto, Eleazar
Berry, Stanley M.
Hassan, Sonia S.
Pedro Kusanovic, Juan
Yoon, Bo Hyun
Edwin, Samuel
Mazor, Moshe
Chaiworapongsa, Tinnakorn
TI Blood pH and gases in fetuses in preterm labor with and without systemic
inflammatory response syndrome
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Base excess; cordocentesis; fetal blood gases; hypoxia; intra-amniotic
infection; pregnancy; PaO2
ID TUMOR-NECROSIS-FACTOR; AMNIOTIC-FLUID INTERLEUKIN-6; ULTRASONOGRAPHIC
CERVICAL LENGTH; CORTICOTROPIN-RELEASING HORMONE; UMBILICAL-CORD PLASMA;
WHITE-MATTER LESIONS; PREMATURE RUPTURE; INTRAAMNIOTIC INFECTION;
INTRAUTERINE INFECTION; MICROBIAL INVASION
AB Objective: Fetal hypoxemia has been proposed to be one of the mechanisms of preterm labor (PTL) and delivery. This may have clinical implications since it may alter: (i) the method/frequency of fetal surveillance and (ii) the indications and duration of tocolysis to an already compromised fetus. The aim of this study was to examine whether there is a difference in the fetal blood gas analysis [pH, PaO2 and base excess (BE)] and in the prevalence of fetal acidemia and hypoxia between: (i) patients in PTL who delivered within 72 hours vs. those who delivered more than 72 hours after cordocentesis and (ii) patients with fetal inflammatory response syndrome (FIRS) vs. those without this condition. Study design: Patients admitted with PTL underwent amniocentesis and cordocentesis. Ninety women with singleton pregnancies and PTL were classified according to (i) those who delivered within 72 hours (n = 30) and after 72 hours of the cordocentesis (n = 60) and (ii) with and without FIRS. FIRS was defined as a fetal plasma concentration of IL-6 > 11 pg/mL. Fetal blood gases were determined. Acidemia and hypoxemia were defined as fetal pH and PaO2 below the 5th percentile for gestational age, respectively. For comparisons between the two study groups, Delta pH and Delta PaO2 were calculated by adjusting for gestational age (. = observed value - mean for gestational age). Non-parametric statistics were employed. Results: No differences in the median Delta pH (-0.026 vs. -0.016), Delta PaO2 (0.25 mmHg vs. 5.9 mmHg) or BE (-2.4 vs. -2.6 mEq/L) were found between patients with PTL who delivered within 72 hours and those who delivered 72 hours after the cordocentesis (p > 0.05 for all comparisons). Fetal plasma IL-6 concentration was determined in 63% (57/90) of fetuses and the prevalence of FIRS was 28% (16/57). There was no difference in fetal pH, PaO2 and BE between fetuses with and without FIRS (p > 0.05 for all comparisons). Moreover, there was no difference in the rate of fetal acidemia between fetuses with and without FIRS (6.3 vs. 9.8%; p > 0.05) and fetal hypoxia between fetuses with or without FIRS (12.5 vs. 19.5%; p > 0.05). Conclusions: Our data do not support a role for acute fetal hypoxemia and metabolic acidemia in the etiology of PTL and delivery.
C1 [Romero, Roberto; Soto, Eleazar; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Detroit, MI 48201 USA.
[Romero, Roberto; Soto, Eleazar; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Bethesda, MD USA.
[Soto, Eleazar; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI 48201 USA.
[Berry, Stanley M.] William Beaumont Hosp, Royal Oak, MI 48072 USA.
[Pedro Kusanovic, Juan] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile.
[Pedro Kusanovic, Juan] Hosp Dr Sotero del Rio, Ctr Perinatal Res, Santiago, Chile.
[Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Seoul, South Korea.
[Edwin, Samuel] Biosurety Div USAMRIID, Frederick, MD USA.
[Mazor, Moshe] Ben Gurion Univ Negev, Soroka Med Ctr, IL-84105 Beer Sheva, Israel.
RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
RI Yoon, Bo Hyun/H-6344-2011
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported, in part, by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
NR 165
TC 12
Z9 12
U1 0
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD JUL
PY 2012
VL 25
IS 7
BP 1160
EP 1170
DI 10.3109/14767058.2011.629247
PG 11
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 964NZ
UT WOS:000305704000059
PM 21988103
ER
PT J
AU Lister, G
Rybin, DV
Colton, T
Heeren, TC
Hunt, CE
Colson, ER
Willinger, M
Corwin, MJ
AF Lister, George
Rybin, Denis V.
Colton, Theodore
Heeren, Timothy C.
Hunt, Carl E.
Colson, Eve R.
Willinger, Marian
Corwin, Michael J.
CA CHIME Study Grp
TI Relationship between Sleep Position and Risk of Extreme
Cardiorespiratory Events
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID INFANT-DEATH-SYNDROME; HOME
AB Objective To determine whether infants at sleep in the prone side positions are at higher risk for an extreme cardiorespiratory event compared with infants at sleep in the supine position.
Study design We used a case-control study to compare sleep position, determined with an accelerometer, in 116 infants during an extreme cardiorespiratory event with that in 231 matched control subjects (2 per case) who did not experience any extreme events during monitoring.
Results From calculation of adjusted ORs and 95% CIs, infants placed in the prone or side position were no more likely to experience an extreme cardiorespiratory event compared with infants at sleep in the supine position. We used conditional logistic regression to account for the matched design of the study and to adjust for potential confounders or effect-modifiers.
Conclusion These findings, coupled with our earlier observation that the peak incidence of severe cardiorespiratory events occurred before the peak incidence of sudden infant death syndrome, strongly suggest that the supine sleeping position decreases the risk of sudden infant death syndrome by mechanisms other than by decreasing extreme cardiorespiratory events detected by monitoring. (J Pediatr 2012;square:square-square).
C1 [Lister, George] Univ Texas SW Med Sch, Dept Pediat, Dallas, TX 75390 USA.
[Rybin, Denis V.] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA.
[Colton, Theodore; Corwin, Michael J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Heeren, Timothy C.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Hunt, Carl E.] Univ Toledo, Hlth Sci Ctr, Dept Pediat, Toledo, OH 43606 USA.
[Colson, Eve R.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Willinger, Marian] NICHHD, NIH, Bethesda, MD 20892 USA.
[Corwin, Michael J.] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA.
[Corwin, Michael J.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA.
[Corwin, Michael J.] Boston Univ, Sch Publ Hlth, Dept Pediat, Boston, MA USA.
RP Lister, G (reprint author), Univ Texas SW Med Sch, Dept Pediat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM george.lister@utsouthwestern.edu
OI Corwin, Michael/0000-0002-6591-209X; Heeren,
Timothy/0000-0001-5643-3559; Rybin, Denis/0000-0002-3657-4829
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development of the National Institutes of Health HD [HD 29067, 29071,
28971, 29073, 29060, 20056, 34625, 59207]
FX Supported by the Eunice Kennedy Shriver National Institute of Child
Health & Human Development of the National Institutes of Health HD
(grants HD 29067, 29071, 28971, 29073, 29060, 20056, 34625, and 59207).
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the Eunice Kennedy Shriver
National Institute of Child Health & Human Development or the National
Institutes of Health. The authors declare no conflicts of interest.
NR 8
TC 0
Z9 1
U1 1
U2 3
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 JUL
PY 2012
VL 161
IS 1
BP 22
EP +
DI 10.1016/j.jpeds.2012.01.035
PG 5
WC Pediatrics
SC Pediatrics
GA 965FX
UT WOS:000305753700008
PM 22364822
ER
PT J
AU Batton, BJ
Li, L
Newman, NS
Das, A
Watterberg, KL
Yoder, BA
Faix, RG
Laughon, MM
Van Meurs, KP
Carlo, WA
Higgins, RD
Walsh, MC
AF Batton, Beau J.
Li, Lei
Newman, Nancy S.
Das, Abhik
Watterberg, Kristi L.
Yoder, Bradley A.
Faix, Roger G.
Laughon, Matthew M.
Van Meurs, Krisa P.
Carlo, Waldemar A.
Higgins, Rosemary D.
Walsh, Michele C.
CA Eunice Kennedy Shriver Natl Inst
TI Feasibility Study of Early Blood Pressure Management in Extremely
Preterm Infants
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID BIRTH-WEIGHT INFANTS; GESTATIONAL-AGE NEWBORNS; 1ST 7 DAYS;
BRONCHOPULMONARY DYSPLASIA; VOLUME EXPANSION; HYPOTENSION; MORBIDITY;
DOPAMINE; HYDROCORTISONE; DEATH
AB Objective To assess the feasibility of a randomized placebo controlled trial (RCT) of blood pressure (BP) management for extremely preterm infants.
Study design This was a prospective pilot RCT of infants 23-0/7 to 26-6/7 weeks gestation who had protocol-defined low BP in the first 24 postnatal hours. Enrolled infants were administered a study infusion (dopamine or placebo) and a study syringe medication (hydrocortisone or placebo).
Results Of the 366 infants screened, 119 (33%) had low BP, 58 (16%) met all entry criteria, and 10 (3%) were enrolled. A total of 161 infants (44%) were ineligible because they received early indomethacin. Only 17% of eligible infants were enrolled. Problems with consent included insufficient time, parent unavailability, and physician unwillingness to enroll critically ill infants. Two infants were withdrawn from the study because of the potential risk of intestinal perforation with simultaneous administration of hydrocortisone and indomethacin.
Conclusions This pilot RCT was not feasible because of low eligibility and consent rates. An RCT of BP management for extremely preterm infants may require a waiver of consent for research in emergency care. The frequent use of early indomethacin and the associated risk of intestinal perforation when used with hydrocortisone may limit future investigations to only inotropic medications. (J Pediatr 2012; 161: 65-9).
C1 [Batton, Beau J.; Newman, Nancy S.; Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Li, Lei] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Watterberg, Kristi L.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Yoder, Bradley A.; Faix, Roger G.] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA.
[Laughon, Matthew M.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
[Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Batton, BJ (reprint author), So Illinois Univ, Sch Med, Dept Pediat, Div Neonatol, POB 19676, Springfield, IL 62794 USA.
EM bbatton@siumed.edu
FU The National Institutes of Health; Eunice Kennedy Shriver National
Institute of Child Health and Human Development; Best Pharmaceuticals
FX The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development provided grant
support, including funding from the Best Pharmaceuticals for Children
Act, for the Neonatal Research Network's Early Blood Pressure Pilot
Study. Data collected at participating sites of the National Institute
of Child Health and Human Development Neonatal Research Network were
transmitted to RTI International, the data coordinating center for the
network, which stored, managed, and analyzed the data for this study.
The authors declare no conflicts of interest.
NR 30
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Z9 17
U1 0
U2 3
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 JUL
PY 2012
VL 161
IS 1
BP 65
EP +
DI 10.1016/j.jpeds.2012.01.014
PG 6
WC Pediatrics
SC Pediatrics
GA 965FX
UT WOS:000305753700016
PM 22336574
ER
PT J
AU De Jesus, LC
Pappas, A
Shankaran, S
Kendrick, D
Das, A
Higgins, RD
Bell, EF
Stoll, BJ
Laptook, AR
Walsh, MC
AF De Jesus, Lilia C.
Pappas, Athina
Shankaran, Seetha
Kendrick, Douglas
Das, Abhik
Higgins, Rosemary D.
Bell, Edward F.
Stoll, Barbara J.
Laptook, Abbot R.
Walsh, Michele C.
CA Eunice Kennedy Shriver Nal Inst
TI Risk Factors for Post-Neonatal Intensive Care Unit Discharge Mortality
among Extremely Low Birth Weight Infants
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID SOCIOECONOMIC DISPARITIES; NEONATAL INFECTION; CHORIOAMNIONITIS;
OUTCOMES; SEPSIS; COHORT; STATES; DEATH; LABOR
AB Objective The study goal was to evaluate maternal and neonatal risk factors associated with post-neonatal intensive care unit (NICU) discharge mortality among extremely low birth weight (ELBW) infants.
Study design This is a retrospective analysis of ELBW (<1000 g) and <27 weeks' gestational age infants born in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network sites between January 2000 and June 2007. Infants were tracked until death or 18 to 22 months' corrected age. Infants who died between NICU discharge and the 18- to 22-month follow-up visit were classified as post-NICU discharge mortality (P-NDM). Association of maternal and infant risk factors with P-NDM was determined using logistic regression analysis. A prediction model with 6 significant predictors was developed and validated.
Results There were 5364 infants who survived to NICU discharge; 557 (10%) infants were lost to follow-up, and 107 infants died following NICU discharge. P-NDM rate was 22.3 per 1000 ELBW infants. In the prediction model, African American race, unknown maternal health insurance, and hospital stay >= 120 days significantly increased risk, and maternal exposure to intrapartum antibiotics was associated with decreased risk of P-NDM.
Conclusion We identified African American race, unknown medical insurance, and prolonged NICU stay as risk factors associated with P-NDM among ELBW infants. (J Pediatr 2012;square:square-square).
C1 [De Jesus, Lilia C.; Pappas, Athina; Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Kendrick, Douglas; Das, Abhik] RTI Int, StatEpi Div, Res Triangle Pk, NC USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Laptook, Abbot R.] Brown Univ, Dept Pediat, Providence, RI 02912 USA.
[Walsh, Michele C.] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA.
RP De Jesus, LC (reprint author), Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
RI Myers , Gary /I-4901-2013
OI Myers , Gary /0000-0003-4317-015X
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD)
FX Supported by grants from the National Institutes of Health and the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) for the Neonatal Research Network's Generic Database
and Follow-up Studies. Data collected at participating sites of the
NICHD Neonatal Research Network were transmitted to RTI International,
the data coordinating center for the network, which stored, managed, and
analyzed the data for this study. The authors declare no conflicts of
interest.
NR 24
TC 6
Z9 6
U1 0
U2 5
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 JUL
PY 2012
VL 161
IS 1
BP 70
EP +
DI 10.1016/j.jpeds.2011.12.038
PG 7
WC Pediatrics
SC Pediatrics
GA 965FX
UT WOS:000305753700017
PM 22325187
ER
PT J
AU Kim, C
McGlynn, KA
McCorkle, R
Li, YH
Erickson, RL
Ma, SG
Niebuhr, DW
Zhang, GS
Zhang, YQ
Bai, YN
Dai, L
Graubard, BI
Zheng, TZ
Aschebrook-Kilfoy, B
Barry, KH
Zhang, YW
AF Kim, Christopher
McGlynn, Katherine A.
McCorkle, Ruth
Li, Yonghong
Erickson, Ralph L.
Ma, Shuangge
Niebuhr, David W.
Zhang, Guangsheng
Zhang, Yaqun
Bai, Yana
Dai, Li
Graubard, Barry I.
Zheng, Tongzhang
Aschebrook-Kilfoy, Briseis
Barry, Kathryn H.
Zhang, Yawei
TI Sexual functioning among testicular cancer survivors: A case-control
study in the U.S.
SO JOURNAL OF PSYCHOSOMATIC RESEARCH
LA English
DT Article
DE Testicular cancer; Sexual function; Military men
ID GERM-CELL TUMORS; LONG-TERM SURVIVORS; QUALITY-OF-LIFE; ERECTILE
DYSFUNCTION; BODY-IMAGE; MEN; CHEMOTHERAPY; RISK; RADIOTHERAPY;
FERTILITY
AB Objective: Sexual function among testicular cancer survivors is a concern because affected men are of reproductive age when diagnosed. We conducted a case-control study among United States military men to examine whether testicular cancer survivors experienced impaired sexual function.
Methods: A total of 246 testicular cancer cases and 236 ethnicity and age matched controls were enrolled in the study in 2008-2009. The Brief Male Sexual Function Inventory (BMSFI) was used to assess sexual function.
Results: Compared to controls, cases scored significantly lower on sex drive (5.77 vs. 5.18), erection (9.40 vs. 8.63), ejaculation (10.83 vs. 9.90), and problem assessment (10.55 vs. 9.54). Cases were significantly more likely to have impaired erection (OR 1.72; 95% CI 1.11-2.64), ejaculation (OR 2.27; 95% CI 1.32-3.91), and problem assessment (OR 2.36; 95% CI 1.43-3.90). In histology and treatment analysis, nonseminoma, chemotherapy and radiation treated cases risk of erectile dysfunction, delayed ejaculation, and/or problem assessment were greater when compared to controls.
Conclusion: This study provides evidence that testicular cancer survivors are more likely to have impaired sexual functioning compared to demographically matched controls. The observed impaired sexual functioning appeared to vary by treatment regimen and histologic subtype. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Kim, Christopher; Ma, Shuangge; Zheng, Tongzhang; Zhang, Yawei] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
[McGlynn, Katherine A.; Graubard, Barry I.; Aschebrook-Kilfoy, Briseis; Barry, Kathryn H.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD 20852 USA.
[McCorkle, Ruth] Yale Univ, Sch Nursing, New Haven, CT 06520 USA.
[Li, Yonghong; Zhang, Guangsheng] China CDC, Chinese Natl Inst Environm Hlth & Related Prod Sa, Beijing, Peoples R China.
[Erickson, Ralph L.; Niebuhr, David W.] Walter Reed Army Inst Res, Forest Glen, MD USA.
[Zhang, Yaqun] Gansu Prov Design & Res Inst Environm Sci, Lanzhou 730000, Gansu, Peoples R China.
[Bai, Yana] Lanzhou Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Lanzhou 730000, Peoples R China.
[Dai, Li] Sichuan Univ, Natl Ctr Birth Defect Monitoring, W China Univ Hosp 2, Chengdu 610041, Peoples R China.
RP Zhang, YW (reprint author), Yale Univ, Sch Publ Hlth, 60 Coll St,LEPH 440, New Haven, CT 06520 USA.
EM yawei.zhang@yale.edu
FU National Cancer Institute (NCI) [CA105666, CA130110]; National Institute
of Health (NIH) [1D43TW008323-01, 1D43TW007864-01]; CTSA from National
Center for Research Resources (NCRR), a component of the NIH [UL1
RR024139]
FX This study is supported by grants CA105666 and CA130110 from the
National Cancer Institute (NCI) and by Fogarty training grants
1D43TW008323-01 and 1D43TW007864-01 from the National Institute of
Health (NIH). This publication was made possible by CTSA Grant number
UL1 RR024139 from the National Center for Research Resources (NCRR), a
component of the NIH and NHL roadmap for medical Research. Its content
is solely the responsibility of the authors and do not necessarily
represent the official view of NCRR. The authors are greatly indebted to
the Study participants, without whom, there would have been no study.
NR 38
TC 9
Z9 9
U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3999
J9 J PSYCHOSOM RES
JI J. Psychosomat. Res.
PD JUL
PY 2012
VL 73
IS 1
BP 68
EP 73
DI 10.1016/j.jpsychores.2012.02.011
PG 6
WC Psychiatry
SC Psychiatry
GA 965NX
UT WOS:000305775600011
PM 22691563
ER
PT J
AU Sims, A
Frank, L
Cross, R
Clauss, S
Dimock, D
Purdy, J
Mikhail, I
Hazra, R
Hadigan, C
Sable, C
AF Sims, Amy
Frank, Lowell
Cross, Russell
Clauss, Sarah
Dimock, David
Purdy, Julia
Mikhail, Irene
Hazra, Rohan
Hadigan, Colleen
Sable, Craig
TI Abnormal Cardiac Strain in Children and Young Adults with HIV Acquired
in Early Life
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
DE Echocardiography; Strain; HIV; Children
ID SPECKLE-TRACKING ECHOCARDIOGRAPHY; PROSPECTIVE (PCHIV)-C-2-H-2
MULTICENTER; 2-DIMENSIONAL SPECKLE; ANTIRETROVIRAL THERAPY; INFECTED
CHILDREN; REFERENCE VALUES; VALIDATION; DYSFUNCTION; MORTALITY; HEART
AB Background: Traditional measures of cardiac function are now often normal in adolescents and young adults treated with antiretroviral therapy for human immunodeficiency virus (HIV) infection. There is, however, evidence of myocardial abnormalities in adults with HIV. Cardiac strain analysis may detect impairment in cardiac function that may be missed by conventional measurements in this population.
Methods: This was a retrospective study in which echocardiograms of HIV-infected subjects (n = 28) aged 7 to 29 years who participate in a natural history study of HIV acquired early in life were analyzed and compared with matched controls. Standard echocardiographic measures, along with speckle tracking-derived strain and strain rate, were assessed.
Results: Among the HIV-infected subjects, the median CD4 count was 667 cells/mm(3), and the mean duration of antiretroviral therapy was 14.6 years. Ejection fractions and fractional shortening were normal. There were no significant differences in measures of systolic or diastolic function between the groups. The HIV-infected group had borderline increased left ventricular mass indices. Global longitudinal and circumferential strain and strain rate, as well as global radial strain rate, were significantly impaired in the HIV-infected group compared with controls. There were no associations identified between left ventricular mass index or strain indices and current CD4 count, CD4 nadir, HIV viral load, or duration of antiretroviral therapy.
Conclusions: HIV-infected participants demonstrated impaired strain and strain rate despite having normal systolic function and ejection fractions. Strain and strain rate may prove to be prognostic factors for long-term myocardial dysfunction. Therefore, asymptomatic children and young adults with long-standing HIV infection may benefit from these more sensitive measures. (J Am Soc Echocardiogr 2012;25:741-8.)
C1 [Dimock, David; Mikhail, Irene; Hadigan, Colleen] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA.
[Sims, Amy; Frank, Lowell; Cross, Russell; Clauss, Sarah; Sable, Craig] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA.
[Purdy, Julia] NCI, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Purdy, Julia; Hazra, Rohan] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA.
RP Hadigan, C (reprint author), NIAID, Immunoregulat Lab, 10 Ctr Dr,Bldg 10,Room 11C103, Bethesda, MD 20892 USA.
EM hadiganc@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 31
TC 14
Z9 14
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 JUL
PY 2012
VL 25
IS 7
BP 741
EP 748
DI 10.1016/j.echo.2012.04.004
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 964NE
UT WOS:000305701600009
PM 22542272
ER
PT J
AU Jain, M
Velez, JI
Acosta, MT
Palacio, LG
Balog, J
Roessler, E
Pineda, D
Londono, AC
Palacio, JD
Arbelaez, A
Lopera, F
Elia, J
Hakonarson, H
Seitz, C
Freitag, CM
Palmason, H
Meyer, J
Romanos, M
Walitza, S
Hemminger, U
Warnke, A
Romanos, J
Renner, T
Jacob, C
Lesch, KP
Swanson, J
Castellanos, FX
Bailey-Wilson, JE
Arcos-Burgos, M
Muenke, M
AF Jain, M.
Velez, J. I.
Acosta, M. T.
Palacio, L. G.
Balog, J.
Roessler, E.
Pineda, D.
Londono, A. C.
Palacio, J. D.
Arbelaez, A.
Lopera, F.
Elia, J.
Hakonarson, H.
Seitz, C.
Freitag, C. M.
Palmason, H.
Meyer, J.
Romanos, M.
Walitza, S.
Hemminger, U.
Warnke, A.
Romanos, J.
Renner, T.
Jacob, C.
Lesch, K-P
Swanson, J.
Castellanos, F. X.
Bailey-Wilson, J. E.
Arcos-Burgos, M.
Muenke, M.
TI A cooperative interaction between LPHN3 and 11q doubles the risk for
ADHD
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE ADHD; genetic interaction; LPHN3; NCAM1; DRD2
ID CELL-ADHESION MOLECULE; LINKAGE ANALYSIS; HAPLOTYPIC VARIANTS;
IN-SILICO; GENE; DRD2; NCAM1; ANKK1; IDENTIFICATION; DEPENDENCE
AB In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P< 1 x 10(-8)) and 11q and 17p (P< 1 x 10(-6)). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q-11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome. Molecular Psychiatry (2012) 17, 741-747; doi:10.1038/mp.2011.59; published online 24 May 2011
C1 [Jain, M.; Velez, J. I.; Acosta, M. T.; Balog, J.; Roessler, E.; Bailey-Wilson, J. E.; Arcos-Burgos, M.; Muenke, M.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Palacio, L. G.; Pineda, D.; Londono, A. C.; Palacio, J. D.; Arbelaez, A.; Lopera, F.] Univ Antioquia, Neurosci Grp, Medellin, Colombia.
[Seitz, C.; Freitag, C. M.] Saarland Univ Hosp, Dept Child & Adolescent Psychiat, Homburg, Saar, Germany.
[Elia, J.; Hakonarson, H.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Palmason, H.; Meyer, J.] Univ Trier, Div Neurobehav Genet, Grad Sch Psychobiol, Trier, Germany.
[Romanos, M.; Walitza, S.; Hemminger, U.; Warnke, A.; Renner, T.; Lesch, K-P] Univ Wurzburg, Dept Child & Adolescent Psychiat & Psychotherapy, Wurzburg, Germany.
[Romanos, J.; Renner, T.; Jacob, C.; Lesch, K-P] Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany.
[Swanson, J.] Univ Calif Irvine, UCI Child Dev Ctr, Irvine, CA USA.
[Castellanos, F. X.] NYU, Ctr Child Study, New York, NY USA.
RP Arcos-Burgos, M (reprint author), NHGRI, Med Genet Branch, NIH, Bldg 35,Room 1B-209, Bethesda, MD 20892 USA.
EM arcosburgosm@mail.nih.gov; mamuenke@mail.nih.gov
RI Renner, Tobias/I-2120-2013; Lesch, Klaus-Peter/J-4906-2013; Romanos,
Marcel/D-7695-2017;
OI Lesch, Klaus-Peter/0000-0001-8348-153X; Bailey-Wilson,
Joan/0000-0002-9153-2920; Walitza, Susanne/0000-0002-8161-8683;
Castellanos, Francisco/0000-0001-9192-9437
FU Division of Intramural Research, National Human Genome Research
Institute, National Institutes of Health; COLCIENCIAS [1115-04-12010,
1115-04-18083]; Deutsche Forschungsgemeinschaft [KFO 125/1-1, SFB 581]
FX We are grateful to the families who participated in this research
endeavor. This research was supported by the Division of Intramural
Research, National Human Genome Research Institute, National Institutes
of Health, and in part by COLCIENCIAS, grants 1115-04-12010,
1115-04-18083, and by the Deutsche Forschungsgemeinschaft (KFO 125/1-1,
SFB 581).
NR 26
TC 19
Z9 20
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JUL
PY 2012
VL 17
IS 7
BP 741
EP 747
DI 10.1038/mp.2011.59
PG 7
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 965ZV
UT WOS:000305807200010
PM 21606926
ER
PT J
AU Lee, TL
Raitano, JM
Rennert, OM
Chan, SW
Chan, WY
AF Lee, Tin-Lap
Raitano, Joan M.
Rennert, Owen M.
Chan, Siu-Wai
Chan, Wai-Yee
TI Accessing the genomic effects of naked nanoceria in murine neuronal
cells
SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
LA English
DT Article
DE Cerium oxide; Nanoceria; Nanoparticles; Neuronal cells; Genomics
ID CERIUM OXIDE NANOPARTICLES; OXYGEN STORAGE CAPACITY; DISEASE GENE
HOMOLOG; HUNTINGTONS-DISEASE; EMBRYONIC LETHALITY; REACTION-MECHANISM;
SURFACE; SIZE; CEO2; OXIDATION
AB Cerium oxide nanoparticles (nanoceria) are engineered nanoparticles whose versatility is due to their unique redox properties. We and others have demonstrated that naked nanoceria can act as antioxidants to protect cells against oxidative damage. Although the redox properties may be beneficial, the genome-wide effects of nanoceria on gene transcription and associated biological processes remain elusive. Here we applied a functional genomic approach to examine the genome-wide effects of nanoceria on global gene transcription and cellular functions in mouse neuronal cells. Importantly, we demonstrated that nanoceria induced chemical- and size-specific changes in the murine neuronal cell transcriptome. The nanoceria contributed more than 83% of the population of uniquely altered genes and were associated with a unique spectrum of genes related to neurological disease, cell cycle control, and growth. These observations suggest that an in-depth assessment of potential health effects of naked nanoceria and other naked nanoparticles is both necessary and imminent.
C1 [Lee, Tin-Lap; Rennert, Owen M.; Chan, Wai-Yee] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin Genom, NIH, Bethesda, MD 20892 USA.
[Raitano, Joan M.; Chan, Siu-Wai] Columbia Univ, Dept Appl Phys & Appl Math, New York, NY USA.
[Lee, Tin-Lap; Chan, Wai-Yee] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China.
RP Chan, WY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin Genom, NIH, Bldg 49,Room 2A08, Bethesda, MD 20892 USA.
EM chanwy@cuhk.edu.hk
RI Lee, Tin-Lap/A-7853-2009
OI Lee, Tin-Lap/0000-0002-6654-0988
FU National Institutes of Health (NIH); Eunice Kennedy Shriver National
Institute of Child Health and Human Development; MRSEC of National
Science Foundation [DMR-0213574]; Department of Energy (DOE) [DE
FG02-05ER15730]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), Eunice Kennedy Shriver National
Institute of Child Health and Human Development, and Department of
Energy under Award Number DOE DE FG02-05ER15730, and the MRSEC Program
of the National Science Foundation (No. DMR-0213574).
NR 55
TC 14
Z9 16
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1549-9634
J9 NANOMED-NANOTECHNOL
JI Nanomed.-Nanotechnol. Biol. Med.
PD JUL
PY 2012
VL 8
IS 5
BP 599
EP 608
DI 10.1016/j.nano.2011.08.005
PG 10
WC Nanoscience & Nanotechnology; Medicine, Research & Experimental
SC Science & Technology - Other Topics; Research & Experimental Medicine
GA 964OF
UT WOS:000305704800007
PM 21889474
ER
PT J
AU Roy, CN
Semba, RD
Sun, K
Bandinelli, S
Varadhan, R
Patel, KV
Guralnik, JM
Ferrucci, L
AF Roy, Cindy N.
Semba, Richard D.
Sun, Kai
Bandinelli, Stefania
Varadhan, Ravi
Patel, Kushang V.
Guralnik, Jack M.
Ferrucci, Luigi
TI Circulating selenium and carboxymethyl-lysine, an advanced glycation
endproduct, are independent predictors of anemia in older
community-dwelling adults
SO NUTRITION
LA English
DT Article
DE Advanced glycation endproducts; Aging; Anemia; Carboxymethyl-lysine;
Oxidative stress; Selenium
ID END-PRODUCTS; HEMOGLOBIN CONCENTRATION; UNITED-STATES; SERUM; INCHIANTI;
MORTALITY; RECEPTOR; MUSCLE; WOMEN; RISK
AB Objective: To assess whether selenium and carboxymethyl-lysine (CML), two biomarkers of oxidative stress, are independent predictors of anemia in older community-dwelling adults.
Methods: Plasma levels of selenium, CML, folate, vitamin B12, and testosterone and markers of iron status and inflammation were measured at baseline in 1036 adults at least 65 y old in the Invecchiare in Chianti Study, a population-based cohort study of aging in Tuscany, Italy, and examined in relation to prevalent anemia and incident anemia over 6 y of follow-up.
Results: At enrollment, 11.6% of participants were anemic. Of 472 participants who were non-anemic at enrollment, 72 (15.3%) developed anemia within 6 y of follow-up. At enrollment, plasma CML in the highest quartile (>425 ng/mL) and plasma selenium in the lowest quartile (<66.6 mu g/L) predicted incident anemia (hazard ratio 1.67, 95% confidence interval 1.07-2.59, P = 0.02; hazard ratio 1.55, 95% confidence interval 1.01-2.38, P = 0.05, respectively) in a multivariate Cox proportional hazards model that adjusted for age, education, body mass index, cognition, inflammation, red blood cell distribution width, ferritin, vitamin B12, testosterone, and chronic diseases.
Conclusion: Elevated plasma CML and low plasma selenium are long-term independent predictors of anemia in older community-dwelling adults. These findings support the idea that oxidative stress contributes to the development of anemia. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Semba, Richard D.; Sun, Kai] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Roy, Cindy N.; Varadhan, Ravi] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Dept Med, Baltimore, MD 21205 USA.
[Bandinelli, Stefania] Azienda Sanit Firenze, Florence, Italy.
[Patel, Kushang V.; Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
EM rdsemba@jhmi.edu
FU National Institute on Aging [R01 AG027012, R01 AG029148, 263 MD 9164,
263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; Italian
Ministry of Health [ICS110.1/RF97.71]; Intramural Research Program,
National Institute on Aging, National Institutes of Health; American
Society of Hematology [RO1 DK082722]; Research Career Development Core
of the Johns Hopkins Older Americans Independence Center [AG021334]
FX The work was supported by grants R01 AG027012 and R01 AG029148 from the
National Institute on Aging, grant ICS110.1/RF97.71 from the Italian
Ministry of Health, contracts 263 MD 9164, 263 MD 821336, N.1-AG-1-1,
N.1-AG-1-2111, and N01-AG-5-0002 from the National Institute on Aging,
and the Intramural Research Program, National Institute on Aging,
National Institutes of Health. C. N. R. also was supported by grant RO1
DK082722 from the American Society of Hematology and grant AG021334 from
the Research Career Development Core of the Johns Hopkins Older
Americans Independence Center. The baseline Invecchiare in Chianti study
(1998-2000) was supported as a "targeted project" by grant
ICS110.1/RF97.71 from the Italian Ministry of Health and in part by
contracts 263 MD 9164 and 263 MD 821336 from the National Institute on
Aging.
NR 41
TC 3
Z9 3
U1 2
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0899-9007
J9 NUTRITION
JI Nutrition
PD JUL-AUG
PY 2012
VL 28
IS 7-8
BP 762
EP 766
DI 10.1016/j.nut.2011.11.005
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 965LO
UT WOS:000305769500012
PM 22325035
ER
PT J
AU Nichols, HB
Trentham-Dietz, A
Newcomb, PA
Titus, LJ
Egan, KM
Hampton, JM
Visvanathan, K
AF Nichols, Hazel B.
Trentham-Dietz, Amy
Newcomb, Polly A.
Titus, Linda J.
Egan, Kathleen M.
Hampton, John M.
Visvanathan, Kala
TI Postoophorectomy Estrogen Use and Breast Cancer Risk
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID HORMONE REPLACEMENT THERAPY; MENSTRUAL FACTORS; BILATERAL OOPHORECTOMY;
POSTMENOPAUSAL WOMEN; TUBAL-STERILIZATION; PHYSICIAN RECORDS;
HYSTERECTOMY; HEALTH; MENOPAUSE; SURGERY
AB OBJECTIVE: To estimate whether the protective effect of premenopausal bilateral oophorectomy on breast cancer risk is mitigated by estrogen therapy use after surgery.
METHODS: In pooled data from four population-based case-control studies spanning 1992-2007, we examined estrogen use after total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) and subsequent breast cancer risk. We identified cases of postmenopausal invasive breast cancer in women (n = 10,449) aged 50-79 years from three state tumor registries and age-matched control group participants without breast cancer (n = 11,787) from driver's license and Medicare lists. Total abdominal hysterectomy with bilateral salpingo-oophorectomy and estrogen use were queried during structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with multivariable logistic regression.
RESULTS: Breast cancer risk comparisons were made relative to women who experienced natural menopause and never used hormones. Overall, breast cancer risk increased 14% among women currently using estrogens after TAHBSO (OR 1.14, 95% CI 1.03-1.28), 32% for estrogen durations less than 10 years (OR 1.32, 95% CI 1.11-1.57), and 22% for estrogen initiation within 5 years of TAHBSO (OR 1.22, 95% CI 1.09 -1.37). Among women who underwent early TAHBSO (younger than 40 years), 24-30% decreases in breast cancer risk were observed among both never (OR 0.70, 95% CI 0.55-0.88) and current (OR 0.76, 95% CI 0.61-0.96) estrogen users.
CONCLUSION: Unopposed estrogen use does not negate the reduction in breast cancer risk associated with early (younger than 40 years) bilateral oophorectomy. However, initiating estrogen therapy after TAHBSO at ages 45 and older can increase breast cancer risk and should be considered carefully. (Obstet Gynecol 2012; 120: 27-36) DOI: 10.1097/AOG.0b013e31825a717b
LEVEL OF EVIDENCE: II
C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA.
Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
Dartmouth Med Sch, Lebanon, NH USA.
Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
Res Inst, Tampa, FL USA.
RP Nichols, HB (reprint author), NIEHS, POB 12233,MD A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM nicholshb@niehs.nih.gov
FU National Cancer Institute at the National Institutes of Health [CA47147,
CA47305, CA069664, CA009314, CA111948]
FX Supported by grants from the National Cancer Institute at the National
Institutes of Health (CA47147, CA47305, CA069664, CA009314, CA111948).
NR 38
TC 7
Z9 7
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD JUL
PY 2012
VL 120
IS 1
BP 27
EP 36
DI 10.1097/AOG.0b013e31825a717b
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 965JS
UT WOS:000305764500008
PM 22914389
ER
PT J
AU Schliep, KC
Stanford, JB
Chen, Z
Zhang, B
Dorais, JK
Johnstone, EB
Hammoud, AO
Varner, MW
Louis, GMB
Peterson, CM
AF Schliep, Karen C.
Stanford, Joseph B.
Chen, Zhen
Zhang, Bo
Dorais, Jessie K.
Johnstone, Erica Boiman
Hammoud, Ahmad O.
Varner, Michael W.
Louis, Germaine M. Buck
Peterson, C. Matthew
CA Endometriosis Nat Hist Diag & Outc
TI Interrater and Intrarater Reliability in the Diagnosis and Staging of
Endometriosis
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID AMERICAN-FERTILITY-SOCIETY; INTEROBSERVER VARIABILITY; CLASSIFICATION;
SYSTEM; REPRODUCIBILITY; INTRAOBSERVER; LAPAROSCOPY; POPULATION;
ADHESIONS; AGREEMENT
AB OBJECTIVE: To estimate the interrater and intrarater reliability of endometriosis diagnosis and severity of disease among gynecologic surgeons viewing operative digital images.
METHODS: The study population comprised a random sample (n = 148 [36%]) of women who participated in the Endometriosis: Natural History, Diagnosis and Outcomes study. Four academic expert and four local, specialized expert surgeons reviewed the images, diagnosed the presence or absence of endometriosis for each woman, and rated severity using the revised American Society for Reproductive Medicine (ASRM) criteria. Interrater-level and intrarater-level agreement were calculated for both endometriosis diagnosis and staging.
RESULTS: The interrater reliability for endometriosis diagnosis among the eight surgeons was substantial: Fleiss kappa = 0.69 (95% confidence interval [CI] 0.64-0.74). Surgeons agreed on revised ASRM endometriosis staging criteria after experienced assessment in a majority of cases (mean 61%, range 52-75%) with moderate interrater reliability: Fleiss kappa = 0.44 (95% CI 0.41-0.47). The intrarater reliability for experienced assessment compared with computer-assisted revised ASRM staging was almost perfect (mean weighted kappa = 0.95, range 0.89-0.99).
CONCLUSION: Substantial reliability was found for revised ASRM endometriosis diagnosis, whereas moderate reliability was observed for staging. Almost perfect reliability was observed for surgeons' rating of disease severity compared with computerized-assisted, checklist-based staging. Findings suggest that reliability in endometriosis diagnosis is not greatly altered by location or composition of surgeons, supporting the conduct of multisite studies or compilation of endometriosis data across clinical centers. Although surgeons appear to be skilled at assessing endometriosis stage intuitively, how staging of disease burden correlates with clinical outcomes remains to be developed. (Obstet Gynecol 2012; 120: 104-12) DOI:10.1097/AOG. 0b013e31825bc6cf
LEVEL OF EVIDENCE: II
C1 [Schliep, Karen C.] Univ Utah, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Salt Lake City, UT 84132 USA.
Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT 84132 USA.
Univ Utah, Dept Obstet & Gynecol, Div Maternal Fetal Med, Salt Lake City, UT 84132 USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Natl Inst Hlth, Rockville, MD USA.
Oregon State Univ, Coll Publ Hlth & Human Sci, Sch Biol & Populat Hlth Sci, Corvallis, OR 97331 USA.
RP Peterson, CM (reprint author), Univ Utah, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, 30 N 1900 E,Suite 2B200, Salt Lake City, UT 84132 USA.
EM peterson@hsc.utah.edu
RI Varner, Michael/K-9890-2013;
OI Varner, Michael/0000-0001-9455-3973; Buck Louis,
Germaine/0000-0002-1774-4490
FU Intramural Research Program, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Institutes of Health
[NO1-DK-6-3428, NO1-DK-6-3427, 1000140602]
FX Funded by the Intramural Research Program, Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health (contracts NO1-DK-6-3428; NO1-DK-6-3427;
1000140602). Ethicon Endo-Surgery, LLC, generously donated the HARMONIC
ACE 36P shears and scalpel blades for use in the study through a signed
Materials Transfer Agreement with the University of Utah and the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 24
TC 13
Z9 13
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD JUL
PY 2012
VL 120
IS 1
BP 104
EP 112
DI 10.1097/AOG.0b013e31825bc6cf
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 965JS
UT WOS:000305764500018
PM 22914398
ER
PT J
AU Edwards, DRV
Aldridge, T
Baird, DD
Funk, MJ
Savitz, DA
Hartmann, KE
AF Edwards, Digna R. Velez
Aldridge, Tiara
Baird, Donna D.
Funk, Michele Jonsson
Savitz, David A.
Hartmann, Katherine E.
TI Periconceptional Over-the-Counter Nonsteroidal Anti-inflammatory Drug
Exposure and Risk for Spontaneous Abortion
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID ADULT-POPULATION; EARLY-PREGNANCY; IMPLANTATION; PROSTAGLANDIN;
MISCARRIAGE; INDOMETHACIN; EXPRESSION; BABOON; WOMEN; USERS
AB OBJECTIVE: To estimate the association between over-the-counter nonsteroidal anti-inflammatory drug (NSAID) exposure during the early first trimester and risk for spontaneous abortion (gestation before 20 weeks of gestation) in a prospective cohort.
METHODS: Women were enrolled in the Right from the Start study (2004-2010). Exposure data regarding over-the-counter NSAID use from the last menstrual period (LMP) through the sixth week of pregnancy were obtained from intake and first-trimester interviews. Pregnancy outcomes were self-reported and verified by medical records. Gestational age was determined from the LMP. Stage of development before loss was determined from study ultrasonography. Cox proportional hazards regression models were used to estimate the association between NSAID exposure and pregnancy outcome taking into account candidate confounders.
RESULTS: Among 2,780 pregnancies, 367 women (13%) experienced a spontaneous abortion. NSAID exposure was reported by 1,185 (43%) women. NSAID exposure was not associated with spontaneous abortion risk in unadjusted models (hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.82-1.24) or models adjusted for maternal age (adjusted HR 1.00, 95% CI 0.81-1.23).
CONCLUSION: Our findings suggest that use of nonprescription over-the-counter NSAIDs in early pregnancy does not put women at increased risk of spontaneous abortion. (Obstet Gynecol 2012; 120: 113-22) DOI:10.1097/AOG.0b013e3182595671
LEVEL OF EVIDENCE: II
C1 [Edwards, Digna R. Velez] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Dept Obstet & Gynecol, Nashville, TN 37203 USA.
Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37203 USA.
Natl Inst Environm Hlth Sci, Epidemiol Branch, Natl Inst Hlth, Res Triangle Pk, NC USA.
Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
Brown Univ, Dept Epidemiol, Providence, RI 02912 USA.
Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA.
RP Edwards, DRV (reprint author), Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Dept Obstet & Gynecol, 2525 W End Ave,Suite 600,6th Floor, Nashville, TN 37203 USA.
EM digna.r.velez.edwards@vanderbilt.edu
RI Jonsson Funk, Michele/F-6885-2011; Velez Edwards, Digna/C-1090-2012;
Baird, Donna/D-5214-2017
OI Jonsson Funk, Michele/0000-0002-3756-7540; Baird,
Donna/0000-0002-5544-2653
FU National Institute of Child and Human Development [R01HD043883,
R01HD049675]; American Water Works Association Research Foundation
[2579]; Building Interdisciplinary Research Careers in Women's Health
career development program [K12HD4383]; Vanderbilt CTSA from National
Center for Research Resources/National Institutes of Health [UL1
RR024975-01]; Agency for Healthcare Research and Quality [K02HS017950];
Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences
FX The field research was supported by grants from the National Institute
of Child and Human Development (R01HD043883 and R01HD049675) and the
American Water Works Association Research Foundation (2579). Additional
funds were provided by the Building Interdisciplinary Research Careers
in Women's Health career development program (K12HD4383) supported in
part by the Vanderbilt CTSA grant UL1 RR024975-01 from National Center
for Research Resources/National Institutes of Health and the Agency for
Healthcare Research and Quality (K02HS017950). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the Agency for Healthcare Research and Quality. This
research was also supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute of
Environmental Health Sciences (ie, support for coauthor Donna D. Baird).
NR 25
TC 14
Z9 14
U1 10
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD JUL
PY 2012
VL 120
IS 1
BP 113
EP 122
DI 10.1097/AOG.0b013e3182595671
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 965JS
UT WOS:000305764500019
PM 22914399
ER
PT J
AU Choi, W
Kolbe, L
Hearing, VJ
AF Choi, Wonseon
Kolbe, Ludger
Hearing, Vincent J.
TI Characterization of the bioactive motif of neuregulin-1, a
fibroblast-derived paracrine factor that regulates the constitutive
color and the function of melanocytes in human skin
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE pigmentation; skin; melanocyte; fibroblast; color
ID PIGMENTATION; RECEPTORS; CELLS
AB Interactions between melanocytes and neighboring cells in the skin (keratinocytes and fibroblasts) play important roles in regulating human skin color. We recently reported that neuregulin-1 (NRG1) is highly expressed in fibroblasts from Fitzpatrick type VI skin (the darkest) and at least in part determines the constitutive color of human skin. We have now characterized the bioactive motif of NRG1 that is involved in modulating melanin production in human melanocytes. We found that 8-mer motifs (PSRYLCKC and LCKCPNEF) increased melanin production but did not increase the proliferation of melanocytes; the minimum fragment that could elicit that effect was the tetrapeptide LCKC. This smaller bioactive peptide might have an advantage in clinical applications in which it modulates only pigmentation and does not stimulate melanocyte proliferation.
C1 [Choi, Wonseon; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Kolbe, Ludger] Beiersdorf AG, R&D Skin Res, Hamburg, Germany.
RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM hearingv@nih.gov
FU National Cancer Institute at the National Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the National Cancer Institute at the National Institutes of Health.
NR 15
TC 1
Z9 2
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD JUL
PY 2012
VL 25
IS 4
BP 477
EP 481
DI 10.1111/j.1755-148X.2012.01002.x
PG 5
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 962AK
UT WOS:000305511200011
PM 22494484
ER
PT J
AU Tilly, K
Checroun, C
Rosa, PA
AF Tilly, Kit
Checroun, Claire
Rosa, Patricia A.
TI Requirements for Borrelia burgdorferi plasmid maintenance
SO PLASMID
LA English
DT Article
DE MiniF; Plasmid stability; Spirochete
ID LYME-DISEASE SPIROCHETE; LINEAR-PLASMID; CIRCULAR-PLASMID; INFECTIOUS
CYCLE; MAMMALIAN HOST; TICK VECTOR; IN-VIVO; REPLICATION; PROTEIN; DNA
AB Borrelia burgdorferi has multiple linear and circular plasmids that are faithfully replicated and partitioned as the bacterium grows and divides. The low copy number of these replicons implies that active partitioning contributes to plasmid stability. Analyzing the requirements for plasmid replication and partition in B. burgdorferi is complicated by the complexity of the genome and the possibility that products may act in trans. Consequently, we have studied the replication-partition region (bbb10-13) of the B. burgdorferi 26 kb circular plasmid (cp26) in Escherichia coli, by fusion with a partition-defective miniF plasmid. Our analysis demonstrated that bbb10, bbb11, and bbb13 are required for stable miniF maintenance, whereas bbb12 is dispensable. To validate these results, we attempted to inactivate two of these genes in B. burgdorferi. bbb12 mutants were obtained at a typical frequency, suggesting that the bbb12 product is dispensable for cp26 maintenance as well. We could not directly measure cp26 stability in the bbb12 mutant, because cp26 carries essential genes, and bacteria that have lost cp26 are inviable. Conversely, we were unable to inactivate bbb10 on cp26 of B. burgdorferi. Our results suggest that bbb12 is dispensable for cp26 maintenance, whereas bbb10, 66611, and bbb13 play crucial roles in that process. Published by Elsevier Inc.
C1 [Tilly, Kit; Checroun, Claire; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Tilly, K (reprint author), 903 S 4th St, Hamilton, MT 59840 USA.
EM ktilly@niaid.nih.gov; prosa@niaid.nih.gov
FU NIH, NIAID
FX We thank Dr. David Lane (CNRS, Toulouse, France) for providing pDAG203
and bacterial strains. We thank Laura Cornelisse for help in
characterizing the stability of the miniF26 Delta bbb12. We thank Dan
Sturdevant (Rocky Mountain Labs Research Technology Branch) for TaqMan
primer-probe set design and Craig Martens (Rocky Mountain Labs Research
Technology Branch) for constructing a phylogenetic tree with bbb12 and
related sequences. We are grateful to Jeff Skinner (Bioinformatics and
Computational Biosciences Branch, NIAID) for advice on statistical
analysis. We thank Paul Beare, John Carlson, Philip Stewart, Daniel
Dulebohn, and Amit Sarkar for their helpful suggestions on the
manuscript. Anita Mora and Austin Athman provided expert figure
preparation. This research was supported by the Intramural Research
Program of the NIH, NIAID.
NR 56
TC 5
Z9 5
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 0147-619X
J9 PLASMID
JI Plasmid
PD JUL
PY 2012
VL 68
IS 1
BP 1
EP 12
DI 10.1016/j.plasmid.2012.01.009
PG 12
WC Genetics & Heredity; Microbiology
SC Genetics & Heredity; Microbiology
GA 964RZ
UT WOS:000305715700001
PM 22289894
ER
PT J
AU Pronk, NP
Krebs-Smith, SM
Galuska, DA
Liu, BM
Kushner, RF
Troiano, RP
Clauser, SB
Ballard-Barbash, R
Smith, AW
AF Pronk, Nicolaas P.
Krebs-Smith, Susan M.
Galuska, Deborah A.
Liu, Benmei
Kushner, Robert F.
Troiano, Richard P.
Clauser, Steven B.
Ballard-Barbash, Rachel
Smith, Ashley Wilder
TI Knowledge of energy balance guidelines and associated clinical care
practices: The U.S. National Survey of Energy Balance Related Care among
Primary Care Physicians
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Energy balance; Primary care; Guidelines; Physical activity; Nutrition;
Body mass index; Knowledge
ID WEIGHT-RELATED CARE; PUBLIC-HEALTH; PROMOTE; DISEASE; DIET; US
AB Objective. To assess primary care physicians' (PCPs) knowledge of energy balance related guidelines and the association with sociodemographic characteristics and clinical care practices.
Method. As part of the 2008 U.S. nationally representative National Survey of Energy Balance Related Care among Primary Care Physicians (EB-PCP), 1776 PCPs from four specialties who treated adults (n = 1060) or children and adolescents (n=716) completed surveys on sociodemographic information, knowledge of energy balance guidelines, and clinical care practices.
Results. EB-PCP response rate was 64.5%. For PCPs treating children, knowledge of guidelines for healthy BMI percentile, physical activity, and fruit and vegetables intake was 36.5%, 27.0%, and 62.9%, respectively. For PCPs treating adults, knowledge of guidelines for overweight, obesity, physical activity, and fruit and vegetables intake was 81.4%, 81.3%, 70.9%, and 63.5%, respectively. Generally, younger, female physicians were more likely to exhibit correct knowledge. Knowledge of weight-related guidelines was associated with assessment of body mass index (BMI) and use of BMI-for-age growth charts.
Conclusion. Knowledge of energy balance guidelines among PCPs treating children is low, among PCPs treating adults it appeared high for overweight and obesity-related clinical guidelines and moderate for physical activity and diet, and was mostly unrelated to clinical practices among all PCPs. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Pronk, Nicolaas P.] HealthPartners, Minneapolis, MN USA.
[Pronk, Nicolaas P.] HealthPartners Res Fdn, Minneapolis, MN USA.
[Pronk, Nicolaas P.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Krebs-Smith, Susan M.; Liu, Benmei; Troiano, Richard P.; Clauser, Steven B.; Ballard-Barbash, Rachel; Smith, Ashley Wilder] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Galuska, Deborah A.] CDC, Div Nutr Phys Act & Obes, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
[Kushner, Robert F.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Pronk, NP (reprint author), HealthPartners, 8170 33rd Ave S, Bloomington, MN 55425 USA.
EM nico.p.pronk@healthpartners.com
OI Troiano, Richard/0000-0002-6807-989X
FU National Cancer Institute [N02-PC-61301]
FX Data collection for this survey was supported by the National Cancer
Institute's contract no. N02-PC-61301. We would like to thank the
following members of the Department of Health and Human Services' survey
development team and outside consultants:; National Cancer Institute:
Ashley Wilder Smith, Steven Clauser, Rachel Ballard-Barbash, Carrie
Klabunde, Susan M. Krebs-Smith, Laurel Borowski, Emily Dowling, Gordon
Willis, Richard Troiano, Audie Atienza, Tanya Agurs-Collins, Bill Davis.
NR 17
TC 4
Z9 4
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
J9 PREV MED
JI Prev. Med.
PD JUL
PY 2012
VL 55
IS 1
BP 28
EP 33
DI 10.1016/j.ypmed.2012.05.005
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 966TX
UT WOS:000305861400005
PM 22609144
ER
PT J
AU Chambers, DA
Pringle, B
Juliano-Bult, D
AF Chambers, David A.
Pringle, Beverly
Juliano-Bult, Denise
TI Connecting Science and Practice in Child and Adolescent Mental Health
Services Research
SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES
RESEARCH
LA English
DT Article
DE Research partnership; Collaborative research; Community-based; CBPR
ID PARTICIPATORY RESEARCH APPROACH; DISORDERS; PSYCHOTHERAPIES;
METAANALYSIS; PREVALENCE; PARTNERS; CARE
AB Collaboration between researchers and stakeholder groups is a potentially powerful mechanism for strengthening the quality of mental health research and for amplifying its public health impact. For stakeholders, collaboration offers opportunities to help shape research questions; participate in data collection and interpretation; and improve local capacity to access and use research findings. For researchers, collaboration can build understanding of what stakeholders want and need from research; enhance capacity to frame research questions and findings in language and metrics of value to stakeholders; and provide opportunities to contribute science-backed knowledge to decision-making processes in real world settings. Key stakeholder groups can include the recipients and providers of care, public and private care systems, health plans, schools, family service and faith-based organizations, correctional systems, and employers providing mental health benefits. This commentary reflects on the path that NIMH has taken in fostering researcher-stakeholder collaboration, particularly regarding child and adolescent mental health research. It describes the goals that NIMH set out to achieve, steps taken to realize those goals, lessons learned from those efforts, and possible next steps.
C1 [Chambers, David A.; Pringle, Beverly; Juliano-Bult, Denise] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
RP Chambers, DA (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd,Room 7164, Bethesda, MD 20892 USA.
EM dchamber@mail.nih.gov
NR 23
TC 1
Z9 1
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0894-587X
J9 ADM POLICY MENT HLTH
JI Adm. Policy. Ment. Health
PD JUL
PY 2012
VL 39
IS 4
SI SI
BP 321
EP 326
DI 10.1007/s10488-011-0399-z
PG 6
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 962OX
UT WOS:000305555800011
PM 22271355
ER
PT J
AU Robertson, EB
Sims, BE
Reider, EE
AF Robertson, Elizabeth B.
Sims, Belinda E.
Reider, Eve E.
TI Partnerships in Drug Abuse Prevention Services Research: Perspectives
from the National Institute on Drug Abuse
SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES
RESEARCH
LA English
DT Editorial Material
C1 [Robertson, Elizabeth B.] NIDA, PRB, DESPR, Bethesda, MD 20892 USA.
RP Robertson, EB (reprint author), NIDA, PRB, DESPR, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM er52h@nih.gov
NR 4
TC 1
Z9 1
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0894-587X
EI 1573-3289
J9 ADM POLICY MENT HLTH
JI Adm. Policy. Ment. Health
PD JUL
PY 2012
VL 39
IS 4
SI SI
BP 327
EP 330
DI 10.1007/s10488-011-0400-x
PG 4
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 962OX
UT WOS:000305555800012
PM 22203328
ER
PT J
AU Biesecker, LG
AF Biesecker, Leslie G.
TI Elements of Morphology: Standard Terminology for the Hands and Feet (vol
149A, pg 93, 2009)
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Correction
C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr,Room 4A56, Bethesda, MD 20892 USA.
EM leslieb@helix.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUL
PY 2012
VL 158A
IS 7
BP 1813
EP 1813
DI 10.1002/ajmg.a.35326
PG 1
WC Genetics & Heredity
SC Genetics & Heredity
GA 959QD
UT WOS:000305327000051
ER
PT J
AU Sabatino, SA
Lawrence, B
Elder, R
Mercer, SL
Wilson, KM
DeVinney, B
Melillo, S
Carvalho, M
Taplin, S
Bastani, R
Rimer, BK
Vernon, SW
Melvin, CL
Taylor, V
Fernandez, M
Glanz, K
AF Sabatino, Susan A.
Lawrence, Briana
Elder, Randy
Mercer, Shawna L.
Wilson, Katherine M.
DeVinney, Barbara
Melillo, Stephanie
Carvalho, Michelle
Taplin, Stephen
Bastani, Roshan
Rimer, Barbara K.
Vernon, Sally W.
Melvin, Cathy Lee
Taylor, Vicky
Fernandez, Maria
Glanz, Karen
CA Community Preventive Serv Task
TI Effectiveness of Interventions to Increase Screening for Breast,
Cervical, and Colorectal Cancers Nine Updated Systematic Reviews for the
Guide to Community Preventive Services
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIAL; AFRICAN-AMERICAN WOMEN; TELEPHONE
COUNSELING INTERVENTION; HEALTH MAINTENANCE ORGANIZATION;
CLIENT-DIRECTED INTERVENTIONS; PRIMARY-CARE PRACTICES; OCCULT
BLOOD-TEST; MAMMOGRAPHY USE; UNITED-STATES; TAILORED INTERVENTIONS
AB Context: Screening reduces mortality from breast, cervical, and colorectal cancers. The Guide to Community Preventive Services previously conducted systematic reviews on the effectiveness of 11 interventions to increase screening for these cancers. This article presents results of updated systematic reviews for nine of these interventions.
Evidence acquisition: Five databases were searched for studies published during January 2004-October 2008. Studies had to (1) be a primary investigation of one or more intervention category; (2) be conducted in a country with a high-income economy; (3) provide information on at least one cancer screening outcome of interest; and (4) include screening use prior to intervention implementation or a concurrent group unexposed to the intervention category of interest. Forty-five studies were included in the reviews.
Evidence synthesis: Recommendations were added for one-on-one education to increase screening with fecal occult blood testing (FOBT) and group education to increase mammography screening. Strength of evidence for client reminder interventions to increase FOBT screening was upgraded from sufficient to strong. Previous findings and recommendations for reducing out-of-pocket costs (breast cancer screening); provider assessment and feedback (breast, cervical, and FOBT screening); one-on-one education and client reminders (breast and cervical cancer screening); and reducing structural barriers (breast cancer and FOBT screening) were reaffirmed or unchanged. Evidence remains insufficient to determine effectiveness for the remaining screening tests and intervention categories.
Conclusions: Findings indicate new and reaffirmed interventions effective in promoting recommended cancer screening, including colorectal cancer screening. Findings can be used in community and healthcare settings to promote recommended care. Important research gaps also are described. (Am J Prev Med 2012;43(1):97-118) (C) 2012 Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Sabatino, Susan A.] Emory Univ, Div Canc PreventionandControl, Natl Ctr Chron Dis Prevent & Hlth Promot, CDC, Atlanta, GA 30341 USA.
[Elder, Randy; Mercer, Shawna L.; Wilson, Katherine M.] Emory Univ, Community Guide Branch, Epidemiol Anal Program Off, Atlanta, GA 30341 USA.
[Carvalho, Michelle] Emory Univ, Off Surveillance Epidemiol & Lab Serv, CDC, Rollins Sch Publ Hlth, Atlanta, GA 30341 USA.
[Lawrence, Briana; Vernon, Sally W.; Fernandez, Maria] Univ Texas Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX USA.
[Taplin, Stephen] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Bastani, Roshan] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Rimer, Barbara K.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Melvin, Cathy Lee] Med Univ S Carolina, Charleston, SC 29425 USA.
[Taylor, Vicky] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Glanz, Karen] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Glanz, Karen] Univ Penn, Dept Biobehav Hlth Sci, Sch Nursing, Philadelphia, PA USA.
RP Sabatino, SA (reprint author), Emory Univ, Div Canc PreventionandControl, Natl Ctr Chron Dis Prevent & Hlth Promot, CDC, 4770 Buford Highway,K-55, Atlanta, GA 30341 USA.
EM SSabatino@cdc.gov
FU Georgia Cancer Coalition Distinguished Scholar Award; CPCRN
FX The authors acknowledge the invaluable contributions of members and
leaders from the Cancer Prevention and Control Research Network (CPCRN)
and logistic support from the Emory Prevention Research Center,
cooperative agreement numbers 3-U48-DP-000050- 1 (University of
Washington); 3-U48-DP000064 (University of California Los Angeles);
3-U48-DP000059- 01 (University of North Carolina); 3-U48-DP000057
(University of Texas Houston); 1-U48-DP000043-S1 (Emory University); and
3-U48-DP000049 (Morehouse University) from the CDC, Prevention Research
Centers Program. In addition to the CPCRNgrant to the Emory Prevention
Research Center, KG was supported by a Georgia Cancer Coalition
Distinguished Scholar Award. BD was hired by CDC as a contractor to
abstract articles for this systematic review.
NR 138
TC 122
Z9 122
U1 6
U2 33
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUL
PY 2012
VL 43
IS 1
BP 97
EP 118
DI 10.1016/j.amepre.2012.04.009
PG 22
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 959VJ
UT WOS:000305344000016
PM 22704754
ER
PT J
AU Adeva, MM
Calvino, J
Souto, G
Donapetry, C
AF Adeva, Maria M.
Calvino, Jesus
Souto, Gema
Donapetry, Cristobal
TI Insulin resistance and the metabolism of branched-chain amino acids in
humans
SO AMINO ACIDS
LA English
DT Article; Proceedings Paper
CT International Congress on Carnosine in Exercise and Disease
CY JUL, 2011
CL Ghent, BELGIUM
DE Insulin resistance; Branched-chain amino acids; Leucine; Isoleucine;
Valine
ID CHRONIC-RENAL-FAILURE; SPLANCHNIC BED UTILIZATION; MUSCLE
PROTEIN-TURNOVER; HEMODIALYSIS-PATIENTS; LEUCINE METABOLISM;
SKELETAL-MUSCLE; DIABETES-MELLITUS; GLUCOSE KINETICS; LEG METABOLISM;
FOREARM MUSCLE
AB Peripheral resistance to insulin action is the major mechanism causing the metabolic syndrome and eventually type 2 diabetes mellitus. The metabolic derangement associated with insulin resistance is extensive and not restricted to carbohydrates. The branched-chain amino acids (BCAAs) are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in conditions featuring insulin resistance, insulin deficiency, or both. Obesity, the metabolic syndrome and diabetes mellitus display a gradual increase in the plasma concentration of BCAAs, from the obesity-related low-grade insulin-resistant state to the severe deficiency of insulin action in diabetes ketoacidosis. Obesity-associated hyperinsulinemia succeeds in maintaining near-normal or slightly elevated plasma concentration of BCAAs, despite the insulin-resistant state. The low circulating levels of insulin and/or the deeper insulin resistance occurring in diabetes mellitus are associated with more marked elevation in the plasma concentration of BCAAs. In diabetes ketoacidosis, the increase in plasma BCAAs is striking, returning to normal when adequate metabolic control is achieved. The metabolism of BCAAs is also disturbed in other situations typically featuring insulin resistance, including kidney and liver dysfunction. However, notwithstanding the insulin-resistant state, the plasma level of BCAAs in these conditions is lower than in healthy subjects, suggesting that these organs are involved in maintaining BCAAs blood concentration. The pathogenesis of the decreased BCAAs plasma level in kidney and liver dysfunction is unclear, but a decreased afflux of these amino acids into the blood stream has been observed.
C1 [Adeva, Maria M.; Donapetry, Cristobal] Hosp Juan Cardona, La Coruna 15406, Spain.
[Calvino, Jesus] Hosp Lucus Augusti, Lugo, Spain.
[Souto, Gema] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Adeva, MM (reprint author), Ave Che Guevara,31-B-3 A, La Coruna 15172, Spain.
EM madevaa@yahoo.com
NR 92
TC 44
Z9 49
U1 3
U2 47
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD JUL
PY 2012
VL 43
IS 1
BP 171
EP 181
DI 10.1007/s00726-011-1088-7
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 958BK
UT WOS:000305210800019
PM 21984377
ER
PT J
AU Pomerantz, O
Terkel, J
Suomi, SJ
Paukner, A
AF Pomerantz, Ori
Terkel, Joseph
Suomi, Stephen J.
Paukner, Annika
TI Stereotypic head twirls, but not pacing, are related to a
'pessimistic'-like judgment bias among captive tufted capuchins (Cebus
apella)
SO ANIMAL COGNITION
LA English
DT Article
DE Stereotypy; Cognitive-bias; Negative affect; Primate welfare
ID STARLINGS STURNUS-VULGARIS; COGNITIVE BIAS; ANIMAL EMOTION; BEHAVIOR;
WELFARE; STRESS; RESPONSES; PATTERNS; SCIENCE; AUTISM
AB Abnormal stereotypic behaviour is widespread among captive non-human primates and is generally associated with jeopardized well-being. However, attributing the same significance to all of these repetitive, unvarying and apparently functionless behaviours may be misleading, as some behaviours may be better indicators of stress than others. Previous studies have demonstrated that the affective state of the individual can be inferred from its bias in appraising neutral stimuli in its environment. Therefore, in the present study, in order to assess the emotional state of stereotyping individuals, 16 captive tufted capuchins (Cebus apella) were tested on a judgment bias paradigm and their faecal corticoid levels were measured in order to assess the intensity of the emotional state. Capuchins with higher levels of stereotypic head twirls exhibited a negative bias while judging ambiguous stimuli and had higher levels of faecal corticoids compared to subjects with lower levels of head twirls. Levels of stereotypic pacing, however, were not correlated with the monkeys' emotional state. This study is the first to reveal a positive correlation between levels of stereotypic behaviour and a 'pessimistic'-like judgment bias in a non-human primate by employing a recently developed cognitive approach. Combining cognitive tests that evaluate the animals' affective valence (positive or negative) with hormonal measurements that provide information on the strength of the emotional state conduces to a better understanding of the animals' affective state and therefore to their well-being.
C1 [Pomerantz, Ori; Terkel, Joseph] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Tel Aviv, Israel.
[Suomi, Stephen J.; Paukner, Annika] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, Natl Inst Hlth Anim Ctr, Poolesville, MD 20837 USA.
RP Pomerantz, O (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Tel Aviv, Israel.
EM oripomer@post.tau.ac.il
RI Pomerantz, Ori/B-1869-2013
FU Intramural NIH HHS [Z99 HD999999]
NR 46
TC 26
Z9 26
U1 2
U2 53
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1435-9448
J9 ANIM COGN
JI Anim. Cogn.
PD JUL
PY 2012
VL 15
IS 4
BP 689
EP 698
DI 10.1007/s10071-012-0497-7
PG 10
WC Behavioral Sciences; Zoology
SC Behavioral Sciences; Zoology
GA 960NR
UT WOS:000305395700024
PM 22526692
ER
PT J
AU Dookeran, KA
Dignam, JJ
Holloway, N
Ferrer, K
Sekosan, M
McCaskill-Stevens, W
Gehlert, S
AF Dookeran, Keith A.
Dignam, James J.
Holloway, Nathaniel
Ferrer, Karen
Sekosan, Marin
McCaskill-Stevens, Worta
Gehlert, Sarah
TI Race and the Prognostic Influence of p53 in Women with Breast Cancer
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID TRIPLE-NEGATIVE PHENOTYPE; AFRICAN-AMERICAN WOMEN; MOLECULAR SUBTYPES;
GENE-MUTATIONS; CARCINOMA; WHITE; POPULATION; ASSOCIATION; EXPRESSION;
SURVIVAL
AB Prior study suggests that p53 status behaves as an independent marker of prognosis in African American (AA) women with breast cancer. We investigate whether the influence of p53 is unique to AAs or is present in other race/ethnic groups, and how this compares with known prognostic factors.
Cox regression models [hazard ratios (HRs), 95% confidence intervals (CIs)] were used to select and evaluate factors prognostic for all-cause mortality in 331 AA and 203 non-AA consecutively treated women.
Statistically significant baseline prognostic factors were as follows. For AAs: stage [(III/I) HR 5.57; 95% CI 3.08-10.09], grade [(higher/low) HR 1.55; 95% CI 1.14-2.11], estrogen receptor (ER)/progesterone receptor (PR) status [(-/+) HR 2.01; 95% CI 1.38-2.93], triple negative (ER-, PR-, HER2-) subtype [(+/-) HR 1.95; 95% CI 1.33-2.85], and p53 status [(+/-) HR 1.69; 95% CI 1.10-2.58]. For non-AAs: stage [HR 11.93; 95% CI 2.80-50.84], grade [HR 1.61; 95% CI 0.96-2.71], and ER/PR status [HR 2.13; 95% CI 1.19-3.81]. There was a differential effect of race within p53 groups (P = 0.05) and in multivariate modeling p53-positive status remained an adverse prognostic factor in AAs only [HR 1.82; 95% CI 1.04-3.17]. Compared to non-AAs, 5-year unadjusted survival was worse for AAs overall (73.4% vs. 63.6%; P = 0.032), and also for AAs with p53-positive status (80.3% vs. 54.2%; P = 0.016), but not for AAs with p53-negative disease (68.4% vs. 67.9%; P = 0.81).
Among women with breast cancer of different race/ethnicity, an adverse prognostic effect as a result of p53 positivity was only observed in AA women.
C1 [Dookeran, Keith A.] Canc Fdn Minor & Underserved Populat, Chicago, IL USA.
[Dignam, James J.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Holloway, Nathaniel] John H Stroger Jr Hosp Cook Cty, Dept Radiat Oncol, Chicago, IL USA.
[Ferrer, Karen; Sekosan, Marin] John H Stroger Jr Hosp Cook Cty, Dept Pathol, Chicago, IL USA.
[McCaskill-Stevens, Worta] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Gehlert, Sarah] Washington Univ, Brown Sch, St Louis, MO USA.
RP Dookeran, KA (reprint author), Canc Fdn Minor & Underserved Populat, Chicago, IL USA.
EM dookeran@uic.edu
OI Dookeran, Keith/0000-0003-3695-9873
FU Cancer Foundation for Minority and Underserved Populations, Chicago, IL,
Public Health Service [NCI P30-CA-14599]; Division of Cancer Prevention,
National Cancer Institute/National Institutes of Health, Bethesda, MD
FX Supported in part by the Cancer Foundation for Minority and Underserved
Populations, Chicago, IL, Public Health Service grant NCI P30-CA-14599,
and the Division of Cancer Prevention, National Cancer
Institute/National Institutes of Health, Bethesda, MD.
NR 40
TC 6
Z9 6
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUL
PY 2012
VL 19
IS 7
BP 2334
EP 2344
DI 10.1245/s10434-011-1934-6
PG 11
WC Oncology; Surgery
SC Oncology; Surgery
GA 962PS
UT WOS:000305558000036
PM 22434242
ER
PT J
AU Beare, PA
Larson, CL
Gilk, SD
Heinzen, RA
AF Beare, Paul A.
Larson, Charles L.
Gilk, Stacey D.
Heinzen, Robert A.
TI Two Systems for Targeted Gene Deletion in Coxiella burnetii
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID IV SECRETION SYSTEM; LEGIONELLA-PNEUMOPHILA; BACTERIAL GENETICS;
BACILLUS-SUBTILIS; ESCHERICHIA-COLI; ALLELIC EXCHANGE; PROTEIN;
REPLICATION; MACROPHAGES; MUTAGENESIS
AB Coxiella burnetii is a ubiquitous zoonotic bacterial pathogen and the cause of human acute Q fever, a disabling influenza-like illness. C. burnetii's former obligate intracellular nature significantly impeded the genetic characterization of putative virulence factors. However, recent host cell-free (axenic) growth of the organism has enabled development of shuttle vector, transposon, and inducible gene expression technologies, with targeted gene inactivation remaining an important challenge. In the present study, we describe two methods for generating targeted gene deletions in C. burnetii that exploit pUC/ColE1 on-based suicide plasmids encoding sacB for positive selection of mutants. As proof of concept, C. burnetii dotA and dotB, encoding structural components of the type IVB secretion system (T4BSS), were selected for deletion. The first method exploited Cre-lox-mediated recombination. Two suicide plasmids carrying different antibiotic resistance markers and a loxP site were integrated into 5' and 3' flanking regions of dotA. Transformation of this strain with a third suicide plasmid encoding Cre recombinase resulted in the deletion of dotA under sucrose counterselection. The second method utilized a loop-in/loop-out strategy to delete dotA and dotB. A single suicide plasmid was first integrated into 5' or 3' target gene flanking regions. Resolution of the plasmid cointegrant by a second crossover event under sucrose counterselection resulted in gene deletion that was confirmed by PCR and Southern blot. Delta dotA and Delta dotB mutants failed to secrete T4BSS substrates and to productively infect host cells. The repertoire of C. burnetii genetic tools now allows ready fulfillment of molecular Koch's postulates for suspected virulence genes.
C1 [Beare, Paul A.; Larson, Charles L.; Gilk, Stacey D.; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,Natl Inst Hlth, Hamilton, MT USA.
RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,Natl Inst Hlth, Hamilton, MT USA.
EM rheinzen@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases
NR 48
TC 40
Z9 40
U1 1
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0099-2240
J9 APPL ENVIRON MICROB
JI Appl. Environ. Microbiol.
PD JUL
PY 2012
VL 78
IS 13
BP 4580
EP 4589
DI 10.1128/AEM.00881-12
PG 10
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 960GS
UT WOS:000305376600005
PM 22522687
ER
PT J
AU Miettinen, M
AF Miettinen, Markku
TI A Simple Method for Generating Multitissue Blocks Without Special
Equipment
SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
LA English
DT Article
DE multitissue block; tissue array; immunohistochemistry; manual; technique
AB The idea of multitumor block to expedite simultaneous analysis of multiple tissue specimens was pioneered by Battifora, and several variations have been published since then. More recently, microarray technology has been introduced to allow placement of up to several hundreds specimens in 1 block using manual or automated sampling devices. This paper reports a manual technique for preparation of a multitissue block. Generation of such blocks requires no special equipment, and flexible block design is possible depending On nature of available material and desired sample size. The first step is dissection of cubical or rectangular samples from paraffin blocks or processed tissue with a razor blade or scalpel. The tissue pieces can be tattooed on cut surface with a permanent marker to facilitate orientation and identification. This marking is preserved during embedding until the block is cut. If a "deep" block is desired, the tissue can be turned 90 degree to provide a greater vertical depth. For embedding, the pieces are laid in paraffin bath in desired order, and when completely melted, they are placed into a deep embedding mold and organized in multiple rows (5 to 10 pieces/row). Scaffolding and control tissue pieces (eg, placental liver or intestinal tissue) can be added as desired. Horizontal or vertical empty space should be preserved to allow for more effective separation of ribbons upon cutting, preventing unnecessary sacrifice of sections. Such blocks can accommodate 30 to 60 cases depending on the tissue size, and they can potentially generate up to several hundreds of sections. This technique is especially suitable when abundant tissue is available, for example, generating blocks containing libraries of normal tissues or defined tumors for antibody screening or tumor immunophenotyping.
C1 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/NIH intramural research program
FX This work was supported by the NCI/NIH intramural research program.
NR 5
TC 15
Z9 15
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1062-3345
J9 APPL IMMUNOHISTO M M
JI Appl. Immunohistochem.
PD JUL
PY 2012
VL 20
IS 4
BP 410
EP 412
PG 3
WC Anatomy & Morphology; Medical Laboratory Technology; Pathology
SC Anatomy & Morphology; Medical Laboratory Technology; Pathology
GA 963DT
UT WOS:000305601000015
PM 22495380
ER
PT J
AU Tolar, J
Deeg, HJ
Arai, S
Horwitz, M
Antin, JH
McCarty, JM
Adams, RH
Ewell, M
Leifer, ES
Gersten, ID
Carter, SL
Horowitz, MM
Nakamura, R
Pulsipher, MA
DiFronzo, NL
Confer, DL
Eapen, M
Anderlini, P
AF Tolar, Jakub
Deeg, H. Joachim
Arai, Sally
Horwitz, Mitchell
Antin, Joseph H.
McCarty, John M.
Adams, Roberta H.
Ewell, Marian
Leifer, Eric S.
Gersten, Iris D.
Carter, Shelly L.
Horowitz, Mary M.
Nakamura, Ryotaro
Pulsipher, Michael A.
DiFronzo, Nancy L.
Confer, Dennis L.
Eapen, Mary
Anderlini, Paolo
TI Fludarabine-Based Conditioning for Marrow Transplantation from Unrelated
Donors in Severe Aplastic Anemia: Early Results of a Cyclophosphamide
Dose Deescalation Study Show Life-Threatening Adverse Events at
Predefined Cyclophosphamide Dose Levels
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Bone marrow transplantation; Stem cell transplantation; Matched
unrelated donor; Antithymocyte globulin
ID TOTAL-BODY IRRADIATION; STEM-CELL TRANSPLANTATION; SAA WORKING PARTY;
ANTITHYMOCYTE GLOBULIN; BONE-MARROW; REGIMEN; BLOOD
AB Excessive adverse events were encountered in a Phase I/II study of cyclophosphamide (CY) dose deescalation in a fludarabine-based conditioning regimen for bone marrow transplantation from unrelated donors in patients with severe aplastic anemia. All patients received fixed doses of antithymocyte globulin, fludarabine, and low-dose total body irradiation. The starting CY dose was 150 mg/kg, with deescalation to 100 mg/kg, 50 mg/kg, or 0 mg/kg. CY dose level 0 mg/kg was closed due to graft failure in 3 of 3 patients. CY dose level 150 mg/kg was closed due to excessive organ toxicity (n = 6) or viral pneumonia (n = 1), resulting in the death of 7 of 14 patients. CY dose levels 50 and 100 mg/kg remain open. Thus, CY at doses of 150 mg/kg in combination with total body irradiation (2 Gy), fludarabine (120 mg/m(2)), and antithymocyte globulin was associated with excessive organ toxicity. Biol Blood Marrow Transplant 18: 1007-1011 (2012) (C) 2012 American Society for Blood and Marrow Transplantation
C1 [Tolar, Jakub] Univ Minnesota, Sch Med, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA.
[Deeg, H. Joachim] Univ Washington, Div Oncol, Seattle, WA 98195 USA.
[Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA USA.
[Arai, Sally] Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA.
[Horwitz, Mitchell] Duke Univ, Sch Med, Div Cellular Therapy, Adult Stem Cell Transplant Program, Durham, NC USA.
[Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[McCarty, John M.] Virginia Commonwealth Univ, Dept Hematol Oncol, Massey Canc Ctr, Richmond, VA USA.
[McCarty, John M.] Virginia Commonwealth Univ, Bone Marrow Transplantat Program, Massey Canc Ctr, Richmond, VA USA.
[Adams, Roberta H.] Phoenix Childrens Hosp, Dept Hematol Oncol, Phoenix, AZ USA.
[Ewell, Marian; Gersten, Iris D.; Carter, Shelly L.] EMMES Corp, Rockville, MD USA.
[Leifer, Eric S.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Horowitz, Mary M.; Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Nakamura, Ryotaro] City Hope Natl Med Ctr, Dept Hematol Hematopoiet Cell Transplantat, Duarte, CA USA.
[Pulsipher, Michael A.] Univ Utah, Dept Pediat, Huntsman Canc Inst, Div Hematol & Hematol Malignancies, Salt Lake City, UT USA.
[DiFronzo, Nancy L.] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
[Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA.
[Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Stem Cell Transplantat, Houston, TX 77030 USA.
RP Tolar, J (reprint author), Univ Minnesota, Sch Med, Dept Pediat, Div Blood & Marrow Transplantat, 420 Delaware St SE,MMC 366, Minneapolis, MN 55455 USA.
EM tolar003@umn.edu
OI Tolar, Jakub/0000-0002-0957-4380
FU National Heart, Lung, and Blood Institute [EQ1 U10HL069294]; National
Cancer Institute
FX We thank Juan Wu and Yanli Wang for help with manuscript preparation,
Erica Sanchez for secretarial assistance, and the clinical investigators
who entered and managed the patients in this study. The BMT CTN is
supported in part by Grant EQ1 U10HL069294 from the National Heart,
Lung, and Blood Institute and the National Cancer Institute.
NR 14
TC 22
Z9 22
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUL
PY 2012
VL 18
IS 7
BP 1007
EP 1011
DI 10.1016/j.bbmt.2012.04.014
PG 5
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 964BE
UT WOS:000305667900005
PM 22546497
ER
PT J
AU Akilov, OE
Grant, C
Frye, R
Bates, S
Piekarz, R
Geskin, LJ
AF Akilov, O. E.
Grant, C.
Frye, R.
Bates, S.
Piekarz, R.
Geskin, L. J.
TI Low-dose electron beam radiation and romidepsin therapy for symptomatic
cutaneous T-cell lymphoma lesions
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITORS; FK228
AB Background Romidepsin is a structurally unique histone deacetylase inhibitor approved by the U. S. Food and Drug Administration for therapy of relapsed or refractory cutaneous T-cell lymphoma (CTCL). Localized electron beam radiation therapy (LEBT) is standard practice in the care of patients with chronically traumatized and painful lesions. Combination therapy of those two modalities may be beneficial for the therapy of CTCL.
Objectives To report observations on supportive LEBT utilized for isolated refractory lesions in patients on romidepsin.
Methods Observations were made during a phase II clinical trial sponsored by the National Cancer Institute (NCI-1312) examining the efficacy of romidepsin for patients with relapsed, refractory or advanced CTCL, stage IB-IVA mycosis fungoides (MF) or Sezary syndrome. Skin responses were assessed by evaluation of five target lesions only. Patients with objective clinical responses in target lesions who had symptomatic nontarget lesions were allowed limited LEBT to isolated lesions for symptomatic relief. Patients who received localized radiation were not considered complete responders at any point.
Results Five patients with advanced MF (three stage IIB and two stage IVA2) received LEBT to symptomatic nontarget lesions while on a protocol with romidepsin. None of these patients experienced additional or unexpected toxicity. Four of the five patients demonstrated fast and durable responses. We noted that significantly lower than standard doses of LEBT effectively treated symptomatic lesions in these patients.
Conclusions LEBT demonstrated significant responses at very low doses without additional toxicity in patients on protocol treatment with the histone deacetylase inhibitor romidepsin. This merits formal investigation in a clinical trial for potential synergy in patients with CTCL.
C1 [Grant, C.; Frye, R.; Bates, S.; Piekarz, R.; Geskin, L. J.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Akilov, O. E.] Univ Pittsburgh, Dept Dermatol, Pittsburgh, PA 15213 USA.
RP Geskin, LJ (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM geskinlj@upmc.edu
FU SPORE NIH [5P50CA121973-03]; Celgene Corporation
FX This work was supported by SPORE NIH 5P50CA121973-03 Project 5 (to
L.J.G.).; Financial support for the editorial assistance was provided by
Celgene Corporation.
NR 15
TC 8
Z9 8
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-0963
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD JUL
PY 2012
VL 167
IS 1
BP 194
EP 197
DI 10.1111/j.1365-2133.2012.10905.x
PG 4
WC Dermatology
SC Dermatology
GA 965TZ
UT WOS:000305791500030
PM 22372971
ER
PT J
AU Salcedo, I
Tweedie, D
Li, YZ
Greig, NH
AF Salcedo, Isidro
Tweedie, David
Li, Yazhou
Greig, Nigel H.
TI Neuroprotective and neurotrophic actions of glucagon-like peptide-1: an
emerging opportunity to treat neurodegenerative and cerebrovascular
disorders
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Review
DE glucagon-like peptide-1; exendin-4; liraglutide; type-2 diabetes
mellitus; neurodegeneration; Alzheimer's disease; stroke; Parkinson's
disease; amyotrophic lateral sclerosis; Huntington's disease; peripheral
neuropathy; traumatic brain injury; neurogenesis; neuroprotection;
neuroplasticity
ID AMYLOID PRECURSOR PROTEIN; AMYOTROPHIC-LATERAL-SCLEROSIS; FAMILIAL
ALZHEIMERS-DISEASE; TYPE-2 DIABETES-MELLITUS; TRAUMATIC BRAIN-INJURY;
LONG-TERM POTENTIATION; GLP-1 RECEPTOR; PC12 CELLS; PARKINSONS-DISEASE;
ANIMAL-MODEL
AB Like type-2 diabetes mellitus (T2DM), neurodegenerative disorders and stroke are an ever increasing, health, social and economic burden for developed Westernized countries. Age is an important risk factor in all of these; due to the rapidly increasing rise in the elderly population T2DM and neurodegenerative disorders, both represent a looming threat to healthcare systems. Whereas several efficacious drugs are currently available to ameliorate T2DM, effective treatments to counteract pathogenic processes of neurodegenerative disorders are lacking and represent a major scientific and pharmaceutical challenge. Epidemiological data indicate an association between T2DM and most major neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Likewise, there is an association between T2DM and stroke incidence. Studies have revealed that common pathophysiological features, including oxidative stress, insulin resistance, abnormal protein processing and cognitive decline, occur across these. Based on the presence of shared mechanisms and signalling pathways in these seemingly distinct diseases, one could hypothesize that an effective treatment for one disorder could prove beneficial in the others. Glucagon-like peptide-1 (GLP-1)-based anti-diabetic drugs have drawn particular attention as an effective new strategy to not only regulate blood glucose but also to reduce apoptotic cell death of pancreatic beta cells in T2DM. Evidence supports a neurotrophic and neuroprotective role of GLP-1 receptor (R) stimulation in an increasing array of cellular and animal neurodegeneration models as well as in neurogenesis. Herein, we review the physiological role of GLP-1 in the nervous system, focused towards the potential benefit of GLP-1R stimulation as an immediately translatable treatment strategy for acute and chronic neurological disorders.
C1 [Salcedo, Isidro; Tweedie, David; Li, Yazhou; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM greign@grc.nia.nih.gov
FU Intramural Research Program, National Institute on Aging, National
Institutes of Health
FX This work was supported by the Intramural Research Program, National
Institute on Aging, National Institutes of Health. The authors declare
no conflicts of interest regarding the contents of this manuscript.
NR 123
TC 55
Z9 56
U1 2
U2 35
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD JUL
PY 2012
VL 166
IS 5
BP 1586
EP 1599
DI 10.1111/j.1476-5381.2012.01971.x
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 962QT
UT WOS:000305560800008
PM 22519295
ER
PT J
AU Vriens, MR
Weng, J
Suh, I
Huynh, N
Guerrero, MA
Shen, WT
Duh, QY
Clark, OH
Kebebew, E
AF Vriens, Menno R.
Weng, Julie
Suh, Insoo
Nhung Huynh
Guerrero, Marlon A.
Shen, Wen T.
Duh, Quan-Yang
Clark, Orlo H.
Kebebew, Electron
TI MicroRNA expression profiling is a potential diagnostic tool for thyroid
cancer
SO CANCER
LA English
DT Article
DE microRNA; thyroid; cancer; biomarker; diagnostic
ID PAPILLARY CARCINOMAS; PROGNOSTIC VALUE; CELL-CYCLE; DEREGULATION;
PREVALENCE; MIR-125B; MIR-222; PROTEIN; TUMORS; GENES
AB BACKGROUND: Approximately 30% of fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate or nondiagnostic. Recent studies suggest microRNA (miRNA, miR) is differentially expressed in malignant tumors and may have a role in carcinogenesis, including thyroid cancer. The authors therefore tested the hypothesis that miRNA expression analysis would identify putative markers that could distinguish benign from malignant thyroid neoplasms that are often indeterminate on FNA biopsy. METHODS: A miRNA array was used to identify differentially expressed genes (5-fold higher or lower) in pooled normal, malignant, and benign thyroid tissue samples. Real-time quantitative polymerase chain reaction was used to confirm miRNA array expression data in 104 tissue samples (7 normal thyroid, 14 hyperplastic nodule, 12 follicular variant of papillary thyroid cancer, 8 papillary thyroid cancer, 15 follicular adenoma, 12 follicular carcinoma, 12 Hurthle cell adenoma, 20 Hurthle cell carcinoma, and 4 anaplastic carcinoma cases), and 125 indeterminate clinical FNA samples. The diagnostic accuracy of differentially expressed genes was determined by analyzing receiver operating characteristics. RESULTS: Ten miRNAs showed >5-fold expression difference between benign and malignant thyroid neoplasms on miRNA array analysis. Four of the 10 miRNAs were validated to be significantly differentially expressed between benign and malignant thyroid neoplasms by quantitative polymerase chain reaction (P < .002): miR-100, miR-125b, miR-138, and miR-768-3p were overexpressed in malignant samples of follicular origin (P < .001), and in Hurthle cell carcinoma samples alone (P < .01). Only miR-125b was significantly overexpressed in follicular carcinoma samples (P < .05). The accuracy for distinguishing benign from malignant thyroid neoplasms was 79% overall, 98% for Hurthle cell neoplasms, and 71% for follicular neoplasms. The miR-138 was overexpressed in the FNA samples (P = .04) that were malignant on final pathology with an accuracy of 75%. CONCLUSIONS: MicroRNA expression differs for normal, benign, and malignant thyroid tissue. Expression analysis of differentially expressed miRNA could help distinguish benign from malignant thyroid neoplasms that are indeterminate on thyroid FNA biopsy. Cancer 2011. (c) 2011 American Cancer Society.
C1 [Vriens, Menno R.] Univ Med Ctr Utrecht, Dept Surg, Div Surg Oncol & Endocrine Surg, NL-3584 CX Utrecht, Netherlands.
[Vriens, Menno R.; Weng, Julie; Suh, Insoo; Nhung Huynh; Shen, Wen T.; Duh, Quan-Yang; Clark, Orlo H.] Univ Calif San Francisco, Dept Endocrine Surg, San Francisco, CA 94143 USA.
[Kebebew, Electron] NIH, Dept Endocrine Surg, Bethesda, MD 20892 USA.
[Guerrero, Marlon A.] Univ Arizona, Dept Endocrine Surg, Tucson, AZ USA.
RP Vriens, MR (reprint author), Univ Med Ctr Utrecht, Dept Surg, Div Surg Oncol & Endocrine Surg, Mailbox G04-228,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.
EM m.r.vriens@umcutrecht.nl
FU Dutch Cancer Society
FX We thank Pamela Derish from the UCSF Department of Surgery Publication
Office for her editorial assistance. M.R.V. was supported by the Dutch
Cancer Society.
NR 29
TC 59
Z9 61
U1 2
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUL 1
PY 2012
VL 118
IS 13
BP 3426
EP 3432
DI 10.1002/cncr.26587
PG 7
WC Oncology
SC Oncology
GA 960LM
UT WOS:000305389500028
PM 22006248
ER
PT J
AU Nakashima, H
Miyake, K
Clark, CR
Bekisz, J
Finbloom, J
Husain, SR
Baron, S
Puri, RK
Zoon, KC
AF Nakashima, Hideyuki
Miyake, Kotaro
Clark, Christopher R.
Bekisz, Joseph
Finbloom, Joel
Husain, Syed R.
Baron, Samuel
Puri, Raj K.
Zoon, Kathryn C.
TI Potent antitumor effects of combination therapy with IFNs and monocytes
in mouse models of established human ovarian and melanoma tumors
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE IFNs; Monocytes; Combination therapy; M1 macrophages; Mouse model
ID MACROPHAGE ACTIVATION; INTERFERON-ALPHA; ADOPTIVE IMMUNOTHERAPY;
CANCER-PATIENTS; NITRIC-OXIDE; CELLS; IMMUNITY; HETEROGENEITY;
POPULATION; APOPTOSIS
AB Interferon-activated monocytes are known to exert cytocidal activity against tumor cells in vitro. Here, we have examined whether a combination of IFN-alpha 2a and IFN-gamma and human monocytes mediate significant antitumor effects against human ovarian and melanoma tumor xenografts in mouse models. OVCAR-3 tumors were treated i.t. with monocytes alone, IFN-alpha 2a and IFN-gamma alone or combination of all three on day 0, 15 or 30 post-tumor implantation. Mice receiving combination therapy beginning day 15 showed significantly reduced tumor growth and prolonged survival including complete regression in 40% mice. Tumor volumes measured on day 80 in mice receiving combination therapy (206 mm(3)) were significantly smaller than those of mice receiving the IFNs alone (1,041 mm(3)), monocytes alone (1,111 mm(3)) or untreated controls (1,728 mm(3)). Similarly, combination therapy with monocytes and IFNs of much larger tumor also inhibited OVCAR-3 tumor growth. Immunohistochemistry studies showed a large number of activated macrophages (CD31(+)/CD68(+)) infiltrating into OVCAR-3 tumors and higher densities of IL-12, IP10 and NOS2, markers of M1 (classical) macrophages in tumors treated with combination therapy compared to the controls. Interestingly, IFNs-activated macrophages induced apoptosis of OVCAR-3 tumor cells as monocytes alone or IFNs alone did not mediate significant apoptosis. Similar antitumor activity was observed in the LOX melanoma mouse model, but not as profound as seen with the OVCAR-3 tumors. Administration of either mixture of monocytes and IFN-alpha 2a or monocytes and IFN-gamma did not inhibit Lox melanoma growth; however, a significant inhibition was observed when tumors were treated with a mixture of monocytes, IFN-alpha 2a and IFN-gamma. These results indicate that monocytes and both IFN-alpha 2a and IFN-gamma may be required to mediate profound antitumor effect against human ovarian and melanoma tumors in mouse models.
C1 [Nakashima, Hideyuki; Husain, Syed R.; Puri, Raj K.] NIH, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Food & Drug Adm,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Miyake, Kotaro; Clark, Christopher R.; Bekisz, Joseph; Finbloom, Joel; Baron, Samuel; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA.
RP Puri, RK (reprint author), NIH, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Food & Drug Adm,Ctr Biol Evaluat & Res, Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA.
EM raj.puri@fda.hhs.gov; kzoon@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI001038-04]
NR 52
TC 7
Z9 7
U1 1
U2 2
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 JUL
PY 2012
VL 61
IS 7
BP 1081
EP 1092
DI 10.1007/s00262-011-1152-x
PG 12
WC Oncology; Immunology
SC Oncology; Immunology
GA 962DM
UT WOS:000305519700012
PM 22159517
ER
PT J
AU Rezvani, K
Yong, ASM
Mielke, S
Savani, BN
Jafarpour, B
Eniafe, R
Le, RQ
Musse, L
Boss, C
Childs, R
Barrett, AJ
AF Rezvani, Katayoun
Yong, Agnes S. M.
Mielke, Stephan
Savani, Bipin N.
Jafarpour, Behnam
Eniafe, Rhoda
Le, Robert Quan
Musse, Laura
Boss, Carole
Childs, Richard
Barrett, A. John
TI Lymphodepletion is permissive to the development of spontaneous T-cell
responses to the self-antigen PR1 early after allogeneic stem cell
transplantation and in patients with acute myeloid leukemia undergoing
WT1 peptide vaccination following chemotherapy
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE PR1; WT1; Vaccine; Lymphopenia-driven homeostasis; Leukemia;
Immunotherapy
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; MINIMAL
RESIDUAL DISEASE; EX-VIVO CHARACTERIZATION; HOMEOSTATIC PROLIFERATION;
MULTIPLE-MYELOMA; MYELODYSPLASTIC SYNDROME; METASTATIC MELANOMA; CANCER
REGRESSION; DENDRITIC CELLS
AB PR1, an HLA-A*0201 epitope shared by proteinase-3 (PR3) and elastase (ELA2) proteins, is expressed in normal neutrophils and overexpressed in myeloid leukemias. PR1-specific T cells have been linked to graft-versus-leukemia (GVL) effect. We hypothesized that lymphopenia induced by chemo-radiotherapy can enhance weak autoimmune responses to self-antigens such as PR1. We measured PR1-specific responses in 27 patients 30-120 days following allogeneic stem cell transplant (SCT) and correlated these with ELA2 and PR3 expression and minimal residual disease (MRD). Post-SCT 10/13 CML, 6/9 ALL, and 4/5 solid tumor patients had PR1 responses correlating with PR3 and ELA2 expression. At day 180 post-SCT, 8/8 CML patients with PR1 responses were BCR-ABL-negative compared with 2/5 BCR-ABL-positive patients (P = 0.025). In contrast, PR1 responses were detected in 2/4 MRD-negative compared with 4/5 MRD-positive ALL patients (P = 0.76). To assess whether the lymphopenic milieu also exaggerates weak T-cell responses in the autologous setting, we measured spontaneous induction of PR1 responses in 3 AML patients vaccinated with WT1-126 peptide following lymphodepletion. In addition to WT1-specific T cells, we detected PR1-specific T cells in 2 patients during hematopoietic recovery. Our findings suggest that lymphopenia induced by chemo-radiotherapy enhances weak autoimmune responses to self-antigens, which may result in GVL if the leukemia expresses the relevant self-antigen.
C1 [Rezvani, Katayoun] Univ London Imperial Coll Sci Technol & Med, Dept Hematol, London W12 0NN, England.
[Rezvani, Katayoun; Yong, Agnes S. M.; Mielke, Stephan; Savani, Bipin N.; Jafarpour, Behnam; Eniafe, Rhoda; Le, Robert Quan; Musse, Laura; Boss, Carole; Childs, Richard; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Mielke, Stephan] Wuerzburg Univ, Wurzburg, Germany.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
RP Rezvani, K (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Hematol, Hammersmith Campus,4th Floor,Commonwealth Bldg,Du, London W12 0NN, England.
EM k.rezvani@imperial.ac.uk
FU NIH; National Institute for Health Research (NIHR) Biomedical Research
Centre
FX This study was supported by an NIH bench-to-bedside award. K. R.
acknowledges the support of the National Institute for Health Research
(NIHR) Biomedical Research Centre. We would like to thank the patients
who participated in the study and the nursing and medical staff at the
Clinical Centre, NHLBI.
NR 57
TC 10
Z9 10
U1 1
U2 4
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 JUL
PY 2012
VL 61
IS 7
BP 1125
EP 1136
DI 10.1007/s00262-011-1187-z
PG 12
WC Oncology; Immunology
SC Oncology; Immunology
GA 962DM
UT WOS:000305519700016
PM 22198310
ER
PT J
AU Martin, MY
Sanders, S
Griffin, JM
Oster, RA
Ritchie, C
Phelan, SM
Atienza, AA
Kahn, K
van Ryn, M
AF Martin, Michelle Y.
Sanders, Sara
Griffin, Joan M.
Oster, Robert A.
Ritchie, Christine
Phelan, Sean M.
Atienza, Audie A.
Kahn, Katherine
van Ryn, Michelle
TI Racial Variation in the Cancer Caregiving Experience A Multisite Study
of Colorectal and Lung Cancer Caregivers
SO CANCER NURSING
LA English
DT Article
DE Cancer; Caregiver; Colorectal; Lung
ID QUALITY-OF-LIFE; INFORMAL CAREGIVERS; FAMILY CAREGIVERS; HEALTH
OUTCOMES; BREAST-CANCER; BURDEN; VARIABLES; RELATIVES; STRESS
AB Background: As cancer care shifts from hospital to outpatient settings, the number of cancer caregivers continues to grow. However, little is known about the cancer caregiving experience. This gap in knowledge is especially evident for racially diverse caregivers. Objective: This study, part of a multisite study of care recipients with either lung or colorectal cancer and their caregivers, examined the caregiving experiences of African American (AA) and white caregivers. Methods: Caregivers were identified by cancer patients in the Cancer Care Outcomes Research and Surveillance consortium. Caregivers completed a self-administered, mailed questionnaire that assessed their characteristics and experiences. Analysis of covariance was used to compare racial groups by objective burden and caregiving resources while controlling for covariates. Results: Despite greater preparedness for the caregiving role (P = .006), AA caregivers reported more weekly hours caregiving than whites did (26.5 +/- 3.1 vs 18.0 +/- 1.7; P = .01). In later phases of caregiving, AAs reported having more social support (P = .02), spending more hours caregiving (31.9 +/- 3.5 vs 16.9 +/- 1.9; P < .001), and performing more instrumental activities of daily living on behalf of their care recipient (P = .021). Conclusion: Racial differences in the caregiving experience exist. Implications for Practice: Nurses play a key role in educating cancer patients and their caregivers on how to effectively cope with and manage cancer. Because AA caregivers seem to spend more time in the caregiving role and perform more caregiving tasks, AA caregivers may benefit from interventions tailored to their specific caregiving experience.
C1 [Martin, Michelle Y.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL 35294 USA.
[Sanders, Sara] Univ Iowa, Sch Social Work, Iowa City, IA 52242 USA.
[Griffin, Joan M.] Ctr Chron Dis Outcomes Res, Minneapolis VA Med Ctr, Minneapolis, MN USA.
[Griffin, Joan M.] Univ Minnesota, Minneapolis, MN 55455 USA.
[Ritchie, Christine] Birmingham VA Med Ctr Geriatr Res, Educ & Clin Ctr, Birmingham, AL USA.
[Phelan, Sean M.; van Ryn, Michelle] Univ Minnesota, Minneapolis, MN USA.
[Atienza, Audie A.] NCI, Bethesda, MD 20892 USA.
[Kahn, Katherine] RAND Corp, Santa Monica, CA USA.
[Kahn, Katherine] Univ Los Angeles, David Geffen Sch Med, Los Angeles, CA USA.
RP Martin, MY (reprint author), Univ Alabama Birmingham, Div Prevent Med, 1530 3rd Ave S,MT 617, Birmingham, AL 35294 USA.
EM mymartin@uab.edu
FU National Cancer Institute [U01 CA93324, U01 CA93326, U01 CA93329, U01
CA93332, U01 CA93339, U01 CA93344, U01 CA93348]; Department of Veterans
Affairs [CRS 02-164]
FX This study was supported by grants from the National Cancer Institute
(U01 CA93324, U01 CA93326, U01 CA93329, U01 CA93332, U01 CA93339, U01
CA93344, and U01 CA93348) and the Department of Veterans Affairs (CRS
02-164).
NR 37
TC 6
Z9 6
U1 3
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0162-220X
J9 CANCER NURS
JI Cancer Nurs.
PD JUL-AUG
PY 2012
VL 35
IS 4
BP 249
EP 256
DI 10.1097/NCC.0b013e3182330850
PG 8
WC Oncology; Nursing
SC Oncology; Nursing
GA 963LW
UT WOS:000305623200007
PM 22088979
ER
PT J
AU Desai, SA
AF Desai, Sanjay A.
TI Ion and nutrient uptake by malaria parasite-infected erythrocytes
SO CELLULAR MICROBIOLOGY
LA English
DT Article
ID SURFACE ANION CHANNEL; RED-BLOOD-CELLS; PLASMODIUM-FALCIPARUM; HOST
ERYTHROCYTE; MEMBRANE; PERMEABILITY; RESISTANCE; TRANSPORT; PERMEATION;
PATHWAYS
AB Erythrocytes infected with malaria parasites have increased permeability to diverse organic and inorganic solutes. While these permeability changes have been known for decades, the molecular basis of transport was unknown and intensively debated. CLAG3, a parasite protein previously thought to function in cytoadherence, has recently been implicated in formation of the plasmodial surface anion channel (PSAC), an unusual small conductance ion channel that mediates uptake of most solutes. Consistent with transport studies, the clag genes are conserved in all plasmodia but are absent from other genera. The encoded protein is integral to the host membrane, as also predicted by electrophysiology. An important question is whether functional channels are formed by CLAG3 alone or through interactions with other proteins. In either case, gene identification should advance our understanding of parasite biology and may lead to new therapeutics.
C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20894 USA.
RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20894 USA.
EM sdesai@niaid.nih.gov
FU National Institutes of Health, NIAID
FX This research was funded by the Intramural Research Program of the
National Institutes of Health, NIAID.
NR 42
TC 25
Z9 25
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-5814
J9 CELL MICROBIOL
JI Cell Microbiol.
PD JUL
PY 2012
VL 14
IS 7
BP 1003
EP 1009
DI 10.1111/j.1462-5822.2012.01790.x
PG 7
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA 959AT
UT WOS:000305282800003
PM 22432505
ER
PT J
AU Do, K
Doroshow, JH
Kummar, S
AF Do, Khanh
Doroshow, James H.
Kummar, Shivaani
TI Antiangiogenic approaches for the treatment of advanced synovial
sarcomas
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE anti-vascular endothelial growth factor therapy; hepatocyte growth
factor receptor; synovial sarcoma
ID ENDOTHELIAL GROWTH-FACTOR; SOFT-TISSUE SARCOMAS; PHASE-II TRIAL;
PROGNOSTIC-FACTORS; GENE-EXPRESSION; RECEPTOR 2; C-MET; ANGIOGENESIS;
INHIBITOR; VEGF
AB Purpose of review
Synovial sarcomas are regarded as chemosensitive tumors compared to other types of soft tissue sarcomas, however, prognosis for advanced refractory disease remains poor. In light of the vascular nature of sarcomas, current molecularly targeted therapies aim at an antiangiogenic approach to management of this disease.
Recent findings
Recent studies with oral vascular endothelial growth factor receptor (VEGFR) inhibitors such as sunitinib, sorafenib and cediranib have shown disease stabilization in patients with advanced synovial sarcoma. Forty-nine percent of patients with synovial sarcoma on the phase II trial of pazopanib had no evidence of disease progression at 12 weeks.
Summary
The overall impact of chemotherapy on survival has been minimal in advanced soft tissue sarcomas. Anti-VEGF therapies have resulted in improved outcomes for patients with various solid tumors, and have shown preliminary evidence of activity in synovial sarcomas. Combinations of anti-VEGF therapies with agents targeting other pathways dysregulated in sarcomas have the potential to improve the outcome of this difficult-to-treat disease.
C1 [Kummar, Shivaani] NCI, Off Director, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Do, Khanh; Doroshow, James H.; Kummar, Shivaani] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Kummar, S (reprint author), NCI, Off Director, Div Canc Treatment & Diag, Bldg 31,Room 3A44,31 Ctr Dr, Bethesda, MD 20892 USA.
EM kummars@mail.nih.gov
NR 36
TC 3
Z9 3
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8746
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD JUL
PY 2012
VL 24
IS 4
BP 425
EP 430
DI 10.1097/CCO.0b013e328354c141
PG 6
WC Oncology
SC Oncology
GA 959SD
UT WOS:000305332200013
PM 22572725
ER
PT J
AU Turkbey, B
Choyke, PL
AF Turkbey, Baris
Choyke, Peter L.
TI Multiparametric MRI and prostate cancer diagnosis and risk
stratification
SO CURRENT OPINION IN UROLOGY
LA English
DT Review
DE multiparametric MRI; prostate cancer; tumor aggressiveness
ID DIFFUSION-WEIGHTED MRI; STEP-SECTION HISTOLOGY; ENDORECTAL MR; RADICAL
PROSTATECTOMY; EXTRACAPSULAR EXTENSION; SEXTANT LOCALIZATION; GUIDED
BIOPSIES; TUMOR VOLUME; 3 T; PREDICTION
AB Purpose of review
Prostate cancer is the most common solid organ cancer type among American men. Screening and imaging aim to detect early-stage disease that is biologically aggressive. The focus of this study is to review multiparametric MRI in the detection and risk stratification of prostate cancer.
Recent findings
MP-MRI has been shown to be the most accurate noninvasive technique to localize prostate cancer. Recent studies reported that using MRI for guidance during prostate biopsies increases the yield of prostate biopsies. Moreover, multiparametric and particular MRI sequences such as apparent diffusion coefficient values of diffusion-weighted MRI have been found to correlate negatively with tumor Gleason scores.
Summary
Among the existing imaging modalities, multiplanar magnetic resonance is the best at detecting prostate cancers. Some risk stratification is possible based on size, extent and apparent diffusion coefficient values. However, prostate MRI remains nonspecific and biopsies must be performed to confirm whether an abnormality is benign or malignant and to assign Gleason scores.
C1 [Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Room B3B69F, Bethesda, MD 20892 USA.
EM pchoyke@mail.nih.gov
NR 38
TC 49
Z9 57
U1 1
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0963-0643
J9 CURR OPIN UROL
JI Curr. Opin. Urol.
PD JUL
PY 2012
VL 22
IS 4
BP 310
EP 315
DI 10.1097/MOU.0b013e32835481c2
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 962LY
UT WOS:000305547800010
PM 22617060
ER
PT J
AU Hoang, AN
Volkin, D
Yerram, NK
Vourganti, S
Nix, J
Linehan, WM
Wood, B
Pinto, PA
AF Hoang, Anthony N.
Volkin, Dmitry
Yerram, Nitin K.
Vourganti, Srinivas
Nix, Jeffrey
Linehan, W. Marston
Wood, Bradford
Pinto, Peter A.
TI Image guidance in the focal treatment of prostate cancer
SO CURRENT OPINION IN UROLOGY
LA English
DT Review
DE enhanced ultrasound modalities; focal therapy; multiparametric MRI;
prostate cancer
ID ENHANCED TRANSRECTAL ULTRASOUND; REAL-TIME ELASTOGRAPHY; RADICAL
PROSTATECTOMY; COLOR DOPPLER; MALE LUMPECTOMY; GLEASON SCORE; DIAGNOSIS;
THERAPY; BIOPSY; CRYOABLATION
AB Purpose of review
The advent of prostate-specific antigen screening has led to a seven-fold increase in the incidence of prostate cancer without a resultant decrease in mortality rate. This has led to the belief that urologists are overdetecting and overtreating clinically insignificant disease. To maintain the delicate balance between high cancer cure rate and overtreatment, which could potentially lead to unnecessary morbidities, focal therapy has emerged as the reasonable middle ground. In this article, we present the conceptual basis and the challenges of focal therapy, while emphasizing the critical role of imaging in focal treatment of prostate cancer.
Recent findings
Multiple phase I trials have demonstrated the feasibility, short-term efficacy, and safety of focal therapy. Fundamental to the success of these trials and the ultimate acceptance of focal therapy is the integral role of imaging in optimal patient selection. Among the different imaging modalities, only ultrasound and multiparametric MRI are intimately involved in the detection, diagnosis, staging, and treatment of prostate cancer. Each modality has its own unique advantages and shortcomings. Recent advances in enhanced ultrasound modalities, functional MRIs, and biopsy platforms have taken focal therapy one step closer to becoming the standard of care.
Summary
Although early results of phase I focal therapy trials are encouraging, long-term oncological outcomes remain to be elucidated. Incorporation of these technological advances into large prospective trials is needed to establish focal therapy as an important asset in the urologist's armamentarium against prostate cancer.
C1 [Hoang, Anthony N.; Volkin, Dmitry; Yerram, Nitin K.; Vourganti, Srinivas; Nix, Jeffrey; Linehan, W. Marston; Wood, Bradford; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Pinto, PA (reprint author), Bldg 10,Rm 2W-5949,10 Ctr Dr,MSC 1210, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
FU NIH Intramural Research Program
FX The study is funded by NIH Intramural Research Program.
NR 42
TC 8
Z9 8
U1 3
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0963-0643
J9 CURR OPIN UROL
JI Curr. Opin. Urol.
PD JUL
PY 2012
VL 22
IS 4
BP 328
EP 335
DI 10.1097/MOU.0b013e32835482cc
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 962LY
UT WOS:000305547800013
PM 22647649
ER
PT J
AU Zhu, L
Du, Q
Blackler, AR
Tangrea, MA
Emmert-Buck, MR
AF Zhu, Liang
Du, Qiang
Blackler, Adele R.
Tangrea, Michael A.
Emmert-Buck, Michael R.
TI In Situ Proteomic Analysis of Histological Sections
SO CURRENT PROTEOMICS
LA English
DT Review
DE Imaging mass spectrometry; immunohistochemistry; in-situ measurement;
layered electrophoretic transfer; layered expression scanning;
proteomics; tissue
ID IMAGING MASS-SPECTROMETRY; PARAFFIN-EMBEDDED TISSUE; DESORPTION
ELECTROSPRAY-IONIZATION; METABOTROPIC GLUTAMATE RECEPTORS; SEMICONDUCTOR
QUANTUM DOTS; ANTIGEN-RETRIEVAL; QUANTITATIVE IMMUNOHISTOCHEMISTRY;
PROTEIN EXPRESSION; SAMPLE PREPARATION; MICROARRAY TECHNOLOGY
AB To fully integrate molecular analysis with histology, it is essential to further develop and evaluate in situ tissue section-based technologies that are sensitive, quantitative, and high-throughput. In the proteomics field, immunohistochemistry (IHC) is the method of choice for in situ measurement of protein levels in histological sections. However, matrix-assisted laser desorption ionization-imaging mass spectrometry (MALDI-IMS) and related methods are emerging as additional multiplex in situ protein analysis tools. In this review, we discuss the application of these techniques in biomedical research and describe three newly developed technologies: multiplex tissue immunoblotting, indirect layered peptide array, and layered electrophoretic transfer (LET). In particular, we emphasize the LET technology as a novel in situ separation tool that allows for a more comprehensive proteomic analysis of a tissue sample while maintaining the important two-dimensional histological architecture.
C1 [Zhu, Liang; Du, Qiang; Blackler, Adele R.; Tangrea, Michael A.; Emmert-Buck, Michael R.] NCI, Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM buckm@mail.nih.gov
RI Zhu, Liang/G-1389-2010
FU Center for Cancer Research in the intramural program of the National
Cancer Institute, NIH
FX This work was supported by the Center for Cancer Research in the
intramural program of the National Cancer Institute, NIH.
NR 90
TC 0
Z9 0
U1 4
U2 11
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-1646
J9 CURR PROTEOMICS
JI Curr. Proteomics
PD JUL
PY 2012
VL 9
IS 2
BP 71
EP 79
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 963VV
UT WOS:000305654000001
ER
PT J
AU Young, HA
AF Young, Howard A.
TI Scientific Apps are here (and more will be coming)
SO CYTOKINE
LA English
DT Article
DE Apps; Mobile devices
AB The world of Apps is now well upon us although the application of this tool was a bit slow in coming to the scientific community. In this column I will briefly take a look at some of the Apps now available that are applicable to biomedical research. I will restrict my coverage to the Apple format, not because I am totally an Apple user (my PC is a Dell) but only because I do not have an Android device. Published by Elsevier Ltd.
C1 NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
RP Young, HA (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
EM younghow@mail.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD JUL
PY 2012
VL 59
IS 1
BP 1
EP 2
DI 10.1016/j.cyto.2012.02.014
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 962ZU
UT WOS:000305590700001
PM 22445786
ER
PT J
AU Wang, XM
Lehky, TJ
Brell, JM
Dorsey, SG
AF Wang, Xiao-Min
Lehky, Tanya J.
Brell, Joanna M.
Dorsey, Susan G.
TI Discovering cytokines as targets for chemotherapy-induced painful
peripheral neuropathy
SO CYTOKINE
LA English
DT Review
DE Peripheral neuropathy; Chemotherapy; Cytokines; Biomarkers
ID STREPTOZOTOCIN-INDUCED HYPERALGESIA; PACLITAXEL-INDUCED NEUROPATHY;
LEUKEMIA INHIBITORY FACTOR; OXIDE SYNTHASE INHIBITORS; DORSAL-ROOT
GANGLIA; DIABETIC-NEUROPATHY; SENSORY NEURONS; SCHWANN-CELLS; RAT MODEL;
VASCULAR-PERMEABILITY
AB Chemotherapy-induced peripheral neuropathy (CIPN), a dose-limiting neurotoxic effect of chemotherapy, is the most common reason for early cessation of cancer treatment. This can result in an increased risk of recurrence and decreased survival rate. Inflammatory cascade activation, proinflammatory cytokine upregulation, and neuro-immune communication pathways play essential roles in the initiation and progression of CIPN. Most notably, TNF-alpha, beta, IL-6, and CCL2 are involved in neuropathic pain. Further elucidation of the role of these cytokines could lead to their development and use as biomarkers for predicting the onset of painful peripheral neuropathy and early axonal damage. In this review, we provide evidence for the involvement of cytokines in CIPN, the possible underlying mechanisms, and their use as potential therapeutic targets and biomarkers to prevent and improve the painful peripheral neuropathy related to chemotherapeutic agents. Published by Elsevier Ltd.
C1 [Wang, Xiao-Min] NINR, NIH, Bethesda, MD 20892 USA.
[Brell, Joanna M.] NCI, NIH, Bethesda, MD 20892 USA.
[Dorsey, Susan G.] Univ Maryland, Sch Nursing, Ctr Pain Studies, Baltimore, MD 21201 USA.
RP Wang, XM (reprint author), NINR, NIH, Bethesda, MD 20892 USA.
EM xmwang@mail.nih.gov
FU NIH; NINR [3P30NR011396, 3R01NR10207]
FX The authors are thankful to Dr. Jane Fall-Dickson from Georgetown
University School of Nursing and Health Studies, and Mary Ryan, MLS,
Biomedical Librarian/Informationist, NIH Library, National Institutes of
Health for their critical reading of this manuscript. The authors are
also gratefully acknowledge Alan Hoofring and Lydia Kibiuk from the NIH
Medical Arts for their help with the illustrations. This work was
supported by NIH Bench-to-Bedside Program Awards to XMW and NINR
3P30NR011396 and 3R01NR10207 to SGD.
NR 83
TC 34
Z9 34
U1 1
U2 14
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD JUL
PY 2012
VL 59
IS 1
BP 3
EP 9
DI 10.1016/j.cyto.2012.03.027
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 962ZU
UT WOS:000305590700002
PM 22537849
ER
PT J
AU Shibui, A
Shimura, E
Nambu, A
Yamaguchi, S
Leonard, WJ
Okumura, K
Sugano, S
Sudo, K
Nakae, S
AF Shibui, Akiko
Shimura, Eri
Nambu, Aya
Yamaguchi, Sachiko
Leonard, Warren J.
Okumura, Ko
Sugano, Sumio
Sudo, Katsuko
Nakae, Susumu
TI Th17 cell-derived IL-17 is dispensable for B cell antibody production
SO CYTOKINE
LA English
DT Article
DE Interleukin-17; Th17 cells; B cells; Antibody production
ID HYPER-IGE SYNDROME; IL-17-DEFICIENT MICE; HELPER-CELLS; RESPONSES;
SUPPRESSION
AB IL-17, which is preferentially produced by Th17 cells, is important for host defense against pathogens and is also involved in the development of autoimmune and allergic disorders. Antibody (Ab) production was shown to be impaired in IL-17-deficient mice, suggesting that IL-17 may promote B cell activation and direct secretion of Ab. However, the precise role of IL-17 in Ab production by B cells remains unclear. In the present study, we found constitutive expression of IL-17R in murine splenic B cells. Nevertheless, IL-17, IL-17F or IL-25 alone could not induce Ab production by B cells even in the presence of agonistic anti-CD40 Ab. IL-17 also could not affect IFN-gamma-, IL-4- or TGF-beta 1-mediated Ig class-switching. Furthermore, in co-cultures of B cells and IL-17(-/-) CD4(+) T cells or IL-17(-/-) Th17 cells, IL-17 deficiency did not influence Ab production by B cells in vitro, suggesting that Th17 cell-derived IL-17 was not required for B cell Ab production through T cell-B cell interaction in vitro. Thus, in vivo, IL-17 may be indirectly involved in Ab production by enhancing production of B cell activator(s) by other immune cells. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Nakae, Susumu] Univ Tokyo, Inst Med Sci, Lab Syst Biol, Ctr Expt Med & Syst Biol,Minato Ku, Tokyo 1088639, Japan.
[Shibui, Akiko; Sugano, Sumio] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genom, Chiba 2778561, Japan.
[Shimura, Eri; Okumura, Ko] Juntendo Univ, Atopy Res Ctr, Tokyo 1138412, Japan.
[Yamaguchi, Sachiko; Nakae, Susumu] Univ Tokyo, Inst Med Sci, Frontier Res Initiat, Tokyo 1088639, Japan.
[Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Sudo, Katsuko] Tokyo Med Univ, Anim Res Ctr, Tokyo 1608402, Japan.
[Nakae, Susumu] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, Kawaguchi, Saitama 3320012, Japan.
RP Nakae, S (reprint author), Univ Tokyo, Inst Med Sci, Lab Syst Biol, Ctr Expt Med & Syst Biol,Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan.
EM snakae@ims.u-tokyo.ac.jp
FU Japan Society for the Promotion of Science; Ministry of Education,
Culture, Sports, Science and Technology, Japan; Restart Postdoctoral
Fellowship; Scientific Research on Priority Areas; Program for
Improvement of Research Environments for Young Researchers; The Special
Coordination Funds for Promoting Science and Technology; Japan Science
and Technology Agency, PRESTO; Division of Intramural Research, National
Heart, Lung, and Blood Institute
FX This work was supported by grants from Japan Society for the Promotion
of Science and the Ministry of Education, Culture, Sports, Science and
Technology, Japan, Grants-in-Aid for Young Scientists (B) (AS., E.S.
A.N. and S.N), Restart Postdoctoral Fellowship (A.S.), Scientific
Research on Priority Areas (S.S.) and the Program for Improvement of
Research Environments for Young Researchers, The Special Coordination
Funds for Promoting Science and Technology (S.N.), by grants from Japan
Science and Technology Agency, PRESTO (S.N.) and by the Division of
Intramural Research, National Heart, Lung, and Blood Institute (W.J.L.).
NR 19
TC 12
Z9 12
U1 0
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD JUL
PY 2012
VL 59
IS 1
BP 108
EP 114
DI 10.1016/j.cyto.2012.03.018
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 962ZU
UT WOS:000305590700019
PM 22503615
ER
PT J
AU Morrill, RJ
Paukner, A
Ferrari, PF
Ghazanfar, AA
AF Morrill, Ryan J.
Paukner, Annika
Ferrari, Pier F.
Ghazanfar, Asif A.
TI Monkey lipsmacking develops like the human speech rhythm
SO DEVELOPMENTAL SCIENCE
LA English
DT Article
ID AUDIOVISUAL SPEECH; NEURONAL OSCILLATIONS; VOCAL PRODUCTION; BRAIN
EVOLUTION; RHESUS MACAQUES; PERSPECTIVE; CHILDREN; INFANTS; CORTEX;
COORDINATION
AB Across all languages studied to date, audiovisual speech exhibits a consistent rhythmic structure. This rhythm is critical to speech perception. Some have suggested that the speech rhythm evolved de novo in humans. An alternative account the one we explored here is that the rhythm of speech evolved through the modification of rhythmic facial expressions. We tested this idea by investigating the structure and development of macaque monkey lipsmacks and found that their developmental trajectory is strikingly similar to the one that leads from human infant babbling to adult speech. Specifically, we show that: (1) younger monkeys produce slower, more variable mouth movements and as they get older, these movements become faster and less variable; and (2) this developmental pattern does not occur for another cyclical mouth movement chewing. These patterns parallel human developmental patterns for speech and chewing. They suggest that, in both species, the two types of rhythmic mouth movements use different underlying neural circuits that develop in different ways. Ultimately, both lipsmacking and speech converge on a similar to 5 Hz rhythm that represents the frequency that characterizes the speech rhythm of human adults. We conclude that monkey lipsmacking and human speech share a homologous developmental mechanism, lending strong empirical support to the idea that the human speech rhythm evolved from the rhythmic facial expressions of our primate ancestors.
C1 [Morrill, Ryan J.; Ghazanfar, Asif A.] Princeton Univ, Inst Neurosci, Princeton, NJ 08540 USA.
[Morrill, Ryan J.; Ghazanfar, Asif A.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08540 USA.
[Paukner, Annika] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Bethesda, MD USA.
[Ferrari, Pier F.] Univ Parma, Dipartimento Biol Evolutiva & Funzionale, I-43100 Parma, Italy.
[Ferrari, Pier F.] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy.
[Ghazanfar, Asif A.] Princeton Univ, Dept Psychol, Princeton, NJ 08540 USA.
RP Ghazanfar, AA (reprint author), Princeton Univ, Inst Neurosci, Princeton, NJ 08540 USA.
EM asifg@princeton.edu
FU Intramural NIH HHS [Z99 HD999999]; NCI NIH HHS [CM-5 P40 RR003640-20];
NCRR NIH HHS [P40 RR003640]; NICHD NIH HHS [P01 HD064653, P01
HD064653-01]; NIH HHS [P40 OD012217]; PHS HHS [NICHD-NIH P01HD064653]
NR 74
TC 15
Z9 15
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1363-755X
J9 DEVELOPMENTAL SCI
JI Dev. Sci.
PD JUL
PY 2012
VL 15
IS 4
BP 557
EP 568
DI 10.1111/j.1467-7687.2012.01149.x
PG 12
WC Psychology, Developmental; Psychology, Experimental
SC Psychology
GA 961HS
UT WOS:000305455700009
PM 22709404
ER
PT J
AU Stancakova, A
Civelek, M
Saleem, NK
Soininen, P
Kangas, AJ
Cederberg, H
Paananen, J
Pihlajamaki, J
Bonnycastle, LL
Morken, MA
Boehnke, M
Pajukanta, P
Lusis, AJ
Collins, FS
Kuusisto, J
Ala-Korpela, M
Laakso, M
AF Stancakova, Alena
Civelek, Mete
Saleem, Niyas K.
Soininen, Pasi
Kangas, Antti J.
Cederberg, Henna
Paananen, Jussi
Pihlajamaki, Jussi
Bonnycastle, Lori L.
Morken, Mario A.
Boehnke, Michael
Pajukanta, Paivi
Lusis, Aldons J.
Collins, Francis S.
Kuusisto, Johanna
Ala-Korpela, Mika
Laakso, Markku
TI Hyperglycemia and a Common Variant of GCKR Are Associated With the
Levels of Eight Amino Acids in 9,369 Finnish Men
SO DIABETES
LA English
DT Article
ID TYPE-2 DIABETES RISK; INSULIN SENSITIVITY; GLUCOSE-TOLERANCE;
GENETIC-VARIATION; FASTING GLUCOSE; SKELETAL-MUSCLE; PROTEIN;
METABOLISM; LEUCINE; HUMANS
AB We investigated the association of glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes with amino acid levels in the population-based Metabolic Syndrome in Men (METSIM) Study, including 9,369 nondiabetic or newly diagnosed type 2 diabetic Finnish men. Plasma levels of eight amino acids were measured with proton nuclear magnetic resonance spectroscopy. Increasing fasting and 2-h plasma glucose levels were associated with increasing levels of several amino acids and decreasing levels of histidine and glutamine. Alanine, leucine, isoleucine, tyrosine, and glutamine predicted incident type 2 diabetes in a 4.7-year follow-up of the METSIM Study, and their effects were largely mediated by insulin resistance (except for glutamine). We also found significant correlations between insulin sensitivity (Matsuda insulin sensitivity index) and mRNA expression of genes regulating amino acid degradation in 200 subcutaneous adipose tissue samples. Only 1 of 43 risk single nucleotide polymorphisms for type 2 diabetes or hyperglycemia, the glucose-increasing major C allele of rs780094 of GCKR, was significantly associated with decreased levels of alanine and isoleucine and elevated levels of glutamine. In conclusion, the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia, reflecting, at least in part, insulin resistance. Only one single nucleotide polymorphism regulating hyperglycemia was significantly associated with amino acid levels. Diabetes 61:1895-1902, 2012
C1 [Stancakova, Alena; Saleem, Niyas K.; Cederberg, Henna; Paananen, Jussi; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Stancakova, Alena; Saleem, Niyas K.; Cederberg, Henna; Paananen, Jussi; Pihlajamaki, Jussi; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Civelek, Mete; Lusis, Aldons J.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Dept Human Genet, Los Angeles, CA USA.
[Civelek, Mete; Lusis, Aldons J.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Soininen, Pasi; Kangas, Antti J.; Ala-Korpela, Mika] Univ Oulu, Inst Clin Med, Computat Med Res Grp, Oulu, Finland.
[Soininen, Pasi; Kangas, Antti J.; Ala-Korpela, Mika] Bioctr Oulu, Oulu, Finland.
[Soininen, Pasi; Ala-Korpela, Mika] Univ Eastern Finland, Nucl Magnet Resonance Metabon Lab, Chem Lab, Dept Biosci, Kuopio, Finland.
[Pihlajamaki, Jussi] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Pihlajamaki, Jussi] Univ Eastern Finland, Dept Clin Nutr, Kuopio, Finland.
[Bonnycastle, Lori L.; Morken, Mario A.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Pajukanta, Paivi] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Ala-Korpela, Mika] Univ Oulu, Clin Res Ctr, Bioctr Oulu, Oulu, Finland.
[Ala-Korpela, Mika] Univ Oulu, Dept Internal Med, SF-90220 Oulu, Finland.
RP Laakso, M (reprint author), Univ Eastern Finland, Dept Med, Kuopio, Finland.
EM markku.laakso@kuh.fi
OI Paananen, Jussi/0000-0001-5100-4907; Civelek, Mete/0000-0002-8141-0284
FU Academy of Finland; Finnish Diabetes Research Foundation; Finnish
Cardiovascular Research Foundation; Jenny and Antti Wihuri Foundation;
Kuopio University Hospital [5263, DK062370, 1Z01 HG000024]; National
Institutes of Health [HL-095056, HL-28481]
FX This work was supported by the Academy of Finland (A.S., M.L., SALVE
program to M.A.-K.), the Finnish Diabetes Research Foundation (M.L.),
the Finnish Cardiovascular Research Foundation (M.L., M.A.-K.), the
Jenny and Antti Wihuri Foundation (A.J.K.), an EVO grant from the Kuopio
University Hospital (5263), DK062370 to M.B., 1Z01 HG000024 to F.S.C.,
and National Institutes of Health Grant HL-095056 to P.P. and Grant
HL-28481 to P.P. and A.J.L.
NR 50
TC 76
Z9 77
U1 1
U2 10
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD JUL
PY 2012
VL 61
IS 7
BP 1895
EP 1902
DI 10.2337/db11-1378
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 962KL
UT WOS:000305543900032
PM 22553379
ER
PT J
AU Liden, Y
Olofsson, N
Landgren, O
Johansson, E
AF Liden, Y.
Olofsson, N.
Landgren, O.
Johansson, E.
TI Pain and anxiety during bone marrow aspiration/biopsy: Comparison of
ratings among patients versus health-care professionals
SO EUROPEAN JOURNAL OF ONCOLOGY NURSING
LA English
DT Article
DE Bone marrow aspiration; Pain; Anxiety; Agreement; Health-care
professionals; Patient
ID QUALITY-OF-LIFE; CANCER-PATIENTS; HOSPITALIZED-PATIENTS; PREOPERATIVE
ANXIETY; POSTOPERATIVE PAIN; EMOTIONAL DISTRESS; NEEDLE PHOBIA; NURSES;
PHYSICIANS; AGREEMENT
AB Purpose: To assess pain and anxiety during bone marrow aspiration/biopsy (BMA) among patients versus health-care professionals (HCPs).
Method: 235 adult hematologic patients undergoing BMA were included. BMA was performed by 16 physicians aided by nine registered nurses (RNs). Questionnaires were used to obtain patients and HCPs ratings of patients' pain and anxiety during BMA. Patterns of ratings for pain and anxiety among patients HCPs were estimated with proportions of agreement P(A), Cohen's kappa coefficient (kappa), and single-measure intra-class correlation (ICC). We also explored if associations of ratings were influenced by age, sex, type and duration of BMA.
Results: The P(A) for occurrence of rated pain during BMA was 73% between patients and RNs, and 70% between patients and physicians, the corresponding kappa was graded as fair (0.37 and 0.33). Agreement between patients and HCPs regarding intensity of pain was moderate (ICC = 0.44 and 0.42). Severe pain (VAS > 54) was identified by RNs and physicians in 34% and 35% of cases, respectively. Anxiety about BMA outcome and needle insertion was underestimated by HCPs. P(A) between patients and RNs and patients and physicians regarding anxiety ranged from 53% to 59%. The corresponding kappa was slight to fair (0.10-0.21). ICC showed poor agreement between patients and HCPs regarding intensity of anxiety (0.13-0.36).
Conclusions: We found a better congruence between patients and HCPs in pain ratings than in anxiety ratings, where the agreement was low. RNs and physicians underestimated severe pain as well as anxiety about BMA outcome and needle insertion. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Liden, Y.; Olofsson, N.] Karolinska Inst, Dept Physiol & Pharmacol, Sect Anesthesiol & Intens Care, Stockholm, Sweden.
[Landgren, O.; Johansson, E.] Karolinska Inst, Dept Med, Div Hematol, Stockholm, Sweden.
[Landgren, O.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Johansson, E.] Red Cross Univ Coll, Stockholm, Sweden.
RP Liden, Y (reprint author), Karolinska Univ Hosp Solna, Ctr Multidisciplinary Pain, Dept Anesthesia Surg Serv & Intens Care, SE-17176 Stockholm, Sweden.
EM ylva.liden@karolinska.se
NR 48
TC 6
Z9 6
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1462-3889
J9 EUR J ONCOL NURS
JI Eur. J. Oncol. Nurs.
PD JUL
PY 2012
VL 16
IS 3
BP 323
EP 329
DI 10.1016/j.ejon.2011.07.009
PG 7
WC Oncology; Nursing
SC Oncology; Nursing
GA 960GX
UT WOS:000305377100019
PM 22341718
ER
PT J
AU Marchand, C
AF Marchand, Christophe
TI The elvitegravir Quad pill: the first once-daily dual-target anti-HIV
tablet
SO EXPERT OPINION ON INVESTIGATIONAL DRUGS
LA English
DT Editorial Material
DE dolutegravir; elvitegravir; HIV-1 integrase; raltegravir
ID TREATMENT-EXPERIENCED PATIENTS; COMBINATION THERAPY; NON-INFERIORITY;
RALTEGRAVIR; RESISTANT; TRIAL; INFECTION; EFFICACY; MUTANTS; PHASE-3
AB Anti-HIV combination therapies in a single formulation currently target only HIV-1 reverse transcriptase via two different mechanisms of action by associating a nucleoside and a non-nucleoside reverse transcriptase inhibitor. These combination therapies are therefore referred to as multi-class combination products. The elvitegravir Quad pill (Gilead Sciences), when approved by the Food and Drug Administration for the treatment of HIV/AIDS, will become the first once-daily dual-target anti-HIV tablet. This "4 in 1" tablet targets HIV-1 integrase by elvitegravir boosted by the pharmaco-enhancer cobicistat and HIV-1 reverse transcriptase by the two nucleoside reverse transcriptase inhibitors emtricitabine + tenofovir disoproxil fumarate. A second pill referred to as the 572-Trii pill (Shionogi-ViiV Healthcare, LLC), also based on the dual inhibition of integrase and reverse transcriptase, is currently in late-phase clinical trials. The availability of these novel once-daily anti-HIV tablets will improve treatment adherence and offer new perspective for patient failing existing antiviral regimens.
C1 NCI, NIH, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
RP Marchand, C (reprint author), NCI, NIH, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
EM marchand@nih.gov
FU Intramural NIH HHS
NR 15
TC 18
Z9 18
U1 1
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1354-3784
J9 EXPERT OPIN INV DRUG
JI Expert Opin. Investig. Drugs
PD JUL
PY 2012
VL 21
IS 7
BP 901
EP 904
DI 10.1517/13543784.2012.685653
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 958ND
UT WOS:000305244600001
PM 22571404
ER
PT J
AU Dimichele, D
AF Dimichele, D.
TI Optimizing clinical trial design for product development in hemophilia
SO HAEMOPHILIA
LA English
DT Meeting Abstract
C1 [Dimichele, D.] NIH, Div Blood Dis & Resources, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-8216
J9 HAEMOPHILIA
JI Haemophilia
PD JUL
PY 2012
VL 18
SU 3
SI SI
BP 14
EP 14
PG 1
WC Hematology
SC Hematology
GA 961IJ
UT WOS:000305457800072
ER
PT J
AU Dimichele, DM
Blanchette, V
Berntorp, E
AF Dimichele, D. M.
Blanchette, V.
Berntorp, E.
TI Clinical trial design in haemophilia
SO HAEMOPHILIA
LA English
DT Article
DE clinical trials; definitions; haemophilia A; health-technology
assessment; haemophilia B; observational studies
ID PROPHYLAXIS; DEFINITIONS; CONSENSUS
AB Progress in the evidence-based care of haemophilia A and B worldwide has been historically challenged by the dearth of evaluable outcome data, including but not limited to the safety and effectiveness of therapeutic interventions. These challenges are partially rooted in the inherent difficulty of conducting prospective clinical trials and observational studies with statistically meaningful endpoints in a rare disease such as haemophilia. Despite the logistical barriers, the need for outcome data has never been more critical than in this time of expansive therapeutic advance tempered by the shrinking economic capacity to fund the rapidly increasing cost of treatment. Given that systematic analyses of published literature have been largely unsuccessful in compensating for the lack of rigorous and purposeful data collection, new approaches to clinical study design and statistical modelling are urgently needed. However, even as these are considered, the lack of broadly accepted and well-defined clinical outcome endpoints poses an additional barrier to progress. The three presentations encompassed by this paper highlight the timely need for quality data from the perspectives of the clinicians, regulatory agencies and health care funders, and describe the ongoing coordinated efforts by the international haemophilia community to further understand and dismantle the barriers to harmonized and standardized data collection on a global scale using well-defined clinical outcome endpoints.
C1 [Dimichele, D. M.] NHLBI, Div Blood Dis & Resources, NIH, Two Rockledge Ctr, Bethesda, MD 20892 USA.
[Blanchette, V.] Univ Toronto, Dept Pediat, Toronto, ON, Canada.
[Berntorp, E.] Lund Univ, Skane Univ Hosp, Ctr Thrombosis & Haemostasis, Malmo, Sweden.
[Blanchette, V.] Univ Toronto, Hosp Sick Children, Pediat Thrombosis & Hemostasis Program, Toronto, ON M5G 1X8, Canada.
RP Dimichele, DM (reprint author), NHLBI, Div Blood Dis & Resources, NIH, Two Rockledge Ctr, Room 9132,6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM dimicheledm@nhlbi.nih.gov
NR 10
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Z9 13
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-8216
J9 HAEMOPHILIA
JI Haemophilia
PD JUL
PY 2012
VL 18
SU 4
SI SI
BP 18
EP 23
DI 10.1111/j.1365-2516.2012.02824.x
PG 6
WC Hematology
SC Hematology
GA 963FL
UT WOS:000305605400003
PM 22726077
ER
PT J
AU Marjamaa, A
Oikarinen, L
Porthan, K
Ripatti, S
Peloso, G
Noseworthy, PA
Viitasalo, M
Nieminen, MS
Toivonen, L
Kontula, K
Peltonen, L
Havulinna, AS
Jula, A
O'Donnell, CJ
Newton-Cheh, C
Perola, M
Salomaa, V
AF Marjamaa, Annukka
Oikarinen, Lasse
Porthan, Kimmo
Ripatti, Samuli
Peloso, Gina
Noseworthy, Peter A.
Viitasalo, Matti
Nieminen, Markku S.
Toivonen, Lauri
Kontula, Kimmo
Peltonen, Leena
Havulinna, Aki S.
Jula, Antti
O'Donnell, Christopher J.
Newton-Cheh, Christopher
Perola, Markus
Salomaa, Veikko
TI A common variant near the KCNJ2 gene is associated with T-peak to T-end
interval
SO HEART RHYTHM
LA English
DT Article
DE Electrocardiogram; Repolarization; T wave; Gene; Polymorphism
ID SUDDEN CARDIAC DEATH; LEFT-VENTRICULAR HYPERTROPHY; LONG-QT-SYNDROME;
POSTMYOCARDIAL INFARCTION PATIENTS; WAVE MORPHOLOGY; HYPERTENSIVE
PATIENTS; FINNISH POPULATION; TEND INTERVAL; DISPERSION; REPOLARIZATION
AB BACKGROUND T-peak to T-end (TPE) interval on the electrocardiogram is a measure of myocardial dispersion of repolarization and is associated with an increased risk of ventricular arrhythmias. The genetic factors affecting the TPE interval are largely unknown.
OBJECTIVE To identify common genetic variants that affect the duration of the TPE interval in the general population.
METHODS We performed a genome-wide association study on 1870 individuals of Finnish origin participating in the Health 2000 Study. The TPE interval was measured from T-peak to T-wave end in leads II, V-2, and V-5 on resting electrocardiograms, and the mean of these TPE intervals was adjusted for age, sex, and Cornell voltage-duration product. We sought replication for a genome-wide significant result in the 3745 subjects from the Framingham Heart Study.
RESULTS We identified a locus on 17q24 that was associated with the TPE interval. The minor allele of the common variant rs7219669 was associated with a 1.8-ms shortening of the TPE interval (P = 1.1 x 10(-10)). The association was replicated in the Framingham Heart Study (-1.5 ms; P = 1.3 x 10(-4)). The overall effect estimate of rs7219669 in the 2 studies was -1.7 ms (P = 5.7 x 10(-14)). The common variant rs7219669 maps downstream of the KCNJ2 gene, in which rare mutations cause congenital long and short QT syndromes.
CONCLUSION The common variant rs7219669 is associated with the TPE interval and is thus a candidate to modify repolarization-related arrhythmia susceptibility in individuals carrying the major allele of this polymorphism.
C1 [Marjamaa, Annukka; Kontula, Kimmo] Univ Helsinki, Res Program Mol Med, Helsinki, Finland.
[Oikarinen, Lasse; Porthan, Kimmo; Viitasalo, Matti; Nieminen, Markku S.; Toivonen, Lauri] Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, Helsinki, Finland.
[Ripatti, Samuli; Peltonen, Leena; Perola, Markus] Univ Helsinki, FIMM, Helsinki, Finland.
[Peloso, Gina; Noseworthy, Peter A.; Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
[Peloso, Gina; Noseworthy, Peter A.; Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA.
[Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Kontula, Kimmo] Univ Helsinki, Dept Med, Helsinki, Finland.
[Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Publ Hlth Genom Unit, Helsinki, Finland.
[O'Donnell, Christopher J.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[O'Donnell, Christopher J.; Newton-Cheh, Christopher] Harvard Univ, Sch Med, Boston, MA USA.
[Peloso, Gina; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, NIH, Bethesda, MD 20892 USA.
RP Marjamaa, A (reprint author), Univ Helsinki, Biomedicum Helsinki, Res Program Mol Med, B327b,POB 700, Huch 00029, Finland.
EM Annukka.Marjamaa@helsinki.fi
RI Ripatti, Samuli/H-9446-2014;
OI Ripatti, Samuli/0000-0002-0504-1202; Perola, Markus/0000-0003-4842-1667
FU Finnish Foundation for Cardiovascular Research; Orion-Farmos Research
Foundation; Finnish Academy SALVE program "Pubgensense" [129322];
Academy of Finland [129494, 139635]; Sigrid Juselius Foundation;
National Heart, Lung, and Blood Institute of the National Institutes of
Health; Boston University School of Medicine [N01-HC-25195]; Affymetrix,
Inc [N02-HL-6-4278]; Doris Duke Charitable Foundation; Burroughs
Wellcome Fund
FX Leena Peltonen is deceased. Dr Porthan, Dr Oikarinen, and Dr Viitasalo
were financially supported by the Finnish Foundation for Cardiovascular
Research. Dr Porthan was also supported by the Orion-Farmos Research
Foundation. Dr Perola was supported by the Finnish Academy SALVE program
"Pubgensense" 129322 and the Finnish Foundation for Cardiovascular
Research. Dr Salomaa was supported by the Academy of Finland (grant
numbers 129494 and 139635). Dr Kontula was supported by grants from the
Sigrid Juselius Foundation and Finnish Foundation for Cardiovascular
Research. The Framingham Heart Study work was supported by the National
Heart, Lung, and Blood Institute of the National Institutes of Health
and Boston University School of Medicine (contract number N01-HC-25195),
its contract with Affymetrix, Inc, for genotyping services (contract
number N02-HL-6-4278), and the Doris Duke Charitable Foundation (to Dr
Newton-Cheh) and Burroughs Wellcome Fund (to Dr Newton-Cheh), based on
analyses by Framingham Heart Study investigators participating in the
SNP Health Association Resource (SHARe) project. Address for reprints
and correspondence: Dr Annukka Marjamaa, MD, PhD, Research Program in
Molecular Medicine, University of Helsinki, Biomedicum Helsinki, B327b,
PO Box 700, 00029 Huch, Finland. E-mail address:
Annukka.Marjamaa@helsinki.fi.
NR 30
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Z9 4
U1 0
U2 3
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 JUL
PY 2012
VL 9
IS 7
BP 1099
EP 1103
DI 10.1016/j.hrthm.2012.02.019
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 963JP
UT WOS:000305616900015
PM 22342860
ER
PT J
AU Warren, DE
Duff, MC
Jensen, U
Tranel, D
Cohen, NJ
AF Warren, David E.
Duff, Melissa C.
Jensen, Unni
Tranel, Daniel
Cohen, Neal J.
TI Hiding in plain view: Lesions of the medial temporal lobe impair online
representation
SO HIPPOCAMPUS
LA English
DT Article
DE memory; STM; WM; MTL; hippocampus; amnesia
ID SHORT-TERM-MEMORY; BILATERAL HIPPOCAMPAL LESIONS; WORKING-MEMORY;
LONG-TERM; ACTIVE MAINTENANCE; PERIRHINAL CORTEX; LARGE-SCALE; AMNESIA;
PERFORMANCE; PERCEPTION
AB The hippocampus is necessary for the normal formation of enduring declarative memories, but its role in cognitive processes spanning short intervals is less well understood. Within the last decade, several reports have described modest behavioral deficits in medial temporal lobe (MTL)-lesion patients when they perform tasks that do not seem likely to rely on enduring memory. An intriguing but sparsely-tested implication of such results is that the MTL is involved in the online representation of information, possibly of an associative/relational nature, irrespective of delay. We administered several tests that simultaneously presented all information necessary for accurate responses to a group of MTL-lesion patients with severe declarative memory deficits but otherwise normal cognition, and to matched brain-damaged and healthy comparison participants. MTL-lesion patients performed less well than either comparison group in the Hooper Visual Organization Test, and several patients performed outside the normal range on the Overlapping Figures Test. A novel follow-up borrowing characteristics of the Overlapping Figures Test revealed impaired identification of novel items by MTL-lesion patients when target items were obscured by distracters, and two additional novel tests of fragmented object identification further implicated the hippocampus/MTL in the integration of information across very brief intervals. These findings suggest that MTL structures including the hippocampus contribute similarly to cognition irrespective of timescale. (C) 2011 Wiley Periodicals, Inc.
C1 [Warren, David E.; Duff, Melissa C.; Tranel, Daniel] Univ Iowa, Coll Med, Dept Neurol, Div Behav Neurol & Cognit Neurosci, Iowa City, IA 52242 USA.
[Duff, Melissa C.] Univ Iowa, Dept Commun Sci & Disorders, Iowa City, IA USA.
[Jensen, Unni] NINDS, NIH, Bethesda, MD 20892 USA.
[Cohen, Neal J.] Univ Illinois, Dept Psychol, Beckman Inst Adv Sci & Technol, Urbana, IL USA.
[Cohen, Neal J.] Univ Illinois, Dept Neurosci, Beckman Inst Adv Sci & Technol, Urbana, IL USA.
RP Warren, DE (reprint author), Univ Iowa, Coll Med, Dept Neurol, Div Behav Neurol & Cognit Neurosci, 200 Hawkins Dr,2192 RCP, Iowa City, IA 52242 USA.
EM davideugenewarren@gmail.com
OI Warren, David/0000-0003-0539-2587
FU NINDS [P01 NS19632]; NIMH [RO1 MH062500]
FX Grant sponsor: NINDS; Grant number: P01 NS19632; Grant sponsor: NIMH;
Grant number: RO1 MH062500.
NR 48
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Z9 24
U1 2
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1050-9631
J9 HIPPOCAMPUS
JI Hippocampus
PD JUL
PY 2012
VL 22
IS 7
BP 1577
EP 1588
DI 10.1002/hipo.21000
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 961FX
UT WOS:000305450700009
PM 22180166
ER
PT J
AU Doumatey, AP
Chen, GJ
Ayele, FT
Zhou, J
Erdos, M
Shriner, D
Huang, HX
Adeleye, J
Balogun, W
Fasanmade, O
Johnson, T
Oli, J
Okafor, G
Amoah, A
Eghan, BA
Agyenim-Boateng, K
Acheampong, J
Adebamowo, C
Gerry, NP
Christman, MF
Adeyemo, A
Rotimi, CN
AF Doumatey, Ayo P.
Chen, Guanjie
Ayele, Fasil Tekola
Zhou, Jie
Erdos, Michael
Shriner, Daniel
Huang, Hanxia
Adeleye, Jokotade
Balogun, Williams
Fasanmade, Olufemi
Johnson, Thomas
Oli, Johnnie
Okafor, Godfrey
Amoah, Albert
Eghan, Benjamin A.
Agyenim-Boateng, Kofi
Acheampong, Joseph
Adebamowo, Clement
Gerry, Norman P.
Christman, Michael F.
Adeyemo, Adebowale
Rotimi, Charles N.
TI C-reactive protein (CRP) promoter polymorphisms influence circulating
CRP levels in a genome-wide association study of African Americans
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CARDIOVASCULAR-DISEASE; METABOLIC-SYNDROME; GENETIC-VARIATION;
SUSCEPTIBILITY GENES; RISK; HEALTH; INTERLEUKIN-6; SEARCH; HNF1A; PHASE
AB C-reactive protein (CRP) is an acute phase reactant protein produced primarily by the liver. Circulating CRP levels are influenced by genetic and non-genetic factors, including infection and obesity. Genome-wide association studies (GWAS) provide an unbiased approach towards identifying loci influencing CRP levels. None of the six GWAS for CRP levels has been conducted in an African ancestry population. The present study aims to: (i) identify genetic variants that influence serum CRP in African Americans (AA) using a genome-wide association approach and replicate these findings in West Africans (WA), (ii) assess transferability of major signals for CRP reported in European ancestry populations (EA) to AA and (iii) use the weak linkage disequilibrium (LD) structure characteristic of African ancestry populations to fine-map the previously reported CRP locus. The discovery cohort comprised 837 unrelated AA, with the replication of significant single-nucleotide polymorphisms (SNPs) assessed in 486 WA. The association analysis was conducted with 2 366 856 genotyped and imputed SNPs under an additive genetic model with adjustment for appropriate covariates. Genome-wide and replication significances were set at P 5 10(8) and P 0.05, respectively. Ten SNPs in(CRP pseudogene-1) CRPP1 and CRP genes were associated with serum CRP (P 2.4 10(09) to 4.3 10(11)). All but one of the top-scoring SNPs associated with CRP in AA were successfully replicated in WA. CRP signals previously identified in EA samples were transferable to AAs, and we were able to fine-map this signal, reducing the region of interest from the 25 kb of LD around the locus in the HapMap CEU sample to only 8 kb in our AA sample.
C1 [Doumatey, Ayo P.; Chen, Guanjie; Ayele, Fasil Tekola; Zhou, Jie; Shriner, Daniel; Huang, Hanxia; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20852 USA.
[Erdos, Michael] NHGRI, Genome Technol Branch, Mol Genet Sect, NIH, Bethesda, MD 20852 USA.
[Adeleye, Jokotade; Balogun, Williams; Adebamowo, Clement] Univ Ibadan, Ibadan, Nigeria.
[Fasanmade, Olufemi; Johnson, Thomas] Univ Lagos, Lagos, Nigeria.
[Oli, Johnnie; Okafor, Godfrey] Univ Nigeria, Teaching Hosp, Enugu, Nigeria.
[Amoah, Albert] Univ Ghana, Sch Med, Accra, Ghana.
[Eghan, Benjamin A.; Agyenim-Boateng, Kofi; Acheampong, Joseph] Univ Sci & Technol, Kumasi, Ghana.
[Adebamowo, Clement] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Gerry, Norman P.; Christman, Michael F.] Coriell Inst Med Res, Camden, NJ USA.
RP Doumatey, AP (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, 12 S Dr Bldg 12A-4047, Bethesda, MD 20852 USA.
EM doumateya@mail.nih.gov
OI Adebamowo, Clement/0000-0002-6571-2880; Adeyemo,
Adebowale/0000-0002-3105-3231; Tekola-Ayele, Fasil/0000-0003-4194-9370
FU Intramural Research Program of the Center for Research on Genomics and
Global Health (CRGGH); Office of the Director, National Institute of
Diabetes and Digestive and Kidney diseases (NIDDK); National Human
Genome Research Institute (NHGRI) at National Institutes of Health
[Z01HG200362]; National Institutes of Health [S06GM008016-320107,
S06GM008016-380111, 2M01RR010284]
FX This work was supported in part by the Intramural Research Program of
the Center for Research on Genomics and Global Health (CRGGH). The CRGGH
is supported by funds from the Office of the Director, National
Institute of Diabetes and Digestive and Kidney diseases (NIDDK) and
National Human Genome Research Institute (NHGRI) at National Institutes
of Health (Z01HG200362). The Howard University Family Study was
supported by National Institutes of Health grants (S06GM008016-320107 to
C. R., S06GM008016-380111 to A. A.). The Howard University General
Clinical Research Center was supported by National Institutes of Health
(grant 2M01RR010284).
NR 39
TC 12
Z9 12
U1 0
U2 3
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 JUL 1
PY 2012
VL 21
IS 13
BP 3063
EP 3072
DI 10.1093/hmg/dds133
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 961II
UT WOS:000305457700019
PM 22492993
ER
PT J
AU Alaro, JR
Angov, E
Lopez, AM
Zhou, H
Long, CA
Burns, JM
AF Alaro, James R.
Angov, Evelina
Lopez, Ana M.
Zhou, Hong
Long, Carole A.
Burns, James M., Jr.
TI Evaluation of the Immunogenicity and Vaccine Potential of Recombinant
Plasmodium falciparum Merozoite Surface Protein 8
SO INFECTION AND IMMUNITY
LA English
DT Article
ID APICAL MEMBRANE ANTIGEN-1; FACTOR-LIKE DOMAINS; MALARIA VACCINE;
MONOCLONAL-ANTIBODY; TERMINAL FRAGMENT; ESCHERICHIA-COLI; DISULFIDE
BONDS; INVASION; YOELII; IMMUNIZATION
AB The C-terminal 19-kDa domain of merozoite surface protein 1 (MSP1(19)) is the target of protective antibodies but alone is poorly immunogenic. Previously, using the Plasmodium yoelii murine model, we fused P. yoelii MSP1(19) (PfMSP1(19)) with full-length P. yoelii merozoite surface protein 8 (MSP8). Upon immunization, the MSP8-restricted T cell response provided help for the production of high and sustained levels of protective PfMSP1(19)- and PyMSP8-specific antibodies. Here, we assessed the vaccine potential of MSP8 of the human malaria parasite, Plasmodium falciparum. Distinct from PfMSP8, P. falciparum MSP8 (PfMSP8) contains an N-terminal asparagine and aspartic acid (Asn/Asp)-rich domain whose function is unknown. Comparative analysis of recombinant full-length PfMSP8 and a truncated version devoid of the Asn/Asp-rich domain, PfMSP8(Delta Asn/Asp), showed that both proteins were immunogenic for T cells and B cells. All T cell epitopes utilized mapped within rPfMSP8(Delta Asn/Asp). The dominant B cell epitopes were conformational and common to both rPfMSP8 and rPfMSP8(Delta Asn/Asp). Analysis of native PfMSP8 expression revealed that PfMSP8 is present intracellularly in late schizonts and merozoites. Following invasion, PfMSP8 is found distributed on the surface of ring- and trophozoite-stage parasites. Consistent with a low and/or transient expression of PfMSP8 on the surface of merozoites, PfMSP8-specific rabbit IgG did not inhibit the in vitro growth of P. falciparum blood-stage parasites. These studies suggest that the further development of PfMSP8 as a malaria vaccine component should focus on the use of PfMSP8(Delta Asn/Asp) and its conserved, immunogenic T cell epitopes as a fusion partner for protective domains of poor immunogens, including PfMSP1(19).
C1 [Alaro, James R.; Lopez, Ana M.; Long, Carole A.; Burns, James M., Jr.] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Ctr Mol Parasitol, Philadelphia, PA 19104 USA.
[Angov, Evelina] Walter Reed Army Inst Res, US Mil Malaria Res Program, Malaria Vaccine Branch, Silver Spring, MD USA.
[Zhou, Hong; Long, Carole A.] NIAID, Malaria Immunol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
RP Burns, JM (reprint author), Drexel Univ, Coll Med, Dept Microbiol & Immunol, Ctr Mol Parasitol, Philadelphia, PA 19104 USA.
EM jburns@drexelmed.edu
FU NIH-NIAID [AI035661]; PATH Malaria Vaccine Initiative
FX This work was supported by NIH-NIAID grant AI035661 (J.M.B.) and the
Intramural Program of NIH-NIAID (C.A.L.).; We thank Kazutoyo Miura
(NIH-NIAID) for providing the GIA data through the GIA Reference Center
that is supported by the PATH Malaria Vaccine Initiative. We thank
Prakash Srinivasan (NIH-NIAID) for assistance with the
immunofluorescence analysis.
NR 54
TC 4
Z9 5
U1 0
U2 0
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 JUL
PY 2012
VL 80
IS 7
BP 2473
EP 2484
DI 10.1128/IAI.00211-12
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 963DD
UT WOS:000305599400023
PM 22585960
ER
PT J
AU Babu, S
Anuradha, R
Kumar, NP
George, PJ
Kumaraswami, V
Nutman, TB
AF Babu, Subash
Anuradha, R.
Kumar, N. Pavan
George, P. Jovvian
Kumaraswami, V.
Nutman, Thomas B.
TI Toll-Like Receptor- and Filarial Antigen-Mediated, Mitogen-Activated
Protein Kinase- and NF-kappa B-Dependent Regulation of Angiogenic Growth
Factors in Filarial Lymphatic Pathology
SO INFECTION AND IMMUNITY
LA English
DT Article
ID ENDOSYMBIOTIC WOLBACHIA-BACTERIA; WUCHERERIA-BANCROFTI;
IMMUNE-RESPONSES; PARASITES; INFECTION; PATHWAYS; DISEASE; INNATE;
CELLS; TLR4
AB Filarial lymphatic pathology is of multifactorial origin, with inflammation, lymphangiogenesis, and innate immune responses all playing important roles. The role of Toll-like receptors (TLRs) in the development of filarial pathology is well characterized. Similarly, the association of pathology with elevated levels of plasma angiogenic factors has also been documented. To examine the association between TLR function and the development of lymphangiogenesis in filarial infections, we examined TLR- and filarial antigen-induced expression and production of various angiogenic growth factors. We demonstrate that TLR ligands (specifically TLR2, -3, and -5 ligands) induce significantly increased expression/production of vascular endothelial growth factor A (VEGF-A) and angiopoietin-1 (Ang-1) in the peripheral blood mononuclear cells of individuals with lymphatic pathology (CP individuals) compared to that in cells of asymptomatic infected (INF) individuals. Similarly, filarial antigens induce significantly enhanced production of VEGF-C in CP compared with INF individuals. TLR2-mediated enhancement of angiogenic growth factor production in CP individuals was shown to be dependent on mitogen-activated protein kinase (MAPK) and NF-kappa B signaling, as pharmacologic inhibition of either extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, or NF-kappa B signaling resulted in significantly diminished production of VEGF-A and Ang-1. Our data therefore strongly suggest an important association between TLR signaling and lymphangiogenesis in the development of pathology in human lymphatic filariasis.
C1 [Babu, Subash; Anuradha, R.; Kumar, N. Pavan; George, P. Jovvian] Int Ctr Excellence Res, NIH, Madras, Tamil Nadu, India.
[Babu, Subash; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Kumaraswami, V.] TB Res Ctr, Madras, Tamil Nadu, India.
RP Babu, S (reprint author), Int Ctr Excellence Res, NIH, Madras, Tamil Nadu, India.
EM sbabu@mail.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
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.
NR 27
TC 7
Z9 8
U1 0
U2 6
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 JUL
PY 2012
VL 80
IS 7
BP 2509
EP 2518
DI 10.1128/IAI.06179-11
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 963DD
UT WOS:000305599400027
PM 22508858
ER
PT J
AU Hicks, CW
Sweeney, DA
Cui, XZ
Li, Y
Eichacker, PQ
AF Hicks, Caitlin W.
Sweeney, Daniel A.
Cui, Xizhong
Li, Yan
Eichacker, Peter Q.
TI An overview of anthrax infection including the recently identified form
of disease in injection drug users
SO INTENSIVE CARE MEDICINE
LA English
DT Review
DE Bacillus anthracis; Anthrax; Pathogenesis; Diagnosis; Treatment
ID DIRECTED MONOCLONAL-ANTIBODY; BIOTERRORISM-RELATED ANTHRAX; PROTECTIVE
ANTIGEN-ANTIBODY; INHALATIONAL ANTHRAX; BACILLUS-ANTHRACIS; LETHAL
TOXIN; INTESTINAL ANTHRAX; CUTANEOUS ANTHRAX; BIOLOGICAL WARFARE;
UNITED-STATES
AB Bacillus anthracis infection (anthrax) can be highly lethal. Two recent outbreaks related to contaminated mail in the USA and heroin in the UK and Europe and its potential as a bioterrorist weapon have greatly increased concerns over anthrax in the developed world.
This review summarizes the microbiology, pathogenesis, diagnosis, and management of anthrax.
Anthrax, a gram-positive bacterium, has typically been associated with three forms of infection: cutaneous, gastrointestinal, and inhalational. However, the anthrax outbreak among injection drug users has emphasized the importance of what is now considered a fourth disease form (i.e., injectional anthrax) that is characterized by severe soft tissue infection. While cutaneous anthrax is most common, its early stages are distinct and prompt appropriate treatment commonly produces a good outcome. However, early symptoms with the other three disease forms can be nonspecific and mistaken for less lethal conditions. As a result, patients with gastrointestinal, inhalational, or injectional anthrax may have advanced infection at presentation that can be highly lethal. Once anthrax is suspected, the diagnosis can usually be made with gram stain and culture from blood or tissue followed by confirmatory testing (e.g., PCR). While antibiotics are the mainstay of anthrax treatment, use of adjunctive therapies such as anthrax toxin antagonists are a consideration. Prompt surgical therapy appears to be important for successful management of injectional anthrax.
C1 [Cui, Xizhong; Li, Yan; Eichacker, Peter Q.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Sweeney, Daniel A.] Washington Hosp, Med Intensivist Program, Fremont, CA USA.
[Hicks, Caitlin W.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44122 USA.
[Hicks, Caitlin W.] Howard Hughes Med Inst, Bethesda, MD 20814 USA.
RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 2C145, Bethesda, MD 20892 USA.
EM peichacker@cc.nih.gov
OI Hicks, Caitlin/0000-0001-7638-1936
FU Intramural NIH HHS [Z99 CL999999]
NR 98
TC 45
Z9 48
U1 6
U2 50
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0342-4642
J9 INTENS CARE MED
JI Intensive Care Med.
PD JUL
PY 2012
VL 38
IS 7
BP 1092
EP 1104
DI 10.1007/s00134-012-2541-0
PG 13
WC Critical Care Medicine
SC General & Internal Medicine
GA 960TK
UT WOS:000305413300003
PM 22527064
ER
PT J
AU Boyce, AM
Chong, WH
Yao, J
Gafni, RI
Kelly, MH
Chamberlain, CE
Bassim, C
Cherman, N
Ellsworth, M
Kasa-Vubu, JZ
Farley, FA
Molinolo, AA
Bhattacharyya, N
Collins, MT
AF Boyce, Alison M.
Chong, William H.
Yao, Jack
Gafni, Rachel I.
Kelly, Marilyn H.
Chamberlain, Christine E.
Bassim, Carol
Cherman, Natasha
Ellsworth, Michelle
Kasa-Vubu, Josephine Z.
Farley, Frances A.
Molinolo, Alfredo A.
Bhattacharyya, Nisan
Collins, Michael T.
TI Denosumab treatment for fibrous dysplasia
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE RANK LIGAND; MCCUNE-ALBRIGHT SYNDROME; HYPERCALCEMIA
ID MCCUNE-ALBRIGHT-SYNDROME; STIMULATORY G-PROTEIN; BONE-MINERAL DENSITY;
FIBROCARTILAGINOUS DYSPLASIA; ACTIVATING MUTATIONS; SKELETAL
PROGENITORS; RANKL EXPRESSION; GENE; DIFFERENTIATION; PAMIDRONATE
AB Fibrous dysplasia (FD) is a skeletal disease caused by somatic activating mutations of the cyclic adenosine monophosphate (cAMP)-regulating protein, a-subunit of the Gs stimulatory protein (Gsa). These mutations lead to replacement of normal bone by proliferative osteogenic precursors, resulting in deformity, fracture, and pain. Medical treatment has been ineffective in altering the disease course. Receptor activator of NF-?B ligand (RANKL) is a cell-surface protein involved in many cellular processes, including osteoclastogenesis, and is reported to be overexpressed in FD-like bone cells. Denosumab is a humanized monoclonal antibody to RANKL approved for treatment of osteoporosis and prevention of skeletal-related events from bone metastases. We present the case of a 9-year-old boy with severe FD who was treated with denosumab for a rapidly expanding femoral lesion. Immunohistochemical staining on a pretreatment bone biopsy specimen revealed marked RANKL expression. He was started on monthly denosumab, with an initial starting dose of 1?mg/kg and planned 0.25?mg/kg dose escalations every 3 months. Over 7 months of treatment he showed marked reduction in pain, bone turnover markers (BTMs), and tumor growth rate. Denosumab did not appear to impair healing of a femoral fracture that occurred while on treatment. With initiation of treatment he developed hypophosphatemia and secondary hyperparathyroidism, necessitating supplementation with phosphorus, calcium, and calcitriol. BTMs showed rapid and sustained suppression. With discontinuation there was rapid and dramatic rebound of BTMs with cross-linked C-telopeptide (reflecting osteoclast activity) exceeding pretreatment levels, accompanied by severe hypercalcemia. In this child, denosumab lead to dramatic reduction of FD expansion and FD-related bone pain. Denosumab was associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation. Denosumab treatment of FD warrants further study to confirm efficacy and determine potential morbidity, as well as to determine the mechanism of RANKL in the pathogenesis of FD and related bone marrow stromal cell diseases. (c) 2012 American Society for Bone and Mineral Research.
C1 [Boyce, Alison M.; Chong, William H.; Gafni, Rachel I.; Kelly, Marilyn H.; Cherman, Natasha; Bhattacharyya, Nisan; Collins, Michael T.] NIDCR, Skeletal Clin Studies Unit, CSDB, NIH, Bethesda, MD 20892 USA.
[Boyce, Alison M.] NICHD, NIH, Bethesda, MD USA.
[Chamberlain, Christine E.] NIH, Dept Pharm, Bethesda, MD 20892 USA.
[Ellsworth, Michelle; Kasa-Vubu, Josephine Z.; Farley, Frances A.] Univ Michigan, Univ Michigan Hlth Syst, Ann Arbor, MI 48109 USA.
[Molinolo, Alfredo A.] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Collins, MT (reprint author), NIDCR, Skeletal Clin Studies Unit, CSDB, NIH, 30 Convent Dr,Bldg 30,Room 228,MSC 4320, Bethesda, MD 20892 USA.
EM mc247k@nih.gov
FU Intramural Research Program of the NIH, NIDCR
FX This research was supported by the Intramural Research Program of the
NIH, NIDCR.
NR 44
TC 39
Z9 41
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD JUL
PY 2012
VL 27
IS 7
BP 1462
EP 1470
DI 10.1002/jbmr.1603
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 959EZ
UT WOS:000305297000004
PM 22431375
ER
PT J
AU Pleil, JD
Blount, BC
Waidyanatha, S
Harper, M
AF Pleil, Joachim D.
Blount, Benjamin C.
Waidyanatha, Suramya
Harper, Martin
TI Establishing exposure science as a distinct scientific discipline
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Editorial Material
C1 [Pleil, Joachim D.] US Environm Protect Agcy EPA, Human Exposure & Atmospher Sci Div, NERL ORD, Res Triangle Pk, NC USA.
[Blount, Benjamin C.] Ctr Dis Control & Prevent CDC, Div Lab Syst, Atlanta, GA USA.
[Waidyanatha, Suramya] Natl Inst Environm Hlth NIEHS, Natl Toxicol Program, Res Triangle Pk, NC USA.
[Harper, Martin] NIOSH, Hlth Effects Lab Div, Morgantown, WV USA.
RP Pleil, JD (reprint author), US Environm Protect Agcy EPA, Human Exposure & Atmospher Sci Div, NERL ORD, Res Triangle Pk, NC USA.
EM pleil.joachim@epa.gov
OI Pleil, Joachim/0000-0001-8211-0796
FU Intramural CDC HHS [CC999999]
NR 4
TC 4
Z9 4
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1559-0631
J9 J EXPO SCI ENV EPID
JI J. Expo. Sci. Environ. Epidemiol.
PD JUL-AUG
PY 2012
VL 22
IS 4
BP 317
EP 319
DI 10.1038/jes.2012.5
PG 3
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 964KR
UT WOS:000305694000001
PM 22713533
ER
PT J
AU Heltshe, SL
Lubin, JH
Koutros, S
Coble, JB
Ji, BT
Alavanja, MCR
Blair, A
Sandler, DP
Hines, CJ
Thomas, KW
Barker, J
Andreotti, G
Hoppin, JA
Freeman, LEB
AF Heltshe, Sonya L.
Lubin, Jay H.
Koutros, Stella
Coble, Joseph B.
Ji, Bu-Tian
Alavanja, Michael C. R.
Blair, Aaron
Sandler, Dale P.
Hines, Cynthia J.
Thomas, Kent W.
Barker, Joseph
Andreotti, Gabriella
Hoppin, Jane A.
Freeman, Laura E. Beane
TI Using multiple imputation to assign pesticide use for non-responders in
the follow-up questionnaire in the Agricultural Health Study
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Article
DE agriculture; cohort studies; missing data; pesticides; precision
ID HOT DECK IMPUTATION
AB The Agricultural Health Study (AHS), a large prospective cohort, was designed to elucidate associations between pesticide use and other agricultural exposures and health outcomes. The cohort includes 57,310 pesticide applicators who were enrolled between 1993 and 1997 in Iowa and North Carolina. A follow-up questionnaire administered 5 years later was completed by 36,342 (63%) of the original participants. Missing pesticide use information from participants who did not complete the second questionnaire impedes both long-term pesticide exposure estimation and statistical inference of risk for health outcomes. Logistic regression and stratified sampling were used to impute key variables related to the use of specific pesticides for 20,968 applicators who did not complete the second questionnaire. To assess the imputation procedure, a 20% random sample of participants was withheld for comparison. The observed and imputed prevalence of any pesticide use in the holdout dataset were 85.7% and 85.3%, respectively. The distribution of prevalence and days/year of use for specific pesticides were similar across observed and imputed in the holdout sample. When appropriately implemented, multiple imputation can reduce bias and increase precision and can be more valid than other missing data approaches.
C1 [Freeman, Laura E. Beane] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20892 USA.
[Heltshe, Sonya L.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA.
[Sandler, Dale P.; Hoppin, Jane A.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Hines, Cynthia J.] NIOSH, Cincinnati, OH 45226 USA.
[Thomas, Kent W.] US EPA, Natl Exposure Res Lab, Res Triangle Pk, NC 27711 USA.
[Barker, Joseph] Informat Management Syst, Rockville, MD USA.
RP Freeman, LEB (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,RM 8112,MSC 7240, Rockville, MD 20892 USA.
EM freemala@mail.nih.gov
RI Beane Freeman, Laura/C-4468-2015;
OI Beane Freeman, Laura/0000-0003-1294-4124; Sandler,
Dale/0000-0002-6776-0018
FU Intramural Research Program of the National Cancer Institute at the
National Institutes of Health [Z01-CP010119]; National Institute of
Environmental Health Sciences at the National Institutes of Health
[Z01-ES049030]
FX This work is supported by the Intramural Research Program of the
National Cancer Institute at the National Institutes of Health (grant
number Z01-CP010119); and the National Institute of Environmental Health
Sciences at the National Institutes of Health (grant number
Z01-ES049030). The United States Environmental Protection Agency through
its Office of Research and Development collaborated in the research
described here. It has been subjected to Agency review and approved for
publication. The findings and conclusions in this report are those of
the authors and do not necessarily represent the views of the National
Institute for Occupational Safety and Health.
NR 22
TC 7
Z9 7
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1559-0631
J9 J EXPO SCI ENV EPID
JI J. Expo. Sci. Environ. Epidemiol.
PD JUL-AUG
PY 2012
VL 22
IS 4
BP 409
EP 416
DI 10.1038/jes.2012.31
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 964KR
UT WOS:000305694000014
PM 22569205
ER
PT J
AU Ward, MM
AF Ward, Michael M.
TI Personalized Therapeutics: A Potential Threat to Health Equity
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
ID PATIENT ASSISTANCE PROGRAMS; ANTIRETROVIRAL THERAPY;
SOCIOECONOMIC-STATUS; MORTALITY; NAVIGATION; RATES
AB Throughout history, medical advances have been adopted first and preferentially by the well educated and economically advantaged groups. The development of personalized therapeutics holds promise to fundamentally alter the practice of clinical medicine, but if it also is used preferentially by economically advantaged groups, this advance will likely worsen socioeconomic disparities in health. Prospective development of strategies to ensure non- differential access to these therapies may help limit this unintended consequence of medical progress for economically disadvantaged groups.
C1 NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases,
National Institutes of Health
FX This work was supported by the Intramural Research Program, National
Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institutes of Health.
NR 22
TC 2
Z9 2
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2012
VL 27
IS 7
BP 868
EP 870
DI 10.1007/s11606-012-2002-z
PG 3
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 962ET
UT WOS:000305524400021
PM 22311335
ER
PT J
AU Bernini, A
Spiga, O
Venditti, V
Prischi, F
Botta, M
Croce, G
Tong, APL
Wong, WT
Niccolai, N
AF Bernini, Andrea
Spiga, Ottavia
Venditti, Vincenzo
Prischi, Filippo
Botta, Mauro
Croce, Gianluca
Tong, Angela Pui-Ling
Wong, Wing-Tak
Niccolai, Neri
TI The use of a ditopic Gd(III) paramagnetic probe for investigating
alpha-bungarotoxin surface accessibility
SO JOURNAL OF INORGANIC BIOCHEMISTRY
LA English
DT Article
DE Protein surface accessibility; NMR spectroscopy; Gd(III) complexes;
Paramagnetic probe; Protein hydration
ID ACETYLCHOLINE-RECEPTOR; CRYSTAL-STRUCTURE; RIBONUCLEASE-A; NMR; MD;
PARAMETERS; RESOLUTION; DYNAMICS; COMPLEX; LIGAND
AB Protein surface accessibility is a critical parameter which drives all intermolecular interaction processes. In this respect a big deal of information has been derived by analyzing paramagnetic perturbation profiles obtained from NMR protein spectra, particularly in the case that the effects due to different soluble paramagnets can be compared. Here Gd(2)L7, a neutral ditopic paramagnetic NMR probe, has been characterized in terms of structure and relaxivity and its paramagnetic perturbations on alpha-bungarotoxin C alpha H signals in H-1-C-13 HSQC (heteronuclear single quantum coherence) spectra have been analyzed. Then, these signal attenuations have been compared with the ones previously obtained in the presence of GdDTPA-BMA (gadolinium(III) diethylenetriamine-N,N,N',N'",N ''-pentaacetate-bis(methylamide)). In spite of the different molecular size and shape, for the two probes a common pathway of approach to the alpha-bungarotoxin surface can be observed with an equally enhanced access of both GdDTPA-BMA and Gd(2)L7 toward the protein surface side where residues involved in the receptor binding are located. The different residence times of the water molecule directly coordinated by the Cd(III) ion measured for the two paramagnets account for the reduced broadening of water signal in the presence of the ditopic probe at equivalent gadolinium concentration. These features make Gd(2)L7 a very suitable probe for investigating protein surface accessibility of complex protein systems. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Bernini, Andrea; Spiga, Ottavia; Niccolai, Neri] Univ Siena, Dipartimento Biotecnol, I-53100 Siena, Italy.
[Spiga, Ottavia; Niccolai, Neri] SienaBioGrafiX Srl, I-53100 Siena, Italy.
[Venditti, Vincenzo] NIH, Bethesda, MD 20892 USA.
[Prischi, Filippo] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London SW7 2AZ, England.
[Botta, Mauro; Croce, Gianluca] Univ Piemonte Orientale Amedeo Avogadro, Dipartimento Sci & Innovaz Tecnol, I-15121 Alessandria, Italy.
[Tong, Angela Pui-Ling; Wong, Wing-Tak] Univ Hong Kong, Dept Chem, Hong Kong, Hong Kong, Peoples R China.
RP Niccolai, N (reprint author), Univ Siena, Dipartimento Biotecnol, Via Fiorentina 1, I-53100 Siena, Italy.
EM neri.niccolai@unisi.it
RI Botta, Mauro/E-9049-2011; Venditti, Vincenzo/A-9411-2013; Bernini,
Andrea/H-9412-2012
OI Bernini, Andrea/0000-0002-7528-2749
FU Istituto Toscano Tumori, University of Siena; University of Eastern
Piedmont; Hong Kong Research Grants Council [HKU7116/02P]; University of
Hong Kong
FX Thanks are due to Caterina Bernini for technical assistance. Thanks are
also due to the Istituto Toscano Tumori, University of Siena and
University of Eastern Piedmont for financial support. W.-T.W. thanks the
Hong Kong Research Grants Council (HKU7116/02P) and the University of
Hong Kong for financial support. A.P.-L.T. thanks The University of Hong
Kong for financial support.
NR 36
TC 5
Z9 5
U1 0
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0162-0134
J9 J INORG BIOCHEM
JI J. Inorg. Biochem.
PD JUL
PY 2012
VL 112
BP 25
EP 31
DI 10.1016/j.jinorgbio.2012.03.004
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear
SC Biochemistry & Molecular Biology; Chemistry
GA 961WX
UT WOS:000305501300004
PM 22542593
ER
PT J
AU Valente, AJ
Clark, RA
Siddesha, JM
Siebenlist, U
Chandrasekar, B
AF Valente, Anthony J.
Clark, Robert A.
Siddesha, Jalahalli M.
Siebenlist, Ulrich
Chandrasekar, Bysani
TI CIKS (Act1 or TRAF3IP2) mediates Angiotensin-II-induced Interleukin-18
expression, and Nox2-dependent cardiomyocyte hypertrophy
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Article
DE RAAS; NADPH oxidase; Act1; TRAF3IP2; Fibrosis; Cardiac hypertrophy
ID NF-KAPPA-B; INDUCED CARDIAC-HYPERTROPHY; NOX2-CONTAINING NADPH OXIDASE;
HEART-FAILURE; SIGNALING PATHWAYS; GENE-EXPRESSION; PROTEIN-KINASE;
IN-VIVO; ACTIVATION; REQUIREMENT
AB Chronic elevation of angiotensin (Ang)-II can lead to myocardial inflammation, hypertrophy and cardiac failure. The adaptor molecule CIKS (connection to IKK and SAPK/JNK) activates the I kappa B kinase/nuclear factor (NF)-kappa B and JNK/activator protein (AP)-1 pathways in autoimmune and inflammatory diseases. Since Ang-II is a potent activator of NF-kappa B and AP-1, we investigated whether CIKS is critical in Ang-II-mediated cardiac hypertrophy. Here we report that Ang-II induced CIKS mRNA and protein expression, CIKS binding to IKK and JNK perhaps functioning as a scaffold protein, CIKS-dependent IKK/NF-kappa B and JNK/AP-1 activation, p65 and c-Jun phosphorylation and nuclear translocation, NF-kappa B- and AP-1-dependent IL-18 and MMP-9 induction, and hypertrophy of adult cardiomyocytes isolated from WT, but not CIKS-null mice. These results were recapitulated in WT-cardiomyocytes following CIKS knockdown. Infusion of Ang-II for 7 days induced cardiac hypertrophy, increased collagen content, and upregulated CIKS mRNA and protein expression in WT mice, whereas cardiac hypertrophy and collagen deposition were markedly attenuated in the CIKS-null mice, despite a similar increase in systolic blood pressure and DPI-inhibitable superoxide generation in both types of animals. Further, Ang-II-induced IKK/p65 and JNK/c-Jun phosphorylation, NF-kappa B and AP-1 activation, and IL-18 and MMP-9 expression were also markedly attenuated in CIKS-null mice. These results demonstrate that CIKS is critical in Ang-II-induced cardiomyocyte hypertrophy and fibrosis, and that CIKS is an important intermediate in Ang-II-induced redox signaling. CIKS is a potential therapeutic target in cardiac hypertrophy, fibrosis, and congestive heart failure. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Siddesha, Jalahalli M.; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA.
[Valente, Anthony J.; Clark, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Valente, Anthony J.; Clark, Robert A.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Chandrasekar, Bysani] SE Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA.
RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL-48, New Orleans, LA 70112 USA.
EM bchandra@tulane.edu
FU Veterans Affairs Office of Research and Development Biomedical
Laboratory Research and Development Service Award [1IO1BX000246];
NIH/NHLBI [HL-86787]
FX This work was supported by Veterans Affairs Office of Research and
Development Biomedical Laboratory Research and Development Service Award
1IO1BX000246 and the NIH/NHLBI Grant HL-86787 (to BC). The contents of
this report do not represent the views of the Department of Veterans
Affairs or the United States Government.
NR 45
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U1 0
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD JUL
PY 2012
VL 53
IS 1
BP 113
EP 124
DI 10.1016/j.yjmcc.2012.04.009
PG 12
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 963AI
UT WOS:000305592100014
PM 22575763
ER
PT J
AU Chen, J
Evans, AN
Liu, Y
Honda, M
Saavedra, JM
Aguilera, G
AF Chen, J.
Evans, A. N.
Liu, Y.
Honda, M.
Saavedra, J. M.
Aguilera, G.
TI Maternal Deprivation in Rats is Associated with Corticotrophin-Releasing
Hormone (CRH) Promoter Hypomethylation and Enhances CRH Transcriptional
Responses to Stress in Adulthood
SO JOURNAL OF NEUROENDOCRINOLOGY
LA English
DT Article
DE maternal deprivation; corticotrophin-releasing hormone; DNA methylation;
hypothalamic pituitary adrenal axis
ID DNA METHYLATION; ANXIETY DISORDERS; MAJOR DEPRESSION; PARENTAL LOSS;
GENE; LIFE; NEUROBIOLOGY; ELEMENT; PSYCHOPATHOLOGY; PHOSPHORYLATION
AB Exposure to stress during early development causes long-lasting alterations in behaviour and hypothalamic pituitary adrenal (HPA) axis activity, including increased expression of corticotrophin-releasing hormone (CRH). To determine whether early-life stress causes epigenetic changes in the CRH promoter leading to increased CRH transcription, 8-week old female and male rats, subjected to maternal deprivation (MD) between days 2 and 13 post-birth, were studied for HPA axis responses to stress and CRH promoter methylation in the hypothalamic paraventricular nucleus (PVN) and central nucleus of the amygdala (CeA). Plasma corticosterone and PVN CRH heteronuclear (hn)RNA responses to acute restraint stress were higher in MD rats of both sexes. DNA methylation analysis of the CRH promoter revealed a significantly lower percentage of methylation in two CpGs preceding (CpG1) and inside (CpG2) the cyclic AMP-response element (CRE) at -230 bp in the CRH promoter in the PVN but not the CeA of MD rats. Gel-shift assays, using nuclear proteins from forskolin-treated hypothalamic 4B cells and CRH promoter CRE oligonucleotides, unmethylated or methylated at CpG1, revealed a strong band that was supershifted by phospho-cAMP response element-binding antibody. This band was 50% weaker using oligonucleotides methylated at CpG2 (intra-CRE), or methylated at both CpG1 and CpG2. These findings demonstrate that HPA axis hypersensitivity caused by neonatal stress causes long-lasting enhanced CRH transcriptional activity in the PVN of both sexes. Hypomethylation of the CRH promoter CRE, a region critical for CRH transcriptional activation, could serve as a mechanism for the increased transcriptional responses to stress observed in MD rats.
C1 [Aguilera, G.] NICHD, Sect Endocrine Physiol, PDEGEN, Dev Endocrinol Branch,NIH,CRC, Bethesda, MD 20892 USA.
[Honda, M.; Saavedra, J. M.] NIMH, Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
RP Aguilera, G (reprint author), NICHD, Sect Endocrine Physiol, PDEGEN, Dev Endocrinol Branch,NIH,CRC, Room 1E-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA.
EM greti_aguilera@nih.gov
OI Evans, Andrew/0000-0002-5366-9942
FU Intramural Research Program of National Institute of Child Health and
Human Development, NIH
FX This work was supported by the Intramural Research Program of National
Institute of Child Health and Human Development, NIH. The authors would
like to thank Dr Jorge Sztein (NIAID, NIH) for his helpful advice with
the cycle synchronisation and breeding protocols.
NR 40
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U1 1
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-8194
J9 J NEUROENDOCRINOL
JI J. Neuroendocrinol.
PD JUL
PY 2012
VL 24
IS 7
BP 1055
EP 1064
DI 10.1111/j.1365-2826.2012.02306.x
PG 10
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 961HC
UT WOS:000305453900008
PM 22375940
ER
PT J
AU Dirks, MS
Butman, JA
Kim, HJ
Wu, TX
Morgan, K
Tran, AP
Lonser, RR
Asthagiri, AR
AF Dirks, Michael S.
Butman, John A.
Kim, H. Jeffrey
Wu, Tianxia
Morgan, Keaton
Tran, Anne P.
Lonser, Russell R.
Asthagiri, Ashok R.
TI Natural history of neurofibromatosis Type 2 tumors Response
SO JOURNAL OF NEUROSURGERY
LA English
DT Editorial Material
C1 [Dirks, Michael S.; Morgan, Keaton; Tran, Anne P.; Lonser, Russell R.; Asthagiri, Ashok R.] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA.
[Wu, Tianxia] NINDS, Clin Neurosci Program, Bethesda, MD 20892 USA.
[Butman, John A.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Kim, H. Jeffrey] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
[Dirks, Michael S.] Walter Reed Army Med Ctr, Dept Neurol Surg, Washington, DC 20307 USA.
RP Dirks, MS (reprint author), NINDS, Surg Neurol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD JUL
PY 2012
VL 117
IS 1
BP 108
EP 108
PG 1
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 962ZC
UT WOS:000305588900020
ER
PT J
AU Dirks, MS
Butman, JA
Kim, HJ
Wu, TX
Morgan, K
Tran, AP
Lonser, RR
Asthagiri, AR
AF Dirks, Michael S.
Butman, John A.
Kim, H. Jeffrey
Wu, Tianxia
Morgan, Keaton
Tran, Anne P.
Lonser, Russell R.
Asthagiri, Ashok R.
TI Long-term natural history of neurofibromatosis Type 2-associated
intracranial tumors Clinical article
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE neurofibromatosis Type 2; intracranial tumor; natural history;
vestibular schwannoma; meningioma; tumor growth; oncology
ID VESTIBULAR SCHWANNOMA GROWTH; HIPPEL-LINDAU-DISEASE; STEREOTACTIC
RADIOSURGERY; ACOUSTIC NEUROMAS; HUMAN MENINGIOMAS; PROGESTERONE;
RECEPTORS; RATES; HEMANGIOBLASTOMAS; PREDICTORS
AB Object. Neurofibromatosis Type 2 (NF2) is a heritable tumor predisposition syndrome that leads to the development of multiple intracranial tumors, including meningiomas and schwannomas. Because the natural history of these tumors has not been determined, their optimal management has not been established. To define the natural history of NF2-associated intracranial tumors and to optimize management strategies, the authors evaluated long-term clinical and radiographic data in patients with NF2.
Methods. Consecutive NF2 patients with a minimum of 4 years of serial clinical and MRI follow-up were analyzed.
Results. Seventeen patients, 9 males and 8 females, were included in this analysis (mean follow-up 9.5 +/- 4.8 years, range 4.0-20.7 years). The mean age at initial evaluation was 33.2 +/- 15.5 years (range 12.3-57.6 years). Patients harbored 182 intracranial neoplasms, 164 of which were assessable for growth rate analysis (18 vestibular schwannomas [VSs], 11 nonvestibular cranial nerve [CN] schwannomas, and 135 meningiomas) and 152 of which were assessable for growth pattern analysis (15 VSs, 9 nonvestibular CN schwannomas, and 128 meningiomas). New tumors developed in patients over the course of the imaging follow-up: 66 meningiomas, 2 VSs, and 2 nonvestibular CN schwannomas. Overall, 45 tumors (29.6%) exhibited linear growth, 17 tumors (11.2%) exhibited exponential growth, and 90 tumors (59.2%) displayed a saltatory growth pattern characterized by alternating periods of growth and quiescence (mean quiescent period 2.3 +/- 2.1 years, range 0.4-11.7 years). Further, the saltatory pattern was the most frequently identified growth pattern for each tumor type: meningiomas 60.9%. VSs 46.7%, and nonvestibular schwannoma 55.6%. A younger age at the onset of NF2-related symptoms (p = 0.01) and female sex (p = 0.05) were associated with an increased growth rate in meningiomas. The identification of saltatory growth in meningiomas increased with the duration of follow-up (p = 0.01).
Conclusions. Neurofibromatosis Type 2 associated intracranial tumors most frequently demonstrated a saltatory growth pattern. Because new tumors can develop in NF2 patients over their lifetime and because radiographic progression and symptom formation are unpredictable, resection may be best reserved for symptom-producing tumors. Moreover, establishing the efficacy of nonsurgical therapeutic interventions must be based on long-term follow-up (several years). (http:://thejns.org/doi/abs/10.3171/2012.3.JNS111649)
C1 [Asthagiri, Ashok R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Wu, Tianxia] NINDS, Clin Neurosci Program, Bethesda, MD 20892 USA.
[Butman, John A.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Kim, H. Jeffrey] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
[Dirks, Michael S.] Walter Reed Army Med Ctr, Dept Neurol Surg, Washington, DC 20307 USA.
RP Asthagiri, AR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 3D20, Bethesda, MD 20892 USA.
EM asthagiria@ninds.nih.gov
RI Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU National Institute of Neurologic Disorders and Stroke at the National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Neurologic Disorders and Stroke at the National
Institutes of Health.
NR 38
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U1 2
U2 6
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
EI 1933-0693
J9 J NEUROSURG
JI J. Neurosurg.
PD JUL
PY 2012
VL 117
IS 1
BP 109
EP 117
DI 10.3171/2012.3.JNS111649
PG 9
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 962ZC
UT WOS:000305588900021
PM 22503123
ER
PT J
AU Lonser, RR
Oldfield, EH
AF Lonser, Russell R.
Oldfield, Edward H.
TI Cushing's disease and dural invasion RESPONSE
SO JOURNAL OF NEUROSURGERY
LA English
DT Letter
ID DIAGNOSIS
C1 [Lonser, Russell R.; Oldfield, Edward H.] NIH, Bethesda, MD 20892 USA.
[Oldfield, Edward H.] Univ Virginia, Charlottesville, VA USA.
RP Lonser, RR (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 7
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD JUL
PY 2012
VL 117
IS 1
BP 190
EP 191
PG 2
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 962ZC
UT WOS:000305588900037
ER
PT J
AU Maas, MB
Lev, MH
Ay, H
Singhal, AB
Greer, DM
Smith, WS
Harris, GJ
Halpern, EF
Koroshetz, WJ
Furie, KL
AF Maas, Matthew B.
Lev, Michael H.
Ay, Hakan
Singhal, Aneesh B.
Greer, David M.
Smith, Wade S.
Harris, Gordon J.
Halpern, Elkan F.
Koroshetz, Walter J.
Furie, Karen L.
TI The Prognosis for Aphasia in Stroke
SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
LA English
DT Article
DE Aphasia; prognosis; stroke; recovery
ID ACUTE ISCHEMIC-STROKE; CAUSATIVE CLASSIFICATION; THROMBOLYSIS; RECOVERY;
SYSTEM
AB Background: Aphasia is a disabling chronic stroke symptom, but the prognosis for patients presenting with aphasia in the hyperacute window has not been well characterized. The purpose of this study is to assess the prognosis for recovery of language function in subjects presenting with aphasia caused by ischemic stroke within 12 hours of symptom onset. Methods: Subjects presenting with aphasia were identified from a prospective cohort study of 669 subjects presenting emergently with acute stroke. Subjects were characterized by demographics, serial clinical examinations, unenhanced computed tomography, and computed tomographic angiography. Aphasia severity was assessed by National Institutes of Health Stroke Scale (NIHSS) examinations performed at baseline, discharge, and 6 months. Demographic, clinical, and imaging factors were assessed for prognostic impact. Results: Aphasia was present in 30% of subjects (n = 204). Of the 166 aphasic patients alive at discharge (median 5 days), aphasia improved in 57% and resolved in 38%. In the 102 aphasic subjects evaluated at 6 months, aphasia improved in 86% and completely resolved in 74% of subjects. Among aphasic subjects with "mild" stroke (initial NIHSS <5), aphasia resolved in 90% of subjects by 6 months. Factors significantly associated with better outcome included clinically and radiographically smaller strokes and lower prestroke disability. Conclusions: The prognosis for full recovery of aphasia present in the hyperacute window is good. Radiographic and clinical markers indicating lesser extent of ischemia correlated to greater recovery. Given the excellent prognosis for language recovery in mild stroke, the net benefit of thrombolysis in such cases is uncertain.
C1 [Maas, Matthew B.; Singhal, Aneesh B.; Greer, David M.; Furie, Karen L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA.
[Lev, Michael H.; Ay, Hakan; Harris, Gordon J.; Halpern, Elkan F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA.
[Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
RP Maas, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 175 Cambridge St,Ste 300, Boston, MA 02114 USA.
EM mmaas@partners.org
FU Agency for Healthcare Research and Quality [R01 HS11392]; National
Institutes of Health [P50NS051343]; Deane Institute for Integrative
research in Stroke and Atrial Fibrillation; Lakeside Foundation
FX Supported by an Agency for Healthcare Research and Quality grant (R01
HS11392). Dr Maas is supported by a National Institutes of Health grant
(P50NS051343). We gratefully acknowledge the support of the Deane
Institute for Integrative research in Stroke and Atrial Fibrillation and
the Lakeside Foundation.
NR 16
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U1 0
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1052-3057
J9 J STROKE CEREBROVASC
JI J. Stroke Cerebrovasc. Dis.
PD JUL
PY 2012
VL 21
IS 5
BP 350
EP 357
DI 10.1016/j.jstrokecerebrovasdis.2010.09.009
PG 8
WC Neurosciences; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 963JM
UT WOS:000305616600002
PM 21185744
ER
PT J
AU Tweddell, JS
Sleeper, LA
Ohye, RG
Williams, IA
Mahony, L
Pizarro, C
Pemberton, VL
Frommelt, PC
Bradley, SM
Cnota, JF
Hirsch, J
Kirshbom, PM
Li, JS
Pike, N
Puchalski, M
Ravishankar, C
Jacobs, JP
Laussen, PC
McCrindle, BW
AF Tweddell, James S.
Sleeper, Lynn A.
Ohye, Richard G.
Williams, Ismee A.
Mahony, Lynn
Pizarro, Christian
Pemberton, Victoria L.
Frommelt, Peter C.
Bradley, Scott M.
Cnota, James F.
Hirsch, Jennifer
Kirshbom, Paul M.
Li, Jennifer S.
Pike, Nancy
Puchalski, Michael
Ravishankar, Chitra
Jacobs, Jeffrey P.
Laussen, Peter C.
McCrindle, Brian W.
CA Pediat Heart Network Investigators
TI Intermediate-term mortality and cardiac transplantation in infants with
single-ventricle lesions: Risk factors and their interaction with shunt
type
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID LEFT-HEART SYNDROME; PULMONARY-ARTERY CONDUIT; BLALOCK-TAUSSIG SHUNT;
NORWOOD-PROCEDURE; MITRAL-STENOSIS; AORTIC ATRESIA; ATRIAL SEPTUM;
OUTCOMES; IMPACT; ABNORMALITIES
AB Objective: The study objective was to identify factors associated with death and cardiac transplantation in infants undergoing the Norwood procedure and to determine differences in associations that might favor the modified Blalock-Taussig shunt or a right ventricle-to-pulmonary artery shunt.
Methods: We used competing risks methodology to analyze death without transplantation, cardiac transplantation, and survival without transplantation. Parametric time-to-event modeling and bootstrapping were used to identify independent predictors.
Results: Data from 549 subjects (follow-up, 2.7 +/- 0.9 years) were analyzed. Mortality risk was characterized by early and constant phases; transplant was characterized by only a constant phase. Early phase factors associated with death included lower socioeconomic status (P = .01), obstructed pulmonary venous return (P < .001), smaller ascending aorta (P = .02), and anatomic subtype. Constant phase factors associated with death included genetic syndrome (P < .001) and lower gestational age (P < .001). The right ventricle-to-pulmonary artery shunt demonstrated better survival in the 51% of subjects who were full term with aortic atresia (P < .001). The modified Blalock-Taussig shunt was better among the 4% of subjects who were preterm with a patent aortic valve (P = .003). Lower pre-Norwood right ventricular fractional area change, pre-Norwood surgery, and anatomy other than hypoplastic left heart syndrome were independently associated with transplantation (all P < .03), but shunt type was not (P = .43).
Conclusions: Independent risk factors for intermediate-term mortality include lower socioeconomic status, anatomy, genetic syndrome, and lower gestational age. Term infants with aortic atresia benefited from a right ventricle-to-pulmonary artery shunt, and preterm infants with a patent aortic valve benefited from a modified Blalock-Taussig shunt. Right ventricular function and anatomy, but not shunt type, were associated with transplantation. (J Thorac Cardiovasc Surg 2012;144:152-9)
C1 [Sleeper, Lynn A.] New England Res Inst Inc, Watertown, MA USA.
[Tweddell, James S.; Frommelt, Peter C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Ohye, Richard G.; Hirsch, Jennifer] Univ Michigan, Ann Arbor, MI 48109 USA.
[Williams, Ismee A.] Columbia Univ, New York, NY USA.
[Mahony, Lynn] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Pizarro, Christian] Nemours Cardiac Ctr, Wilmington, DE USA.
[Pemberton, Victoria L.] NHLBI, Bethesda, MD 20892 USA.
[Bradley, Scott M.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Cnota, James F.] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Kirshbom, Paul M.] Emory Univ, Atlanta, GA 30322 USA.
[Li, Jennifer S.] Duke Univ, Durham, NC USA.
[Pike, Nancy] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Puchalski, Michael] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA.
[Ravishankar, Chitra] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Jacobs, Jeffrey P.] Congenital Heart Inst Florida, St Petersburg, FL USA.
[Laussen, Peter C.] Childrens Hosp Boston, Boston, MA USA.
[McCrindle, Brian W.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
RP Sleeper, LA (reprint author), New England Res Inst, Ctr Stat Anal & Res, 9 Galen St, Watertown, MA 02472 USA.
EM LSleeper@neriscience.com
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068292, HL068290, HL068288, HL085057]
FX Supported by U01 grants from the National Heart, Lung, and Blood
Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292,
HL068290, HL068288, HL085057). Its contents are solely the
responsibility of the authors and do not necessarily represent the
official views of the National Heart, Lung, and Blood Institute.
Clinical Trial Registration NCT00115934.
NR 25
TC 46
Z9 47
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD JUL
PY 2012
VL 144
IS 1
BP 152
EP +
DI 10.1016/j.jtcvs.2012.01.016
PG 10
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 960TB
UT WOS:000305412200026
PM 22341427
ER
PT J
AU Wan, WZ
Gao, JL
AF Wan, Wuzhou
Gao, Ji-Liang
TI Leukocyte chemoattractant receptor FPR2 may accelerate atherogenesis
SO MEDICAL HYPOTHESES
LA English
DT Article
ID PROTEIN-COUPLED RECEPTOR; SERUM-AMYLOID-A; CCL2 PRODUCTION;
ATHEROSCLEROSIS; INFLAMMATION; CHEMOKINES; ACTIVATION; DISEASE; CELLS
AB Atherosclerosis is a chronic inflammatory disease and the number one cause of mortality worldwide. The fundamental causes of atherosclerosis have not been precisely delineated, although pathogenesis clearly involves endothelial dysfunction and both innate and adaptive immunity. Recent evidence suggests that formyl peptide receptor 2 (FPR2), a G protein-coupled receptor (GPCR), mediates a range of inflammatory responses including superoxide production in neutrophils, chemotaxis of monocytes and neutrophils, CCL2 production in endothelial cells (ECs) and monocytes, and increased CXCL8 expression in neutrophils, which are all related with atherogenesis. Therefore, we propose that FPR2 may play a pathogenic role in atherogenesis. Published by Elsevier Ltd.
C1 [Wan, Wuzhou; Gao, Ji-Liang] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Wan, WZ (reprint author), NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike,Bldg 10,Rm11N107, Bethesda, MD 20892 USA.
EM wanwu@niaid.nih.gov
RI Wan, Wuhzou/H-8556-2013
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
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.
NR 18
TC 1
Z9 2
U1 0
U2 1
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0306-9877
J9 MED HYPOTHESES
JI Med. Hypotheses
PD JUL
PY 2012
VL 79
IS 1
BP 101
EP 103
DI 10.1016/j.mehy.2012.04.014
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 960GI
UT WOS:000305375600027
PM 22541858
ER
PT J
AU Abdelmohsen, K
Srikantan, S
Tominaga, K
Kang, MJ
Yaniv, Y
Martindale, JL
Yang, XL
Park, SS
Becker, KG
Subramanian, M
Maudsley, S
Lal, A
Gorospe, M
AF Abdelmohsen, Kotb
Srikantan, Subramanya
Tominaga, Kumiko
Kang, Min-Ju
Yaniv, Yael
Martindale, Jennifer L.
Yang, Xiaoling
Park, Sung-Soo
Becker, Kevin G.
Subramanian, Murugan
Maudsley, Stuart
Lal, Ashish
Gorospe, Myriam
TI Growth Inhibition by miR-519 via Multiple p21-Inducing Pathways
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; ENDOPLASMIC-RETICULUM STRESS; HUMAN-DIPLOID
FIBROBLASTS; REPLICATIVE SENESCENCE; CELL-PROLIFERATION; P21 EXPRESSION;
CALCIUM-PUMP; DNA-DAMAGE; CA2+ ENTRY; HUR LEVELS
AB The microRNA miR-519 robustly inhibits cell proliferation, in turn triggering senescence and decreasing tumor growth. However, the molecular mediators of miR-519-elicited growth inhibition are unknown. Here, we systematically investigated the influence of miR-519 on gene expression profiles leading to growth cessation in HeLa human cervical carcinoma cells. By analyzing miR-519-triggered changes in protein and mRNA expression patterns and by identifying mRNAs associated with biotinylated miR-519, we uncovered two prominent subsets of miR-519-regulated mRNAs. One subset of miR-519 target mRNAs encoded DNA maintenance proteins (including DUT1, EXO1, RPA2, and POLE4); miR-519 repressed their expression and increased DNA damage, in turn raising the levels of the cyclin-dependent kinase (cdk) inhibitor p21. The other subset of miR-519 target mRNAs encoded proteins that control intracellular calcium levels (notably, ATP2C1 and ORAI1); their downregulation by miR-519 aberrantly elevated levels of cytosolic [Ca2+] storage in HeLa cells, similarly increasing p21 levels in a manner dependent on the Ca2+-activated kinases CaMKII and GSK3 beta. The rises in levels of DNA damage, the Ca2+ concentration, and p21 levels stimulated an autophagic phenotype in HeLa and other human carcinoma cell lines. As a consequence, ATP levels increased, and the level of activity of the AMP-activated protein kinase (AMPK) declined, further contributing to the elevation in the abundance of p21. Our results indicate that miR-519 promotes DNA damage, alters Ca2+ homeostasis, and enhances energy production; together, these processes elevate the expression level of p21, promoting growth inhibition and cell survival.
C1 [Abdelmohsen, Kotb; Srikantan, Subramanya; Tominaga, Kumiko; Kang, Min-Ju; Martindale, Jennifer L.; Yang, Xiaoling; Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
[Yaniv, Yael] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Park, Sung-Soo; Maudsley, Stuart] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
[Becker, Kevin G.] NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
[Subramanian, Murugan; Lal, Ashish] NCI, NIH, Bethesda, MD 20892 USA.
RP Abdelmohsen, K (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
EM abdelmohsenk@grc.nia.nih.gov; myriam-gorospe@nih.gov
RI Yaniv, Yael/B-3311-2015;
OI Yaniv, Yael/0000-0002-5183-6284; srikantan,
subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810;
Becker, Kevin/0000-0002-6794-6656
FU NIA-IRP, NIH
FX This work was supported in part by the NIA-IRP, NIH.
NR 62
TC 27
Z9 30
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUL
PY 2012
VL 32
IS 13
BP 2530
EP 2548
DI 10.1128/MCB.00510-12
PG 19
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 961XX
UT WOS:000305503900017
PM 22547681
ER
PT J
AU Sunagar, K
Johnson, WE
O'Brien, SJ
Vasconcelos, V
Antunes, A
AF Sunagar, Kartik
Johnson, Warren E.
O'Brien, Stephen J.
Vasconcelos, Vitor
Antunes, Agostinho
TI Evolution of CRISPs Associated with Toxicoferan-Reptilian Venom and
Mammalian Reproduction
SO MOLECULAR BIOLOGY AND EVOLUTION
LA English
DT Article
DE CRISP; positive selection; toxicoferan-reptilian venom evolution;
adaptive evolution; cysteine-rich secretory proteins; mammalian
reproduction; mammalian immune system
ID RICH SECRETORY PROTEINS; AMINO-ACID SITES; DETECTING MOLECULAR
ADAPTATION; CODON-SUBSTITUTION MODELS; SNAKE-VENOM; POSITIVE SELECTION;
PHYLOGENETIC ANALYSIS; MAXIMUM-LIKELIHOOD; CRYSTAL-STRUCTURE; FUNCTIONAL
DIVERGENCE
AB Cysteine-rich secretory proteins (CRISPs) are glycoproteins found exclusively in vertebrates and have broad diversified functions. They are hypothesized to play important roles in mammalian reproduction and in reptilian venom, where they disrupt homeostasis of the prey through several mechanisms, including among others, blockage of cyclic nucleotide-gated and voltage-gated ion channels and inhibition of smooth muscle contraction. We evaluated the molecular evolution of CRISPs in toxicoferan reptiles at both nucleotide and protein levels relative to their nonvenomous mammalian homologs. We show that the evolution of CRISP gene in these reptiles is significantly influenced by positive selection and in snakes (omega = 3.84) more than in lizards (omega = 2.33), whereas mammalian CRISPs were under strong negative selection (CRISP1 = 0.55, CRISP2 = 0.40, and CRISP3 = 0.68). The use of ancestral sequence reconstruction, mapping of mutations on the three-dimensional structure, and detailed evaluation of selection pressures suggests that the toxicoferan CRISPs underwent accelerated evolution aided by strong positive selection and directional mutagenesis, whereas their mammalian homologs are constrained by negative selection. Gene and protein-level selection analyses identified 41 positively selected sites in snakes and 14 sites in lizards. Most of these sites are located on the molecular surface (nearly 76% in snakes and 79% in lizards), whereas the backbone of the protein retains a highly conserved structural scaffold. Nearly 46% of the positively selected sites occur in the cysteine-rich domain of the protein. This directional mutagenesis, where the hotspots of mutations are found on the molecular surface and functional domains of the protein, acts as a diversifying mechanism for the exquisite biological targeting of CRISPs in toxicoferan reptiles. Finally, our analyses suggest that the evolution of toxicoferan-CRISP venoms might have been influenced by the specific predatory mechanism employed by the organism. CRISPs in Elapidae, which mostly employ neurotoxins, have experienced less positive selection pressure (omega = 2.86) compared with the "nonvenomous" colubrids (omega = 4.10) that rely on grip and constriction to capture the prey, and the Viperidae, a lineage that mostly employs haemotoxins (omega = 4.19). Relatively lower omega estimates in Anguimorph lizards (omega = 2.33) than snakes (omega = 3.84) suggests that lizards probably depend more on pace and powerful jaws for predation than venom.
C1 [Sunagar, Kartik; Vasconcelos, Vitor; Antunes, Agostinho] Univ Porto, Ctr Interdisciplinar Invest Marinha & Ambiental, CIMAR CIIMAR, P-4100 Oporto, Portugal.
[Sunagar, Kartik; Vasconcelos, Vitor; Antunes, Agostinho] Univ Porto, Fac Ciencias, Dept Biol, P-4100 Oporto, Portugal.
[Johnson, Warren E.; O'Brien, Stephen J.; Antunes, Agostinho] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
[O'Brien, Stephen J.] St Petersburg State Univ, Theodosius Dobzhansky Ctr Genome Bioinformat, St Petersburg, Russia.
RP Antunes, A (reprint author), Univ Porto, Ctr Interdisciplinar Invest Marinha & Ambiental, CIMAR CIIMAR, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
EM aantunes@ciimar.up.pt
RI Vasconcelos, Vitor/A-8933-2008; Scientific output, CIIMAR/E-5122-2012;
Johnson, Warren/D-4149-2016;
OI Vasconcelos, Vitor/0000-0003-3585-2417; Scientific output,
CIIMAR/0000-0001-6270-2153; Johnson, Warren/0000-0002-5954-186X;
O'Brien, Stephen J./0000-0001-7353-8301; Antunes,
Agostinho/0000-0002-1328-1732; Sunagar, Kartik/0000-0003-0998-1581
FU FCT (Fundacao para a Ciencia e a Tecnologia) [SFRH/BD/61959/2009]; FCT
[PTDC/BIA-BDE/69144/2006 (FCOMP-01-0124-FEDER-007065),
PTDC/AAC-AMB/104983/2008 (FCOMP-01-0124-FEDER-008610),
PTDC/AAC-AMB/121301/2010 (FCOMP-01-0124-FEDER-019490)]
FX We are indebted to Joao Paulo Machado, Rute Fonseca, Debapriyo
Chakroborty, Rui Borges, and Emanuel Maldonado for support and
discussions. We are also thankful to the anonymous reviewers for their
valuable comments and suggestions, which led to the improvement of the
manuscript. This research is supported by FCT (Fundacao para a Ciencia e
a Tecnologia) grant SFRH/BD/61959/2009 conferred to K. S. and in part by
the FCT project PTDC/BIA-BDE/69144/2006 (FCOMP-01-0124-FEDER-007065),
PTDC/AAC-AMB/104983/2008 (FCOMP-01-0124-FEDER-008610), and
PTDC/AAC-AMB/121301/2010 (FCOMP-01-0124-FEDER-019490).
NR 82
TC 36
Z9 37
U1 3
U2 25
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0737-4038
J9 MOL BIOL EVOL
JI Mol. Biol. Evol.
PD JUL
PY 2012
VL 29
IS 7
BP 1807
EP 1822
DI 10.1093/molbev/mss058
PG 16
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 960SE
UT WOS:000305409000012
PM 22319140
ER
PT J
AU Zhao, XQ
Xie, JD
Chen, XG
Sim, HM
Zhang, X
Liang, YJ
Singh, S
Talele, TT
Sun, YL
Ambudkar, SV
Chen, ZS
Fu, LW
AF Zhao, Xiao-qin
Xie, Jing-dun
Chen, Xing-gui
Sim, Hong May
Zhang, Xu
Liang, Yong-ju
Singh, Satyakam
Talele, Tanaji T.
Sun, Yueli
Ambudkar, Suresh V.
Chen, Zhe-Sheng
Fu, Li-wu
TI Neratinib Reverses ATP-Binding Cassette B1-Mediated Chemotherapeutic
Drug Resistance In Vitro, In Vivo, and Ex Vivo
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID MEDIATED MULTIDRUG-RESISTANCE; TYROSINE KINASE INHIBITOR; SUBFAMILY-B
MEMBER-1; CELL LUNG-CANCER; P-GLYCOPROTEIN; BREAST-CANCER; PHASE-I;
PACLITAXEL; OVEREXPRESSION; TRANSPORTER
AB Neratinib, an irreversible inhibitor of epidermal growth factor receptor and human epidermal receptor 2, is in phase III clinical trials for patients with human epidermal receptor 2-positive, locally advanced or metastatic breast cancer. The objective of this study was to explore the ability of neratinib to reverse tumor multidrug resistance attributable to overexpression of ATP-binding cassette (ABC) transporters. Our results showed that neratinib remarkably enhanced the sensitivity of ABCB1-overexpressing cells to ABCB1 substrates. It is noteworthy that neratinib augmented the effect of chemotherapeutic agents in inhibiting the growth of ABCB1-overexpressing primary leukemia blasts and KBv200 cell xenografts in nude mice. Furthermore, neratinib increased doxorubicin accumulation in ABCB1-overexpressing cell lines and Rhodamine 123 accumulation in ABCB1-overexpressing cell lines and primary leukemia blasts. Neratinib stimulated the ATPase activity of ABCB1 at low concentrations but inhibited it at high concentrations. Likewise, neratinib inhibited the photolabeling of ABCB1 with [I-125] iodoarylazidoprazosin in a concentration-dependent manner (IC50 = 0.24 mu M). Neither the expression of ABCB1 at the mRNA and protein levels nor the phosphorylation of Akt was affected by neratinib at reversal concentrations. Docking simulation results were consistent with the binding conformation of neratinib within the large cavity of the transmembrane region of ABCB1, which provides computational support for the cross-reactivity of tyrosine kinase inhibitors with human ABCB1. In conclusion, neratinib can reverse ABCB1-mediated multidrug resistance in vitro, ex vivo, and in vivo by inhibiting its transport function.
C1 [Zhao, Xiao-qin; Xie, Jing-dun; Chen, Xing-gui; Zhang, Xu; Liang, Yong-ju; Fu, Li-wu] Sun Yat Sen Univ, State Key Lab Oncol S China, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China.
[Sim, Hong May; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Singh, Satyakam; Talele, Tanaji T.; Sun, Yueli; Chen, Zhe-Sheng] St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA.
RP Fu, LW (reprint author), Sun Yat Sen Univ, State Key Lab Oncol S China, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China.
EM fulw@mail.sysu.edu.cn
OI Singh, Satyakam/0000-0001-9115-3296
FU National Natural Sciences Foundation of China [81072669, 81061160];
Natural Sciences Foundation of Guangdong Province [2008B030301331];
National Institutes of Health National Cancer Institute, Center for
Cancer Research
FX This work was funded by the National Natural Sciences Foundation of
China [Grants 81072669, 81061160] and the Natural Sciences Foundation of
Guangdong Province [Grant 2008B030301331]. H. M. S. and S. V. A. were
supported by the Intramural Research Program of the National Institutes
of Health National Cancer Institute, Center for Cancer Research.
NR 47
TC 27
Z9 27
U1 0
U2 6
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JUL
PY 2012
VL 82
IS 1
BP 47
EP 58
DI 10.1124/mol.111.076299
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 961MZ
UT WOS:000305470000006
PM 22491935
ER
PT J
AU Sohl, CD
Kasiviswanathan, R
Kim, J
Pradere, U
Schinazi, RF
Copeland, WC
Mitsuya, H
Baba, M
Anderson, KS
AF Sohl, Christal D.
Kasiviswanathan, Rajesh
Kim, Jiae
Pradere, Ugo
Schinazi, Raymond F.
Copeland, William C.
Mitsuya, Hiroaki
Baba, Masanori
Anderson, Karen S.
TI Balancing Antiviral Potency and Host Toxicity: Identifying a Nucleotide
Inhibitor with an Optimal Kinetic Phenotype for HIV-1 Reverse
Transcriptase
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID MITOCHONDRIAL-DNA POLYMERASE; IMMUNODEFICIENCY-VIRUS ACTIVITY;
NUCLEOSIDE ANALOGS; REPLICATION FIDELITY; MOLECULAR MECHANISM; STAVUDINE
ANALOG; TYPE-1 ACTIVITY; GAMMA; TRIPHOSPHATE; RESISTANCE
AB Two novel thymidine analogs, 3'-fluoro-3'-deoxythymidine (FLT) and 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine (Ed4T), have been investigated as nucleoside reverse transcriptase inhibitors (NRTIs) for treatment of HIV infection. Ed4T seems very promising in phase II clinical trials, whereas toxicity halted FLT development during this phase. To understand these different molecular mechanisms of toxicity, pre-steady-state kinetic studies were used to examine the interactions of FLT and Ed4T with wild-type (WT) human mitochondrial DNA polymerase gamma (pol gamma), which is often associated with NRTI toxicity, as well as the viral target protein, WT HIV-1 reverse transcriptase (RT). We report that Ed4T-triphosphate (TP) is the first analog to be preferred over native nucleotides by RT but to experience negligible incorporation by WT pol gamma, with an ideal balance between high antiretroviral efficacy and minimal host toxicity. WT pol gamma could discriminate Ed4T-TP from dTTP 12,000-fold better than RT, with only an 8.3-fold difference in discrimination being seen for FLT-TP. A structurally related NRTI, 2',3'-didehydro-2'3'-dideoxythymidine, is the only other analog favored by RT over native nucleotides, but it exhibits only a 13-fold difference (compared with 12,000-fold for Ed4T) in discrimination between the two enzymes. We propose that the 4'-ethynyl group of Ed4T serves as an enzyme selectivity moiety, critical for discernment between RT and WT pol gamma. We also show that the pol gamma mutation R964C, which predisposes patients to mitochondrial toxicity when receiving 2',3'-didehydro-2',3'-dideoxythymidine to treat HIV, produced some loss of discrimination for FLT-TP and Ed4T-TP. These molecular mechanisms of analog incorporation, which are critical for understanding pol gamma-related toxicity, shed light on the unique toxicity profiles observed during clinical trials.
C1 [Sohl, Christal D.; Kim, Jiae; Anderson, Karen S.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA.
[Kasiviswanathan, Rajesh; Copeland, William C.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Pradere, Ugo; Schinazi, Raymond F.] Emory Univ, Sch Med, Dept Pediat, Ctr AIDS Res, Atlanta, GA USA.
[Pradere, Ugo; Schinazi, Raymond F.] Dept Vet Affairs, Atlanta, GA USA.
[Mitsuya, Hiroaki] Kumamoto Univ, Dept Infect Dis, Grad Sch Med Sci, Kumamoto, Japan.
[Mitsuya, Hiroaki] Kumamoto Univ, Dept Hematol, Grad Sch Med Sci, Kumamoto, Japan.
[Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Baba, Masanori] Kagoshima Univ, Div Antiviral Chemotherapy, Ctr Chron Viral Dis, Grad Sch Med & Dent Sci, Kagoshima 890, Japan.
RP Anderson, KS (reprint author), Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St,SHM B350, New Haven, CT 06520 USA.
EM karen.anderson@yale.edu
RI Baba, Masanori/G-3867-2011; Schinazi, Raymond/B-6777-2017
FU National Institutes of Health Institute of General Medical Sciences
[GM049551, GM099289]; National Institutes of Health Center for Applied
Research [2P30-AI-050409]; National Institutes of Health National
Institute of Environmental Health Sciences Intramural Research program
[ES065080]; Atlanta Department of Veteran Affairs
FX This work was supported by the National Institutes of Health Institute
of General Medical Sciences [Grants GM049551, GM099289]; the National
Institutes of Health Center for Applied Research [Grant 2P30-AI-050409];
the National Institutes of Health National Institute of Environmental
Health Sciences Intramural Research program [Grant ES065080]; and the
Atlanta Department of Veteran Affairs.
NR 54
TC 8
Z9 8
U1 0
U2 7
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JUL
PY 2012
VL 82
IS 1
BP 125
EP 133
DI 10.1124/mol.112.078758
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 961MZ
UT WOS:000305470000014
PM 22513406
ER
PT J
AU Cannons, JL
Lu, KT
Schwartzberg, PL
AF Cannons, Jennifer L.
Lu, Kristina T.
Schwartzberg, Pamela L.
TI Lymph node choreography: B cells take the lead
SO NATURE IMMUNOLOGY
LA English
DT Editorial Material
ID FOLLICULAR HELPER-CELLS; T-CELLS; HELMINTH INFECTION; DIFFERENTIATION;
ANTIBODIES; IMMUNITY
AB The role of T cells in providing help to B cells is well established; however, the converse-that B cells provide signals to help initiate T cell-mediated immunity-is less well appreciated. New data now show B cells modulate the earliest stages of T cell activation in a T helper type 2 response.
C1 [Cannons, Jennifer L.; Lu, Kristina T.; Schwartzberg, Pamela L.] NHGRI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Cannons, JL (reprint author), NHGRI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM pams@mail.nih.gov
NR 16
TC 3
Z9 4
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUL
PY 2012
VL 13
IS 7
BP 630
EP 632
DI 10.1038/ni.2349
PG 4
WC Immunology
SC Immunology
GA 961QZ
UT WOS:000305483800005
PM 22713820
ER
PT J
AU Xu, HX
Zhu, J
Smith, S
Foldi, J
Zhao, BH
Chung, AY
Outtz, H
Kitajewski, J
Shi, C
Weber, S
Saftig, P
Li, YM
Ozato, K
Blobel, CP
Ivashkiv, LB
Hu, XY
AF Xu, Haixia
Zhu, Jimmy
Smith, Sinead
Foldi, Julia
Zhao, Baohong
Chung, Allen Y.
Outtz, Hasina
Kitajewski, Jan
Shi, Chao
Weber, Silvio
Saftig, Paul
Li, Yueming
Ozato, Keiko
Blobel, Carl P.
Ivashkiv, Lionel B.
Hu, Xiaoyu
TI Notch-RBP-J signaling regulates the transcription factor IRF8 to promote
inflammatory macrophage polarization
SO NATURE IMMUNOLOGY
LA English
DT Article
ID SEQUENCE-BINDING-PROTEIN; P35 GENE-TRANSCRIPTION; NF-KAPPA-B; DENDRITIC
CELLS; INTERLEUKIN-12 EXPRESSION; IMMUNE-RESPONSES; MYELOID CELLS;
CROSS-TALK; ACTIVATION; CONSENSUS
AB Emerging concepts suggest that the functional phenotype of macrophages is regulated by transcription factors that define alternative activation states. We found that RBP-J, the main nuclear transducer of signaling via Notch receptors, augmented Toll-like receptor 4 (TLR4)-induced expression of key mediators of classically activated M1 macrophages and thus of innate immune responses to Listeria monocytogenes. Notch-RBP-J signaling controlled expression of the transcription factor IRF8 that induced downstream M1 macrophage-associated genes. RBP-J promoted the synthesis of IRF8 protein by selectively augmenting kinase IRAK2-dependent signaling via TLR4 to the kinase MNK1 and downstream translation-initiation control through eIF4E. Our results define a signaling network in which signaling via Notch-RBP-J and TLRs is integrated at the level of synthesis of IRF8 protein and identify a mechanism by which heterologous signaling pathways can regulate the TLR-induced inflammatory polarization of macrophages.
C1 [Xu, Haixia; Zhu, Jimmy; Smith, Sinead; Zhao, Baohong; Chung, Allen Y.; Blobel, Carl P.; Ivashkiv, Lionel B.; Hu, Xiaoyu] Hosp Special Surg, Arthrit & Tissue Degenerat Program, New York, NY 10021 USA.
[Xu, Haixia] Sun Yat Sen Univ, Dept Endocrinol, Affiliated Hosp 3, Guangzhou 510275, Guangdong, Peoples R China.
[Foldi, Julia; Shi, Chao; Ivashkiv, Lionel B.] Weill Cornell Grad Sch Med Sci, Grad Program Immunol & Microbial Pathogenesis, New York, NY USA.
[Outtz, Hasina; Kitajewski, Jan] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA.
[Shi, Chao; Li, Yueming] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Weber, Silvio; Saftig, Paul] Univ Kiel, Inst Biochem, D-2300 Kiel, Germany.
[Ozato, Keiko] NICHHD, NIH, Bethesda, MD 20892 USA.
[Hu, Xiaoyu] Weill Cornell Med Coll, Dept Med, New York, NY USA.
RP Hu, XY (reprint author), Hosp Special Surg, Arthrit & Tissue Degenerat Program, 535 E 70th St, New York, NY 10021 USA.
EM hux@hss.edu
RI Shi, Chao/B-5455-2008; Saftig, Paul/A-7966-2010; Hu, Xiaoyu/D-5403-2017;
OI Hu, Xiaoyu/0000-0002-4289-6998; Smith, Sinead/0000-0003-3460-3590
FU American College of Rheumatology; US National Institutes of Health
FX We thank T. Honjo (Kyoto University) for Rbpjflox/flox mice;
T. Gridley (Maine Medical Center Research Institute) for
Notch1+/- mice; R. Kopan (Washington University) for NICD1
expression plasmids; S. Smale (University of California, Los Angeles)
for Il12b promoter reporter constructs; M. Takami (Showa University) for
the IRF8 expression construct; S. Akira (Osaka University) for IRAK2
retroviral constructs; J.A. Cooper (Fred Hutchinson Cancer Research
Center) for MNK1 expression plasmids; E. Kieff (Harvard Medical School);
J.C. Aster (Harvard Medical School) for anti-RBP-J rabbit serum; E. G.
Pamer for discussions about the L. monocytogenes infection experiments;
and K. Au for technical assistance. Supported by the American College of
Rheumatology (X.H.) and the US National Institutes of Health (L.B.I. and
X.H.).
NR 50
TC 115
Z9 125
U1 6
U2 51
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUL
PY 2012
VL 13
IS 7
BP 642
EP +
DI 10.1038/ni.2304
PG 11
WC Immunology
SC Immunology
GA 961QZ
UT WOS:000305483800009
PM 22610140
ER
PT J
AU Chen, HB
Ndhlovu, ZM
Liu, DF
Porter, LC
Fang, JW
Darko, S
Brockman, MA
Miura, T
Brumme, ZL
Schneidewind, A
Piechocka-Trocha, A
Cesa, KT
Sela, J
Cung, TD
Toth, I
Pereyra, F
Yu, XG
Douek, DC
Kaufmann, DE
Allen, TM
Walker, BD
AF Chen, Huabiao
Ndhlovu, Zaza M.
Liu, Dongfang
Porter, Lindsay C.
Fang, Justin W.
Darko, Sam
Brockman, Mark A.
Miura, Toshiyuki
Brumme, Zabrina L.
Schneidewind, Arne
Piechocka-Trocha, Alicja
Cesa, Kevin T.
Sela, Jennifer
Cung, Thai D.
Toth, Ildiko
Pereyra, Florencia
Yu, Xu G.
Douek, Daniel C.
Kaufmann, Daniel E.
Allen, Todd M.
Walker, Bruce D.
TI TCR clonotypes modulate the protective effect of HLA class I molecules
in HIV-1 infection
SO NATURE IMMUNOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD8(+) T-CELLS; VIRAL LOAD; ELITE
CONTROLLERS; REPLICATION CAPACITY; DISEASE PROGRESSION; LYMPHOCYTE
ESCAPE; IMMUNE CONTROL; RESPONSES; EPITOPE
AB The human leukocyte antigens HLA-B*27 and HLA-B*57 are associated with protection against progression of disease that results from infection with human immunodeficiency virus type 1 (HIV-1), yet most people with alleles encoding HLA-B*27 and HLA-B*57 are unable to control HIV-1. Here we found that HLA-B*27-restricted CD8(+) T cells in people able to control infection with HIV-1 (controllers) and those who progress to disease after infection with HIV-1 (progressors) differed in their ability to inhibit viral replication through targeting of the immunodominant epitope of group-associated antigen (Gag) of HIV-1. This was associated with distinct T cell antigen receptor (TCR) clonotypes, characterized by superior control of HIV-1 replication in vitro, greater cross-reactivity to epitope variants and enhanced loading and delivery of perforin. We also observed clonotype-specific differences in antiviral efficacy for an immunodominant HLA-B*57-restricted response in controllers and progressors. Thus, the efficacy of such so-called 'protective alleles' is modulated by specific TCR clonotypes selected during natural infection, which provides a functional explanation for divergent HIV-1 outcomes.
C1 [Chen, Huabiao; Ndhlovu, Zaza M.; Liu, Dongfang; Porter, Lindsay C.; Fang, Justin W.; Brockman, Mark A.; Miura, Toshiyuki; Brumme, Zabrina L.; Schneidewind, Arne; Piechocka-Trocha, Alicja; Cesa, Kevin T.; Sela, Jennifer; Cung, Thai D.; Toth, Ildiko; Pereyra, Florencia; Yu, Xu G.; Kaufmann, Daniel E.; Allen, Todd M.; Walker, Bruce D.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA.
[Chen, Huabiao; Ndhlovu, Zaza M.; Liu, Dongfang; Porter, Lindsay C.; Fang, Justin W.; Brockman, Mark A.; Miura, Toshiyuki; Brumme, Zabrina L.; Schneidewind, Arne; Piechocka-Trocha, Alicja; Cesa, Kevin T.; Sela, Jennifer; Cung, Thai D.; Toth, Ildiko; Pereyra, Florencia; Yu, Xu G.; Kaufmann, Daniel E.; Allen, Todd M.; Walker, Bruce D.] Harvard Univ, Boston, MA 02115 USA.
[Chen, Huabiao; Ndhlovu, Zaza M.; Piechocka-Trocha, Alicja; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Darko, Sam; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Brockman, Mark A.; Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada.
[Miura, Toshiyuki] Univ Tokyo, Inst Med Sci, Tokyo, Japan.
[Schneidewind, Arne] Univ Hosp Regensburg, Dept Internal Med, Regensburg, Germany.
RP Walker, BD (reprint author), Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA.
EM bwalker@partners.org
RI Allen, Todd/F-5473-2011;
OI Brockman, Mark/0000-0001-6432-1426
FU Harvard University Center for AIDS Research [5 P30 AI060354-04]; Bill
and Melinda Gates Foundation; Doris Duke Charitable Foundation; US
National Institutes of Health [AI030914, AI074415]; Howard Hughes
Medical Institute; Mark and Lisa Schwartz Foundation; Office of AIDS
Research of the US National Institutes of Health; Canadian Institutes
for Health Research; Canada Research Chair in Viral Pathogenesis and
Immunity; US National Institutes of Health
FX We thank J. Wong (Massachusetts General Hospital) for monoclonal
antibody 12F6 to CD3 and monoclonal antibody CD3: 8 bispecific for CD3
and CD8; and all study participants for their contributions. Supported
by the Harvard University Center for AIDS Research (5 P30 AI060354-04),
the Bill and Melinda Gates Foundation (B. D. W. and D. C. D.), the Doris
Duke Charitable Foundation (B. D. W.), the US National Institutes of
Health (AI030914 to B. D. W. and AI074415 to T. M. A.), the Howard
Hughes Medical Institute (B. D. W.), the Mark and Lisa Schwartz
Foundation (B. D. W.), the Intramural Research Program and the Office of
AIDS Research of the US National Institutes of Health (D. C. D. and S.
D.), the Canadian Institutes for Health Research (New Investigator Award
to Z.L.B.) and the Canada Research Chair in Viral Pathogenesis and
Immunity (M.A.B.).
NR 50
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUL
PY 2012
VL 13
IS 7
BP 691
EP +
DI 10.1038/ni.2342
PG 12
WC Immunology
SC Immunology
GA 961QZ
UT WOS:000305483800015
PM 22683743
ER
PT J
AU Sawyer, EK
Mun, J
Nye, JA
Kimmel, HL
Voll, RJ
Stehouwer, JS
Rice, KC
Goodman, MM
Howell, LL
AF Sawyer, Eileen K.
Mun, Jiyoung
Nye, Jonathon A.
Kimmel, Heather L.
Voll, Ronald J.
Stehouwer, Jeffrey S.
Rice, Kenner C.
Goodman, Mark M.
Howell, Leonard L.
TI Neurobiological Changes Mediating the Effects of Chronic Fluoxetine on
Cocaine Use
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE fluoxetine; cocaine; self-administration; reinstatement; nonhuman
primate; 5HT2A
ID SEROTONIN REUPTAKE INHIBITORS; IN-VIVO; 5-HT2A RECEPTORS; EXTRACELLULAR
SEROTONIN; DOPAMINE TRANSPORTER; INTRAVENOUS COCAINE; DEPENDENT
PATIENTS; NONHUMAN-PRIMATES; SQUIRREL-MONKEYS; MENSTRUAL-CYCLE
AB Acute SSRI (selective serotonin reuptake inhibitor) treatment has been shown to attenuate the abuse-related effects of cocaine; however, SSRIs have had limited success in clinical trials for cocaine abuse, possibly due to neurobiological changes that occur during chronic administration. In order to better understand the role of serotonin (5HT) in cocaine abuse and treatment, we examined the effects of chronic treatment with the SSRI fluoxetine at clinically relevant serum concentrations on cocaine-related neurobiology and behavior. Rhesus macaques self-administering cocaine underwent a 6-week dosing regimen with fluoxetine designed to approximate serum concentrations observed in humans. Self-administration and reinstatement were monitored throughout the treatment and washout period. In vivo microdiaylsis was used to assess changes in dopaminergic and serotonergic neurochemistry. Positron emission tomography was used to assess changes in the 5HT transporter and 2A receptor binding potential (BP). Functional output of the 5HT system was assessed using prolactin levels. Cocaine-primed reinstatement and cocaine-elicited dopamine overflow were significantly suppressed following chronic fluoxetine treatment. 5HT2A receptor BP was increased in the frontal cortex following treatment while prolactin release was blunted, suggesting desensitization of the 5HT2A receptor. These effects persisted after a 6-week washout period. Measures of pre-synaptic serotonergic function and cocaine self-administration were unaffected. These data demonstrate that acute and chronic fluoxetine treatments exert different effects on cocaine-related behavior. Furthermore, chronic fluoxetine treatment causes alterations in 5HT2A receptors in the frontal cortex that may selectively disrupt cocaine-primed reinstatement. Fluoxetine may not be useful for treatment of ongoing cocaine abuse but may be useful in relapse prevention. Neuropsychopharmacology (2012) 37, 1816-1824; doi:10.1038/npp.2012.29; published online 21 March 2012
C1 [Howell, Leonard L.] Emory Univ, Yerkes Natl Primate Res Ctr, Div Neuropharmacol & Neurol Dis, Atlanta, GA 30329 USA.
[Sawyer, Eileen K.] Emory Univ, Neurosci Program, Atlanta, GA 30329 USA.
[Mun, Jiyoung; Nye, Jonathon A.; Voll, Ronald J.; Stehouwer, Jeffrey S.; Goodman, Mark M.] Emory Univ, Dept Radiol & Imaging Sci, Atlanta, GA 30329 USA.
[Kimmel, Heather L.; Howell, Leonard L.] Emory Univ, Dept Pharmacol, Atlanta, GA 30329 USA.
[Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Bethesda, MD USA.
[Rice, Kenner C.] NIAAA, NIH, Bethesda, MD USA.
[Howell, Leonard L.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30329 USA.
RP Howell, LL (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, Div Neuropharmacol & Neurol Dis, 954 Gatewood Rd, Atlanta, GA 30329 USA.
EM lhowell@emory.edu
RI Kimmel, Heather/A-6617-2008; Kimmel, Heather/E-9135-2014
OI Kimmel, Heather/0000-0001-8278-0095; Kimmel, Heather/0000-0001-8278-0095
FU National Institute on Drug Abuse; National Institute on Alcohol Abuse
and Alcoholism; [DA10344]; [DA000517]; [T-32 DA015040]; [RR00065]
FX The authors declare that, except for income received from primary
employers, no financial support or compensation has been received from
any individual or corporate entity over the past 3 years for research or
professional service and there are no personal financial holdings that
could be perceived as constituting a potential conflict of interest.
This work was supported by DA10344 (LLH), DA000517 (LLH), T-32 DA015040
(EKS), and RR00065 (YNPRC). A portion of this work was also supported by
the Intramural Research Programs of the National Institute on Drug Abuse
and the National Institute on Alcohol Abuse and Alcoholism.
NR 50
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U1 2
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUL
PY 2012
VL 37
IS 8
BP 1816
EP 1824
DI 10.1038/npp.2012.29
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 960EZ
UT WOS:000305372100005
PM 22434223
ER
PT J
AU Panlilio, LV
Justinova, Z
Mascia, P
Pistis, M
Luchicchi, A
Lecca, S
Barnes, C
Redhi, GH
Adair, J
Heishman, SJ
Yasar, S
Aliczki, M
Haller, J
Goldberg, SR
AF Panlilio, Leigh V.
Justinova, Zuzana
Mascia, Paola
Pistis, Marco
Luchicchi, Antonio
Lecca, Salvatore
Barnes, Chanel
Redhi, Godfrey H.
Adair, Jordan
Heishman, Stephen J.
Yasar, Sevil
Aliczki, Mano
Haller, Jozsef
Goldberg, Steven R.
TI Novel Use of a Lipid-Lowering Fibrate Medication to Prevent Nicotine
Reward and Relapse: Preclinical Findings
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE nicotine; reward; relapse; dopamine signaling; PPAR alpha; fibrate
ID VENTRAL TEGMENTAL AREA; PROLIFERATOR-ACTIVATED RECEPTORS; CUE-INDUCED
REINSTATEMENT; NUCLEUS-ACCUMBENS SHELL; DOPAMINE NEURONS;
SMOKING-CESSATION; SEEKING BEHAVIOR; UNITED-STATES; TOBACCO USE; RATS
AB Experimental drugs that activate alpha-type peroxisome proliferator-activated receptors (PPAR alpha) have recently been shown to reduce the rewarding effects of nicotine in animals, but these drugs have not been approved for human use. The fibrates are a class of PPAR alpha-activating medications that are widely prescribed to improve lipid profiles and prevent cardiovascular disease, but these drugs have not been tested in animal models of nicotine reward. Here, we examine the effects of clofibrate, a representative of the fibrate class, on reward-related behavioral, electrophysiological, and neurochemical effects of nicotine in rats and squirrel monkeys. Clofibrate prevented the acquisition of nicotine-taking behavior in naive animals, substantially decreased nicotine taking in experienced animals, and counteracted the relapse-inducing effects of re-exposure to nicotine or nicotine-associated cues after a period of abstinence. In the central nervous system, clofibrate blocked nicotine's effects on neuronal firing in the ventral tegmental area and on dopamine release in the nucleus accumbens shell. All of these results suggest that fibrate medications might promote smoking cessation. The fact that fibrates are already approved for human use could expedite clinical trials and subsequent implementation of fibrates as a treatment for tobacco dependence, especially in smokers with abnormal lipid profiles. Neuropsychopharmacology (2012) 37, 1838-1847; doi:10.1038/npp.2012.31; published online 28 March 2012
C1 [Goldberg, Steven R.] Natl Inst Drug Abuse, Intramural Res Program, Preclin Pharmacol Sect, Dept Hlth & Human Serv,NIH,Biomed Res Ctr, Baltimore, MD 21224 USA.
[Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
[Pistis, Marco; Luchicchi, Antonio; Lecca, Salvatore] Univ Cagliari, BB Brodie Dept Neurosci, Cagliari, Italy.
[Heishman, Stephen J.] Natl Inst Drug Abuse, Intramural Res Program, Psychopharmacol Sect, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA.
[Yasar, Sevil] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA.
[Aliczki, Mano; Haller, Jozsef] Hungarian Acad Sci, Inst Expt Med, Dept Behav Neurosci, Budapest, Hungary.
RP Goldberg, SR (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Preclin Pharmacol Sect, Dept Hlth & Human Serv,NIH,Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sgoldber@intra.nida.nih.gov
RI Justinova, Zuzana/A-9109-2011; Pistis, Marco/A-3773-2013;
OI Justinova, Zuzana/0000-0001-5793-7484; Pistis,
Marco/0000-0002-4622-3205; Haller, Jozsef/0000-0002-1953-3726;
Luchicchi, Antonio/0000-0002-0189-4347
FU National Institute on Drug Abuse, National Institutes of Health,
Department of Health and Human Services; National Institute on Drug
Abuse Residential Research Support Services [N01 DA59909]; Regione
Autonoma della Sardegna (Italy); Division of Geriatric Medicine and
Gerontology, Johns Hopkins University School of Medicine, Baltimore
FX This study was supported by the Intramural Research Program of the
National Institute on Drug Abuse, National Institutes of Health,
Department of Health and Human Services; National Institute on Drug
Abuse Residential Research Support Services Contract No. N01 DA59909
(Kelly PI); the Regione Autonoma della Sardegna (Italy), Assessorato
alla Programmazione; and the Division of Geriatric Medicine and
Gerontology, Johns Hopkins University School of Medicine, Baltimore.
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U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUL
PY 2012
VL 37
IS 8
BP 1838
EP 1847
DI 10.1038/npp.2012.31
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 960EZ
UT WOS:000305372100007
PM 22453137
ER
PT J
AU Robinson, OJ
Overstreet, C
Allen, PS
Pine, DS
Grillon, C
AF Robinson, Oliver J.
Overstreet, Cassie
Allen, Phillip S.
Pine, Daniel S.
Grillon, Christian
TI Acute Tryptophan Depletion Increases Translational Indices of Anxiety
but not Fear: Serotonergic Modulation of the Bed Nucleus of the Stria
Terminalis?
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE ATD; serotonin; anxiety; startle; depression
ID CORTICOTROPIN-RELEASING HORMONE; UNPREDICTABLE AVERSIVE EVENTS; RESEARCH
DOMAIN CRITERIA; POTENTIATED STARTLE; PREFRONTAL CORTEX; MAJOR
DEPRESSION; CONTEXTUAL FEAR; RAPHE NUCLEUS; NEGATIVE MOOD; HUMANS
AB Serotonin is strongly implicated in the mammalian stress response, but surprisingly little is known about its mode of action. Recent data suggest that serotonin can inhibit aversive responding in humans, but this remains underspecified. In particular, data in rodents suggest that global serotonin depletion may specifically increase long-duration bed nucleus of the stria terrninalis (BNST)-mediated aversive responses (ie, anxiety), but not short-duration BNST-independent responses (ie, fear). Here, we extend these findings to humans. In a balanced, placebo-controlled crossover design, healthy volunteers (n = 20) received a controlled diet with and without the serotonin precursor tryptophan (acute.tryptophan depletion; ATD). Aversive states were indexed by translational acoustic startle measures. Fear and anxiety were operationally defined as the increase in startle reactivity during short- and long-duration threat periods evoked by predictable shock (fear-potentiated startle) and by the context in which the shocks were administered (anxiety-potentiated startle), respectively. ATD significantly increased long-duration anxiety-potentiated startle but had no effect on short-duration fear-potentiated startle. These results suggest that serotonin depletion in humans selectively increases anxiety but not fear. Current translational frameworks support the proposition that ATD thus disinhibits dorsal raphe-originating serotonergic control of corticotropin-releasing hormone-mediated excitation of the BNST. This generates a candidate neuropharmacological mechanism by which depleted serotonin may increase response to sustained threats, alongside clear implications for our understanding of the manifestation and treatment of mood and anxiety disorders. Neuropsychopharmacology (2012) 37, 1963-1971; doi:10.1038/npp.2012.43; published online 11 April 2012
C1 [Robinson, Oliver J.; Overstreet, Cassie; Allen, Phillip S.; Grillon, Christian] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
[Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, NIH, Bethesda, MD 20892 USA.
RP Robinson, OJ (reprint author), NIMH, Sect Neurobiol Fear & Anxiety, NIH, 15K North Dr, Bethesda, MD 20892 USA.
EM oliver.j.robinson@gmail.com
RI Robinson, Oliver/B-3646-2011
OI Robinson, Oliver/0000-0002-3100-1132
FU Intramural Research Program of the National Institutes of Mental Health
FX This research was supported by the Intramural Research Program of the
National Institutes of Mental Health. We are grateful to Michael
Jackson, Angie Wu, Joan Mallinger, and Allison Letkiewicz for enormous
amounts of help and support.
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U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUL
PY 2012
VL 37
IS 8
BP 1963
EP 1971
DI 10.1038/npp.2012.43
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 960EZ
UT WOS:000305372100019
PM 22491355
ER
PT J
AU Sharpe, CM
Capparelli, EV
Mower, A
Farrell, MJ
Soldin, SJ
Haas, RH
AF Sharpe, Cynthia M.
Capparelli, Edmund V.
Mower, Andrew
Farrell, Michael J.
Soldin, Steven J.
Haas, Richard H.
TI A seven-day study of the pharmacokinetics of intravenous levetiracetam
in neonates: marked changes in pharmacokinetics occur during the first
week of life
SO PEDIATRIC RESEARCH
LA English
DT Article
ID ANTIEPILEPTIC DRUGS; VALPROIC ACID; SEIZURES; CHILDREN; EPILEPSY;
MODELS; BRAIN; AGE
AB INTRODUCTION: Levetiracetam (LEV) is increasingly used in the treatment of neonatal seizures. The aim of this study was to determine pharmacokinetics in neonates with seizures and to obtain preliminary safety and efficacy data.
METHODS: Eighteen term neonates with seizures persisting after 20mg/kg of phenobarbital received intravenous LEV for 1 wk. LEV was administered as a 20 or 40 mg/kg bolus followed by 5-10 mg/kg/d. Pharmacokinetic data were analyzed using a nonlinear mixed-effects population approach. Continuous electroencephalogram monitoring allowed preliminary assessment of the efficacy of LEV in this population.
RESULTS: LEV clearance (CL) increased from a mean of 0.7 ml/min/kg (SD 0.27 ml/min/kg) on day 1 to 1.33 ml/min/kg (SD 0.35 ml/min/kg) by day 7. Mean half-life was 18.5 h (SD 7.1 h) on day 1 of the study and decreased to 9.1 h (SD 2.0 h) by day 7. The mean volume of distribution was 1.01 l/kg (SD 0.13 l/kg). No study-related serious adverse events were observed.
DISCUSSION: CL of LEV in neonates was higher than expected on the basis of immature renal function in term infants and increased significantly during the first week of life. More frequent dosing of LEV is needed in term infants to maintain serum concentrations in the range seen in children and adults.
C1 [Capparelli, Edmund V.; Farrell, Michael J.; Haas, Richard H.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
[Sharpe, Cynthia M.] Starship Childrens Hosp, Dept Neuroserv, Auckland, New Zealand.
[Mower, Andrew; Haas, Richard H.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
[Soldin, Steven J.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Haas, RH (reprint author), Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
EM rhaas@ucsd.edu
FU grant from the Thrasher Foundation [02825-1]
FX This work was supported by a grant from the Thrasher Foundation
(Thrasher award no. 02825-1). Levetiracetam and UCB057 for assay
development were provided by UCB Pharma.
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0031-3998
J9 PEDIATR RES
JI Pediatr. Res.
PD JUL
PY 2012
VL 72
IS 1
BP 43
EP 49
DI 10.1038/pr.2012.51
PG 7
WC Pediatrics
SC Pediatrics
GA 961BY
UT WOS:000305440100007
PM 22495532
ER
PT J
AU Bartels, E
Jenetzky, E
Solomon, BD
Ludwig, M
Schmiedeke, E
Grasshoff-Derr, S
Schmidt, D
Marzheuser, S
Hosie, S
Weih, S
Holland-Cunz, S
Palta, M
Leonhardt, J
Schafer, M
Kujath, C
Rissmann, A
Nothen, MM
Reutter, H
Zwink, N
AF Bartels, Enrika
Jenetzky, Ekkehart
Solomon, Benjamin D.
Ludwig, Michael
Schmiedeke, Eberhard
Grasshoff-Derr, Sabine
Schmidt, Dominik
Maerzheuser, Stefanie
Hosie, Stuart
Weih, Sandra
Holland-Cunz, Stefan
Palta, Markus
Leonhardt, Johannes
Schaefer, Mattias
Kujath, Christina
Rissmann, Anke
Noethen, Markus M.
Reutter, Heiko
Zwink, Nadine
TI Inheritance of the VATER/VACTERL association
SO PEDIATRIC SURGERY INTERNATIONAL
LA English
DT Article
DE Inheritance; VATER; VACTERL; Association; First-degree relatives
ID VATER ASSOCIATION; VACTERL-ASSOCIATION; DEFINITION; SPECTRUM
AB VATER/VACTERL association refers to the non-random co-occurrence of the following component features: vertebral defects, anal atresia, cardiac malformations, tracheoesophageal atresia, renal abnormalities, and limb defects. Recently, Solomon et al. (Hum Genet 127:731-733, 2010) observed an increased prevalence of component features among first-degree relatives of VATER/VACTERL patients suggesting that in some patients, the disorder may be inherited. To replicate these findings, we investigated 87 VATER/VACTERL patients with the presence of a minimum of three component features and their first-degree relatives (n = 271). No increase in the overall prevalence of component features was observed in first-degree relatives compared to the general population (chi A(2)A = 2.68, p = 0.10). Separate analysis for the prevalence of single component features showed a higher prevalence of tracheoesophageal fistula/atresia among first-degree relatives compared to the general population (OR 17.65, 95 % CI 2.47-126.05). However, this was based on occurrence in one family only. Our findings suggest that although familial occurrence renders a genetic contribution likely, the overall risk of recurrence among the first-degree relatives of patients with VATER/VACTERL association is probably very low. Since the patients in the present study were young and no offspring could be studied, estimation of the role of de novo mutations in the development of VATER/VACTERL was not possible.
C1 [Bartels, Enrika; Schmiedeke, Eberhard; Noethen, Markus M.; Reutter, Heiko] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Jenetzky, Ekkehart; Zwink, Nadine] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany.
[Solomon, Benjamin D.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Ludwig, Michael] Univ Bonn, Dept Clin Chem & Clin Pharmacol, Bonn, Germany.
[Schmiedeke, Eberhard] Hosp Bremen Mitte, Ctr Child & Adolescent Hlth, Dept Pediat Surg & Urol, Bremen, Germany.
[Grasshoff-Derr, Sabine] Univ Hosp Wurzburg, Dept Pediat Surg, Wurzburg, Germany.
[Schmidt, Dominik; Maerzheuser, Stefanie] Charite, Campus Virchow Clin, Dept Pediat Surg, Berlin, Germany.
[Hosie, Stuart] Tech Univ Munich, Klinikum Schwabing, Dept Pediat Surg, Munich, Germany.
[Weih, Sandra; Holland-Cunz, Stefan] Heidelberg Univ, Dept Pediat Surg, Heidelberg, Germany.
[Palta, Markus] Evangel Krankenhaus Hamm, Dept Pediat Surg, Hamm, Germany.
[Leonhardt, Johannes] St Bernward Hosp, Dept Pediat Surg, Hildesheim, Germany.
[Schaefer, Mattias] Cnopfsche Klin, Dept Pediat Surg & Urol, Nurnberg, Germany.
[Kujath, Christina] Ernst Moritz Arndt Univ Greifswald, Dept Pediat Surg, Greifswald, Germany.
[Rissmann, Anke] Otto Von Guericke Univ, Malformat Monitoring Ctr Saxony Anhalt, Magdeburg, Germany.
[Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany.
[Reutter, Heiko] Univ Bonn, Dept Neonatol, Childrens Hosp, Bonn, Germany.
RP Bartels, E (reprint author), Univ Bonn, Inst Human Genet, Bonn, Germany.
EM enrika.bartels@uni-bonn.de
OI Nothen, Markus/0000-0002-8770-2464
FU German Federal Ministry of Education and Research (Bundesministerium fur
Bildung und Forschung, BMBF) [01GM08107]
FX E.B., E.J., M.L., E.S., S.G.-D., S.M., S.H.-C., M.M.N., H.R., and N.Z.
are members of the "Network for the Systematic Investigation of the
Molecular Causes, Clinical Implications, and Psychosocial Outcome of
Congenital Uro-Rectal Malformations (CURE-Net)", which is supported by a
research grant (01GM08107) from the German Federal Ministry of Education
and Research (Bundesministerium fur Bildung und Forschung, BMBF). We
thank all the family members for their cooperation, and the German
self-help organization for people with anorectal malformations (SoMA
e.V.) for their assistance with recruitment. We thank Dr. Christine
Schmael for her expert advice on the manuscript.
NR 9
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U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0179-0358
EI 1437-9813
J9 PEDIATR SURG INT
JI Pediatr. Surg. Int.
PD JUL
PY 2012
VL 28
IS 7
BP 681
EP 685
DI 10.1007/s00383-012-3100-z
PG 5
WC Pediatrics; Surgery
SC Pediatrics; Surgery
GA 961OX
UT WOS:000305476600005
PM 22581124
ER
PT J
AU Clarke, K
Tchabanenko, K
Pawlosky, R
Carter, E
Knight, NS
Murray, AJ
Cochlin, LE
King, MT
Wong, AW
Roberts, A
Robertson, J
Veech, RL
AF Clarke, Kieran
Tchabanenko, Kirill
Pawlosky, Robert
Carter, Emma
Knight, Nicholas S.
Murray, Andrew J.
Cochlin, Lowri E.
King, M. Todd
Wong, Andrea W.
Roberts, Ashley
Robertson, Jeremy
Veech, Richard L.
TI Oral 28-day and developmental toxicity studies of (R)-3-hydroxybutyl
(R)-3-hydroxybutyrate
SO REGULATORY TOXICOLOGY AND PHARMACOLOGY
LA English
DT Article
DE (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate; Developmental toxicity;
Ketones; Toxicity; Safety
ID BETA-HYDROXYBUTYRATE; KETOGENIC DIET; RAT; 1,3-BUTANEDIOL; BLOOD;
METABOLISM; EMBRYOS; HUNGER; ADULTS; BRAIN
AB (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate (ketone monoester) has been developed as an oral source of ketones, which may be utilized for energy. In a 28-day toxicity study, Crl:WI (Wistar) rats received diets containing, as 30% of the calories, ketone monoester (12 and 15 g/kg body weight/day for male and female rats, respectively). Control groups received either carbohydrate- or fat-based diets. Rats in the test group consumed less feed and gained less weight than control animals; similar findings have been documented in studies of ketogenic diets. Between-group differences were noted in selected hematology, coagulation, and serum chemistry parameters; however, values were within normal physiological ranges and/or were not accompanied by other changes indicative of toxicity. Upon gross and microscopic evaluation, there were no findings associated with the ketone monoester. In a developmental toxicity study, pregnant Crl:WI (Han) rats were administered 2 g/kg body weight/day ketone monoester or water (control) via gavage on days 6 through 20 of gestation. No Caesarean-sectioning or litter parameters were affected by the test article. The overall incidence of fetal alterations was higher in the test group; however, there were no specific alterations attributable to the test substance. The results of these studies support the safety of ketone monoester. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Clarke, Kieran; Carter, Emma; Knight, Nicholas S.; Murray, Andrew J.; Cochlin, Lowri E.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England.
[Tchabanenko, Kirill; Robertson, Jeremy] Univ Oxford, Dept Chem, Oxford OX1 3PT, England.
[Pawlosky, Robert; King, M. Todd; Veech, Richard L.] NIAAA, Lab Metab Control, NIH, Rockville, MD 20852 USA.
[Wong, Andrea W.; Roberts, Ashley] Intertek Cantox, Mississauga, ON, Canada.
RP Clarke, K (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Sherrington Bldg,Parks Rd, Oxford OX1 3PT, England.
EM kieran.clarke@dpag.ox.ac.uk
RI Murray, Andrew/B-3130-2010
OI Murray, Andrew/0000-0002-0929-9315
FU Intramural NIH HHS [ZID AA000112-09]
NR 39
TC 18
Z9 18
U1 4
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0273-2300
EI 1096-0295
J9 REGUL TOXICOL PHARM
JI Regul. Toxicol. Pharmacol.
PD JUL
PY 2012
VL 63
IS 2
BP 196
EP 208
DI 10.1016/j.yrtph.2012.04.001
PG 13
WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology
SC Legal Medicine; Pharmacology & Pharmacy; Toxicology
GA 960IJ
UT WOS:000305380900003
PM 22504461
ER
PT J
AU Collins, F
AF Collins, Francis
TI How to Fulfill the True Promise of "mHealth"
SO SCIENTIFIC AMERICAN
LA English
DT Editorial Material
C1 Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Collins, F (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA.
NR 0
TC 15
Z9 16
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0036-8733
J9 SCI AM
JI Sci.Am.
PD JUL
PY 2012
VL 307
IS 1
BP 16
EP 16
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961WT
UT WOS:000305500900011
PM 22779258
ER
PT J
AU Gioia, R
Panaroni, C
Besio, R
Palladini, G
Merlini, G
Giansanti, V
Scovassi, IA
Villani, S
Villa, I
Villa, A
Vezzoni, P
Tenni, R
Rossi, A
Marini, JC
Forlino, A
AF Gioia, Roberta
Panaroni, Cristina
Besio, Roberta
Palladini, Giovanni
Merlini, Giampaolo
Giansanti, Vincenzo
Scovassi, Ivana A.
Villani, Simona
Villa, Isabella
Villa, Anna
Vezzoni, Paolo
Tenni, Ruggero
Rossi, Antonio
Marini, Joan C.
Forlino, Antonella
TI Impaired Osteoblastogenesis in a Murine Model of Dominant Osteogenesis
Imperfecta: A New Target for Osteogenesis Imperfecta Pharmacological
Therapy
SO STEM CELLS
LA English
DT Article
DE Osteogenesis imperfecta; Adult stem cell; Osteoblastogenesis;
Adipogenesis; Adult stem cells differentiation; Autophagy
ID MESENCHYMAL STEM-CELLS; MULTIPLE-MYELOMA PATIENTS; MARROW STROMAL CELLS;
IV MOUSE MODEL; IN-VIVO; PROTEASOME INHIBITORS; TRANS-DIFFERENTIATION;
BONE; MICE; BORTEZOMIB
AB The molecular basis underlying the clinical phenotype in bone diseases is customarily associated with abnormal extracellular matrix structure and/or properties. More recently, cellular malfunction has been identified as a concomitant causative factor and increased attention has focused on stem cells differentiation. Classic osteogenesis imperfecta (OI) is a prototype for heritable bone dysplasias: it has dominant genetic transmission and is caused by mutations in the genes coding for collagen I, the most abundant protein in bone. Using the Brtl mouse, a well-characterized knockin model for moderately severe dominant OI, we demonstrated an impairment in the differentiation of bone marrow progenitor cells toward osteoblasts. In mutant mesenchymal stem cells (MSCs), the expression of early (Runx2 and Sp7) and late (Col1a1 and Ibsp) osteoblastic markers was significantly reduced with respect to wild type (WT). Conversely, mutant MSCs generated more colony-forming unit-adipocytes compared to WT, with more adipocytes per colony, and increased number and size of triglyceride drops per cell. Autophagy upregulation was also demonstrated in mutant adult MSCs differentiating toward osteogenic lineage as consequence of endoplasmic reticulum stress due to mutant collagen retention. Treatment of the Brtl mice with the proteasome inhibitor Bortezomib ameliorated both osteoblast differentiation in vitro and bone properties in vivo as demonstrated by colony-forming unit-osteoblasts assay and peripheral quantitative computed tomography analysis on long bones, respectively. This is the first report of impaired MSC differentiation to osteoblasts in OI, and it identifies a new potential target for the pharmacological treatment of the disorder. STEM CELLS 2012;30:1465-1476
C1 [Gioia, Roberta; Panaroni, Cristina; Besio, Roberta; Palladini, Giovanni; Merlini, Giampaolo; Tenni, Ruggero; Rossi, Antonio; Forlino, Antonella] Univ Pavia, Dept Mol Med, Biochem Sect, I-27100 Pavia, Italy.
[Villani, Simona] Univ Pavia, Dept Hlth Sci, Sect Med Stat & Epidemiol, I-27100 Pavia, Italy.
[Panaroni, Cristina; Villa, Anna; Vezzoni, Paolo] CNR, Milan Unit, Ist Ric Genet & Biomed, I-20133 Milan, Italy.
[Palladini, Giovanni; Merlini, Giampaolo] Fdn IRCCS Policlin San Matteo, Biotechnol Res Labs, Amyloidosis Res & Treatment Ctr, Pavia, Italy.
[Giansanti, Vincenzo; Scovassi, Ivana A.] CNR, Inst Mol Genet, I-27100 Pavia, Italy.
[Villa, Isabella] Ist Sci San Raffaele, Bone Metab Unit, I-20132 Milan, Italy.
[Villa, Anna; Vezzoni, Paolo] Ist Clin Humanitas, Rozzano, Italy.
[Marini, Joan C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA.
RP Forlino, A (reprint author), Univ Pavia, Dept Mol Med, Biochem Sect, Via Taramelli 3-B, I-27100 Pavia, Italy.
EM aforlino@unipv.it
RI Rossi, Antonio/E-9935-2012; Palladini, Giovanni/G-1763-2010; Forlino,
Antonella/H-5385-2015;
OI Palladini, Giovanni/0000-0001-5994-5138; Forlino,
Antonella/0000-0002-6385-1182; Scovassi, Anna Ivana/0000-0003-3484-9881;
Villa, Anna/0000-0003-4428-9013; Merlini, Giampaolo/0000-0001-7680-3254;
/0000-0003-2517-6515
FU PRIN [2008XA48SC, 200999KRFW-002]; Fondazione Cariplo; Progetto Premiale
CNR Invecchiamento; Progetto Regione Lombardia [cod. SAL/45]; Collegio
Ghislieri, Pavia, Italy, fellowship
FX We thank Dr. Lupi A. for initial set up of MSCs culture and Dr. Vaghi P.
(Centro Grandi Strumenti, University of Pavia, Italy) for technical
assistance for Confocal Microscopy. This work was supported by PRIN 2008
(2008XA48SC) to A. F., by PRIN 200999KRFW-002 to P. V., by Fondazione
Cariplo 2007 to A. F. and P.V., by Progetto Premiale CNR Invecchiamento
to P. V., and by Progetto Regione Lombardia (cod. SAL/45) "Dalla scienza
dei materiali alla medicina molecolare" to A. F. G. V. was supported by
Collegio Ghislieri, Pavia, Italy, fellowship.
NR 56
TC 25
Z9 28
U1 2
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD JUL
PY 2012
VL 30
IS 7
BP 1465
EP 1476
DI 10.1002/stem.1107
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 961PB
UT WOS:000305477000015
PM 22511244
ER
PT J
AU Tryndyak, VP
Latendresse, JR
Montgomery, B
Ross, SA
Beland, FA
Rusyn, I
Pogribny, IP
AF Tryndyak, Volodymyr P.
Latendresse, John R.
Montgomery, Beverly
Ross, Sharon A.
Beland, Frederick A.
Rusyn, Ivan
Pogribny, Igor P.
TI Plasma microRNAs are sensitive indicators of inter-strain differences in
the severity of liver injury induced in mice by a choline- and
folate-deficient diet
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Inter-individual differences; microRNAs; Mouse; Nonalcoholic fatty liver
disease
ID NONALCOHOLIC STEATOHEPATITIS; HEPATOCELLULAR-CARCINOMA; CIRCULATING
MICRORNAS; METABOLIC SYNDROME; ANIMAL-MODELS; UNITED-STATES;
HEPATITIS-C; DISEASE; EXPRESSION; BIOMARKERS
AB MicroRNAs (miRNAs) are a class of small, conserved, tissue-specific regulatory non-coding RNAs that modulate a variety of biological processes and play a fundamental role in the pathogenesis of major human diseases, including nonalcoholic fatty liver disease (NAFLD). However, the association between inter-individual differences in susceptibility to NAFLD and altered miRNA expression is largely unknown. In view of this, the goals of the present study were (i) to determine whether or not individual differences in the extent of NAFLD-induced liver injury are associated with altered miRNA expression, and (ii) assess if circulating blood miRNAs may be used as potential biomarkers for the noninvasive evaluation of the severity of NAFLD. A panel of seven genetically diverse strains of inbred male mice (A/J, C57BL/6J, C3H/HeJ, 129S/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ) were fed a choline- and folate-deficient (CFD) diet for 12 weeks. This diet induced liver injury in all mouse strains; however, the extent of NAFLD-associated pathomorphological changes in the livers was strain-specific, with A/J, C57BL/6J, and C3H/HeJ mice being the least sensitive and WSB/EiJ mice being the most sensitive. The morphological changes in the livers were accompanied by differences in the levels of hepatic and plasma miRNAs. The levels of circulating miR-34a, miR-122, miR-181a, miR-192, and miR-200b miRNAs were significantly correlated with a severity of NAFLD-specific liver pathomorphological features, with the strongest correlation occurring with miR-34a. These observations suggest that the plasma levels of miRNAs may be used as biomarkers for noninvasive monitoring the extent of NAFLD-associated liver injury and susceptibility to NAFLD. Published by Elsevier Inc.
C1 [Tryndyak, Volodymyr P.; Montgomery, Beverly; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Latendresse, John R.] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA.
[Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA.
RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM igor.pogribny@fda.hhs.gov
RI Rusyn, Ivan/S-2426-2016
FU NIEHS NIH HHS [R01 ES015241]
NR 39
TC 38
Z9 39
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD JUL 1
PY 2012
VL 262
IS 1
BP 52
EP 59
DI 10.1016/j.taap.2012.04.018
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 960IW
UT WOS:000305382200006
PM 22561871
ER
PT J
AU Sharkey, LC
Simpson, RM
Wellman, ML
Craig, LE
Birkebak, TA
Kock, ND
Miller, MA
Harris, RK
Munson, L
AF Sharkey, L. C.
Simpson, R. M.
Wellman, M. L.
Craig, L. E.
Birkebak, T. A.
Kock, N. D.
Miller, M. A.
Harris, R. K.
Munson, L.
CA ACVP Training Program Dev Task
TI The Value of Biomedical Research Training for Veterinary Anatomic and
Clinical Pathologists
SO VETERINARY PATHOLOGY
LA English
DT Editorial Material
DE biomedical research; veterinary pathology; education; training; best
practices
ID GUIDELINES
AB Veterinary pathologists traditionally have been actively engaged in research as principal investigators and as collaborators. Pathologists frequently obtain advanced training in research; however, it appears that in the last 10 years there has been a reversal of a previous trend toward increasing numbers of pathologists obtaining PhD degrees. This has arisen despite an established shortage of veterinarians engaged in research. This article evaluates the benefits of research training for individual pathologists, including a wide spectrum of professional opportunities and additional skill development beyond that usually provided by diagnostic pathology training alone. Various training models are discussed, including combined and sequential diagnostic residency and research degree training as well as the nondegree research fellowship programs more commonly pursued in human medicine. Best-practice recommendations for program infrastructure, mentorship, time management, and a team approach to research and research training are advocated to facilitate the development of successful programs and to encourage a continued emphasis on integrated training for pathologists as both clinical diagnosticians and experimentalists. This article is intended to help prospective and active pathology trainees, their mentors, and educational administrators optimize opportunities to ensure the future vitality of veterinary pathologists, and their contributions, in basic and applied research.
C1 [Sharkey, L. C.] Univ Minnesota, St Paul, MN 55108 USA.
[Simpson, R. M.] NCI, Bethesda, MD 20892 USA.
[Wellman, M. L.] Ohio State Univ, Columbus, OH 43210 USA.
[Craig, L. E.] Univ Tennessee, Knoxville, TN USA.
[Kock, N. D.] Wake Forrest Univ, Winston Salem, NC USA.
[Miller, M. A.] Purdue Univ, W Lafayette, IN 47907 USA.
[Harris, R. K.] Univ Georgia, Athens, GA 30602 USA.
[Munson, L.] Univ Calif Davis, Davis, CA 95616 USA.
RP Sharkey, LC (reprint author), C339 VMC, St Paul, MN 55108 USA.
EM shark009@umn.edu
OI Craig, Linden/0000-0003-0013-7544
NR 10
TC 1
Z9 1
U1 4
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
EI 1544-2217
J9 VET PATHOL
JI Vet. Pathol.
PD JUL
PY 2012
VL 49
IS 4
BP 581
EP 585
DI 10.1177/0300985811420583
PG 5
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 961SN
UT WOS:000305489100001
PM 21971986
ER
PT J
AU Michaud, CR
Ragland, DR
Shea, KI
Zerfas, PM
Kastenmayer, RJ
St Claire, MC
Elkins, WR
Gozalo, AS
AF Michaud, C. R.
Ragland, D. R.
Shea, K. I.
Zerfas, P. M.
Kastenmayer, R. J.
St Claire, M. C.
Elkins, W. R.
Gozalo, A. S.
TI Spontaneous Pulmonary Alveolar Proteinosis in Captive "Moustached
Tamarins" (Saguinus mystax)
SO VETERINARY PATHOLOGY
LA English
DT Article
DE nonhuman primate; lung; surfactant proteins; immunohistochemistry;
electron microscopy
ID COLONY-STIMULATING FACTOR; PATHOGENESIS; PATHOLOGY; KL-6
AB Pulmonary alveolar proteinosis is a rare human disease characterized by accumulation of surfactant in alveoli without generating an inflammatory response. Lung lesions resembling pulmonary alveolar proteinosis were observed in 7 adult tamarins (5 males and 2 females). Gross lesions were characterized by areas of discoloration, slight bulging over the lung parenchyma, and occasional consolidation. Histologic examination of tamarin lung samples revealed intra-alveolar accumulation of amorphous, amphophilic, periodic acid-Schiff-positive, finely granular to dense material. In some cases, type II pneumocyte hypertrophy and hyperplasia were observed with pleural and septal thickening and fibrosis. Large numbers of intra-alveolar foamy macrophages were noted surrounding and/or in the vicinity of the lesions. Immunohistochemical analysis of the lung lesions using polyclonal (surfactant proteins A, B, and C) and monoclonal (surfactant protein D) antibodies revealed the granular material to be composed largely of surfactant protein B, followed by surfactant protein A. Surfactant proteins C and D were present in lesser quantities, with the latter observed surrounding the lipoproteinaceous deposits. Transmission electron microscopy of the affected lungs showed numerous, irregularly shaped osmiophilic lamellar bodies in type II pneumocytes. The cytoplasm in alveolar macrophages was expanded, containing ingested surfactant with swollen mitochondria and rough endoplasmic reticulum. Thoracic radiographs, available in 1 animal, depicted the lesions as small multifocal opacities randomly distributed in cranial and diaphragmatic lung lobes. This is, to the authors' knowledge, the first report of spontaneous pulmonary alveolar proteinosis in nonhuman primates.
C1 [Michaud, C. R.; Shea, K. I.; Kastenmayer, R. J.; Elkins, W. R.; Gozalo, A. S.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
[Ragland, D. R.; St Claire, M. C.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Ragland, D. R.] Charles River Labs, Germantown, MD USA.
[Shea, K. I.; Gozalo, A. S.] SoBran Inc, Bethesda, MD USA.
[Zerfas, P. M.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
RP Gozalo, AS (reprint author), 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gozaloa@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases (NIAID), Comparative Medicine Branch, the Office of
Research Services; NIAID
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases (NIAID), Comparative Medicine Branch, the Office of
Research Services, and a NIAID contract to SoBran Inc. We thank Dr
Robert Purcell and Dr Sue Emerson for kindly letting us use tamarin
tissue samples from their previous studies and Dr Richard Herbert for
providing Saguinus mystax radiographs and tissue samples.
NR 26
TC 1
Z9 1
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
J9 VET PATHOL
JI Vet. Pathol.
PD JUL
PY 2012
VL 49
IS 4
BP 629
EP 635
DI 10.1177/0300985811412619
PG 7
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 961SN
UT WOS:000305489100010
PM 21734058
ER
PT J
AU Ku, STH
AF Ku, Sharon Tsai-hsuan
TI Forming interdisciplinary expertise: one organization's journey on the
road to translational nanomedicine
SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
LA English
DT Review
ID UNITED-STATES; NANOTECHNOLOGY; DISCIPLINE; HISTORY; SCIENCE
AB This paper provides a sociological account of how researchers of different disciplines become experts in translational nanomedicine. Using a case study of the Nanotechnology Characterization Laboratory (NCL) at the National Cancer Institute (NCI), the author argues that the relationship between the different disciplines involved in translational nanomedicine should be understood in the broader sociopolitical context of the boundary politics between the academy, industry, and government. This study suggests that the process of training the nanobio expert is not simply a process of inculcating skills; it is also a process of institution building. In the case of the NCL, sustaining the laboratory's existence at the interface between the university, industry, and government informed how researchers practiced interdisciplinarity and cultivated their interdisciplinary expertise. It required mobilizing institutional resources through administrative/managerial strategies. Viewing the formation of a professional identity as a social process helps clarify the meaning of interdisciplinarity and provides insight in evaluating the performance of interdisciplinary collaboration and the design of nanoscience education. WIREs Nanomed Nanobiotechnol 2012, 4:366377. doi: 10.1002/wnan.1172 For further resources related to this article, please visit the .
C1 NIH, Off Hist, Bethesda, MD 20892 USA.
RP Ku, STH (reprint author), NIH, Off Hist, Bldg 10, Bethesda, MD 20892 USA.
EM sharon.ku@nih.gov
FU NCI; NIH Office of History
FX This project is co-sponsored by the NCI and NIH Office of History. I
gratefully acknowledge the support and cooperation of the NCL staff,
especially Scott McNeil and Marina Dobrovolskaia.
NR 26
TC 0
Z9 0
U1 2
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1939-5116
EI 1939-0041
J9 WIRES NANOMED NANOBI
JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol.
PD JUL-AUG
PY 2012
VL 4
IS 4
BP 366
EP 377
DI 10.1002/wnan.1172
PG 12
WC Nanoscience & Nanotechnology; Medicine, Research & Experimental
SC Science & Technology - Other Topics; Research & Experimental Medicine
GA 961JO
UT WOS:000305460900002
ER
PT J
AU Lansford, JE
Skinner, AT
Sorbring, E
Di Giunta, L
Deater-Deckard, K
Dodge, KA
Malone, PS
Oburu, P
Pastorelli, C
Tapanya, S
Tirado, LMU
Zelli, A
Al-Hassan, SM
Alampay, LP
Bacchini, D
Bombi, AS
Bornstein, MH
Chang, L
AF Lansford, Jennifer E.
Skinner, Ann T.
Sorbring, Emma
Di Giunta, Laura
Deater-Deckard, Kirby
Dodge, Kenneth A.
Malone, Patrick S.
Oburu, Paul
Pastorelli, Concetta
Tapanya, Sombat
Tirado, Liliana Maria Uribe
Zelli, Arnaldo
Al-Hassan, Suha M.
Pena Alampay, Liane
Bacchini, Dario
Bombi, Anna Silvia
Bornstein, Marc H.
Chang, Lei
TI Boys' and Girls' Relational and Physical Aggression in Nine Countries
SO AGGRESSIVE BEHAVIOR
LA English
DT Article
DE cross-cultural; gender; international; physical aggression; relational
aggression
ID SOCIAL-PSYCHOLOGICAL ADJUSTMENT; CROSS-CULTURAL RESEARCH;
GENDER-DIFFERENCES; CHILDHOOD; CHILDRENS; BEHAVIOR; PEER; ADOLESCENTS;
CONTINUITY; OVERT
AB Distinguishing between relational and physical aggression has become a key feature of many developmental studies in North America and Western Europe, but very little information is available on relational and physical aggression in more diverse cultural contexts. This study examined the factor structure of, associations between, and gender differences in relational and physical aggression in China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States. Children ages 710 years (N = 1,410) reported on their relationally and physically aggressive behavior. Relational and physical aggression shared a common factor structure across countries. In all nine countries, relational and physical aggression were significantly correlated (average r = .49). Countries differed in the mean levels of both relational and physical aggression that children reported using and with respect to whether children reported using more physical than relational aggression or more relational than physical aggression. Boys reported being more physically aggressive than girls across all nine countries; no consistent gender differences emerged in relational aggression. Despite mean-level differences in relational and physical aggression across countries, the findings provided support for cross-country similarities in associations between relational and physical aggression as well as links between gender and aggression. Aggr. Behav. 38:298-308, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Lansford, Jennifer E.] Duke Univ, Ctr Child & Family Policy, Durham, NC 27708 USA.
[Sorbring, Emma] Univ West, Trollhattan, Sweden.
[Di Giunta, Laura; Pastorelli, Concetta; Tirado, Liliana Maria Uribe; Bombi, Anna Silvia] Univ Roma La Sapienza, Rome, Italy.
[Deater-Deckard, Kirby] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA.
[Malone, Patrick S.] Univ S Carolina, Columbia, SC 29208 USA.
[Oburu, Paul] Maseno Univ, Kisumu, Kenya.
[Tapanya, Sombat] Chiang Mai Univ, Chiang Mai 50000, Thailand.
[Tirado, Liliana Maria Uribe] Univ San Buenaventura, Medellin, Colombia.
[Zelli, Arnaldo] Univ Rome Foro Ital, Rome, Italy.
[Al-Hassan, Suha M.] Hashemite Univ, Zarqa, Jordan.
[Pena Alampay, Liane] Ateneo Manila Univ, Quezon City, Philippines.
[Bacchini, Dario] Univ Naples 2, Naples, Italy.
[Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Chang, Lei] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China.
RP Lansford, JE (reprint author), Duke Univ, Ctr Child & Family Policy, Box 90545, Durham, NC 27708 USA.
EM Lansford@duke.edu
RI Malone, Patrick/F-6851-2011; Eclevia, Marian/I-6486-2013; ZELLI,
ARNALDO/N-2333-2015;
OI Malone, Patrick/0000-0002-8364-6987; ZELLI, ARNALDO/0000-0003-4020-8159;
Bacchini, Dario/0000-0001-6140-9377
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [RO1-HD054805]; Fogarty International Center [RO3-TW008141];
National Institute on Drug Abuse [K01DA024116, 2K05 DA015226];
NIH/NICHD; [2KO5DA015226]
FX Contract grant sponsor: Eunice Kennedy Shriver National Institute of
Child Health and Human Development; Contract grant number: RO1-HD054805;
Contract grant sponsor: Fogarty International Center; Contract grant
number: RO3-TW008141; Contract grant number: 2KO5DA015226; Contract
grant sponsor: National Institute on Drug Abuse; Contract grant sponsor:
National Institute on Drug Abuse; Contract grant number: K01DA024116;
Contract grant sponsor: Intramural Research Program of the NIH/NICHD.;
KAD is supported by Senior Scientist award 2K05 DA015226 from the
National Institute on Drug Abuse. PSM is supported by grant K01DA024116
from the National Institute on Drug Abuse. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIH or NICHD.
NR 62
TC 29
Z9 29
U1 3
U2 47
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0096-140X
EI 1098-2337
J9 AGGRESSIVE BEHAV
JI Aggressive Behav.
PD JUL-AUG
PY 2012
VL 38
IS 4
BP 298
EP 308
DI 10.1002/ab.21433
PG 11
WC Behavioral Sciences; Psychology, Multidisciplinary
SC Behavioral Sciences; Psychology
GA 957QP
UT WOS:000305178100006
PM 23935227
ER
PT J
AU Gibson, TM
Wang, SS
Cerhan, JR
Maurer, MJ
Hartge, P
Habermann, TM
Davis, S
Cozen, W
Lynch, CF
Severson, RK
Rothman, N
Chanock, SJ
Morton, LM
AF Gibson, Todd M.
Wang, Sophia S.
Cerhan, James R.
Maurer, Matthew J.
Hartge, Patricia
Habermann, Thomas M.
Davis, Scott
Cozen, Wendy
Lynch, Charles F.
Severson, Richard K.
Rothman, Nathaniel
Chanock, Stephen J.
Morton, Lindsay M.
TI Inherited genetic variation and overall survival following follicular
lymphoma
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; UNITED-STATES; HUMAN COLON;
CANCER; POLYMORPHISMS; PREDICTION; PATTERNS; BIOLOGY
AB Follicular lymphoma (FL) has variable progression and survival, and improved identification of patients at high risk for progression would aid in identifying patients most likely to benefit from alternative therapy. In a sample of 244 FL cases identified during a population-based case-control study of non-Hodgkin lymphoma (NHL), we examined 6,679 tag SNPs in 488 gene regions for associations with overall FL survival. Over a median follow-up of 89 months with 65 deaths in this preliminary study, we identified 5 gene regions (BMP7, GALNT12, DUSP2, GADD45B, and ADAM17) that were associated with overall survival from FL. Results did not meet the criteria for statistical significance after adjustment for multiple hypothesis testing. These results, which support a role for host factors in determining the variable progression of FL, serve as an initial examination that can inform future studies of genetic variation and FL survival. However, they require replication in independent populations, as well as assessment in rituximab-treated patients.
C1 [Gibson, Todd M.; Hartge, Patricia; Rothman, Nathaniel; Chanock, Stephen J.; Morton, Lindsay M.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD USA.
[Gibson, Todd M.] NCI, Dept Hlth & Human Serv, Canc Prevent Fellowship Program, Ctr Canc Training,NIH, Rockville, MD USA.
[Wang, Sophia S.] Beckman Res Inst & City Hope, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA.
[Cerhan, James R.; Maurer, Matthew J.; Habermann, Thomas M.] Mayo Clin, Coll Med, Div Epidemiol, Rochester, MN USA.
[Davis, Scott] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
[Davis, Scott] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
[Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Severson, Richard K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
[Severson, Richard K.] Karmanos Canc Inst, Detroit, MI USA.
[Chanock, Stephen J.] NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD USA.
RP Gibson, TM (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 6120 Execut Blvd, Rockville, MD USA.
EM gibsontm@mail.nih.gov
RI Morton, Lindsay/B-5234-2015;
OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N01 PC065064, N01
PC067008, R01-CA96704, N01 PC067010, N01-PC-67009, N02-PC-71105, P30
CA015704, P50 CA097274, R01 CA096704, N01 PC067009]
NR 27
TC 5
Z9 5
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUL
PY 2012
VL 87
IS 7
BP 724
EP 726
DI 10.1002/ajh.23184
PG 3
WC Hematology
SC Hematology
GA 958BA
UT WOS:000305209700020
PM 22473939
ER
PT J
AU Walker, R
Hunt, YM
Olivier, J
Grothe, KB
Dubbert, PM
Burke, RS
Cushman, WC
AF Walker, Robrina
Hunt, Yvonne M.
Olivier, Jake
Grothe, Karen B.
Dubbert, Patricia M.
Burke, Randy S.
Cushman, William C.
TI Descriptive Characteristics and Cluster Analysis of Male Veteran
Hazardous Drinkers in an Alcohol Moderation Intervention
SO AMERICAN JOURNAL ON ADDICTIONS
LA English
DT Article
ID SUBSTANCE USE DISORDERS; GENERAL-POPULATION; DRINKING BEHAVIOR;
GENDER-DIFFERENCES; MARITAL-STATUS; OLDER WOMEN; DSM-IV; DEPENDENCE;
SUBTYPES; CLASSIFICATION
AB Current efforts underway to develop the fifth edition of the Diagnostic and Statistical Manual (DSM-5) have reignited discussions for classifying the substance use disorders. This study's aim was to contribute to the understanding of abusive alcohol use and its validity as a diagnosis. Cluster analysis was used to identify relatively homogeneous groups of hazardous, nondependent drinkers by using data collected from the Prevention and Treatment of Hypertension Study (PATHS), a multisite trial that examined the ability of a cognitive-behavioral-based alcohol reduction intervention, compared to a control condition, to reduce alcohol use. Participants for this study (N = 511) were male military veterans. Variables theoretically associated with alcohol use (eg, demographic, tobacco use, and mental health) were used to create the clusters and a priori, empirically based external criteria were used to assess discriminant validity. Bivariate correlations among cluster variables were generally consistent with previous findings in the literature. Analyses of internal and discriminant validity of the identified clusters were largely nonsignificant, suggesting meaningful differences between clusters could not be identified. Although the typology literature has contributed supportive validity for the alcohol dependence diagnosis, this study's results do not lend supportive validity for the construct of alcohol abuse. (Am J Addict 2012;21:335-342)
C1 [Walker, Robrina] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[Hunt, Yvonne M.] NCI, Tobacco Control Res Branch, NIH, Bethesda, MD 20892 USA.
[Olivier, Jake] Univ New S Wales, NSW Injury Risk Management Res Ctr, Sydney, Australia.
[Grothe, Karen B.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA.
[Dubbert, Patricia M.] Vet Affairs Geriatr Res Educ & Clin Ctr, Little Rock, AR USA.
[Dubbert, Patricia M.] S Cent Vet Affairs Mental Illness Res Educ & Clin, N Little Rock, AR USA.
[Burke, Randy S.] GV Sonny Montgomery VA Med Ctr, Jackson, MS USA.
[Burke, Randy S.] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA.
[Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA.
RP Walker, R (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Robrina.Walker@utsouthwestern.edu
RI Olivier, Jake/D-2034-2012
OI Olivier, Jake/0000-0002-3144-4507
FU NHLBI NIH HHS [1Y01 HC 90103-00]
NR 44
TC 0
Z9 0
U1 3
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1055-0496
J9 AM J ADDICTION
JI Am. J. Addict.
PD JUL-AUG
PY 2012
VL 21
IS 4
BP 335
EP 342
DI 10.1111/j.1521-0391.2012.00247.x
PG 8
WC Substance Abuse
SC Substance Abuse
GA 956XH
UT WOS:000305122400006
PM 22691012
ER
PT J
AU Momtazi, S
AF Momtazi, Saeed
TI Methamphetamine Induced Psychotic Disorder in Iran, Psychopathology and
Demographic Features
SO AMERICAN JOURNAL ON ADDICTIONS
LA English
DT Meeting Abstract
C1 [Momtazi, Saeed] Univ Calif Los Angeles, Integrated Subst Abuse Program, NIDA, Los Angeles, CA 90024 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1055-0496
J9 AM J ADDICTION
JI Am. J. Addict.
PD JUL-AUG
PY 2012
VL 21
IS 4
MA 15
BP 386
EP 387
PG 2
WC Substance Abuse
SC Substance Abuse
GA 956XH
UT WOS:000305122400026
ER
PT J
AU Koshiol, J
Lin, SW
AF Koshiol, Jill
Lin, Shih-Wen
TI Can Tissue-Based Immune Markers be Used for Studying the Natural History
of Cancer?
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Editorial Material
ID REGULATORY T-CELLS; GENE-EXPRESSION SIGNATURE; NON-HODGKIN-LYMPHOMA;
HUMAN-PAPILLOMAVIRUS; CIGARETTE-SMOKING; PROGNOSTIC-SIGNIFICANCE; LUNG
ADENOCARCINOMA; CERVICAL NEOPLASIA; PROTEIN EXPRESSION;
COLORECTAL-CANCER
C1 [Koshiol, Jill; Lin, Shih-Wen] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Lin, Shih-Wen] NCI, Canc Prevent Fellowship Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Koshiol, J (reprint author), NCI, Infect & Immunepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7070, Rockville, MD 20852 USA.
EM koshiolj@mail.nih.gov
FU Intramural NIH HHS [ZIA CP010218-01]
NR 92
TC 8
Z9 8
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD JUL
PY 2012
VL 22
IS 7
BP 520
EP 530
DI 10.1016/j.annepidem.2012.03.001
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 959GT
UT WOS:000305301600008
PM 22481034
ER
PT J
AU Zhang, F
Huang, XL
Zhu, L
Guo, N
Niu, G
Swierczewska, M
Lee, S
Xu, H
Wang, AY
Mohamedali, KA
Rosenblum, MG
Lu, GM
Chen, XY
AF Zhang, Fan
Huang, Xinglu
Zhu, Lei
Guo, Ning
Niu, Gang
Swierczewska, Magdalena
Lee, Seulki
Xu, Hong
Wang, Andrew Y.
Mohamedali, Khalid A.
Rosenblum, Michael G.
Lu, Guangming
Chen, Xiaoyuan
TI Noninvasive monitoring of orthotopic glioblastoma therapy response using
RGD-conjugated iron oxide nanoparticles
SO BIOMATERIALS
LA English
DT Article
DE Magnetic resonance imaging (MRI); Iron oxide nanoparticles (IONPs); RGD
peptides; Tumor targeting; Therapy response
ID RESONANCE-IMAGING CONTRAST; BLOOD-BRAIN-BARRIER; IN-VIVO; INTEGRIN
ALPHA(V)BETA(3); MAGNETIC NANOPARTICLES; MALIGNANT GLIOMA; SOLID TUMORS;
VEGF(121)/RGEL; NANOCRYSTALS; XENOGRAFTS
AB Noninvasive imaging techniques have been considered important strategies in the clinic to monitor tumor early response to therapy. In the present study, we applied RGD peptides conjugated to iron oxide nanoparticles (IONP-RGD) as contrast agents in magnetic resonance imaging (MRI) to noninvasively monitor the response of a vascular disrupting agent VEGF(121)/rGel in an orthotopic glioblastoma model. RGD peptides were firstly coupled to IONPs coated with a crosslinked PEGylated amphiphilic triblock copolymer. In vitro binding assays confirmed that cellular uptake of particles was mainly dependent on the interaction between RGD and integrin alpha(v)beta(3) of human umbilical vein endothelial cells (HUVEC). The tumor targeting of IONP-RGD was observed in an orthotopic U87 glioblastoma model. Finally, noninvasive monitoring of the tumor response to VEGF(121)/rGel therapy at early stages of treatment was successfully accomplished using IONP-RGD as a contrast agent for MRI, a superior method over common anatomical approaches which are based on tumor size measurements. This preclinical study can accelerate anticancer drug development and promote clinical translation of nanoprobes. Published by Elsevier Ltd.
C1 [Huang, Xinglu; Zhu, Lei; Niu, Gang; Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Zhang, Fan; Lu, Guangming] Nanjing Univ, Dept Radiol, Nanjing Jinling Hosp, Clin Sch,Med Coll, Nanjing 210002, Jiangsu, Peoples R China.
[Zhu, Lei; Guo, Ning; Chen, Xiaoyuan] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361005, Peoples R China.
[Xu, Hong; Wang, Andrew Y.] Ocean NanoTech LLC, Springdale, AR 72764 USA.
[Mohamedali, Khalid A.; Rosenblum, Michael G.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77230 USA.
RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
EM cjr.luguangming@vip.163.com; shawn.chen@nih.gov
RI Zhu, Lei/P-9786-2016
OI Zhu, Lei/0000-0002-1820-4795
FU NIBIB, NIH, NCI [R41CA137960-01]; Henry M. Jackson Foundation; National
Science Foundation of China (NSFC) [81028009]; NSFC [30930028]
FX This work was supported in part, by the Intramural Research Program of
the NIBIB, NIH, NCI R41CA137960-01, the Henry M. Jackson Foundation, the
International Cooperative Program of the National Science Foundation of
China (NSFC) (81028009), and the NSFC grant No. 30930028.
NR 35
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U1 2
U2 71
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 JUL
PY 2012
VL 33
IS 21
BP 5414
EP 5422
DI 10.1016/j.biomaterials.2012.04.032
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 956QY
UT WOS:000305105400024
PM 22560667
ER
PT J
AU Troisi, R
Altantsetseg, D
Davaasambuu, G
Rich-Edwards, J
Davaalkham, D
Tretli, S
Hoover, RN
Frazier, AL
AF Troisi, Rebecca
Altantsetseg, Dalkhjav
Davaasambuu, Ganmaa
Rich-Edwards, Janet
Davaalkham, Dambadarjaa
Tretli, Steinar
Hoover, Robert N.
Frazier, A. Lindsay
TI Breast cancer incidence in Mongolia
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Mongolia; Breast cancer; Urban-rural; Asia; International
ID ASIAN-AMERICAN WOMEN; HEPATITIS-C VIRUS; HORMONE LEVELS; VITAMIN-D;
RISK; PREVALENCE; PATTERNS; BIRTH; RATES; AGE
AB Data on international variation in breast cancer incidence may help to identify additional risk factors. Substantially lower breast cancer rates in Asia than in North America and Western Europe are established, but differences within Asia have been largely ignored despite heterogeneity in lifestyles and environments. Mongolia's breast cancer experience is of interest because of its shared genetics but vastly different diet compared with other parts of Asia.
Age-standardized breast cancer incidence and mortality rates obtained from the International Association of Cancer Registries are presented for several Asian countries. Mongolian incidence rates obtained from its cancer registry describe incidence within the country.
Breast cancer incidence in Mongolia (age standardized 8.0/100,000) is almost a third of rates in China (21.6/100,000), and over five times that of Japan (42.7/100,000) and Russia (43.2/100,000). Rates within Mongolia appear to have increased slightly over the last decade and are higher in urban than rural areas (annual percentage increase of age-standardized rates from 1998 to 2005 was 3.60 and 2.57 %, respectively). The increase in breast cancer incidence with age plateaus at menopause, as in other Asian populations.
Mongolia's low breast cancer incidence is of particular interest because of their unusual diet (primarily red meat and dairy) compared with other Asian countries. More intensive study of potential dietary, reproductive and lifestyle factors in Mongolia with comparison to other Asian populations may provide more clarity in what drives the international breast cancer rate differences.
C1 [Troisi, Rebecca] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03756 USA.
[Troisi, Rebecca; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Altantsetseg, Dalkhjav] Mongolian Natl Oncol Ctr, Ulaanbaator, Mongol Peo Rep.
[Davaasambuu, Ganmaa] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Rich-Edwards, Janet] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA.
[Davaalkham, Dambadarjaa] Hlth Sci Univ Mongolia, Ulaanbaator, Mongol Peo Rep.
[Tretli, Steinar] Canc Registry Norway, Oslo, Norway.
[Frazier, A. Lindsay] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Troisi, R (reprint author), Dartmouth Hitchcock Med Ctr, Room 854,7297 Rubin Bldg,1 Med Ctr Dr, Lebanon, NH 03756 USA.
EM troisir@mail.nih.gov
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, US Department of Health and Human
Services
FX We thank Ms. Narantuya Khad, senior officer and research fellow in the
Public Health Sector Policy Research Unit of the Health Department, for
her work at the Registry. This work was supported by the Division of
Cancer Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health, US Department of Health and Human Services.
NR 35
TC 11
Z9 13
U1 4
U2 10
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUL
PY 2012
VL 23
IS 7
BP 1047
EP 1053
DI 10.1007/s10552-012-9973-2
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 953WW
UT WOS:000304905400006
PM 22543542
ER
PT J
AU Friesen, MC
Betenia, N
Costello, S
Eisen, EA
AF Friesen, Melissa C.
Betenia, Nicole
Costello, Sadie
Eisen, Ellen A.
TI Metalworking fluid exposure and cancer risk in a retrospective cohort of
female autoworkers
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Metalworking fluids; Cancer mortality; Colon cancer; Women's health;
Cohort studies
ID AUTOMOBILE-INDUSTRY; OCCUPATIONAL-CANCER; BLADDER-CANCER; BREAST-CANCER;
UNITED-STATES; LUNG-CANCER; MORTALITY; GENDER; WOMEN; EPIDEMIOLOGY
AB Metalworking fluids (MWFs) have been associated with cancer of several sites, but the risks have been primarily examined in men or in studies that adjusted for gender in analyses. To evaluate whether risks were similar in women, we report cancer mortality risk among 4,825 female autoworkers within the united autoworkers-general motors autoworkers cohort.
Standardized mortality rates (SMRs) were calculated based on Michigan death rates (1980-2004). Internal comparisons (1941-2004) were examined using Cox regression for straight, soluble, and synthetic MWFs, and their corresponding oil- and water-based fractions.
MWF exposure levels in the female cohort were generally less than two-third the MWF levels in the male cohort. Female autoworkers had an excess of cancer from all sites (SMR, 1.10; 95 % confidence interval (CI), 0.98-1.22) and lung cancer (SMR, 2.08; 95 % CI, 1.71-2.52). Colon cancer risk increased with straight (mineral oil) MWF exposure (exposure > median; hazard ratio = 3.1; 95 % CI, 1.2-8.0). A protective effect was observed for ovarian cancer with the soluble MWFs and water-based MWF metrics. Although bladder, rectal, and laryngeal cancers and malignant melanoma have been associated with straight MWF exposure and pancreatic cancer with synthetic MWF in men, there were too few deaths in this female subcohort to examine exposure-response relations for these sites. Results were null for lung and breast cancer.
Our findings support an association between colon cancer and straight MWFs, but we found limited evidence of risk for other tumor sites at the lower exposure levels experienced by the female autoworkers.
C1 [Friesen, Melissa C.] NCI, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA.
[Betenia, Nicole; Costello, Sadie; Eisen, Ellen A.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
RP Friesen, MC (reprint author), NCI, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM friesenmc@mail.nih.gov; eeisen@berkeley.edu
RI Friesen, Melissa/A-5362-2009
FU National Institute for Occupational Safety and Health, Centers for
Disease Control and Prevention, Department of Health and Human Services
[R01 OH008927]
FX This work was supported by Grant R01 OH008927 from the National
Institute for Occupational Safety and Health, Centers for Disease
Control and Prevention, Department of Health and Human Services.
NR 40
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Z9 2
U1 0
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUL
PY 2012
VL 23
IS 7
BP 1075
EP 1082
DI 10.1007/s10552-012-9976-z
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 953WW
UT WOS:000304905400009
PM 22562220
ER
PT J
AU Major, JM
Oliver, MN
Doubeni, CA
Hollenbeck, AR
Graubard, BI
Sinha, R
AF Major, Jacqueline M.
Oliver, M. Norman
Doubeni, Chyke A.
Hollenbeck, Albert R.
Graubard, Barry I.
Sinha, Rashmi
TI Socioeconomic status, healthcare density, and risk of prostate cancer
among African American and Caucasian men in a large prospective study
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Cohort; Prostate cancer; Multilevel; Neighborhood; Socioeconomic
deprivation; Healthcare availability; Census
ID ASSOCIATION; DIAGNOSIS; UROLOGIST; SURVIVAL; IMPACT
AB The purpose of this study was to separately examine the impact of neighborhood socioeconomic deprivation and availability of healthcare resources on prostate cancer risk among African American and Caucasian men.
In the large, prospective NIH-AARP Diet and Health Study, we analyzed baseline (1995-1996) data from adult men, aged 50-71 years. Incident prostate cancer cases (n = 22,523; 1,089 among African Americans) were identified through December 2006. Lifestyle and health risk information was ascertained by questionnaires administered at baseline. Area-level socioeconomic indicators were ascertained by linkage to the US Census and the Area Resource File. Multilevel Cox models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs).
A differential effect among African Americans and Caucasians was observed for neighborhood deprivation (p-interaction = 0.04), percent uninsured (p-interaction = 0.02), and urologist density (p-interaction = 0.01). Compared to men living in counties with the highest density of urologists, those with fewer had a substantially increased risk of developing advanced prostate cancer (HR = 2.68, 95 % CI = 1.31, 5.47) among African American.
Certain socioeconomic indicators were associated with an increased risk of prostate cancer among African American men compared to Caucasians. Minimizing differences in healthcare availability may be a potentially important pathway to minimizing disparities in prostate cancer risk.
C1 [Major, Jacqueline M.; Graubard, Barry I.; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA.
[Oliver, M. Norman] Univ Virginia, Sch Med, Dept Family Med, Charlottesville, VA 22908 USA.
[Doubeni, Chyke A.] Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA 01655 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC 20049 USA.
RP Major, JM (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM Jacqueline.major@nih.gov
RI Sinha, Rashmi/G-7446-2015;
OI Sinha, Rashmi/0000-0002-2466-7462; Doubeni, Chyke/0000-0001-7495-0285
FU NIH, National Cancer Institute
FX 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. This research was supported [in part] by the Intramural
Research Program of the NIH, National Cancer Institute.
NR 29
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U1 2
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUL
PY 2012
VL 23
IS 7
BP 1185
EP 1191
DI 10.1007/s10552-012-9988-8
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 953WW
UT WOS:000304905400019
PM 22674292
ER
PT J
AU Sanchez, MA
Vinson, CA
La Porta, M
Viswanath, K
Kerner, JF
Glasgow, RE
AF Sanchez, Michael A.
Vinson, Cynthia A.
La Porta, Madeline
Viswanath, Kasisomayajula
Kerner, Jon F.
Glasgow, Russell E.
TI Evolution of Cancer Control PLANET: moving research into practice
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Dissemination; Implementation; Evidence-based; Cancer control; Program
planning; Internet; Web resources
ID EVIDENCE-BASED INTERVENTIONS; PROMOTE PHYSICAL-ACTIVITY; PUBLIC-HEALTH;
PARTNERSHIPS; DEPARTMENTS; PREVENTION; DIFFUSION; EDUCATION; TRENDS;
POLICY
AB Evidence-based interventions (EBIs) are not broadly implemented, despite widespread availability of programs, policies, and guidelines. Systematic processes for integrating EBIs with community preference remain challenging for cancer control and prevention, as well as other areas. The Cancer Control P.L.A.N.E.T. (P.L.A.N.E.T) Web portal provides a platform to access data, EBIs, and resources to foster local partnerships and assist public health researchers and practitioners design, implement, and evaluate evidence-based cancer control programs. This article summarizes the evolution of P.L.A.N.E.T. and describes effective and innovative Web 2.0 strategies to increase Web visits, create more interactive platforms for researchers and practitioners to integrate evidence-based resources, community preferences, and the complex context in which programs and policies are implemented. Lessons learned could benefit public health settings and reach low-income, high-risk communities. Researchers, community practitioners, and government partnerships should continue to develop and test innovative ways to address pressing issues in cancer control, health disparities, and health delivery.
C1 [Sanchez, Michael A.; Vinson, Cynthia A.; La Porta, Madeline; Glasgow, Russell E.] NCI, EPN, Rockville, MD 20852 USA.
[Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kerner, Jon F.] Canadian Partnership Canc, Toronto, ON, Canada.
RP Sanchez, MA (reprint author), NCI, EPN, 6130 Execut Blvd,Room 6131A, Rockville, MD 20852 USA.
EM sanchezgarciama@mail.nih.gov
OI Kerner, Jon/0000-0002-8792-3830
FU National Cancer Institute [CA132651]
FX The findings and conclusions in this report are those of the authors and
do not necessarily represent the views of the National Cancer Institute
or the Canadian Partnership Against Cancer. Viswanath's effort was
funded by a grant from the National Cancer Institute, CA132651.
Christopher Politis of the Primary Prevention Program of Canadian
Partnership Against Cancer provided additional support for data
analysis.
NR 30
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U1 1
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUL
PY 2012
VL 23
IS 7
BP 1205
EP 1212
DI 10.1007/s10552-012-9987-9
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 953WW
UT WOS:000304905400021
PM 22674294
ER
PT J
AU Kibe, R
Zhang, S
Guo, D
Marrero, L
Tsien, F
Rodriguez, P
Khan, S
Zieske, A
Huang, J
Li, W
Durum, SK
Iwakuma, T
Cui, Y
AF Kibe, R.
Zhang, S.
Guo, D.
Marrero, L.
Tsien, F.
Rodriguez, P.
Khan, S.
Zieske, A.
Huang, J.
Li, W.
Durum, S. K.
Iwakuma, T.
Cui, Y.
TI IL-7R alpha deficiency in p53(null) mice exacerbates thymocyte telomere
erosion and lymphomagenesis
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
DE IL-7R alpha; p53; telomere dysfunction; genomic instability;
lymphomagenesis
ID SEVERE COMBINED IMMUNODEFICIENCY; DNA-DAMAGE CHECKPOINT; OF-FUNCTION
MUTATIONS; P53; APOPTOSIS; TUMORIGENESIS; DYSFUNCTION; MOUSE; IL7R;
PHOSPHORYLATION
AB Interleukin-7 (IL-7) is an essential T-cell survival cytokine. IL-7 receptor (IL-7R alpha) deficiency severely impairs T-cell development due to substantial apoptosis. We hypothesized that IL-7R alpha(null)-induced apoptosis is partially contributed by an elevated p53 activity. To investigate the genetic association of IL-7/IL-7R alpha signaling with the p53 pathway, we generated IL-7R alpha(null)p53(null) (DKO) mice. DKO mice exhibited a marked reduction of apoptosis in developing T cells and an augmented thymic lymphomagenesis with telomere erosions and exacerbated chromosomal anomalies, including chromosome duplications, breaks, and translocations. In particular, Robertsonian translocations, in which telocentric chromosomes fuse at the centromeric region, and a complete loss of telomeres at the fusion site occurred frequently in DKO thymic lymphomas. Cellular and molecular investigations revealed that IL-7/IL-7R alpha signaling withdrawal diminished the protein synthesis of protection of telomere 1 (POT1), a subunit of telomere protective complex shelterin, leading to telomere erosion and the activation of the p53 pathway. Blockade of IL-7/IL-7R alpha signaling in IL-7-dependent p53(null) cells reduced POT1 expression and caused telomere and chromosome abnormalities similar to those observed in DKO lymphomas. This study underscores a novel function of IL-7/IL-7R alpha during T-cell development in regulating telomere integrity via POT1 expression and provides new insights into cytokine-mediated survival signals and T-cell lymphomagenesis. Cell Death and Differentiation (2012) 19, 1139-1151; doi: 10.1038/cdd.2011.203; published online 27 January 2012
C1 [Kibe, R.; Zhang, S.; Marrero, L.; Khan, S.; Cui, Y.] Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, New Orleans, LA 70112 USA.
[Guo, D.; Tsien, F.; Iwakuma, T.; Cui, Y.] Dept Genet, New Orleans, LA 70112 USA.
[Tsien, F.; Rodriguez, P.; Iwakuma, T.; Cui, Y.] Dept Stanley Scott Canc Ctr, New Orleans, LA 70112 USA.
[Zieske, A.] Dept Pathol, New Orleans, LA 70112 USA.
[Huang, J.; Li, W.; Durum, S. K.] NCI, Sect Cytokines & Immun, Frederick, MD 21702 USA.
RP Cui, Y (reprint author), Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, 533 Bolivar St, New Orleans, LA 70112 USA.
EM ycui@lsuhsc.edu
FU LGTRC; LCRC; NIH [CA112065, P20RR021970, P20RR020152]
FX We thank Drs. Alistair Ramsay, Wanguo Liu, Jay K Kolls, and Drew Pardoll
for constructive suggestions; Ms. Heidi Davis for editorial assistance;
Drs. Beatriz Finkel-Jimenez, Sandra Burkett, Marilyn Li, and Kong Chen
for technical assistance; and Ms. Yunping Huang for animal breeding.
This work is supported in part by funds from the LGTRC, LCRC, NIH grants
to YC (CA112065 and P20RR021970) and TI (P20RR020152).
NR 40
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD JUL
PY 2012
VL 19
IS 7
BP 1139
EP 1151
DI 10.1038/cdd.2011.203
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 959EJ
UT WOS:000305295300006
PM 22281704
ER
PT J
AU Saavedra, JM
AF Saavedra, Juan M.
TI In Memoriam Zofia Zukowska, MD PhD
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Biographical-Item
C1 NIMH, Pharmacol Sect, Div Intramural Res Programs, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Div Intramural Res Programs, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
EM Saavedrj@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD JUL
PY 2012
VL 32
IS 5
SI SI
BP 643
EP 644
DI 10.1007/s10571-012-9855-x
PG 2
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 960OD
UT WOS:000305396900002
ER
PT J
AU Goldstein, DS
AF Goldstein, David S.
TI Stress, Allostatic Load, Catecholamines, and Other Neurotransmitters in
Neurodegenerative Diseases
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article; Proceedings Paper
CT 10th Symposium on Catecholamines and Other Neurotransmittersin Stress
CY JUN 25-30, 2011
CL Smolenice Castle, SLOVAKIA
DE Stress; Allostasis; Catecholamines; Homeostasis; Parkinson disease
ID ALPHA-SYNUCLEIN; PARKINSON-DISEASE; DOPAMINE; DENERVATION; METABOLITE;
ALDEHYDE; FAILURE
AB As populations age, the prevalence of geriatric neurodegenerative diseases will increase. These diseases generally are multifactorial, arising from complex interactions among genes, environment, concurrent morbidities, treatments, and time. This essay provides a concept for the pathogenesis of Lewy body diseases such as Parkinson disease, by considering them in the context of allostasis and allostatic load. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators-"homeostats." Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. "Allostatic load" refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of an idling car, the revolutions per minute of the engine can be maintained at any of a variety of levels (allostatic states). Just as allostatic load (cumulative wear and tear) reflects design and manufacturing variations, byproducts of combustion, and time, eventually leading to engine breakdown, allostatic load in catecholaminergic neurons might eventually lead to Lewy body diseases. Central to the argument is that catecholaminergic neurons leak vesicular contents into the cytoplasm continuously during life and that catecholamines in the neuronal cytoplasm are autotoxic. These neurons therefore depend on vesicular sequestration to limit autotoxicity of cytosolic transmitter. Parkinson disease might be a disease of the elderly because of allostatic load, which depends on genetic predispositions, environmental exposures, repeated stress-related catecholamine release, and time.
C1 Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, NIH, 10 Ctr Dr,MSC 1620,Bldg 10,Room 5N220, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU intramural research program of the National Institute of Neurological
Disorders and Stroke
FX Research leading to the concepts in this essay was supported by the
intramural research program of the National Institute of Neurological
Disorders and Stroke. The author thanks Drs. Yehonatan Sharabi, Basil
Eldadah, Graeme Eisenhofer, and Irwin J. Kopin for many valuable
discussions.
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PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
EI 1573-6830
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD JUL
PY 2012
VL 32
IS 5
SI SI
BP 661
EP 666
DI 10.1007/s10571-011-9780-4
PG 6
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 960OD
UT WOS:000305396900004
PM 22297542
ER
PT J
AU Saavedra, JM
AF Saavedra, Juan M.
TI Angiotensin II AT(1) Receptor Blockers Ameliorate Inflammatory Stress: A
Beneficial Effect for the Treatment of Brain Disorders
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article; Proceedings Paper
CT 10th Symposium on Catecholamines and Other Neurotransmittersin Stress
CY JUN 25-30, 2011
CL Smolenice Castle, SLOVAKIA
DE Brain Renin-Angiotensin system; Angiotensin II AT(1) receptor blockers;
Stress; Brain inflammation; Depression; Anxiety; Mood disorders;
Neurodegenerative disorders; Alzheimer's disease; Stroke; Cognition
ID SPONTANEOUSLY HYPERTENSIVE-RATS; INNATE IMMUNE-RESPONSE;
CEREBRAL-BLOOD-FLOW; TYPE-1 RECEPTOR; AT(2) RECEPTOR; MICROVASCULAR
INFLAMMATION; THERAPEUTIC INTERVENTIONS; VASCULAR INFLAMMATION; RETINAL
INFLAMMATION; ANTAGONIST LOSARTAN
AB Excessive allostatic load as a consequence of deregulated brain inflammation participates in the development and progression of multiple brain diseases, including but not limited to mood and neurodegenerative disorders. Inhibition of the peripheral and brain Renin-Angiotensin System by systemic administration of Angiotensin II AT(1) receptor blockers (ARBs) ameliorates inflammatory stress associated with hypertension, cold-restraint, and bacterial endotoxin administration. The mechanisms involved include: (a) decreased inflammatory factor production in peripheral organs and their release to the circulation; (b) reduced progression of peripherally induced inflammatory cascades in the cerebral vasculature and brain parenchyma; and (c) direct anti-inflammatory effects in cerebrovascular endothelial cells, microglia, and neurons. In addition, ARBs reduce bacterial endotoxin-induced anxiety and depression. Further pre-clinical experiments reveal that ARBs reduce brain inflammation, protect cognition in rodent models of Alzheimer's disease, and diminish brain inflammation associated with genetic hypertension, ischemia, and stroke. The anti-inflammatory effects of ARBs have also been reported in circulating human monocytes. Clinical studies demonstrate that ARBs improve mood, significantly reduce cognitive decline after stroke, and ameliorate the progression of Alzheimer's disease. ARBs are well-tolerated and extensively used to treat cardiovascular and metabolic disorders such as hypertension and diabetes, where inflammation is an integral pathogenic mechanism. We propose that including ARBs in a novel integrated approach for the treatment of brain disorders such as depression and Alzheimer's disease may be of immediate translational relevance.
C1 NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH, 10 Ctr Dr,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA.
EM Saavedrj@mail.nih.gov
FU Division of Intramural Research Programs, National Institute of Mental
Health, National Institutes of Health, Department of Health and Human
Services, USA
FX This study was supported by the Division of Intramural Research
Programs, National Institute of Mental Health, National Institutes of
Health, Department of Health and Human Services, USA.
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U2 21
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
EI 1573-6830
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD JUL
PY 2012
VL 32
IS 5
SI SI
BP 667
EP 681
DI 10.1007/s10571-011-9754-6
PG 15
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 960OD
UT WOS:000305396900005
PM 21938488
ER
PT J
AU Kvetnansky, R
Ukropec, J
Laukova, M
Manz, B
Pacak, K
Vargovic, P
AF Kvetnansky, R.
Ukropec, J.
Laukova, M.
Manz, B.
Pacak, K.
Vargovic, P.
TI Stress Stimulates Production of Catecholamines in Rat Adipocytes
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article; Proceedings Paper
CT 10th Symposium on Catecholamines and Other Neurotransmittersin Stress
CY JUN 25-30, 2011
CL Smolenice Castle, SLOVAKIA
DE Mesenteric adipocytes; Stromal vascular fraction; Catecholamine
production; Immobilization; Cold; Novel stressors
ID WHITE ADIPOSE-TISSUE; TYROSINE-HYDROXYLASE GENE; IMMOBILIZATION STRESS;
SYMPATHETIC INNERVATION; ADRENAL-MEDULLA; INDUCED OBESITY;
MESSENGER-RNA; PLASMA-LEVELS; STEM-CELLS; BODY-FAT
AB The sympathoadrenal system is the main source of catecholamines (CAs) in adipose tissues and therefore plays the key role in the regulation of adipose tissue metabolism. We recently reported existence of an alternative CA-producing system directly in adipose tissue cells, and here we investigated effect of various stressors-physical (cold) and emotional stress (immobilization) on dynamics of this system. Acute or chronic cold exposure increased intracellular norepinephrine (NE) and epinephrine (EPI) concentration in isolated rat mesenteric adipocytes. Gene expression of CA biosynthetic enzymes did not change in adipocytes but was increased in stromal vascular fraction (SVF) after 28 day cold. Exposure of rats to a single IMO stress caused increases in NE and EPI levels, and also gene expression of CA biosynthetic enzymes in adipocytes. In SVF changes were similar but more pronounced. Animals adapted to a long-term cold exposure (28 days, 4A degrees C) did not show those responses found after a single IMO stress either in adipocytes or SVF. Our data indicate that gene machinery accommodated in adipocytes, which is able to synthesize NE and EPI de novo, is significantly activated by stress. Cold-adapted animals keep their adaptation even after an exposure to a novel stressor. These findings suggest the functionality of CAs produced endogenously in adipocytes. Taken together, the newly discovered CA synthesizing system in adipocytes is activated in stress situations and might significantly contribute to regulation of lipolysis and other metabolic or thermogenetic processes.
C1 [Kvetnansky, R.; Ukropec, J.; Laukova, M.; Vargovic, P.] Slovak Acad Sci, Inst Expt Endocrinol, SK-83306 Bratislava, Slovakia.
[Manz, B.] LDN Lab Diagnost N, Nordhorn, Germany.
[Pacak, K.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Kvetnansky, R (reprint author), Slovak Acad Sci, Inst Expt Endocrinol, Vlarska 3, SK-83306 Bratislava, Slovakia.
EM richard.kvetnansky@savba.sk
FU Slovak Research and Development Agency [APVV-0088-10, 0148-06]; TRANSMED
2 [ITMS: 26240120030]; VEGA [2/0188/09, 2/0036/11]; EFSD
FX This research was supported by Slovak Research and Development Agency
(No. APVV-0088-10 and 0148-06); TRANSMED 2, ITMS: 26240120030; VEGA
Grants (2/0188/09 and 2/0036/11) and EFSD New Horizonts Grant.
NR 63
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U1 3
U2 12
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
EI 1573-6830
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD JUL
PY 2012
VL 32
IS 5
SI SI
BP 801
EP 813
DI 10.1007/s10571-012-9822-6
PG 13
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 960OD
UT WOS:000305396900017
PM 22402834
ER
PT J
AU Imrich, R
Nikolov, NP
Bebris, L
Alevizos, I
Goldstein, DS
Holmes, CS
Illei, GG
AF Imrich, Richard
Nikolov, Nikolay P.
Bebris, Lolita
Alevizos, Ilias
Goldstein, David S.
Holmes, Courtney S.
Illei, Gabor G.
TI Adrenomedullary Response to Glucagon in Patients with Primary Sjogren's
Syndrome
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article; Proceedings Paper
CT 10th Symposium on Catecholamines and Other Neurotransmittersin Stress
CY JUN 25-30, 2011
CL Smolenice Castle, SLOVAKIA
DE Primary Sjogren's syndrome; Epinephrine; Adrenal medulla; Norepinephrine
ID RHEUMATOID-ARTHRITIS; PREMENOPAUSAL WOMEN; CYTOKINE PROFILES; IN-VITRO;
HYPOGLYCEMIA; EXPRESSION; PLASMA; NOREPINEPHRINE; DYSFUNCTION; DOPAMINE
AB Several studies showed signs of autonomic dysfunction in patients with primary Sjogren's syndrome (pSS). Adrenomedullary function might be of importance for pSS pathogenesis by affecting salivary gland functions and modulating immune responses. The aim of the study was to evaluate the adrenomedullary hormonal system in patients with pSS. The glucagon test (1 mg i.v.) was performed in 18 pSS patients and 13 control subjects. During the test each patient had electrocardiographic and impedance cardiographic monitoring. Plasma epinephrine and norepinephrine were assayed by liquid chromatography with electrochemical detection after batch alumina extraction. Baseline concentrations of epinephrine and norepinephrine were comparable between pSS and controls. Glucagon administration induced a significant increase in systolic blood pressure, diastolic blood pressure, heart rate, cardiac output (P < 0.01), and stroke volume; however, the changes were comparable between pSS and controls. Epinephrine levels increased (P < 0.01) in response to glucagon administration while norepinephrine concentration did not change. There was no significant difference in neurochemical responses to glucagon between pSS and controls. In conclusion, the present results suggest normal adrenomedullary function in pSS.
C1 [Imrich, Richard] Slovak Acad Sci, Inst Expt Endocrinol, Ctr Mol Med, Bratislava 83101, Slovakia.
[Nikolov, Nikolay P.; Bebris, Lolita; Alevizos, Ilias; Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Bethesda, MD USA.
[Goldstein, David S.; Holmes, Courtney S.] Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Bethesda, MD USA.
[Nikolov, Nikolay P.; Bebris, Lolita; Alevizos, Ilias; Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Bethesda, MD USA.
[Goldstein, David S.; Holmes, Courtney S.] Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Bethesda, MD USA.
[Imrich, Richard] Slovak Acad Sci, Inst Expt Endocrinol, Ctr Mol Med, Bratislava 83101, Slovakia.
RP Illei, GG (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Bethesda, MD USA.
EM richard.imrich@savba.sk; illeig@nidcr.nih.gov
FU National Institute of Dental and Craniofacial Research; National
Institute of Neurological Disorders and Stroke
FX The research project was supported by the intramural research programs
of the National Institute of Dental and Craniofacial Research and the
National Institute of Neurological Disorders and Stroke.
NR 19
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U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
EI 1573-6830
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD JUL
PY 2012
VL 32
IS 5
SI SI
BP 903
EP 906
DI 10.1007/s10571-011-9787-x
PG 4
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 960OD
UT WOS:000305396900027
PM 22350211
ER
PT J
AU Armah, KA
McGinnis, K
Baker, J
Gibert, C
Butt, AA
Bryant, KJ
Goetz, M
Tracy, R
Oursler, KK
Rimland, D
Crothers, K
Rodriguez-Barradas, M
Crystal, S
Gordon, A
Kraemer, K
Brown, S
Gerschenson, M
Leaf, DA
Deeks, SG
Rinaldo, C
Kuller, LH
Justice, A
Freiberg, M
AF Armah, Kaku A.
McGinnis, Kathleen
Baker, Jason
Gibert, Cynthia
Butt, Adeel A.
Bryant, Kendall J.
Goetz, Matthew
Tracy, Russell
Oursler, Krisann K.
Rimland, David
Crothers, Kristina
Rodriguez-Barradas, Maria
Crystal, Steve
Gordon, Adam
Kraemer, Kevin
Brown, Sheldon
Gerschenson, Mariana
Leaf, David A.
Deeks, Steven G.
Rinaldo, Charles
Kuller, Lewis H.
Justice, Amy
Freiberg, Matthew
TI HIV Status, Burden of Comorbid Disease, and Biomarkers of Inflammation,
Altered Coagulation, and Monocyte Activation
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID C-REACTIVE PROTEIN; APPARENTLY HEALTHY-MEN; T-CELL DEPLETION;
MYOCARDIAL-INFARCTION; MICROBIAL TRANSLOCATION; DIABETES-MELLITUS;
ANTIRETROVIRAL THERAPY; BLOOD-PRESSURE; SOLUBLE CD14; INFECTION
AB Background. Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)-infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS).
Methods. Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (D-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities.
Results. HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA >= 500 copies/mL or CD4 count <200 cells/mu L had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.14-2.09; OR, 2.25; 95% CI, 1.60-3.16, respectively) and D-dimer (OR, 1.97; 95% CI, 1.44-2.71, OR, 1.68; 95% CI, 1.22-2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/mu L had significantly higher prevalence of elevated sCD14 compared to uninfected veterans (OR, 2.60; 95% CI, 1.64-4.14). These associations still persisted after restricting the analysis to veterans without known confounding comorbid conditions.
Conclusions. These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of and in addition to the substantial contribution from comorbid conditions.
C1 [Armah, Kaku A.; Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Gordon, Adam] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Sch Med, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15260 USA.
[Baker, Jason] Univ Minnesota, Dept Med, Hennepin Cty Med Ctr, Minneapolis, MN 55455 USA.
[Gibert, Cynthia] VA Med Ctr, Washington, DC USA.
[Gibert, Cynthia] George Washington Univ, Med Ctr, Washington, DC 20037 USA.
[Butt, Adeel A.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates.
[Bryant, Kendall J.] NIAAA, NIH, Bethesda, MD USA.
[Goetz, Matthew; Leaf, David A.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA.
[Tracy, Russell] Univ Vermont, Dept Pathol, Coll Med, Burlington, VT 05405 USA.
[Tracy, Russell] Univ Vermont, Dept Biochem, Coll Med, Burlington, VT 05405 USA.
[Oursler, Krisann K.] Univ Maryland, Baltimore VA Med Ctr, Sch Med, Baltimore, MD USA.
[Rimland, David] Emory Univ, Sch Med, VA Med Ctr, Atlanta, GA USA.
[Crothers, Kristina] Univ Washington, Div Pulm & Crit Care, Dept Internal Med, Seattle, WA 98195 USA.
[Rodriguez-Barradas, Maria] Baylor Coll Med, Houston, TX 77030 USA.
[Rodriguez-Barradas, Maria] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Crystal, Steve] Rutgers State Univ, Ctr Pharmacotherapy Chron Dis Management & Outcom, Inst Hlth, New Brunswick, NJ 08903 USA.
[Crystal, Steve] Rutgers State Univ, Sch Social Work, New Brunswick, NJ 08903 USA.
[Gordon, Adam] Univ Pittsburgh, Sch Med, Ctr Hlth Equity Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA.
[Gordon, Adam] Univ Pittsburgh, Sch Med, Ctr Res Healthcare, Pittsburgh, PA 15260 USA.
[Kraemer, Kevin] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA.
[Brown, Sheldon] Mt Sinai Med Ctr, Dept Internal Med, New York, NY 10029 USA.
[Brown, Sheldon] Bronx Vet Affairs Med Ctr, New York, NY USA.
[Gerschenson, Mariana] Univ Hawaii Manoa, Hawaii AIDS Clin Res Program, Dept Med, Honolulu, HI 96822 USA.
[Gerschenson, Mariana] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA.
[Deeks, Steven G.] San Francisco Gen Hosp, Dept Med, Posit Hlth Program, San Francisco, CA 94110 USA.
[Rinaldo, Charles] Presbyterian Univ Hosp, Dept Microbiol, Dept Pathol, Pittsburgh, PA USA.
[Justice, Amy] Yale Univ, Sch Med, Sect Gen Med, New Haven, CT USA.
[Justice, Amy] VA Connecticut Healthcare Syst, West Haven, CT USA.
[Freiberg, Matthew] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA.
RP Freiberg, M (reprint author), 230 McKee Pl,Ste 623, Pittsburgh, PA 15213 USA.
EM freibergms@upmc.edu
OI Goetz, Matthew/0000-0003-4542-992X
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National
Heart Lung and Blood Institute (NHLBI) at the National Institutes of
Health (NIH) [K23AA015914-0651, R01HC095136-04, 5R01HC095126-04,
U10AA013566-10]; NIH/NHLBI/NIAAA; Yale University; US Department of
Veterans Affairs (VA) through the University of Pittsburgh
FX This work was supported by the National Institute on Alcohol Abuse and
Alcoholism (NIAAA) and National Heart Lung and Blood Institute (NHLBI)
at the National Institutes of Health (NIH; grant numbers
K23AA015914-0651, R01HC095136-04, 5R01HC095126-04 to M. F.; and
U10AA013566-10 to A. J.).; K. A., K. A. O., A. G., K. K., S. B., S. D.,
A. J., and M. F. received NIH/NHLBI/NIAAA grant funding for this work.
M. G. has received grant funding and support from Yale University for
this work. R. T. has received grant funding from the US Department of
Veterans Affairs (VA) through the University of Pittsburgh for this
work. R. T. owns Haematologic Technologies and has received funding from
Tibotec, Merck, and Abbott, none of which pertain to this work. All
other authors report no potential conflicts.
NR 37
TC 94
Z9 94
U1 1
U2 13
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUL 1
PY 2012
VL 55
IS 1
BP 126
EP 136
DI 10.1093/cid/cis406
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 956KM
UT WOS:000305088500020
PM 22534147
ER
PT J
AU Ranjan, A
Pothayee, N
Seleem, MN
Boyle, SM
Kasimanickam, R
Riffle, JS
Sriranganathan, N
AF Ranjan, Ashish
Pothayee, Nikorn
Seleem, Mohamed N.
Boyle, Stephen M.
Kasimanickam, Ramanathan
Riffle, Judy S.
Sriranganathan, Nammalwar
TI Nanomedicine for intracellular therapy
SO FEMS MICROBIOLOGY LETTERS
LA English
DT Review
DE intracelluar infection; drug delivery; nanoparticle
ID ENTERICA SEROVAR TYPHIMURIUM; CORE-SHELL NANOSTRUCTURES;
LIPOSOME-ENCAPSULATED GENTAMICIN; AMPICILLIN-LOADED NANOPARTICLES;
PH-SENSITIVE LIPOSOMES; SALMONELLA-ENTERICA; IN-VIVO; LISTERIOLYSIN-O;
ANTIBACTERIAL EFFICACY; INFECTION MODEL
AB Intracellular pathogens like Salmonella evade host phagocytic killing by various mechanisms. Classical antimicrobial therapy requires multiple dosages and frequent administration of drugs for a long duration. Intracellular delivery of antimicrobials using nanoparticle may effectively devise therapies for bacterial infections. This review will address the mechanisms used by Salmonella to avoid host pathogenic killing, reasons for therapeutic failure and advances in nanoparticle drug delivery technology for efficient intracellular bacterial clearance.
C1 [Ranjan, Ashish] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Pothayee, Nikorn; Riffle, Judy S.] Virginia Tech, Macromol & Interfaces Inst, Blacksburg, VA USA.
[Seleem, Mohamed N.] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA.
[Boyle, Stephen M.; Sriranganathan, Nammalwar] Virginia Tech, Dept Biomed Sci & Pathobiol, Blacksburg, VA USA.
[Kasimanickam, Ramanathan] Washington State Univ, Pullman, WA 99164 USA.
RP Ranjan, A (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
EM ashishvet06@gmail.com
NR 88
TC 10
Z9 10
U1 2
U2 32
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0378-1097
EI 1574-6968
J9 FEMS MICROBIOL LETT
JI FEMS Microbiol. Lett.
PD JUL
PY 2012
VL 332
IS 1
BP 1
EP 9
DI 10.1111/j.1574-6968.2012.02566.x
PG 9
WC Microbiology
SC Microbiology
GA 956GX
UT WOS:000305079200001
PM 22471308
ER
PT J
AU Fabrega, A
Rosner, JL
Martin, RG
Sole, M
Vila, J
AF Fabrega, Anna
Rosner, Judah L.
Martin, Robert G.
Sole, Mar
Vila, Jordi
TI SoxS-dependent coregulation of ompN and ydbK in a multidrug-resistant
Escherichia coli strain
SO FEMS MICROBIOLOGY LETTERS
LA English
DT Article
DE porin; gene regulation; SoxS; superoxide resistance; antibiotic
resistance
ID MULTIPLE-ANTIBIOTIC-RESISTANCE; SUPEROXIDE STRESS; REGULON;
IDENTIFICATION; BINDING; PROTEIN; GENE; MARA; EXPRESSION; MUTATIONS
AB SoxS , MarA , and Rob are homologous transcriptional activators of numerous superoxide- and antibiotic resistance genes but many of the regulated genes are yet to be characterized. In this study, microarrays and RT-PCR analysis were used to show the overexpression of the ompN porin and its upstream gene, ydbK , in an Escherichia coli multidrug-resistant mutant and in a strain constitutive for SoxS . However, transcriptional fusions revealed that SoxS (not MarA or Rob ) only activated the ydbK promoter but not the ompN upstream region. RT-PCR experiments showed the overexpression of a combined ydbK ompN transcript in the SoxS -overexpressing strain. Surprisingly, a bioinformatic approach revealed no soxbox upstream of the ydbK promoter. Thus, the ydbK and ompN genes are coexpressed in an operon and are likely activated by SoxS indirectly. It is known that YdbK is involved in superoxide resistance. Thus, individual ompN and ydbK mutants were tested for superoxide susceptibility. Nonetheless, only the ydbK mutant was susceptible to paraquat, a superoxide generator. These mutants, as well as an OmpN -overproducing strain, were further tested for antibiotic resistance. No significant decreased susceptibility was observed. Thus, ydbK plays a role in superoxide resistance but no role for either gene is found in resistance to the antibiotics tested.
C1 [Vila, Jordi] Univ Barcelona, Fac Med, Barcelona Ctr Int Hlth Res, Microbiol Serv,Hosp Clin,CRESIB, Barcelona 08036, Spain.
[Rosner, Judah L.; Martin, Robert G.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Vila, Jordi] Univ Barcelona, Sch Med, Hosp Clin, Dept Microbiol, E-08036 Barcelona, Spain.
RP Vila, J (reprint author), Univ Barcelona, Fac Med, Barcelona Ctr Int Hlth Res, Microbiol Serv,Hosp Clin,CRESIB, Villarroel 170, Barcelona 08036, Spain.
EM jvila@ub.edu
RI Luan, Gan/B-3211-2015; Vila, Jordi/P-3613-2016;
OI Vila, Jordi/0000-0002-8025-3926; Fabrega-Santamaria,
Anna/0000-0002-3866-2291
FU Intramural NIH HHS
NR 25
TC 4
Z9 4
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0378-1097
EI 1574-6968
J9 FEMS MICROBIOL LETT
JI FEMS Microbiol. Lett.
PD JUL
PY 2012
VL 332
IS 1
BP 61
EP 67
DI 10.1111/j.1574-6968.2012.02577.x
PG 7
WC Microbiology
SC Microbiology
GA 956GX
UT WOS:000305079200009
PM 22515487
ER
PT J
AU Chen, LS
Saccone, NL
Culverhouse, RC
Bracci, PM
Chen, CH
Dueker, N
Han, YH
Huang, HY
Jin, GF
Kohno, T
Ma, JZ
Przybeck, TR
Sanders, AR
Smith, JA
Sung, YJ
Wenzlaff, AS
Wu, C
Yoon, D
Chen, YT
Cheng, YC
Cho, YS
David, SP
Duan, JB
Eaton, CB
Furberg, H
Goate, AM
Gu, DF
Hansen, HM
Hartz, S
Hu, ZB
Kim, YJ
Kittner, SJ
Levinson, DF
Mosley, TH
Payne, TJ
Rao, DC
Rice, JP
Rice, TK
Schwantes-An, TH
Shete, SS
Shi, JX
Spitz, MR
Sun, YV
Tsai, FJ
Wang, JC
Wrensch, MR
Xian, H
Gejman, PV
He, J
Hunt, SC
Kardia, SL
Li, MD
Lin, DX
Mitchell, BD
Park, T
Schwartz, AG
Shen, HB
Wiencke, JK
Wu, JY
Yokota, J
Amos, CI
Bierut, LJ
AF Chen, Li-Shiun
Saccone, Nancy L.
Culverhouse, Robert C.
Bracci, Paige M.
Chen, Chien-Hsiun
Dueker, Nicole
Han, Younghun
Huang, Hongyan
Jin, Guangfu
Kohno, Takashi
Ma, Jennie Z.
Przybeck, Thomas R.
Sanders, Alan R.
Smith, Jennifer A.
Sung, Yun Ju
Wenzlaff, Angie S.
Wu, Chen
Yoon, Dankyu
Chen, Ying-Ting
Cheng, Yu-Ching
Cho, Yoon Shin
David, Sean P.
Duan, Jubao
Eaton, Charles B.
Furberg, Helena
Goate, Alison M.
Gu, Dongfeng
Hansen, Helen M.
Hartz, Sarah
Hu, Zhibin
Kim, Young Jin
Kittner, Steven J.
Levinson, Douglas F.
Mosley, Thomas H.
Payne, Thomas J.
Rao, D. C.
Rice, John P.
Rice, Treva K.
Schwantes-An, Tae-Hwi
Shete, Sanjay S.
Shi, Jianxin
Spitz, Margaret R.
Sun, Yan V.
Tsai, Fuu-Jen
Wang, Jen C.
Wrensch, Margaret R.
Xian, Hong
Gejman, Pablo V.
He, Jiang
Hunt, Steven C.
Kardia, Sharon L.
Li, Ming D.
Lin, Dongxin
Mitchell, Braxton D.
Park, Taesung
Schwartz, Ann G.
Shen, Hongbing
Wiencke, John K.
Wu, Jer-Yuarn
Yokota, Jun
Amos, Christopher I.
Bierut, Laura J.
TI Smoking and Genetic Risk Variation Across Populations of European,
Asian, and African American AncestryuA Meta-Analysis of Chromosome
15q25(vol 36, pg 525, 2010)
SO GENETIC EPIDEMIOLOGY
LA English
DT Correction
C1 [Chen, Li-Shiun; Przybeck, Thomas R.; Goate, Alison M.; Hartz, Sarah; Rice, John P.; Wang, Jen C.; Bierut, Laura J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Saccone, Nancy L.; Schwantes-An, Tae-Hwi] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Culverhouse, Robert C.; Xian, Hong] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
[Bracci, Paige M.] UCSF, Dept Epidemiol & Biostat, San Francisco, CA USA.
[Chen, Chien-Hsiun; Chen, Ying-Ting; Wu, Jer-Yuarn] Acad Sinica, Natl Genotyping Ctr, Inst Biomed Sci, Taipei 115, Taiwan.
[Chen, Chien-Hsiun; Wu, Jer-Yuarn] China Med Univ, Grad Inst Chinese Med Sci, Taichung, Taiwan.
[Dueker, Nicole] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Han, Younghun; Shete, Sanjay S.; Spitz, Margaret R.; Amos, Christopher I.] Univ Texas MD, Dept Epidemiol Anderson Canc Ctr, Houston, TX USA.
[Huang, Hongyan; Sung, Yun Ju; Rao, D. C.; Rice, Treva K.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Jin, Guangfu; Hu, Zhibin; Shen, Hongbing] Nanjing Med Univ, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China.
[Kohno, Takashi] Natl Canc Ctr, Res Inst, Div Genome Biol, Tokyo 104, Japan.
[Ma, Jennie Z.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Sanders, Alan R.; Duan, Jubao; Gejman, Pablo V.] Univ Chicago, Dept Psychiat & Behav Sci, N Shore Univ Hlth Syst Res Inst, Chicago, IL 60637 USA.
[Smith, Jennifer A.; Mosley, Thomas H.; Sun, Yan V.; Kardia, Sharon L.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Wenzlaff, Angie S.; Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Wu, Chen; Lin, Dongxin] Chinese Acad Med Sci, Dept Etiol, Beijing 100730, Peoples R China.
[Yoon, Dankyu; Kim, Young Jin] Seoul Natl Univ, Interdisciplinary Program Bioinformat Coll Nat Sc, Seoul, South Korea.
[Yoon, Dankyu] Natl Inst Hlth, Ctr Immunol & Pathol, Seoul, South Korea.
[Cheng, Yu-Ching] Univ Maryland, Dept Med, Med Ctr, Baltimore, MD 21201 USA.
[Cho, Yoon Shin; Mitchell, Braxton D.] Natl Inst Hlth, Ctr Genome Sci, Seoul, South Korea.
[Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon, South Korea.
[David, Sean P.; Kim, Young Jin] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA.
[David, Sean P.; Eaton, Charles B.] Brown Univ, Dept Family Med, Providence, RI 02912 USA.
[Furberg, Helena] Mem Sloan Kettering Canc Ctr, Dept Epidemiol, New York, NY 10021 USA.
[Gu, Dongfeng] Chinese Acad Med Sci, Fuwai Hosp, Beijing 100730, Peoples R China.
[Gu, Dongfeng] Chinese Natl Ctr Cardiovasc Dis Control & Res, Beijing, Peoples R China.
[Hansen, Helen M.; Wrensch, Margaret R.; Wiencke, John K.] Helen Diller Family Canc Ctr, Neurol Surg Div Epidemiol, San Francisco, CA USA.
[Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
[Payne, Thomas J.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Shi, Jianxin] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Tsai, Fuu-Jen] China Med Univ, Sch Post Baccalaureate Chinese Med, Taichung, Taiwan.
[He, Jiang] Tulane Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
[Hunt, Steven C.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA.
[Li, Ming D.] Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA USA.
[Park, Taesung] Seoul Natl Univ, Coll Nat Sci, Seoul 151742, South Korea.
[Yokota, Jun] Natl Canc Ctr, Res Inst, Div Multistep Carcinogenesis, Tokyo 104, Japan.
[Park, Taesung] Seoul Natl Univ, Dept Stat, Seoul, South Korea.
[David, Sean P.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Gu, Dongfeng] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Kittner, Steven J.] Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA.
[Wu, Chen; Lin, Dongxin] Chinese Acad Med Sci, Carcinogenesis Canc Inst, Beijing 100730, Peoples R China.
RP Chen, LS (reprint author), Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
RI Tsai, Fuu-Jen/J-4140-2015
NR 1
TC 1
Z9 1
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD JUL
PY 2012
VL 36
IS 5
BP 525
EP 526
DI 10.1002/gepi.21654
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 956YP
UT WOS:000305125800012
ER
PT J
AU Ntzani, EE
Liberopoulos, G
Manolio, TA
Ioannidis, JPA
AF Ntzani, Evangelia E.
Liberopoulos, George
Manolio, Teri A.
Ioannidis, John P. A.
TI Consistency of genome-wide associations across major ancestral groups
SO HUMAN GENETICS
LA English
DT Article
ID COMMON DISEASES; AFRICAN-AMERICANS; GENETIC-STRUCTURE; FTO GENE;
POPULATION; VARIANTS; RISK; METAANALYSIS; REPLICATION; UNCERTAINTY
AB It is not well known whether genetic markers identified through genome-wide association studies (GWAS) confer similar or different risks across people of different ancestry. We screened a regularly updated catalog of all published GWAS curated at the NHGRI website for GWAS-identified associations that had reached genome-wide significance (p a parts per thousand currency sign 5 x 10(-8)) in at least one major ancestry group (European, Asian, African) and for which replication data were available for comparison in at least two different major ancestry groups. These groups were compared for the correlation between and differences in risk allele frequencies and genetic effects' estimates. Data on 108 eligible GWAS-identified associations with a total of 900 datasets (European, n = 624; Asian, n = 217; African, n = 60) were analyzed. Risk-allele frequencies were modestly correlated between ancestry groups, with > 10% absolute differences in 75-89% of the three pairwise comparisons of ancestry groups. Genetic effect (odds ratio) point estimates between ancestry groups correlated modestly (pairwise comparisons' correlation coefficients: 0.20-0.33) and point estimates of risks were opposite in direction or differed more than twofold in 57%, 79%, and 89% of the European versus Asian, European versus African, and Asian versus African comparisons, respectively. The modest correlations, differing risk estimates, and considerable between-association heterogeneity suggest that differential ancestral effects can be anticipated and genomic risk markers may need separate further evaluation in different ancestry groups.
C1 [Ioannidis, John P. A.] Stanford Univ, Dept Med, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA.
[Ntzani, Evangelia E.; Liberopoulos, George; Ioannidis, John P. A.] Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Manolio, Teri A.] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA.
RP Ioannidis, JPA (reprint author), Stanford Univ, Dept Med, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA.
EM jioannid@stanford.edu
NR 53
TC 28
Z9 28
U1 1
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD JUL
PY 2012
VL 131
IS 7
BP 1057
EP 1071
DI 10.1007/s00439-011-1124-4
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 957VV
UT WOS:000305195400004
PM 22183176
ER
PT J
AU Jin, GF
Lu, LY
Cooney, KA
Ray, AM
Zuhlke, KA
Lange, EM
Cannon-Albright, LA
Camp, NJ
Teerlink, CC
FitzGerald, LM
Stanford, JL
Wiley, KE
Isaacs, SD
Walsh, PC
Foulkes, WD
Giles, GG
Hopper, JL
Severi, G
Eeles, R
Easton, D
Kote-Jarai, Z
Guy, M
Rinckleb, A
Maier, C
Vogel, W
Cancel-Tassin, G
Egrot, C
Cussenot, O
Thibodeau, SN
McDonnell, SK
Schaid, DJ
Wiklund, F
Gronberg, H
Emanuelsson, M
Whittemore, AS
Oakley-Girvan, I
Hsieh, CL
Wahlfors, T
Tammela, T
Schleutker, J
Catalona, WJ
Zheng, SL
Ostrander, EA
Isaacs, WB
Xu, JF
AF Jin, Guangfu
Lu, Lingyi
Cooney, Kathleen A.
Ray, Anna M.
Zuhlke, Kimberly A.
Lange, Ethan M.
Cannon-Albright, Lisa A.
Camp, Nicola J.
Teerlink, Craig C.
FitzGerald, Liesel M.
Stanford, Janet L.
Wiley, Kathleen E.
Isaacs, Sarah D.
Walsh, Patrick C.
Foulkes, William D.
Giles, Graham G.
Hopper, John L.
Severi, Gianluca
Eeles, Ros
Easton, Doug
Kote-Jarai, Zsofia
Guy, Michelle
Rinckleb, Antje
Maier, Christiane
Vogel, Walther
Cancel-Tassin, Geraldine
Egrot, Christophe
Cussenot, Olivier
Thibodeau, Stephen N.
McDonnell, Shannon K.
Schaid, Daniel J.
Wiklund, Fredrik
Gronberg, Henrik
Emanuelsson, Monica
Whittemore, Alice S.
Oakley-Girvan, Ingrid
Hsieh, Chih-Lin
Wahlfors, Tiina
Tammela, Teuvo
Schleutker, Johanna
Catalona, William J.
Zheng, S. Lilly
Ostrander, Elaine A.
Isaacs, William B.
Xu, Jianfeng
TI Validation of prostate cancer risk-related loci identified from
genome-wide association studies using family-based association analysis:
evidence from the International Consortium for Prostate Cancer Genetics
(ICPCG)
SO HUMAN GENETICS
LA English
DT Article
ID VARIANTS; 8Q24; LINKAGE; SUSCEPTIBILITY; HEREDITARY; DISEASE; TESTS
AB Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case-control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk alleles for 8 of the 17 loci were significantly over-transmitted from parents to affected offspring, including SNPs residing in 8q24 (regions 1, 2 and 3), 10q11, 11q13, 17q12 (region 1), 17q24 and Xp11. In subgroup analyses, three loci, at 8q24 (regions 1 and 2) plus 17q12, were significantly over-transmitted in hereditary PCa families with five or more affected members, while loci at 3p12, 8q24 (region 2), 11q13, 17q12 (region 1), 17q24 and Xp11 were significantly over-transmitted in HPC families with an average age of diagnosis at 65 years or less. Our results indicate that at least a subset of PCa risk-related loci identified by case-control GWAS are also associated with disease risk in HPC families.
C1 [Jin, Guangfu; Lu, Lingyi; Zheng, S. Lilly; Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Data Coordinating Ctr ICPCG, Winston Salem, NC 27157 USA.
[Jin, Guangfu; Lu, Lingyi; Zheng, S. Lilly; Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC 27157 USA.
[Cooney, Kathleen A.; Ray, Anna M.; Zuhlke, Kimberly A.; Lange, Ethan M.] Univ Michigan, ICPCG Grp, Ann Arbor, MI 48109 USA.
[Cooney, Kathleen A.; Ray, Anna M.; Zuhlke, Kimberly A.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Cooney, Kathleen A.; Ray, Anna M.; Zuhlke, Kimberly A.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA.
[Lange, Ethan M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Lange, Ethan M.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Cannon-Albright, Lisa A.; Camp, Nicola J.; Teerlink, Craig C.] Univ Utah, Sch Med, Dept Med, ICPCG Grp,Div Genet Epidemiol, Salt Lake City, UT 84108 USA.
[Cannon-Albright, Lisa A.] Vet Affairs Med Ctr, George E Wahlen Dept, Salt Lake City, UT 84148 USA.
[FitzGerald, Liesel M.; Stanford, Janet L.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98195 USA.
[Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.] Johns Hopkins Univ, ICPCG Grp, Dept Urol, Johns Hopkins Med Inst, Baltimore, MD 21287 USA.
[Foulkes, William D.] McGill Univ, Program Canc Genet, Montreal, PQ H3T 1E2, Canada.
[Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic 3053, Australia.
[Giles, Graham G.; Hopper, John L.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia.
[Eeles, Ros; Kote-Jarai, Zsofia; Guy, Michelle] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
[Easton, Doug] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
[Easton, Doug] Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England.
[Rinckleb, Antje; Maier, Christiane] Univ Ulm, Dept Urol, Ulm, Germany.
[Rinckleb, Antje; Maier, Christiane; Vogel, Walther] Univ Ulm, Inst Human Genet, Ulm, Germany.
[Cancel-Tassin, Geraldine; Egrot, Christophe; Cussenot, Olivier] Hop Tenon, AP HP, CeRePP ICPCG Grp, F-75020 Paris, France.
[Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[McDonnell, Shannon K.; Schaid, Daniel J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Emanuelsson, Monica] Umea Univ, Ctr Oncol, S-90187 Umea, Sweden.
[Oakley-Girvan, Ingrid] Canc Prevent Inst Calif, Fremont, CA 94538 USA.
[Oakley-Girvan, Ingrid] Stanford Sch Med, Stanford Canc Inst, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Hsieh, Chih-Lin] Univ So Calif, Dept Urol, Los Angeles, CA 90089 USA.
[Hsieh, Chih-Lin] Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA.
[Wahlfors, Tiina] Univ Tampere, Inst Biomed Technol, BioMediTech, FIN-33101 Tampere, Finland.
[Wahlfors, Tiina] Tampere Univ Hosp, Ctr Lab Med, Tampere 33520, Finland.
[Tammela, Teuvo] Univ Tampere, Dept Urol, Tampere 33520, Finland.
[Schleutker, Johanna] Univ Turku, Dept Med Biochem & Genet, Turku 20014, Finland.
[Catalona, William J.] Northwestern Univ, Feinberg Sch Med, ICPCG Grp, Chicago, IL 60611 USA.
[Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Xu, JF (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Data Coordinating Ctr ICPCG, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
EM eostrand@mail.nih.gov; wisaacs@jhmi.edu; jxu@wakehealth.edu
RI Whittemore, Alice/F-9925-2014;
OI Eeles, Rosalind/0000-0002-3698-6241; Teerlink,
Craig/0000-0002-1992-2326; albright, lisa/0000-0003-2602-3668; foulkes,
william/0000-0001-7427-4651; Giles, Graham/0000-0003-4946-9099;
Ostrander, Elaine/0000-0001-6075-9738; Cancel-Tassin,
Geraldine/0000-0002-9583-6382
FU National Institutes of Health [U01 CA89600]; University of Utah Huntsman
Cancer Institute; Fred Hutchinson Cancer Research Center; National Human
Genome Research Institute; CR-UK [A8385]; NIHR; Royal Marsden NHS
Foundation Trust; Swedish Cancer Society; Umea University Hospital,
Umea, Sweden; Pirkanmaa Hospital District [9L091]; Reino Lahtikari
Foundation; Finnish Cancer Organisations; Sigrid Juselius Foundation;
Academy of Finland [116437, 126714]; Robert H. Lurie Comprehensive
Cancer Center; Urological Research Foundation; NIH [P50 CA69568, R01
CA79596]; University of Michigan Comprehensive Cancer Center; NCI
[CA119069, CA129684]
FX We would like to express our gratitude to the many families who
participated in the studies involved in the International Consortium for
Prostate Cancer Genetics (ICPCG). The ICPCG, including the consortium's
Data Coordinating Center (DCC), is made possible by a grant from the
National Institutes of Health U01 CA89600 (to William B. Isaacs).
Additional support to participating groups, or members within groups, is
as follows: University of Utah Group: The authors appreciate the support
of the University of Utah Huntsman Cancer Institute (to Lisa A.
Cannon-Albright). FHCRC/NHGRI Group: Partial support was provided by the
Fred Hutchinson Cancer Research Center (to Janet L. Stanford) and
National Human Genome Research Institute (to Elaine A. Ostrander).
ACTANE Group: We appreciate the support of the CR-UK grant A8385 and the
NIHR to the Biomedical Research Centre at The Institute of Cancer
Research and Royal Marsden NHS Foundation Trust (to Ros Eeles), and
Cancer Research UK (to Doug Easton). University of Umea Group: Partial
support was provided by the Swedish Cancer Society and a Spear grant
from the Umea University Hospital, Umea, Sweden (to Henrik Gronberg).
University of Tampere Group: We appreciate the support of the
Competitive Research Funding of the Pirkanmaa Hospital District (9L091),
Reino Lahtikari Foundation, Finnish Cancer Organisations, Sigrid
Juselius Foundation and Academy of Finland (116437 and 126714) (to
Johanna Schleutker). Northwestern University Group: Partial support was
provided from Robert H. Lurie Comprehensive Cancer Center and the
Urological Research Foundation (to William J. Catalona). University of
Michigan Group: Partial support was provided by NIH P50 CA69568, NIH R01
CA79596 (to Kathleen Cooney), and the University of Michigan
Comprehensive Cancer Center. Data Coordinating Center: Partial support
was provided by NCI CA119069 and CA129684 (to Jianfeng Xu). We also
thank other investigators who contributed to this work: ACTANE Group:
Daniel Leongamornlert, Ed Saunders, Malgorzata Tymrakiewicz, Lynne
O'Brien, Emma Sawyer, Rosemary Wilkinson, and Stephen Edwards from The
Institute of Cancer Research, Sutton, Surrey. University of Ulm Group:
Manuel Luedeke and Mark Schrader from Department of Urology, University
of Ulm, Germany; Josef Hoegel and Christian Kubisch from Institute of
Human Genetics, University of Ulm, Germany; and Kathleen Herkommer from
Department of Urology, Technical University of Munich, Germany.
NR 20
TC 10
Z9 11
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD JUL
PY 2012
VL 131
IS 7
BP 1095
EP 1103
DI 10.1007/s00439-011-1136-0
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 957VV
UT WOS:000305195400008
PM 22198737
ER
PT J
AU Mills, MB
Hudgins, L
Balise, RR
Abramson, DH
Kleinerman, RA
AF Mills, Melissa B.
Hudgins, Louanne
Balise, Raymond R.
Abramson, David H.
Kleinerman, Ruth A.
TI Mutation risk associated with paternal and maternal age in a cohort of
retinoblastoma survivors
SO HUMAN GENETICS
LA English
DT Article
ID SPORADIC HEREDITARY RETINOBLASTOMA; LONG-TERM SURVIVORS; PARENTAL AGE;
CANCER; GENE; ORIGIN
AB Autosomal dominant conditions are known to be associated with advanced paternal age, and it has been suggested that retinoblastoma (Rb) also exhibits a paternal age effect due to the paternal origin of most new germline RB1 mutations. To further our understanding of the association of parental age and risk of de novo germline RB1 mutations, we evaluated the effect of parental age in a cohort of Rb survivors in the United States. A cohort of 262 Rb patients was retrospectively identified at one institution, and telephone interviews were conducted with parents of 160 survivors (65.3%). We classified Rb survivors into three groups: those with unilateral Rb were classified as sporadic if they had no or unknown family history of Rb, those with bilateral Rb were classified as having a de novo germline mutation if they had no or unknown family history of Rb, and those with unilateral or bilateral Rb, who had a family history of Rb, were classified as familial. We built two sets of nested logistic regression models to detect an increased odds of the de novo germline mutation classification related to older parental age compared to sporadic and familial Rb classifications. The modeling strategy evaluated effects of continuous increasing maternal and paternal age and 5-year age increases adjusted for the age of the other parent. Mean maternal ages for survivors classified as having de novo germline mutations and sporadic Rb were similar (28.3 and 28.5, respectively) as were mean paternal ages (31.9 and 31.2, respectively), and all were significantly higher than the weighted general US population means. In contrast, maternal and paternal ages for familial Rb did not differ significantly from the weighted US general population means. Although we noted no significant differences between mean maternal and paternal ages between each of the three Rb classification groups, we found increased odds of a survivor being in the de novo germline mutation group for each 5-year increase in paternal age, but these findings were not statistically significant (de novo vs. sporadic ORs 30-34 = 1.7 [0.7-4], a parts per thousand yen35 = 1.3 [0.5-3.3]; de novo vs. familial ORs 30-34 = 2.8 [1.0-8.4], a parts per thousand yen35 = 1.6 [0.6-4.6]). Our study suggests a weak paternal age effect for Rb resulting from de novo germline mutations consistent with the paternal origin of most of these mutations.
C1 [Mills, Melissa B.] Stanford Univ, Dept Genet, Sch Med, Lucile Packard Childrens Hosp, Stanford, CA 94304 USA.
[Hudgins, Louanne] Stanford Univ, Div Med Genet, Dept Pediat, Sch Med, Stanford, CA 94304 USA.
[Abramson, David H.] Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10065 USA.
[Kleinerman, Ruth A.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Mills, MB (reprint author), Stanford Univ, Dept Genet, Sch Med, Lucile Packard Childrens Hosp, 300 Pasteur Dr,Boswell Bldg A097, Stanford, CA 94304 USA.
EM mmills@lpch.org
OI Kleinerman, Ruth/0000-0001-7415-2478
FU Stanford University School of Medicine; National Institutes of Health,
the National Cancer Institute, Division of Cancer Epidemiology and
Genetics
FX We are grateful for the support of the Stanford University School of
Medicine Master's Program in Human Genetics and Genetic Counseling. This
research was supported in part by the Intramural Research Program of the
National Institutes of Health, the National Cancer Institute, Division
of Cancer Epidemiology and Genetics.
NR 27
TC 2
Z9 2
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD JUL
PY 2012
VL 131
IS 7
BP 1115
EP 1122
DI 10.1007/s00439-011-1126-2
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 957VV
UT WOS:000305195400010
PM 22203219
ER
PT J
AU Wang, ZM
Parikh, H
Jia, JP
Myers, T
Yeager, M
Jacobs, KB
Hutchinson, A
Burdett, L
Ghosh, A
Thun, MJ
Gapstur, SM
Diver, WR
Virtamo, J
Albanes, D
Cancel-Tassin, G
Valeri, A
Cussenot, O
Offit, K
Giovannucci, E
Ma, J
Stampfer, MJ
Gaziano, J
Hunter, DJ
Dutra-Clarke, A
Kirchhoff, T
Alavanja, M
Freeman, LB
Koutros, S
Hoover, R
Berndt, SI
Hayes, RB
Agalliu, I
Burk, RD
Wacholder, S
Thomas, G
Amundadottir, L
AF Wang, Zhaoming
Parikh, Hemang
Jia, Jinping
Myers, Timothy
Yeager, Meredith
Jacobs, Kevin B.
Hutchinson, Amy
Burdett, Laurie
Ghosh, Arpita
Thun, Michael J.
Gapstur, Susan M.
Diver, W. Ryan
Virtamo, Jarmo
Albanes, Demetrius
Cancel-Tassin, Geraldine
Valeri, Antoine
Cussenot, Olivier
Offit, Kenneth
Giovannucci, Ed
Ma, Jing
Stampfer, Meir J.
Gaziano, J. Michael
Hunter, David J.
Dutra-Clarke, Ana
Kirchhoff, Tomas
Alavanja, Michael
Freeman, Laura B.
Koutros, Stella
Hoover, Robert
Berndt, Sonja I.
Hayes, Richard B.
Agalliu, Ilir
Burk, Robert D.
Wacholder, Sholom
Thomas, Gilles
Amundadottir, Laufey
TI Y chromosome haplogroups and prostate cancer in populations of European
and Ashkenazi Jewish ancestry
SO HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; SEQUENCE VARIANTS; RISK
LOCUS; IDENTIFICATION; HAPLOTYPES; MORTALITY; SWEDEN; COHORT; 8Q24
AB Genetic variation on the Y chromosome has not been convincingly implicated in prostate cancer risk. To comprehensively analyze the role of inherited Y chromosome variation in prostate cancer risk in individuals of European ancestry, we genotyped 34 binary Y chromosome markers in 3,995 prostate cancer cases and 3,815 control subjects drawn from four studies. In this set, we identified nominally significant association between a rare haplogroup, E1b1b1c, and prostate cancer in stage I (P = 0.012, OR = 0.51; 95% confidence interval 0.30-0.87). Population substructure of E1b1b1c carriers suggested Ashkenazi Jewish ancestry, prompting a replication phase in individuals of both European and Ashkenazi Jewish ancestry. The association was not significant for prostate cancer overall in studies of either Ashkenazi Jewish (1,686 cases and 1,597 control subjects) or European (686 cases and 734 control subjects) ancestry (P (meta) = 0.078), but a meta-analysis of stage I and II studies revealed a nominally significant association with prostate cancer risk (P (meta) = 0.010, OR = 0.77; 95% confidence interval 0.62-0.94). Comparing haplogroup frequencies between studies, we noted strong similarities between those conducted in the US and France, in which the majority of men carried R1 haplogroups, resembling Northwestern European populations. On the other hand, Finns had a remarkably different haplogroup distribution with a preponderance of N1c and I1 haplogroups. In summary, our results suggest that inherited Y chromosome variation plays a limited role in prostate cancer etiology in European populations but warrant follow-up in additional large and well characterized studies of multiple ethnic backgrounds.
C1 [Amundadottir, Laufey] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA.
[Thomas, Gilles] Univ Lyon 1, Synergie Lyon Canc, Ctr Leon Berard, F-69373 Lyon 08, France.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, New York, NY 10461 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY 10461 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat, New York, NY 10461 USA.
[Agalliu, Ilir; Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY 10461 USA.
[Wang, Zhaoming; Parikh, Hemang; Jia, Jinping; Myers, Timothy; Yeager, Meredith; Jacobs, Kevin B.; Hutchinson, Amy; Burdett, Laurie; Ghosh, Arpita; Albanes, Demetrius; Alavanja, Michael; Freeman, Laura B.; Koutros, Stella; Hoover, Robert; Berndt, Sonja I.; Wacholder, Sholom; Amundadottir, Laufey] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Wang, Zhaoming; Myers, Timothy; Yeager, Meredith; Jacobs, Kevin B.; Hutchinson, Amy; Burdett, Laurie] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Parikh, Hemang; Jia, Jinping; Myers, Timothy; Amundadottir, Laufey] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20877 USA.
[Thun, Michael J.; Gapstur, Susan M.; Diver, W. Ryan] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00300, Finland.
[Cancel-Tassin, Geraldine; Valeri, Antoine; Cussenot, Olivier] Hop Tenon, AP HP, Ctr Rech Pathol Prostat CeRePP, F-75020 Paris, France.
[Offit, Kenneth; Dutra-Clarke, Ana; Kirchhoff, Tomas] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, Dept Med, New York, NY 10065 USA.
[Giovannucci, Ed; Ma, Jing; Stampfer, Meir J.; Gaziano, J. Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Div Prevent Med,Dept Med, Boston, MA 02115 USA.
[Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Dept Epidemiol, Boston, MA 02115 USA.
[Kirchhoff, Tomas; Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, Dept Environm Med, New York, NY 10016 USA.
RP Amundadottir, L (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA.
EM amundadottirl@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015; Amundadottir, Laufey/L-7656-2016; Beane
Freeman, Laura/C-4468-2015
OI Hayes, Richard/0000-0002-0918-661X; Kirchhoff,
Tomas/0000-0002-9055-2364; Cancel-Tassin, Geraldine/0000-0002-9583-6382;
Amundadottir, Laufey/0000-0003-1859-8971; Beane Freeman,
Laura/0000-0003-1294-4124
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health (NIH)
FX This study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health (NIH). The authors acknowledge and thank
both staff and participants in all studies for donating their time and
making this study possible. The authors acknowledge support and
constructive comments from Dr. Stephen J. Chanock, LTG, DCEG, National
Cancer Institute. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products or
organizations imply endorsement by the US Government.
NR 45
TC 2
Z9 2
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD JUL
PY 2012
VL 131
IS 7
BP 1173
EP 1185
DI 10.1007/s00439-012-1139-5
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 957VV
UT WOS:000305195400016
PM 22271044
ER
PT J
AU Hosgood, HD
Wang, WC
Hong, YC
Wang, JC
Chen, KX
Chang, IS
Chen, CJ
Lu, DR
Yin, ZH
Wu, C
Zheng, W
Qian, BY
Park, JY
Kim, YH
Chatterjee, N
Chen, Y
Chang, GC
Hsiao, CF
Yeager, M
Tsai, YH
Wei, H
Kim, YT
Wu, W
Zhao, ZH
Chow, WH
Zhu, XL
Lo, YL
Sung, SW
Chen, KY
Yuenger, J
Kim, JH
Huang, LM
Chen, YH
Gao, YT
Kim, JH
Huang, MS
Jung, TH
Caporaso, N
Zhao, XY
Huan, Z
Yu, DK
Kim, CH
Su, WC
Shu, XO
Kim, IS
Bassig, B
Chen, YM
Cha, SI
Tan, W
Chen, HY
Yang, TY
Sung, JS
Wang, CL
Li, XL
Park, KH
Yu, CJ
Ryu, JS
Xiang, YB
Hutchinson, A
Kim, JS
Cai, QY
Landi, MT
Lee, KM
Hung, JY
Park, JY
Tucker, M
Lin, CC
Ren, YW
Perng, RP
Chen, CY
Jin, L
Chen, KC
Li, YJ
Chiu, YF
Tsai, FY
Yang, PC
Fraumeni, JF
Seow, A
Lin, DX
Zhou, BS
Chanock, S
Hsiung, CA
Rothman, N
Lan, Q
AF Hosgood, H. Dean, III
Wang, Wen-Chang
Hong, Yun-Chul
Wang, Jiu-Cun
Chen, Kexin
Chang, I-Shou
Chen, Chien-Jen
Lu, Daru
Yin, Zhihua
Wu, Chen
Zheng, Wei
Qian, Biyun
Park, Jae Yong
Kim, Yeul Hong
Chatterjee, Nilanjan
Chen, Ying
Chang, Gee-Chen
Hsiao, Chin-Fu
Yeager, Meredith
Tsai, Ying-Huang
Wei, Hu
Kim, Young Tae
Wu, Wei
Zhao, Zhenhong
Chow, Wong-Ho
Zhu, Xiaoling
Lo, Yen-Li
Sung, Sook Whan
Chen, Kuan-Yu
Yuenger, Jeff
Kim, Joo Hyun
Huang, Liming
Chen, Ying-Hsiang
Gao, Yu-Tang
Kim, Jin Hee
Huang, Ming-Shyan
Jung, Tae Hoon
Caporaso, Neil
Zhao, Xueying
Huan, Zhang
Yu, Dianke
Kim, Chang Ho
Su, Wu-Chou
Shu, Xiao-Ou
Kim, In-San
Bassig, Bryan
Chen, Yuh-Min
Cha, Sung Ick
Tan, Wen
Chen, Hongyan
Yang, Tsung-Ying
Sung, Jae Sook
Wang, Chih-Liang
Li, Xuelian
Park, Kyong Hwa
Yu, Chong-Jen
Ryu, Jeong-Seon
Xiang, Yongbing
Hutchinson, Amy
Kim, Jun Suk
Cai, Qiuyin
Landi, Maria Teresa
Lee, Kyoung-Mu
Hung, Jen-Yu
Park, Ju-Yeon
Tucker, Margaret
Lin, Chien-Chung
Ren, Yangwu
Perng, Reury-Perng
Chen, Chih-Yi
Jin, Li
Chen, Kun-Chieh
Li, Yao-Jen
Chiu, Yu-Fang
Tsai, Fang-Yu
Yang, Pan-Chyr
Fraumeni, Joseph F., Jr.
Seow, Adeline
Lin, Dongxin
Zhou, Baosen
Chanock, Stephen
Hsiung, Chao Agnes
Rothman, Nathaniel
Lan, Qing
TI Genetic variant in TP63 on locus 3q28 is associated with risk of lung
adenocarcinoma among never-smoking females in Asia
SO HUMAN GENETICS
LA English
DT Article
ID COAL COMBUSTION EMISSIONS; GENOME-WIDE ASSOCIATION; INDOOR
AIR-POLLUTION; CANCER RISK; SUSCEPTIBILITY LOCUS; CHINESE WOMEN;
XUAN-WEI; POLYMORPHISMS; POPULATIONS; METAANALYSIS
AB A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 x 10(-12)); however, this association did not achieve genome-wide significance (p a parts per thousand currency sign 10(-7)) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 x 10(-8); allelic risk = 0.80, 95% confidence interval (CI) = 0.74-0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67-0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.
C1 [Hosgood, H. Dean, III; Chatterjee, Nilanjan; Yeager, Meredith; Wei, Hu; Chow, Wong-Ho; Yuenger, Jeff; Caporaso, Neil; Bassig, Bryan; Hutchinson, Amy; Landi, Maria Teresa; Tucker, Margaret; Fraumeni, Joseph F., Jr.; Chanock, Stephen; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wang, Wen-Chang; Hsiao, Chin-Fu; Lo, Yen-Li; Chen, Ying-Hsiang; Chiu, Yu-Fang; Hsiung, Chao Agnes] Natl Hlth Res Inst, Div Biostat & Bioinformat, Inst Populat Hlth Sci, Zhunan, Taiwan.
[Hong, Yun-Chul; Lee, Kyoung-Mu] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Inst Environm Med, Seoul, South Korea.
[Wang, Jiu-Cun; Lu, Daru; Zhao, Zhenhong; Zhao, Xueying; Chen, Hongyan; Jin, Li] Fudan Univ, Minist Educ, Key Lab Contemporary Anthropol, State Key Lab Genet Engn,Sch Life Sci, Shanghai 200433, Peoples R China.
[Chen, Kexin; Qian, Biyun; Zhu, Xiaoling; Huan, Zhang] Tianjin Med Univ, Canc Hosp & Inst, Dept Epidemiol & Biostat, Tianjin 300060, Peoples R China.
[Chang, I-Shou; Tsai, Fang-Yu] Natl Hlth Res Inst, Natl Inst Canc Res, Zhunan, Taiwan.
[Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan.
[Chen, Chien-Jen; Li, Yao-Jen] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan.
[Yin, Zhihua; Wu, Wei; Li, Xuelian; Ren, Yangwu; Zhou, Baosen] China Med Univ, Sch Publ Hlth, Dept Epidemiol, Shenyang 110001, Peoples R China.
[Wu, Chen; Huang, Liming; Yu, Dianke; Tan, Wen; Lin, Dongxin] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Wu, Chen; Huang, Liming; Yu, Dianke; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol, Beijing 100730, Peoples R China.
[Wu, Chen; Huang, Liming; Yu, Dianke; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Carcinogenesis, Beijing 100730, Peoples R China.
[Wu, Chen; Huang, Liming; Yu, Dianke; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100730, Peoples R China.
[Zheng, Wei; Shu, Xiao-Ou; Cai, Qiuyin] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med,Vanderbilt Epidemiol Ctr,Inst Med & Publ, Nashville, TN 37212 USA.
[Jung, Tae Hoon; Kim, Chang Ho; Cha, Sung Ick] Kyungpook Natl Univ, Sch Med, Dept Internal Med, Taegu, South Korea.
[Kim, In-San] Kyungpook Natl Univ, Sch Med, Dept Biochem, Taegu, South Korea.
Kyungpook Natl Univ Hosp, Canc Res Ctr, Taegu, South Korea.
[Kim, Yeul Hong; Sung, Jae Sook; Park, Kyong Hwa; Kim, Jun Suk] Korea Univ, Genom Res Ctr Lung & Breast Ovarian Canc, Anam Hosp, Seoul, South Korea.
[Kim, Yeul Hong; Sung, Jae Sook; Kim, Jun Suk] Korea Univ, Coll Med, Div Brain, Dept Internal Med, Seoul 136705, South Korea.
[Kim, Yeul Hong; Park, Kyong Hwa; Kim, Jun Suk] Korea Univ, Coll Med, Div Oncol Hematol, Dept Internal Med, Seoul 136705, South Korea.
[Chen, Ying; Seow, Adeline] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore.
[Chang, Gee-Chen; Yang, Tsung-Ying; Chen, Kun-Chieh] Taichung Vet Gen Hosp, Dept Internal Med, Div Chest Med, Taichung, Taiwan.
[Chang, Gee-Chen] Natl Chung Hsing Univ, Inst Biomed Sci, Taichung 40227, Taiwan.
[Chang, Gee-Chen] China Med Univ, Sch Med, Taichung, Taiwan.
[Chang, Gee-Chen; Chen, Yuh-Min] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.
[Yeager, Meredith; Yuenger, Jeff; Hutchinson, Amy; Chanock, Stephen] NCI, Dept Hlth & Human Serv, Core Genotyping Facil,NIH, Adv Technol Program,Sci Applicat Int Corp Frederi, Frederick, MD USA.
[Tsai, Ying-Huang; Wang, Chih-Liang] Chang Gung Mem Hosp, Dept Pulm & Crit Care, Chiayi, Taiwan.
[Tsai, Ying-Huang] Chang Gung Univ, Dept Resp Care, Tao Yuan, Taiwan.
[Kim, Young Tae] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea.
[Kim, Young Tae] Seoul Natl Univ Hosp, Dept Thorac & Cardiovasc Surg, Clin Res Inst, Seoul 110744, South Korea.
[Sung, Sook Whan] Seoul Natl Univ, Coll Med, Dept Thorac & Cardiovasc Surg, Seoul, South Korea.
[Sung, Sook Whan] Seoul Natl Univ, Bundang Hosp, Dept Thorac & Cardiovasc Surg, Geongi Do, South Korea.
[Chen, Kuan-Yu; Yu, Chong-Jen; Yang, Pan-Chyr] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan.
[Chen, Kuan-Yu; Yu, Chong-Jen; Yang, Pan-Chyr] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan.
[Gao, Yu-Tang; Xiang, Yongbing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Huang, Ming-Shyan; Hung, Jen-Yu] Kaohsiung Med Univ, Sch Med, Kaohsiung, Taiwan.
[Huang, Ming-Shyan; Hung, Jen-Yu] Kaohsiung Med Univ Hosp, Dept Internal Med, Kaohsiung, Taiwan.
[Chen, Yuh-Min; Perng, Reury-Perng] Natl Cheng Kung Univ, Coll Med, Tainan 70101, Taiwan.
[Chen, Yuh-Min; Perng, Reury-Perng] Taipei Vet Gen Hosp, Chest Dept, Taipei, Taiwan.
[Su, Wu-Chou; Lin, Chien-Chung] Natl Cheng Kung Univ Hosp, Dept Internal Med, Tainan 70428, Taiwan.
[Ryu, Jeong-Seon] Inha Univ, Coll Med, Dept Internal Med, Inchon, South Korea.
[Chen, Chih-Yi] China Med Univ Hosp, Ctr Canc, Taipei, Taiwan.
RP Hosgood, HD (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8118,MCS 7240, Bethesda, MD 20892 USA.
EM hosgoodd@mail.nih.gov
RI Chang, I-Shou/D-2084-2010; Chen, Chien-Jen/C-6976-2008; Hsiung, Chao
Agnes/E-3994-2010; Hu, Wei/M-3524-2013; Wang, Jiucun/J-8744-2012; Hsiao,
Chin-Fu/E-3993-2010; Jin, Li/C-1468-2009; 김, 인산/I-8988-2014; Tucker,
Margaret/B-4297-2015; Library, JinyoungPark/F-3767-2011; Hong,
Yun-Chul/J-5725-2012; Kim, Young/J-2744-2012;
OI Wang, Jiucun/0000-0003-2765-0620; Jin, Li/0000-0002-4546-2415; Yu,
Chong-Jen/0000-0001-5664-9392; Library,
JinyoungPark/0000-0003-0952-1374; YANG, PAN-CHYR/0000-0001-6330-6048
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [R01 CA070867, R37
CA070867]
NR 34
TC 16
Z9 16
U1 2
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD JUL
PY 2012
VL 131
IS 7
BP 1197
EP 1203
DI 10.1007/s00439-012-1144-8
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 957VV
UT WOS:000305195400018
PM 22367405
ER
PT J
AU Netzel-Arnett, S
Buzza, MS
Shea-Donohue, T
Desilets, A
Leduc, R
Fasano, A
Bugge, TH
Antalis, TM
AF Netzel-Arnett, Sarah
Buzza, Marguerite S.
Shea-Donohue, Terez
Desilets, Antoine
Leduc, Richard
Fasano, Alessio
Bugge, Thomas H.
Antalis, Toni M.
TI Matriptase protects against experimental colitis and promotes intestinal
barrier recovery
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE serine protease; TTSP; DSS; colitis; IBD; matriptase
ID INFLAMMATORY-BOWEL-DISEASE; HEPATOCYTE GROWTH-FACTOR; EPITHELIAL
BARRIER; ULCERATIVE-COLITIS; CROHNS-DISEASE; TIGHT JUNCTIONS; PROTEASE;
PERMEABILITY; CELLS; MICE
AB Background: Matriptase is a membrane-anchored serine protease encoded by suppression of tumorigenicity-14 (ST14) that is required for epithelial barrier homeostasis. However, its functional role in inflammatory bowel disease (IBD) is unexplored. Methods: Matriptase expression in control, Crohn's disease, and ulcerative colitis tissue specimens was studied by quantitative polymerase chain reaction (qPCR) and immunostaining. Matriptase function was investigated by subjecting St14 hypomorphic and control littermates to dextran sodium sulfate (DSS)-induced colitis and by siRNA silencing in cultured monolayers. Mice were analyzed for clinical, histological, molecular, and cellular effects. Results: Matriptase protein and ST14 mRNA levels are significantly downregulated in inflamed colonic tissues from Crohn's disease and ulcerative colitis patients. Matriptase-deficient St14 hypomorphic mice administered DSS for 7 days followed by water without DSS for 3 days develop a severe colitis, with only 30% of the St14 hypomorphic mice surviving to day 14, compared with 100% of control littermates. Persistent colitis in surviving St14 hypomorphic mice was associated with sustained cytokine production, an inability to recover barrier integrity, and enhanced claudin-2 expression. Cytokines implicated in barrier disruption during IBD suppress matriptase expression in T84 epithelial monolayers and restoration of matriptase improves barrier integrity in the cytokine-perturbed monolayers. Conclusions: These data demonstrate a critical role for matriptase in restoring barrier function to injured intestinal mucosa during colitis, which is suppressed by excessive activation of the immune system. Strategies to enhance matriptase-mediated barrier recovery could be important for intervening in the cycle of inflammation associated with IBD. (Inflamm Bowel Dis 2011;)
C1 [Netzel-Arnett, Sarah; Buzza, Marguerite S.; Antalis, Toni M.] Univ Sherbrooke, Fac Med & Hlth Sci, Ctr Vasc & Inflammatory Dis, Quebec City, PQ, Canada.
[Netzel-Arnett, Sarah; Buzza, Marguerite S.; Antalis, Toni M.] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Physiol, Quebec City, PQ, Canada.
[Shea-Donohue, Terez; Fasano, Alessio] Univ Sherbrooke, Fac Med & Hlth Sci, Mucosal Biol Res Ctr, Quebec City, PQ, Canada.
[Desilets, Antoine; Leduc, Richard] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Pharmacol, Quebec City, PQ, Canada.
[Bugge, Thomas H.] Natl Inst Dent & Cranofacial Res, Proteases & Tissue Remodeling Sect, NIH, Bethesda, MD USA.
RP Antalis, TM (reprint author), Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, 800 W Baltimore St, Baltimore, MD 21201 USA.
EM tantalis@som.umaryland.edu
FU National Institutes of Health [DK48373, AI/DK49316, DK081376, CA098369,
HL084387]; Maryland Stem Cell Research Fund [0145-00]; Canadian
Institutes of Health Research; National Health and Medical Research
Council, Australia [384359]; [HL07698]
FX Supported in part by grants from the National Institutes of Health:
DK48373 (to A. F.); AI/DK49316 (to T. S. D.); DK081376, CA098369, and
HL084387 (to T. M. A.); the Maryland Stem Cell Research Fund 0145-00 (to
S.N.A.); HL07698 (to S.N.A.); the NIH Intramural Program (to T. H. B.);
and the Canadian Institutes of Health Research (to R. L.). M. B. was
supported by a CJ Martin Training Fellowship (#384359) from the National
Health and Medical Research Council, Australia.
NR 44
TC 22
Z9 22
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1078-0998
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD JUL
PY 2012
VL 18
IS 7
BP 1303
EP 1314
DI 10.1002/ibd.21930
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 956IP
UT WOS:000305083600016
PM 22081509
ER
PT J
AU Starks, SE
Gerr, F
Kamel, F
Lynch, CF
Alavanja, MC
Sandler, DP
Hoppin, JA
AF Starks, Sarah E.
Gerr, Fred
Kamel, Freya
Lynch, Charles F.
Alavanja, Michael C.
Sandler, Dale P.
Hoppin, Jane A.
TI High pesticide exposure events and central nervous system function among
pesticide applicators in the Agricultural Health Study
SO INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH
LA English
DT Article
DE Agricultural workers; Epidemiology; Neurobehavioral testing; Pesticide
exposure; High pesticide exposure event
ID LONG-TERM EXPOSURE; NEUROBEHAVIORAL PERFORMANCE; ORGANOPHOSPHATE
PESTICIDES; OCCUPATIONAL-EXPOSURE; NEUROPSYCHOLOGICAL PERFORMANCE;
PYRETHROID INSECTICIDES; METHYL-BROMIDE; SHEEP FARMERS; WORKERS;
NEUROTOXICITY
AB While acute pesticide poisoning can be associated with persistent adverse central nervous system (CNS) effects, little is known about the effect of one or more episodic and unusually high pesticide exposure events (HPEE) that typically do not result in acute poisoning. The objective of this investigation was to examine the association between ever having an HPEE and CNS function among licensed pesticide applicators enrolled in the Agricultural Health Study (AHS).
In 2006-2008, 693 male participants with no history of a physician-diagnosed pesticide poisoning completed nine neurobehavioral tests to assess memory, motor speed, sustained attention, verbal learning, and visual scanning and processing. Information on ever having an HPEE and pesticide poisonings was obtained from previous AHS interviews. Associations between ever having an HPEE and neurobehavioral outcomes were estimated with linear regression controlling for age and outcome-specific covariates.
A history of ever having an HPEE was reported by 156 (23%) participants. Adverse associations were observed between ever having an HPEE and two of the nine neurobehavioral tests. On a test of visual scanning and processing (Digit-Symbol), participants who ever had an HPEE were 4.2 s slower (95% CI: -7.27, -1.11) than those without an HPEE, equivalent to the effect of 3.9 years of age in this population. On a test of visual scanning and motor speed (Sequences A), participants who ever had an HPEE were 2.5 s slower (95% CI: -4.53, -0.41) than those without an HPEE, equivalent to the effect of 3.9 years of age. No significant associations were observed between participants who ever had an HPEE and the remaining neurobehavioral tests.
One or more HPEE may contribute to adverse CNS outcomes independent of diagnosed pesticide poisoning.
C1 [Starks, Sarah E.; Gerr, Fred] Univ Iowa, Dept Occupat & Environm Hlth, Iowa City, IA 52242 USA.
[Kamel, Freya; Sandler, Dale P.; Hoppin, Jane A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA.
[Alavanja, Michael C.] NCI, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA.
RP Gerr, F (reprint author), Univ Iowa, Dept Occupat & Environm Hlth, Univ Iowa Res Pk,140 IREH, Iowa City, IA 52242 USA.
EM fred-gerr@uiowa.edu
OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018
FU National Institute of Environmental Health Sciences [R01-ES013067-03,
Z01ES049039]; NIH; National Cancer Institute [Z01CP010119]
FX We thank Mr. Stuart Long for data analysis support and the Iowa and
North Carolina field station staff (Ms. Ellen Heywood and Ms. Margaret
Hayslip). We are especially grateful to the late Richard Letz, PhD, for
his valuable technical assistance with the design of the neurobehavioral
testing procedures as well as his in-kind contribution of the NES3
software. This study was supported by a grant from the National
Institute of Environmental Health Sciences (R01-ES013067-03), and, in
part, by funding from the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences (Z01ES049039), and
National Cancer Institute (Z01CP010119).
NR 57
TC 8
Z9 8
U1 2
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-0131
J9 INT ARCH OCC ENV HEA
JI Int. Arch. Occup. Environ. Health
PD JUL
PY 2012
VL 85
IS 5
BP 505
EP 515
DI 10.1007/s00420-011-0694-8
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 957AQ
UT WOS:000305131300005
PM 21927986
ER
PT J
AU Bekelman, JE
Deye, JA
Vikram, B
Bentzen, SM
Bruner, D
Curran, WJ
Dignam, J
Efstathiou, JA
FitzGerald, TJ
Hurkmans, C
Ibbott, GS
Lee, JJ
Merchant, TE
Michalski, J
Palta, JR
Simon, R
Ten Haken, RK
Timmerman, R
Tunis, S
Coleman, CN
Purdy, J
AF Bekelman, Justin E.
Deye, James A.
Vikram, Bhadrasain
Bentzen, Soren M.
Bruner, Deborah
Curran, Walter J., Jr.
Dignam, James
Efstathiou, Jason A.
FitzGerald, T. J.
Hurkmans, Coen
Ibbott, Geoffrey S.
Lee, J. Jack
Merchant, Thomas E.
Michalski, Jeff
Palta, Jatinder R.
Simon, Richard
Ten Haken, Randal K.
Timmerman, Robert
Tunis, Sean
Coleman, C. Norman
Purdy, James
TI Redesigning Radiotherapy Quality Assurance: Opportunities to Develop an
Efficient, Evidence-Based System to Support Clinical Trials-Report of
the National Cancer Institute Work Group on Radiotherapy Quality
Assurance
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Review
DE Clinical trial design; Credentialing; Radiotherapy; Quality assurance
ID PEDIATRIC-ONCOLOGY-GROUP; RADIATION-THERAPY; DOSIMETRY; IMPACT
AB Purpose: In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute sponsored a 2-day workshop to examine challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design.
Methods and Materials: Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. The lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities such as proton beam therapy, and the international harmonization of clinical trial QA.
Results: Four recommendations were made: (1) to develop a tiered (and more efficient) system for radiotherapy QA and tailor the intensity of QA to the clinical trial objectives (tiers include general credentialing, trial-specific credentialing, and individual case review); (2) to establish a case QA repository; (3) to develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and (4) to explore the feasibility of consolidating clinical trial QA in the United States.
Conclusion: Radiotherapy QA can affect clinical trial accrual, cost, outcomes, and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based. (C) 2012 Elsevier Inc.
C1 [Bekelman, Justin E.; Bruner, Deborah] Univ Penn, Philadelphia, PA 19104 USA.
[Deye, James A.; Vikram, Bhadrasain; Coleman, C. Norman] NCI, Bethesda, MD 20892 USA.
[Bentzen, Soren M.] Univ Wisconsin, Madison, WI USA.
[Curran, Walter J., Jr.] Emory Univ, Atlanta, GA 30322 USA.
[Dignam, James] Univ Chicago, Chicago, IL 60637 USA.
[Efstathiou, Jason A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[FitzGerald, T. J.] Univ Massachusetts, Boston, MA 02125 USA.
[Hurkmans, Coen] European Org Res Treatment Canc, Brussels, Belgium.
[Ibbott, Geoffrey S.; Lee, J. Jack] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Merchant, Thomas E.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Michalski, Jeff] Washington Univ, St Louis, MO USA.
[Palta, Jatinder R.] Univ Florida, Miami, FL USA.
[Simon, Richard] NIH, Bethesda, MD 20892 USA.
[Ten Haken, Randal K.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Timmerman, Robert] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Tunis, Sean] Ctr Med Technol Policy, Baltimore, MD USA.
[Purdy, James] Univ Calif Davis, Davis, CA 95616 USA.
RP Bekelman, JE (reprint author), Univ Penn, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM bekelman@uphs.upenn.edu
RI Bentzen, Soren/E-3997-2012; Timmerman, Robert/C-2222-2013
OI Bentzen, Soren/0000-0002-7444-7564;
FU National Institutes of Health; National Cancer Institute Radiation
Research Program
FX Dr. Fitzgerald received National Institutes of Health funding to his
institution to support the Quality Assurance Review Center. Dr.
Michalski received National Institutes of Health funding to his
institution to support the Advanced Technology Consortium.; We
acknowledge the support of the National Cancer Institute Radiation
Research Program in sponsoring the conference. We are grateful to the
anonymous reviewers for constructive comments that improved the report.
NR 21
TC 25
Z9 25
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 1
PY 2012
VL 83
IS 3
BP 782
EP 790
DI 10.1016/j.ijrobp.2011.12.080
PG 9
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 958QR
UT WOS:000305256000025
PM 22425219
ER
PT J
AU Braunschweig, D
Duncanson, P
Boyce, R
Hansen, R
Ashwood, P
Pessah, IN
Hertz-Picciotto, I
Van de Water, J
AF Braunschweig, Daniel
Duncanson, Paul
Boyce, Robert
Hansen, Robin
Ashwood, Paul
Pessah, Isaac N.
Hertz-Picciotto, Irva
Van de Water, Judy
TI Behavioral Correlates of Maternal Antibody Status Among Children with
Autism
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Autism; Maternal antibodies; Autoantibodies; Fetal brain
ID FETAL-BRAIN; SPECTRUM DISORDER; IMMUNOGLOBULIN-G; AUTOANTIBODIES;
PREGNANCY; TRANSPORT; MOTHERS; CHARGE
AB Autism spectrum disorders (ASDs) affect approximately 1 in 110 children in the United States. This report profiles fetal-brain reactive autoantibodies of a large cohort of mothers of children with autism and controls, yielding significant associations between the presence of IgG reactivity to fetal brain proteins at 37 and 73 kDa and a childhood diagnosis of full autism (p = 0.0005), which also correlated with lower expressive language scores (p = 0.005). Additionally, we report on reactivity to proteins at 39 and 73 kDa, which correlated with the broader diagnosis of ASD (p = 0.0007) and increased irritability on the Aberrant Behavioral Checklist (p = 0.05). This study provides evidence of multiple patterns of reactivity to fetal brain proteins by maternal antibodies associated with ASD and specific childhood behavioral outcomes.
C1 [Braunschweig, Daniel; Duncanson, Paul; Boyce, Robert; Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA.
[Braunschweig, Daniel; Hansen, Robin; Ashwood, Paul; Pessah, Isaac N.; Hertz-Picciotto, Irva; Van de Water, Judy] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA.
[Braunschweig, Daniel; Hansen, Robin; Ashwood, Paul; Pessah, Isaac N.; Hertz-Picciotto, Irva; Van de Water, Judy] Univ Calif Davis, NIEHS, Ctr Childrens Environm Hlth, Davis, CA 95616 USA.
[Hansen, Robin] Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA.
[Ashwood, Paul] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA.
[Pessah, Isaac N.] Univ Calif Davis, Dept Vet Mol Biosci, Davis, CA 95616 USA.
[Hertz-Picciotto, Irva] Univ Calif Davis, Dept Publ Hlth Sci, Div Epidemiol, Davis, CA 95616 USA.
RP Van de Water, J (reprint author), Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, 451 E Hlth Sci Dr,Suite 6510 GBSF, Davis, CA 95616 USA.
EM javandewater@ucdavis.edu
FU NIEHS NIH HHS [1 P01 ES11269-01, P01 ES011269]
NR 31
TC 32
Z9 33
U1 0
U2 7
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD JUL
PY 2012
VL 42
IS 7
BP 1435
EP 1445
DI 10.1007/s10803-011-1378-7
PG 11
WC Psychology, Developmental
SC Psychology
GA 958IV
UT WOS:000305231000015
PM 22012245
ER
PT J
AU Tai, B
McLellan, AT
AF Tai, Betty
McLellan, A. Thomas
TI Integrating information on substance use disorders into electronic
health record systems
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Substance abuse; Health information; Electronic health record system;
Patient confidentiality; Patient safety
ID ALCOHOL-USE DISORDERS; PRIMARY-CARE SETTINGS; ABUSE SCREENING-TEST;
BRIEF INTERVENTIONS; COLLABORATIVE PROJECT; BREAST-CANCER; DRUG-USE;
CONSUMPTION; RISK; METAANALYSIS
AB For reasons of safety and effectiveness, many forces in health care, especially the Affordable Care Act of 2010, are pressing for improved identification and management of substance use disorders within mainstream health care. Thus, standard information about patient substance use will have to be collected and used by providers within electronic health record systems (EHRS). Although there are many important technical, legal, and patient confidentiality issues that must be dealt with to achieve integration, this article focuses upon efforts by the National Institute on Drug Abuse and other federal agencies to develop a common set of core questions to screen, diagnose, and initiate treatment for substance use disorders as part of national EHRS. This article discusses the background and rationale for these efforts and presents the work to date to identify the questions and to promote information sharing among health care providers. Published by Elsevier Inc.
C1 [Tai, Betty] Natl Inst Drug Abuse, Clin Trials Network, Natl Inst Hlth, Bethesda, MD USA.
[McLellan, A. Thomas] Univ Penn, Sch Med, Penn Ctr Substance Abuse Solut, Philadelphia, PA 19104 USA.
RP Tai, B (reprint author), Natl Inst Drug Abuse, Clin Trials Network, Natl Inst Hlth, Bethesda, MD USA.
EM btai@nida.nih.gov
FU Intramural NIH HHS [Z99 DA999999]
NR 55
TC 10
Z9 10
U1 4
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD JUL
PY 2012
VL 43
IS 1
BP 12
EP 19
DI 10.1016/j.jsat.2011.10.010
PG 8
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 959JI
UT WOS:000305308300002
PM 22154827
ER
PT J
AU Simonetti, A
Mariotto, A
Krapcho, M
Feuer, EJ
AF Simonetti, Arianna
Mariotto, Angela
Krapcho, Martin
Feuer, Eric J.
TI Improved population-based probability of developing cancer when direct
estimates of the cancer-free population are available
SO LIFETIME DATA ANALYSIS
LA English
DT Article
DE Lifetime risk; Cancer; Prevalence; Life table
ID AGE-CONDITIONAL PROBABILITIES; DEVELOPING BREAST-CANCER; REGISTRY DATA;
PREVALENCE; VARIANCE; LIFETIME
AB Age-conditional probabilities of developing a first cancer represent the transition from being cancer-free to developing a first cancer. Natural inputs into their calculation are rates of first cancer per person-years alive and cancer-free. However these rates are not readily available because they require information on the cancer-free population. Instead rates of first cancer per person-years alive, calculated using as denominator the mid-year populations, available from census data, can be easily calculated from cancer registry data. Methods have been developed to estimate age-conditional probabilities of developing cancer based on these easily available rates per person-years alive that do not directly account for the cancer-free population. In the last few years models (Merrill et al., Int J Epidemiol 29(2):197-207, 2000; Mariotto et al., SEER Cancer Statistics Review, 2002; Clegg et al., Biometrics 58(3):684-688, 2002; Gigli et al., Stat Methods Med Res 15(3):235-253, 2006, and software (ComPrev:Complete Prevalence Software, Version 1.0, 2005) have been developed that allow estimation of cancer prevalence (DevCan: Probability of Developing or Dying of Cancer Software, Version 6.0, 2005). Estimates of population-based cancer prevalence allows for the estimation of the cancer-free population and consequently of rates per person-years alive and cancer-free. In this paper we present a method that directly estimates the age-conditional probabilities of developing a first cancer using rates per person-years alive and cancer-free obtained from prevalence estimates. We explore conditions when the previous and the new estimators give similar or different values using real data from the Surveillance, Epidemiology and End Results (SEER) program.
C1 [Simonetti, Arianna] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Simonetti, Arianna] Ist Super Sanita, Dept Canc Epidemiol, Natl Ctr Epidemiol Surveillance & Hlth Promot, I-00161 Rome, Italy.
[Simonetti, Arianna] Univ Roma La Sapienza, Dept Stat Probabil & Appl Stat, Rome, Italy.
[Mariotto, Angela; Feuer, Eric J.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Krapcho, Martin] Informat Management Serv IMS Inc, Silver Spring, MD USA.
RP Simonetti, A (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM 210 WOC1,Suite 316N, Rockville, MD 20852 USA.
EM Arianna.Simonetti@fda.hhs.gov
FU National Cancer Institute (NCI) Office of International Affairs (OIA)
FX This work was partially funded by the National Cancer Institute (NCI)
Office of International Affairs (OIA) Scientific Exchange Program.
NR 18
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1380-7870
J9 LIFETIME DATA ANAL
JI Lifetime Data Anal.
PD JUL
PY 2012
VL 18
IS 3
BP 284
EP 301
DI 10.1007/s10985-012-9216-6
PG 18
WC Mathematics, Interdisciplinary Applications; Statistics & Probability
SC Mathematics
GA 958FG
UT WOS:000305221300002
PM 22430932
ER
PT J
AU Liu, CY
Liu, YC
Venkatesh, BA
Lima, JAC
Bluemke, DA
Steenbergen, C
AF Liu, Chia-Ying
Liu, Yuan Chang
Venkatesh, Bharath Ambale
Lima, Joao A. C.
Bluemke, David A.
Steenbergen, Charles
TI Heterogeneous distribution of myocardial steatosis-An ex vivo evaluation
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE cardiac steatosis; magnetic resonance spectroscopy; heterogeneity; ex
vivo
ID LOCALIZED PROTON SPECTROSCOPY; DIASTOLIC DYSFUNCTION; TRIGLYCERIDE
CONTENT; RESONANCE-SPECTROSCOPY; INDEPENDENT PREDICTOR; FAT
QUANTIFICATION; DIABETES-MELLITUS; IN-VIVO; HUMANS; HEART
AB Myocardial fat accumulation could occur in diseased hearts. The degree of heterogeneity is unknown because accurate assessment is difficult using conventional proton magnetic resonance spectroscopy techniques in a beating heart. The purpose of this study was to characterize the distribution of intramyocellular lipid content and to determine its association with disease characteristics. Proton magnetic resonance spectroscopy was performed on formalin-fixed slices of human hearts at various circumferential locations (N = 55). Twenty-nine percent of the hearts had the highest fat content measured in the septum, followed by posterior (27%), lateral (26%), and anterior (18%) wall. Age was significantly correlated with the mean fat percentages (r2 = 0.12, P = 0.007). Those who died from cardiovascular disease demonstrated significantly higher and more heterogeneous fat distribution than those who did not (1.62% +/- 1.1% vs. 0.59% +/- 0.4%, P = 0.002). In summary, septal fat content is representative of mean fat percentage. Fat content increases with age; fat distribution may be heterogeneous when associated with cardiovascular disease. Magn Reson Med, 2012. (C) 2012 Wiley Periodicals, Inc.
C1 [Liu, Chia-Ying; Liu, Yuan Chang; Venkatesh, Bharath Ambale; Lima, Joao A. C.; Bluemke, David A.] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA.
[Bluemke, David A.] NIH, Bethesda, MD 20892 USA.
[Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
RP Liu, CY (reprint author), Johns Hopkins Univ Hosp, Dept Radiol, MRI Room 110,600 N Wolfe St, Baltimore, MD 21287 USA.
EM Cliu51@jhmi.edu
RI Ambale Venkatesh, Bharath/F-4941-2016;
OI Ambale Venkatesh, Bharath/0000-0002-2330-2373; Bluemke,
David/0000-0002-8323-8086
FU NIH [R21HL098827]
FX Grant sponsor: NIH; Grant number: R21HL098827.
NR 30
TC 4
Z9 4
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUL
PY 2012
VL 68
IS 1
BP 1
EP 7
DI 10.1002/mrm.24332
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 956WA
UT WOS:000305119100001
PM 22576623
ER
PT J
AU Moriyama, B
Henning, SA
Leung, J
Falade-Nwulia, O
Jarosinski, P
Penzak, SR
Walsh, TJ
AF Moriyama, Brad
Henning, Stacey A.
Leung, Janice
Falade-Nwulia, Oluwaseun
Jarosinski, Paul
Penzak, Scott R.
Walsh, Thomas J.
TI Adverse interactions between antifungal azoles and vincristine: review
and analysis of cases
SO MYCOSES
LA English
DT Review
DE Azole antifungal; vincristine; drug interactions
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DRUG-INTERACTIONS; INDUCED NEUROTOXICITY;
CLINICAL-RELEVANCE; CYP2C19 GENOTYPE; CANCER-PATIENTS; ORAL SOLUTION;
ITRACONAZOLE; PHARMACOKINETICS; VORICONAZOLE
AB Triazole and imidazole antifungal agents inhibit metabolism of vincristine, leading to excess vinca alkaloid exposure and severe neurotoxicity. Recent reports of debilitating interactions between vincristine and itraconazole, as well as posaconazole, voriconazole and ketoconazole underscore the need to improve medical awareness of this adverse combination. We, therefore, undertook a comprehensive analysis of reports of adverse drug interactions (ADIs) with the combination of vincristine and azole antifungal agents, established a new classification, and provided a detailed summary of these toxicities. In patients who had sufficient data for analysis, 47 individuals were identified who had an ADI with the combination of vincristine and antifungal azoles. Median age was 8 years (1.368 years) with 33(70%) having a diagnosis of acute lymphoblastic leukaemia. Median time to ADI with vincristine was 9.5 days with itraconazole, 13.5 days posaconazole and 30 days voriconazole. The median number of vincristine doses preceding the ADI was 2 doses with itraconazole, 3 doses posaconazole and 2 doses voriconazole. The most common severe ADIs included gastrointestinal toxicity, peripheral neuropathy, hyponatremia/SIADH, autonomic neuropathy and seizures. Recovery from these ADIs occurred in 80.6% of patients. We recommend using alternative antifungal agents if possible in patients receiving vincristine to avoid this serious and potentially life-threatening drug interaction.
C1 [Walsh, Thomas J.] Cornell Univ, Weill Cornell Med Ctr, Div Infect Dis, Transplantat Oncol Infect Dis Program, New York, NY 10065 USA.
[Moriyama, Brad; Henning, Stacey A.; Jarosinski, Paul; Penzak, Scott R.] NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA.
[Leung, Janice; Falade-Nwulia, Oluwaseun] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
RP Walsh, TJ (reprint author), Cornell Univ, Weill Cornell Med Ctr, Div Infect Dis, Transplantat Oncol Infect Dis Program, 1300 York Ave,A-421, New York, NY 10065 USA.
EM thw2003@med.cornell.edu
FU National Institutes of Health; Vestagen
FX This study was supported in part by the intramural research program of
the National Institutes of Health.; Dr Walsh is the recipient of a
research grant from Vestagen and has served on advisory boards of
Novartis, Ico, and Trius.
NR 39
TC 32
Z9 33
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0933-7407
EI 1439-0507
J9 MYCOSES
JI Mycoses
PD JUL
PY 2012
VL 55
IS 4
BP 290
EP 297
DI 10.1111/j.1439-0507.2011.02158.x
PG 8
WC Dermatology; Mycology
SC Dermatology; Mycology
GA 956WV
UT WOS:000305121200003
PM 22126626
ER
PT J
AU Wilcox, AJ
Buekens, P
AF Wilcox, Allen J.
Buekens, Pierre
TI Jean Golding - an Appreciation
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Editorial Material
C1 [Wilcox, Allen J.] NIEHS, Epidemiol Branch, Durham, NC 27709 USA.
[Buekens, Pierre] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
RP Wilcox, AJ (reprint author), NIEHS, Epidemiol Branch, MD A3-05,POB 12233, Durham, NC 27709 USA.
EM wilcox@niehs.nih.gov
OI Wilcox, Allen/0000-0002-3376-1311
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD JUL
PY 2012
VL 26
IS 4
BP 302
EP 302
DI 10.1111/j.1365-3016.2012.01297.x
PG 1
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 956WY
UT WOS:000305121500002
PM 22686376
ER
PT J
AU Dixon, D
Reed, CE
Moore, AB
Gibbs-Flournoy, EA
Hines, EP
Wallace, EA
Stanko, JP
Lu, Y
Jefferson, WN
Newbold, RR
Fenton, SE
AF Dixon, Darlene
Reed, Casey E.
Moore, Alicia B.
Gibbs-Flournoy, Eugene A.
Hines, Erin P.
Wallace, Elizabeth A.
Stanko, Jason P.
Lu, Yi
Jefferson, Wendy N.
Newbold, Retha R.
Fenton, Suzanne E.
TI Histopathologic changes in the uterus, cervix and vagina of immature
CD-1 mice exposed to low doses of perfluorooctanoic acid (PFOA) in a
uterotrophic assay
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Article
DE PFOA; Immature mice; Uterotrophic assay; Uterus; Cervix; Vagina;
Pathology; Estradiol
ID MAMMARY-GLAND DEVELOPMENT; MINNOWS GOBIOCYPRIS-RARUS; PERFLUOROALKYL
ACIDS; RAINBOW-TROUT; FEMALE RATS; MOUSE; EXPRESSION; ESTROGEN;
EPITHELIUM; MILK
AB The estrogenic and antiestrogenic potential of perfluorooctanoic acid (PFOA) was assessed using an immature mouse uterotrophic assay and by histologic evaluation of the uterus, cervix and vagina following treatment. Female offspring of CD-1 dams were weaned at 18 days old and assigned to groups of equal weight, and received 0, 0.01, 0.1, or 1 mg PFOA/kg BW/d by gavage with or without 17-beta estradiol (E-2. 500 mu g/kg/d) from PND 18-20 (n = 8/treatment/block). At 24h after the third dose (PND 21), uteri were removed and weighed. Absolute and relative uterine weights were significantly increased in the 0.01 mg/kg PFOA only group. Characteristic estrogenic changes were present in all E-2-treated mice; however, they were minimally visible in the 0.01 PFOA only mice. These data suggest that at a low dose PFOA produces minimal histopathologic changes in the reproductive tract of immature female mice, and does not antagonize the histopathologic effects of E-2. Published by Elsevier Inc.
C1 [Dixon, Darlene; Reed, Casey E.; Moore, Alicia B.; Wallace, Elizabeth A.; Stanko, Jason P.; Fenton, Suzanne E.] Natl Inst Environm Hlth Sci, Natl Toxicol Program NTP Labs Branch, Div NTP, Natl Inst Hlth,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Gibbs-Flournoy, Eugene A.] Univ N Carolina, Toxicol Curriculum, Chapel Hill, NC 27599 USA.
[Hines, Erin P.] US EPA, Environm Media Assessment Grp, NCEA, ORD, Res Triangle Pk, NC 27711 USA.
[Lu, Yi] Social & Sci Syst Inc, Durham, NC 27703 USA.
[Jefferson, Wendy N.] Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Div Intramural Res, Natl Inst Hlth,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Newbold, Retha R.] Natl Inst Environm Hlth Sci, NTP, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Fenton, SE (reprint author), Natl Inst Environm Hlth Sci, Natl Toxicol Program NTP Labs Branch, Div NTP, Natl Inst Hlth,Dept Hlth & Human Serv, POB 12233,MDE1-08 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM dixon@niehs.nih.gov; fentonse@niehs.nih.gov
OI Hines, Erin Pias/0000-0002-2458-6267
FU Division of the National Toxicology Program of the NIH; National
Institute of Environmental Health Sciences; U.S. EPA's National Health
and Environmental Effects Laboratory
FX This research was supported by the Division of the National Toxicology
Program of the NIH, National Institute of Environmental Health Sciences
and the U.S. EPA's National Health and Environmental Effects Laboratory.
The authors would like to thank Drs. Ronald Herbert and Mark Cesta for
their critical review of the manuscript. Ms. Casey E. Reed is a contract
employee of the National Toxicology Program, National Institute of
Environmental Health Sciences.
NR 42
TC 9
Z9 10
U1 0
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD JUL
PY 2012
VL 33
IS 4
SI SI
BP 506
EP 512
DI 10.1016/j.reprotox.2011.10.011
PG 7
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA 959HI
UT WOS:000305303100009
PM 22146484
ER
PT J
AU Iben, JR
Maraia, RJ
AF Iben, James R.
Maraia, Richard J.
TI tRNAomics: tRNA gene copy number variation and codon use provide
bioinformatic evidence of a new anticodon: codon wobble pair in a
eukaryote
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE copy number variation; tRNA
ID SCHIZOSACCHAROMYCES-POMBE; POLYMERASE-III; FISSION YEAST;
ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; EXPRESSED GENES; LA PROTEIN;
GENOMIC SEQUENCE; CELL-CYCLE; USAGE
AB tRNA genes are interspersed throughout eukaryotic DNA, contributing to genome architecture and evolution in addition to translation of the transcriptome. Codon use correlates with tRNA gene copy number in noncomplex organisms including yeasts. Synonymous codons impact translation with various outcomes, dependent on relative tRNA abundances. Availability of whole-genome sequences allowed us to examine tRNA gene copy number variation (tgCNV) and codon use in four Schizosaccharomyces species and Saccharomyces cerevisiae. tRNA gene numbers vary from 171 to 322 in the four Schizosaccharomyces despite very high similarity in other features of their genomes. In addition, we performed whole-genome sequencing of several related laboratory strains of Schizosaccharomyces pombe and found tgCNV at a cluster of tRNA genes. We examined for the first time effects of wobble rules on correlation of tRNA gene number and codon use and showed improvement for S. cerevisiae and three of the Schizosaccharomyces species. In contrast, correlation in Schizosaccharomyces japonicus is poor due to markedly divergent tRNA gene content, and much worsened by the wobble rules. In japonicus, some tRNA iso-acceptor genes are absent and others are greatly reduced relative to the other yeasts, while genes for synonymous wobble iso-acceptors are amplified, indicating wobble use not apparent in any other eukaryote. We identified a subset of japonicus-specific wobbles that improves correlation of codon use and tRNA gene content in japonicus. We conclude that tgCNV is high among Schizo species and occurs in related laboratory strains of S. pombe (and expectedly other species), and tRNAome-codon analyses can provide insight into species-specific wobble decoding.
C1 [Iben, James R.; Maraia, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Maraia, Richard J.] US PHS, Commissioned Corps, Rockville, MD 20852 USA.
RP Maraia, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM maraiar@mail.nih.gov
FU Intramural Research Program on Genomics of Differentiation in the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX We thank N. Rhind and others at the Broad Institute for making Sz.
octosporus, Sz. japonicus, and Sz. cryophilus sequence data available
and for providing the wild-type Sz. pombe strain yFS101; and I.
Targanski and V. Cherkasova for insightful comments. This work was
supported by the Intramural Research Program on Genomics of
Differentiation in the Eunice Kennedy Shriver National Institute of
Child Health and Human Development.
NR 58
TC 24
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U1 1
U2 11
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1355-8382
J9 RNA
JI RNA-Publ. RNA Soc.
PD JUL
PY 2012
VL 18
IS 7
BP 1358
EP 1372
DI 10.1261/rna.032151.111
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 959WP
UT WOS:000305349000006
PM 22586155
ER
PT J
AU Murphy, EL
Sabino, E
Ribeiro, A
Salemi, V
Antunes, A
Menezes, M
Ianni, B
Nastari, L
Fernandez, F
Patavino, G
Sachdev, V
Capuani, L
Neto, CD
Oliveira, CD
Carrick, D
Wright, D
Custer, B
Busch, MP
Murphy, EL
AF Murphy, E. L.
Sabino, E.
Ribeiro, A.
Salemi, V
Antunes, A.
Menezes, M.
Ianni, B.
Nastari, L.
Fernandez, F.
Patavino, G.
Sachdev, V
Capuani, L.
De Almeida Neto, C.
Di Lorenzo Oliveira, C.
Carrick, D.
Wright, D.
Custer, B.
Busch, M. P.
Murphy, E. L.
TI TEN-YEAR INCIDENCE OF CHAGAS CARDIOMYOPATHY AMONG ASYMPTOMATIC T. CRUZI
SEROPOSITIVE, FORMER BLOOD DONORS
SO VOX SANGUINIS
LA English
DT Meeting Abstract
C1 [Murphy, E. L.; Custer, B.; Busch, M. P.; Murphy, E. L.] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA.
[Sabino, E.; Patavino, G.; De Almeida Neto, C.] Univ Sao Paulo, Sao Paulo, Brazil.
[Ribeiro, A.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil.
[Salemi, V; Ianni, B.] INCOR HCFMUSP, Sao Paulo, Brazil.
[Antunes, A.; Menezes, M.; Di Lorenzo Oliveira, C.] Fundacao Hemominas, Belo Horizonte, MG, Brazil.
[Nastari, L.; Fernandez, F.] Inst Heart, Sao Paulo, Brazil.
[Sachdev, V] NHLBI, NIH, Bethesda, MD 20892 USA.
[Capuani, L.] Hemoctr Sao Paulo, Fundacao Pro Sangue, Sao Paulo, Brazil.
[Carrick, D.; Wright, D.] Westat Corp, Rockville, MD USA.
RI Nastari, Luciano/C-8528-2012; Ribeiro, Antonio/C-2707-2009; de
Almeida-Neto, Cesar/O-9224-2014; Sabino, Ester/F-7750-2010; Salemi,
Vera/C-9104-2013; Ianni, Barbara/C-7689-2012
OI Nastari, Luciano/0000-0002-7959-3827; Ribeiro,
Antonio/0000-0002-2740-0042; Sabino, Ester/0000-0003-2623-5126; Salemi,
Vera/0000-0002-7152-1810; Ianni, Barbara/0000-0002-1588-5492
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0042-9007
J9 VOX SANG
JI Vox Sang.
PD JUL
PY 2012
VL 103
SU 1
SI SI
BP 180
EP 181
PG 2
WC Hematology
SC Hematology
GA 960SP
UT WOS:000305410601134
ER
PT J
AU von Zabern, I
Doescher, A
Flegel, WA
Wagner, FF
Gropp, A
Scharberg, EA
Burkhart, J
AF von Zabern, I
Doescher, A.
Flegel, W. A.
Wagner, F. F.
Gropp, A.
Scharberg, E. A.
Burkhart, J.
TI THE HYBRID RHD ALLELE RHD-CE(3-4)-D REPRESENTS DFR-5, A NEW MEMBER IN
THE DFR FAMILY OF PARTIAL D
SO VOX SANGUINIS
LA English
DT Meeting Abstract
C1 [von Zabern, I] Inst Clin Transfus Med & Immunogenet Ulm, Ulm, Germany.
[Doescher, A.] Inst Oldenburg, DRK Blood Donor Serv NSTOB, Oldenburg, Germany.
[Flegel, W. A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Wagner, F. F.] Inst Springe, DRK Blood Donor Serv NSTOB, Springe, Germany.
[Gropp, A.] Univ Freiburg, Cent Facil Transfus Med, D-79106 Freiburg, Germany.
[Scharberg, E. A.] Inst Baden Baden, DRK Blood Donor Serv Baden Wurtt Hessen, Baden Baden, Germany.
[Burkhart, J.] Inst Munich, BRK Blood Donor Serv, Munich, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0042-9007
J9 VOX SANG
JI Vox Sang.
PD JUL
PY 2012
VL 103
SU 1
SI SI
BP 213
EP 213
PG 1
WC Hematology
SC Hematology
GA 960SP
UT WOS:000305410601235
ER
PT J
AU Lai, JP
Raffeld, M
Tsokos, M
Rosenberg, S
Lee, CC
AF Lai, Jinping
Raffeld, Mark
Tsokos, Maria
Rosenberg, Steven
Lee, Chyi-chia
TI NY-ESO-1 Differentiates Synovial Sarcoma From Other Sarcomas
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Meeting Abstract
C1 [Lai, Jinping; Raffeld, Mark; Tsokos, Maria; Lee, Chyi-chia] NCI, Pathol, NIH, Bethesda, MD 20892 USA.
[Rosenberg, Steven] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9173
EI 1943-7722
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD JUL 1
PY 2012
VL 138
SU 1
MA 230
BP A230
EP A230
PG 1
WC Pathology
SC Pathology
GA V45XG
UT WOS:000209848700215
ER
PT J
AU Bekker, LG
Beyrer, C
Quinn, TC
AF Bekker, Linda-Gail
Beyrer, Chris
Quinn, Thomas C.
TI Behavioral and Biomedical Combination Strategies for HIV Prevention
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID SEXUALLY-TRANSMITTED INFECTIONS; SUB-SAHARAN AFRICA; ACTIVE
ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED
CONTROLLED-TRIAL; FEMALE SEX WORKERS; HOMOSEXUAL BISEXUAL MEN;
HERPES-SIMPLEX-VIRUS; MALE CIRCUMCISION; HETEROSEXUAL TRANSMISSION
AB Around 2.5 million people become infected with HIV each year. This extraordinary toll on human life and public health worldwide will only be reversed with effective prevention. What's more, in the next few years, it is likely at least, that no single prevention strategy will be sufficient to contain the spread of the disease. There is a need for combination prevention as there is for combination treatment, including biomedical, behavioral, and structural interventions. Expanded HIV prevention must be grounded in a systematic analysis of the epidemic's dynamics in local contexts. Although 85% of HIV is transmitted sexually, effective combinations of prevention have been shown for people who inject drugs. Combination prevention should be based on scientifically derived evidence, with input and engagement from local communities that fosters the successful integration of care and treatment.
C1 [Bekker, Linda-Gail] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa.
[Bekker, Linda-Gail] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa.
[Beyrer, Chris] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Quinn, Thomas C.] NIAID, Sect Int HIV STD Res, NIH, Bethesda, MD 20892 USA.
RP Bekker, LG (reprint author), Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa.
EM Linda-gail.bekker@hiv-research.org.za
NR 145
TC 0
Z9 0
U1 1
U2 1
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD JUL
PY 2012
VL 4
IS 7
AR a007435
DI 10.1101/cshperspect.a007435
PG 23
WC Cell Biology
SC Cell Biology
GA 995RH
UT WOS:000308029300005
ER
PT J
AU Sizemore, CF
Schleif, AC
Bernstein, JB
Heilman, CA
AF Sizemore, Christine F.
Schleif, Amanda C.
Bernstein, Jessica B.
Heilman, Carole A.
TI The role of biomedical research in global tuberculosis control: gaps and
challenges A perspective from the US National Institute of Allergy and
Infectious Diseases, National Institutes of Health
SO EMERGING MICROBES & INFECTIONS
LA English
DT Review
DE biomedical research; TB diagnostics; TB therapeutics; TB vaccines;
tuberculosis (TB); US National Institute of Allergy and Infectious
Diseases (NIAID); US National Institutes of Health (NIH)
AB Tuberculosis (TB) has been a persistent public health concern for hundreds of years. Despite advances in medicine and science, eliminating this disease has been beyond our reach. Several organizations, including the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), have expressed their commitment to advancing biomedical research in TB in order to increase our understanding of the causative pathogen and the disease. This basic knowledge is a critical first step in the development and implementation of new therapeutics, vaccines and diagnostics. Collaboration between researchers is a key component to accomplishing this goal; product development can no longer be limited to separate programs. Rather, the interconnectedness and possible combination of interventions must be investigated. This review will discuss ongoing TB research including NIAID's role, as well as future research that is needed to improve TB control. Emphasizing the importance of coordination among researchers, funders and advocacy groups, we aim to illustrate the fact that biomedical research, and particularly basic research, is a vital part of a complementary approach to eliminating TB across the globe.
C1 [Sizemore, Christine F.; Schleif, Amanda C.; Bernstein, Jessica B.; Heilman, Carole A.] NIAID, Bethesda, MD 20892 USA.
RP Schleif, AC (reprint author), NIAID, 6610 Rockledge Dr, Bethesda, MD 20892 USA.
EM schleifac@niaid.nih.gov
NR 59
TC 3
Z9 3
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2222-1751
J9 EMERG MICROBES INFEC
JI Emerg. Microbes Infect.
PD JUL
PY 2012
VL 1
AR e9
DI 10.1038/emi.2012.21
PG 6
WC Immunology; Microbiology
SC Immunology; Microbiology
GA V33DF
UT WOS:000208998800006
PM 26038420
ER
PT J
AU Barber, MD
Janz, N
Kenton, K
Hsu, Y
Greer, WJ
Dyer, K
White, A
Meikle, S
Ye, W
AF Barber, Matthew D.
Janz, Nancy
Kenton, Kim
Hsu, Yvonne
Greer, W. Jerod
Dyer, Keisha
White, Amanda
Meikle, Susan
Ye, Wen
TI Validation of the Surgical Pain Scales in Women Undergoing Pelvic
Reconstructive Surgery
SO FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY
LA English
DT Article
DE postoperative pain; scales; pelvic reconstructive surgery; pelvic organ
prolapse
AB Objective: Surgical pain scales (SPS) consist of 4 items that measure pain at rest, during normal activities, and during work/exercise and quantify unpleasantness of worst pain, which are valid and responsive in men undergoing hernia repair. Our objective was to evaluate the psychometric properties of SPS in women undergoing vaginal surgery for pelvic organ prolapse and stress urinary incontinence.
Methods: We modified SPS by converting original response scales from a visual analog scale to numerical rating scales. Numerical rating scales have lower error rates and higher validity than visual analog scale. The sample included 169 women with stage II to IV pelvic organ prolapse and stress urinary incontinence in a randomized trial comparing sacrospinous ligament fixation to uterosacral vault suspension with and without pelvic floor muscle training. Participants completed SPS and SF-36 at baseline, and 2 weeks and 6 months after surgery. Construct validity and responsiveness were examined in cross-sectional and longitudinal data using Pearson correlation and analysis of variance.
Results: Pain at rest, during normal activities, and during work/exercise worsened at 2 weeks (P < 0.05); and all measures of pain improved from baseline to 6 months (P < 0.0001). Construct validity was demonstrated by correlations of 0.51 to 0.74 between SPS and the SF-36 Bodily Pain Scale (P < 0.0001). Pain worsened on SF-36 between baseline and 2 weeks in 63% of the participants, and this group demonstrated a mean (SD) increase in pain of 1.9 (2.8) on the SPS (effect size, 0.99), confirming responsiveness of the scale.
Conclusions: The modified SPS are valid and responsive in women after pelvic reconstructive surgery.
C1 [Barber, Matthew D.] Cleveland Clin, Cleveland, OH 44195 USA.
[Barber, Matthew D.] Cleveland Clin, Womens Hlth Inst, Cleveland, OH 44195 USA.
[Janz, Nancy; Ye, Wen] Univ Michigan, Data Coordinating Ctr, Ann Arbor, MI 48109 USA.
[Kenton, Kim] Loyola Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
[Kenton, Kim] Loyola Univ, Dept Urol, Chicago, IL 60611 USA.
[Hsu, Yvonne] Univ Utah, Med Ctr, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA.
[Greer, W. Jerod] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
[Dyer, Keisha] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92103 USA.
[White, Amanda] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA.
[Meikle, Susan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Barber, MD (reprint author), Cleveland Clin, 9500 Euclid Ave,Desk A81, Cleveland, OH 44195 USA.
EM barberm2@ccf.org
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; NIH Office of Research on Women's Health [U01 HD41249, U10
HD41250, U10 HD41261, U10 HD41267, U10 HD54136, U10 HD54214, U10
HD54215, U10 HD54241]
FX This work was supported by grants from The Eunice Kennedy Shriver
National Institute of Child Health and Human Development and the NIH
Office of Research on Women's Health (U01 HD41249, U10 HD41250, U10
HD41261, U10 HD41267, U10 HD54136, U10 HD54214, U10 HD54215, and U10
HD54241).
NR 16
TC 4
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2151-8378
J9 FEMALE PELVIC MED RE
JI Female Pelvic Med. Reconstr. Surg.
PD JUL-AUG
PY 2012
VL 18
IS 4
BP 198
EP 204
DI 10.1097/SPV.0b013e31825d65aa
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA V35XJ
UT WOS:000209178200003
PM 22777367
ER
PT J
AU Barber, MD
Kenton, K
Janz, NK
Hsu, Y
Dyer, KY
Greer, WJ
White, A
Meikle, S
Ye, W
AF Barber, Matthew D.
Kenton, Kim
Janz, Nancy K.
Hsu, Yvonne
Dyer, Keisha Y.
Greer, W. Jerod
White, Amanda
Meikle, Susie
Ye, Wen
TI Validation of the Activities Assessment Scale in Women Undergoing Pelvic
Reconstructive Surgery
SO FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY
LA English
DT Article
DE functional activity; postoperative activity; scales; pelvic
reconstructive surgery; pelvic organ prolapse
AB Objective: The Activities Assessment Scale (AAS) is a 13-item postoperative functional activity scale validated in men who underwent hernia surgery. We evaluated the psychometric characteristics of the AAS in women who underwent vaginal surgery for pelvic organ prolapse (POP) and stress urinary incontinence (SUI).
Methods: Participants included 163 women with POP and SUI enrolled in a randomized trial comparing sacrospinous ligament fixation to uterosacral vault suspension with and without perioperative pelvic floor muscle training. Participants completed the AAS and SF-36 at baseline and 2 weeks and 6 months postoperatively. Internal reliability of the AAS was evaluated using Cronbach alpha. Construct validity and responsiveness were examined in cross-sectional and longitudinal data using Pearson correlation coefficient and analysis of variance. The AAS is scored from zero to 100 (higher scores = better function).
Results: Mean (SD) baseline AAS score was 87 (17.3) (range, 25-100). Functional activity declined from baseline to 2 weeks postoperatively (mean change, -4.5; 95% confidence interval, -7.6 to -1.42) but improved above baseline at 6 months (mean change, +10.9; 95% confidence interval, 7.8-14.0). Internal reliability of the AAS was excellent (Cronbach alpha = 0.93). Construct validity was demonstrated by a correlation of 0.59 to 0.60 between the AAS and SF-36 physical functioning scale (P < 0.0001) and lower correlations between the AAS and other SF-36 scales. Patients who improved in physical functioning based on the SF-36 between 2 weeks and 6 months postoperatively showed an effect size of 0.86 for change in the AAS over the same period.
Conclusions: The AAS is a valid, reliable, and responsive measure for evaluation of physical function in women after pelvic reconstructive surgery.
C1 [Barber, Matthew D.] Cleveland Clin, Cleveland, OH 44195 USA.
[Barber, Matthew D.] Cleveland Clin, Womens Hlth Inst, Cleveland, OH 44195 USA.
[Kenton, Kim] Loyola Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
[Kenton, Kim] Loyola Univ, Dept Urol, Chicago, IL 60611 USA.
[Janz, Nancy K.; Ye, Wen] Univ Michigan, Data Coordinating Ctr, Ann Arbor, MI 48109 USA.
[Hsu, Yvonne] Univ Utah, Med Ctr, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA.
[Dyer, Keisha Y.] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92103 USA.
[Greer, W. Jerod] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
[White, Amanda] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA.
[Meikle, Susie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Barber, MD (reprint author), Cleveland Clin, 9500 Euclid Ave,Desk A81, Cleveland, OH 44195 USA.
EM barberm2@ccf.org
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; NIH Office of Research on Women's Health [U01 HD41249, U10
HD41250, U10 HD41261, U10 HD41267, U10 HD54136, U10 HD54214, U10
HD54215, U10 HD54241]
FX This work was supported by grants from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development and the NIH
Office of Research on Women's Health (U01 HD41249, U10 HD41250, U10
HD41261, U10 HD41267, U10 HD54136, U10 HD54214, U10 HD54215, and U10
HD54241).
NR 21
TC 5
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2151-8378
J9 FEMALE PELVIC MED RE
JI Female Pelvic Med. Reconstr. Surg.
PD JUL-AUG
PY 2012
VL 18
IS 4
BP 205
EP 210
DI 10.1097/SPV.0b013e31825e6422
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA V35XJ
UT WOS:000209178200004
PM 22777368
ER
PT J
AU Mancini, M
Carlson-Kuhta, P
Zampieri, C
Nutt, JG
Chiari, L
Horak, FB
AF Mancini, Martina
Carlson-Kuhta, Patricia
Zampieri, Cris
Nutt, John G.
Chiari, Lorenzo
Horak, Fay B.
TI Postural sway as a marker of progression in Parkinson's disease: A pilot
longitudinal study
SO GAIT & POSTURE
LA English
DT Article
DE Parkinson's disease progression; Posture; Accelerometry
ID BALANCE; INSTABILITY; STANCE; QUIET; LEVODOPA; ONSET; TRUNK; LOOP
AB Objective measures of postural control that are sensitive to Parkinson's disease (PD) progression would improve patient care and accelerate clinical trials. Although measures of postural sway during quiet stance in untreated PD have been shown to differ from age-matched control subjects, it is not known if sway measures change with disease progression in early PD. In this pilot study, we asked whether accelerometer-based metrics of sway could provide a practical tool for monitoring progression of postural dyscontrol in people with untreated or newly treated PD.
We examined 13 subjects with PD and 12 healthy, age-matched control subjects. The PD subjects had been recently diagnosed and had not started any antiparkinsonian medications at the baseline session. All subjects were tested 3-6 months and 12 months after the baseline session. Subjects were asked to stand quietly for two minutes while wearing an inertial sensor on their posterior trunk that measured trunk linear acceleration.
Our results suggested that objective sway measures deteriorated over one year despite minimal changes in UPDRS motor scores. Medio-lateral (ML) sway measures were more sensitive than anteroposterior sway measures in detecting progression. The ML JERK was larger in the PD group than the control group across all three testing sessions. The ML sway dispersion and ML sway velocity were also significantly higher in PD compared to control subjects by the 12-month evaluation. It is feasible to measure progression of PD prior to onset of treatment using accelerometer-based measures of quiet standing. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Mancini, Martina; Carlson-Kuhta, Patricia; Nutt, John G.; Horak, Fay B.] Oregon Hlth & Sci Univ, Dept Neurol, Sch Med, Beaverton, OR 97006 USA.
[Mancini, Martina; Chiari, Lorenzo] Univ Bologna, Biomed Engn Unit, Dept Elect Comp Sci & Syst, Alma Mater Studiorum, I-40136 Bologna, Italy.
[Zampieri, Cris] NIH, Funct & Appl Biomech Lab, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Mancini, M (reprint author), Dept Neurol, Balance Disorder Lab, OHSU 505 NW 185th Ave, Beaverton, OR USA.
EM mancinim@ohsu.edu
OI Chiari, Lorenzo/0000-0002-2318-4370
FU Kinetics Foundation; National Institute on Aging (NIA) [006457];
Intramural Research Program of the NIH
FX We thank all the participants, Triana Nagel for recruiting subjects and
data collection assistance, and Edward King for technical assistance.
This research was supported by grants from the Kinetics Foundation and
the National Institute on Aging (NIA, 006457). This research was also
supported in part by the Intramural Research Program of the NIH. Dr.
Horak was a consultant for Kinetics Foundation.
NR 25
TC 47
Z9 49
U1 0
U2 14
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0966-6362
J9 GAIT POSTURE
JI Gait Posture
PD JUL
PY 2012
VL 36
IS 3
BP 471
EP 476
DI 10.1016/j.gaitpost.2012.04.010
PG 6
WC Neurosciences; Orthopedics; Sport Sciences
SC Neurosciences & Neurology; Orthopedics; Sport Sciences
GA 157OP
UT WOS:000319908600027
PM 22750016
ER
PT J
AU Deverka, PA
Schully, SD
Ishibe, N
Carlson, JJ
Freedman, A
Goddard, KAB
Khoury, MJ
Ramsey, SD
AF Deverka, Patricia A.
Schully, Sheri D.
Ishibe, Naoko
Carlson, Josh J.
Freedman, Andrew
Goddard, Katrina A. B.
Khoury, Muin J.
Ramsey, Scott D.
TI Stakeholder assessment of the evidence for cancer genomic tests:
insights from three case studies
SO GENETICS IN MEDICINE
LA English
DT Article
DE EGFR testing; evidence-based decision making; genomic testing; Lynch
syndrome; Oncotype DX; stakeholder engagement
ID CELL LUNG-CANCER; BREAST-CANCER; AMERICAN SOCIETY; GENE-EXPRESSION;
ONCOLOGY; RECOMMENDATIONS; PREVENTION; MEDICINE
AB Purpose: Insufficient evidence on the net benefits and harms of genomic tests in real-world settings is a translational barrier for genomic medicine. Understanding stakeholders' assessment of the current evidence base for clinical practice and coverage decisions should be a critical step in influencing research, policy, and practice.
Methods: Twenty-two stakeholders participated in a workshop exploring the evidence of genomic tests for clinical and coverage decision making. Stakeholders completed a survey prior to and during the meeting. They also discussed if they would recommend for or against current clinical use of each test.
Results: At baseline, the level of confidence in the clinical validity and clinical utility of each test varied, although the group expressed greater confidence for epidermal growth factor receptor mutation and Lynch syndrome testing than for Oncotype DX. Following the discussion, survey results reflected even less confidence for Oncotype DX and epidermal growth factor receptor mutation testing, but not for Lynch syndrome testing. The majority of stakeholders would consider clinical use for all three tests, but under the conditions of additional research or a shared clinical decision-making approach.
Conclusion: Stakeholder engagement in unbiased settings is necessary to understand various perspectives about evidentiary thresholds in genomic medicine. Participants recommended the use of various methods for evidence generation and synthesis.
C1 [Schully, Sheri D.; Ishibe, Naoko; Freedman, Andrew; Khoury, Muin J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Deverka, Patricia A.] Ctr Med Technol Policy, Baltimore, MD USA.
[Carlson, Josh J.] Univ Washington, Seattle, WA 98195 USA.
[Goddard, Katrina A. B.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA.
[Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Schully, SD (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM schullys@mail.nih.gov
FU National Cancer Institute (NCI); CANCER-GEN (Comparative Effectiveness
Research in Cancer Genomics) through the American Recovery and
Reinvestment Act by the NCI, National Institutes of Health [RC2CA138570]
FX Funding for the workshop was provided by the National Cancer Institute
(NCI). This study was also supported, in part, by CANCER-GEN
(Comparative Effectiveness Research in Cancer Genomics) through the
American Recovery and Reinvestment Act of 2009 by the NCI, National
Institutes of Health, under agency award no. RC2CA138570 (S.D.R.,
principal investigator). The authors acknowledge the contributions of
Camilla Marie Benedicto, public health advisor, and Kelly Bennett,
presidential management fellow, for their roles in planning the meeting.
NR 25
TC 10
Z9 10
U1 0
U2 4
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 JUL
PY 2012
VL 14
IS 7
BP 656
EP 662
DI 10.1038/gim.2012.3
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 971YB
UT WOS:000306241800004
PM 22481130
ER
PT J
AU Hayes, LM
AF Hayes, Lindsay M.
TI National Study of Jail Suicide: 20 Years Later
SO JOURNAL OF CORRECTIONAL HEALTH CARE
LA English
DT Article
DE jail; suicide prevention; correctional health care
AB Findings from a national study of jail suicide are provided, including the extent and distribution of suicides in holding and detention facilities, and descriptive data on demographic characteristics of each victim, incident, and facility. Among significant findings are that suicides were evenly distributed from first few days of confinement to over several months of confinement, many suicides occurred during waking hours, most inmates were not under the influence of drugs and/or alcohol at the time of death, and many suicides occurred in close proximity to a court hearing. Suicide prevention programming was found to be uneven in most facilities that experienced suicides. There has been a significant decrease in the rate of suicide in detention facilities.
C1 [Hayes, Lindsay M.] Natl Ctr Inst & Alternat, Mansfield, MA USA.
RP Hayes, LM (reprint author), 40 Lantern Lane, Mansfield, MA 02058 USA.
EM lhayesta@msn.com
NR 36
TC 11
Z9 11
U1 0
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1078-3458
EI 1940-5200
J9 J CORRECT HEALTH CAR
JI J. Correct. Health Care
PD JUL
PY 2012
VL 18
IS 3
BP 233
EP 245
DI 10.1177/1078345812445457
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA V32ZN
UT WOS:000208989200006
PM 22569904
ER
PT J
AU Parascandola, M
AF Parascandola, Mark
TI The Smokeless Tobacco Industry's Use Of Sports Medicine In Marketing And
Promotion
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Parascandola, Mark] NCI, Rockville, MD USA.
EM markparascandola@yahoo.com
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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2012
VL 27
SU 2
MA 1359
BP 276
EP 276
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V35IG
UT WOS:000209142901116
ER
PT J
AU Brown, JC
Huedo-Medina, TB
Johnson, BT
Pescatello, SM
Ryan, SM
Ferrer, RA
Pescatello, LS
AF Brown, Justin C.
Huedo-Medina, Tania B.
Johnson, Blair T.
Pescatello, Shannon M.
Ryan, Stacey M.
Ferrer, Rebecca A.
Pescatello, Linda S.
TI The Efficacy Of Exercise Interventions On Depression Among
Cancer-Survivors: A Meta-Analysis
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Brown, Justin C.; Huedo-Medina, Tania B.; Johnson, Blair T.; Pescatello, Linda S.] Univ Connecticut, Storrs, CT USA.
[Pescatello, Shannon M.] Western New England Coll, Springfield, MA USA.
[Ryan, Stacey M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Ferrer, Rebecca A.] NCI, Rockville, MD 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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2012
VL 27
SU 2
MA 1362
BP 277
EP 278
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V35IG
UT WOS:000209142901119
ER
PT J
AU DellaValle, DM
Haas, JD
AF DellaValle, Diane M.
Haas, Jere D.
TI What Is The Impact Of Iron Supplementation On Training Quality In
Non-anemic Female Rowers?
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [DellaValle, Diane M.] NIH, Bethesda, MD 20892 USA.
[Haas, Jere D.] Cornell Univ, Ithaca, NY 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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2012
VL 27
SU 2
MA 2004
BP 510
EP 510
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V35IG
UT WOS:000209142902116
ER
PT J
AU Caserotti, P
Rasmussen, C
Lysdahlgaard, M
Puggaard, L
Harris, T
Aagaard, P
AF Caserotti, Paolo
Rasmussen, Cuno
Lysdahlgaard, Morten
Puggaard, Lis
Harris, Tamara
Aagaard, Per
TI Effects of Heavy-resistance Power Training on Force Steadiness in Old
and Very Old Women
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Caserotti, Paolo; Harris, Tamara] NIH, Maryland, WA USA.
[Rasmussen, Cuno] Univ Aarhus, Aarhus, Denmark.
[Lysdahlgaard, Morten; Puggaard, Lis; Aagaard, Per] Univ Southern Denmark, Odense, Denmark.
EM paagaard@health.sdu.dk
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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2012
VL 27
SU 2
MA 2014
BP 513
EP 513
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V35IG
UT WOS:000209142902126
ER
PT J
AU Volshoj, E
Thorlund, JB
Andrijauskaite, Z
Caserotti, P
Aagaard, P
AF Volshoj, Esben
Thorlund, Jonas B.
Andrijauskaite, Zita
Caserotti, Paolo
Aagaard, Per
TI Transitional Postural Stability Differs Between Male and Female Team
Handball Players: Potential Implications for ACL Injury
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Volshoj, Esben; Thorlund, Jonas B.; Aagaard, Per] Univ Southern Denmark, Odense, Denmark.
[Andrijauskaite, Zita] Lithuanian Acad Phys Educ, Kaunas, Lithuania.
[Caserotti, Paolo] NIH, Maryland, WA USA.
EM paagaard@health.sdu.dk
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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2012
VL 27
SU 2
MA 2062
BP 530
EP 531
PG 3
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V35IG
UT WOS:000209142902174
ER
PT J
AU Aagaard, P
Eie, R
Harris, T
Caserotti, P
AF Aagaard, Per
Eie, Rune
Harris, Tamara
Caserotti, Paolo
TI Explosive-type Heavy-resistance Strength Training Leads To Improved
Postural Stability in 60 And 80-yr Old Women
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Aagaard, Per; Eie, Rune] Inst Sports Sci & Clin Biomech, Odense, Denmark.
[Harris, Tamara; Caserotti, Paolo] NIH, Bethesda, MD USA.
EM paagaard@health.sdu.dk
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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2012
VL 27
SU 2
MA 2063
BP 531
EP 531
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V35IG
UT WOS:000209142902175
ER
PT J
AU Gabriel, KKP
McClain, JJ
Schmid, KK
High, RR
Whitfield, GP
Ainsworth, BE
AF Gabriel, Kelley K. Pettee
McClain, James J.
Schmid, Kendra K.
High, Robin R.
Whitfield, Geoffrey P.
Ainsworth, Barbara E.
TI Descriptive Study Of Accelerometer-derived Measures Of Sedentary
Behavior In Middle-aged Women
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Gabriel, Kelley K. Pettee; Whitfield, Geoffrey P.] Univ Texas Austin, Sch Publ Hlth, Austin, TX 78712 USA.
[McClain, James J.] Canc Prevent Fellowship Program, Bethesda, MD USA.
[McClain, James J.] NCI, Bethesda, MD 20892 USA.
[Schmid, Kendra K.; High, Robin R.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Ainsworth, Barbara E.] Arizona State Univ, Mesa, AZ USA.
EM Kelley.P.Gabriel@uth.tmc.edu
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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2012
VL 27
SU 2
MA 2084
BP 538
EP 538
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V35IG
UT WOS:000209142902196
ER
PT J
AU McClain, JJ
Troiano, RP
Berrigan, D
Brychta, RJ
Koster, A
AF McClain, James J.
Troiano, Richard P.
Berrigan, David
Brychta, Robert J.
Koster, Annemarie
TI Principal Component Analysis of Accelerometer-Assessed Daily Physical
Activity and Inactivity Among Adults
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [McClain, James J.; Troiano, Richard P.; Berrigan, David] NCI, Bethesda, MD 20892 USA.
[Brychta, Robert J.] NIDDK, Bethesda, MD USA.
[Koster, Annemarie] NIA, Bethesda, MD 20892 USA.
EM james.mcclain@nih.gov
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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2012
VL 27
SU 2
MA 2087
BP 539
EP 539
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V35IG
UT WOS:000209142902199
ER
PT J
AU Hoehner, CM
Handy, SL
Yan, Y
Blair, SN
Berrigan, D
AF Hoehner, Christine M.
Handy, Susan L.
Yan, Yan
Blair, Steven N.
Berrigan, David
TI Association Between Neighborhood Walkability, Cardiorespiratory Fitness,
And Body-Mass Index
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Hoehner, Christine M.; Yan, Yan] Washington Univ, St Louis, MO USA.
[Handy, Susan L.] Univ Calif Davis, Davis, CA 95616 USA.
[Blair, Steven N.] Univ S Carolina, Columbia, SC 29208 USA.
[Berrigan, David] NCI, Bethesda, MD 20892 USA.
EM hoehnerc@wustl.edu
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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2012
VL 27
SU 2
MA 2169
BP 569
EP 570
PG 3
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V35IG
UT WOS:000209142902281
ER
PT J
AU Cunningham, B
Sellers, SL
Bonham, VL
Cooper, LA
AF Cunningham, Brooke
Sellers, Sherrill L.
Bonham, Vence L.
Cooper, Lisa A.
TI PHYSICIAN ANXIETY DUE TO UNCERTAINTY AND THE USE OF RACE IN MEDICAL
DECISION MAKING
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Cunningham, Brooke; Cooper, Lisa A.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Sellers, Sherrill L.] Miami Univ, Oxford, OH 45056 USA.
[Bonham, Vence L.] NHGRI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2012
VL 27
SU 2
BP S273
EP S273
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V35IG
UT WOS:000209142900410
ER
PT J
AU Phillips, KA
Epstein, DH
Reamer, D
Bart, G
Preston, KL
AF Phillips, Karran A.
Epstein, David H.
Reamer, Dave
Bart, Gavin
Preston, Kenzie L.
TI METHADONE DOSE-RELATED INCREASE IN QTC WITHOUT CLINICALLY SIGNIFICANT
PROLONGATION OR ARRHYTHMIA
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Phillips, Karran A.; Epstein, David H.; Reamer, Dave; Preston, Kenzie L.] NIDA, NIH, Baltimore, MD USA.
[Bart, Gavin] Univ Minnesota, Minneapolis, MN 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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2012
VL 27
SU 2
BP S247
EP S247
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V35IG
UT WOS:000209142900349
ER
PT J
AU Prithviraj, R
Trunova, S
Giniger, E
AF Prithviraj, Ranjini
Trunova, Svetlana
Giniger, Edward
TI Ex vivo Culturing of Whole, Developing Drosophila Brains
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Neuroscience; Issue 65; Developmental Biology; Physiology; Drosophila;
mushroom body; ex vivo; organ culture; pruning; pharmacology
AB We describe a method for ex vivo culturing of whole Drosophila brains. This can be used as a counterpoint to chronic genetic manipulations for investigating the cell biology and development of central brain structures by allowing acute pharmacological interventions and live imaging of cellular processes. As an example of the technique, prior work from our lab(1) has shown that a previously unrecognized subcellular compartment lies between the axonal and somatodendritic compartments of axons of the Drosophila central brain. The development of this compartment, referred to as the axon initial segment (AIS)(2), was shown genetically to depend on the neuron-specific cyclin-dependent kinase, Cdk5. We show here that ex vivo treatment of wild-type Drosophila larval brains with the Cdk5-specific pharmacological inhibitors roscovitine and olomoucine(3) causes acute changes in actin organization, and in localization of the cell-surface protein Fasciclin 2, that mimic the changes seen in mutants that lack Cdk5 activity genetically.
A second example of the ex vivo culture technique is provided for remodeling of the connections of embryonic mushroom body (MB) gamma neurons during metamorphosis from larva to adult. The mushroom body is the center of olfactory learning and memory in the fly(4), and these gamma neurons prune their axonal and dendritic branches during pupal development and then re-extend branches at a later timepoint to establish the adult innervation pattern(5). Pruning of these neurons of the MB has been shown to occur via local degeneration of neurite branches(6), by a mechanism that is triggered by ecdysone, a steroid hormone, acting at the ecdysone receptor B1(7), and that is dependent on the activity of the ubiquitin-proteasome system(6). Our method of ex vivo culturing can be used to interrogate further the mechanism of developmental remodeling. We found that in the ex vivo culture setting, gamma neurons of the MB recapitulated the process of developmental pruning with a time course similar to that in vivo. It was essential, however, to wait until 1.5 hours after puparium formation before explanting the tissue in order for the cells to commit irreversibly to metamorphosis; dissection of animals at the onset of pupariation led to little or no metamorphosis in culture. Thus, with appropriate modification, the ex vivo culture approach can be applied to study dynamic as well as steady state aspects of central brain biology.
C1 [Prithviraj, Ranjini; Trunova, Svetlana; Giniger, Edward] NINDS, Bethesda, MD 20892 USA.
[Prithviraj, Ranjini; Trunova, Svetlana; Giniger, Edward] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Giniger, E (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM ginigere@ninds.nih.gov
RI Giniger, Edward/C-1764-2015
OI Giniger, Edward/0000-0002-8340-6158
FU Basic Neuroscience Program of the NINDS Intramural Research Program, NIH
[Z01 NS003106]
FX We would like to thank all the members of our lab for their advice,
useful discussions and comments on the manuscript. We would also
particularly like to thank Marta Koch and Bassem Hassan for the
excellent suggestion that we wait until 1.5 hours APF before dissecting
brains for culturing in remodeling experiments. We also thank the NHGRI
imaging facility for the use of their confocal microscope. This work was
supported by the Basic Neuroscience Program of the NINDS Intramural
Research Program, NIH (Z01 NS003106).
NR 13
TC 1
Z9 1
U1 2
U2 5
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD JUL
PY 2012
IS 65
AR UNSP e4270
DI 10.3791/4270
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36PJ
UT WOS:000209223200050
ER
PT J
AU Coviello, AD
Haring, R
Wellons, M
Vaidya, D
Lehtimaki, T
Keildson, S
Lunetta, KL
He, CY
Fornage, M
Lagou, V
Mangino, M
Onland-Moret, NC
Chen, B
Eriksson, J
Garcia, M
Mei, Y
Koster, A
Lohman, K
Lyytikainen, LP
Petersen, AK
Prescott, J
Stolk, L
Vandenput, L
Wood, AR
Zhuang, WV
Ruokonen, A
Hartikainen, AL
Pouta, A
Bandinelli, S
Biffar, R
Brabant, G
Cox, DG
Chen, YH
Cummings, S
Ferrucci, L
Gunter, MJ
Hankinson, SE
Martikainen, H
Hofman, A
Homuth, G
Illig, T
Jansson, JO
Johnson, AD
Karasik, D
Karlsson, M
Kettunen, J
Kiel, DP
Kraft, P
Liu, J
Ljunggren, O
Lorentzon, M
Maggio, M
Markus, MRP
Mellstrom, D
Miljkovic, I
Mirel, D
Nelson, S
Papunen, LM
Peeters, PHM
Prokopenko, I
Raffel, L
Reincke, M
Reiner, AP
Rexrode, K
Rivadeneira, F
Schwartz, SM
Siscovick, D
Soranzo, N
Stockl, D
Tworoger, S
Uitterlinden, AG
van Gils, CH
Vasan, RS
Wichmann, HE
Zhai, GJ
Bhasin, S
Bidlingmaier, M
Chanock, SJ
De Vivo, I
Harris, TB
Hunter, DJ
Kahonen, M
Liu, SM
Ouyang, P
Spector, TD
van der Schouw, YT
Viikari, J
Wallaschofski, H
McCarthy, MI
Frayling, TM
Murray, A
Franks, S
Jarvelin, MR
de Jong, FH
Raitakari, O
Teumer, A
Ohlsson, C
Murabito, JM
Perry, JRB
AF Coviello, Andrea D.
Haring, Robin
Wellons, Melissa
Vaidya, Dhananjay
Lehtimaki, Terho
Keildson, Sarah
Lunetta, Kathryn L.
He, Chunyan
Fornage, Myriam
Lagou, Vasiliki
Mangino, Massimo
Onland-Moret, N. Charlotte
Chen, Brian
Eriksson, Joel
Garcia, Melissa
Mei, Yong
Koster, Annemarie
Lohman, Kurt
Lyytikainen, Leo-Pekka
Petersen, Ann-Kristin
Prescott, Jennifer
Stolk, Lisette
Vandenput, Liesbeth
Wood, Andrew R.
Zhuang, Wei Vivian
Ruokonen, Aimo
Hartikainen, Anna-Liisa
Pouta, Anneli
Bandinelli, Stefania
Biffar, Reiner
Brabant, Georg
Cox, David G.
Chen, Yuhui
Cummings, Steven
Ferrucci, Luigi
Gunter, Marc J.
Hankinson, Susan E.
Martikainen, Hannu
Hofman, Albert
Homuth, Georg
Illig, Thomas
Jansson, John-Olov
Johnson, Andrew D.
Karasik, David
Karlsson, Magnus
Kettunen, Johannes
Kiel, Douglas P.
Kraft, Peter
Liu, Jingmin
Ljunggren, Osten
Lorentzon, Mattias
Maggio, Marcello
Markus, Marcello R. P.
Mellstrom, Dan
Miljkovic, Iva
Mirel, Daniel
Nelson, Sarah
Papunen, Laure Morin
Peeters, Petra H. M.
Prokopenko, Inga
Raffel, Leslie
Reincke, Martin
Reiner, Alex P.
Rexrode, Kathryn
Rivadeneira, Fernando
Schwartz, Stephen M.
Siscovick, David
Soranzo, Nicole
Stockl, Doris
Tworoger, Shelley
Uitterlinden, Andre G.
van Gils, Carla H.
Vasan, Ramachandran S.
Wichmann, H. -Erich
Zhai, Guangju
Bhasin, Shalender
Bidlingmaier, Martin
Chanock, Stephen J.
De Vivo, Immaculata
Harris, Tamara B.
Hunter, David J.
Kahonen, Mika
Liu, Simin
Ouyang, Pamela
Spector, Tim D.
van der Schouw, Yvonne T.
Viikari, Jorma
Wallaschofski, Henri
McCarthy, Mark I.
Frayling, Timothy M.
Murray, Anna
Franks, Steve
Jarvelin, Marjo-Riitta
de Jong, Frank H.
Raitakari, Olli
Teumer, Alexander
Ohlsson, Claes
Murabito, Joanne M.
Perry, John R. B.
TI A Genome-Wide Association Meta-Analysis of Circulating Sex
Hormone-Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid
Hormone Regulation
SO PLOS GENETICS
LA English
DT Article
ID POLYCYSTIC-OVARY-SYNDROME; RECEPTOR TYROSINE KINASE; HAN CHINESE
POPULATION; INSULIN-RECEPTOR; GENE-EXPRESSION; SHBG GENE; MEDICAL
PROGRESS; GCKR RS780094; RISK; POLYMORPHISM
AB Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8x10(-106)), PRMT6 (rs17496332, 1p13.3, p=1.4x10(-11)), GCKR (rs780093, 2p23.3, p=2.2x10(-16)), ZBTB10 (rs440837, 8q21.13, p=3.4x10(-09)), JMJD1C (rs7910927, 10q21.3, p=6.1x10(-35)), SLCO1B1 (rs4149056, 12p12.1, p=1.9x10(-08)), NR2F2 (rs8023580, 15q26.2, p=8.3x10(-12)), ZNF652 (rs2411984, 17q21.32, p=3.5x10(-14)), TDGF3 (rs1573036, Xq22.3, p=4.1x10(-14)), LHCGR (rs10454142, 2p16.3, p=1.3x10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p=2.7x10(-08)), and UGT2B15 (rs293428, 4q13.2, p=5.5x10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5x10(-08), women p=0.66, heterogeneity p=0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained similar to 15.6% and similar to 8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
C1 [Coviello, Andrea D.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
[Coviello, Andrea D.; Bhasin, Shalender] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
[Coviello, Andrea D.; Vasan, Ramachandran S.] Natl Heart Lng & Blood Inst Framingham Heart Stud, Framingham, MA USA.
[Haring, Robin; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Univ Med, Greifswald, Germany.
[Wellons, Melissa] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Wellons, Melissa] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
[Vaidya, Dhananjay] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Lehtimaki, Terho] Tampere Univ Hosp, Fimlab Labs, Dept Clin Chem, Tampere, Finland.
[Lehtimaki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Keildson, Sarah; Lagou, Vasiliki; Chen, Yuhui; Prokopenko, Inga; Perry, John R. B.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Lunetta, Kathryn L.; Zhuang, Wei Vivian] Boston Univ, Sch Publ Hlth, Dept Biostat, 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.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Lagou, Vasiliki] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Soranzo, Nicole; Zhai, Guangju; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Onland-Moret, N. Charlotte; van Gils, Carla H.; van der Schouw, Yvonne T.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Chen, Brian] Univ Calif Los Angeles, Program Genom & Nutr, Los Angeles, CA USA.
[Chen, Brian] Univ Calif Los Angeles, Ctr Metab Dis Prevent, Sch Publ Hlth, Los Angeles, CA USA.
[Eriksson, Joel; Vandenput, Liesbeth; Jansson, John-Olov; Lorentzon, Mattias; Mellstrom, Dan; Ohlsson, Claes] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden.
[Garcia, Melissa; Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Mei, Yong; Lohman, Kurt] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Mei, Yong] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Petersen, Ann-Kristin] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Prescott, Jennifer; De Vivo, Immaculata; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Prescott, Jennifer; Hankinson, Susan E.; Tworoger, Shelley; De Vivo, Immaculata; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Prescott, Jennifer; Hankinson, Susan E.; Karasik, David; Kiel, Douglas P.; Tworoger, Shelley; De Vivo, Immaculata; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA.
[Stolk, Lisette; Uitterlinden, Andre G.; de Jong, Frank H.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Stolk, Lisette; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Netherlands Consortium Healthy Aging, Rotterdam, Netherlands.
[Wood, Andrew R.; Frayling, Timothy M.; Murray, Anna; Perry, John R. B.] Univ Exeter, Peninsula Med Sch, Exeter, Devon, England.
[Ruokonen, Aimo] Univ Oulu, Inst Diagnost, Oulu, Finland.
[Hartikainen, Anna-Liisa; Papunen, Laure Morin] Univ Hosp Oulu, Dept Obstet & Gynecol, Oulu, Finland.
[Pouta, Anneli] Univ Oulu, Natl Inst Hlth & Welf, Oulu, Finland.
[Pouta, Anneli] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy.
[Biffar, Reiner] Ernst Moritz Arndt Univ Greifswald, Dept Prosthet Dent Gerostomatol & Dent Mat, Greifswald, Germany.
[Brabant, Georg] Med Univ Lubeck, D-23538 Lubeck, Germany.
[Cox, David G.] INSERM, U1052, Canc Res Ctr Lyon, F-69008 Lyon, France.
[Cox, David G.; Gunter, Marc J.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Cummings, Steven] Calif Pacific Med Ctr, San Francisco, CA USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
[Hankinson, Susan E.] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Hofman, Albert; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Homuth, Georg; Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Illig, Thomas] Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-3000 Hannover, Germany.
[Karasik, David; Kiel, Douglas P.] Hebrew SeniorLife Inst Aging Res, Boston, MA USA.
[Karlsson, Magnus] Lund Univ, Clin Mol Osteoporosis Res Unit, Dept Clin Sci, Malmo, Sweden.
[Karlsson, Magnus] Lund Univ, Dept Orthopaed, Malmo, Sweden.
[Kettunen, Johannes] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Kettunen, Johannes] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA USA.
[Liu, Jingmin] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Womens Hlth Initiat Clin Coordinating Ctr, Seattle, WA 98104 USA.
[Ljunggren, Osten] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Maggio, Marcello] Univ Parma, Sect Geriatr, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy.
[Markus, Marcello R. P.] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
[Miljkovic, Iva] Univ Pittsburgh, Pittsburgh, PA USA.
[Mirel, Daniel] Broad Inst Harvard & MIT, Program Med & Populat Genet, Gene Environm Initiat, Boston, MA USA.
[Nelson, Sarah] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Raffel, Leslie] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA.
[Reincke, Martin; Bidlingmaier, Martin] Univ Munich, Med Klin & Poliklin 4, Munich, Germany.
[Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Rexrode, Kathryn] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA.
[Schwartz, Stephen M.; Siscovick, David] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Soranzo, Nicole] Wellcome Trust Sanger Inst, Hinxton, England.
[Stockl, Doris] Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Stockl, Doris] Univ Munich, Dept Obstet & Gynaecol, Munich, Germany.
[Wichmann, H. -Erich] 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.
[Zhai, Guangju] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF, Canada.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Liu, Simin] Univ Calif Los Angeles, Dept Epidemiol, Program Genom & Nutr, Los Angeles, CA USA.
[Ouyang, Pamela] Johns Hopkins Bayview Med Ctr, Div Cardiol, Baltimore, MD USA.
[Viikari, Jorma] Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland.
[Viikari, Jorma] Univ Turku, Turku, Finland.
[McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England.
[Franks, Steve] Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London, England.
[Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, MRC HPA Ctr Environm & Hlth, Fac Med, Dept Biostat & Epidemiol,Sch Publ Hlth, London, England.
[Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Univ Oulu, Natl Inst Hlth & Welf, Oulu, Finland.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Murabito, Joanne M.] Boston Univ, Sch Med, Sect Gen Internal Med, Boston, MA 02118 USA.
RP Coviello, AD (reprint author), Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
EM murabito@bu.edu; John.perry@pms.ac.uk
RI Onland-Moret, N. Charlotte/G-9185-2011; Rivadeneira,
Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; Lyytikainen,
Leo-Pekka/C-8544-2016; mangino, massimo/F-5134-2011; Koster,
Annemarie/E-7438-2010; Johnson, Andrew/G-6520-2013; Cox,
David/A-2023-2009; Lagou, Vasiliki/N-8451-2013; Stockl,
Doris/B-5352-2014; van der Schouw, Yvonne/F-8327-2014; Liu,
Simin/I-3689-2014
OI Karasik, David/0000-0002-8826-0530; Schwartz,
Stephen/0000-0001-7499-8502; Jarvelin, Marjo-Riitta/0000-0002-2149-0630;
Vandenput, Liesbeth/0000-0002-1712-6131; Markus, Marcello Ricardo
Paulista/0000-0002-6234-4955; Vaidya, Dhananjay/0000-0002-7164-1601;
Lunetta, Kathryn/0000-0002-9268-810X; Murray, Anna/0000-0002-2351-2522;
Miljkovic, Iva/0000-0002-3155-9777; Bidlingmaier,
Martin/0000-0002-4681-6668; Tworoger, Shelley/0000-0002-6986-7046;
Rexrode, Kathryn/0000-0003-3387-8429; Ramachandran,
Vasan/0000-0001-7357-5970; Soranzo, Nicole/0000-0003-1095-3852; Kiel,
Douglas/0000-0001-8474-0310; Rivadeneira, Fernando/0000-0001-9435-9441;
Prokopenko, Inga/0000-0003-1624-7457; Lyytikainen,
Leo-Pekka/0000-0002-7200-5455; mangino, massimo/0000-0002-2167-7470;
Murabito, Joanne/0000-0002-0192-7516; Cox, David/0000-0002-2152-9259;
van der Schouw, Yvonne/0000-0002-4605-435X; Liu,
Simin/0000-0003-2098-3844
FU NIA [R21AG032598, R01HL094755, R01AG31206, R01 AR/AG 41398, N01AG62101,
N01AG62103, N01AG62106, 1R01AG032098-01A1]; National Heart, Lung, and
Blood Institute's Framingham Heart Study [N01-HC-25195, N02-HL-6-4278];
Robert Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine and Boston Medical Center; Swedish
Research Council [K2010-54X-09894-19-3, 2006-3832,
K2010-52X-20229-05-3]; Swedish Foundation for Strategic Research;
ALF/LUA research grant in Gothenburg; Lundberg Foundation; Torsten and
Ragnar Soderberg's Foundation; Petrus and Augusta Hedlunds Foundation;
Vastra Gotaland Foundation; Goteborg Medical Society; Novo Nordisk
foundation; European Commission [HEALTH-F2-2008-201865-GEFOS,
QLG1-CT-2000-01643]; German Bundesministerium fuer Forschung und
Technology [01 AK 803, 01 IG 07015 G]; National Institutes of Health
[HHSN268200782096C]; Intramural Research Program of the National
Institute on Aging, NIH, Bethesda, Maryland; Italian Ministry of Health
[ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263
MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; National Institute
on Aging, National Institutes of Health, Baltimore, Maryland; Helmholtz
Zentrum Munich, German Research Center for Environmental Health; German
Federal Ministry of Education and Research (BMBF); State of Bavaria;
German National Genome Research Network [NGFN-2, NGFNPlus: 01GS0823];
Munich Center of Health Sciences (MC Health) as part of LMUinnovativ;
National Heart, Lung, and Blood Institute (NHLBI); MESA; NHLBI
[N02-HL-6-4278, 5R01HL087679-02, 1RL1MH083268-01]; Academy of Finland
[104781, 120315, 129269, 1114194, 134309, 126925, 121584, 124282,
129378, 117787, 41071]; University Hospital Oulu; Biocenter; University
of Oulu, Finland [75617]; NIH/NIMH [5R01MH63706: 02]; ENGAGE project;
Medical Research Council UK [G0500539, G0600705]; Wellcome Trust
[GR069224]; U.S. National Heart, Lung, and Blood Institute [HL087679];
U.S. National Institutes of Health [MH083268, GM053275-14, U54
RR020278]; National Science Foundation [DMS-0239427]; Medical Research
Council of the UK; EURO-BLCS; European Community
[HEALTH-F2-2008-201865-GEFOS, HEALTH-F4-2007-201413]; Netherlands
Organisation of Scientific Research NWO Investments [175.010.2005.011,
911-03-012]; Research Institute for Diseases in the Elderly
[014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands
Organisation for Scientific Research (NWO) [050-060-810]; European
Commision [HEALTH-F2-2008-201865, HEALTH-F2-2008-35627]; Erasmus Medical
Center and Erasmus University, Rotterdam; Netherlands Organization for
the Health Research and Development (ZonMw); Research Institute for
Diseases in the Elderly (RIDE); Ministry of Education, Culture, and
Science; Ministry for Health, Welfare, and Sports; European Commission
(DG XII); Municipality of Rotterdam; Federal Ministry of Education and
Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural
Affairs; Social Ministry of the Federal State of Mecklenburg, West
Pomerania; Siemens Healthcare, Erlangen, Germany; Federal State of
Mecklenburg, West Pomerania; Ministry of Cultural Affairs of the Federal
State of Mecklenburg, West Pomerania [03IS2061A]; Siemens Healthcare
Diagnostics, Eschborn; Novo Nordisk; Pfizer; Wellcome Trust; ENGAGE
[HEALTH-F4-2007-201413]; FP-5 GenomEUtwin Project [QLG2-CT-2002-01254];
Department of Health via the National Institute for Health Research
(NIHR) comprehensive Biomedical Research Centre; St. Thomas' NHS
Foundation Trust; King's College London; Biotechnology and Biological
Sciences Research Council (BBSRC) [G20234]; National Eye Institute via
an NIH/CIDR genotyping project (PI: Terri Young); Social Insurance
Institution of Finland; Kuopio, Tampere, and Turku University Hospital
Medical Funds [9M048, 9N035]; Juho Vainio Foundation; Paavo Nurmi
Foundation; Finnish Foundation of Cardiovascular Research; Tampere
Tuberculosis Foundation; Emil Aaltonen Foundation; National Heart, Lung,
and Blood Institute; National Institutes of Health; U.S. Department of
Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9,
32111-13, 32115, 32118-32119, 32122, 4210726, 42129-32, 44221]; National
Heart, Lung, and Blood Institute [R01-HL065611]; National Human Genome
Research Institute; Career Development Award [5-K23-HL087114]; "Europe
against Cancer'' Programme of the European Commission (SANCO); Dutch
Ministry of Health, Welfare, and Sports; ZONMw; National Cancer
Institute [CA87969, CA49449, CA40356, CA128034, U01-CA98233]; Finnish
Cultural Foundation; [N01 HC-95159]; [N01-HC-95160]; [N01-HC-95161];
[N01-HC-95162]; [N01-HC-95163]; [N01-HC-95164]; [N01-HC-95165];
[N01-HC-95166]; [N01-HC-95167]; [N01-HC-95168]; [N01-HC-95169];
[RR-024156]; [HL074406]; [HL074338]; [N01-HC-95095]; [N01-HC-48047];
[N01-HC-48048]; [N01-HC-48049]; [N01-HC-48050]; [N01-HC-45134];
[N01-HC-05187]; [N01-HC-45205]; [N01-HC-45204]; [U01-HG-004729];
[U01-HG-004446]; [U01-HG-004424]; [R01-HL-084099]
FX This meta-analysis is a collaborative effort involving data from many
individual studies and many sources of funding. The details of funding
sources for each study are detailed in Text S1 as well as below.
Framingham Heart Study (FHS): The phenotype-genotype association
analyses were funded through grants from the NIA R21AG032598 (JM
Murabito, KL Lunetta), R01HL094755 (AD Coviello, RS Vasan, S
Bandinelli), and R01AG31206 (RS Vasan, S Bandinelli), R01 AR/AG 41398
(DP Kiel). This research was conducted in part using data and resources
from the Framingham Heart Study of the National Heart, Lung, and Blood
Institute of the National Institutes of Health and Boston University
School of Medicine. The analyses reflect intellectual input and resource
development from the Framingham Heart Study investigators participating
in the SNP Health Association Resource (SHARe) project. This work was
partially supported by the National Heart, Lung, and Blood Institute's
Framingham Heart Study (Contract No. N01-HC-25195) and its contract with
Affymetrix for genotyping services (Contract No. N02-HL-6-4278). A
portion of this research utilized the Linux Cluster for Genetic Analysis
(LinGA-II), funded by the Robert Dawson Evans Endowment of the
Department of Medicine at Boston University School of Medicine and
Boston Medical Center. Gothenburg Osteoporosis and Obesity Determinants
(GOOD) Study: Financial support was received from the Swedish Research
Council (K2010-54X-09894-19-3, 2006-3832, and K2010-52X-20229-05-3), the
Swedish Foundation for Strategic Research, the ALF/LUA research grant in
Gothenburg, the Lundberg Foundation, the Torsten and Ragnar Soderberg's
Foundation, Petrus and Augusta Hedlunds Foundation, the Vastra Gotaland
Foundation, the Goteborg Medical Society, the Novo Nordisk foundation,
and the European Commission grant HEALTH-F2-2008-201865-GEFOS. We would
like to acknowledge Maria Nethander at the genomics core facility at
University of Gothenburg for statistical analyses. We would also like to
thank Dr. Tobias A. Knoch, Luc V. de Zeeuw, Anis Abuseiris, and Rob de
Graaf as well as their institutions the Erasmus Computing Grid,
Rotterdam, The Netherlands, and especially the national German MediGRID
and Services@MediGRID part of the German D-Grid, both funded by the
German Bundesministerium fuer Forschung und Technology under grants #01
AK 803 A-H and #01 IG 07015 G for access to their grid resources. We
would also like to thank Karol Estrada, Department of Internal Medicine,
Erasmus MC, Rotterdam, The Netherlands, for advice regarding the grid
resources. Health, Aging, and Body Composition (Health ABC) Study: This
Health ABC Study was supported by NIA contracts N01AG62101, N01AG62103,
and N01AG62106. The genome-wide association study was funded by NIA
grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and
genotyping services were provided by the Center for Inherited Disease
Research (CIDR). CIDR is fully funded through a federal contract from
the National Institutes of Health to The Johns Hopkins University,
contract number HHSN268200782096C. This research was also supported in
part by the Intramural Research Program of the National Institute on
Aging, NIH, Bethesda, Maryland. Invecchiare in Chianti (InCHIANTI): The
InCHIANTI study baseline (1998-2000) was supported as a "targeted
project'' (ICS110.1/RF97.71) by the Italian Ministry of Health and in
part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and
263 MD 821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the
U.S.; National Institute on Aging (Contracts: N.1-AG-1-1 and
N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004-2010)
were financed by the U.S. National Institute on Aging (Contract:
N01-AG-5-0002), supported in part by the Intramural research program of
the National Institute on Aging, National Institutes of Health,
Baltimore, Maryland. JRB Perry is a Sir Henry Wellcome Postdoctoral
Research Fellow (092447/Z/10/Z). Cooperative Health Research in the
Region of Augsburg (KORA): The KORA research platform was initiated and
financed by the Helmholtz Zentrum Munich, German Research Center for
Environmental Health, which is funded by the German Federal Ministry of
Education and Research (BMBF) and by the State of Bavaria. Part of this
work was financed by the German National Genome Research Network (NGFN-2
and NGFNPlus: 01GS0823). Our research was supported within the Munich
Center of Health Sciences (MC Health) as part of LMUinnovativ.
Multi-Ethnic Study of Atherosclerosis (MESA): MESA and the MESA SHARe
project are conducted and supported by the National Heart, Lung, and
Blood Institute (NHLBI) in collaboration with MESA investigators.
Support is provided by grants and contracts N01 HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, and RR-024156.
Funding support for the sex hormone dataset was provided by grants
HL074406 and HL074338. Funding for SHARe genotyping was provided by
NHLBI Contract N02-HL-6-4278. Genotyping was performed at the Broad
Institute of Harvard and MIT (Boston, Massachusetts, USA) and at
Affymetrix (Santa Clara, California, USA) using the Affymetric
Genome-Wide Human SNP Array 6.0. Northern Finland Birth Cohort 1966
Study (NFBC-66): NFBC1966 received financial support from the Academy of
Finland (project grants 104781, 120315, 129269, 1114194, Center of
Excellence in Complex Disease Genetics, and SALVE), University Hospital
Oulu, Biocenter, University of Oulu, Finland (75617), the European
Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643), NHLBI
grant 5R01HL087679-02 through the STAMPEED program(1RL1MH083268-01),
NIH/NIMH (5R01MH63706: 02), ENGAGE project and grant agreement
HEALTH-F4-2007-201413, the Medical Research Council UK (G0500539,
G0600705, PrevMetSyn/SALVE), and the Wellcome Trust (project grant
GR069224). We acknowledge the support of U.S. National Heart, Lung, and
Blood Institute grant HL087679 through the STAMPEED program; grants
MH083268, GM053275-14, and U54 RR020278 from the U.S. National
Institutes of Health; grant DMS-0239427 from the National Science
Foundation; the Medical Research Council of the UK, EURO-BLCS,
QLG1-CT-2000-01643 and the European Community's Seventh Framework
Programme (FP7/2007-2013); ENGAGE project and grant agreement
HEALTH-F4-2007-201413. The authors would like to thank the Center of
Excellence in Common Disease Genetics of the Academy of Finland and
Nordic Center of Excellence in Disease Genetics, the Sydantautisaatio
(Finnish Foundation of Heart Diseases), the Broad Genotyping Center, D.
Mirel, H. Hobbs, J. DeYoung, P. Rantakallio, M. Koiranen, and M.
Isohanni for advice and assistance. Rotterdam study (RS1): The
generation and management of GWAS genotype data for the Rotterdam Study
are supported by the Netherlands Organisation of Scientific Research NWO
Investments (nr. 175.010.2005.011, 911-03-012).; This study is funded by
the Research Institute for Diseases in the Elderly (014-93-015; RIDE2),
the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for
Scientific Research (NWO) project nr. 050-060-810, and funding from the
European Commision (HEALTH-F2-2008-201865, GEFOS; HEALTH-F2-2008-35627,
TREAT-OA). The Rotterdam Study is funded by Erasmus Medical Center and
Erasmus University, Rotterdam; Netherlands Organization for the Health
Research and Development (ZonMw); the Research Institute for Diseases in
the Elderly (RIDE); the Ministry of Education, Culture, and Science; the
Ministry for Health, Welfare, and Sports; the European Commission (DG
XII); and the Municipality of Rotterdam. We thank Pascal Arp, Mila
Jhamai, Dr. Michael Moorhouse, Marijn Verkerk, and Sander Bervoets for
their help in creating the GWAS database. The authors are grateful to
the study participants, the staff from the Rotterdam Study and the
participating general practitioners and pharmacists. We would like to
thank Dr. Tobias A. Knoch, Karol Estrada, Luc V. de Zeeuw, Anis
Abuseiris, and Rob de Graaf as well as their institutions the Erasmus
Computing Grid, Rotterdam, The Netherlands, and especially the national
German MediGRID and Services@MediGRID part of the German D-Grid, both
funded by the German Bundesministerium fuer Forschung und Technology
under grants #01 AK 803 A-H and #01 IG 07015 G for access to their grid
resources. Study of Health in Pomerania (SHIP): SHIP is part of the
Community Medicine Research Net of the University of Greifswald,
Germany, which is funded by the Federal Ministry of Education and
Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), and the Ministry
of Cultural Affairs, as well as the Social Ministry of the Federal State
of Mecklenburg, West Pomerania. Genome-wide data have been supported by
the Federal Ministry of Education and Research (grant no. 03ZIK012) and
a joint grant from Siemens Healthcare, Erlangen, Germany, and the
Federal State of Mecklenburg, West Pomerania. The University of
Greifswald is a member of the "Center of Knowledge Interchange'' program
of the Siemens AG. This work is also part of the research project
Greifswald Approach to Individualized Medicine (GANI_MED). The GANI_MED
consortium is funded by the Federal Ministry of Education and Research
and the Ministry of Cultural Affairs of the Federal State of
Mecklenburg, West Pomerania (03IS2061A). The SHBG reagents used were
sponsored by Siemens Healthcare Diagnostics, Eschborn, formerly DPC
Biermann GmbH, Bad Nauheim, Germany. Novo Nordisk provided partial grant
support for the determination of serum samples and data analysis. R
Haring received honorarium for lectures by Bayer Pharma AG. H
Wallaschofski has received research grants from Novo Nordisk and Pfizer
for research unrelated to the contents of this manuscript and honorarium
for lectures by Bayer Pharma AG. TWINS UK: The study was funded by the
Wellcome Trust, European Community's Seventh Framework Programme
(FP7/2007-2013) grant agreement HEALTH-F2-2008-201865-GEFOS and
(FP7/2007-2013), ENGAGE project grant agreement HEALTH-F4-2007-201413,
and the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254). The study also
receives support from the Department of Health via the National
Institute for Health Research (NIHR) comprehensive Biomedical Research
Centre award to Guy's and St. Thomas' NHS Foundation Trust in
partnership with King's College London. TD Spector is an NIHR senior
Investigator.; The project also received support from a Biotechnology
and Biological Sciences Research Council (BBSRC) project grant (G20234).
The authors acknowledge the funding and support of the National Eye
Institute via an NIH/CIDR genotyping project (PI: Terri Young). We thank
the staff from the Genotyping Facilities at the Wellcome Trust Sanger
Institute for sample preparation, quality control, and genotyping led by
Leena Peltonen and Panos Deloukas; Le Centre National de Genotypage,
France, led by Mark Lathrop, for genotyping; Duke University, North
Carolina, USA, led by David Goldstein, for genotyping; and the Finnish
Institute of Molecular Medicine, Finnish Genome Center, University of
Helsinki, led by Aarno Palotie. Genotyping was also performed by CIDR as
part of an NEI/NIH project grant. The Cardiovascular Risk in Young Finns
Study (YFS): The Young Finns Study has been financially supported by the
Academy of Finland: grants 134309 (Eye), 126925, 121584, 124282, 129378
(Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance
Institution of Finland; Kuopio, Tampere, and Turku University Hospital
Medical Funds (grant 9M048 for 9N035 for TeLeht); Juho Vainio
Foundation; Paavo Nurmi Foundation; Finnish Foundation of Cardiovascular
Research and Finnish Cultural Foundation; Tampere Tuberculosis
Foundation; and Emil Aaltonen Foundation (T Lehtimaki). The expert
technical assistance in the statistical analyses by Irina Lisinen and
Ville Aalto are gratefully acknowledged. Women's Health Initiative
(WHI): Genotyping was performed at the Broad Institute (Cambridge, MA)
through the NHGRI-funded Genomics and Randomized Clinical Network (U01
HG005152) or GARNET. The WHI programis funded by the National Heart,
Lung, and Blood Institute, National Institutes of Health, U.S.
Department of Health and Human Services through contracts N01WH22110,
24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
4210726, 42129-32, and 44221. The authors thank the WHI investigators
and staff for their dedication, and the study participants for making
the program possible. A listing of WHI investigators can be found at
http://www.whiscience.org/publications/WHI_investigators_shortlist.pdf.
Coronary Artery Risk Development in Young Adults (CARDIA) Women's Study:
The CARDIA study is funded by contracts N01-HC-95095, N01-HC-48047,
N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187,
N01-HC-45205, and N01-HC-45204 and by the CARDIA Women's study by
R01-HL065611 from the National Heart, Lung, and Blood Institute to the
CARDIA investigators. Genotyping of the CARDIA participants was
supported by grants U01-HG-004729, U01-HG-004446, and U01-HG-004424 from
the National Human Genome Research Institute. Statistical analyses were
supported by grants U01-HG-004729 and R01-HL-084099 to M Fornage. M
Wellons is supported by the Career Development Award 5-K23-HL087114.
European Prospective Investigation into Cancer and Nutrition
(Prospect-EPIC): The Prospect-EPIC study was funded by "Europe against
Cancer'' Programme of the European Commission (SANCO); the Dutch
Ministry of Health, Welfare, and Sports (VWS); and ZONMw.; Osteoporotic
fractures in men (MrOS) study Sweden: Financial support was received
from the Swedish Research Council (2006-3832), the Swedish Foundation
for Strategic Research, the ALF/LUA research grant in Gothenburg, the
Lundberg Foundation, the Torsten and Ragnar Soderberg's Foundation,
Petrus and Augusta Hedlunds Foundation, the Vastra Gotaland Foundation,
the Goteborg Medical Society, the Novo Nordisk Foundation, and the
European Commission grant HEALTH-F2-2008-201865-GEFOS. Nurses' Health
Study (NHS): The NHS breast cancer GWAS was performed as part of the
Cancer Genetic Markers of Susceptibility (CGEMS) initiative of the NCI.
We particularly acknowledge the contributions of R. Hoover, A.
Hutchinson, K. Jacobs and G. Thomas. The current research is supported
by CA87969, CA49449, CA40356, CA128034, and U01-CA98233 from the
National Cancer Institute. We acknowledge the study participants in the
NHS for their contribution in making this study possible. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 78
TC 50
Z9 51
U1 0
U2 18
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JUL
PY 2012
VL 8
IS 7
AR e1002805
DI 10.1371/journal.pgen.1002805
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 979SP
UT WOS:000306840400020
PM 22829776
ER
PT J
AU Cherpitel, CJ
Ye, Y
Bond, J
Borges, G
Chou, P
Nilsen, P
Ruan, JN
Xiang, XJ
AF Cherpitel, Cheryl J.
Ye, Yu
Bond, Jason
Borges, Guilherme
Chou, Patricia
Nilsen, Per
Ruan, June
Xiang, Xiaojun
TI Multi-level analysis of alcohol-related injury and drinking pattern:
emergency department data from 19 countries
SO ADDICTION
LA English
DT Article
DE Alcohol; BAC; causal attribution; ED; injury; policy
ID ANALYSIS-PROJECT ERCAAP; ROOM; CONSUMPTION; RISK; VOLUME
AB Aim While drinking in the event is an important factor in injury occurrence, the pattern of usual drinking may also be important in risk of injury. Explored here is the relationship of an alcohol-related injury with an individual usual drinking pattern. Design Alcohol-related injury is examined using hierarchical linear models, taking into account individual usual volume of consumption over the past 12 months, as well as aggregate-level detrimental drinking pattern (DDP) and alcohol policy measures. Setting Data analyzed are from emergency departments (EDs) in 19 countries, comprising three collaborative studies on alcohol and injury, all of which used a similar methodology. Participants The sample comprised 14 132 injured drinkers across 46 emergency room (ER) studies. Measurements Alcohol-related injury was measured, separately, by any self-reported drinking prior to injury, a blood alcohol concentration (BAC) = 0.08 and self-reported causal attribution of injury to drinking. Findings While individual usual volume strongly predicted an alcohol-related injury for all three measures, usual drinking pattern also predicted an alcohol-related injury (controlling for volume), with episodic heavy and frequent heavy drinking both more predictive of alcohol-related injury than other drinking patterns. When individual usual volume and drinking pattern were controlled, DDP was no longer a significant predictor of alcohol-related injury. Alcohol policy measures were predictive of both BAC and causal attribution (the stronger the policy the lower the rates of alcohol-related injury). Conclusions Volume of alcohol typically consumed and occurrence of heavy drinking episodes are associated independently with incidence of alcohol-related injury. The stronger the anti-alcohol policies in a country, the lower the rates of alcohol-related injury.
C1 [Cherpitel, Cheryl J.; Ye, Yu; Bond, Jason] Alcohol Res Grp, Emeryville, CA 94608 USA.
[Borges, Guilherme] Univ Autonoma Metropolitana, Inst Nacl Psiquiatria, Mexico City, DF, Mexico.
[Chou, Patricia; Ruan, June] NIAAA, Rockville, MD 20852 USA.
[Nilsen, Per] Linkoping Univ, Linkoping, Sweden.
[Xiang, Xiaojun] Cent S Univ, Changsha, Hunan, Peoples R China.
RP Cherpitel, CJ (reprint author), Alcohol Res Grp, 6475 Christie Ave,Suite 400, Emeryville, CA 94608 USA.
EM ccherpitel@arg.org
OI Borges, Guilherme/0000-0002-3269-0507
FU US National Institute on Alcohol Abuse and Alcoholism [RO1 2
AA013750-04]; World Health Organization
FX Presented at the Research Society on Alcoholism annual meeting, Atlanta,
GA, 25-29 June 2011, supported by a grant from the US National Institute
on Alcohol Abuse and Alcoholism (RO1 2 AA013750-04).; The paper is based
in part on data collected by the following collaborators participating
in the Emergency Room Collaborative Alcohol Analysis Project (ERCAAP):
Preben Bendtsen (Sweden), Guilherme Borges (Mexico), Won Cook (US),
Mariana Cremonte (Argentina), Norman Giesbrecht (Canada), Gerhard Gmel
(Switzerland), Ann Hope (Ireland), Scott Macdonald (Canada), Jacek
Moskalewicz (Poland), Per Nilsen (Sweden), Juan Rhodes (Spain), Tim
Stockwell (Canada) and Grazyna Swiathiewicz (Poland). This paper is also
based in part on the data and experience obtained during the
participation of the authors in the WHO Collaborative Study on Alcohol
and Injuries, sponsored by the World Health Organization and implemented
by the WHO Collaborative Study Group on Alcohol and Injuries that
includes: V. Benegal (India); G. Borges (Mexico); S. Casswell (New
Zealand); C. Cherpitel (USA); M. Cremonte (Argentina); R. Evsegneev
(Belarus); N. Figlie (Brazil); N. Giesbrecht (Canada); W. Hao (China);
G. Humphrey (New Zealand); R. Larajeira (Brazil); S. Macdonald (Canada);
S. Larsson (Sweden); S. Marais (South Africa); O. Neves (Mozambique); M.
Peden (WHO, Switzerland); V. Poznyak (WHO, Switzerland); J. Rehm
(Switzerland); R. Room (Sweden); H. Sovinova (Czech Republic); and M.
Stafstrom (Sweden). A list of other staff contributing to the project
can be found in the Main Report of the Collaborative Study on Alcohol
and Injuries, WHO, Geneva. This paper is also based in part on the data
obtained by the US National Institute on Alcohol Abuse and Alcoholism
and implemented by the following: Bridget Grant (NIAAA, USA), Patricia
Chou (NIAAA, USA), Wei Hao (China) and Sungsoo Chun (Korea). The authors
alone are responsible for views expressed in this paper, which do not
necessarily represent those of the other investigators participating in
the WHO Collaborative Study on Alcohol and Injuries nor the views or
policy of the World Health Organization or of the US National Institute
on Alcohol Abuse and Alcoholism.
NR 14
TC 22
Z9 23
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD JUL
PY 2012
VL 107
IS 7
BP 1263
EP 1272
DI 10.1111/j.1360-0443.2012.03793.x
PG 10
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 953HS
UT WOS:000304858400015
PM 22236278
ER
PT J
AU Elkashef, A
Kahn, R
Yu, E
Iturriaga, E
Li, SH
Anderson, A
Chiang, N
Ait-Daoud, N
Weiss, D
McSherry, F
Serpi, T
Rawson, R
Hrymoc, M
Weis, D
McCann, M
Pham, T
Stock, C
Dickinson, R
Campbell, J
Gorodetzky, C
Haning, W
Carlton, B
Mawhinney, J
Li, MD
Johnson, BA
AF Elkashef, Ahmed
Kahn, Roberta
Yu, Elmer
Iturriaga, Erin
Li, Shou-Hua
Anderson, Ann
Chiang, Nora
Ait-Daoud, Nassima
Weiss, David
McSherry, Frances
Serpi, Tracey
Rawson, Richard
Hrymoc, Mark
Weis, Dennis
McCann, Michael
Pham, Tony
Stock, Christopher
Dickinson, Ruth
Campbell, Jan
Gorodetzky, Charles
Haning, William
Carlton, Barry
Mawhinney, Joseph
Li, Ming D.
Johnson, Bankole A.
TI Topiramate for the treatment of methamphetamine addiction: a
multi-center placebo-controlled trial
SO ADDICTION
LA English
DT Article
DE Abstinence facilitation; methamphetamine abuse; topiramate; treatment
ID RANDOMIZED CONTROLLED-TRIAL; COCAINE DEPENDENCE; ALCOHOL DEPENDENCE;
DOUBLE-BLIND; DEPRESSION; SEEKING
AB Aims Topiramate has shown efficacy at facilitating abstinence from alcohol and cocaine abuse. This double-blind, placebo-controlled out-patient trial tested topiramate for treating methamphetamine addiction. Design Participants (n = 140) were randomized to receive topiramate or placebo (13 weeks) in escalating doses from 50 mg/day to the target maintenance of 200 mg/day in weeks 612 (tapered in week 13). Medication was combined with weekly brief behavioral compliance enhancement treatment. Setting The trial was conducted at eight medical centers in the United States. Participants One hundred and forty methamphetamine-dependent adults took part in the trial. Measurements The primary outcome was abstinence from methamphetamine during weeks 612. Secondary outcomes included use reduction versus baseline, as well as psychosocial variables. Findings In the intent-to-treat analysis, topiramate did not increase abstinence from methamphetamine during weeks 612. For secondary outcomes, topiramate reduced weekly median urine methamphetamine levels and observer-rated severity of dependence scores significantly. Subjects with negative urine before randomization (n = 26) had significantly greater abstinence on topiramate versus placebo during study weeks 612. Topiramate was safe and well tolerated. Conclusions Topiramate does not appear to promote abstinence in methamphetamine users but can reduce the amount taken and reduce relapse rates in those who are already abstinent.
C1 [Ait-Daoud, Nassima; Li, Ming D.; Johnson, Bankole A.] Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA 22908 USA.
[Elkashef, Ahmed; Kahn, Roberta; Iturriaga, Erin; Li, Shou-Hua; Anderson, Ann; Chiang, Nora] Natl Inst Drug Abuse, NIH, Bethesda, MD USA.
[Yu, Elmer] Vet Adm Med Ctr, Philadelphia, PA 19104 USA.
[Weiss, David; McSherry, Frances; Serpi, Tracey] Dept Vet Affairs Cooperat Studies Program Coordin, Perry Point, MD USA.
[Weis, Dennis] Lutheran Hosp Off Res, Des Moines, IA USA.
[Rawson, Richard; Hrymoc, Mark] UCLA Integrated Substance Abuse Programs, Los Angeles, CA USA.
[McCann, Michael; Pham, Tony] Matrix Inst Addict, Costa Mesa, CA USA.
[Stock, Christopher; Dickinson, Ruth] Salt Lake City Hlth Care Syst, Dept Vet Affairs, Salt Lake City, UT USA.
[Campbell, Jan; Gorodetzky, Charles] Univ Missouri, Dept Psychiat, Kansas City, MO 64110 USA.
[Haning, William; Carlton, Barry] Pacific Addict Res Ctr, Honolulu, HI USA.
[Mawhinney, Joseph] S Bay Treatment Ctr, San Diego, CA USA.
RP Johnson, BA (reprint author), Univ Virginia, Dept Psychiat & Neurobehav Sci, POB 800623, Charlottesville, VA 22908 USA.
EM bankolejohnson@virginia.edu
FU National Institute on Drug Abus through the Department of Veterans
Affairs [Y1-DA4006]
FX We are grateful to the National Institute on Drug Abuse for its generous
support through the Department of Veterans Affairs Cooperative Studies
Program (Interagency Agreement no. Y1-DA4006). We also thank Robert H.
Cormier Jr BA, for his assistance with manuscript preparation.
NR 20
TC 37
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U1 3
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD JUL
PY 2012
VL 107
IS 7
BP 1297
EP 1306
DI 10.1111/j.1360-0443.2011.03771.x
PG 10
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 953HS
UT WOS:000304858400019
PM 22221594
ER
PT J
AU Mattson, MP
AF Mattson, Mark P.
TI Evolutionary aspects of human exercise-Born to run purposefully
SO AGEING RESEARCH REVIEWS
LA English
DT Review
DE Adaptive advantage; Competition; Endurance; Energy intake and
expenditure; Evolution; Learning and memory
ID FIBROBLAST-GROWTH-FACTOR; NF-KAPPA-B; NEUROTROPHIC FACTOR;
UP-REGULATION; HIPPOCAMPAL NEUROGENESIS; CONTRACTILE ACTIVITY; CALORIC
RESTRICTION; PHYSICAL-ACTIVITY; SKELETAL-MUSCLE; DIABETIC MICE
AB This article is intended to raise awareness of the adaptive value of endurance exercise (particularly running) in the evolutionary history of humans, and the implications of the genetic disposition to exercise for the aging populations of modern technology-driven societies. The genome of Homo sapiens has evolved to support the svelte phenotype of an endurance runner, setting him/her apart from all other primates. The cellular and molecular mechanisms underlying the competitive advantages conferred by exercise capacity in youth can also provide a survival benefit beyond the reproductive period. These mechanisms include up-regulation of genes encoding proteins involved in protecting cells against oxidative stress, disposing of damaged proteins and organelles, and enhancing bioenergetics. Particularly fascinating are the signaling mechanisms by which endurance running changes the structure and functional capabilities of the brain and, conversely, the mechanisms by which the brain integrates metabolic, cardiovascular and behavioral responses to exercise. As an emerging example. I highlight the roles of brain-derived neurotrophic factor (BDNF) as a mediator of the effects of exercise on the brain, and BDNF's critical role in regulating metabolic and cardiovascular responses to endurance running. A better understanding of such 'healthspan-extending' actions of endurance exercise may lead to new approaches for improving quality of life as we advance in the coming decades and centuries. Published by Elsevier B.V.
C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012
FU NIH, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging.
NR 62
TC 29
Z9 29
U1 1
U2 41
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1568-1637
J9 AGEING RES REV
JI Ageing Res. Rev.
PD JUL
PY 2012
VL 11
IS 3
SI SI
BP 347
EP 352
DI 10.1016/j.arr.2012.01.007
PG 6
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 954VV
UT WOS:000304977000001
PM 22394472
ER
PT J
AU Mercken, EM
Carboneau, BA
Krzysik-Walker, SM
de Cabo, R
AF Mercken, Evi M.
Carboneau, Bethany A.
Krzysik-Walker, Susan M.
de Cabo, Rafael
TI Of mice and men: The benefits of caloric restriction, exercise, and
mimetics
SO AGEING RESEARCH REVIEWS
LA English
DT Review
DE Caloric restriction; Exercise; Aging; Mimetic; Healthspan; Metabolic
disorder
ID ACTIVATED PROTEIN-KINASE; EXTENDS LIFE-SPAN; HER-2/NEU TRANSGENIC MICE;
INDUCED DIABETIC-RATS; FEMALE SHR MICE; SKELETAL-MUSCLE; DIETARY
RESTRICTION; RHESUS-MONKEYS; INSULIN SENSITIVITY; PHYSICAL-ACTIVITY
AB During aging there is an increasing imbalance of energy intake and expenditure resulting in obesity, frailty, and metabolic disorders. For decades, research has shown that caloric restriction (CR) and exercise can postpone detrimental aspects of aging. These two interventions invoke a similar physiological signature involving pathways associated with stress responses and mitochondrial homeostasis. Nonetheless, CR is able to delay aging processes that result in an increase of both mean and maximum lifespan, whereas exercise primarily increases healthspan. Due to the strict dietary regime necessary to achieve the beneficial effects of CR, most studies to date have focused on rodents and non-human primates. As a consequence, there is vast interest in the development of compounds such as resveratrol, metformin and rapamycin that would activate the same metabolic- and stress-response pathways induced by these interventions without actually restricting caloric intake. Therefore the scope of this review is to (i) describe the benefits of CR and exercise in healthy individuals, (ii) discuss the role of these interventions in the diseased state, and (iii) examine some of the promising pharmacological alternatives such as CR- and exercise-mimetics. Published by Elsevier B.V.
C1 [Mercken, Evi M.; Carboneau, Bethany A.; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Krzysik-Walker, Susan M.] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA.
RP de Cabo, R (reprint author), NIA, Lab Expt Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM decabora@grc.nia.nih.gov
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU NIH, National Institute on Aging
FX We thank Ann Carboneau and Chris Lyman for the critical reading of this
manuscript. This research was supported entirely by the Intramural
Research Program of the NIH, National Institute on Aging.
NR 144
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U1 3
U2 46
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1568-1637
J9 AGEING RES REV
JI Ageing Res. Rev.
PD JUL
PY 2012
VL 11
IS 3
SI SI
BP 390
EP 398
DI 10.1016/j.arr.2011.11.005
PG 9
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 954VV
UT WOS:000304977000005
PM 22210414
ER
PT J
AU Kim, SY
Romero, R
Tarca, AL
Bhatti, G
Kim, CJ
Lee, J
Elsey, A
Than, NG
Chaiworapongsa, T
Hassan, SS
Kang, GH
Kim, JS
AF Kim, Sun Young
Romero, Roberto
Tarca, Adi L.
Bhatti, Gaurav
Kim, Chong Jai
Lee, JoonHo
Elsey, Amelia
Than, Nandor Gabor
Chaiworapongsa, Tinnakorn
Hassan, Sonia S.
Kang, Gyeong Hoon
Kim, Jung-Sun
TI Methylome of Fetal and Maternal Monocytes and Macrophages at the
Feto-Maternal Interface
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Review
DE Decidua; DNA methylation; DNA methyltransferase; epigenetics; epigenome;
Hofbauer cell; placenta; pregnancy
ID INFLAMMATORY RESPONSE SYNDROME; REGULATORY T-CELLS; HOFBAUER CELLS;
METABOLIC CHARACTERISTICS; PRETERM LABOR; DECIDUAL MACROPHAGES;
GENE-EXPRESSION; HUMAN PLACENTA; IN-UTERO; HLA-G
AB Problem Decidual macrophages (dMf) of the mother and placental macrophages (Hofbauer cells, HC) of the fetus are deployed at a critical location: the feto-maternal interface. This study was conducted to compare the DNA methylome of maternal and fetal monocytes, dMf, and HC and thereby to determine the immunobiological importance of DNA methylation in pregnancy. Method of Study Paired samples were obtained from normal pregnant women at term not in labor and their neonates. Maternal monocytes (MMo) and fetal monocytes (FMo) were isolated from the peripheral blood of mothers and fetal cord blood, respectively. dMf and HC were obtained from the decidua of fetal membranes and placentas, respectively. DNA methylation profiling was performed using the Illumina Infinium Human Methylation27 BeadChip. Quantitative real-time PCR and Western Blot were performed for validation experiments. Results (i) Significant differences in DNA methylation were found in each comparison (MMo versus FMo, 65 loci; dMf versus HC, 266 loci; MMo versus dMf, 199 loci; FMo versus HC, 1030 loci). (ii) Many of the immune response-related genes were hypermethylated in fetal cells (FMo and HC) compared to maternal cells (MMo and dMf). (iii) Genes encoding markers of classical macrophage activation were hypermethylated, and genes encoding alternative macrophage activation were hypomethylated in dMf and HC compared to MMo and FMo, respectively. (iv) mRNA expressions of DNMT1, DNMT3A, and DNMT3B were significantly lower in dMf than in HC. (v) 5-azacytidine treatment increased expression of INCA1 in dMf. Conclusions The findings herein indicate that DNA methylation patterns change during monocytemacrophage differentiation at the feto-maternal interface. It is also suggested that DNA methylation is an important component of the biological machinery conferring an anti-inflammatory phenotype to macrophages at the feto-maternal interface.
C1 [Kim, Jung-Sun] Sungkyunkwan Univ, Samsung Med Ctr, Dept Pathol, Sch Med, Seoul 135710, South Korea.
[Kim, Sun Young; Romero, Roberto; Tarca, Adi L.; Bhatti, Gaurav; Kim, Chong Jai; Lee, JoonHo; Elsey, Amelia; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Kim, Jung-Sun] Hutzel Womens Hosp, Perinatol Res Branch, NIH, DHHS,NICHD, Detroit, MI 48201 USA.
[Tarca, Adi L.; Bhatti, Gaurav] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA.
[Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
[Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Kang, Gyeong Hoon] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea.
RP Kim, JS (reprint author), Sungkyunkwan Univ, Samsung Med Ctr, Dept Pathol, Sch Med, 50 Irwon Dong, Seoul 135710, South Korea.
EM prbchiefstaff@med.wayne.edu; jsunkim@skku.edu
RI Kang, Gyeong Hoon/F-1051-2010
OI Kang, Gyeong Hoon/0000-0003-2380-6675
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, U.S. Department of Health
and Human Services
FX This work was supported in part by the Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, U.S. Department of Health and Human Services.
NR 126
TC 21
Z9 22
U1 1
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD JUL
PY 2012
VL 68
IS 1
BP 8
EP 27
DI 10.1111/j.1600-0897.2012.01108.x
PG 20
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 952RF
UT WOS:000304809200002
PM 22385097
ER
PT J
AU Xu, JF
Yuan, A
Zheng, G
AF Xu, Jinfeng
Yuan, Ao
Zheng, Gang
TI Bayes Factor Based on the Trend Test Incorporating Hardy-Weinberg
Disequilibrium: More Power to Detect Genetic Association
SO ANNALS OF HUMAN GENETICS
LA English
DT Article
DE Bayes factor; comparing association studies; Genome-wide association
studies; Hardy-Weinberg disequilibrium; Pearson's test; trend test
ID GENOME-WIDE ASSOCIATION; RISK LOCI
AB In the analysis of case-control genetic association, the trend test and Pearsons test are the two most commonly used tests. In genome-wide association studies (GWAS), Bayes factor (BF) is a useful tool to support significant P-values, and a better measure than P-value when results are compared across studies with different sample sizes. When reporting the P-value of the trend test, we propose a BF directly based on the trend test. To improve the power to detect association under recessive or dominant genetic models, we propose a BF based on the trend test and incorporating HardyWeinberg disequilibrium in cases. When the true model is unknown, or both the trend test and Pearsons test or other robust tests are applied in genome-wide scans, we propose a joint BF, combining the previous two BFs. All three BFs studied in this paper have closed forms and are easy to compute without integrations, so they can be reported along with P-values, especially in GWAS. We discuss how to use each of them and how to specify priors. Simulation studies and applications to three GWAS are provided to illustrate their usefulness to detect nonadditive gene susceptibility in practice.
C1 [Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Xu, Jinfeng] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore.
[Yuan, Ao] Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA.
RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM zhengg@nhlbi.nih.gov
OI Xu, Jinfeng/0000-0002-3165-2015
FU National University of Singapore [R-155-000-112-112]; National Center
for Research Resources at NIH [2G12RR003048]
FX The work of J. Xu is supported by a grant from the National University
of Singapore (R-155-000-112-112). The work of A. Yuan is supported in
part by the National Center for Research Resources at NIH grant
2G12RR003048. We thank two reviewers for the helpful suggestions and
comments. There is no conflict of interest.
NR 19
TC 7
Z9 7
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0003-4800
EI 1469-1809
J9 ANN HUM GENET
JI Ann. Hum. Genet.
PD JUL
PY 2012
VL 76
BP 301
EP 311
DI 10.1111/j.1469-1809.2012.00714.x
PN 4
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 956EH
UT WOS:000305072200005
PM 22607017
ER
PT J
AU Bear, KA
Solomon, BD
Roessler, E
Alvarez, DEP
Kubendran, S
O'Hara, M
Muenke, M
AF Bear, Kelly A.
Solomon, Benjamin D.
Roessler, Erich
Alvarez, Daniel E. Pineda
Kubendran, Shobana
O'Hara, Margaret
Muenke, Maximilian
TI Evidence for SHH as a candidate gene for encephalocele
SO CLINICAL DYSMORPHOLOGY
LA English
DT Article
ID NEURAL-TUBE DEFECTS; SONIC HEDGEHOG; PARTIAL TRISOMY; MOUSE; BRAIN
C1 [Bear, Kelly A.; Solomon, Benjamin D.; Roessler, Erich; Alvarez, Daniel E. Pineda; Kubendran, Shobana; O'Hara, Margaret; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, Bldg 35,Room 1B-203, Bethesda, MD 20892 USA.
EM mamuenke@mail.nih.gov
FU Division of Intramural Research, National Human Genome Research
Institute, National Institutes of Health, Department of Health and Human
Services, USA
FX This research was supported by the Division of Intramural Research,
National Human Genome Research Institute, National Institutes of Health,
Department of Health and Human Services, USA. The authors would like to
express their gratitude to the patient and family involved. Pertaining
to Dr Bear, the views expressed in this article are those of the author
and do not necessarily reflect the official policy or position of the
Department of the Army, nor the US Government.
NR 17
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0962-8827
J9 CLIN DYSMORPHOL
JI Clin. Dysmorphol.
PD JUL
PY 2012
VL 21
IS 3
BP 148
EP 151
DI 10.1097/MCD.0b013e3283518eb0
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 951XZ
UT WOS:000304754900008
PM 22354285
ER
PT J
AU Hasni, SA
AF Hasni, Sarfaraz Ahmed
TI Role of helicobacter pylori infection in autoimmune diseases
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE autoimmune diseases; etiology; H. pylori; infection
ID RHEUMATOID-ARTHRITIS; SYSTEMIC-SCLEROSIS; SJOGRENS-SYNDROME;
HIGH-PREVALENCE; ASSOCIATION; SEROPREVALENCE; ACTIVATION; ANTIBODIES;
GASTRITIS; AUTOANTIBODIES
AB Purpose of review
The etiology of most autoimmune diseases remains elusive. Prevailing evidence suggests an environmental trigger in a genetically susceptible individual. Helicobacter pylori (H. pylori) have managed to survive in a hostile environment in their host for long period and have evaded eradication by the immune system. Its chronic interaction with the immune system and the ubiquitous presence worldwide makes H. pylori an ideal candidate to study as a trigger of autoimmune phenomena. In this review, we would present data regarding the interplay between H. pylori and various components of the immune system and its association with various autoimmune diseases.
Recent findings
Strong associations of H. pylori with some autoimmune diseases such as immune thrombocytopenia have been found; but most other autoimmune disease studies have revealed conflicting data. The chronic survival of H. pylori in humans is possible because of an overall downregulation of the body's immune response. In addition to this overall effect on the immune system, there are clinical and epidemiological data suggestive of H. pylori infection having a protective role in some autoimmune diseases.
Summary
Based on our review H. pylori status should be checked and treated only in certain autoimmune diseases such as ITP. For the majority of the autoimmune diseases, the role of H. pylori remains controversial signifying need for further research.
C1 [Hasni, Sarfaraz Ahmed] NIAMSD, Bethesda, MD 20892 USA.
RP Hasni, SA (reprint author), NIH, 9000 Rockville Pike,Bldg 10,Room 5-5521, Bethesda, MD 20892 USA.
EM hasnisa@mail.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases,
National Institutes of Health
FX This study was supported by the Intramural Research Programs of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases,
National Institutes of Health.
NR 49
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Z9 22
U1 3
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8711
EI 1531-6963
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD JUL
PY 2012
VL 24
IS 4
BP 429
EP 434
DI 10.1097/BOR.0b013e3283542d0b
PG 6
WC Rheumatology
SC Rheumatology
GA 956IR
UT WOS:000305083800014
PM 22617822
ER
PT J
AU Corcoran, CA
Pierre, PJ
Haddad, T
Bice, C
Suomi, SJ
Grant, KA
Friedman, DP
Bennett, AJ
AF Corcoran, Christopher A.
Pierre, Peter J.
Haddad, Tyler
Bice, Christina
Suomi, Stephen J.
Grant, Kathleen A.
Friedman, David P.
Bennett, Allyson J.
TI Long-term effects of differential early rearing in rhesus macaques:
Behavioral reactivity in adulthood
SO DEVELOPMENTAL PSYCHOBIOLOGY
LA English
DT Article
DE rhesus monkey; early experience; human intruder; affective behavior;
adult; lifespan
ID NONHUMAN PRIMATE MODELS; IRON-DEFICIENCY ANEMIA; ANXIOUS TEMPERAMENT;
DEFENSIVE BEHAVIORS; ENVIRONMENT INTERACTIONS; EARLY EXPERIENCE; MONKEY
INFANTS; MACACA-MULATTA; BRAIN ACTIVITY; EARLY STRESS
AB Adverse early experiences are associated with a range of deleterious health outcomes in humans, including higher risk for affective disorders. Studies using a long-standing model of nonhuman primate model of early adversity have demonstrated that nursery-reared (NR) monkeys exhibit alterations in multiple aspects of biobehavioral development; however, few studies have evaluated the persistence of socioaffective behavioral changes through adulthood. We evaluated the effects of early rearing experience on adult animals' response to a well-validated assessment of anxiety-like behavior, the human intruder paradigm (HIP). We tested 22 rhesus monkeys who were either nursery-reared (NR) or reared with their mothers (mother-reared; MR). NR monkeys were inhibited in their behavior compared to MR monkeys, with reduced locomotion and exploratory behaviors. NR animals showed a marginal increase in freezing. Together these findings demonstrate that the consequences of differential infant rearing experience on socioaffective behavior persist into adulthood, with evidence of greater inhibition in NR monkeys. (c) 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 546555, 2012.
C1 [Bennett, Allyson J.] Univ Wisconsin, Dept Psychol, Harlow Ctr Biol Psychol, Madison, WI 53715 USA.
[Corcoran, Christopher A.; Haddad, Tyler; Bice, Christina; Friedman, David P.] Wake Forest Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC USA.
[Pierre, Peter J.] Univ Wisconsin, Behav Management Unit, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
[Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, Poolesville, MD USA.
[Grant, Kathleen A.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Portland, OR 97201 USA.
RP Bennett, AJ (reprint author), Univ Wisconsin, Dept Psychol, Harlow Ctr Biol Psychol, 22 N Charter St, Madison, WI 53715 USA.
EM ajbennett2@wisc.edu
FU Translational Center for Neurobehavioral Alcohol Research [AA017056];
NIH [MH084980, AA013995, AA014106]
FX We are grateful to Maria Blevins, Tara Chavanne, Jessica Christenson,
and Ken Szeliga for technical assistance and for the efforts of the
Animal Resources Program at the Wake Forest University School of
Medicine. We are also indebted to Keith F. Groach for invaluable
assistance in preparation of this manuscript. This research was
partially supported by the Translational Center for Neurobehavioral
Alcohol Research (AA017056), as well as NIH grants MH084980 (AJB, PJP),
AA013995 (AJB), and AA014106 (DPF).
NR 57
TC 17
Z9 18
U1 2
U2 35
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0012-1630
J9 DEV PSYCHOBIOL
JI Dev. Psychobiol.
PD JUL
PY 2012
VL 54
IS 5
BP 546
EP 555
DI 10.1002/dev.20613
PG 10
WC Developmental Biology; Psychology
SC Developmental Biology; Psychology
GA 952RK
UT WOS:000304809700007
PM 22072233
ER
PT J
AU Lipsitch, M
Abdullahi, O
D'Amour, A
Xie, W
Weinberger, DM
Tchetgen, ET
Scott, JAG
AF Lipsitch, Marc
Abdullahi, Osman
D'Amour, Alexander
Xie, Wen
Weinberger, Daniel M.
Tchetgen, Eric Tchetgen
Scott, J. Anthony G.
TI Estimating Rates of Carriage Acquisition and Clearance and Competitive
Ability for Pneumococcal Serotypes in Kenya With a Markov Transition
Model
SO EPIDEMIOLOGY
LA English
DT Article
ID STREPTOCOCCUS-PNEUMONIAE; NASOPHARYNGEAL CARRIAGE; CONJUGATE VACCINE;
EPIDEMIOLOGIC EVIDENCE; TRANSMISSION PARAMETERS; ACQUIRED-IMMUNITY;
MOUSE MODEL; IN-VITRO; DISEASE; CHILDREN
AB Background: There are more than 90 serotypes of Streptococcus pneumoniae, with varying biologic and epidemiologic properties. Animal studies suggest that carriage induces an acquired immune response that reduces duration of colonization in a nonserotypespecific fashion.
Methods: We studied pneumococcal nasopharyngeal carriage longitudinally in Kenyan children 3-59 months of age, following up positive swabs at days 2, 4, 8, 16, and 32 and then monthly thereafter until 2 swabs were negative for the original serotype. As previously reported, 1868/2840 (66%) of children swabbed at baseline were positive. We estimated acquisition, clearance, and competition parameters for 27 serotypes using a Markov transition model.
Results: Point estimates of type-specific acquisition rates ranged from 0.00025/d (type 1) to 0.0031/d (type 19F). Point estimates of time to clearance (inverse of type-specific immune clearance rate) ranged from 28 days (type 20) to 124 days (type 6A). For the serotype most resistant to competition (type 19F), acquisition of other serotypes was 52% less likely (95% confidence interval = 37%-63%) than in an uncolonized host. Fitness components (carriage duration, acquisition rate, lack of susceptibility to competition) were positively correlated with each other and with baseline prevalence, and were associated with biologic properties previously shown to associate with serotype. Duration of carriage declined with age for most serotypes.
Conclusions: Common S. pneumoniae serotypes appear superior in many dimensions of fitness. Differences in rate of immune clearance are attenuated as children age and become capable of more rapid clearance of the longest-lived serotypes. These findings provide information for comparison after introduction of pneumococcal conjugate vaccine.
C1 [Lipsitch, Marc; Tchetgen, Eric Tchetgen] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Lipsitch, Marc; Tchetgen, Eric Tchetgen] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
[Lipsitch, Marc; Abdullahi, Osman; Xie, Wen; Weinberger, Daniel M.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Abdullahi, Osman; Scott, J. Anthony G.] Kenya Govt Med Res Ctr, Wellcome Trust Res Programme, Kilifi, Kenya.
[D'Amour, Alexander] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA.
[Weinberger, Daniel M.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Tchetgen, Eric Tchetgen] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Scott, J. Anthony G.] Univ Oxford, Nuffield Dept Clin Med, Oxford, England.
RP Lipsitch, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM mlipsitc@hsph.harvard.edu
OI Xie, Wen/0000-0003-3856-9887; Lipsitch, Marc/0000-0003-1504-9213;
Weinberger, Daniel/0000-0003-1178-8086
FU US National Institutes of Health [R01 AI04893]; Wellcome Trust of Great
Britain [081835]; Pfizer; Novartis; Outcome Sciences; AIR Worldwide;
GlaxoSmithKline
FX Supported by research grant R01 AI04893 from the US National Institutes
of Health (to M.L.) and by a clinical fellowship from the Wellcome Trust
of Great Britain (No. 081835) (to J.A.G.S.). M.L. has received
consulting fees or honoraria from Pfizer, Novartis, Outcome Sciences,
and AIR Worldwide. J.A.G.S. has received grant funding from
GlaxoSmithKline and has received study vaccines without cost from
Pfizer/Wyeth. The authors reported no other financial interests related
to this research.
NR 53
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD JUL
PY 2012
VL 23
IS 4
BP 510
EP 519
DI 10.1097/EDE.0b013e31824f2f32
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 954AV
UT WOS:000304916900002
PM 22441543
ER
PT J
AU Pitzer, VE
Basta, NE
AF Pitzer, Virginia E.
Basta, Nicole E.
TI Linking Data and Models The Importance of Statistical Analyses to Inform
Models for the Transmission Dynamics of Infections
SO EPIDEMIOLOGY
LA English
DT Editorial Material
ID PNEUMOCOCCAL CARRIAGE; STREPTOCOCCUS-PNEUMONIAE; SEROTYPE REPLACEMENT;
VACCINATION; PARAMETERS; VACCINES; FAMILIES; DISEASE
C1 [Pitzer, Virginia E.; Basta, Nicole E.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Pitzer, Virginia E.; Basta, Nicole E.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Basta, Nicole E.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
RP Pitzer, VE (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, 212 Eno Hall, Princeton, NJ 08544 USA.
EM vepitzer@princeton.edu
RI Basta, Nicole/B-4157-2013;
OI Pitzer, Virginia/0000-0003-1015-2289
FU NIAID NIH HHS [R37 AI032042, 2R37AI032042, R03 AI092121, R03AI092121];
NIH HHS [7DP5OD009162, DP5 OD009162]
NR 19
TC 2
Z9 2
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD JUL
PY 2012
VL 23
IS 4
BP 520
EP 522
DI 10.1097/EDE.0b013e31825902ab
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 954AV
UT WOS:000304916900003
PM 22659545
ER
PT J
AU Grad, YH
Miller, JC
Lipsitch, M
AF Grad, Yonatan H.
Miller, Joel C.
Lipsitch, Marc
TI Cholera Modeling Challenges to Quantitative Analysis and Predicting the
Impact of Interventions
SO EPIDEMIOLOGY
LA English
DT Article
ID ACUTE RESPIRATORY SYNDROME; TRANSMISSION DYNAMICS; REPRODUCTIVE NUMBERS;
PANDEMIC INFLUENZA; EPIDEMIC CHOLERA; DISEASE DYNAMICS; VIBRIO-CHOLERAE;
UNITED-STATES; EL TOR; SPREAD
AB Several mathematical models of epidemic cholera have recently been proposed in response to outbreaks in Zimbabwe and Haiti. These models aim to estimate the dynamics of cholera transmission and the impact of possible interventions, with a goal of providing guidance to policy makers in deciding among alternative courses of action, including vaccination, provision of clean water, and antibiotics. Here, we discuss concerns about model misspecification, parameter uncertainty, and spatial heterogeneity intrinsic to models for cholera. We argue for caution in interpreting quantitative predictions, particularly predictions of the effectiveness of interventions. We specify sensitivity analyses that would be necessary to improve confidence in model-based quantitative prediction, and suggest types of monitoring in future epidemic settings that would improve analysis and prediction.
C1 [Grad, Yonatan H.; Miller, Joel C.; Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Dept Epidemiol, Boston, MA 02115 USA.
[Grad, Yonatan H.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Miller, Joel C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Lipsitch, M (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Dept Epidemiol, 677 Huntington Ave,Kresge Bldg,Room 506, Boston, MA 02115 USA.
EM mlipsitc@hsph.harvard.edu
RI Miller, Joel/C-4229-2015;
OI Miller, Joel/0000-0003-4426-0405; Lipsitch, Marc/0000-0003-1504-9213
FU National Institute of General Medical Sciences [U54GM088558]; National
Institutes of Allergy and Infectious Disease [AI007061]; Department of
Homeland Security; Fogarty International Center, National Institutes of
Health
FX Supported by Award Number U54GM088558 to M.L. from the National
Institute of General Medical Sciences. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institute of General Medical Sciences or
the National Institutes of Health. Y.H.G. received support from National
Institutes of Allergy and Infectious Disease (T32 grant AI007061).
J.C.M. received support from the RAPIDD program of the Science and
Technology Directorate, Department of Homeland Security and the Fogarty
International Center, National Institutes of Health. The authors
reported no other financial interests related to this research.
NR 62
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U1 1
U2 36
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD JUL
PY 2012
VL 23
IS 4
BP 523
EP 530
DI 10.1097/EDE.0b013e3182572581
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 954AV
UT WOS:000304916900004
PM 22659546
ER
PT J
AU Ghosh, A
Hartge, P
Purdue, MP
Chanock, SJ
Amundadottir, L
Wang, ZM
Wentzensen, N
Chatterjee, N
Wacholder, S
AF Ghosh, Arpita
Hartge, Patricia
Purdue, Mark P.
Chanock, Stephen J.
Amundadottir, Laufey
Wang, Zhaoming
Wentzensen, Nicolas
Chatterjee, Nilanjan
Wacholder, Sholom
TI Assessing Disease Risk in Genome-wide Association Studies Using Family
History
SO EPIDEMIOLOGY
LA English
DT Article
ID PROSTATE-CANCER SUSCEPTIBILITY; OVARIAN-CANCER; PANCREATIC-CANCER;
MULTIPLE LOCI; 8Q24; IDENTIFICATION
AB We show how to use reports of cancer in family members to discover additional genetic associations or confirm previous findings in genome-wide association (GWA) studies conducted in case-control, cohort, or cross-sectional studies. Our novel family history-based approach allows economical association studies for multiple cancers, without genotyping of relatives (as required in family studies), follow-up of participants (as required in cohort studies), or oversampling of specific cancer cases (as required in case-control studies). We empirically evaluate the performance of the proposed family history-based approach in studying associations with prostate and ovarian cancers, using data from GWA studies previously conducted within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The family history-based method may be particularly useful for investigating genetic susceptibility to rare diseases for which accruing cases may be very difficult, by using disease information from nongenotyped relatives of participants in multiple case-control and cohort studies designed primarily for other purposes.
C1 [Ghosh, Arpita] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Ghosh, A (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5054, Rockville, MD 20852 USA.
EM ghosha3@mail.nih.gov
RI Purdue, Mark/C-9228-2016; Amundadottir, Laufey/L-7656-2016
OI Purdue, Mark/0000-0003-1177-3108; Amundadottir,
Laufey/0000-0003-1859-8971
FU National Cancer Institute
FX This study was supported by intramural funding from the National Cancer
Institute. The authors reported no other financial interests related to
this research.
NR 23
TC 7
Z9 7
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD JUL
PY 2012
VL 23
IS 4
BP 616
EP 622
DI 10.1097/EDE.0b013e31825583a0
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 954AV
UT WOS:000304916900014
PM 22575968
ER
PT J
AU Liedo, P
Carey, JR
Ingram, DK
Zou, SG
AF Liedo, Pablo
Carey, James R.
Ingram, Donald K.
Zou, Sige
TI The interplay among dietary fat, sugar, protein and acai (Euterpe
oleracea Mart.) pulp in modulating lifespan and reproduction in a
Tephritid fruit fly
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article
DE Palmitic acid; Lifespan; Dietary intervention; Nutraceutical; Palm
fruit; Anastrepha ludens
ID DROSOPHILA-MELANOGASTER; RESTRICTION; LONGEVITY
AB Macronutrient balance is a critical contributor in modulating lifespan and health. Consumption of diets rich in fruits and vegetables provides numerous health benefits. The interactions among macronutrients and botanicals and how they influence aging and health remain elusive. Here we employed a nutritional geometry approach to investigate the interplay among dietary fat, sugar, protein and antioxidant-and polyphenolic-rich freeze-dried acai pulp in modulating lifespan and reproductive output in the Mexican fruit fly, Anastrepha ludens (Loew). Individual flies were cultured on one of the 24 diets made from a combination of 1) sugar and yeast extract (SY) at four ratios, 2) palmitic acid, a saturated fat, at two concentrations and 3) freeze-dried acai pulp at three concentrations. Fat addition decreased lifespan in females on the sugar only diet and the diet with a low SY ratio, while decreasing lifetime reproductive output in flies on the diet with the low SY ratio when compared to SY ratio-matched low fat controls. A ai supplementation promoted survival, while decreasing lifetime reproductive output, in flies on diets with high fat and high sugar but not other diets when compared to diet-matched non-supplemented controls. These findings reveal that the impact of fat and a ai on lifespan and reproductive output depends on the dietary content of other macronutrients. Our results reveal the intricate interplay among macronutrients and nutraceuticals, and underscore the importance of taking macronutrient balance into consideration in designing dietary interventions for aging and health. Published by Elsevier Inc.
C1 [Zou, Sige] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
[Liedo, Pablo] Colegio Frontera Sur, Dept Entomol, Tapachula 30700, Chiapas, Mexico.
[Carey, James R.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Ingram, Donald K.] Louisiana State Univ, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA.
RP Zou, SG (reprint author), NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
EM zous@grc.nia.nih.gov
RI Liedo, Pablo/E-9313-2010
OI Liedo, Pablo/0000-0002-0004-1721
FU AIBMR Life Science Inc. (Puyallup, WA); MonaVie LLC (South Jordan, UT);
National Institute on Aging, NIH
FX We thank A. Oropeza, R. Bustamente, E. de Leon, S. Salgado, S.
Rodriguez, R. Rincon and G. Rodas for excellent technical support, E.
Spangler and A. G. Schauss for critical reading of the manuscript, and
the Moscamed-Moscafrut facility in Metapa, Chiapas, Mexico, for
providing mexflies and lab space. This work was supported partly by a
grant from AIBMR Life Science Inc. (Puyallup, WA) and MonaVie LLC (South
Jordan, UT) to P. L., J.C. and D. K. I., and partly by funding from the
Intramural Research Program at the National Institute on Aging, NIH to
S.Z.
NR 15
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U1 2
U2 20
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0531-5565
J9 EXP GERONTOL
JI Exp. Gerontol.
PD JUL
PY 2012
VL 47
IS 7
BP 536
EP 539
DI 10.1016/j.exger.2012.05.001
PG 4
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 952SR
UT WOS:000304813200008
PM 22580089
ER
PT J
AU Kim, KP
Miller, DL
de Gonzalez, AB
Balter, S
Kleinerman, RA
Ostroumova, E
Simon, SL
Linet, MS
AF Kim, Kwang Pyo
Miller, Donald L.
de Gonzalez, Amy Berrington
Balter, Stephen
Kleinerman, Ruth A.
Ostroumova, Evgenia
Simon, Steven L.
Linet, Martha S.
TI OCCUPATIONAL RADIATION DOSES TO OPERATORS PERFORMING
FLUOROSCOPICALLY-GUIDED PROCEDURES
SO HEALTH PHYSICS
LA English
DT Article
DE exposure, occupational; fluoroscopy; medical radiation; radiation
protection
ID INTERVENTIONAL CARDIOLOGY PROCEDURES; ENDOSCOPIC RETROGRADE
CHOLANGIOPANCREATOGRAPHY; CARDIAC-CATHETERIZATION PROCEDURES;
PERCUTANEOUS NEPHROLITHOTOMY; RADIOLOGY PROCEDURES; STAFF DOSIMETRY;
MEDICAL STAFF; RAD-IR; NEUROINTERVENTIONAL PROCEDURES; ORTHOPEDIC
SURGEONS
AB In the past 30 y, the numbers and types of fluoroscopically-guided (FG) procedures have increased dramatically. The objective of the present study is to provide estimated radiation doses to physician specialists, other than cardiologists, who perform FG procedures. The authors searched Medline to identify English-language journal articles reporting radiation exposures to these physicians. They then identified several primarily therapeutic FG procedures that met specific criteria: well-defined procedures for which there were at least five published reports of estimated radiation doses to the operator, procedures performed frequently in current medical practice, and inclusion of physicians from multiple medical specialties. These procedures were percutaneous nephrolithotomy (PCNL), vertebroplasty, orthopedic extremity nailing for treatment of fractures, biliary tract procedures, transjugular intrahepatic portosystemic shunt creation (TIPS), head/neck endovascular therapeutic procedures, and endoscopic retrograde cholangiopancreatography (ERCP). Radiation doses and other associated data were abstracted, and effective dose to operators was estimated. Operators received estimated doses per patient procedure equivalent to doses received by interventional cardiologists. The estimated effective dose per case ranged from 1.7-56 mu Sv for PCNL, 0.1-101 mu Sv for vertebroplasty, 2.5-88 mu Sv for orthopedic extremity nailing, 2.0-46 mu Sv for biliary tract procedures, 2.5-74 mu Sv for TIPS, 1.8-53 mu Sv for head/neck endovascular therapeutic procedures, and 0.2-49 mu Sv for ERCP. Overall, mean operator radiation dose per case measured over personal protective devices at different anatomic sites on the head and body ranged from 19-800 (median = 113) mu Sv at eye level, 6-1,180 (median = 75) mu Sv at the neck, and 2-1,600 (median = 302) mu Sv at the trunk. Operators' hands often received greater doses than the eyes, neck, or trunk. Large variations in operator doses suggest that optimizing procedure protocols and proper use of protective devices and shields might reduce occupational radiation dose substantially. Health Phys. 103(1): 0-99; 2012
C1 [Kim, Kwang Pyo] Kyung Hee Univ, Dept Nucl Engn, Yongin, Gyeonggi Do, South Korea.
[Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[de Gonzalez, Amy Berrington; Kleinerman, Ruth A.; Ostroumova, Evgenia; Simon, Steven L.; Linet, Martha S.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Balter, Stephen] Columbia Univ, Med Ctr, Dept Radiol, New York, NY 10027 USA.
[Balter, Stephen] Columbia Univ, Med Ctr, Dept Med, New York, NY 10027 USA.
RP Kim, KP (reprint author), Kyung Hee Univ, Dept Nucl Engn, 1 Seocheon Dong, Yongin, Gyeonggi Do, South Korea.
EM kpkim@khu.ac.kr
OI Kleinerman, Ruth/0000-0001-7415-2478
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health
FX This study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health.
NR 121
TC 31
Z9 33
U1 2
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD JUL
PY 2012
VL 103
IS 1
BP 80
EP 99
DI 10.1097/HP.0b013e31824dae76
PG 20
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 955MY
UT WOS:000305025300016
PM 22647920
ER
PT J
AU Lambrechts, D
Truong, T
Justenhoven, C
Humphreys, MK
Wang, J
Hopper, JL
Dite, GS
Apicella, C
Southey, MC
Schmidt, MK
Broeks, A
Cornelissen, S
van Hien, R
Sawyer, E
Tomlinson, I
Kerin, M
Miller, N
Milne, RL
Zamora, MP
Perez, JIA
Benitez, J
Hamann, U
Ko, YD
Bruning, T
Chang-Claude, J
Eilber, U
Hein, R
Nickels, S
Flesch-Janys, D
Wang-Gohrke, S
John, EM
Miron, A
Winqvist, R
Pylkas, K
Jukkola-Vuorinen, A
Grip, M
Chenevix-Trench, G
Beesley, J
Chen, XQ
Menegaux, F
Cordina-Duverger, E
Shen, CY
Yu, JC
Wu, PE
Hou, MF
Andrulis, IL
Selander, T
Glendon, G
Mulligan, AM
Anton-Culver, H
Ziogas, A
Muir, KR
Lophatananon, A
Rattanamongkongul, S
Puttawibul, P
Jones, M
Orr, N
Ashworth, A
Swerdlow, A
Severi, G
Baglietto, L
Giles, G
Southey, M
Marme, F
Schneeweiss, A
Sohn, C
Burwinkel, B
Yesilyurt, BT
Neven, P
Paridaens, R
Wildiers, H
Brenner, H
Muller, H
Arndt, V
Stegmaier, C
Meindl, A
Schott, S
Bartram, CR
Schmutzler, RK
Cox, A
Brock, IW
Elliott, G
Cross, SS
Fasching, PA
Schulz-Wendtland, R
Ekici, AB
Beckmann, MW
Fletcher, O
Johnson, N
Silva, ID
Peto, J
Nevanlinna, H
Muranen, TA
Aittomaki, K
Blomqvist, C
Dork, T
Schurmann, P
Bremer, M
Hillemanns, P
Bogdanova, NV
Antonenkova, NN
Rogov, YI
Karstens, JH
Khusnutdinova, E
Bermisheva, M
Prokofieva, D
Gancev, S
Jakubowska, A
Lubinski, J
Jaworska, K
Durda, K
Nordestgaard, BG
Bojesen, SE
Lanng, C
Mannermaa, A
Kataja, V
Kosma, VM
Hartikainen, JM
Radice, P
Peterlongo, P
Manoukian, S
Bernard, L
Couch, FJ
Olson, JE
Wang, XS
Fredericksen, Z
Alnaes, GG
Kristensen, V
Borresen-Dale, AL
Devilee, P
Tollenaar, RAEM
Seynaeve, CM
Hooning, MJ
Garcia-Closas, M
Chanock, SJ
Lissowska, J
Sherman, ME
Hall, P
Liu, JJ
Czene, K
Kang, D
Yoo, KY
Noh, DY
Lindblom, A
Margolin, S
Dunning, AM
Pharoah, PDP
Easton, DF
Guenel, P
Brauch, H
AF Lambrechts, Diether
Truong, Therese
Justenhoven, Christina
Humphreys, Manjeet K.
Wang, Jean
Hopper, John L.
Dite, Gillian S.
Apicella, Carmel
Southey, Melissa C.
Schmidt, Marjanka K.
Broeks, Annegien
Cornelissen, Sten
van Hien, Richard
Sawyer, Elinor
Tomlinson, Ian
Kerin, Michael
Miller, Nicola
Milne, Roger L.
Pilar Zamora, M.
Arias Perez, Jose Ignacio
Benitez, Javier
Hamann, Ute
Ko, Yon-Dschun
Bruening, Thomas
Chang-Claude, Jenny
Eilber, Ursel
Hein, Rebecca
Nickels, Stefan
Flesch-Janys, Dieter
Wang-Gohrke, Shan
John, Esther M.
Miron, Alexander
Winqvist, Robert
Pylkas, Katri
Jukkola-Vuorinen, Arja
Grip, Mervi
Chenevix-Trench, Georgia
Beesley, Jonathan
Chen, Xiaoqing
Menegaux, Florence
Cordina-Duverger, Emilie
Shen, Chen-Yang
Yu, Jyh-Cherng
Wu, Pei-Ei
Hou, Ming-Feng
Andrulis, Irene L.
Selander, Teresa
Glendon, Gord
Mulligan, Anna Marie
Anton-Culver, Hoda
Ziogas, Argyrios
Muir, Kenneth R.
Lophatananon, Artitaya
Rattanamongkongul, Suthee
Puttawibul, Puttisak
Jones, Michael
Orr, Nicholas
Ashworth, Alan
Swerdlow, Anthony
Severi, Gianluca
Baglietto, Laura
Giles, Graham
Southey, Melissa
Marme, Federik
Schneeweiss, Andreas
Sohn, Christof
Burwinkel, Barbara
Yesilyurt, Betul T.
Neven, Patrick
Paridaens, Robert
Wildiers, Hans
Brenner, Hermann
Mueller, Heiko
Arndt, Volker
Stegmaier, Christa
Meindl, Alfons
Schott, Sarah
Bartram, Claus R.
Schmutzler, Rita K.
Cox, Angela
Brock, Ian W.
Elliott, Graeme
Cross, Simon S.
Fasching, Peter A.
Schulz-Wendtland, Ruediger
Ekici, Arif B.
Beckmann, Matthias W.
Fletcher, Olivia
Johnson, Nichola
Silva, Isabel dos Santos
Peto, Julian
Nevanlinna, Heli
Muranen, Taru A.
Aittomaki, Kristiina
Blomqvist, Carl
Doerk, Thilo
Schuermann, Peter
Bremer, Michael
Hillemanns, Peter
Bogdanova, Natalia V.
Antonenkova, Natalia N.
Rogov, Yuri I.
Karstens, Johann H.
Khusnutdinova, Elza
Bermisheva, Marina
Prokofieva, Darya
Gancev, Shamil
Jakubowska, Anna
Lubinski, Jan
Jaworska, Katarzyna
Durda, Katarzyna
Nordestgaard, Borge G.
Bojesen, Stig E.
Lanng, Charlotte
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Radice, Paolo
Peterlongo, Paolo
Manoukian, Siranoush
Bernard, Loris
Couch, Fergus J.
Olson, Janet E.
Wang, Xianshu
Fredericksen, Zachary
Alnaes, Grethe Grenaker
Kristensen, Vessela
Borresen-Dale, Anne-Lise
Devilee, Peter
Tollenaar, Robert A. E. M.
Seynaeve, Caroline M.
Hooning, Maartje J.
Garcia-Closas, Montserrat
Chanock, Stephen J.
Lissowska, Jolanta
Sherman, Mark E.
Hall, Per
Liu, Jianjun
Czene, Kamila
Kang, Daehee
Yoo, Keun-Young
Noh, Dong-Young
Lindblom, Annika
Margolin, Sara
Dunning, Alison M.
Pharoah, Paul D. P.
Easton, Douglas F.
Guenel, Pascal
Brauch, Hiltrud
CA GENICA Network
KConFab Investigators
Australian Ovarian Canc Study Grp
TI 11q13 is a susceptibility locus for hormone receptor positive breast
cancer
SO HUMAN MUTATION
LA English
DT Article
DE breast cancer susceptibility; polymorphisms; genome-wide association;
risk factors; hormone receptor status; 11q13
ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; TUMOR
CHARACTERISTICS; OVARIAN-CANCER; CONFER SUSCEPTIBILITY; FAMILY REGISTRY;
COMMON VARIANTS; BRCA1 MUTATIONS; REPAIR GENES; IDENTIFIES 5
AB A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10, and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we genotyped the variants rs2380205, rs1011970, rs704010, rs614367, and rs10995190 in 39 studies from the Breast Cancer Association Consortium (BCAC), involving 49,608 cases and 48,772 controls of predominantly European ancestry. Four of the variants showed clear evidence of association (P = 3 X 10-9) and weak evidence was observed for rs2380205 (P = 0.06). The strongest evidence was obtained for rs614367, located on 11q13 (per-allele odds ratio 1.21, P = 4 X 10-39). The association for rs614367 was specific to estrogen receptor (ER)-positive disease and strongest for ER plus progesterone receptor (PR)-positive breast cancer, whereas the associations for the other three loci did not differ by tumor subtype. Hum Mutat 33:11231132, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Justenhoven, Christina; Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany.
[Justenhoven, Christina; Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
[Ko, Yon-Dschun] Johanniter Krankenhaus, Dept Internal Med, Evangel Kliniken Bonn gGmbH, Bonn, Germany.
Univ Bonn, Inst Pathol, Fac Med, Bonn, Germany.
[Bruening, Thomas] German Social Accid Insurance IPA, Inst Prevent & Occupat Med, Bochum, Germany.
Univ Saarland, Fac Med, D-6650 Homburg, Germany.
[GENICA Network] Univ Saarland, Med Ctr, Inst & Outpatient Clin Occupat Med, D-6650 Homburg, Germany.
[Lambrechts, Diether; Yesilyurt, Betul T.] Katholieke Univ Leuven, Vesalius Res Ctr VRC, VIB, Louvain, Belgium.
[Truong, Therese; Menegaux, Florence; Cordina-Duverger, Emilie; Guenel, Pascal] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, F-94807 Villejuif, France.
[Truong, Therese; Menegaux, Florence; Cordina-Duverger, Emilie; Guenel, Pascal] Univ Paris 11, UMRS 1018, Villejuif, France.
[Humphreys, Manjeet K.; Wang, Jean; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
[Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Giles, Graham] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
[Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; van Hien, Richard] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
[Sawyer, Elinor] Guys & St Thomas NHS Fdn Trust Partnership Kings, Div Canc Studies, NIHR Comprehens Biomed Res Ctr, London, England.
[Tomlinson, Ian] Univ Oxford, Welcome Trust Ctr Human Genet, Oxford OX1 2JD, England.
[Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford OX1 2JD, England.
[Kerin, Michael; Miller, Nicola] Univ Hosp Galway, Inst Clin Sci, Galway, Ireland.
[Milne, Roger L.] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Human Canc Genet Programme, Madrid, Spain.
[Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Human Canc Genet Programme, Madrid, Spain.
[Pilar Zamora, M.] Hosp Univ La Paz, Med Oncol Serv, Madrid, Spain.
[Arias Perez, Jose Ignacio] Hosp Monte Naranco, Serv Cirug Gen & Especialidades, Oviedo, Spain.
[Chang-Claude, Jenny; Eilber, Ursel; Hein, Rebecca; Nickels, Stefan] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[John, Esther M.] Stanford Canc Inst, Stanford, CA USA.
[Miron, Alexander] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Canc Genet Lab, Dept Clin Genet, Oulu, Finland.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Jukkola-Vuorinen, Arja] Univ Oulu, Dept Oncol, Oulu Univ Hosp, Oulu, Finland.
[Grip, Mervi] Univ Oulu, Dept Surg, Oulu Univ Hosp, Oulu, Finland.
[Chenevix-Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[KConFab Investigators; Australian Ovarian Canc Study Grp] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Shen, Chen-Yang; Wu, Pei-Ei] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
[Shen, Chen-Yang; Wu, Pei-Ei] Taiwan Biobank, Taipei, Taiwan.
[Yu, Jyh-Cherng] Tri Serv Gen Hosp, Dept Surg, Taipei, Taiwan.
[Hou, Ming-Feng] Kaohsiung Med Univ, Ctr Canc, Chung Ho Mem Hosp, Kaohsiung, Taiwan.
[Hou, Ming-Feng] Kaohsiung Med Univ, Dept Surg, Chung Ho Mem Hosp, Kaohsiung, Taiwan.
[Andrulis, Irene L.] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada.
[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.
[Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Muir, Kenneth R.; Lophatananon, Artitaya] Univ Warwick, Hlth Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
[Rattanamongkongul, Suthee] Srinakhrainwirot Univ, Dept Prevent Med, Ongkharak, Nakhon Nayok, Thailand.
[Puttawibul, Puttisak] Prince Songkla Univ, Dept Surg, Sch Med, Hat Yai, Thailand.
[Jones, Michael; Swerdlow, Anthony] Inst Canc Res, Epidemiol Sect, Sutton, Surrey, England.
[Orr, Nicholas; Ashworth, Alan] Inst Canc Res, Chester Beatty Labs, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Severi, Gianluca; Baglietto, Laura; Giles, Graham; Southey, Melissa] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Marme, Federik; Schneeweiss, Andreas] Univ Heidelberg, Natl Ctr Tumor Dis, Heidelberg, Germany.
[Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany.
[Neven, Patrick; Paridaens, Robert; Wildiers, Hans] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium.
[Brenner, Hermann; Mueller, Heiko; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany.
[Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany.
[Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, Munich, Germany.
[Schott, Sarah] Univ Heidelberg, Dept Obstet & Gynecol, Heidelberg, Germany.
[Bartram, Claus R.] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Div Mol Gynecooncol, Dept Obstet & Gynaecol, Ctr Mol Med Cologne CMMC, Cologne, Germany.
[Cox, Angela; Brock, Ian W.; Elliott, Graeme] Univ Sheffield, Inst Canc Studies, Dept Oncol, Sheffield S10 2TN, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield S10 2TN, S Yorkshire, England.
[Fasching, Peter A.; Beckmann, Matthias W.] Univ Hosp Erlangen, Univ Breast Ctr, Dept Obstet & Gynecol, Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Schulz-Wendtland, Ruediger] Univ Hosp Erlangen, Inst Diagnost Radiol, Erlangen, Germany.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany.
[Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, London WC1, England.
[Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Biomedicum Helsinki, FIN-00290 Helsinki, Finland.
[Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland.
[Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland.
[Doerk, Thilo; Schuermann, Peter; Hillemanns, Peter; Bogdanova, Natalia V.; Karstens, Johann H.] Hannover Med Sch, Dept Obstet & Gynaecol, D-3000 Hannover, Germany.
[Bremer, Michael; Bogdanova, Natalia V.] 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.
[Khusnutdinova, Elza; Bermisheva, Marina; Prokofieva, Darya] Russian Acad Sci, Inst Biochem & Genet, Ufa Sci Ctr, Ufa 450001, Russia.
[Gancev, Shamil] Bashkirian Med Univ, Ufa, Russia.
[Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
[Jaworska, Katarzyna] Warsaw Med Univ, Postgrad Sch Mol Med, Warsaw, Poland.
[Nordestgaard, Borge G.; Bojesen, Stig E.] Univ Copenhagen, Copenhagen Gen Populat Study, Herlev Univ Hosp, Copenhagen, Denmark.
[Nordestgaard, Borge G.; Bojesen, Stig E.] Univ Copenhagen, Dept Clin Biochem, Herlev Univ Hosp, Copenhagen, Denmark.
[Lanng, Charlotte] Univ Copenhagen, Dept Breast Surg, Herlev Univ Hosp, Copenhagen, Denmark.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Sch Med, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
[Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Bioctr Kuopio, SF-70210 Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Dept Clin Pathol, SF-70210 Kuopio, Finland.
[Kataja, Vesa] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland.
[Kataja, Vesa] Univ Eastern Finland, Sch Med, Inst Clin Med, Kuopio, Finland.
[Radice, Paolo; Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predicted Med, Milan, Italy.
[Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predicted Med, Milan, Italy.
[Radice, Paolo; Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy.
[Bernard, Loris] Ist Europeo Oncol IEO, Dept Expt Oncol, Milan, Italy.
[Bernard, Loris] Consortium Genom Technol Cogentech, Milan, Italy.
[Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Olson, Janet E.; Fredericksen, Zachary] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Alnaes, Grethe Grenaker; Kristensen, Vessela; Borresen-Dale, Anne-Lise] Radiumhosp, Dept Genet, Inst Canc Res, Oslo Univ Hosp, Oslo, Norway.
[Kristensen, Vessela; Borresen-Dale, Anne-Lise] Univ Oslo, Fac Med, Fac Div Ahus, N-0316 Oslo, Norway.
[Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Tollenaar, Robert A. E. M.] Leiden Univ, Dept Surg, Med Ctr, Leiden, Netherlands.
[Seynaeve, Caroline M.; Hooning, Maartje J.] MC Daniel den Hoed Canc Ctr, Dept Med Oncol, Rotterdam Family Canc Clin, Rotterdam, Netherlands.
[Garcia-Closas, Montserrat; Chanock, Stephen J.; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Hall, Per; Liu, Jianjun; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young] Seoul Natl Univ, Coll Med, Seoul, South Korea.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
RP Brauch, H (reprint author), Dr Margarete Fischer Bosch Inst Clin Pharmacol, Auerbachstr 112, D-70376 Stuttgart, Germany.
EM hiltrud.brauch@ikp-stuttgart.de
RI Jakubowska, Anna/O-8050-2014; Garcia-Closas, Montserrat /F-3871-2015;
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; Andrulis,
Irene/E-7267-2013; Dzhemileva, Lilya/K-8636-2013; Radice,
Paolo/O-3119-2013; Dork, Thilo/J-8620-2012; Bernard, Loris/K-5953-2014;
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; Kerin,
Michael/D-6748-2013; Ekici, Arif/C-3971-2013;
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Bowtell,
David/0000-0001-9089-7525; Bruning, Thomas/0000-0001-9560-5464; Brenner,
Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562;
Dite, Gillian/0000-0002-2448-2548; Czene, Kamila/0000-0002-3233-5695;
Cross, Simon/0000-0003-2044-1754; Lissowska,
Jolanta/0000-0003-2695-5799; Dunning, Alison
Margaret/0000-0001-6651-7166; Dzhemileva, Lilya/0000-0003-3315-4746;
Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva,
Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Giles,
Graham/0000-0003-4946-9099; Muranen, Taru/0000-0002-5895-1808; Arndt,
Volker/0000-0001-9320-8684
FU European Community [223175, HEALTH-F2-2009-223175]; Cancer Research UK
[C1287/A10118, C1287/A12014]; European Union COST [BM0606]; United
States National Cancer Institute, National Institutes of Health (NIH)
[RFA-CA-06-503]; Cancer Prevention Institute of California [U01
CA69417]; University of Melbourne [U01 CA69638]; National Health and
Medical Research Council of Australia; New South Wales Cancer Council;
Victorian Health Promotion Foundation (Australia); Victorian Breast
Cancer Research Consortium; Dutch Cancer Society [NKI DCS 2007-3839,
2009-4363, UL1997-1505]; Dutch National Genomics Initiative; Breast
Cancer Research Trust; ELAN of the University Hospital of Erlangen;
Cancer Research UK; Breakthrough Breast Cancer; NHS; National Cancer
Research Network (NCRN); NIHR Comprehensive Biomedical Research Centre,
Guy's and St. Thomas' NHS Foundation Trust; King's College London;
Oxford Biomedical Research Centre; Dietmar-Hopp Foundation; Helmholtz
Society; German Cancer Research Center (DKFZ); Fondation de France
[2004012618, 2007005156]; Institut National du Cancer (INCa) [2007-1
SPC2, 2008-1-CP-4, 2009-1-SHS SP-04]; Association pour la Recherche
contre le Cancer (ARC) [2008-1-CP-4]; Genome Spain Foundation; Red
Tematica de Investigacion Cooperativa en Cancer; Asociacion Espanola
Contra el Cancer; Fondo de Investigacion Sanitario [PI081583, PI081120];
Chief Physician Johan Boserup and Lise Boserup Fund; Danish Medical
Research Council; Herlev Hospital; Baden Wurttemberg Ministry of
Science, Research and Arts; German Cancer Aid (Deutsche Krebshilfe)
[107054]; Federal Ministry of Education and Research (BMBF), Germany
[01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation,
Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg;
Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn;
Institute for Prevention and Occupational Medicine of the German Social
Accident Insurance (IPA), Bochum, Germany; "Stichting tegen Kanker"
[232-2008, 196-2010]; German Cancer Research Centre (DKFZ); Rudolf
Bartling Foundation; Hannover Medical School; Helsinki University
Central Hospital; Academy of Finland [132473]; Finnish Cancer Society;
Sigrid Juselius Foundation; German Academic Exchange Program; Friends of
Hannover Medical School; German Federal Ministry of Research and
Education [RUS08/017]; Swedish Cancer Society; Gustav V Jubilee
Foundation; National Breast Cancer Foundation; NHMRC; Queensland Cancer
Fund; Cancer Council of New South Wales; Cancer Council of Victoria;
Cancer Council of Tasmania; Cancer Council of South Australia; Cancer
Foundation of Western Australia; NHMRC [145684, 288704, 454508, 199600,
209057, 251533, 396414, 504711, 504715]; United States Army Medical
Research and Materiel Command [DAMD17-01-1-0729]; Kuopio University
Hospital; Cancer Fund of North Savo; Finnish Cancer Organizations;
Academy of Finland; University of Eastern Finland; Deutsche Krebshilfe
e.V. [70-2892-BR I]; Hamburg Cancer Society; German Cancer Research
Center; Federal Ministry of Education and Research (BMBF) Germany
[01KH0402]; Ministero della Salute; Ministero dell'Universita' e Ricerca
[RBLAO3-BETH]; Fondazione Italiana per la Ricerca sul Cancro;
Associazione Italiana per la Ricerca sul Cancro [4017]; NIH [CA122340,
CA128978, CA58860, CA92044]; Specialized Program of Research Excellence
(SPORE) in Breast Cancer [CA116201]; Cancer Council Victoria; Norwegian
Research council [155218/V40, 175240/S10]; FUGE-NFR [181600/V11]; Swizz
Bridge Award; Finnish Cancer Foundation; University of Oulu; Oulu
University Hospital; National Cancer Institute, Department of Health and
Human Services, USA; Yorkshire Cancer Research; Breast Cancer Campaign;
Ministry of Health and Welfare, Republic of Korea [AO30001]; Polish
Foundation of Science; Institute of Biomedical Sciences, Academia
Sinica, Taiwan; Lon V Smith Foundation [LVS39420]; Dutch Cancer Society
d [UL1997-1505]; Biobanking and Biomolecular Resources Research
Infrastructure [BBMRI-NL CP16]; Institute of Cancer Research;
[PBZ_KBN_122/P05/2004]
FX Contract grant sponsors: Part of this work was supported by the European
Community's Seventh Framework Programme under grant agreement number
223175 (grant number HEALTH-F2-2009-223175) (COGS). The BCAC is funded
by Cancer Research UK (C1287/A10118 and C1287/A12014). Meetings of the
BCAC have been funded by the European Union COST program (BM0606). D. F.
E. is a Principal Research Fellow of Cancer Research UK. The ABCFS,
NC-BCFR, and OFBCR work was supported by the United States National
Cancer Institute, National Institutes of Health (NIH) under
RFA-CA-06-503, and through cooperative agreements with members of the
Breast Cancer Family Registry (BCFR) and Principal Investigators,
including Cancer Care Ontario (U01 CA69467), Cancer Prevention Institute
of California (U01 CA69417), and University of Melbourne (U01 CA69638).
Samples from the NC-BCFR were processed and distributed by the Coriell
Institute for Medical Research. The content of this manuscript does not
necessarily reflect the views or policies of the National Cancer
Institute or any of the collaborating centers in the BCFR, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government or the BCFR. The ABCFS was also
supported by the National Health and Medical Research Council of
Australia, the New South Wales Cancer Council, the Victorian Health
Promotion Foundation (Australia) and the Victorian Breast Cancer
Research Consortium. J.L.H. is a National Health and Medical Research
Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research
Consortium Group Leader. M. C. S. is a NHMRC Senior Research Fellow and
a Victorian Breast Cancer Research Consortium Group Leader. The ABCS
study was supported by the Dutch Cancer Society (grants NKI DCS
2007-3839 and 2009-4363) and the Dutch National Genomics Initiative. The
ACP is funded by the Breast Cancer Research Trust. The work of the BBCC
was partly funded by ELAN Fond of the University Hospital of Erlangen.
The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer
and acknowledges NHS funding to the NIHR Biomedical Research Centre, and
the National Cancer Research Network (NCRN). BIGGS: E. S. is supported
by NIHR Comprehensive Biomedical Research Centre, Guy's and St. Thomas'
NHS Foundation Trust in partnership with King's College London. I. T. is
supported by the Oxford Biomedical Research Centre. The BSUCH study was
supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the
German Cancer Research Center (DKFZ). CECILE study was funded by
Fondation de France (grant 2004012618; 2007005156), Institut National du
Cancer (INCa grant 2007-1 SPC2; 2008-1-CP-4; 2009-1-SHS SP-04),
Association pour la Recherche contre le Cancer (ARC grant 2008-1-CP-4).
The CNIO-BCS was supported by the Genome Spain Foundation, the Red
Tematica de Investigacion Cooperativa en Cancer and grants from the
Asociacion Espanola Contra el Cancer and the Fondo de Investigacion
Sanitario (PI081583 and PI081120). The CGPS was supported by the Chief
Physician Johan Boserup and Lise Boserup Fund, the Danish Medical
Research Council and Herlev Hospital. The ESTHER study was supported by
a grant from the Baden Wurttemberg Ministry of Science, Research and
Arts. Additional cases were recruited in the context of the VERDI study,
which was supported by a grant from the German Cancer Aid (Deutsche
Krebshilfe).; The GENICA Network was funded by the Federal Ministry of
Education and Research (BMBF), Germany, grants 01KW9975/5, 01KW9976/8,
01KW9977/0, and 01KW0114; the Robert Bosch Foundation, Stuttgart;
Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Evangelische
Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn; Institute for
Prevention and Occupational Medicine of the German Social Accident
Insurance (IPA), Bochum, Germany. The LMBC was supported by the
"Stichting tegen Kanker" (grants 232-2008 and 196-2010). The GC-HBOC was
supported by Deutsche Krebshilfe (107054), the Dietmar-Hopp Foundation,
the Helmholtz society, and the German Cancer Research Centre (DKFZ). The
HABCS study was supported by the Rudolf Bartling Foundation and by an
intramural grant from Hannover Medical School. The HEBCS study has been
financially supported by the Helsinki University Central Hospital
Research Fund, Academy of Finland (132473), the Finnish Cancer Society,
and the Sigrid Juselius Foundation. The HM-BCS was supported by
short-term fellowships from the German Academic Exchange Program (to
N.B), and the Friends of Hannover Medical School (to N.B.). The HUBCS
was supported by a grant from the German Federal Ministry of Research
and Education (RUS08/017). The KARBAC work was supported by the Swedish
Cancer Society and the Gustav V Jubilee Foundation. kConFab is supported
by grants from the National Breast Cancer Foundation; the NHMRC; the
Queensland Cancer Fund; the Cancer Councils of New South Wales,
Victoria, Tasmania, and South Australia; and the Cancer Foundation of
Western Australia. The kConFab Clinical Follow Up Study was funded by
the NHMRC (145684, 288704, and 454508). Financial support for the AOCS
was provided by the United States Army Medical Research and Materiel
Command (DAMD17-01-1-0729), the Cancer Council of Tasmania and Cancer
Foundation of Western Australia and the NHMRC (199600). G. C. T. and P.
W. are supported by the NHMRC. The KBCP was financially supported by the
special Government Funding (EVO) of Kuopio University Hospital grants,
Cancer Fund of North Savo, the Finnish Cancer Organizations, the Academy
of Finland, and by the strategic funding of the University of Eastern
Finland. The MARIE study was supported by the Deutsche Krebshilfe e. V.
(70-2892-BR I), the Hamburg Cancer Society, the German Cancer Research
Center, and the genotype work in part by the Federal Ministry of
Education and Research (BMBF) Germany (01KH0402). MBCSG is supported by
grants from Ministero della Salute (Extraordinary National Cancer
Program 2006 "Alleanza contro il Cancro", and "Progetto Tumori
Femminili" to P. R.), Ministero dell'Universita' e Ricerca (RBLAO3-BETH
to PR), Fondazione Italiana per la Ricerca sul Cancro (Special Project
"Hereditary tumors"), Associazione Italiana per la Ricerca sul Cancro
(4017 and by funds from Italian citizens who allocated the 5/1000 share
of their tax payment in support of the Fondazione IRCCS Istituto
Nazionale Tumori, according to Italian laws (INT-Institutional strategic
projects "5 x 1000"). The MCBCS was supported by the NIH grants
[CA122340, CA128978] and a Specialized Program of Research Excellence
(SPORE) in Breast Cancer [CA116201]. MCCS is supported by Cancer Council
Victoria and by NHMRC (grants 209057, 251533, 396414, 504711, and
504715). The NBCS was supported by grants from the Norwegian Research
council, 155218/V40, 175240/S10 to ALBD, FUGE-NFR 181600/V11 to VNK and
a Swizz Bridge Award to ALBD.; The OBCS was supported by research grants
from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the
Academy of Finland, the University of Oulu, and the Oulu University
Hospital. The PBCS was funded by Intramural Research Funds of the
National Cancer Institute, Department of Health and Human Services, USA.
The SBCS was supported by Yorkshire Cancer Research and the Breast
Cancer Campaign. The SEBCS was supported by the Korea Health 21 R&D
Project [AO30001], Ministry of Health and Welfare, Republic of Korea.
The SZBCS was supported by Grant PBZ_KBN_122/P05/2004; Katarzyna
Jaworska is a fellow of International Ph.D. program, Postgraduate School
of Molecular Medicine, Warsaw Medical University, supported by the
Polish Foundation of Science. The TWBCS is supported by the Taiwan
Biobank project of the Institute of Biomedical Sciences, Academia
Sinica, Taiwan. The UCIBCS component of this research was supported by
the NIH [CA58860, CA92044] and the Lon V Smith Foundation (LVS39420).
ORIGO were funded by grants from the Dutch Cancer Society (UL1997-1505)
and the Biobanking and Biomolecular Resources Research Infrastructure
(BBMRI-NL CP16). The UKBGS thank Breakthrough Breast Cancer and the
Institute of Cancer Research for funding. The ICR acknowledge NHS
funding to the NIHR Biomedical Research Centre.
NR 73
TC 22
Z9 24
U1 4
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD JUL
PY 2012
VL 33
IS 7
BP 1123
EP 1132
DI 10.1002/humu.22089
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 952TK
UT WOS:000304815100017
PM 22461340
ER
PT J
AU Le Grange, D
Swanson, SA
Crow, SJ
Merikangas, KR
AF Le Grange, Daniel
Swanson, Sonja A.
Crow, Scott J.
Merikangas, Kathleen R.
TI Eating disorder not otherwise specified presentation in the US
population
SO INTERNATIONAL JOURNAL OF EATING DISORDERS
LA English
DT Article
DE anorexia nervosa; bulimia nervosa; EDNOS; EDNOS-subtypes;
classification; DSM
ID COMORBIDITY SURVEY REPLICATION; SUPPLEMENT NCS-A; BULIMIA-NERVOSA; FIELD
PROCEDURES; DSM-V; ADOLESCENTS; DESIGN; CLASSIFICATION; EDNOS; NOS
AB Objective: To examine prevalence and clinical correlates of eating disorder not otherwise specified (EDNOS) in the US population. Method: Two cross-sectional surveys of adults and adolescents used the WHO CIDI to assess DSM-IV criteria for anorexia nervosa (AN), bulimia nervosa (BN), and EDNOS. Results: Lifetime prevalence of EDNOS was 4.78% in adolescents and 4.64% in adults. The majority of adolescents and adults with an eating disorder presented with EDNOS. Three-quarters of participants with EDNOS met criteria for comorbid disorders, while one-quarter endorsed suicidality. Severity correlates were equally prevalent in EDNOS and AN, whereas comparisons between EDNOS and BN varied by specific correlate and sample. Adolescents with subthreshold AN (SAN) endorsed more anxiety than AN (p < .05), and adolescents and adults with SAN endorsed more suicidal plans than AN (p's < .05). Discussion: Findings increase our understanding of the clinical relevance of EDNOS. Eating disorder diagnostic nomenclature requires modification to capture the full spectrum. (c) 2012 by Wiley Periodicals, Inc. Int J Eat Disord 2012.
C1 [Swanson, Sonja A.; Merikangas, Kathleen R.] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA.
[Le Grange, Daniel] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
[Swanson, Sonja A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Crow, Scott J.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA.
RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, Intramural Res Program, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
EM kathleen.merikangas@nih.gov
FU NCS-A [Z08-MH002808, U01-MH60220]; National Institute of Mental Health
[R01 MH079979]; Baker Foundation (Australia); Pfizer; GlaxoSmithKline;
Ortho-McNeil; Intramural Research Program
FX Supported by Z08-MH002808 and U01-MH60220 from NCS-A and National
Institute of Mental Health, by R01 MH079979 from National Institute of
Mental Health and by the Baker Foundation (Australia), and from Pfizer,
GlaxoSmithKline, Ortho-McNeil, Intramural Research Program, and National
Institute of Mental Health.
NR 31
TC 34
Z9 35
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0276-3478
J9 INT J EAT DISORDER
JI Int. J. Eating Disord.
PD JUL
PY 2012
VL 45
IS 5
BP 711
EP 718
DI 10.1002/eat.22006
PG 8
WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology
SC Psychology; Nutrition & Dietetics; Psychiatry
GA 955CC
UT WOS:000304993700011
PM 22407912
ER
PT J
AU Ramadan, E
Chang, LS
Chen, M
Ma, KZ
Hall, FS
Uhl, GR
Rapoport, SI
Basselin, M
AF Ramadan, Epolia
Chang, Lisa
Chen, Mei
Ma, Kaizong
Hall, F. Scott
Uhl, George R.
Rapoport, Stanley I.
Basselin, Mireille
TI Knocking Out the Dopamine Reuptake Transporter (DAT) Does not Change the
Baseline Brain Arachidonic Acid Signal in the Mouse
SO INTERNATIONAL JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE arachidonic acid; dopamine; dopamine transporter; knockout; mouse;
phospholipase A(2)
ID PHOSPHOLIPASE A(2); MICE LACKING; UNANESTHETIZED RATS; KNOCKOUT MICE;
MONOAMINE TRANSPORTER; DOCOSAHEXAENOIC ACID; PARKINSONS-DISEASE;
AMPHETAMINE; SEROTONIN; RECEPTORS
AB Background. Dopamine transporter (DAT) homozygous knockout (DAT(-/-)) mice have a 10-fold higher extracellular Dopamine (DA) concentration in the caudate-putamen and nucleus accumbens than do wildtype (DAT(+/+)) mice, but show reduced presynaptic DA synthesis and fewer postsynaptic D-2 receptors. One aspect of neurotransmission involves DA binding to postsynaptic D-2-like receptors coupled to cytosolic phospholipase A(2) (cPLA(2)), which releases the second messenger, arachidonic acid (AA), from synaptic membrane phospholipid. We hypothesized that tonic overactivation of D-2-like receptors in DAT(-/-) mice due to the excess DA would not increase brain AA signaling, because of compensatory downregulation of postsynaptic DA signaling mechanisms. Methods: [1-C-14] AA was infused intravenously for 3 min in unanesthetized DAT(+/+), heterozygous (DAT(+/-)), and DAT(-/-) mice. AA incorporation coefficients k* and rates J(in), markers of AA metabolism and signaling, were imaged in 83 brain regions using quantitative autoradiography; brain cPLA(2)-IV activity also was measured. Results: Neither k* nor J(in) for AA in any brain region, or brain cPLA(2)-IV activity, differed significantly among DAT(-/-), DAT(+/-), and DAT(+/+) mice. Conclusions: These results differ from reported increases in k* and J(in) for AA, and in brain cPLA(2) expression, in serotonin reuptake transporter (5-HTT) knockout mice, and suggest that postsynaptic dopaminergic neurotransmission mechanisms involving AA are downregulated despite elevated DA in DAT(-/-) mice.
C1 [Ramadan, Epolia; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.; Basselin, Mireille] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Hall, F. Scott; Uhl, George R.] NIA, Mol Neurobiol Branch, NIH, Bethesda, MD 20892 USA.
RP Ramadan, E (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126, Bethesda, MD 20892 USA.
EM ramadanir@mail.nih.gov
RI Hall, Frank/C-3036-2013
OI Hall, Frank/0000-0002-0822-4063
FU National Institute of Aging; National Institute on Drug Abuse at NIH
FX This research was supported by the Intramural Research Programs of the
National Institute of Aging and National Institute on Drug Abuse at NIH.
No author has a financial or other conflict of interest regarding this
work. We thank Eugene Streicher for proofreading the paper.
NR 56
TC 3
Z9 3
U1 1
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0020-7454
J9 INT J NEUROSCI
JI Int. J. Neurosci.
PD JUL
PY 2012
VL 122
IS 7
BP 373
EP 380
DI 10.3109/00207454.2012.665972
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 955IS
UT WOS:000305011800008
PM 22376027
ER
PT J
AU Ropero-Miller, JD
Huestis, MA
Stout, PR
AF Ropero-Miller, Jeri D.
Huestis, Marilyn A.
Stout, Peter R.
TI Cocaine Analytes in Human Hair: Evaluation of Concentration Ratios in
Different Cocaine Sources, Drug-User Populations and
Surface-Contaminated Specimens
SO JOURNAL OF ANALYTICAL TOXICOLOGY
LA English
DT Article
ID CAPILLARY GAS-CHROMATOGRAPHY; TESTING HUMAN HAIR; ILLICIT COCAINE;
EXTERNAL CONTAMINATION; MASS-SPECTROMETRY; SOUTH-AMERICAN; METABOLITES;
COCAETHYLENE; CODEINE; DISPOSITION
AB Hair specimens were analyzed for cocaine (COC), benzoylecgonine (BE), cocaethylene (CE) and norcocaine (NCOC) by liquid chromatographytandem mass spectrometry. Drug-free hair was contaminated in vitro with COC from different sources with varied COC analyte concentrations. Results were compared to COC analyte concentrations in drug users' hair following self-reported COC use (Street) and in hair from participants in controlled COC administration studies (Clinical) on a closed clinical research unit. Mean standard error analyte concentrations in Street drug users' hair were COC 27,889 7,846 (n 38); BE 8,132 2,523 (n 38); CE 901 320 (n 20); NCOC 345 72 pg/mg (n 32). Mean percentages to COC concentration were BE 29, CE 3 and NCOC 1. Concentrations in hair were lower for Clinical participants. COC contamination with higher CE, BE or NCOC content produced significantly higher concentrations (P 0.0001) of all analytes. CE/COC and NCOC/COC ratios did not improve differentiation of COC use from COC contamination. COC concentrations in illicit and pharmaceutical COC affect concentrations in contaminated hair. Criteria for distinguishing COC use from contamination under realistic concentrations were not significantly improved by adding CE and NCOC criteria to COC cutoff concentration and BE/COC ratio criteria. Current criteria for COC hair testing in many forensic drug-testing laboratories may not effectively discriminate between COC use and environmental COC exposure.
C1 [Ropero-Miller, Jeri D.; Stout, Peter R.] RTI Int, Ctr Forens Sci, Res Triangle Pk, NC USA.
[Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD USA.
RP Ropero-Miller, JD (reprint author), RTI Int, Ctr Forens Sci, Res Triangle Pk, NC USA.
EM jerimiller@rti.org
NR 36
TC 22
Z9 22
U1 0
U2 18
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0146-4760
J9 J ANAL TOXICOL
JI J. Anal. Toxicol.
PD JUL
PY 2012
VL 36
IS 6
SI SI
BP 390
EP 398
DI 10.1093/jat/bks050
PG 9
WC Chemistry, Analytical; Toxicology
SC Chemistry; Toxicology
GA 952ZQ
UT WOS:000304835800004
PM 22593566
ER
PT J
AU Schwope, DM
Bosker, WM
Ramaekers, JG
Gorelick, DA
Huestis, MA
AF Schwope, David M.
Bosker, Wendy M.
Ramaekers, Johannes G.
Gorelick, David A.
Huestis, Marilyn A.
TI Psychomotor Performance, Subjective and Physiological Effects and Whole
Blood (9)-Tetrahydrocannabinol Concentrations in Heavy, Chronic Cannabis
Smokers Following Acute Smoked Cannabis
SO JOURNAL OF ANALYTICAL TOXICOLOGY
LA English
DT Article
ID ORAL FLUID; DELTA-9-TETRAHYDROCANNABINOL THC;
DELTA(9)-TETRAHYDROCANNABINOL THC; HEPATIC MICROSOMES; SMOKING
MARIJUANA; MOTOR CONTROL; TETRAHYDROCANNABINOL; METABOLISM; SERUM; USERS
AB Delta(9)-tetrahydrocannabinol (THC) is the illicit drug most frequently observed in accident and driving under the influence of drugs investigations. Whole blood is often the only available specimen collected during such investigations, yet few studies have examined relationships between cannabis effects and whole blood concentrations following cannabis smoking.
Nine male and one female heavy, chronic cannabis smokers resided on a closed research unit and smoked ad libitum one 6.8 THC cannabis cigarette. THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC were quantified in whole blood and plasma. Assessments were performed before and up to 6 h after smoking, including subjective [visual analog scales (VAS) and Likert scales], physiological (heart rate, blood pressure and respirations) and psychomotor (critical-tracking and divided-attention tasks) measures.
THC significantly increased VAS responses and heart rate, with concentration-effect curves demonstrating counter-clockwise hysteresis. No significant differences were observed for critical-tracking or divided-attention task performance in this cohort of heavy, chronic cannabis smokers. The cannabis influence factor was not suitable for quantifying psychomotor impairment following cannabis consumption and was not precise enough to determine recent cannabis use with accuracy.
These data inform our understanding of impairment and subjective effects following acute smoked cannabis and interpretation of whole blood cannabinoid concentrations in forensic investigations.
C1 [Schwope, David M.; Gorelick, David A.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Bosker, Wendy M.; Ramaekers, Johannes G.] Maastricht Univ, Fac Psychol & Neurosci, Dept Neuropsychol & Psychopharmacol, NL-6200 MD Maastricht, Netherlands.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU National Institute on Drug Abuse, National Institutes of Health
FX We acknowledge Erin Karschner and Karl Scheidweiler for technical
assistance in manuscript preparation and the NIDA Intramural Research
Program clinical research team, especially Rebecca Price, John Etter,
Janeen Nichels and Daniel Lipstein, for clinical support. This research
was supported by the Intramural Research Program of the National
Institute on Drug Abuse, National Institutes of Health.
NR 42
TC 25
Z9 25
U1 1
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0146-4760
J9 J ANAL TOXICOL
JI J. Anal. Toxicol.
PD JUL
PY 2012
VL 36
IS 6
SI SI
BP 405
EP 412
DI 10.1093/jat/bks044
PG 8
WC Chemistry, Analytical; Toxicology
SC Chemistry; Toxicology
GA 952ZQ
UT WOS:000304835800006
PM 22589524
ER
PT J
AU Chio, A
Restagno, G
Brunetti, M
Ossola, I
Calvo, A
Canosa, A
Moglia, C
Floris, G
Tacconi, P
Marrosu, F
Marrosu, MG
Murru, MR
Majounie, E
Renton, AE
Abramzon, Y
Pugliatti, M
Sotgiu, MA
Traynor, BJ
Borghero, G
AF Chio, Adriano
Restagno, Gabriella
Brunetti, Maura
Ossola, Irene
Calvo, Andrea
Canosa, Antonio
Moglia, Cristina
Floris, Gianluca
Tacconi, Paolo
Marrosu, Francesco
Marrosu, Maria Giovanna
Murru, Maria Rita
Majounie, Elisa
Renton, Alan E.
Abramzon, Yvegeniya
Pugliatti, Maura
Sotgiu, Maria Alessandra
Traynor, Bryan J.
Borghero, Giuseppe
CA SARDINIALS Consortium
TI ALS/FTD phenotype in two Sardinian families carrying both C9ORF72 and
TARDBP mutations
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; HEXANUCLEOTIDE REPEAT EXPANSION; SOD1
MUTATIONS; ALS; POPULATION; GENE; FTD
AB Background In the isolated population of Sardinia, a Mediterranean island, similar to 25% of ALS cases carry either a p.A382T mutation of the TARDBP gene or a GGGGCC hexanucleotide repeat expansion in the first intron of the C9ORF72 gene.
Objective To describe the co-presence of two genetic mutations in two Sardinian ALS patients.
Methods We identified two index ALS cases carrying both the p center dot A382T missense mutation of TARDBP gene and the hexanucleotide repeat expansion of C9ORF72 gene.
Results The index case of Family A had bulbar ALS and frontemporal dementia (FTD) at 43. His father, who carried the hexanucleotide repeat expansion of C9ORF72 gene, had spinal ALS and FTD at 64 and his mother, who carried the TARDBP gene p center dot A382T missense mutation, had spinal ALS and FTD at 69. The index case of Family B developed spinal ALS without FTD at 35 and had a rapid course to respiratory failure. His parents are healthy at 62 and 63. The two patients share the known founder risk haplotypes across both the C9ORF72 9p21 locus and the TARDBP 1p36.22 locus.
Conclusions Our data show that in rare neurodegenerative causing genes can co-exist within the same individuals and are associated with a more severe disease course.
C1 [Chio, Adriano; Calvo, Andrea; Canosa, Antonio; Moglia, Cristina] Univ Turin, Dept Neurosci, ALS Ctr, I-10126 Turin, Italy.
[Chio, Adriano; Calvo, Andrea; Canosa, Antonio; Moglia, Cristina] Univ San Giovanni Battista, Azienda Osped, Turin, Italy.
[Restagno, Gabriella; Brunetti, Maura; Ossola, Irene] ASOOIRM St Anna, Mol Genet Unit, Dept Clin Pathol, Turin, Italy.
[Floris, Gianluca; Tacconi, Paolo; Marrosu, Francesco; Borghero, Giuseppe] Univ Cagliari, I-09124 Cagliari, Italy.
[Floris, Gianluca; Tacconi, Paolo; Marrosu, Francesco; Borghero, Giuseppe] Azienda Univ Osped Cagliari, Dept Neurol, Cagliari, Italy.
[Marrosu, Maria Giovanna; Murru, Maria Rita] Univ Cagliari, Multiple Sclerosis Ctr, Binaghi Hosp, I-09124 Cagliari, Italy.
[Majounie, Elisa] NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Renton, Alan E.; Abramzon, Yvegeniya; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Pugliatti, Maura] Univ Sassari, Dept Neurosci, I-07100 Sassari, Italy.
[Sotgiu, Maria Alessandra] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy.
RP Chio, A (reprint author), Univ Turin, Dept Neurosci, ALS Ctr, Via Cherasco 15, I-10126 Turin, Italy.
EM achio@usa.net
RI Traynor, Bryan/G-5690-2010; Calvo, Andrea/K-4141-2016; Moglia,
Cristina/K-4142-2016;
OI Calvo, Andrea/0000-0002-5122-7243; Moglia, Cristina/0000-0001-7377-7222;
Chio, Adriano/0000-0001-9579-5341; Cammarosano,
Stefania/0000-0002-0981-5252; Ilardi, Antonio/0000-0002-8305-0518;
SOLINAS, GIULIANA/0000-0003-2174-0983; Marrosu, Maria
Giovanna/0000-0003-2334-2081
FU National Institute on Aging [Z01-AG000949-02]; Packard Center for ALS
Research at Hopkins; ALS Association; Microsoft Research; Federazione
Italiana Giuoco Calcio; European Community [259867]; NIH
FX This work was supported by the Intramural Research Programs of the NIH,
National Institute on Aging (Z01-AG000949-02), the Packard Center for
ALS Research at Hopkins, the ALS Association, Microsoft Research,
Federazione Italiana Giuoco Calcio (grant 2010, #2) and European
Community's Health Seventh Framework Programme (FP7/2007-2013) under
grant agreement 259867. Dr. Traynor reports that a patent is pending
based on the discovery of the hexanucleotide repeat expansion of
C9ORF72.
NR 19
TC 23
Z9 23
U1 0
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
EI 1468-330X
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD JUL
PY 2012
VL 83
IS 7
BP 730
EP 733
DI 10.1136/jnnp-2012-302219
PG 4
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 953XQ
UT WOS:000304907500013
PM 22550220
ER
PT J
AU Wadiwala, MF
Kamal, AK
AF Wadiwala, Muhammad Faisal
Kamal, Ayeesha Kamran
TI Long term effect of carotid surgery in asymptomatic stenosis
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Kamal, Ayeesha Kamran] Aga Khan Univ Hosp, Stroke Serv, Fogarty Int Ctr, Karachi, Pakistan.
Aga Khan Univ Hosp, Vasc Fellowship Program, Fogarty Int Ctr, Int Ccrebrovasc Translat Clin Res Training Progra, Karachi, Pakistan.
Aga Khan Univ Hosp, Vasc Fellowship Program, Natl Inst Neurol Disorders & Stroke, Int Ccrebrovasc Translat Clin Res Training Progra, Karachi, Pakistan.
Aga Khan Univ Hosp, Stroke Serv, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan.
RP Kamal, AK (reprint author), Aga Khan Univ Hosp, Stroke Serv, Fogarty Int Ctr, Karachi, Pakistan.
EM ayeesha.kamal@aku.edu
FU FIC NIH HHS [D43TW008660, D43 TW008660]
NR 1
TC 0
Z9 0
U1 0
U2 0
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 JUL
PY 2012
VL 62
IS 7
BP 739
EP 740
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 954WP
UT WOS:000304979000028
PM 23866531
ER
PT J
AU Griffioen, KJ
Wan, RQ
Brown, TR
Okun, E
Camandola, S
Mughal, MR
Phillips, TM
Mattson, MP
AF Griffioen, Kathleen J.
Wan, Ruiqian
Brown, Tashalee R.
Okun, Eitan
Camandola, Simonetta
Mughal, Mohamed R.
Phillips, Terry M.
Mattson, Mark P.
TI Aberrant heart rate and brainstem brain-derived neurotrophic factor
(BDNF) signaling in a mouse model of Huntington's disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Huntington's disease; Brainstem; BDNF
ID STRESS; MICE; EXPRESSION; RECEPTOR
AB Huntington's disease (HD) is associated with profound autonomic dysfunction including dysregulation of cardiovascular control often preceding cognitive or motor symptoms. Brain-derived neurotrophic factor (BDNF) levels are decreased in the brains of HD patients and HD mouse models, and restoring BDNF levels prevents neuronal loss and extends survival in HD mice. We reasoned that heart rate changes in HD may be associated with altered BDNF signaling in cardiovascular control nuclei in the brainstem. Here we show that heart rate is elevated in HD (N171-82Q) mice at presymptomatic and early disease stages, and heart rate responses to restraint stress are attenuated. BDNF levels were significantly reduced in brainstem regions containing cardiovascular nuclei in HD mice and human HD patients. Central administration of BDNF restored the heart rate to control levels. Our findings establish a link between diminished BDNF expression in brainstem cardiovascular nuclei and abnormal heart rates in HD mice, and suggest a novel therapeutic target for correcting cardiovascular dysfunction in HD. Published by Elsevier Inc.
C1 [Griffioen, Kathleen J.; Wan, Ruiqian; Brown, Tashalee R.; Camandola, Simonetta; Mughal, Mohamed R.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Brown, Tashalee R.] Weill Cornell Rockefeller Sloan Kettering Triinst, New York, NY USA.
[Okun, Eitan] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.
[Phillips, Terry M.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Baltimore, MD USA.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012; okun, eitan/K-1314-2016
OI okun, eitan/0000-0001-8474-1487
FU National Institute on Aging
FX The first two authors contributed equally to this work. This research
was supported by the Intramural Research Program of the National
Institute on Aging.
NR 19
TC 3
Z9 3
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUL
PY 2012
VL 33
IS 7
AR 1481.e1
DI 10.1016/j.neurobiolaging.2011.11.030
PG 5
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 953GG
UT WOS:000304854300038
PM 22209255
ER
PT J
AU Hernandez, DG
Nalls, MA
Moore, M
Chong, S
Dillman, A
Trabzuni, D
Gibbs, JR
Ryten, M
Arepalli, S
Weale, ME
Zonderman, AB
Troncoso, J
O'Brien, R
Walker, R
Smith, C
Bandinelli, S
Traynor, BJ
Hardy, J
Singleton, AB
Cookson, MR
AF Hernandez, Dena G.
Nalls, Mike A.
Moore, Matthew
Chong, Sean
Dillman, Allissa
Trabzuni, Daniah
Gibbs, J. Raphael
Ryten, Mina
Arepalli, Sampath
Weale, Michael E.
Zonderman, Alan B.
Troncoso, Juan
O'Brien, Richard
Walker, Robert
Smith, Colin
Bandinelli, Stefania
Traynor, Bryan J.
Hardy, John
Singleton, Andrew B.
Cookson, Mark R.
TI Integration of GWAS SNPs and tissue specific expression profiling reveal
discrete eQTLs for human traits in blood and brain
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE eQTL; GWAS; Brain; Blood
ID GENOME-WIDE ASSOCIATION; HUMAN GENE-EXPRESSION; CORONARY-ARTERY-DISEASE;
SUSCEPTIBILITY LOCI; CROHNS-DISEASE; PLASMA-LEVELS; RISK LOCI;
METAANALYSIS; VARIANTS; DETERMINANTS
AB Genome-wide association studies have nominated many genetic variants for common human traits, including diseases, but in many cases the underlying biological reason for a trait association is unknown. Subsets of genetic polymorphisms show a statistical association with transcript expression levels, and have therefore been nominated as expression quantitative trait loci (eQTL). However, many tissue and cell types have specific gene expression patterns and so it is not clear how frequently eQTLs found in one tissue type will be replicated in others. In the present study we used two appropriately powered sample series to examine the genetic control of gene expression in blood and brain. We find that while many eQTLs associated with human traits are shared between these two tissues, there are also examples where blood and brain differ, either by restricted gene expression patterns in one tissue or because of differences in how genetic variants are associated with transcript levels. These observations suggest that design of eQTL mapping experiments should consider tissue of interest for the disease or other traits studied. Published by Elsevier Inc.
C1 [Cookson, Mark R.] NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Hernandez, Dena G.; Trabzuni, Daniah; Gibbs, J. Raphael; Ryten, Mina; Hardy, John] UCL Inst Neurol, Dept Mol Neurosci, London, England.
[Weale, Michael E.] Kings Coll London, Dept Med & Mol Genet, London, England.
[Zonderman, Alan B.] NIA, Res Resources Branch, NIH, Bethesda, MD 20892 USA.
[Troncoso, Juan; O'Brien, Richard] Johns Hopkins Univ, Brain Resource Ctr, Baltimore, MD USA.
[Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy.
[Walker, Robert; Smith, Colin] Univ Edinburgh, Dept Pathol, Edinburgh, Midlothian, Scotland.
[Dillman, Allissa] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, NIH, 35 Convent Dr, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov
RI Hardy, John/C-2451-2009; Weale, Michael/F-2587-2010; Singleton,
Andrew/C-3010-2009; Traynor, Bryan/G-5690-2010;
OI Weale, Michael/0000-0003-4593-1186; Walker, Robert/0000-0001-7383-7846;
Zonderman, Alan B/0000-0002-6523-4778
FU NIH; National Institute on Aging [ZO1-AG000947, Z01-AG000185]; UK
Medical Research Council; Italian Ministry of Health [ICS110.1/RF97.71];
U.S. National Institute on Aging [263 MD 9164, 263 MD 821336]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging (ZO1-AG000947 and Z01-AG000185)
and in part by the UK Medical Research Council. The InCHIANTI study
baseline (1998-2000) was supported as a "targeted project"
(ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the
U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD
821336). There is no conflict of interest to disclose.
NR 49
TC 41
Z9 41
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 0969-9961
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD JUL
PY 2012
VL 47
IS 1
BP 20
EP 28
DI 10.1016/j.nbd.2012.03.020
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 952KP
UT WOS:000304791700003
PM 22433082
ER
PT J
AU Bhattacharjee, AK
White, L
Chang, LS
Ma, KZ
Harry, GJ
Deutsch, J
Rapoport, SI
AF Bhattacharjee, Abesh Kumar
White, Laura
Chang, Lisa
Ma, Kaizong
Harry, G. Jean
Deutsch, Joseph
Rapoport, Stanley I.
TI Bilateral Common Carotid Artery Ligation Transiently Changes Brain Lipid
Metabolism in Rats
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Arachidonic acid; Ischemia; Carotid; Ligation; Acyl-CoA; Brain; CPLA2;
SPLA2; Rat; Brain; Neuroinflammation
ID CHRONIC CEREBRAL HYPOPERFUSION; CYTOSOLIC PHOSPHOLIPASE A(2);
ARACHIDONIC-ACID METABOLISM; ACYL-COA CONCENTRATIONS; FREE FATTY-ACID;
ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; BLOOD-FLOW; NEURODEGENERATIVE
DISEASES; COGNITIVE IMPAIRMENT
AB Brain lipid metabolism was studied in rats following permanent bilateral common carotid artery ligation (BCCL), a model for chronic cerebral hypoperfusion. Unesterified (free) fatty acids (uFA) and acyl-CoA concentrations were measured 6 h, 24 h, and 7 days after BCCL or sham surgery, in high energy-microwaved brain. In BCCL compared to sham rats, cytosolic phospholipase A(2) (cPLA(2)) immunoreactivity in piriform cortex, and concentrations of total uFA and arachidonoyl-CoA, an intermediate for arachidonic acid reincorporation into phospholipids, were increased only at 6 h. At 24 h, immunoreactivity for secretory phospholipase A(2) (sPLA(2)), which may regulate blood flow, was increased near cortical and hippocampal blood vessels. BCCL did not affect levels of brain IB4+ microglia, glial fibrillary acidic protein (GFAP)+ astrocytes, cyclooxygenase-2 (COX-2) immunoreactivity at any time, but increased cPLA(2) immunoreactivity in one region at 6 h. Thus, BCCL affected brain lipid metabolism transiently, likely because of compensatory sPLA(2)-mediated vasodilation, without producing evidence of neuroinflammation.
C1 [Bhattacharjee, Abesh Kumar; White, Laura; Chang, Lisa; Ma, Kaizong; Deutsch, Joseph; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Harry, G. Jean] NIEHS, Neurotoxicol Grp, NIH, Res Triangle Pk, NC 27709 USA.
[Deutsch, Joseph] Hebrew Univ Jerusalem, Sch Pharm, IL-91120 Jerusalem, Israel.
RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sir@helix.nih.gov
FU National Institute on Aging; National Institute of Environmental Health
Science, NIH
FX This research was supported entirely by the Intramural Research Program
of the National Institute on Aging, and by the National Institute of
Environmental Health Science, NIH.
NR 62
TC 2
Z9 3
U1 0
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
EI 1573-6903
J9 NEUROCHEM RES
JI Neurochem. Res.
PD JUL
PY 2012
VL 37
IS 7
BP 1490
EP 1498
DI 10.1007/s11064-012-0740-2
PG 9
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 953OG
UT WOS:000304878200014
PM 22422289
ER
PT J
AU Saranjam, HR
Sidransky, E
Levine, WZ
Zimran, A
Elstein, D
AF Saranjam, H. R.
Sidransky, E.
Levine, W. Z.
Zimran, A.
Elstein, D.
TI Mandibular and dental manifestations of Gaucher disease
SO ORAL DISEASES
LA English
DT Review
DE Gaucher disease; Gaucher cells; glucocerebroside; mandible; maxilla;
enzyme replacement therapy
ID ENZYME REPLACEMENT THERAPY; FUNCTION ABNORMALITIES; NEUTROPHIL
CHEMOTAXIS; INVOLVEMENT; GLUCOCEREBROSIDASE; BISPHOSPHONATE; OSTEOPENIA;
CHILDREN
AB Oral Diseases (2012) 18, 421429 Gaucher disease is a systemic lysosomal storage disorder with a high prevalence among Ashkenazi Jews. It is caused by an inherited deficiency of the lysosomal enzyme glucocerebrosidase. Common signs and symptoms include hepatosplenomegaly, anemia, thrombocytopenia, and skeletal involvement. Oral and dental manifestations are less commonly seen. These manifestations are often asymptomatic, although they may be detected by routine dental x-rays. There are several case reports and a few larger series published describing patients with Gaucher disease who have mandibulo-maxillofacial involvement. This review aims to examine the oral manifestations observed in Gaucher disease and to suggest practical guidelines for dealing with these often worrisome signs. Among the critical issues are the benign nature of Gaucher cell infiltration of the mandible and the critical importance of being prepared for postprocedure bleeding and/or infections. Therefore, it is essential that dental practitioners be aware of the possible oral and dental complications of Gaucher disease, as well as the available treatment modalities.
C1 [Saranjam, H. R.; Sidransky, E.] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Zimran, A.; Elstein, D.] Hebrew Univ Jerusalem, Hadassah Med Ctr, Shaare Zedek Med Ctr, Gaucher Clin, Jerusalem, Israel.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU National Human Genome Research Institute; National Institutes of Health
FX This work was supported by the Intramural Research Programs of the
National Human Genome Research Institute and the National Institutes of
Health. We acknowledge the helpful suggestions of Dr Grisel Lopez and Dr
Nahid Tayebi. The clinical experience of Dr Alan Elstein (DDS) is
gratefully acknowledged.
NR 61
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
J9 ORAL DIS
JI Oral Dis.
PD JUL
PY 2012
VL 18
IS 5
BP 421
EP 429
DI 10.1111/j.1601-0825.2011.01898.x
PG 9
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 953LT
UT WOS:000304869800001
PM 22251146
ER
PT J
AU Zheng, C
Baum, BJ
AF Zheng, C.
Baum, B. J.
TI Including the p53 ELAV-like protein-binding site in vector cassettes
enhances transgene expression in rat submandibular gland
SO ORAL DISEASES
LA English
DT Article
DE salivary glands; HuR protein; HuR protein-binding site; gene expression
ID MEDIATED GENE-TRANSFER; MESSENGER-RNA STABILITY; SALIVARY-GLANDS;
CELL-LINE; EPITHELIAL-CELLS; MAMMALIAN-CELLS; IN-VIVO; ADENOVIRUS; HUR;
TRANSLATION
AB Oral Diseases (2012) 18, 477484 Objective: ELAV-like proteins regulate mRNA stability and/or translation. We evaluated whether inclusion of binding sites for ELAV-like HuR proteins in vector cassettes could improve transgene expression in the salivary gland. Methods: Western blots and immunofluorescence staining were used to determine whether HuR protein was expressed in salivary cells and tissue. HuR binding sites were inserted into the pACEF1aluc-BGH expression plasmid. Cell lines were transfected with plasmids in vitro and luciferase expression measured. Rat submandibular glands were transfected in vivo with plasmids containing ELAV-like HuR protein-binding sites. An adenoviral vector with p53 ELAV-like HuR protein-binding site was generated and also tested in vivo. Four unique 29mer HuR shRNA constructs were used in A5 cells to evaluate whether there was a specific interaction between HuR protein and the p53 HuR protein-binding site. Results: Salivary cells express HuR protein. Inclusion of the p53 ELAV-like HuR protein-binding site resulted in high luciferase activity in salivary cells in vitro, with similar results in vivo. In vitro shRNA data demonstrated that the high luciferase activity was mediated by the interaction between HuR protein and the p53 HuR protein-binding site. The AdEF1a-luc-p53BGH, including this binding site, mediated very high luciferase activity, similar to 4-fold that seen with the CMV promoter, in rat submandibular glands. Conclusions: Including the p53 ELAV-like protein-binding site in transgene cassettes may enhance therapeutic vectors intended for use with salivary glands.
C1 [Zheng, C.; Baum, B. J.] NIDCR, MPTB, NIH, Bethesda, MD 20892 USA.
RP Zheng, C (reprint author), NIDCR, MPTB, NIH, Bldg 10,Room 1A01,MSC 1190,10 Ctr Dr, Bethesda, MD 20892 USA.
EM czheng@dir.nidcr.nih.gov
FU Division of Intramural Research, National Institute of Dental and
Craniofacial Research, NIH
FX The Division of Intramural Research, National Institute of Dental and
Craniofacial Research, NIH, provided all support for this research. We
thank Dr. Shyh-Ing Jang and Dr. Paola Perez Riveros for their helpful
comments on this manuscript.
NR 39
TC 3
Z9 3
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
EI 1601-0825
J9 ORAL DIS
JI Oral Dis.
PD JUL
PY 2012
VL 18
IS 5
BP 477
EP 484
DI 10.1111/j.1601-0825.2011.01895.x
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 953LT
UT WOS:000304869800006
PM 22251132
ER
PT J
AU Kamo, K
Aebig, J
Guaragna, MA
James, C
Hsu, HT
Jordan, R
AF Kamo, Kathryn
Aebig, Joan
Guaragna, Mary Ann
James, Charity
Hsu, Hei-ti
Jordan, Ramon
TI Gladiolus plants transformed with single-chain variable fragment
antibodies to Cucumber mosaic virus
SO PLANT CELL TISSUE AND ORGAN CULTURE
LA English
DT Article
DE Flower bulb crops; Virus resistance; Monoclonal antibody genes
ID SPOTTED-WILT-VIRUS; NICOTIANA-TABACUM; RESISTANCE; EXPRESSION;
INFECTION; CULTURES; TOBACCO; CELLS
AB Plants of Gladiolus 'Peter Pears' or 'Jenny Lee' were transformed with single-chain variable fragments (scFv) to Cucumber mosaic virus (CMV) subgroup I or II. The CMV subgroup I heavy and light chain scFv fragments were placed under control of either the duplicated CaMV 35S or sugarcane Ubi9 promoters. Integration of the transgenes was verified by Southern hybridization. Plants were challenged in vitro by inoculating with purified CMV using the Helios hand-held gene gun. An initial pathogen challenge was performed using six plants/plant line for the 51 lines containing the CMV subgroup I and 37 lines with the CMV subgroup II scFv fragments. Four plant lines with the CMV subgroup I scFv and four lines with the CMV subgroup II scFv were selected for further challenging. Less than 30% of the plants challenged from two plant lines with the CMV subgroup I scFv and three plant lines with the CMV subgroup II scFv contained CMV as compared to 70% for the non-transformed control plants. Less than 40% of the plants from two other plant lines with the CMV subgroup I scFv contained CMV 1-2 months after challenge. These eight plant lines that showed resistance and two susceptible lines expressed the transgene as determined by Northern hybridization and reverse transcriptase PCR.
C1 [Kamo, Kathryn; Guaragna, Mary Ann; James, Charity; Hsu, Hei-ti; Jordan, Ramon] USDA, Floral & Nursery Plants Res Unit, US Natl Arboretum, Beltsville, MD 20705 USA.
[Aebig, Joan] NIAID, NIH, MVDU, Rockville, MD 20850 USA.
RP Kamo, K (reprint author), USDA, Floral & Nursery Plants Res Unit, US Natl Arboretum, Beltsville, MD 20705 USA.
EM Kathryn.Kamo@ars.usda.gov
OI Kamo, Kathryn/0000-0001-6862-2410
NR 27
TC 3
Z9 3
U1 0
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6857
J9 PLANT CELL TISS ORG
JI Plant Cell Tissue Organ Cult.
PD JUL
PY 2012
VL 110
IS 1
BP 13
EP 21
DI 10.1007/s11240-012-0124-y
PG 9
WC Biotechnology & Applied Microbiology; Plant Sciences
SC Biotechnology & Applied Microbiology; Plant Sciences
GA 950QR
UT WOS:000304664300002
ER
PT J
AU Kenworthy, L
Wallace, GL
Powell, K
Anselmo, C
Martin, A
Black, DO
AF Kenworthy, Lauren
Wallace, Gregory L.
Powell, Kelly
Anselmo, Cheryl
Martin, Alex
Black, David O.
TI Early language milestones predict later language, but not autism
symptoms in higher functioning children with autism spectrum disorders
SO RESEARCH IN AUTISM SPECTRUM DISORDERS
LA English
DT Article
DE Autistic disorder; Outcome studies; Language; Communication; Milestones
ID ASPERGER-SYNDROME; PSYCHOLINGUISTIC MARKERS; DIAGNOSTIC INTERVIEW;
FOLLOW-UP; IMPAIRMENT; PHENOTYPE; SPEECH; INDIVIDUALS; VALIDITY; BRAIN
AB Language ability is a known predictor of outcome in children with autism but plays a more controversial role for higher functioning children with autism spectrum disorders (ASD). We studied the relationship between early language milestones and later structural language, adaptive functioning and autism symptoms in a sample of 76 children (mean age = 9.1 years) with an ASD, using two different language milestones: first phrase by 24 or 36 months. After controlling for age and nonverbal abilities, retrospectively reported early language milestones were predictive of later structural language abilities, measured by a sentence repetition task, and adaptive communication skills, but not autism symptoms or adaptive social skills. Acquisition of phrase speech by 24 months was sensitive to language and communication impairments in our ASD group, the majority (84%) of which had already acquired phrase speech by 36 months of age. Early available and easily collectable milestone data may be a useful marker of later language performance even in higher functioning, verbal children on the autism spectrum. When a detailed assessment of language is not possible, data on early milestones may be useful for identifying children at-risk in clinical settings and for language phenotyping in the laboratory. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Kenworthy, Lauren; Anselmo, Cheryl] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD 20850 USA.
[Wallace, Gregory L.; Martin, Alex] Natl Inst Mental Hlth, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Powell, Kelly] American Univ, Dept Psychol, Washington, DC 20016 USA.
[Black, David O.] Natl Inst Mental Hlth, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA.
RP Kenworthy, L (reprint author), Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, 15245 Shady Grove Rd,South Bldg,Suite 350, Rockville, MD 20850 USA.
EM lkenwort@cnmc.org; gregwallace@mail.nih.gov; alexmartin@mail.nih.gov;
blackdavid@mail.nih.gov
OI Wallace, Gregory/0000-0003-0329-5054
NR 56
TC 2
Z9 2
U1 1
U2 12
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1750-9467
J9 RES AUTISM SPECT DIS
JI Res. Autism Spectr. Disord.
PD JUL-SEP
PY 2012
VL 6
IS 3
BP 1194
EP 1202
DI 10.1016/j.rasd.2012.03.009
PG 9
WC Education, Special; Psychology, Developmental; Psychiatry;
Rehabilitation
SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation
GA 956RS
UT WOS:000305107400029
ER
PT J
AU Inchauste, SM
Lanier, BJ
Libutti, SK
Phan, GQ
Nilubol, N
Steinberg, SM
Kebebew, E
Hughes, MS
AF Inchauste, Suzanne M.
Lanier, Brock J.
Libutti, Steven K.
Phan, Giao Q.
Nilubol, Naris
Steinberg, Seth M.
Kebebew, Electron
Hughes, Marybeth S.
TI Rate of Clinically Significant Postoperative Pancreatic Fistula in
Pancreatic Neuroendocrine Tumors
SO WORLD JOURNAL OF SURGERY
LA English
DT Article
ID INTERNATIONAL STUDY-GROUP; ISLET CELL TUMORS; RISK-FACTORS; CONSECUTIVE
PANCREATICODUODENECTOMIES; LINDAU DISEASE; COMPLICATIONS; SURGERY;
GASTRINOMA; RESECTION; OUTCOMES
AB In 2005, the International Study Group of Pancreatic Fistula (ISGPF) developed a definition and grading system for postoperative pancreatic fistula (POPF). The authors sought to determine the rate of POPF after enucleation and/or resection of pancreatic neuroendocrine tumors (PNET) and to identify clinical, surgical, or pathologic factors associated with POPF.
A retrospective analysis of pancreatic enucleations and resections performed from March 1998 to April 2010. We defined a clinically significant POPF as a grade B that required nonoperative intervention and grade C.
One hundred twenty-two patients were identified; 62 patients had enucleations and 60 patients had resections of PNET. The rate of clinically significant POPF was 23.7 % (29/122). For pancreatic enucleation, the POPF rate was 27.4 % (17/62, 14 grade B, 3 grade C). The pancreatic resection group had a POPF rate of 20 % (12/60, 10 grade B, 2 grade C). This difference was not significant (p = 0.4). In univariate analyses, patients in the enucleation group with hereditary syndromes (p = 0.02) and non-insulinoma tumors (p = 0.02) had a higher POPF rate. Patients in the resection group with body mass index (BMI) > 25 (p < 0.01), multiple endocrine neoplasia type 1 (MEN-1; p < 0.01) and those who underwent simultaneous multiple procedures (p = 0.02) had a higher POPF rate. Multivariate analyses revealed that hereditary syndromes were able to predict POPF in the enucleation group, while having BMI > 25 and increasing lesion size were also associated with POPF in the group undergoing resection.
We found a clinically significant POPF rate after surgery in PNET to be 23.7 % with no difference by the type of operation. Our POPF rate is comparable to that reported in the literature for pancreatic resection for other types of tumors. Certain inherited genetic diseases-von Hippel-Lindau disease (VHL) and MEN-1-were associated with higher POPF rates.
C1 [Inchauste, Suzanne M.; Lanier, Brock J.; Phan, Giao Q.; Nilubol, Naris; Kebebew, Electron; Hughes, Marybeth S.] NCI, Endocrine Oncol Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Libutti, Steven K.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Surg, Bronx, NY 10467 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Hughes, MS (reprint author), NCI, Endocrine Oncol Sect, Surg Branch, Ctr Canc Res, 10 Ctr Dr,MSC1201,Rm 4W-5940, Bethesda, MD 20892 USA.
EM hughesm@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 48
TC 25
Z9 29
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2313
J9 WORLD J SURG
JI World J.Surg.
PD JUL
PY 2012
VL 36
IS 7
BP 1517
EP 1526
DI 10.1007/s00268-012-1598-9
PG 10
WC Surgery
SC Surgery
GA 953OX
UT WOS:000304880600009
PM 22526042
ER
PT J
AU Bu, LH
Xie, J
Chen, K
Huang, J
Aguilar, ZP
Wang, A
Sun, KW
Chua, MS
So, S
Cheng, Z
Eden, HS
Shen, BZ
Chen, XY
AF Bu, Lihong
Xie, Jin
Chen, Kai
Huang, Jing
Aguilar, Zoraida P.
Wang, Andrew
Sun, Kin Wai
Chua, Mei-Sze
So, Samuel
Cheng, Zhen
Eden, Henry S.
Shen, Baozhong
Chen, Xiaoyuan
TI Assessment and comparison of magnetic nanoparticles as MRI contrast
agents in a rodent model of human hepatocellular carcinoma
SO CONTRAST MEDIA & MOLECULAR IMAGING
LA English
DT Article
DE iron oxide nanoparticle (IONP); hepatocarcinoma (HCC); magnetic
resonance imaging (MRI); liver contrast agent
ID IRON-OXIDE NANOPARTICLES; TIME-RESOLVED MRI; IN-VIVO; SIZE;
NANOCRYSTALS; NANOPROBES; RELAXIVITY; KINETICS
AB The purpose of this study was to synthesize, characterize and tailor the surface properties of magnetic nanoparticles with biocompatible copolymer coatings and to evaluate the efficiency of the resulting nanoconjugates as magnetic resonance imaging (MRI) contrast agents for liver imaging. Magnetic nanoparticles with core diameters of 10 and 30?nm were synthesized by pyrolysis and were subsequently coated with a copolymer containing either carboxyl (SHP) or methoxy groups as termini. All four formulas, and ferumoxides (Feridex I.V.(R)), were individually injected intravenously into separate, normal Balb/C mice (at 2.5, 1.0 and 0.56?mg Fe kg-1), and the animals underwent T2-weighted MRI at multiple time points post injection (p.i.) to evaluate the hepatic uptake and clearance. Furthermore, we compared the abilities of the new formulas and Feridex to detect tumors in an orthotropic Huh7 tumor model. Transmission electron microscopy (TEM) revealed a narrow size distribution of both the 10 and 30?nm nanoparticles, in contrast to a wide size distribution of Feridex. MTT, apoptosis and cyclin/DNA flow cytometry assays showed that the polymer coated nanoparticles had no adverse effect on cell growth. Among all the tested formulas, including Feridex, SHP-30 showed the highest macrophage uptake at the in vitro level. In vivo MRI studies on normal mice confirmed the superiority of SHP-30 in inducing hypointensities in the liver tissue, especially at clinical dose (0.56?mg Fe kg-1) and 3?T field. SHP-30 showed better contrast-to-noise ratio than Feridex on the orthotropic Huh7 tumor model. SHP-30 was found to be an efficient contrast agent for liver MR imaging. The success of this study suggests that, by improving the synthetic approach and by tuning the surface properties of IONPs, one can arrive at better formulas than Feridex for clinical practice. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Bu, Lihong; Xie, Jin; Cheng, Zhen; Eden, Henry S.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
[Bu, Lihong; Shen, Baozhong] Harbin Med Univ, Dept Radiol, Hosp 4, Harbin, Heilongjiang, Peoples R China.
[Bu, Lihong; Chen, Kai; Huang, Jing] Stanford Univ, Sch Med, Mol Imaging Program Stanford, Dept Radiol, Stanford, CA 94305 USA.
[Aguilar, Zoraida P.; Wang, Andrew] Ocean NanoTech LLC, Springdale, AR USA.
[Sun, Kin Wai; Chua, Mei-Sze; So, Samuel] Stanford Univ, Sch Med, Dept Surg, Asian Liver Ctr, Stanford, CA 94305 USA.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
EM shenbzh@vip.sina.com; Shawn.Chen@nih.gov
RI Cheng, Zhen/K-2843-2012
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB),
NIH; NIH SBIR/STTR [HHSN261200800062C, 1R41CA137960]; National Science
Foundation of China (NSFC) [81028009]; Chinese Ministry of Sciences and
Technology [2009DFB30040]; National Natural Science Foundation of China
(NSFC) [30970807]; project of Harbin Tackle Key Problem Items
[2007AA3CS085]; NIH Pathway to Independence [K99/R00]
FX This work was supported in part, by the intramural research program of
the National Institute of Biomedical Imaging and Bioengineering (NIBIB),
NIH and NIH SBIR/STTR program (HHSN261200800062C and 1R41CA137960), the
International Cooperative Program of the National Science Foundation of
China (NSFC) (81028009), the International Cooperation Projects of the
Chinese Ministry of Sciences and Technology (2009DFB30040), the project
of National Natural Science Foundation of China (NSFC) (30970807), and
by the project of Harbin Tackle Key Problem Items (2007AA3CS085). Dr Jin
Xie was partially supported by the NIH Pathway to Independence (K99/R00)
Award. The authors wish to thank Mrs Yan Hou from Harbin Medical
University for statistical analysis.
NR 23
TC 22
Z9 22
U1 4
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1555-4309
J9 CONTRAST MEDIA MOL I
JI Contrast Media Mol. Imaging
PD JUL-AUG
PY 2012
VL 7
IS 4
BP 363
EP 372
DI 10.1002/cmmi.494
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 950QZ
UT WOS:000304665100002
PM 22649042
ER
PT J
AU Deshpande, M
Notari, L
Subramanian, P
Notario, V
Becerra, SP
AF Deshpande, Monika
Notari, Luigi
Subramanian, Preeti
Notario, Vicente
Becerra, S. Patricia
TI Inhibition of tumor cell surface ATP synthesis by pigment
epithelium-derived factor: Implications for antitumor activity
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE PEDF; ATP synthase; tumor cell; cell viability; ATP; ATP synthesis
ID VASCULAR ENDOTHELIAL-CELLS; FACTOR PEDF; EXTRACELLULAR ATP;
BINDING-SITE; AUROVERTIN-B; BETA-SUBUNIT; I RECEPTOR; SYNTHASE;
IDENTIFICATION; PROTEIN
AB Recently, we have shown that the antiangiogenic pigment epithelium-derived factor (PEDF) can bind the catalytic beta-subunit of F1-ATP synthase and inhibit endothelial cell surface ATP synthase activity. This factor can additionally restrict tumor growth, invasion and metastasis, and can directly induce death on several tumor cell types. Active cell surface ATP synthase is also present in certain tumor cells and its ATP product is considered a stimulus for tumor growth. The present study aimed to elucidate the biological implications of the interactions between the extracellular PEDF and tumor cell surface ATP synthase. Incubation of T24 human urinary bladder carcinoma cells in media containing human recombinant PEDF protein for 48-96 h dramatically decreased cell viability in a concentration-dependent fashion as monitored by real-time cell impedance with a microelectronic system, microscopic imaging and biomarkers of live cells. Intact tumor cells exhibited cell surface ATP synthesis activity, which was inhibited by piceatannol, a specific inhibitor of F1/F0-ATP synthase. Immunoblotting revealed that the beta subunit of F1-ATP synthase was present in plasma membrane fractions of these cells. Interestingly, pre-incubation of tumor cells with PEDF inhibited the activity of cell surface ATP synthase in a concentration-dependent fashion. The PEDF-derived peptide 34-mer decreased tumor cell viability and inhibited extracellular ATP synthesis to the same extent as full-length PEDF. Moreover, ATP additions attenuated both the PEDF-mediated decrease in tumor cell viability and the inhibition of endothelial cell tube formation. The results lead to conclude that PEDF is a novel inhibitor of tumor cell surface ATP synthase activity that exhibits a cytotoxic effect on tumor cells, and that the structural determinants for these properties are within the peptide region 34-mer of the PEDF polypeptide. The data strongly suggest a role for the interaction between the 34-mer region of PEDF and tumor cell-surface ATP synthase in promoting tumor cell death.
C1 [Deshpande, Monika; Subramanian, Preeti; Becerra, S. Patricia] NIH NEI, Sect Prot Struct & Funct, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA.
[Notari, Luigi] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Notari, Luigi] Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA.
[Notario, Vicente] Georgetown Univ, Med Ctr, Dept Radiat Med, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
RP Becerra, SP (reprint author), NIH NEI, Sect Prot Struct & Funct, Lab Retinal Cell & Mol Biol, 6 Ctr Dr,MSC 0608, Bethesda, MD 20892 USA.
EM becerrap@nei.nih.gov
FU National Institutes of Health NEI; National Cancer Institute [CA 134727]
FX This work was supported in part by National Institutes of Health NEI
Intramural Research Program and by the National Cancer Institute Grant
no. CA 134727 (to V.N.).
NR 45
TC 13
Z9 13
U1 1
U2 4
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
J9 INT J ONCOL
JI Int. J. Oncol.
PD JUL
PY 2012
VL 41
IS 1
BP 219
EP 227
DI 10.3892/ijo.2012.1431
PG 9
WC Oncology
SC Oncology
GA 949LX
UT WOS:000304578800027
PM 22504705
ER
PT J
AU Josefsson, L
Eriksson, S
Sinclair, E
Ho, T
Killian, M
Epling, L
Shao, W
Lewis, B
Bacchetti, P
Loeb, L
Custer, J
Poole, L
Hecht, FM
Palmer, S
AF Josefsson, Lina
Eriksson, Susanne
Sinclair, Elizabeth
Ho, Terence
Killian, Maudi
Epling, Lorrie
Shao, Wei
Lewis, Bradley
Bacchetti, Peter
Loeb, Lisa
Custer, Jeff
Poole, Lauren
Hecht, Frederick M.
Palmer, Sarah
TI Hematopoietic Precursor Cells Isolated From Patients on Long-term
Suppressive HIV Therapy Did Not Contain HIV-1 DNA
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; VIRUS TYPE-1 VIREMIA;
RESIDUAL VIREMIA; PROGENITOR CELLS; REPLICATION; INDIVIDUALS; INFECTION;
PROVIRUS; BLOOD
AB Background. We address the key emerging question of whether Lin(-)/CD34(+) hematopoietic precursor cells (HPCs) represent an important latent reservoir of human immunodeficiency virus type 1 (HIV-1) during long-term suppressive therapy.
Methods. To estimate the frequency of HIV-1 infection in bone marrow, we sorted Lin(-)/CD34(+) HPCs and 3 other cell types (Lin(-)/CD34(-), Lin(-)/CD4(+), and Lin(+)/CD4(+)) from 8 patients who had undetectable viral loads for 3-12 years. Using a single-proviral sequencing method, we extracted, amplified, and sequenced multiple single HIV-1 DNA molecules from these cells and memory CD4(+) T cells from contemporaneous peripheral blood samples.
Results. We analyzed 100 000-870 000 bone marrow Lin(-)/CD34(+) HPCs from the 8 patients and found no HIV-1 DNA. We did isolate HIV-1 DNA from their bone marrow Lin(+)/CD4(+) cells that was genetically similar to HIV-1 DNA from lymphoid cells located in the peripheral blood, indicating an exchange of infected cells between these compartments.
Conclusions. The absence of infected HPCs provides strong evidence that the HIV-1 infection frequency of Lin(-)/CD34(+) HPCs from bone marrow, if it occurred, was <.003% (highest upper 95% confidence interval) in all 8 patients. These results strongly suggest that Lin(-)/CD34(+) HPCs in bone marrow are not a source of persistent HIV-1 in patients on long-term suppressive therapy.
C1 [Palmer, Sarah] Karolinska Inst, Swedish Inst Communicable Dis Control, Dept Microbiol Tumor & Cell Biol, Dept Diagnost & Vaccinol, S-17182 Solna, Sweden.
[Sinclair, Elizabeth; Ho, Terence; Killian, Maudi; Epling, Lorrie; Lewis, Bradley; Loeb, Lisa; Custer, Jeff; Poole, Lauren; Hecht, Frederick M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Lewis, Bradley] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Shao, Wei] NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Palmer, S (reprint author), Karolinska Inst, Swedish Inst Communicable Dis Control, Dept Microbiol Tumor & Cell Biol, Dept Diagnost & Vaccinol, Nobels Vag 18, S-17182 Solna, Sweden.
EM sarah.palmer@smi.se
FU amfAR; Foundation for AIDS Research, amfAR Research Consortium on HIV
Eradication (ARCHE) [107857-48-RGRL]; Swedish International Development
Agency [SWE-2009-046]; Swedish Research Council [K2011-56X-21749-01-6];
US National Institutes of Health (NIH) [AI071713]; University of
California, San Francisco (UCSF) Center for AIDS Research [NIH P30
MH59037]; UCSF-GIVI Center for AIDS Research [P30AI027763]; NIH/National
Center for Research Resources UCSF-Clinical & Translational Science
Institute [UL1RR024131]
FX This work was supported by amfAR; the Foundation for AIDS Research as
part of the amfAR Research Consortium on HIV Eradication (ARCHE)
(107857-48-RGRL); the Swedish International Development Agency
(SWE-2009-046); the Swedish Research Council (K2011-56X-21749-01-6); the
US National Institutes of Health (NIH) (AI071713); the University of
California, San Francisco (UCSF) Center for AIDS Research (NIH P30
MH59037); the UCSF-GIVI Center for AIDS Research (P30AI027763); and the
NIH/National Center for Research Resources UCSF-Clinical & Translational
Science Institute (UL1RR024131).
NR 14
TC 40
Z9 41
U1 0
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 1
PY 2012
VL 206
IS 1
BP 28
EP 34
DI 10.1093/infdis/jis301
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 948YN
UT WOS:000304540200005
PM 22536001
ER
PT J
AU Bloom-Feshbach, K
Simonsen, L
Viboud, C
Molbak, K
Miller, MA
Gottfredsson, M
Andreasen, V
AF Bloom-Feshbach, Kimberly
Simonsen, Lone
Viboud, Cecile
Molbak, Kare
Miller, Mark A.
Gottfredsson, Magnus
Andreasen, Viggo
TI Fertility Fluctuations in Times of War and Pandemic Influenza Reply
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Letter
C1 [Bloom-Feshbach, Kimberly; Simonsen, Lone; Viboud, Cecile; Miller, Mark A.; Gottfredsson, Magnus; Andreasen, Viggo] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Bloom-Feshbach, Kimberly] Mt Sinai Sch Med, New York, NY USA.
[Simonsen, Lone] George Washington Univ, Dept Global Hlth, Washington, DC USA.
[Molbak, Kare] Statens Serum Inst, Dept Epidemiol, DK-2300 Copenhagen, Denmark.
[Andreasen, Viggo] Roskilde Univ, Dept Sci Syst & Models, Roskilde, Denmark.
[Gottfredsson, Magnus] Univ Iceland, Fac Med, Reykjavik, Iceland.
RP Bloom-Feshbach, K (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 16,Stone House,MSC 6705, Bethesda, MD 20892 USA.
EM kimberlybf@gmail.com
NR 14
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 1
PY 2012
VL 206
IS 1
BP 141
EP +
DI 10.1093/infdis/jis316
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 948YN
UT WOS:000304540200021
ER
PT J
AU Robinson, OJ
Overstreet, C
Letkiewicz, A
Grillon, C
AF Robinson, O. J.
Overstreet, C.
Letkiewicz, A.
Grillon, C.
TI Depressed mood enhances anxiety to unpredictable threat
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Anxiety; co-morbidity; depression; mood; sadness; startle reflex
ID AFFECTIVE STARTLE MODULATION; NATIONAL COMORBIDITY SURVEY; RESEARCH
DOMAIN CRITERIA; PANIC DISORDER; MAJOR DEPRESSION; NEGATIVE MOOD;
PSYCHIATRIC-DISORDERS; TRYPTOPHAN DEPLETION; POTENTIATED STARTLE;
UNIPOLAR DEPRESSION
AB Background. Depression and anxiety disorders (ADs) are highly co-morbid, but the reason for this co-morbidity is unclear. One possibility is that they predispose one another. An informative way to examine interactions between disorders without the confounds present in patient populations is to manipulate the psychological processes thought to underlie the pathological states in healthy individuals. In this study we therefore asked whether a model of the sad mood in depression can enhance psychophysiological responses (startle) to a model of the anxiety in ADs. We predicted that sad mood would increase anxious anxiety-potentiated startle responses.
Method. In a between-subjects design, participants (n=36) completed either a sad mood induction procedure (MIP; n=18) or a neutral MIP (n=18). Startle responses were assessed during short-duration predictable electric shock conditions (fear-potentiated startle) or long-duration unpredictable threat of shock conditions (anxiety-potentiated startle).
Results. Induced sadness enhanced anxiety-but not fear-potentiated startle.
Conclusions. This study provides support for the hypothesis that sadness can increase anxious responding measured by the affective startle response. This, taken together with prior evidence that ADs can contribute to depression, provides initial experimental support for the proposition that ADs and depression are frequently co-morbid because they may be mutually reinforcing.
C1 [Robinson, O. J.; Overstreet, C.; Letkiewicz, A.; Grillon, C.] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
RP Robinson, OJ (reprint author), NIMH, Sect Neurobiol Fear & Anxiety, NIH, 15K North Dr,Bldg 15K,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 [MH002798]
FX This research was supported by the Intramural Research Program of the
National Institutes of Mental Health (MH002798).
NR 77
TC 6
Z9 6
U1 2
U2 23
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD JUL
PY 2012
VL 42
IS 7
BP 1397
EP 1407
DI 10.1017/S0033291711002583
PG 11
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 947PH
UT WOS:000304441500005
PM 22088577
ER
PT J
AU Verma, M
AF Verma, Mukesh
TI Cancer Control and Prevention by Nutrition and Epigenetic Approaches
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID PROSTATE-CANCER; DNA METHYLATION; BREAST-CANCER; HISTONE MODIFICATIONS;
GENE-EXPRESSION; RAT-LIVER; CELLS; FOLATE; COLON; HYPERTENSION
AB Significance: Epigenetics involves alterations in gene expression without changing the nucleotide sequence. Because some epigenetic changes can be reversed chemically, epigenetics has tremendous implications for disease intervention and treatment. Recent Advances: After epigenetic components in cancer were characterized, genes and pathways are being characterized in other diseases such as diabetes, obesity, and neurological disorders. Observational, experimental, and clinical studies in different diseases have shown that nutrients influence epigenetic regulation. Nutrients such as folic acid that supply methyl groups have been shown to have a protective effect in colon cancer. Critical Issues: Identifying steps during epigenetic regulation and developing intervention and treatment agents are the critical issues in the field. Future Directions: Following completion and validation of key observational studies in nutritional epigenetics, strategies can be developed for cancer control and treatment. Antioxid. Redox Signal. 17, 355-364.
C1 [Verma, Mukesh] NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD USA.
RP Verma, M (reprint author), NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, NIH, 6130 Execut Blvd,Suite 5100, Bethesda, MD 20892 USA.
EM vermam@mail.nih.gov
NR 89
TC 12
Z9 13
U1 1
U2 14
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD JUL
PY 2012
VL 17
IS 2
BP 355
EP 364
DI 10.1089/ars.2011.4388
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 944MQ
UT WOS:000304207700012
PM 22047027
ER
PT J
AU Teicher, BA
AF Teicher, Beverly A.
TI Searching for molecular targets in sarcoma
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Sarcoma; Gene expression; Ewing's sarcoma; Rhabdomyosarcoma;
Osteosarcoma liposarcoma
ID SOFT-TISSUE SARCOMAS; GROWTH-FACTOR RECEPTOR; MESENCHYMAL STEM-CELL;
GENE-EXPRESSION; EWINGS-SARCOMA; THERAPEUTIC TARGETS; TYROSINE KINASE;
PART SARCOMA; SYNOVIAL SARCOMAS; FUSION PROTEINS
AB Sarcoma are about 1% of cancers. Within that 1% are widely varied tumors now divided into types and subtypes. Sarcoma occur in patients of all ages with frequency spread evenly over the human age range. Although the specific cell of origin of many sarcoma remains unclear, sarcoma are all tumors of mesenchymal origin. The mesenchymal stem cell, a pluripotent cell, which gives rise to varied differentiated cells including osteocytes, adipocytes, chondrocytes, muscle cells, fibroblasts, neural cells and stromal cells, is the most likely ultimate cell of origin for sarcoma. When mesenchymal stem cell genetics go awry and malignant transformation occurs sarcoma including osteosarcoma. Ewing's sarcoma, chondrosarcoma, rhabdomyosarcoma, synovial sarcoma fibrosarcoma, liposarcoma and many others can initiate. Our knowledge of sarcoma genetics is increasing rapidly. Two general groups, sarcoma arising from chromosomal translocations and sarcoma with very complex genetics, can be identified. Genes that are frequently mutated in sarcoma include TP53, NF1, PIK3CA, HDAC1, IDH1 and 2, KDR, KIT and MED12. Genes that are frequently amplified in sarcoma include CDK4, YEATS4, HMGA2, MDM2, JUN, DNM3, FLT4, MYCN, MAP3K5, GLI1 and the microRNAs miR-214 and miR-199a2. Genes that are upregulated in sarcoma include MUC4, CD24, FOXL1, ANGPTL2, HIF1 alpha, MDK, cMET, TIMP-2, PRL, PCSK1, IGFR-1, TIE1, KDR, TEK, FLT1 and several microRNAs. While some alterations occur in specific subtypes of sarcoma, others cross several sarcoma types. Discovering and developing new therapeutic approaches for these relentless diseases is critical. The detailed knowledge of sarcoma genetics may allow development of sarcoma subtype-targeted therapeutics. Published by Elsevier Inc.
C1 NCI, Mol Pharmacol Branch, Dev Therapeut Program, Rockville, MD 20852 USA.
RP Teicher, BA (reprint author), NCI, Mol Pharmacol Branch, Dev Therapeut Program, MSC 7458,Room 8156,6130 Execut Blvd, Rockville, MD 20852 USA.
EM Beverly.Teicher@nih.gov
NR 100
TC 27
Z9 27
U1 5
U2 21
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD JUL 1
PY 2012
VL 84
IS 1
BP 1
EP 10
DI 10.1016/j.bcp.2012.02.009
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 948KT
UT WOS:000304502800001
PM 22387046
ER
PT J
AU Williams, J
Nansel, TR
Weaver, NL
Tse, J
AF Williams, Janice
Nansel, Tonja R.
Weaver, Nancy L.
Tse, Julia
TI Safe N' Sound An Evidence-Based Tool to Prioritize Injury Messages for
Pediatric Health Care
SO FAMILY & COMMUNITY HEALTH
LA English
DT Article; Proceedings Paper
CT 15th Annual Conference on Forging New Frontiers - Making Communities
Safe for Children and Their Families Injury Free Coalition for Kids
(IFCK)
CY NOV 12-14, 2010
CL Chicago, IL
DE anticipatory guidance; childhood injury; tailored communication;
unintentional injury
ID PREVENTION; COMMUNICATION; STRATEGIES
AB Safe N' Sound is a computer-based tool that prioritizes key injury risks for toddlers and infants and provides tailored feedback. The program was implemented in 5 pediatric sites. Caregiver risk behaviors were analyzed and compared with corresponding national and state morbidity and mortality data. The priority risks identified were generally consistent with the incidence of injury. Frequencies of several risk behaviors varied across sites and differences were observed across ages. Use of a prioritization scheme may facilitate risk behavior counseling and reasonably result in a decrease in injury mortality or morbidity.
C1 [Williams, Janice] Carolinas Med Ctr, Carolinas Ctr Injury Prevent, Charlotte, NC 28232 USA.
[Nansel, Tonja R.; Tse, Julia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Weaver, Nancy L.] St Louis Univ, Dept Behav Sci & Hlth Educ, Sch Publ Hlth, St Louis, MO 63103 USA.
RP Williams, J (reprint author), Carolinas Med Ctr, Carolinas Ctr Injury Prevent, POB 32861,MEB 3, Charlotte, NC 28232 USA.
EM janice.williams@carolinashealthcare.org
OI Nansel, Tonja/0000-0002-8298-7595
FU Intramural NIH HHS [Z01 HD002402-09]
NR 18
TC 4
Z9 4
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0160-6379
J9 FAM COMMUNITY HEALTH
JI Fam. Community Health
PD JUL-SEP
PY 2012
VL 35
IS 3
BP 212
EP 224
DI 10.1097/FCH.0b013e318250bcc3
PG 13
WC Family Studies; Public, Environmental & Occupational Health
SC Family Studies; Public, Environmental & Occupational Health
GA 946NN
UT WOS:000304358700005
PM 22617412
ER
PT J
AU Casey, W
AF Casey, Warren
TI Validating High-throughput Test Methods for Tox21; the Technology Has
Changed, but the Objective Remains the Same
SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
LA English
DT Meeting Abstract
C1 [Casey, Warren] Natl Inst Environm Hlth Sci, NTP Interagency Ctr Evaluat Alternat Toxicol Meth, Res Triangle Pk, NC 27709 USA.
EM warren.casey@nih.gov
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 1071-2690
J9 IN VITRO CELL DEV-AN
JI In Vitro Cell. Dev. Biol.-Anim.
PD JUL
PY 2012
VL 48
SU 1
BP 13
EP 14
PG 2
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 947BU
UT WOS:000304402400032
ER
PT J
AU Ciancio, M
Duminie, S
Manalastas, M
Evans, C
LePard, K
AF Ciancio, M.
Duminie, S.
Manalastas, M.
Evans, C.
LePard, K.
TI Selectively Expressed Heat Shock Protein 70 Prevents Diet-induced
Changes in Pancreatic Structure and Function
SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
LA English
DT Meeting Abstract
C1 [Ciancio, M.; Manalastas, M.] Midwestern Univ, Program Biomed Sci, Downers Grove, IL 60515 USA.
[Ciancio, M.; LePard, K.] Midwestern Univ, Dept Physiol, Downers Grove, IL 60515 USA.
[Duminie, S.] Midwestern Univ, NIH NIDDK Step Up Program, Downers Grove, IL 60515 USA.
[Evans, C.] Midwestern Univ, Phys Therapy Dept, Downers Grove, IL 60515 USA.
EM mcianc@midwestern.edu
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1071-2690
J9 IN VITRO CELL DEV-AN
JI In Vitro Cell. Dev. Biol.-Anim.
PD JUL
PY 2012
VL 48
SU 1
BP 45
EP 45
PG 1
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 947BU
UT WOS:000304402400113
ER
PT J
AU Parvaz, MA
Konova, AB
Tomasi, D
Volkow, ND
Goldstein, RZ
AF Parvaz, Muhammad A.
Konova, Anna B.
Tomasi, Dardo
Volkow, Nora D.
Goldstein, Rita Z.
TI Structural Integrity of the Prefrontal Cortex Modulates Electrocortical
Sensitivity to Reward
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID EVENT-RELATED POTENTIALS; COERULEUS-NOREPINEPHRINE SYSTEM; HUMAN
ORBITOFRONTAL CORTEX; VOXEL-BASED MORPHOMETRY; MONETARY REWARD;
GRAY-MATTER; HUMAN BRAIN; CORTICAL GENERATORS; SOURCE LOCALIZATION;
OPTIMAL PERFORMANCE
AB The P300 is a known ERP component assessing stimulus value, including the value of a monetary reward. In parallel, the incentive value of reinforcers relies on the PFC, a major cortical projection region of the mesocortical reward pathway. Here we show a significant positive correlation between P300 response to money (vs. no money) with PFC gray matter volume in the OFC, ACC, and dorsolateral and ventrolateral PFC in healthy control participants. In contrast, individuals with cocaine use disorders showed compromises in both P300 sensitivity to money and PFC gray matter volume in the ventrolateral PFC and OFC and their interdependence. These results document for the first time the importance of gray matter structural integrity of subregions of PFC to the reward-modulated P300 response.
C1 [Parvaz, Muhammad A.; Konova, Anna B.; Goldstein, Rita Z.] Brookhaven Natl Lab, Upton, NY 11973 USA.
[Konova, Anna B.] SUNY Stony Brook, Stony Brook, NY USA.
[Tomasi, Dardo] Natl Inst Alcohol & Alcoholism, Bethesda, MD USA.
[Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA.
RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, 30 Bell Ave,Bldg 490, Upton, NY 11973 USA.
EM rgoldstein@bnl.gov
RI Tomasi, Dardo/J-2127-2015;
OI Parvaz, Muhammad/0000-0002-2671-2327
FU National Institute on Drug Abuse [1R01DA023579]; General Clinical
Research Center [5-MO1-RR-10710]; U.S. Department of Energy
[DE-AC02-98CHI-886]
FX We would like to thank Thomas Maloney, Nelly Alia-Klein, Patricia A.
Woicik, and Frank Telang for their assistance in participant
recruitment, assessment, and study conduct and Ruiliang Wang for the
technical support in MRI acquisition and data reconstruction. This work
was supported by grants from the National Institute on Drug Abuse (Grant
1R01DA023579 to R. Z. G.) and General Clinical Research Center (Grant
5-MO1-RR-10710). This manuscript has been authored by Brookhaven Science
Associates, LLC, under contract DE-AC02-98CHI-886 with the U.S.
Department of Energy. The U.S. Government retains and, by accepting the
article for publication, the publisher acknowledges a worldwide license
to publish or reproduce the published form of this manuscript, or allow
others to do so, for the U.S. Government purposes.
NR 74
TC 9
Z9 9
U1 2
U2 5
PU MIT PRESS
PI CAMBRIDGE
PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA
SN 0898-929X
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD JUL
PY 2012
VL 24
IS 7
BP 1560
EP 1570
PG 11
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 949RK
UT WOS:000304593300005
PM 22098260
ER
PT J
AU Gonzo, EE
Wuertz, S
Rajal, VB
AF Emilio Gonzo, Elio
Wuertz, Stefan
Rajal, Veronica B.
TI Continuum heterogeneous biofilm model-A simple and accurate method for
effectiveness factor determination
SO BIOTECHNOLOGY AND BIOENGINEERING
LA English
DT Article
DE biofilm model; effectiveness factor; continuum heterogeneous biofilm
ID SUBSTRATE UPTAKE REACTION; MASS-TRANSFER; PSEUDOANALYTICAL SOLUTION;
HYDRODYNAMIC CONDITIONS; EFFECTIVE DIFFUSIVITY; FLOW VELOCITIES;
MICROBIAL FILMS; SIMULATION; KINETICS; REACTORS
AB We present a novel analytical approach to describe biofilm processes considering continuum variation of both biofilm density and substrate effective diffusivity. A simple perturbation and matching technique was used to quantify biofilm activity using the steady-state diffusionreaction equation with continuum variable substrate effective diffusivity and biofilm density, along the coordinate normal to the biofilm surface. The procedure allows prediction of an effectiveness factor, ?, defined as the ratio between the observed rate of substrate utilization (reaction rate with diffusion resistance) and the rate of substrate utilization without diffusion limitation. Main assumptions are that (i) the biofilm is a continuum, (ii) substrate is transferred by diffusion only and is consumed only by microorganisms at a rate according to Monod kinetics, (iii) biofilm density and substrate effective diffusivity change in the x direction, (iv) the substrate concentration above the biofilm surface is known, and (v) the substratum is impermeable. With this approach one can evaluate, in a fast and efficient way, the effect of different parameters that characterize a heterogeneous biofilm and the kinetics of the rate of substrate consumption on the behavior of the biological system. Based on a comparison of ? profiles the activity of a homogeneous biofilm could be as much as 47.8% higher than that of a heterogeneous biofilm, under the given conditions. A comparison of ? values estimated for first order kinetics and ? values obtained by numerical techniques showed a maximum deviation of 1.75% in a narrow range of modified Thiele modulus values. When external mass transfer resistance, is also considered, a global effectiveness factor, ?0, can be calculated. The main advantage of the approach lies in the analytical expression for the calculation of the intrinsic effectiveness factor ? and its implementation in a computer program. For the test cases studied convergence was achieved quickly after four or five iterations. Therefore, the simulation and scale-up of heterogeneous biofilm reactors can be easily carried out. Biotechnol. Bioeng. 2012; 109:17791790. (C) 2012 Wiley Periodicals, Inc.
C1 [Emilio Gonzo, Elio; Rajal, Veronica B.] Univ Nacl Salta, INIQUI CONICET, Fac Ingn, RA-4400 Salta, Argentina.
[Wuertz, Stefan] Nanyang Technol Univ, Sch Biol Sci, Singapore Ctr Environm Life Sci Engn SCELSE, Singapore, Singapore.
[Wuertz, Stefan] Nanyang Technol Univ, Sch Civil & Environm Engn, Singapore, Singapore.
[Wuertz, Stefan] Univ Calif Davis, Dept Civil & Environm Engn, Davis, CA 95616 USA.
[Rajal, Veronica B.] Univ Calif Davis, Fogarty Int Ctr, Davis, CA 95616 USA.
RP Gonzo, EE (reprint author), Univ Nacl Salta, INIQUI CONICET, Fac Ingn, Av Bolivia 5150, RA-4400 Salta, Argentina.
EM gonzo@unsa.edu.ar
FU CONICET; Universidad Nacional de Salta in Argentina; Fogarty
International Center at the University of California, Davis, in USA;
Singapore Ministry of Education; National Research Foundation through a
RCE; Fogarty International Center at the University of California,
Davis; National Research Foundation
FX The authors gratefully acknowledge the financial support provided by
CONICET and Universidad Nacional de Salta in Argentina as well as the
Fogarty International Center at the University of California, Davis, in
USA. SW was supported by the Singapore Ministry of Education and
National Research Foundation through a RCE award to Singapore Centre on
Environmental Life Sciences Engineering (SCELSE).; Contract grant
sponsor: Fogarty International Center at the University of California,
Davis; Contract grant sponsor: Singapore Ministry of Education and
National Research Foundation
NR 55
TC 5
Z9 5
U1 0
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-3592
J9 BIOTECHNOL BIOENG
JI Biotechnol. Bioeng.
PD JUL
PY 2012
VL 109
IS 7
BP 1779
EP 1790
DI 10.1002/bit.24441
PG 12
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 942ZA
UT WOS:000304089000018
PM 22252922
ER
PT J
AU McCormick, BJJ
Alonso, WJ
Miller, MA
AF McCormick, B. J. J.
Alonso, W. J.
Miller, M. A.
TI An exploration of spatial patterns of seasonal diarrhoeal morbidity in
Thailand
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Article
DE Climate - impact of; diarrhoea
ID ROTAVIRUS INFECTIONS; REPORTED INCIDENCE; WEST-AFRICA; CHILDREN;
DISEASES; BACTERIAL; BRAZIL; HOSPITALIZATIONS; ENTEROPATHOGENS;
MORTALITY
AB Studies of temporal and spatial patterns of diarrhoeal disease can suggest putative aetiological agents and environmental or socioeconomic drivers. Here, the seasonal patterns of monthly acute diarrhoeal morbidity in Thailand, where diarrhoeal morbidity is increasing, are explored. Climatic data (2003-2006) and Thai Ministry of Health annual reports (2003-2009) were used to construct a spatially weighted panel regression model. Seasonal patterns of diarrhoeal disease were generally bimodal with aetiological agents peaking at different times of the year. There is a strong association between daily mean temperature and precipitation and the incidence of hospitalization due to acute diarrhoea in Thailand leading to a distinct spatial pattern in the seasonal pattern of diarrhoea. Model performance varied across the country in relation to per capita GDP and population density. While climatic factors are likely to drive the general pattern of diarrhoeal disease in Thailand, the seasonality of diarrhoeal disease is dampened in affluent urban populations.
C1 [McCormick, B. J. J.; Alonso, W. J.; Miller, M. A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP McCormick, BJJ (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM ben.mccormick@nih.gov
FU Malnutrition and Enteric Diseases (Mal-ED); Bill and Melinda Gates
Foundation; Fogarty International Center of the National Institutes of
Health
FX We thank Ramya Ambikapathi for her assistance in locating appropriate
disease data and Cynthia Schuck-Paim for insightful comments on the
manuscript. This study was funded as part of the Malnutrition and
Enteric Diseases (Mal-ED) project, sponsored by the Bill and Melinda
Gates Foundation and the Fogarty International Center of the National
Institutes of Health.
NR 36
TC 6
Z9 6
U1 0
U2 11
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0950-2688
EI 1469-4409
J9 EPIDEMIOL INFECT
JI Epidemiol. Infect.
PD JUL
PY 2012
VL 140
IS 7
BP 1236
EP 1243
DI 10.1017/S0950268811001919
PG 8
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 942AY
UT WOS:000304013100009
PM 21923967
ER
PT J
AU Gandhi, R
Kim, YA
Lee, S
Ryu, J
Wan, PJ
AF Gandhi, Rajiv
Kim, Yoo-Ah
Lee, Seungjoon
Ryu, Jiho
Wan, Peng-Jun
TI Approximation Algorithms for Data Broadcast in Wireless Networks
SO IEEE TRANSACTIONS ON MOBILE COMPUTING
LA English
DT Article
DE Ad hoc networking; approximation algorithms; broadcast algorithms;
wireless scheduling
ID AD-HOC NETWORKS; RADIO NETWORKS; LATENCY
AB Broadcasting is a fundamental operation in wireless networks and plays an important role in the communication protocol design. In multihop wireless networks, however, interference at a node due to simultaneous transmissions from its neighbors makes it nontrivial to design a minimum-latency broadcast algorithm, which is known to be NP-complete. We present a simple 12-approximation algorithm for the one-to-all broadcast problem that improves all previously known guarantees for this problem. We then consider the all-to-all broadcast problem where each node sends its own message to all other nodes. For the all-to-all broadcast problem, we present two algorithms with approximation ratios of 20 and 34, improving the best result available in the literature. Finally, we report experimental evaluation of our algorithms. Our studies indicate that our algorithms perform much better in practice than the worst-case guarantees provided in the theoretical analysis and achieve up to 37 percent performance improvement over existing schemes.
C1 [Gandhi, Rajiv] Rutgers State Univ, Dept Comp Sci, Camden, NJ 08102 USA.
[Kim, Yoo-Ah] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Lee, Seungjoon] AT&T Labs Res, Florham Pk, NJ 07932 USA.
[Ryu, Jiho] UNIST, Ulsan 330708, South Korea.
[Wan, Peng-Jun] IIT, Dept Comp Sci, Chicago, IL 60616 USA.
RP Gandhi, R (reprint author), Rutgers State Univ, Dept Comp Sci, Camden, NJ 08102 USA.
EM rajivg@camden.rutgers.edu; kimy3@ncbi.nlm.nih.gov;
slee@research.att.com; jihoryu@unist.ac.kr; wan@cs.iit.edu
FU US National Science Foundation [CCF-0830569, CCF-1048606]; National
Research Foundation of Korea; Korean Government
[NRF-2012R1A6A3A01012020]
FX A preliminary version of this paper appeared in the Proceedings of the
28th IEEE INFOCOM, 2009. This work was supported by US National Science
Foundation Awards CCF-0830569 and CCF-1048606. This work was supported
in part by the National Research Foundation of Korea Grant funded by the
Korean Government (NRF-2012R1A6A3A01012020).
NR 25
TC 14
Z9 16
U1 0
U2 4
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
SN 1536-1233
EI 1558-0660
J9 IEEE T MOBILE COMPUT
JI IEEE. Trans. Mob. Comput.
PD JUL
PY 2012
VL 11
IS 7
BP 1237
EP 1248
DI 10.1109/TMC.2011.162
PG 12
WC Computer Science, Information Systems; Telecommunications
SC Computer Science; Telecommunications
GA 943TU
UT WOS:000304148900013
ER
PT J
AU Kang, MH
Reynolds, CP
Houghton, PJ
Alexander, D
Morton, CL
Kolb, EA
Gorlick, R
Keir, ST
Carol, H
Lock, R
Maris, JM
Wozniak, A
Smith, MA
AF Kang, Min H.
Reynolds, C. Patrick
Houghton, Peter J.
Alexander, Denise
Morton, Christopher L.
Kolb, E. Anders
Gorlick, Richard
Keir, Stephen T.
Carol, Hernan
Lock, Richard
Maris, John M.
Wozniak, Amy
Smith, Malcolm A.
TI Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the
pediatric preclinical testing program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; hsp90 inhibitors; preclinical testing
ID PHASE-I; BREAST-CANCER; SOLID TUMORS; ESCAPE; MODELS; CELLS
AB AT13387, a non-geldanamycin inhibitor of heat-shock protein 90 (HSP90), was tested against the PPTP in vitro panel (1.0?nM to 10 mu M) and against the PPTP in vivo panels (40 or 60?mg/kg) administered orally twice weekly. In vitro AT13387 showed a median EC50 value of 41?nM and exhibited activity consistent with a cytotoxic effect. In vivo AT13387 induced significant differences in EFS distribution compared to controls in 17% evaluable solid tumor xenografts, but in none of the ALL xenografts. No objective tumor responses were observed. In vivo AT13387 demonstrated only modest single agent activity. Pediatr Blood Cancer 2012; 59: 185188. (C) 2011 Wiley Periodicals, Inc.
C1 [Kang, Min H.; Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Houghton, Peter J.; Alexander, Denise] Nationwide Childrens Hosp, Columbus, OH USA.
[Morton, Christopher L.; Wozniak, Amy] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Carol, Hernan; Lock, Richard] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Kang, MH (reprint author), Texas Tech Univ, Hlth Sci Ctr, 3601 4th St STOP 9445, Lubbock, TX 79430 USA.
EM min.kang@ttuhsc.edu
RI Carol, Hernan/F-5750-2013; Houghton, Peter/E-3265-2011; Lock,
Richard/G-4253-2013;
OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C.
Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]; Astex
Therapeutics [AT13387]
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216,
CA21765, CA108786; Grant sponsor: Astex Therapeutics.; This work was
supported by NO1-CM-42216, CA21765, and CA108786 from the National
Cancer Institute, and AT13387 was provided by Astex Therapeutics. In
addition to the authors represents work contributed by the following:
Sherry Ansher, Joshua Courtright, Edward Favours, Henry S. Friedman,
Debbie Payne-Turner, Charles Stopford, Mayamin Tajbakhsh, Chandra
Tucker, Catherine Billups, Joe Zeidner, Ellen Zhang, and Jian Zhang.
Children's Cancer Institute Australia for Medical Research is affiliated
with the University of New South Wales and Sydney Children's Hospital.
NR 20
TC 5
Z9 5
U1 1
U2 2
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2012
VL 59
IS 1
BP 185
EP 188
DI 10.1002/pbc.23154
PG 4
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 943RK
UT WOS:000304142700037
PM 21538821
ER
PT J
AU Duan, FH
Smith, LM
Gustafson, DM
Zhang, CN
Dunlevy, MJ
Gastier-Foster, JM
Barr, FG
AF Duan, Fenghai
Smith, Lynette M.
Gustafson, Donna M.
Zhang, Chune
Dunlevy, Mandy J.
Gastier-Foster, Julie M.
Barr, Frederic G.
TI Genomic and clinical analysis of fusion gene amplification in
rhabdomyosarcoma: A report from the Children's Oncology Group
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID TUMOR ALVEOLAR RHABDOMYOSARCOMA; GROWTH SUPPRESSIVE ACTIVITIES;
INTERGROUP RHABDOMYOSARCOMA; PAX3-FKHR; PAX3; ONCOPROTEIN
AB Alveolar rhabdomyosarcoma (RMS) is an aggressive pediatric cancer of the myogenic lineage with frequent chromosomal translocations involving the PAX3 or PAX7 and FOXO1 genes. Based on previous studies indicating that the fusion genes are amplified in a subset of these cancers, we conducted a comprehensive molecular and clinical investigation of these amplification events. Using oligonucleotide arrays to localize amplicons, we found that the minimal 1p36 amplicon measured 0.13 Mb and only contained PAX7 whereas the minimal 13q14 amplicon measured 0.53 Mb and contained FOXO1 and the poorly characterized LOC646982 gene. Application of a fluorescence in situ hybridization assay to over 100 fusion-positive cases revealed that the fusion gene is amplified in 93% of PAX7-FOXO1-positive and 9% of PAX3-FOXO1-positive cases. While most cells in amplified PAX7-FOXO1-positive cases contained the amplicon, only a fraction of cells in the amplified PAX3-FOXO1-positive cases contained the amplicon. Expression studies demonstrated that the fusion transcripts were generally expressed at higher levels in amplified cases, and that the PAX7-FOXO1 fusion transcript was expressed at higher levels than the PAX3-FOXO1 fusion transcript. Finally, fusion gene amplification and PAX7-FOXO1 fusion status were each associated with significantly improved outcome; a multivariate analysis demonstrated that this predictive value was independent of other standard prognostic parameters. These findings therefore provide further evidence for a novel good prognosis subset of fusion-positive RMS. (c) 2012 Wiley Periodicals, Inc.
C1 [Duan, Fenghai] Brown Univ, Ctr Stat Sci, Dept Biostat, Providence, RI 02912 USA.
[Smith, Lynette M.] Univ Nebraska Med Ctr, Dept Biostat, Coll Publ Hlth, Omaha, NE USA.
[Gustafson, Donna M.; Zhang, Chune; Barr, Frederic G.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Dunlevy, Mandy J.; Gastier-Foster, Julie M.] Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH USA.
[Gastier-Foster, Julie M.] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA.
[Gastier-Foster, Julie M.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA.
RP Barr, FG (reprint author), NCI, Pathol Lab, 10 Ctr Dr,Room 3B55,MSC 1500, Bethesda, MD 20892 USA.
RI Gastier-Foster, Julie/E-3105-2011; Duan, Fenghai/J-3709-2014
OI Duan, Fenghai/0000-0002-5084-0070
FU NIH [R01 CA104896, U10 CA098543, U10 CA098413, U24 CA114766, U01
CA054021]; Hartwell Foundation; Alex's Lemonade Stand Foundation;
Alveolar Rhabdomyosarcoma Research Fund
FX Supported by: NIH, Grant numbers: R01 CA104896, U10 CA098543, U10
CA098413, and U24 CA114766; The Hartwell Foundation; Alex's Lemonade
Stand Foundation; the Alveolar Rhabdomyosarcoma Research Fund.; The
authors would like to thank Lucas Kocia for his technical assistance.
Tissue samples were provided by the Pediatric Division of the
Cooperative Human Tissue Network, which is funded by NIH grant U01
CA054021.
NR 22
TC 12
Z9 12
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1045-2257
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD JUL
PY 2012
VL 51
IS 7
BP 662
EP 674
DI 10.1002/gcc.21953
PG 13
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 938VV
UT WOS:000303762500004
PM 22447499
ER
PT J
AU Osinusi, A
Naggie, S
Poonia, S
Trippler, M
Hu, ZH
Funk, E
Schlaak, J
Fishbein, D
Masur, H
Polis, M
Kottilil, S
AF Osinusi, Anu
Naggie, Susanna
Poonia, Seerat
Trippler, Martin
Hu, Zonghui
Funk, Emily
Schlaak, Joerg
Fishbein, Dawn
Masur, Henry
Polis, Michael
Kottilil, Shyam
TI ITPA gene polymorphisms significantly affect hemoglobin decline and
treatment outcomes in patients coinfected with HIV and HCV
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Article
DE ribavirin-induced hemolytic anemia; ITPA; HIV; HCV; pharmacogenomics
ID CHRONIC HEPATITIS-C; RIBAVIRIN-INDUCED ANEMIA;
HUMAN-IMMUNODEFICIENCY-VIRUS; WEIGHT-BASED RIBAVIRIN; UNITED-STATES;
PEGINTERFERON ALPHA-2B; AMERICAN PATIENTS; HEMOLYTIC-ANEMIA; PLUS
RIBAVIRIN; INFECTION
AB Published studies have described a strong association with a single-nucleotide polymorphism (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene and ribavirin (RBV)-induced hemolytic anemia in HCV-infected patients receiving pegylated interferon (pegIFN) and RBV. This study sought to evaluate the effect of these polymorphisms on anemia, hemoglobin reduction, HCV kinetics, and treatment outcomes. Sixty-three patients coinfected with HIV and HCV and 58 patients infected with HCV only were treated with pegIFN/RBV were genotyped using the ABI TaqMan allelic discrimination kit for the 2 ITPA SNP variants rs1127354 and rs7270101. A composite variable of ITPA deficiency using both SNPs was created as previously reported. Statistical analysis was performed using Mann-Whitney test or Chi square/Fishers exact test for categorical data and mixed model analysis for multiple variables. Thirty-five patients (30%) were predicted to have reduced ITPA activity. ITPA deficiency was found to be protective against the development of hemoglobin reduction >3?g/dl over the course of treatment. The rates of hemoglobin reduction >3?g/dl decreased in correlation with the severity of ITPA deficiency. ITPA deficiency was associated with slower hemoglobin decline early in treatment (week 4, P?=?0.020) and rapid virologic response (RVR) at week 4 (P?=?0.017) in patients coinfected with HIV and HCV. ITPA polymorphisms are associated with hemoglobin decline and in patients coinfected with HIV and HCV it is also associated with early virologic outcomes. Determination of ITPA polymorphisms may allow prediction of RBV-induced anemia and earlier initiation of supportive care to ensure optimal therapeutic outcomes. J. Med. Virol. 84: 11061114, 2012. Published 2012. This is a US Government work and as such is in the public domain in the United States of America.
C1 [Osinusi, Anu; Poonia, Seerat; Funk, Emily; Polis, Michael; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Osinusi, Anu; Fishbein, Dawn] NCI, CMRP, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Naggie, Susanna] Duke Clin Res Inst, Durham, NC USA.
[Trippler, Martin; Schlaak, Joerg] Univ Hosp Essen, Essen, Germany.
[Hu, Zonghui] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Masur, Henry] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
RP Osinusi, A (reprint author), Bldg10,Rm 6A-33A 10 Ctr Dr, Bethesda, MD 20892 USA.
EM osinusia@niaid.nih.gov
OI Polis, Michael/0000-0002-9151-2268; Schlaak, Joerg/0000-0002-9499-1014
FU National Cancer Institute; National Institutes of Health
[HHSN261200800001E]; NIH (National Institute of Allergy and Infectious
Diseases)
FX Grant sponsor: National Cancer Institute (in whole or in part); Grant
sponsor: National Institutes of Health (in whole or in part); Grant
number: HHSN261200800001E; Grant sponsor: Intramural Research Program of
the NIH (National Institute of Allergy and Infectious Diseases) (in
whole or in part).
NR 28
TC 6
Z9 7
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0146-6615
J9 J MED VIROL
JI J. Med. Virol.
PD JUL
PY 2012
VL 84
IS 7
BP 1106
EP 1114
DI 10.1002/jmv.23302
PG 9
WC Virology
SC Virology
GA 941VH
UT WOS:000303994200016
PM 22585729
ER
PT J
AU Schwartz, CM
Tavakoli, T
Jamias, C
Park, SS
Maudsley, S
Martin, B
Phillips, TM
Yao, PJ
Itoh, K
Ma, W
Rao, MS
Arenas, E
Mattson, MP
AF Schwartz, Catherine M.
Tavakoli, Tahereh
Jamias, Charmaine
Park, Sung-Soo
Maudsley, Stuart
Martin, Bronwen
Phillips, Terry M.
Yao, Pamela J.
Itoh, Katsuhiko
Ma, Wu
Rao, Mahendra S.
Arenas, Ernest
Mattson, Mark P.
TI Stromal factors SDF1 alpha, sFRP1, and VEGFD induce dopaminergic neuron
differentiation of human pluripotent stem cells
SO JOURNAL OF NEUROSCIENCE RESEARCH
LA English
DT Article
DE dopaminergic neurons; neuronal differentiation; stromal cell-derived
inducing activity; embryonic stem cells
ID ENDOTHELIAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; PARKINSONS-DISEASE;
IN-VIVO; GENERATION; SURVIVAL; CULTURE; TRANSPLANTATION; EXPRESSION;
COCULTURE
AB Human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons hold potential for treating Parkinson's disease (PD) through cell replacement therapy. Generation of DA neurons from hESCs has been achieved by coculture with the stromal cell line PA6, a source of stromal cell-derived inducing activity (SDIA). However, the factors produced by stromal cells that result in SDIA are largely undefined. We previously reported that medium conditioned by PA6 cells can generate functional DA neurons from NTera2 human embryonal carcinoma stem cells. Here we show that PA6-conditioned medium can induce DA neuronal differentiation in both NTera2 cells and the hESC I6 cell line. To identify the factor(s) responsible for SDIA, we used large-scale microarray analysis of gene expression combined with mass spectrometric analysis of PA6-conditioned medium (CM). The candidate factors, hepatocyte growth factor (HGF), stromal cell-derived factor-1 a (SDF1a), secreted frizzled-related protein 1 (sFRP1), and vascular endothelial growth factor D (VEGFD) were identified, and their concentrations in PA6 CM were established by immunoaffinity capillary electrophoresis. Upon addition of SDF1a, sFRP1, and VEGFD to the culture medium, we observed an increase in the number of cells expressing tyrosine hydroxylase (a marker for DA neurons) and beta III-tubulin (a marker for immature neurons) in both the NTera2 and I6 cell lines. These results indicate that SDF1a, sFRP1, and VEGFD are major components of SDIA and suggest the potential use of these defined factors to elicit DA differentiation of pluripotent human stem cells for therapeutic intervention in PD. (c) 2012 Wiley Periodicals, Inc.
C1 [Mattson, Mark P.] NIA, Lab Neurosci, NIH, Biomed Res Ctr,Intramural Res Program, Baltimore, MD 21224 USA.
[Schwartz, Catherine M.; Arenas, Ernest] Karolinska Inst, Dept Med Biochem & Biophys, Mol Neurobiol Lab, Stockholm, Sweden.
[Tavakoli, Tahereh; Ma, Wu] Amer Type Culture Collect, Stem Cell Ctr, Dev Biol, Manassas, VA USA.
[Phillips, Terry M.] Natl Inst Biomed Imaging & Bioengn, NIH, Lab Bioengn & Phys Sci, Baltimore, MD 21224 USA.
[Itoh, Katsuhiko] Kyoto Univ, Dept Clin Mol Biol, Kyoto, Japan.
[Rao, Mahendra S.] Life Technol Inc, Invitrogen Corp, Frederick, MD USA.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Mattson, MP (reprint author), NIA, Lab Neurosci, NIH, Biomed Res Ctr,Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012;
OI Arenas, Ernest/0000-0003-0197-6577
FU National Institute on Aging; National Institute for Biomedical Imaging
and Bioengineering
FX Contract grant sponsor: Intramural Research Program of the National
Institute on Aging; Contract grant sponsor: Intramural Research Program
of the National Institute for Biomedical Imaging and Bioengineering.
NR 49
TC 17
Z9 17
U1 1
U2 12
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0360-4012
J9 J NEUROSCI RES
JI J. Neurosci. Res.
PD JUL
PY 2012
VL 90
IS 7
BP 1367
EP 1381
DI 10.1002/jnr.23064
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 939YQ
UT WOS:000303857400008
PM 22535492
ER
PT J
AU Esposito, G
Nakazawa, J
Venuti, P
Bornstein, MH
AF Esposito, G.
Nakazawa, J.
Venuti, P.
Bornstein, M. H.
TI Perceptions of distress in young children with autism compared to
typically developing children: A cultural comparison between Japan and
Italy
SO RESEARCH IN DEVELOPMENTAL DISABILITIES
LA English
DT Article
DE Autism; Expression of distress; Cry; Cross-Cultural Comparison; ASD
ID AFFECTIVE EXPRESSION; DOWN-SYNDROME; INFANT; CRY; AGE; HYPOTHESIS;
DISORDER; AMYGDALA; SIGNALS; MOTHERS
AB This study investigates how adults in two contrasting cultures (Italian and Japanese) perceive episodes of crying of typically developing (TD) children and children with Autism Disorder (AD). Although cries of children with AD have been reported to elicit more distress in Western cultures, it is not known whether similar findings hold in Eastern cultures. In Experiment 1, we artificially modified structural parameters (fundamental frequency, duration of pauses, waveform modulation) of cries and asked Italian and Japanese adults to judge levels of expressed and felt distress in the cries. In Experiment 2, we asked Italian and Japanese adults to report these levels of distress on hearing cries of AD and TD children. In both cultures, cries with higher fundamental frequency and shorter pause durations were judged more distressing and distressed and observers perceived cries of children with AD as more distressing and distressed than cries of TD children. The similar responses in adults from two contrasting societies constitute evidence that reactions to cries of children with AD might be universal. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Esposito, G.] RIKEN Brain Sci Inst, Kuroda Res Unit Affiliat Social Behav, Wako, Saitama 3510198, Japan.
[Esposito, G.; Venuti, P.] Univ Trent, Observat & Funct Diag Lab DiSCoF, Trento, Italy.
[Nakazawa, J.] Chiba Univ, Fac Educ, Dept Dev Sci, Chiba, Japan.
[Bornstein, M. H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Esposito, G (reprint author), RIKEN Brain Sci Inst, Kuroda Res Unit Affiliat Social Behav, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
EM gesposito@brain.riken.jp
RI Esposito, Gianluca/B-1374-2012; Esposito, Gianluca/K-9353-2013
OI Esposito, Gianluca/0000-0002-9442-0254; Esposito,
Gianluca/0000-0002-9442-0254
FU Intramural NIH HHS [Z01 HD001119-20]
NR 35
TC 11
Z9 12
U1 1
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0891-4222
J9 RES DEV DISABIL
JI Res. Dev. Disabil.
PD JUL-AUG
PY 2012
VL 33
IS 4
BP 1059
EP 1067
DI 10.1016/j.ridd.2012.01.014
PG 9
WC Education, Special; Rehabilitation
SC Education & Educational Research; Rehabilitation
GA 937XW
UT WOS:000303698500011
PM 22502830
ER
PT J
AU Fujimoto, M
Hayashi, T
Urfer, R
Mita, S
Su, TP
AF Fujimoto, Michiko
Hayashi, Teruo
Urfer, Roman
Mita, Shiro
Su, Tsung-Ping
TI Sigma-1 receptor chaperones regulate the secretion of brain-derived
neurotrophic factor
SO SYNAPSE
LA English
DT Article
DE sigma-1 receptor; sigma receptor; BDNF; GDNF; cutamesine; SA4503;
antidepressant; depression; cleavage; secretion; neuroprotection
ID NEUROBLASTOMA-CELLS; MAJOR DEPRESSION; FACTOR BDNF; ANTIDEPRESSANTS;
MODULATION; RELEASE; LIGAND; HIPPOCAMPUS; EXPRESSION; SURVIVAL
AB The sigma-1 receptor (Sig-1R) is a novel endoplasmic reticulum (ER) molecular chaperone that regulates protein folding and degradation. The Sig-1R activation by agonists is known to improve memory, promote cell survival, and exert an antidepressant-like action in animals. Cutamesine (SA4503), a selective Sig-1R ligand, was shown to increase BDNF in the hippocampus of rats. How exactly the intracellular chaperone Sig-1R or associated ligand causes the increase of BDNF or any other neurotrophins is unknown. We examined here whether the action of Sig-1Rs may relate to the post-translational processing and release of BDNF in neuroblastoma cell lines. We used in vitro assays and confirmed that cutamesine possesses the bona fide Sig-1R agonist property by causing the dissociation of BiP from Sig-1Rs. The C-terminus of Sig-1Rs exerted robust chaperone activity by completely blocking the aggregation of BDNF and GDNF in vitro. Chronic treatment with cutamesine in rat B104 neuroblastoma caused a time- and dose-dependent potentiation of the secretion of BDNF without affecting the mRNA level of BDNF. Cutamesine decreased the intracellular level of pro-BDNF and mature BDNF whereas increased the extracellular level of mature BDNF. The pulse-chase experiment indicated that the knockdown of Sig-1Rs decreased the secreted mature BDNF in B104 cells without affecting the synthesis of BDNF. Our findings indicate that, in contrast to clinically used antidepressants that promote the transcriptional upregulation of BDNF, the Sig-1R agonist cutamesine potentiates the post-translational processing of neurotrophins. This unique pharmacological profile may provide a novel therapeutic opportunity for the treatment of neuropsychiatric disorders. Synapse, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Fujimoto, Michiko; Hayashi, Teruo; Su, Tsung-Ping] NIDA, Intramural Res Program, NIH, Cellular Stress Signaling Unit, Baltimore, MD 21224 USA.
[Urfer, Roman; Mita, Shiro] Ms Sci Corp, Kobe, Hyogo, Japan.
[Fujimoto, Michiko; Hayashi, Teruo; Su, Tsung-Ping] NIDA, Cellular Pathobiol Sect, Integrat Neurosci Branch, Baltimore, MD 21224 USA.
RP Hayashi, T (reprint author), NIDA, Intramural Res Program, NIH, Cellular Stress Signaling Unit, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM thayashi@mail.nih.gov; tsu@intra.nida.nih.gov
FU Intramural Research Program; NIDA; NIH; DHHS; M-CRADA [02493-2009];
Japan Society for the Promotion of Sciences (JSPS)
FX Contract grant sponsor: Intramural Research Program, NIDA, NIH, DHHS,
and M-CRADA; Contract grant number: 02493-2009; Contract grant sponsor:
Japan Society for the Promotion of Sciences (JSPS) Fellowship for
Japanese Biochemical and Behavioral Researchers at NIH.
NR 39
TC 33
Z9 34
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-4476
EI 1098-2396
J9 SYNAPSE
JI Synapse
PD JUL
PY 2012
VL 66
IS 7
BP 630
EP 639
DI 10.1002/syn.21549
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 940UV
UT WOS:000303919500006
PM 22337473
ER
PT J
AU Goldenberg, DM
Zagzag, D
Heselmeyer-Haddad, KM
Garcia, LYB
Ried, T
Loo, M
Chang, CH
Gold, DV
AF Goldenberg, David M.
Zagzag, David
Heselmeyer-Haddad, Kerstin M.
Garcia, Lissa Y. Berroa
Ried, Thomas
Loo, Meiyu
Chang, Chien-Hsing
Gold, David V.
TI Horizontal transmission and retention of malignancy, as well as
functional human genes, after spontaneous fusion of human glioblastoma
and hamster host cells in vivo
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE cell fusion; cancer stroma; metastasis; gene transfer; glioblastoma
ID TUMOR-CELLS; NUDE-MICE; STROMAL CELLS; LUNG METASTASIS; STEM-CELLS;
CANCER; TRANSFORMATION; MURINE; IDENTIFICATION; HYBRIDIZATION
AB Cell fusion in vitro has been used to study cancer, gene mapping and regulation, and the production of antibodies via hybridomas. However, in-vivo heterosynkaryon formation by cellcell fusion has received less attention. This investigation describes the spontaneous fusion of a human glioblastoma with normal hamster cells after xenogeneic transplantation, resulting in malignant cells that express both human and hamster genes and gene products, and retention of glioblastoma traits with an enhanced ability to metastasize. Three of 7 human genes found showed translation of their proteins during serial propagation in vivo or in vitro for years; namely, CD74, CXCR4 and PLAGL2, each implicated with malignancy or glioblastoma. This supports the thesis that genetic hybridization of cancer and normal cells can transmit malignancy and also, as first described herein, regulatory genes involved in the tumor's organotypic morphology. Evidence also is increasing that even cell-free human cancer DNA can induce malignancy and transfer genetic information to normal cells. Hence, we posit that the transfer of genetic information between tumor and stromal cells, whether by cellcell fusion or other mechanisms, is implicated in the progression of malignancy, and may further define the crosstalk between cancer cells and their stromal neighbors.
C1 [Goldenberg, David M.; Gold, David V.] Garden State Canc Ctr, Ctr Mol Med & Immunol, Morris Plains, NJ 07950 USA.
[Zagzag, David] NYU Med Ctr, Dept Pathol, New York, NY 10016 USA.
[Zagzag, David] NYU Med Ctr, Dept Neurosurg, New York, NY 10016 USA.
[Heselmeyer-Haddad, Kerstin M.; Garcia, Lissa Y. Berroa; Ried, Thomas] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Loo, Meiyu; Chang, Chien-Hsing] Immunomedics Inc, Morris Plains, NJ USA.
RP Goldenberg, DM (reprint author), Garden State Canc Ctr, Ctr Mol Med & Immunol, 300 Amer Way, Morris Plains, NJ 07950 USA.
EM dmg.gscancer@att.net
FU American Cancer Society [IN-581]; USPHS (National Institutes of Health)
[CA12374]; National Cancer Institute, NIH, Damon Runyon Memorial Fund
for Cancer Research; National Cancer Institute, NIH; Damon Runyon
Memorial Fund for Cancer Research
FX Grant sponsor: American Cancer Society; Grant number: IN-581; Grant
sponsor: USPHS (National Institutes of Health); Grant number: CA12374;
Grant sponsor: National Cancer Institute, NIH, Damon Runyon Memorial
Fund for Cancer Research; The authors are grateful to the late Dr. Gary
Stone and to Dr. Polina Perelman from the National Cancer Institute,
Frederick Campus, for the generous gift of the golden hamster
X-chromosome probe and expert advice. They appreciate crucial advice and
discussions with Dr. Hesed Padilla-Nash, Genetics Branch, National
Cancer Institute, regarding interspecies FISH hybridization, and the
preparation of FISH figures by Buddy Chen. Supported in part by the
intramural research program of the National Cancer Institute, NIH
(T.R.), the Damon Runyon Memorial Fund for Cancer Research and USPHS
grant CA12374 from the National Institutes of Health (D.M.G.) for
establishing the GB-749 tumor.
NR 50
TC 15
Z9 22
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 1
PY 2012
VL 131
IS 1
BP 49
EP 58
DI 10.1002/ijc.26327
PG 10
WC Oncology
SC Oncology
GA 929GU
UT WOS:000303050100006
PM 21796629
ER
PT J
AU Kreimer, AR
Schiffman, M
Herrero, R
Hildesheim, A
Gonzalez, P
Burk, RD
Porras, C
Sherman, ME
Demuth, F
Cheung, L
Bratti, C
Rodriguez, AC
AF Kreimer, Aimee R.
Schiffman, Mark
Herrero, Rolando
Hildesheim, Allan
Gonzalez, Paula
Burk, Robert D.
Porras, Carolina
Sherman, Mark E.
Demuth, Franklin
Cheung, Li
Bratti, Concepcion
Cecilia Rodriguez, Ana
TI Long-term risk of recurrent cervical human papillomavirus infection and
precancer and cancer following excisional treatment
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE HPV; LEEP; cervical pre-cancer; post-treatment; recurrence
ID LOOP ELECTROSURGICAL EXCISION; SQUAMOUS INTRAEPITHELIAL LESIONS;
RANDOMIZED CLINICAL-TRIAL; HPV-DNA DETECTION; COSTA-RICA; NEOPLASIA;
WOMEN; CONIZATION; LASER; CIN
AB Risk of recurrent CIN2+ (including cervical intraepithelial neoplasia grade 2 [CIN2], CIN3, carcinoma and in situ, adenocarcinoma in situ or cancer) remains elevated for years following treatment. The role of long-term post-treatment human papillomavirus (HPV) presence on subsequent risk of CIN2+ was evaluated in the 10,049-women Guanacaste cohort. Six hundred eighty-one women were referred to colposcopy because of high-grade cytology, positive cervicography and/or suspicion of cancer based on visual assessment; 486 were judged to require treatment. After excluding women with <12 months of follow-up (N = 88), prior cancer or hysterectomy (N = 37) or other reasons (N = 14), 347 were included in the analysis. Infections were categorized as persistent if present at both pre- and post-treatment visits and new if detected only post-treatment. Median time between the treatment and post-treatment visits was 6.7 years (interquartile range 3.87.8). At the post-treatment visit, 8 (2.4%), 2 (0.6%) and 8 (2.4%) of the 347 treated women had persistent HPV16, HPV18 or other carcinogenic HPV, respectively. Two (0.8%), 3 (1.0%) and 13 (4.0%) had new HPV16, HPV18 and other carcinogenic HPV, respectively. Six CIN2+ cases were identified at the post-treatment visit, all with persistent infections (three HPV16, one HPV18 and two other carcinogenic HPV). No recurrent disease was observed among women with new HPV infections during the follow-up period. Thus, persistence of HPV infection a median of six years after treatment was uncommon but, when present, posed a substantial risk of subsequent CIN2+. Serial follow-up data from other studies would further strengthen these conclusions.
C1 [Herrero, Rolando; Gonzalez, Paula; Porras, Carolina; Bratti, Concepcion; Cecilia Rodriguez, Ana] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica.
[Kreimer, Aimee R.; Schiffman, Mark; Hildesheim, Allan; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA.
[Herrero, Rolando] Int Agcy Res Canc, Early Detect & Prevent Sect, F-69372 Lyon, France.
[Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA.
[Demuth, Franklin; Cheung, Li] Informat Management Syst Inc, Rockville, MD USA.
RP Rodriguez, AC (reprint author), Fdn INCIENSA, Proyecto Epidemiol Guanacaste, 7Mo Piso, San Jose, Costa Rica.
EM acrodriguez@racsa.co.cr
RI Hildesheim, Allan/B-9760-2015; Kreimer, Aimee/H-1687-2015;
OI Hildesheim, Allan/0000-0003-0257-2363; Cheung, Li/0000-0003-1625-4331
FU National Cancer Institute (NCI); National Institutes of Health (NIH);
Department of Health and Human Services of the United States of America;
NIH Office for Research on Women's Health [N01-CP-11005]; National
Cancer Institute [CA78527]; Einstein Cancer Research Center; CFAR
FX Grant sponsors: National Cancer Institute (NCI), National Institutes of
Health (NIH), Department of Health and Human Services of the United
States of America, NIH Office for Research on Women's Health, Grant
number: N01-CP-11005; Grant sponsor: National Cancer Institute; Grant
number: CA78527; Grant sponsors: Einstein Cancer Research Center and
CFAR
NR 29
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U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 1
PY 2012
VL 131
IS 1
BP 211
EP 218
DI 10.1002/ijc.26349
PG 8
WC Oncology
SC Oncology
GA 929GU
UT WOS:000303050100022
PM 21823117
ER
PT J
AU Fargo, J
Kratz, C
Giri, N
Savage, S
Wong, C
Backer, K
Alter, B
Glader, B
AF Fargo, John
Kratz, Christian
Giri, Neelam
Savage, Sharon
Wong, Carolyn
Backer, Karen
Alter, Blanche
Glader, Bertil
TI ADENOSINE DEAMINASE: HOW GOOD IS IT FOR THE DIAGNOSIS OF
DIAMOND-BLACKFAN ANEMIA?
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Fargo, John; Kratz, Christian; Giri, Neelam; Savage, Sharon; Wong, Carolyn; Backer, Karen; Alter, Blanche; Glader, Bertil] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2012
VL 58
IS 7
SI SI
BP 1016
EP 1016
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 926XC
UT WOS:000302864200010
ER
PT J
AU Salzer, W
Jones, T
Dreyer, Z
Gore, L
Winick, N
Sung, LL
Raetz, E
Devidas, M
Carroll, W
Hunger, S
Hilden, J
Brown, P
AF Salzer, Wanda
Jones, Tamekia
Dreyer, ZoAnn
Gore, Lia
Winick, Naomi
Sung, Lillian
Raetz, Elizabeth
Devidas, Meenakshi
Carroll, William
Hunger, Stephen
Hilden, Joanne
Brown, Patrick
TI DECREASED INDUCTION MORBIDITY AND MORTALITY WITH CHANGES TO INDUCTION
THERAPY IN INFANTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA ENROLLED ON
CHILDREN'S ONCOLOGY GROUP (COG) TRIAL AALL0631
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Salzer, Wanda; Jones, Tamekia; Dreyer, ZoAnn; Gore, Lia; Winick, Naomi; Sung, Lillian; Raetz, Elizabeth; Devidas, Meenakshi; Carroll, William; Hunger, Stephen; Hilden, Joanne; Brown, Patrick] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2012
VL 58
IS 7
SI SI
BP 1016
EP 1016
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 926XC
UT WOS:000302864200011
ER
PT J
AU Reed, H
Giri, N
Savage, S
Stratton, P
Alter, B
AF Reed, Helen
Giri, Neelam
Savage, Sharon
Stratton, Pamela
Alter, Blanche
TI FETAL LOSS AMONG MOTHERS OF PATIENTS WITH INHERITED BONE MARROW FAILURE
SYNDROMES
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Reed, Helen; Giri, Neelam; Savage, Sharon; Stratton, Pamela; Alter, Blanche] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2012
VL 58
IS 7
SI SI
BP 1023
EP 1024
PG 2
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 926XC
UT WOS:000302864200035
ER
PT J
AU Shah, N
Stetler-Stevenson, M
Yuan, C
Richards, K
Delbrook, C
Civin, C
Kreitman, R
Pastan, I
Wayne, A
AF Shah, Nirali
Stetler-Stevenson, Maryalice
Yuan, Constance
Richards, Kelly
Delbrook, Cindy
Civin, Curt
Kreitman, Robert
Pastan, Ira
Wayne, Alan
TI CD22 EXPRESSION IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Shah, Nirali; Stetler-Stevenson, Maryalice; Yuan, Constance; Richards, Kelly; Delbrook, Cindy; Civin, Curt; Kreitman, Robert; Pastan, Ira; Wayne, Alan] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2012
VL 58
IS 7
SI SI
BP 1040
EP 1041
PG 2
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 926XC
UT WOS:000302864200092
ER
PT J
AU Hammad, M
Elborai, Y
Hafez, H
Moussa, E
Hussein, H
Lehmann, L
Elhaddad, A
AF Hammad, Mahmoud
Elborai, Yasser
Hafez, Hanafy
Moussa, Emad
Hussein, Hany
Lehmann, Leslie
Elhaddad, Alaa
TI RENAL, HEPATIC AND INFECTIOUS COMPLICATIONS IN 2 DIFFERENT CONDITIONING
REGIMENS (BUSULFAN/MELPHALAN & CARBOPLATIN/ETOPOSIDE/MELPHALAN) FOR
ADVANCED STAGE NEUROBLASTOMA: A COMPARISON OF THE CAIRO AND BOSTON
EXPERIENCE
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 NCI, Bethesda, MD 20892 USA.
Cairo Univ, Cairo, Egypt.
CCHE, Edmonton, AB, Canada.
DFCHCC, Turners Falls, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2012
VL 58
IS 7
SI SI
BP 1078
EP 1078
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 926XC
UT WOS:000302864200220
ER
PT J
AU Orifici, AC
Krueger, R
AF Orifici, Adrian C.
Krueger, Ronald
TI Benchmark assessment of automated delamination propagation capabilities
in finite element codes for static loading
SO FINITE ELEMENTS IN ANALYSIS AND DESIGN
LA English
DT Article
DE Laminated composite materials; Delamination; Fracture mechanics;
Benchmarking
ID CRACK CLOSURE TECHNIQUE; RELEASE RATE CALCULATION; FRACTURE-TOUGHNESS;
COMPOSITES; FRONT
AB With the increasing implementation into commercial finite element (FE) codes of capabilities for simulating delamination propagation in composite materials, the need for benchmarking and assessing these capabilities is critical. In this study, the capabilities of the commercial FE code Marc (TM) 2008r1 with implementation of the Virtual Crack Closure Technique (VCCT) was assessed. Benchmark delamination propagation results for several specimen configurations were generated using a numerical approach. Specimens were analyzed with three-dimensional and two-dimensional models, and compared with previous analyses using Abaqus (R) with the VCCT implemented. The results demonstrated that the VCCT implementation in Marc (TM) was capable of accurately replicating the benchmark delamination growth results. The analyses in Marc (TM) were significantly more computationally efficient than previous analyses in Abaqus (R). This was due to a lack of convergence issues, and a solution process that maintained the use of large time increments. The results demonstrated the advantages of numerical over experimental and analytical benchmarks, particularly with regards to comparison of capabilities a cross codes. More broadly, the results illustrated key similarities and differences between two commercial FE codes implementing the same analysis technique, which reinforces the need for rigorous benchmarking and assessment. (C) 2012 Elsevier B. V. All rights reserved.
C1 [Orifici, Adrian C.] RMIT Univ, Melbourne, Vic 3001, Australia.
[Krueger, Ronald] NIA, Hampton, VA 23666 USA.
[Krueger, Ronald] NASA Langley Res Ctr, Damage Tolerance & Reliabil Branch, Hampton, VA 23681 USA.
RP Orifici, AC (reprint author), RMIT Univ, GPO Box 2476, Melbourne, Vic 3001, Australia.
EM adrian.orifici@rmit.edu.au
RI Krueger, Ronald/G-5356-2015; Orifici, Adrian/J-7842-2016
OI Orifici, Adrian/0000-0001-8573-7228
FU National Aeronautics and Space Administration, Langley Research Center
[NNL09AA00A]; NASA; RMIT University; Per Nordlund of MSC.Software
Corporation
FX This material is based on the work supported by National Aeronautics and
Space Administration, Langley Research Center under Research Cooperative
Agreement no. NNL09AA00A awarded to the National Institute of Aerospace.
The research was supported by the Aircraft Aging and Durability Project
as part of NASA's Aviation Safety Program, and an RMIT University
Research Leave Award. The analyses were performed at the Durability,
Damage Tolerance and Reliability Branch at NASA Langley Research Center,
Hampton, Virginia, USA. The authors would like to thank Per Nordlund of
MSC.Software Corporation for his support and advice.
NR 30
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U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-874X
J9 FINITE ELEM ANAL DES
JI Finite Elem. Anal. Des.
PD JUL
PY 2012
VL 54
BP 28
EP 36
DI 10.1016/j.finel.2012.01.006
PG 9
WC Mathematics, Applied; Mechanics
SC Mathematics; Mechanics
GA 905FU
UT WOS:000301258500003
ER
PT J
AU Finger, EC
Marsh, A
Blair, KS
Majestic, C
Evangelou, I
Gupta, K
Schneider, MR
Sims, C
Pope, K
Fowler, K
Sinclair, S
Tovar-Moll, F
Pine, D
Blair, RJ
AF Finger, Elizabeth Carrie
Marsh, Abigail
Blair, Karina Simone
Majestic, Catherine
Evangelou, Iordanis
Gupta, Karan
Schneider, Marguerite Reid
Sims, Courtney
Pope, Kayla
Fowler, Katherine
Sinclair, Stephen
Tovar-Moll, Fernanda
Pine, Daniel
Blair, Robert James
TI Impaired functional but preserved structural connectivity in limbic
white matter tracts in youth with conduct disorder or oppositional
defiant disorder plus psychopathic traits
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Psychopathic traits; Conduct disorder; Oppositional defiant disorder;
Diffusion tensor imaging; Functional connectivity
ID CALLOUS-UNEMOTIONAL TRAITS; VENTROMEDIAL PREFRONTAL CORTEX; DISRUPTIVE
BEHAVIOR DISORDERS; COMMON STEREOTACTIC SPACE; SUBJECT DIFFUSION DATA;
FEARFUL EXPRESSIONS; SPATIAL STATISTICS; VOXELWISE ANALYSIS; CHILDREN;
BRAIN
AB Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD + PT) are at high risk of adult antisocial behavior and psychopathy. Neuroimaging studies demonstrate functional abnormalities in orbitofrontal cortex and the amygdala in both youths and adults with psychopathic traits. Diffusion tensor imaging in psychopathic adults demonstrates disrupted structural connectivity between these regions (uncinate fasiculus). The current study examined whether functional neural abnormalities present in youths with CD/ODD + PT are associated with similar white matter abnormalities. Youths with CD/ODD + PT and comparison participants completed 3.0 T diffusion tensor scans and functional magnetic resonance imaging scans. Diffusion tensor imaging did not reveal disruption in structural connections within the uncinate fasiculus or other white matter tracts in youths with CD/ODD + PT, despite the demonstration of disrupted amygdala-prefrontal functional connectivity in these youths. These results suggest that disrupted amygdala-frontal white matter connectivity as measured by fractional anisotropy is less sensitive than imaging measurements of functional perturbations in youths with psychopathic traits. If white matter tracts are intact in youths with this disorder, childhood may provide a critical window for intervention and treatment, before significant structural brain abnormalities solidify. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Finger, Elizabeth Carrie; Gupta, Karan] Univ Western Ontario, Dept Clin Neurol Sci, Schulich Sch Med, London, ON N6A 5A5, Canada.
[Marsh, Abigail] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA.
[Blair, Karina Simone; Majestic, Catherine; Schneider, Marguerite Reid; Sims, Courtney; Pope, Kayla; Fowler, Katherine; Sinclair, Stephen; Pine, Daniel; Blair, Robert James] NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Evangelou, Iordanis] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Tovar-Moll, Fernanda] LABS DOr Hosp Network, Cognit & Behav Neurosci Unit, Rio De Janeiro, Brazil.
RP Finger, EC (reprint author), Univ Western Ontario, Dept Clin Neurol Sci, Schulich Sch Med, B10-004,339 Windermere Rd, London, ON N6A 5A5, Canada.
EM Elizabeth.Finger@lhsc.on.ca
RI Neurociencia, Inct/I-1011-2013; Finger, Elizabeth/B-6453-2015
FU Intramural Research Program of the National Institute of Mental Health
FX This research was funded through the Intramural Research Program of the
National Institute of Mental Health.
NR 51
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U1 4
U2 32
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD JUN 30
PY 2012
VL 202
IS 3
BP 239
EP 244
DI 10.1016/j.pscychresns.2011.11.002
PG 6
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 007NT
UT WOS:000308896100007
PM 22819939
ER
PT J
AU Brennan, LA
Kantorow, WL
Chauss, D
McGreal, R
He, SY
Mattucci, L
Wei, JN
Riazuddin, SA
Cvekl, A
Hejtmancik, JF
Kantorow, M
AF Brennan, Lisa Ann
Kantorow, Wanda Lee
Chauss, Daniel
McGreal, Rebecca
He, Shuying
Mattucci, Lyndzie
Wei, Jianning
Riazuddin, S. Amer
Cvekl, Ales
Hejtmancik, J. Fielding
Kantorow, Marc
TI Spatial expression patterns of autophagy genes in the eye lens and
induction of autophagy in lens cells
SO MOLECULAR VISION
LA English
DT Article
ID OXIDATIVE STRESS RESPONSES; TUMOR-SUPPRESSOR ACTIVITY; REGULATES
AUTOPHAGY; NEURODEGENERATIVE DISEASES; SELECTIVE AUTOPHAGY;
PARKINSONS-DISEASE; EPITHELIAL-CELLS; MAMMALIAN-CELLS; LC3 LIPIDATION;
PROTEIN
AB Purpose: Mutation of the autophagy gene FYVE (named after the four cysteine-rich proteins: Fab 1 [yeast orthologue of PIKfyve], YOTB, Vac 1 [vesicle transport protein], and EEA1) and coiled coil containing 1 (fyco1) causes human cataract suggesting a role for autophagy in lens function. Here, we analyzed the range and spatial expression patterns of lens autophagy genes and we evaluated whether autophagy could be induced in lens cells exposed to stress.
Methods: Autophagy gene expression levels and their spatial distribution patterns were evaluated between microdissected human lens epithelium and fibers at the mRNA and protein levels by microarray data analysis, real-time PCR and western blot analysis. Selected autophagy protein spatial expression patterns were also examined in newborn mouse lenses by immunohistochemistry. The autophagosomal content of cultured human lens epithelial cells was determined by counting the number of microtubule-associated protein 1 light chain 3B (LC3B)-positive puncta in cells cultured in the presence or absence of serum.
Results: A total of 42 autophagy genes were detected as being expressed by human lens epithelium and fibers. The autophagosomal markers LC3B and FYCO1 were detected throughout the newborn mouse lens. Consistently, the autophagy active form of LC3B (LC3B II) was detected in microdissected human lens fibers. An increased number of LC3B-positive puncta was detected in cultured lens cells upon serum starvation suggesting induction of autophagy in lens cells under stress conditions.
Conclusions: The data provide evidence that autophagy is an important component for the function of lens epithelial and fiber cells. The data are consistent with the notion that disruption of lens autophagy through mutation or inactivation of specific autophagy proteins could lead to loss of lens resistance to stress and/or loss of lens differentiation resulting in cataract formation.
C1 [Brennan, Lisa Ann; Kantorow, Wanda Lee; Chauss, Daniel; McGreal, Rebecca; Mattucci, Lyndzie; Wei, Jianning; Kantorow, Marc] Florida Atlantic Univ, Dept Biomed Sci, Boca Raton, FL 33431 USA.
[He, Shuying; Cvekl, Ales] Albert Einstein Coll Med, Dept Ophthalmol & Visual Sci, Bronx, NY 10467 USA.
[He, Shuying; Cvekl, Ales] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA.
[Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Hejtmancik, J. Fielding] NEI, OGVFB, NIH, Bethesda, MD 20892 USA.
RP Kantorow, M (reprint author), Florida Atlantic Univ, Dept Biomed Sci, 777 Glades Rd, Boca Raton, FL 33431 USA.
EM mkantoro@fau.edu
RI Cvekl, Ales/B-2427-2013
FU [RO1 EY13022]
FX This work was supported by grant RO1 EY13022 (M.K.).
NR 95
TC 18
Z9 20
U1 0
U2 4
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JUN 30
PY 2012
VL 18
IS 183-84
BP 1773
EP 1786
PG 14
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 973AJ
UT WOS:000306323100001
PM 22815631
ER
PT J
AU Li, QQ
Skinner, J
Bennett, JE
AF Li, Qingdi Quentin
Skinner, Jeff
Bennett, John E.
TI Evaluation of reference genes for real-time quantitative PCR studies in
Candida glabrata following azole treatment
SO BMC MOLECULAR BIOLOGY
LA English
DT Article
DE Candida glabrata; Azole resistance gene; Fluconazole; hkgFinder;
Housekeeping gene; Reference gene; RT-qPCR
ID MESSENGER-RNA EXPRESSION; POLYMERASE-CHAIN-REACTION; RT-PCR;
HOUSEKEEPING GENE; BETA-ACTIN; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE;
UP-REGULATION; RIBOSOMAL-RNA; SELECTION; VALIDATION
AB Background: The selection of stable and suitable reference genes for real-time quantitative PCR (RT-qPCR) is a crucial prerequisite for reliable gene expression analysis under different experimental conditions. The present study aimed to identify reference genes as internal controls for gene expression studies by RT-qPCR in azole-stimulated Candida glabrata.
Results: The expression stability of 16 reference genes under fluconazole stress was evaluated using fold change and standard deviation computations with the hkgFinder tool. Our data revealed that the mRNA expression levels of three ribosomal RNAs (RDN5.8, RDN18, and RDN25) remained stable in response to fluconazole, while PGK1, UBC7, and UBC13 mRNAs showed only approximately 2.9-, 3.0-, and 2.5-fold induction by azole, respectively. By contrast, mRNA levels of the other 10 reference genes (ACT1, EF1 alpha, GAPDH, PPIA, RPL2A, RPL10, RPL13A, SDHA, TUB1, and UBC4) were dramatically increased in C. glabrata following antifungal treatment, exhibiting changes ranging from 4.5- to 32.7-fold. We also assessed the expression stability of these reference genes using the 2(-Delta Delta CT) method and three other software packages. The stability rankings of the reference genes by geNorm and the 2(-Delta Delta CT) method were identical to those by hkgFinder, whereas the stability rankings by BestKeeper and NormFinder were notably different. We then validated the suitability of six candidate reference genes (ACT1, PGK1, RDN5.8, RDN18, UBC7, and UBC13) as internal controls for ten target genes in this system using the comparative C-T method. Our validation experiments passed for all six reference genes analyzed except RDN18, where the amplification efficiency of RDN18 was different from that of the ten target genes. Finally, we demonstrated that the relative quantification of target gene expression varied according to the endogenous control used, highlighting the importance of the choice of internal controls in such experiments.
Conclusions: We recommend the use of RDN5.8, UBC13, and PGK1 alone or the combination of RDN5.8 plus UBC13 or PGK1 as reference genes for RT-qPCR analysis of gene expression in C. glabrata following azole treatment. In contrast, we show that ACT1 and other commonly used reference genes (GAPDH, PPIA, RPL13A, TUB1, etc.) were not validated as good internal controls in the current model.
C1 [Li, Qingdi Quentin; Bennett, John E.] NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Skinner, Jeff] NIAID, Bioinformat & Computat Biosciences Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Li, QQ (reprint author), NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM liquenti@niaid.nih.gov
OI Skinner, Jeff/0000-0001-5697-0442
FU National Institute of Allergy and Infectious Diseases, the National
Institutes of Health
FX We sincerely thank Huei-Fung Tsai, Jason Noble, and Bryan Walker for
useful discussions and gratefully acknowledge Jason Noble for helpful
technical assistance. This research was supported by the Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases, the National Institutes of Health.
NR 61
TC 20
Z9 31
U1 1
U2 29
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2199
J9 BMC MOL BIOL
JI BMC Mol. Biol.
PD JUN 29
PY 2012
VL 13
AR 22
DI 10.1186/1471-2199-13-22
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 027NH
UT WOS:000310358900001
PM 22747760
ER
PT J
AU Raghavachari, N
Barb, J
Yang, YQ
Liu, PC
Woodhouse, K
Levy, D
O'Donnell, CJ
Munson, PJ
Kato, GJ
AF Raghavachari, Nalini
Barb, Jennifer
Yang, Yanqin
Liu, Poching
Woodhouse, Kimberly
Levy, Daniel
O'Donnell, Christopher J.
Munson, Peter J.
Kato, Gregory J.
TI A systematic comparison and evaluation of high density exon arrays and
RNA-seq technology used to unravel the peripheral blood transcriptome of
sickle cell disease
SO BMC MEDICAL GENOMICS
LA English
DT Article
DE Sickle cell disease; RNA-Seq; Exon arrays; Transcriptome; Clinical
genomics
ID GENE-EXPRESSION PROFILES; MESSENGER-RNA; DISCOVERY; MEDICINE; SYNTHASE;
PCR
AB Background: Transcriptomic studies in clinical research are essential tools for deciphering the functional elements of the genome and unraveling underlying disease mechanisms. Various technologies have been developed to deduce and quantify the transcriptome including hybridization and sequencing-based approaches. Recently, high density exon microarrays have been successfully employed for detecting differentially expressed genes and alternative splicing events for biomarker discovery and disease diagnostics. The field of transcriptomics is currently being revolutionized by high throughput DNA sequencing methodologies to map, characterize, and quantify the transcriptome.
Methods: In an effort to understand the merits and limitations of each of these tools, we undertook a study of the transcriptome in sickle cell disease, a monogenic disease comparing the Affymetrix Human Exon 1.0 ST microarray (Exon array) and Illumina's deep sequencing technology (RNA-seq) on whole blood clinical specimens.
Results: Analysis indicated a strong concordance (R = 0.64) between Exon array and RNA-seq data at both gene level and exon level transcript expression. The magnitude of differential expression was found to be generally higher in RNA-seq than in the Exon microarrays. We also demonstrate for the first time the ability of RNA-seq technology to discover novel transcript variants and differential expression in previously unannotated genomic regions in sickle cell disease. In addition to detecting expression level changes, RNA-seq technology was also able to identify sequence variation in the expressed transcripts.
Conclusions: Our findings suggest that microarrays remain useful and accurate for transcriptomic analysis of clinical samples with low input requirements, while RNA-seq technology complements and extends microarray measurements for novel discoveries.
C1 [Raghavachari, Nalini; Yang, Yanqin; Liu, Poching; Woodhouse, Kimberly] NHLBI, Genom Core Facil, NIH, Bethesda, MD 20892 USA.
[Barb, Jennifer; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Kato, Gregory J.] NIH, Hematol Branch, Bethesda, MD 20892 USA.
[Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] NHLBI, Ctr Cardiovasc Genom, Bethesda, MD 20892 USA.
RP Raghavachari, N (reprint author), NHLBI, Genom Core Facil, NIH, 10 Ctr Dr,Bldg 10,8C 103B, Bethesda, MD 20892 USA.
EM nraghavachari@nhlbi.nih.gov
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU NHLBI Division of Intramural Research [1 ZIA HL006013-03]; CIT Division
of Computational Bioscience
FX We gratefully acknowledge Drs. Kairong Cui and Keji Zhao for their help
in library construction and sequencing. We thank Dr. Shurjo Sen NHGRI
for his valuable time and advice in analyzing the sequence data. We
acknowledge the help of Ms. Marlene Peters-Lawrence for her assistance
in collecting these specimens from volunteers and thank the sickle cell
and healthy control subjects who participated in this study. This work
was funded by the NHLBI Division of Intramural Research (1 ZIA
HL006013-03) and by the CIT Division of Computational Bioscience.
NR 38
TC 34
Z9 34
U1 2
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD JUN 29
PY 2012
VL 5
AR 28
DI 10.1186/1755-8794-5-28
PG 20
WC Genetics & Heredity
SC Genetics & Heredity
GA 996MB
UT WOS:000308091400001
PM 22747986
ER
PT J
AU Yuan, QP
Zhou, ZF
Lindell, SG
Higley, JD
Ferguson, B
Thompson, RC
Lopez, JF
Suomi, SJ
Baghal, B
Baker, M
Mash, DC
Barr, CS
Goldman, D
AF Yuan, Qiaoping
Zhou, Zhifeng
Lindell, Stephen G.
Higley, J. Dee
Ferguson, Betsy
Thompson, Robert C.
Lopez, Juan F.
Suomi, Stephen J.
Baghal, Basel
Baker, Maggie
Mash, Deborah C.
Barr, Christina S.
Goldman, David
TI The rhesus macaque is three times as diverse but more closely equivalent
in damaging coding variation as compared to the human
SO BMC GENETICS
LA English
DT Article
DE Rhesus macaque; Human; Single nucleotide polymorphism; Diversity;
Comparative genomics
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; MACACA-MULATTA; LINKAGE DISEQUILIBRIUM;
CANDIDATE GENES; MUTATION-RATES; INDIAN-ORIGIN; CHINESE; GENOME; SNPS;
INHERITANCE
AB Background: As a model organism in biomedicine, the rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of genetic variation of this species to humans. Comparative analysis of functional and nonfunctional diversity in this highly abundant and adaptable non-human primate could inform its use as a model for human biology, and could reveal how variation in population history and size alters patterns and levels of sequence variation in primates.
Results: We sequenced the mRNA transcriptome and H3K4me3-marked DNA regions in hippocampus from 14 humans and 14 rhesus macaques. Using equivalent methodology and sampling spaces, we identified 462,802 macaque SNPs, most of which were novel and disproportionately located in the functionally important genomic regions we had targeted in the sequencing. At least one SNP was identified in each of 16,797 annotated macaque genes. Accuracy of macaque SNP identification was conservatively estimated to be >90%. Comparative analyses using SNPs equivalently identified in the two species revealed that rhesus macaque has approximately three times higher SNP density and average nucleotide diversity as compared to the human. Based on this level of diversity, the effective population size of the rhesus macaque is approximately 80,000 which contrasts with an effective population size of less than 10,000 for humans. Across five categories of genomic regions, intergenic regions had the highest SNP density and average nucleotide diversity and CDS (coding sequences) the lowest, in both humans and macaques. Although there are more coding SNPs (cSNPs) per individual in macaques than in humans, the ratio of d(N)/d(S) is significantly lower in the macaque. Furthermore, the number of damaging nonsynonymous cSNPs (have damaging effects on protein functions from PolyPhen 2 prediction) in the macaque is more closely equivalent to that of the human.
Conclusions: This large panel of newly identified macaque SNPs enriched for functionally significant regions considerably expands our knowledge of genetic variation in the rhesus macaque. Comparative analysis reveals that this widespread, highly adaptable species is approximately three times as diverse as the human but more closely equivalent in damaging variation.
C1 [Yuan, Qiaoping; Zhou, Zhifeng; Lindell, Stephen G.; Baghal, Basel; Baker, Maggie; Barr, Christina S.; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Higley, J. Dee] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA.
[Ferguson, Betsy] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA.
[Thompson, Robert C.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48104 USA.
[Lopez, Juan F.] Univ Michigan, Med Ctr, Mental Hlth Res Inst, Ann Arbor, MI 48104 USA.
[Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA.
[Mash, Deborah C.] Univ Miami, Sch Med, Dept Neurol, Miami, FL 33136 USA.
RP Barr, CS (reprint author), NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM cbarr@mail.nih.gov; davidgoldman@mail.nih.gov
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health. We thank Elisa Moore for IT support. An earlier version of
the paper appeared in the Proceedings of the 2011 International
Conference on Bioinformatics & Computational Biology.
NR 34
TC 15
Z9 15
U1 1
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2156
J9 BMC GENET
JI BMC Genet.
PD JUN 29
PY 2012
VL 13
AR 52
DI 10.1186/1471-2156-13-52
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 994PP
UT WOS:000307943600001
PM 22747632
ER
PT J
AU Harzer, K
Blech-Hermoni, Y
Goldin, E
Felderhoff-Mueser, U
Igney, C
Sidransky, E
Yildiz, Y
AF Harzer, Klaus
Blech-Hermoni, Yotam
Goldin, Ehud
Felderhoff-Mueser, Ursula
Igney, Claudia
Sidransky, Ellen
Yildiz, Yildiz
TI Beta-glucosidase 1 (GBA1) is a second bile acid beta-glucosidase in
addition to beta-glucosidase 2 (GBA2). Study in beta-glucosidase
deficient mice and humans
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE beta-Glucosidase 1 (GBA1); beta-Glucosidase 2 (GBA2); Bile acid
beta-glucosidases; Glucosylceramide lipidosis; beta-Glucosidase null
mice; Isofagomine
ID TYPE-2 GAUCHER-DISEASE; HUMAN-LIVER; BETA-GLUCOSIDASE-2; IDENTIFICATION;
GLUCOCEREBROSIDASE; ACCUMULATION; PURIFICATION; ISOFAGOMINE; MUTATION
AB Beta-glucosidase 1 (GBA1; lysosomal glucocerebrosidase) and beta-glucosidase 2 (GBA2, non-lysosomal glucocerebrosidase) both have glucosylceramide as a main natural substrate. The enzyme-deficient conditions with glucosylceramide accumulation are Gaucher disease (GBA-/- in humans), modelled by the Gba-/- mouse, and the syndrome with male infertility in the Gba2-/- mouse, respectively. Before the leading role of glucosylceramide was recognised for both deficient conditions, bile acid-3-O-beta-glucoside (BG), another natural substrate, was viewed as the main substrate of GBA2. Given that GBA2 hydrolyses both BG and glucosylceramide, it was asked whether vice versa GBA1 hydrolyses both glucosylceramide and BG. Here we show that GBA1 also hydrolyses BG. We compared the residual BG hydrolysing activities in the GBA1-/-, Gba1-/- conditions (where GBA2 is the almost only active beta-glucosidase) and those in the Gba2-/- condition (GBA1 active), with wild-type activities, but we used also the GBA1 inhibitor isofagomine. GBA1 and GBA2 activities had characteristic differences between the studied fibroblast, liver and brain samples. Independently, the hydrolysis of BG by pure recombinant GBA1 was shown. The fact that both GBA1 and GBA2 are glucocerebrosidases as well as bile acid beta-glucosidases raises the question, why lysosomal accumulation of glucosylceramide in GBA1 deficiency, and extra-lysosomal accumulation in GBA2 deficiency, are not associated with an accumulation of BG in either condition. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Yildiz, Yildiz] Univ Clin, Dept Internal Med 1, D-53105 Bonn, Germany.
[Harzer, Klaus] Univ Tubingen, Neurometabol Lab, Klin Kinder & Jugendmed, Tubingen, Germany.
[Blech-Hermoni, Yotam; Goldin, Ehud; Sidransky, Ellen] NIH, NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Felderhoff-Mueser, Ursula] Univ Essen Gesamthsch, Kinderklin, Essen, Germany.
[Igney, Claudia] Siemens MRT Grp, Erlangen, Germany.
[Yildiz, Yildiz] Univ Clin Bonn, Dept Internal Med 1, Bonn, Germany.
RP Yildiz, Y (reprint author), Univ Clin, Dept Internal Med 1, Sigmund Freud Str 25, D-53105 Bonn, Germany.
EM yildiz.yildiz@ukb.uni-bonn.de
FU DFG [YI 100/1, SFB 645]; National Human Genome Research Institute;
National Institutes of Health
FX The work was supported by DFG Grants YI 100/1 and SFB 645. It was also
supported in part by the intramural research programme of the National
Human Genome Research Institute and the National Institutes of Health.
We thank Dr. B. Kustermann-Kuhn, Neurometabolic Laboratory, Children's
Hospital, University of Tubingen, Germany, for help with cell cultures,
Dr. A. Rolfs, Department of Neurology, University of Rostock, Germany,
for mutation analysis of patients G2, and Dr. A. Gal, Department of
Human Genetics, University of Hamburg, Germany, for the mutation
analysis of patient,G4.
NR 18
TC 4
Z9 4
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUN 29
PY 2012
VL 423
IS 2
BP 308
EP 312
DI 10.1016/j.bbrc.2012.05.117
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 974NR
UT WOS:000306443500018
PM 22659419
ER
PT J
AU Sricholpech, M
Perdivara, I
Yokoyama, M
Nagaoka, H
Terajima, M
Tomer, KB
Yamauchi, M
AF Sricholpech, Marnisa
Perdivara, Irina
Yokoyama, Megumi
Nagaoka, Hideaki
Terajima, Masahiko
Tomer, Kenneth B.
Yamauchi, Mitsuo
TI Lysyl Hydroxylase 3-mediated Glucosylation in Type I Collagen MOLECULAR
LOCI AND BIOLOGICAL SIGNIFICANCE
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CROSS-LINKING; BONE-COLLAGEN; OSTEOGENESIS IMPERFECTA; TRABECULAR BONE;
POSTTRANSLATIONAL MODIFICATIONS; MATRIX MINERALIZATION;
ARTICULAR-CARTILAGE; GLYCOSYLATED COLLAGEN; AMINO-ACIDS; RAT
AB Recently, by employing the short hairpin RNA technology, we have generated MC3T3-E1 (MC)-derived clones stably suppressing lysyl hydroxylase 3 (LH3) (short hairpin (Sh) clones) and demonstrated the LH3 function as glucosyltransferase in type I collagen (Sricholpech, M., Perdivara, I., Nagaoka, H., Yokoyama, M., Tomer, K. B., and Yamauchi, M. (2011) Lysyl hydroxylase 3 glucosylates galactosylhydroxylysine residues in type I collagen in osteoblast culture. J. Biol. Chem. 286, 8846-8856). To further elucidate the biological significance of this modification, we characterized and compared type I collagen phenotypes produced by Sh clones and two control groups, MC and those transfected with empty vector. Mass spectrometric analysis identified five glycosylation sites in type I collagen (i.e. alpha 1,2-87, alpha 1,2-174, and alpha 2-219. Of these, the predominant glycosylation site was alpha 1-87, one of the major helical cross-linking sites. In Sh collagen, the abundance of glucosylgalactosylhydroxylysine was significantly decreased at all of the five sites with a concomitant increase in galactosylhydroxylysine at four of these sites. The collagen cross-links were significantly diminished in Sh clones, and, for the major cross-link, dihydroxylysinonorleucine (DHLNL), glucosylgalactosyl-DHLNL was diminished with a concomitant increase in galactosyl-DHLNL. When subjected to in vitro incubation, in Sh clones, the rate of decrease in DHLNL was lower, whereas the rate of increase in its maturational cross-link, pyridinoline, was comparable with controls. Furthermore, in Sh clones, the mean diameters of collagen fibrils were significantly larger, and the onset of mineralized nodule formation was delayed when compared with those of controls. These results indicate that the LH3-mediated glucosylation occurs at the specific molecular loci in the type I collagen molecule and plays critical roles in controlling collagen cross-linking, fibrillogenesis, and mineralization.
C1 [Yamauchi, Mitsuo] Univ N Carolina, NC Oral Hlth Inst, Sch Dent, Chapel Hill, NC 27599 USA.
[Perdivara, Irina; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Yamauchi, M (reprint author), Univ N Carolina, NC Oral Hlth Inst, Sch Dent, CB 7454, Chapel Hill, NC 27599 USA.
EM mitsuo_yamauchi@dentistry.unc.edu
RI Tomer, Kenneth/E-8018-2013;
OI Sricholpech, Marnisa/0000-0003-2139-0688
FU National Institutes of Health [R21 DE019569, DE020909, AR060978];
National Institutes of Health, NIEHS [ES050171]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R21 DE019569, DE020909, and AR060978 and the Intramural
Research Program of National Institutes of Health, NIEHS, Project
ES050171.
NR 81
TC 33
Z9 35
U1 1
U2 28
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 29
PY 2012
VL 287
IS 27
BP 22998
EP 23009
DI 10.1074/jbc.M112.343954
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 975GB
UT WOS:000306495000056
PM 22573318
ER
PT J
AU Chen, G
Ghosh, P
O'Farrell, T
Munk, R
Rezanka, LJ
Sasaki, CY
Longo, DL
AF Chen, Gang
Ghosh, Paritosh
O'Farrell, Thomas
Munk, Rachel
Rezanka, Louis J.
Sasaki, Carl Y.
Longo, Dan L.
TI Transforming Growth Factor beta 1 (TGF-beta 1) Suppresses Growth of
B-cell Lymphoma Cells by p14(ARF)-dependent Regulation of Mutant p53
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ARF TUMOR-SUPPRESSOR; FUNCTION PHENOTYPE; GENE-EXPRESSION; CYCLE ARREST;
WILD-TYPE; IN-VIVO; GAIN; P19(ARF); MDM2; PROTEINS
AB Previously we reported that TGF-beta 1-induced growth suppression was associated with a decrease in mutant p53 levels in B-cell lymphoma cells. The goal of the present study was to understand the mechanism involved in TGF-beta 1-mediated down-regulation of mutant p53. In RL and CA46, two B-cell lymphoma cell lines, TGF-beta 1 treatment caused down-regulation of E2F-1 transcription factor resulting in the down-regulation of both p14(ARF) and mutant p53, leading to growth arrest. Experimental overexpression of E2F-1 increased p14(ARF) level and blocked TGF-beta 1-induced down-regulation of p14(ARF). Overexpression of p14(ARF) blocked the down-regulation of mutant p53 and prevented growth arrest. p14(ARF) also attenuated TGF-beta 1-induced p21(Cip1/WAF1) induction, which was reversible by p53 siRNA, indicating the involvement of mutant p53 in controlling the TGF-beta 1-induced expression of p21(Cip1/WAF1). The interaction observed between phospho-Smad2 and mutant p53 in the nucleus could be the mechanism responsible for blocking the growth-suppressive effects of TGF-beta 1. In RL cells, p14(ARF) is present in a trimer consisting of mutant p53-Mdm2-p14(ARF) and in a dimer consisting of Mdm2-p14(ARF). Because it is known that Mdm2 can degrade p53, it is possible that, in its trimeric form, p14(ARF) is able to stabilize mutant p53 by inhibiting Mdm2. In its dimeric form, p14(ARF) may be sequestering Mdm2, limiting its ability to degrade p53. Collectively, these data demonstrate a unique mechanism in which the inhibition of TGF-beta 1-mediated growth suppression by mutant p53 can be reversed by the down-regulation of its stabilizing protein p14(ARF). This work suggests that the high levels of p14(ARF) often found in tumor cells could be a potential therapeutic target.
C1 [Ghosh, Paritosh] NIA, Lymphocyte Cell Biol Unit, Lab Mol Biol & Immunol, Biomed Res Ctr,Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Ghosh, P (reprint author), NIA, Lymphocyte Cell Biol Unit, Lab Mol Biol & Immunol, Biomed Res Ctr,Intramural Res Program,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM ghoshp@grc.nia.nih.gov
FU NIA, National Institutes of Health Intramural Research Program
FX This work was supported, in whole or in part, by the NIA, National
Institutes of Health Intramural Research Program.
NR 57
TC 4
Z9 4
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 29
PY 2012
VL 287
IS 27
BP 23184
EP 23195
DI 10.1074/jbc.M112.351411
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 975GB
UT WOS:000306495000073
PM 22621932
ER
PT J
AU Sato, Y
Hatta, M
Karim, MF
Sawa, T
Wei, FY
Sato, S
Magnuson, MA
Gonzalez, FJ
Tomizawa, K
Akaike, T
Yoshizawa, T
Yamagata, K
AF Sato, Yoshifumi
Hatta, Mitsutoki
Karim, Md Fazlul
Sawa, Tomohiro
Wei, Fan-Yan
Sato, Shoki
Magnuson, Mark A.
Gonzalez, Frank J.
Tomizawa, Kazuhito
Akaike, Takaaki
Yoshizawa, Tatsuya
Yamagata, Kazuya
TI Anks4b, a Novel Target of HNF4 alpha Protein, Interacts with GRP78
Protein and Regulates Endoplasmic Reticulum Stress-induced Apoptosis in
Pancreatic beta-Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NUCLEAR FACTOR 4-ALPHA; INSULIN-SECRETION; HYPERINSULINEMIC
HYPOGLYCEMIA; ALPHA-GENE; HEPATOCYTE; TRANSCRIPTION; EXPRESSION;
MUTATIONS; MODY1; HNF-4-ALPHA
AB Mutations of the HNF4A gene cause a form of maturity-onset diabetes of the young (MODY1) that is characterized by impairment of pancreatic beta-cell function. HNF4 alpha is a transcription factor belonging to the nuclear receptor superfamily (NR2A1), but its target genes in pancreatic beta-cells are largely unknown. Here, we report that ankyrin repeat and sterile alpha motif domain containing 4b (Anks4b) is a target of HNF4 alpha in pancreatic beta-cells. Expression of Anks4b was decreased in both beta HNF4 alpha KO islets and HNF4 alpha knockdown MIN6 beta-cells, and HNF4 alpha activated Anks4b promoter activity. Anks4b bound to glucose-regulated protein 78 (GRP78), a major endoplasmic reticulum (ER) chaperone protein, and overexpression of Anks4b enhanced the ER stress response and ER stress-associated apoptosis of MIN6 cells. Conversely, suppression of Anks4b reduced beta-cell susceptibility to ER stress-induced apoptosis. These results indicate that Anks4b is a HNF4 alpha target gene that regulates ER stress in beta-cells by interacting with GRP78, thus suggesting that HNF4 alpha is involved in maintenance of the ER.
C1 [Sato, Yoshifumi; Hatta, Mitsutoki; Karim, Md Fazlul; Sato, Shoki; Yoshizawa, Tatsuya; Yamagata, Kazuya] Kumamoto Univ, Fac Life Sci, Dept Med Biochem, Kumamoto 8608556, Japan.
[Sawa, Tomohiro; Akaike, Takaaki] Kumamoto Univ, Fac Life Sci, Dept Microbiol, Kumamoto 8608556, Japan.
[Sawa, Tomohiro] Japan Sci & Technol Agcy JST, PRESTO, Kawaguchi, Saitama 332001, Japan.
[Wei, Fan-Yan; Tomizawa, Kazuhito] Kumamoto Univ, Fac Life Sci, Dept Mol Physiol, Kumamoto 8608556, Japan.
[Magnuson, Mark A.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20814 USA.
RP Yamagata, K (reprint author), Kumamoto Univ, Fac Life Sci, Dept Med Biochem, Kumamoto 8608556, Japan.
EM k-yamaga@kumamoto-u.ac.jp
RI Tomizawa, Kazuhito/F-2405-2015; Magnuson, Mark/B-1335-2009
OI Tomizawa, Kazuhito/0000-0002-5663-2627; Magnuson,
Mark/0000-0002-8824-6499
FU Ministry of Health Labour and Welfare; Takeda Science Foundation; Novo
Nordisk Insulin Research Foundation; Banyu Life Science Foundation
International; Japan Diabetes Foundation; International Priority
Graduate Programs Advanced Graduate Courses for International Students,
Ministry of Education, Culture, Sports, Science, and Technology in Japan
FX This work was supported by a grant-in-aid for scientific research (B), a
grant-in-aid for scientific research (S), a grant-in-aid for scientific
research in innovative areas, a grant from the Ministry of Health Labour
and Welfare, a grant from Takeda Science Foundation, a grant from Novo
Nordisk Insulin Research Foundation, a grant from Banyu Life Science
Foundation International, and a grant from Japan Diabetes Foundation.;
Supported by a scholarship from the International Priority Graduate
Programs Advanced Graduate Courses for International Students, Ministry
of Education, Culture, Sports, Science, and Technology in Japan.
NR 41
TC 11
Z9 12
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 29
PY 2012
VL 287
IS 27
BP 23236
EP 23245
DI 10.1074/jbc.M112.368779
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 975GB
UT WOS:000306495000078
PM 22589549
ER
PT J
AU Kageyama, R
Cannons, JL
Zhao, F
Yusuf, I
Lao, C
Locci, M
Schwartzberg, PL
Crotty, S
AF Kageyama, Robin
Cannons, Jennifer L.
Zhao, Fang
Yusuf, Isharat
Lao, Christopher
Locci, Michela
Schwartzberg, Pamela L.
Crotty, Shane
TI The Receptor Ly108 Functions as a SAP Adaptor-Dependent On-Off Switch
for T Cell Help to B Cells and NKT Cell Development
SO IMMUNITY
LA English
DT Article
ID LINKED LYMPHOPROLIFERATIVE-DISEASE; SLAM FAMILY RECEPTORS;
NATURAL-KILLER-CELLS; PROTEIN-TYROSINE-PHOSPHATASE; MOLECULE-ASSOCIATED
PROTEIN; CHRONIC VIRAL-INFECTION; HUMORAL IMMUNITY; GERMINAL-CENTER;
CUTTING EDGE; GENE-PRODUCT
AB Humans and mice deficient in the adaptor protein SAP (Sh2d1a) have a major defect in humoral immunity, resulting from a lack of T cell help for B cells. The role of SAP in this process is incompletely understood. We found that deletion of receptor Ly108 (Slamf6) in CD4(+) T cells reversed the Sh2d1a(-/-) phenotype, eliminating the SAP requirement for germinal centers. This potent negative signaling by Ly108 required immunotyrosine switch motifs (ITSMs) and SHP-1 recruitment, resulting in high amounts of SHP-1 at the T cell:B cell synapse, limiting T cell:B cell adhesion. Ly108-negative signaling was important not only in CD4(+) T cells; we found that NKT cell differentiation was substantially restored in Slamf6(-/-)Sh2d1a(-/-) mice. The ability of SAP to regulate both positive and negative signals in T cells can explain the severity of SAP deficiency and highlights the importance of SAP and SHP-1 competition for Ly108 ITSM binding as a rheostat for the magnitude of T cell help to B cells.
C1 [Kageyama, Robin; Yusuf, Isharat; Lao, Christopher; Locci, Michela; Crotty, Shane] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA.
[Cannons, Jennifer L.; Zhao, Fang; Schwartzberg, Pamela L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Zhao, Fang] Addenbrookes Hosp, Cambridge Inst Med Res, Dept Med, Cambridge CB2 0XY, England.
[Crotty, Shane] Univ Calif San Diego, Dept Med, Sch Med, La Jolla, CA 92037 USA.
RP Crotty, S (reprint author), La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA.
EM shane@liai.org
FU NIH; LIAI; NIH NHGRI
FX We thank I. Engel and M. Kronenberg for technical advice. Slamf6 mice
were obtained through the NIH KOMP Repository program. This work was
supported by NIH grants and LIAI institutional funds (S.C.) and the NIH
NHGRI intramural program (P.L.S., J.L.C., F.Z.). F.Z. is a Scholar in
the NIH-Oxford-Cambridge Scholars in Biomedical Research program.
NR 86
TC 68
Z9 69
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JUN 29
PY 2012
VL 36
IS 6
BP 986
EP 1002
DI 10.1016/j.immuni.2012.05.016
PG 17
WC Immunology
SC Immunology
GA 969ZE
UT WOS:000306097100016
PM 22683125
ER
PT J
AU Zhao, F
Cannons, JL
Dutta, M
Griffiths, GM
Schwartzberg, PL
AF Zhao, Fang
Cannons, Jennifer L.
Dutta, Mala
Griffiths, Gillian M.
Schwartzberg, Pamela L.
TI Positive and Negative Signaling through SLAM Receptors Regulate Synapse
Organization and Thresholds of Cytolysis
SO IMMUNITY
LA English
DT Article
ID LINKED LYMPHOPROLIFERATIVE-DISEASE; NATURAL-KILLER-CELLS;
PROTEIN-TYROSINE-PHOSPHATASE; T-CELL; IMMUNOLOGICAL SYNAPSE; IMMUNE
SYNAPSE; CYTOKINE PRODUCTION; SECRETORY DOMAIN; INFECTED CELLS; ENCODING
GENE
AB X-linked lymphoproliferative syndrome, characterized by fatal responses to Epstein-Barr virus infection, is caused by mutations affecting the adaptor SAP, which links SLAM family receptors to downstream signaling. Although cytotoxic defects in SAP-deficient T cells are documented, the mechanism remains unclear. We show that SAP-deficient murine CD8(+) T cells exhibited normal cytotoxicity against fibrosarcoma targets, yet had impaired adhesion to and killing of B cell and low-avidity T cell targets. SAP-deficient cytotoxic lymphocytes showed specific defects in immunological synapse organization with these targets, resulting in inefficient actin clearance. In the absence of SAP, signaling through the SLAM family members Ly108 and 2B4 resulted in increased recruitment of the SHP-1 phosphatase, associated with altered SHP-1 localization and decreased activation of Src kinases at the synapse. Hence, SAP and SLAM receptors regulate positive and negative signals required for organizing the T cell:B cell synapse and setting thresholds for cytotoxicity against distinct cellular targets.
C1 [Zhao, Fang; Griffiths, Gillian M.] Addenbrookes Hosp, Cambridge Inst Med Res, Dept Med, Cambridge CB2 0XY, England.
[Zhao, Fang; Cannons, Jennifer L.; Dutta, Mala; Schwartzberg, Pamela L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP Griffiths, GM (reprint author), Addenbrookes Hosp, Cambridge Inst Med Res, Dept Med, Hills Rd, Cambridge CB2 0XY, England.
EM gg305@cam.ac.uk; pams@mail.nih.gov
OI Griffiths, Gillian/0000-0003-0434-5842
FU National Human Genome Research Institute; Wellcome Trust [085880]
FX The authors would like to thank J. Reilley, R. Handon, S. Wincovitch, S.
Anderson, and J. Fekecs for assistance. This work was funded in part by
the intramural program of the National Human Genome Research Institute
and by the Wellcome Trust (085880 to G.M.G.). F.Z. was a Scholar in the
NIH-Oxford-Cambridge Scholars in Biomedical Research program.
NR 56
TC 46
Z9 46
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JUN 29
PY 2012
VL 36
IS 6
BP 1003
EP 1016
DI 10.1016/j.immuni.2012.05.017
PG 14
WC Immunology
SC Immunology
GA 969ZE
UT WOS:000306097100017
PM 22683123
ER
PT J
AU Hirahara, K
Ghoreschi, K
Yang, XP
Takahashi, H
Laurence, A
Vahedi, G
Sciume, G
Hall, AO
Dupont, CD
Francisco, LM
Chen, Q
Tanaka, M
Kanno, Y
Sun, HW
Sharpe, AH
Hunter, CA
O'Shea, JJ
AF Hirahara, Kiyoshi
Ghoreschi, Kamran
Yang, Xiang-Ping
Takahashi, Hayato
Laurence, Arian
Vahedi, Golnaz
Sciume, Giuseppe
Hall, Aisling O'Hara
Dupont, Christopher D.
Francisco, Loise M.
Chen, Qian
Tanaka, Masao
Kanno, Yuka
Sun, Hong-Wei
Sharpe, Arlene H.
Hunter, Christopher A.
O'Shea, John J.
TI Interleukin-27 Priming of T Cells Controls IL-17 Production In trans via
Induction of the Ligand PD-L1
SO IMMUNITY
LA English
DT Article
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PROINFLAMMATORY CYTOKINE
PRODUCTION; TH1 DIFFERENTIATION; GRAVES-DISEASE; CUTTING EDGE; C-MAF;
IL-27; EXPRESSION; RECEPTOR; INFLAMMATION
AB Interleukin-27 (IL-27) is a key immunosuppressive cytokine that counters T helper 17 (Th17) cell-mediated pathology. To identify mechanisms by which IL-27 might exert its immunosuppressive effect, we analyzed genes in T cells rapidly induced by IL-27. We found that IL-27 priming of naive T cells upregulated expression of programmed death ligand 1 (PD-L1) in a signal transducer and activator of transcription 1 (STAT1)-dependent manner. When cocultured with naive CD4(+) T cells, IL-27-primed T cells inhibited the differentiation of Th17 cells in trans through a PD-1-PD-L1 interaction. In vivo, coadministration of naive TCR transgenic T cells (2D2 T cells) with IL-27-primed T cells expressing PD-L1 inhibited the development of Th17 cells and protected from severe autoimmune encephalomyelitis. Thus, these data identify a suppressive activity of IL-27, by which CD4(+) T cells can restrict differentiation of Th17 cells in trans.
C1 [Hirahara, Kiyoshi; Ghoreschi, Kamran; Yang, Xiang-Ping; Takahashi, Hayato; Laurence, Arian; Vahedi, Golnaz; Sciume, Giuseppe; Kanno, Yuka; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Qian] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Tanaka, Masao] NIAMSD, Translat Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Sun, Hong-Wei] NIAMSD, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA.
[Hall, Aisling O'Hara; Dupont, Christopher D.; Hunter, Christopher A.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA.
[Francisco, Loise M.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
RP Hirahara, K (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
EM hiraharak@mail.nih.gov; osheajo@mail.nih.gov
RI Kanno, Yuka/B-5802-2013; Laurence, Arian/A-8770-2009; Sciume,
Giuseppe/K-8985-2016; Hirahara, Kiyoshi/E-2460-2017;
OI Laurence, Arian/0000-0003-0942-8292; Sciume,
Giuseppe/0000-0003-0131-512X; Hirahara, Kiyoshi/0000-0002-9128-9449;
Kanno, Yuka/0000-0001-5668-9319
FU NIAMS; JSPS at NIH; Istituto Pasteur-Fondazione Cenci-Bolognetti; NIH
[R01 AI 42334, R01 AI 40614, R37 AI 38310]; NIAID
FX We thank M. Pelletier (Autoimmunity Branch, NIAMS), J. Simone, J. Lay
(Flow Cytometry Section, NIAMS), and the NIAMS LACU staff for their
excellent technical support. We thank A. Villarino for critically
reading this manuscript and providing helpful suggestions. This work was
supported by the Intramural Research Programs of NIAMS, NIAID, the JSPS
Research Fellowship for Japanese Biomedical and Behavioral Researchers
at NIH (K.H. and H.T.), Istituto Pasteur-Fondazione Cenci-Bolognetti
(G.S.), NIH R01 AI 42334 (C.A.H.), NIH R01 AI 40614 (A.H.S.), and NIH
R37 AI 38310 (A.H.S.). K.H. and K.G. designed, performed, analyzed, and
interpreted all the experiments and wrote the manuscript. X.-P.Y., H.T.,
A.L., G.S., A.O'H.H., C.D.D., L.M.F., Q.C., and M.T. helped with
performing experiments. H.-W.S. and G.V. interpreted the microarray
experiments and ChIP-seq data. Y.K., A.H.S., and C.A.H. contributed to
the experimental design and data interpretation and made helpful
suggestions. J.J.O'S. contributed to experiment design, analyzed and
interpreted all acquired data, and helped to write the manuscript.
NR 51
TC 90
Z9 97
U1 3
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JUN 29
PY 2012
VL 36
IS 6
BP 1017
EP 1030
DI 10.1016/j.immuni.2012.03.024
PG 14
WC Immunology
SC Immunology
GA 969ZE
UT WOS:000306097100018
PM 22726954
ER
PT J
AU Goldszmid, RS
Caspar, P
Rivollier, A
White, S
Dzutsev, A
Hieny, S
Kelsall, B
Trinchieri, G
Sher, A
AF Goldszmid, Romina S.
Caspar, Pat
Rivollier, Aymeric
White, Sandy
Dzutsev, Amiran
Hieny, Sara
Kelsall, Brian
Trinchieri, Giorgio
Sher, Alan
TI NK Cell-Derived Interferon-gamma Orchestrates Cellular Dynamics and the
Differentiation of Monocytes into Dendritic Cells at the Site of
Infection
SO IMMUNITY
LA English
DT Article
ID TOXOPLASMA-GONDII INFECTION; NECROSIS-FACTOR-ALPHA;
NATURAL-KILLER-CELLS; INNATE IMMUNE DEFENSE; IFN-GAMMA; IN-VIVO;
INFLAMMATORY MONOCYTES; IL-12 PRODUCTION; CUTTING EDGE; RESISTANCE
AB Dendritic cells (DCs), monocytes, and/or macrophages initiate host-protective immune responses to intracellular pathogens in part through interleukin-12 (IL-12) production, although the relative contribution of tissue resident versus recruited cells has been unclear. Here, we showed that after intra-peritoneal infection with Toxoplasma gondii cysts, resident mononuclear phagocytes are replaced by circulating monocytes that differentiate in situ into inflammatory DCs (moDCs) and F4/80(+) macrophages. Importantly, NK cell-derived interferon-gamma (IFN-gamma) was required for both the loss of resident mononuclear phagocytes and the local differentiation of monocytes into macrophages and moDCs. This newly generated moDC population and not the resident DCs (or macrophages) served as the major source of IL-12 at the site of infection. Thus, NK cell-derived IFN-gamma is important in both regulating inflammatory cell dynamics and in driving the local differentiation of monocytes into the cells required for initiating the immune response to an important intracellular pathogen.
C1 [Goldszmid, Romina S.; Dzutsev, Amiran; Trinchieri, Giorgio] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,Natl Inst Hlth, Frederick, MD 21702 USA.
[Goldszmid, Romina S.; Caspar, Pat; White, Sandy; Hieny, Sara; Trinchieri, Giorgio; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Rivollier, Aymeric; Kelsall, Brian] NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Dzutsev, Amiran] SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Goldszmid, RS (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,Natl Inst Hlth, Frederick, MD 21702 USA.
EM rgoldszmid@mail.nih.gov; trinchig@mail.nih.gov; asher@niaid.nih.gov
FU MAID; NCI; NIH
FX We are grateful to the NIAID Flow Cytometry core facility and in
particular T. Moyer for performing sorting. We are also indebted to R.
Locksley for kindly providing the Yet40 mice and M. Grigg for the RFP
expressing parasites. We also gratefully acknowledge D. McVicar, K.
Mayer-Barber, and D. Barber for critical reading of the manuscript. This
research was supported by the Intramural Research Program of the MAID
and NCI, NIH. The authors have no conflicting financial interests.
NR 50
TC 96
Z9 98
U1 1
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JUN 29
PY 2012
VL 36
IS 6
BP 1047
EP 1059
DI 10.1016/j.immuni.2012.03.026
PG 13
WC Immunology
SC Immunology
GA 969ZE
UT WOS:000306097100020
PM 22749354
ER
PT J
AU Hinnebusch, AG
AF Hinnebusch, Alan G.
TI Translational Homeostasis via elF4E and 4E-BP1
SO MOLECULAR CELL
LA English
DT Editorial Material
AB In this issue of Molecular Cell, Yanagiya et al. (2012) describe a regulatory mechanism that couples the abundance of the translational repressor 4E-BP1 with its target elF4E via proteasomal degradation of 4E-BP1, thus maintaining translation in cells depleted of elF4E.
C1 Eunice Kennedy Shriver NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Hinnebusch, AG (reprint author), Eunice Kennedy Shriver NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
EM ahinnebusch@nih.gov
FU Intramural NIH HHS
NR 5
TC 10
Z9 10
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD JUN 29
PY 2012
VL 46
IS 6
BP 717
EP 719
DI 10.1016/j.molcel.2012.06.001
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 969ZD
UT WOS:000306097000002
PM 22749396
ER
PT J
AU Ammosova, T
Platonov, M
Yedavalli, VRK
Obukhov, Y
Gordeuk, VR
Jeang, KT
Kovalskyy, D
Nekhai, S
AF Ammosova, Tatiana
Platonov, Maxim
Yedavalli, Venkat R. K.
Obukhov, Yuri
Gordeuk, Victor R.
Jeang, Kuan-Teh
Kovalskyy, Dmytro
Nekhai, Sergei
TI Small Molecules Targeted to a Non-Catalytic "RVxF" Binding Site of
Protein Phosphatase-1 Inhibit HIV-1
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNA-POLYMERASE-II; TYPE-1 TAT; P-TEFB;
DEPENDENT TRANSACTIVATION; TRANSCRIPTION; PHOSPHORYLATION; ACTIVATION;
SP1; REPLICATION
AB HIV-1 Tat protein recruits host cell factors including CDK9/cyclin T1 to HIV-1 TAR RNA and thereby induces HIV-1 transcription. An interaction with host Ser/Thr protein phosphatase-1 (PP1) is critical for this function of Tat. PP1 binds to a Tat sequence, Q(35)VCF(38), which resembles the PP1-binding "RVxF" motif present on PP1-binding regulatory subunits. We showed that expression of PP1 binding peptide, a central domain of Nuclear Inhibitor of PP1, disrupted the interaction of HIV-1 Tat with PP1 and inhibited HIV-1 transcription and replication. Here, we report small molecule compounds that target the "RVxF"-binding cavity of PP1 to disrupt the interaction of PP1 with Tat and inhibit HIV-1 replication. Using the crystal structure of PP1, we virtually screened 300,000 compounds and identified 262 small molecules that were predicted to bind the "RVxF"-accommodating cavity of PP1. These compounds were then assayed for inhibition of HIV-1 transcription in CEM T cells. One of the compounds, 1H4, inhibited HIV-1 transcription and replication at non-cytotoxic concentrations. 1H4 prevented PP1-mediated dephosphorylation of a substrate peptide containing an RVxF sequence in vitro. 1H4 also disrupted the association of PP1 with Tat in cultured cells without having an effect on the interaction of PP1 with the cellular regulators, NIPP1 and PNUTS, or on the cellular proteome. Finally, 1H4 prevented the translocation of PP1 to the nucleus. Taken together, our study shows that HIV-inhibition can be achieved through using small molecules to target a non-catalytic site of PP1. This proof-of-principle study can serve as a starting point for the development of novel antiviral drugs that target the interface of HIV-1 viral proteins with their host partners.
C1 [Ammosova, Tatiana; Gordeuk, Victor R.; Nekhai, Sergei] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA.
[Ammosova, Tatiana; Obukhov, Yuri; Nekhai, Sergei] Howard Univ, RCMI Prote Core Facil, Washington, DC 20059 USA.
[Ammosova, Tatiana; Nekhai, Sergei] Howard Univ, Dept Med, Washington, DC 20059 USA.
[Platonov, Maxim; Kovalskyy, Dmytro] Natl Taras Shevchenko Univ, ChemBio Ctr, Kiev, Ukraine.
[Platonov, Maxim; Kovalskyy, Dmytro] Natl Acad Sci Ukraine, Inst Mol Biol & Genet, Kiev, Ukraine.
[Yedavalli, Venkat R. K.; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Gordeuk, Victor R.] Univ Illinois, Sickle Cell Ctr, Chicago, IL USA.
RP Ammosova, T (reprint author), Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA.
EM snekhai@howard.edu
RI Platonov, Maxim/D-3238-2015
OI Platonov, Maxim/0000-0002-3205-3305
FU Civilian Research and Development Foundation [UKB2-2927-KV-07]; National
Institutes of Health (NIH) [2 R25 HL003679-08]; Office of Research on
Minority Health [2MO1 RR10284, 1SC1GM082325-01, K25GM097501]; Howard
University; RCMI-NIH from the Research Centers in Minority Institutions
(RCMI) Program (Division of Research Infrastructure, National Center for
Research Resources, NIH) [RCMI-NIH 2G12RR003048]; National Heart, Lung,
and Blood Institute
FX This project was supported by Civilian Research and Development
Foundation [Grant UKB2-2927-KV-07] (to SN and DK), National Institutes
of Health (NIH) Research grants [Grant 2 R25 HL003679-08] (to VRG)
funded by the National Heart, Lung, and Blood Institute and The Office
of Research on Minority Health [Grant 2MO1 RR10284] (to VRG), [Grant
1SC1GM082325-01] (to SN); [Grant K25GM097501] (to YO); by Howard
University Seed Grant (to SN) and RCMI-NIH grant [Grant RCMI-NIH
2G12RR003048] (to SN) from the Research Centers in Minority Institutions
(RCMI) Program (Division of Research Infrastructure, National Center for
Research Resources, NIH). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 46
TC 12
Z9 12
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 29
PY 2012
VL 7
IS 6
AR e39481
DI 10.1371/journal.pone.0039481
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 967FO
UT WOS:000305892100052
PM 22768081
ER
PT J
AU Bloes, DA
Otto, M
Peschel, A
Kretschmer, D
AF Bloes, Dominik Alexander
Otto, Michael
Peschel, Andreas
Kretschmer, Dorothee
TI Enterococcus faecium Stimulates Human Neutrophils via the Formyl-Peptide
Receptor 2
SO PLOS ONE
LA English
DT Article
ID STAPHYLOCOCCUS-AUREUS; VIRULENCE DETERMINANTS; ACTIVATES NEUTROPHILS;
SENSING SYSTEM; SEX-PHEROMONES; FAECALIS; INFECTIONS; RESISTANCE;
PLASMID; IDENTIFICATION
AB The human formyl-peptide receptor 2 (FPR2/ALX) senses phenol-soluble modulin (PSM) peptide toxins produced by pathogenic staphylococcal species and plays a crucial role in directing neutrophil influx during staphylococcal infection. However, it has remained unclear if FPR2 responds also to molecules from other bacterial pathogens. Here we analyzed a variety of Gram-positive and Gram-negative pathogens and found that apart from staphylococci only certain enterococcal strains have the capacity to stimulate FPR2/ALX. Most of the analyzed Enterococcus faecium but only sporadic Enterococcus faecalis strains released FPR2/ALX-stimulating molecules leading to neutrophil calcium ion fluxes, chemotaxis, and complement receptor upregulation. Among ten test strains vancomycin-resistant E. faecium had a significantly higher capacity to stimulate FPR2/ALX than vancomycin-susceptible strains, suggesting an association of strong FPR2/ALX activation with health-care associated strains. The enterococcal FPR2/ALX agonists were found to be peptides or proteins, which appear, however, to be unrelated to staphylococcal PSMs in sequence and physicochemical properties. Enterococci are among the most frequent invasive bacterial pathogens but the basis of enterococcal virulence and immune activation has remained incompletely understood. Our study indicates that previously unrecognized proteinaceous agonists contribute to Enterococcus-host interaction and underscores the importance of FPR2/ALX in host defense against major endogenous bacterial pathogens.
C1 [Bloes, Dominik Alexander; Peschel, Andreas; Kretschmer, Dorothee] Univ Tubingen, Cellular & Mol Microbiol Sect, Interfac Inst Microbiol & Infect Med, Tubingen, Germany.
[Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, US NIH, Bethesda, MD 20892 USA.
RP Bloes, DA (reprint author), Univ Tubingen, Cellular & Mol Microbiol Sect, Interfac Inst Microbiol & Infect Med, Tubingen, Germany.
EM andreas.peschel@uni-tuebingen.de
OI Otto, Michael/0000-0002-2222-4115
FU German Research Foundation [SFB685, TRR34]; German Ministry of Education
and Research (SkinStaph, Menage); University of Tubingen Medical
Faculty; National Institute of Allergy and Infectious Diseases (NIAID),
U.S. National Institutes of Health
FX This work was financed by the German Research Foundation grants SFB685
and TRR34 and the German Ministry of Education and Research (SkinStaph,
Menage) to AP; the Fortune program of the University of Tubingen Medical
Faculty to DK; and the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases (NIAID), U.S. National
Institutes of Health to MO. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 44
TC 4
Z9 5
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 29
PY 2012
VL 7
IS 6
AR e39910
DI 10.1371/journal.pone.0039910
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 967FO
UT WOS:000305892100135
PM 22768166
ER
PT J
AU Edwards, NC
Hing, ZA
Perry, A
Blaisdell, A
Kopelman, DB
Fathke, R
Plum, W
Newell, J
Allen, CE
Geetha, S
Shapiro, A
Okunji, C
Kosti, I
Shomron, N
Grigoryan, V
Przytycka, TM
Sauna, ZE
Salari, R
Mandel-Gutfreund, Y
Komar, AA
Kimchi-Sarfaty, C
AF Edwards, Nathan C.
Hing, Zachary A.
Perry, Avital
Blaisdell, Adam
Kopelman, David B.
Fathke, Robert
Plum, William
Newell, Jordan
Allen, Courtni E.
Geetha, S.
Shapiro, Aaron
Okunji, Chinyere
Kosti, Idit
Shomron, Noam
Grigoryan, Vahan
Przytycka, Teresa M.
Sauna, Zuben E.
Salari, Raheleh
Mandel-Gutfreund, Yael
Komar, Anton A.
Kimchi-Sarfaty, Chava
TI Characterization of Coding Synonymous and Non-Synonymous Variants in
ADAMTS13 Using Ex Vivo and In Silico Approaches
SO PLOS ONE
LA English
DT Article
ID THROMBOTIC THROMBOCYTOPENIC PURPURA; RNA SECONDARY STRUCTURE;
MESSENGER-RNA; CODON USAGE; CLEAVING PROTEASE; ENDOPLASMIC-RETICULUM;
GENE-EXPRESSION; ESCHERICHIA-COLI; QUALITY-CONTROL; MUTATIONS
AB Synonymous variations, which are defined as codon substitutions that do not change the encoded amino acid, were previously thought to have no effect on the properties of the synthesized protein(s). However, mounting evidence shows that these "silent" variations can have a significant impact on protein expression and function and should no longer be considered "silent". Here, the effects of six synonymous and six non-synonymous variations, previously found in the gene of ADAMTS13, the von Willebrand Factor (VWF) cleaving hemostatic protease, have been investigated using a variety of approaches. The ADAMTS13 mRNA and protein expression levels, as well as the conformation and activity of the variants have been compared to that of wild-type ADAMTS13. Interestingly, not only the non-synonymous variants but also the synonymous variants have been found to change the protein expression levels, conformation and function. Bioinformatic analysis of ADAMTS13 mRNA structure, amino acid conservation and codon usage allowed us to establish correlations between mRNA stability, RSCU, and intracellular protein expression. This study demonstrates that variants and more specifically, synonymous variants can have a substantial and definite effect on ADAMTS13 function and that bioinformatic analysis may allow development of predictive tools to identify variants that will have significant effects on the encoded protein.
C1 [Edwards, Nathan C.; Hing, Zachary A.; Perry, Avital; Blaisdell, Adam; Kopelman, David B.; Fathke, Robert; Plum, William; Newell, Jordan; Allen, Courtni E.; Geetha, S.; Shapiro, Aaron; Okunji, Chinyere; Sauna, Zuben E.; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Kosti, Idit; Mandel-Gutfreund, Yael] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.
[Shomron, Noam] Tel Aviv Univ, Dept Cell & Dev Biol, IL-69978 Tel Aviv, Israel.
[Grigoryan, Vahan; Przytycka, Teresa M.; Salari, Raheleh] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Komar, Anton A.] Cleveland State Univ, Dept Biol Geol & Environm Sci, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA.
RP Edwards, NC (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
EM a.komar@csuohio.edu; chava.kimchi-sarfaty@fda.hhs.gov
FU Food and Drug Administration, Intramural Research Program of the
National Institutes of Health, National Library of Medicine; HFSP
[RGP0024]
FX This research was supported by the Food and Drug Administration,
Intramural Research Program of the National Institutes of Health,
National Library of Medicine and by HFSP RGP0024 to AAK. The funders had
no role in study design, data collection, and analysis, decision to
publish, or preparation of the manuscript.
NR 75
TC 15
Z9 15
U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 29
PY 2012
VL 7
IS 6
AR e38864
DI 10.1371/journal.pone.0038864
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 967FO
UT WOS:000305892100020
PM 22768050
ER
PT J
AU Giladi, M
Sasson, Y
Fang, XY
Hiller, R
Buki, T
Wang, YX
Hirsch, JA
Khananshvili, D
AF Giladi, Moshe
Sasson, Yehezkel
Fang, Xianyang
Hiller, Reuben
Buki, Tal
Wang, Yun-Xing
Hirsch, Joel A.
Khananshvili, Daniel
TI A Common Ca2+-Driven Interdomain Module Governs Eukaryotic NCX
Regulation
SO PLOS ONE
LA English
DT Article
ID CARDIAC NA+-CA2+ EXCHANGER; SODIUM-CALCIUM EXCHANGE; CA2+ BINDING
DOMAINS; NA+/CA2+ EXCHANGER; CRYSTAL-STRUCTURE; CA2+-BINDING DOMAIN;
EVOLUTIONARY CONSERVATION; MUTATIONAL ANALYSIS; PROTEIN; MECHANISM
AB Na+/Ca2+ exchanger (NCX) proteins mediate Ca2+-fluxes across the cell membrane to maintain Ca2+ homeostasis in many cell types. Eukaryotic NCX contains Ca2+-binding regulatory domains, CBD1 and CBD2. Ca2+ binding to a primary sensor (Ca3-Ca4 sites) on CBD1 activates mammalian NCXs, whereas CALX, a Drosophila NCX ortholog, displays an inhibitory response to regulatory Ca2+. To further elucidate the underlying regulatory mechanisms, we determined the 2.7 angstrom crystal structure of mammalian CBD12-E454K, a two-domain construct that retains wild-type properties. In conjunction with stopped-flow kinetics and SAXS (small-angle X-ray scattering) analyses of CBD12 mutants, we show that Ca2+ binding to Ca3-Ca4 sites tethers the domains via a network of interdomain salt-bridges. This Ca2+-driven interdomain switch controls slow dissociation of "occluded" Ca2+ from the primary sensor and thus dictates Ca2+ sensing dynamics. In the Ca2+-bound conformation, the interdomain angle of CBD12 is very similar in NCX and CALX, meaning that the interdomain distances cannot account for regulatory diversity in NCX and CALX. Since the two-domain interface is nearly identical among eukaryotic NCXs, including CALX, we suggest that the Ca2+-driven interdomain switch described here represents a general mechanism for initial conduction of regulatory signals in NCX variants.
C1 [Giladi, Moshe; Hiller, Reuben; Buki, Tal; Khananshvili, Daniel] Tel Aviv Univ, Sackler Sch Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel.
[Sasson, Yehezkel; Hirsch, Joel A.] Tel Aviv Univ, Dept Biochem & Mol Biol, Fac Life Sci, IL-69978 Tel Aviv, Israel.
[Fang, Xianyang; Wang, Yun-Xing] NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21701 USA.
RP Giladi, M (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel.
EM jhirsch@post.tau.ac.il; dhanan@post.tau.ac.il
OI Giladi, Moshe/0000-0002-8589-6920
FU Israeli Ministry of Health [2010-3-6266]; USA-Israel Binational
Foundation Research [2009-334]; Israel Science Foundation [23/10];
DIP-DFG
FX This work was partially funded by the Israeli Ministry of Health Grant #
2010-3-6266, the USA-Israel Binational Foundation Research Grant #
2009-334, the Israel Science Foundation Grant # 23/10 to DK and a
DIP-DFG grant to JAH. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 41
TC 15
Z9 16
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 29
PY 2012
VL 7
IS 6
AR e39985
DI 10.1371/journal.pone.0039985
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 967FO
UT WOS:000305892100163
PM 22768191
ER
PT J
AU Kirchhoff, T
Gaudet, MM
Antoniou, AC
McGuffog, L
Humphreys, MK
Dunning, AM
Bojesen, SE
Nordestgaard, BG
Flyger, H
Kang, D
Yoo, KY
Noh, DY
Ahn, SH
Dork, T
Schurmann, P
Karstens, JH
Hillemanns, P
Couch, FJ
Olson, J
Vachon, C
Wang, XS
Cox, A
Brock, I
Elliott, G
Reed, MWR
Burwinkel, B
Meindl, A
Brauch, H
Hamann, U
Ko, YD
Broeks, A
Schmidt, MK
van 't Veer, LJ
Braaf, LM
Johnson, N
Fletcher, O
Gibson, L
Peto, J
Turnbull, C
Seal, S
Renwick, A
Rahman, N
Wu, PE
Yu, JC
Hsiung, CN
Shen, CY
Southey, MC
Hopper, JL
Hammet, F
Van Dorpe, T
Dieudonne, AS
Hatse, S
Lambrechts, D
Andrulis, IL
Bogdanova, N
Antonenkova, N
Rogov, JI
Prokofieva, D
Bermisheva, M
Khusnutdinova, E
van Asperen, CJ
Tollenaar, RAEM
Hooning, MJ
Devilee, P
Margolin, S
Lindblom, A
Milne, RL
Arias, JI
Zamora, MP
Benitez, J
Severi, G
Baglietto, L
Giles, GG
Spurdle, AB
Beesley, J
Chen, XQ
Holland, H
Healey, S
Wang-Gohrke, S
Chang-Claude, J
Mannermaa, A
Kosma, VM
Kauppinen, J
Kataja, V
Agnarsson, BA
Caligo, MA
Godwin, AK
Nevanlinna, H
Heikkinen, T
Fredericksen, Z
Lindor, N
Nathanson, KL
Domchek, SM
Loman, N
Karlsson, P
Askmalm, MS
Melin, B
von Wachenfeldt, A
Hogervorst, FBL
Verheus, M
Rookus, MA
Seynaeve, C
Oldenburg, RA
Ligtenberg, MJ
Ausems, MGEM
Aalfs, CM
Gille, HJP
Wijnen, JT
Garcia, EBG
Peock, S
Cook, M
Oliver, CT
Frost, D
Luccarini, C
Pichert, G
Davidson, R
Chu, C
Eccles, D
Ong, KR
Cook, J
Douglas, F
Hodgson, S
Evans, DG
Eeles, R
Gold, B
Pharoah, PDP
Offit, K
Chenevix-Trench, G
Easton, DF
AF Kirchhoff, Tomas
Gaudet, Mia M.
Antoniou, Antonis C.
McGuffog, Lesley
Humphreys, Manjeet K.
Dunning, Alison M.
Bojesen, Stig E.
Nordestgaard, Borge G.
Flyger, Henrik
Kang, Daehee
Yoo, Keun-Young
Noh, Dong-Young
Ahn, Sei-Hyun
Dork, Thilo
Schuermann, Peter
Karstens, Johann H.
Hillemanns, Peter
Couch, Fergus J.
Olson, Janet
Vachon, Celine
Wang, Xianshu
Cox, Angela
Brock, Ian
Elliott, Graeme
Reed, Malcolm W. R.
Burwinkel, Barbara
Meindl, Alfons
Brauch, Hiltrud
Hamann, Ute
Ko, Yon-Dschun
Broeks, Annegien
Schmidt, Marjanka K.
Van 't Veer, Laura J.
Braaf, Linde M.
Johnson, Nichola
Fletcher, Olivia
Gibson, Lorna
Peto, Julian
Turnbull, Clare
Seal, Sheila
Renwick, Anthony
Rahman, Nazneen
Wu, Pei-Ei
Yu, Jyh-Cherng
Hsiung, Chia-Ni
Shen, Chen-Yang
Southey, Melissa C.
Hopper, John L.
Hammet, Fleur
Van Dorpe, Thijs
Dieudonne, Anne-Sophie
Hatse, Sigrid
Lambrechts, Diether
Andrulis, Irene L.
Bogdanova, Natalia
Antonenkova, Natalia
Rogov, Juri I.
Prokofieva, Daria
Bermisheva, Marina
Khusnutdinova, Elza
van Asperen, Christi J.
Tollenaar, Robert A. E. M.
Hooning, Maartje J.
Devilee, Peter
Margolin, Sara
Lindblom, Annika
Milne, Roger L.
Ignacio Arias, Jose
Pilar Zamora, M.
Benitez, Javier
Severi, Gianluca
Baglietto, Laura
Giles, Graham G.
Spurdle, Amanda B.
Beesley, Jonathan
Chen, Xiaoqing
Holland, Helene
Healey, Sue
Wang-Gohrke, Shan
Chang-Claude, Jenny
Mannermaa, Arto
Kosma, Veli-Matti
Kauppinen, Jaana
Kataja, Vesa
Agnarsson, Bjarni A.
Caligo, Maria A.
Godwin, Andrew K.
Nevanlinna, Heli
Heikkinen, Tuomas
Fredericksen, Zachary
Lindor, Noralane
Nathanson, Katherine L.
Domchek, Susan M.
Loman, Niklas
Karlsson, Per
Askmalm, Marie Stenmark
Melin, Beatrice
von Wachenfeldt, Anna
Hogervorst, Frans B. L.
Verheus, Martijn
Rookus, Matti A.
Seynaeve, Caroline
Oldenburg, Rogier A.
Ligtenberg, Marjolijn J.
Ausems, Margreet G. E. M.
Aalfs, Cora M.
Gille, Hans J. P.
Wijnen, Juul T.
Garcia, Encarna B. Gomez
Peock, Susan
Cook, Margaret
Oliver, Clare T.
Frost, Debra
Luccarini, Craig
Pichert, Gabriella
Davidson, Rosemarie
Chu, Carol
Eccles, Diana
Ong, Kai-Ren
Cook, Jackie
Douglas, Fiona
Hodgson, Shirley
Evans, D. Gareth
Eeles, Rosalind
Gold, Bert
Pharoah, Paul D. P.
Offit, Kenneth
Chenevix-Trench, Georgia
Easton, Douglas F.
CA GENICA Network
kConFab
AOCS Study Grp
SWE-BRCA
HEBON
EMBRACE
BCAC-CIMBA
TI Breast Cancer Risk and 6q22.33: Combined Results from Breast Cancer
Association Consortium and Consortium of Investigators on Modifiers of
BRCA1/2
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; VARIANTS; ALLELES; FGFR2;
GENE
AB Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I-2 = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95% CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
C1 [Kirchhoff, Tomas; Gaudet, Mia M.; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA.
[Kirchhoff, Tomas] NYU, Inst Canc, Dept Environm Med, New York, NY USA.
[Gaudet, Mia M.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Antoniou, Antonis C.; McGuffog, Lesley; Humphreys, Manjeet K.; Dunning, Alison M.; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Studies Epidemiol & Risk Factors Canc Hered SEARC, Dept Oncol, Cambridge, England.
[Antoniou, Antonis C.; McGuffog, Lesley; Humphreys, Manjeet K.; Dunning, Alison M.; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Bojesen, Stig E.; Nordestgaard, Borge G.] Univ Copenhagen, Dept Clin Biochem, Copenhagen Breast Canc Study, DK-1168 Copenhagen, Denmark.
[Bojesen, Stig E.; Nordestgaard, Borge G.] Univ Copenhagen, Dept Clin Biochem, Copenhagen Gen Populat Study, DK-1168 Copenhagen, Denmark.
[Flyger, Henrik] Univ Copenhagen, Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, DK-1168 Copenhagen, Denmark.
[Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun] Seoul Natl Univ, Coll Med, Seoul Breast Canc Study SEBCS, Seoul, South Korea.
[Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun] Natl Canc Ctr, Seoul, South Korea.
[Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun] Univ Ulsan, Coll Med, Dept Surg, Ulsan 680749, South Korea.
[Dork, Thilo; Schuermann, Peter; Karstens, Johann H.; Hillemanns, Peter] Hannover Med Sch, Hannover Breast Canc Study HABCS, Clin Obstet & Gynecol, D-3000 Hannover, Germany.
[Dork, Thilo; Schuermann, Peter; Karstens, Johann H.; Hillemanns, Peter] Hannover Med Sch, Hannover Breast Canc Study HABCS, Clin Radiat Oncol, D-3000 Hannover, Germany.
[Couch, Fergus J.; Olson, Janet; Vachon, Celine; Wang, Xianshu] Mayo Clin, MCBCS, Rochester, MN USA.
[Cox, Angela; Brock, Ian; Elliott, Graeme; Reed, Malcolm W. R.] Univ Sheffield, Sch Med, Dept Oncol, SBCS, Sheffield, S Yorkshire, England.
[Burwinkel, Barbara] German Canc Res Ctr, Inst Human Genet, GC HBOC, D-6900 Heidelberg, Germany.
[Meindl, Alfons] Tech Univ Munich, Div Tumor Genet, Dept Obstet & Gynecol, Munich, Germany.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Gene Environm Interact & Breast Canc Germany GENI, D-7000 Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
[Hamann, Ute] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany.
[Ko, Yon-Dschun] Evangel Kliniken Bonn gGmbH, Johanniter Krankenhaus, Dept Internal Med, Bonn, Germany.
Univ Bonn, Fac Med, Inst Pathol, Bonn, Germany.
German Social Accid Insurance, Inst Prevent & Occupat Med, Bochum, Germany.
[Broeks, Annegien; Schmidt, Marjanka K.; Van 't Veer, Laura J.; Braaf, Linde M.] Netherlands Canc Inst, ABCS, Dept Expt Therapy, Amsterdam, Netherlands.
[Broeks, Annegien; Schmidt, Marjanka K.; Van 't Veer, Laura J.; Braaf, Linde M.] Netherlands Canc Inst, ABCS, Dept Epidemiol, Amsterdam, Netherlands.
[Broeks, Annegien; Schmidt, Marjanka K.; Van 't Veer, Laura J.; Braaf, Linde M.] Netherlands Canc Inst, ABCS, Dept Mol Pathol, Amsterdam, Netherlands.
[Johnson, Nichola; Fletcher, Olivia] Inst Canc Res, Breakthrough Breast Canc Res Ctr, BBCS, London SW3 6JB, England.
[Gibson, Lorna; Peto, Julian] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England.
[Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Rahman, Nazneen] Inst Canc Res, Sect Canc Genet, ICR Familial Breast Canc Study FBCS, Sutton, Surrey, England.
[Hsiung, Chia-Ni; Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taiwanese Breast Canc Study TWBCS, Taipei, Taiwan.
[Wu, Pei-Ei] Acad Sinica, Taiwan Biobank, Taipei, Taiwan.
[Yu, Jyh-Cherng] Tri Serv Gen Hosp, Dept Surg, Taipei, Taiwan.
[Southey, Melissa C.; Hammet, Fleur] Univ Melbourne, Genet Epidemiol Lab, Dept Pathol, ABCFS, Melbourne, Vic 3010, Australia.
[Hopper, John L.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia.
[Van Dorpe, Thijs; Dieudonne, Anne-Sophie; Hatse, Sigrid] Katholieke Univ Leuven, Multidisciplinary Breast Clin, LMBC, Louvain, Belgium.
[Lambrechts, Diether] Vesalius Res Ctr, Louvain, Belgium.
[Andrulis, Irene L.] Canc Care Ontario, Ontario Canc Genet Network, OFBCR, Toronto, ON, Canada.
[Andrulis, Irene L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Juri I.] NN Alexandrov Res Inst Oncol & Med Radiol, HMBCS, Minsk, Byelarus.
[Prokofieva, Daria; Bermisheva, Marina; Khusnutdinova, Elza] Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, HUBCS, Ufa, Russia.
[Hooning, Maartje J.] Erasmus MC, Dept Med Oncol, Leiden Univ Med Ctr Breast Canc Study ORIGO, Rotterdam, Netherlands.
[Tollenaar, Robert A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, Leiden, Netherlands.
[van Asperen, Christi J.] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet & Pathol, Leiden, Netherlands.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Karolinska Breast Canc Study KARBAC, S-10401 Stockholm, Sweden.
[Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, S-10401 Stockholm, Sweden.
[Margolin, Sara] Karolinska Univ, Stockholm, Sweden.
[Milne, Roger L.] Spanish Natl Canc Ctr, Genet & Mol Epidemiol Grp, Spanish Natl Canc Ctr Breast Canc Study CNIO BCS, Madrid, Spain.
[Benitez, Javier] Spanish Natl Canc Ctr, Human Genet Grp, Madrid, Spain.
[Benitez, Javier] Ctr Invest Biomed Red Enfermedades Rares, Valencia, Spain.
[Ignacio Arias, Jose] Monte Naranco Hosp, Oviedo, Spain.
[Pilar Zamora, M.] La Paz Univ Hosp, Madrid, Spain.
[Southey, Melissa C.; Severi, Gianluca; Baglietto, Laura; Giles, Graham G.] Canc Council, Canc Epidemiol Ctr, MCCS, Melbourne, Vic, Australia.
[Southey, Melissa C.; Severi, Gianluca; Baglietto, Laura; Giles, Graham G.] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia.
[Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Holland, Helene; Healey, Sue; Chenevix-Trench, Georgia] Queensland Inst Med Res, Kathleen Cuningham Fdn Consortium Res Familial Br, Brisbane, Qld 4006, Australia.
[Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Holland, Helene; Healey, Sue; Chenevix-Trench, Georgia] Peter MacCallum Canc Ctr, Australian Ovarian Canc Study Grp, Melbourne, Vic, Australia.
[Chang-Claude, Jenny] German Canc Res Ctr DFKZ, Div Canc Epidemiol, Genet Epidemiol Study Breast Canc Age 50 GESBC, Heidelberg, Germany.
[Wang-Gohrke, Shan] Univ Ulm, Dept Gynecol & Obstet, Mol Biol Lab, Ulm, Germany.
[Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana] Univ Eastern Finland, Dept Pathol, Inst Clin Med, KBCP, Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana] Kuopio Univ Hosp, Bioctr Kuopio, SF-70210 Kuopio, Finland.
[Kataja, Vesa] Vaasa Cent Hosp, Dept Oncol, Vaasa, Finland.
[Kataja, Vesa] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland.
[Agnarsson, Bjarni A.] Landspitali Univ Hosp, Dept Pathol, ILUH, Reykjavik, Iceland.
[Agnarsson, Bjarni A.] Univ Iceland, Sch Med, Reykjavik, Iceland.
[Caligo, Maria A.] Univ Pisa, Dept Oncol, Div Surg Mol & Ultrastruct Pathol, Pisa, Italy.
[Caligo, Maria A.] Pisa Univ Hosp, Pisa, Italy.
[Godwin, Andrew K.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki Breast Canc Study HEBCS, FIN-00290 Helsinki, Finland.
[Couch, Fergus J.; Fredericksen, Zachary; Lindor, Noralane] Mayo Clin, Mayo Clin Familial Breast & Ovarian Canc Study MA, Rochester, MN USA.
[Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Dept Med, Univ Penn UPENN, Philadelphia, PA 19104 USA.
[Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Loman, Niklas] Univ Lund Hosp, Dept Oncol, Swedish BRCA1 & BRCA2 Study Collaborators SWE BRC, S-22185 Lund, Sweden.
[Karlsson, Per] Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden.
[Askmalm, Marie Stenmark] Linkoping Univ Hosp, Dept Oncol, S-58185 Linkoping, Sweden.
[Melin, Beatrice] Umea Univ, Dept Radiat Sci, Umea, Sweden.
[von Wachenfeldt, Anna] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden.
[Hogervorst, Frans B. L.; Verheus, Martijn; Rookus, Matti A.] Netherlands Canc Inst, Coordinating Ctr, Hereditary Breast & Ovarian Canc Res Grp Netherla, Amsterdam, Netherlands.
[Seynaeve, Caroline; Oldenburg, Rogier A.] Erasmus MC, Rotterdam, Netherlands.
[Ligtenberg, Marjolijn J.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Ausems, Margreet G. E. M.] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Aalfs, Cora M.] Amsterdam Med Ctr, Amsterdam, Netherlands.
[Gille, Hans J. P.] Vrije Univ, Univ Med Ctr, Amsterdam, Netherlands.
[Garcia, Encarna B. Gomez] Univ Hosp Maastricht, Maastricht, Netherlands.
[Peock, Susan; Cook, Margaret; Oliver, Clare T.; Frost, Debra; Luccarini, Craig] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Epidemiol Study BRCA1 & BRCA2 Mutat Carriers EMBR, Cambridge, England.
[Evans, D. Gareth] Cent Manchester Univ Hosp Natl Hlth Serv NHS Fdn, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Eeles, Rosalind] Inst Canc Res, Oncogenet Team, London SW3 6JB, England.
[Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London, England.
[Pichert, Gabriella] Guys & St Thomas NHS Fdn Trust, London, England.
[Davidson, Rosemarie] Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland.
[Chu, Carol] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England.
[Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England.
[Ong, Kai-Ren] Birmingham Womens Hosp Healthcare NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England.
[Cook, Jackie] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England.
[Douglas, Fiona] Newcastle Tyne Hosp NHS Trust, Ctr Life, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England.
[Hodgson, Shirley] Univ London, St Georges Hosp, Dept Clin Genet, London, England.
[Gold, Bert] NCI, Clin Genet Branch, Rockville, MD USA.
RP Kirchhoff, T (reprint author), Mem Sloan Kettering Canc Ctr, Clin Genet Serv, 1275 York Ave, New York, NY 10021 USA.
EM offitk@mskcc.org
RI Bruning, Thomas/G-8120-2015; Khusnutdinova, Elza/A-4810-2013; Rahman,
Nazneen/D-2802-2013; Wyld, David/B-8893-2015; Spurdle,
Amanda/A-4978-2011; Shen, CY/F-6271-2010; Verdrengh,
Evelien/H-4571-2012; Bowtell, David/H-1007-2016; Noh,
Dong-Young/G-5531-2011; Yoo, Keun-Young/J-5548-2012; friedlander,
michael/G-3490-2013; Hoogerbrugge, Nicoline/O-1016-2013; Oosterwijk, Jan
C./G-5770-2011; Dork, Thilo/J-8620-2012; Ehrencrona, Hans/M-5619-2014;
Hartikainen, Jaana/E-6256-2015; Ligtenberg, Marjolijn/N-9666-2013
OI Dunning, Alison Margaret/0000-0001-6651-7166; Jacobs,
Chris/0000-0002-9557-9080; Giles, Graham/0000-0003-4946-9099; Evans,
Gareth/0000-0002-8482-5784; Bruning, Thomas/0000-0001-9560-5464; Rahman,
Nazneen/0000-0003-4376-0440; Wyld, David/0000-0001-9523-4333; Eeles,
Rosalind/0000-0002-3698-6241; Nordling, Margareta/0000-0002-4047-4994;
Nathanson, Katherine/0000-0002-6740-0901; Spurdle,
Amanda/0000-0003-1337-7897; Nevanlinna, Heli/0000-0002-0916-2976; Cox,
Angela/0000-0002-5138-1099; Kirchhoff, Tomas/0000-0002-9055-2364;
Bowtell, David/0000-0001-9089-7525; friedlander,
michael/0000-0002-6488-0604; Ehrencrona, Hans/0000-0002-5589-3622;
Ligtenberg, Marjolijn/0000-0003-1290-1474
FU Cancer Research UK [10124, 10118, 11174]; Medical Research Council
[G0700491]
NR 24
TC 5
Z9 5
U1 2
U2 17
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 29
PY 2012
VL 7
IS 6
AR e35706
DI 10.1371/journal.pone.0035706
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 967FO
UT WOS:000305892100001
PM 22768030
ER
PT J
AU Park, YN
Zhao, XH
Norton, M
Taylor, JP
Eisenberg, E
Greene, LE
AF Park, Yang-Nim
Zhao, Xiaohong
Norton, Mark
Taylor, J. Paul
Eisenberg, Evan
Greene, Lois E.
TI Huntingtin Fragments and SOD1 Mutants Form Soluble Oligomers in the Cell
SO PLOS ONE
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; FLUORESCENCE CORRELATION SPECTROSCOPY;
INCLUSION-BODY FORMATION; WILD-TYPE SOD1; POLYGLUTAMINE PROTEIN;
SUPEROXIDE-DISMUTASE; MAMMALIAN-CELLS; NEURONAL DEATH; MOUSE MODELS;
LIVING CELLS
AB Diffusion coefficients of huntingtin (Htt) fragments and SOD1 mutants expressed in cells were measured using fluorescence correlation spectroscopy. The diffusion mobilities of both non-pathological Htt fragments (25 polyQs) and pathological Htt fragments (103 polyQs) were much slower than expected for monomers suggesting that they oligomerize. The mobility of these fragments was unaffected by duration of expression or by over-expression of Hsp70 and Hsp40. However in cells with HttQ103 inclusions, diffusion measurements showed that the residual cytosolic HttQ103 was monomeric. These results suggest that both non-pathological and pathological Htt fragments form soluble oligomers in the cytosol with the properties of the oligomers determining whether they cause pathology. SOD1 with point mutations (A4V, G37R, and G85R) also had slower diffusional mobility than the wild-type protein whose mobility was consistent with that of a dimer. However, the decrease in mobility of the different SOD1 mutantsdid not correlate with their known pathology. Therefore, while soluble oligomers always seem to be present under conditions where cell pathology occurs, the presence of the oligomers, in itself, does not determine the extent of neuropathology.
C1 [Park, Yang-Nim; Zhao, Xiaohong; Norton, Mark; Eisenberg, Evan; Greene, Lois E.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Taylor, J. Paul] St Jude Childrens Hosp, Memphis, TN 38105 USA.
RP Park, YN (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM greenel@helix.nih.gov
FU National Institutes of Health
FX This research was funded by the National Institutes of Health
(intramural program). The funder had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 60
TC 3
Z9 3
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 29
PY 2012
VL 7
IS 6
AR e40329
DI 10.1371/journal.pone.0040329
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 967FO
UT WOS:000305892100250
PM 22768276
ER
PT J
AU Ravin, R
Blank, PS
Steinkamp, A
Rappaport, SM
Ravin, N
Bezrukov, L
Guerrero-Cazares, H
Quinones-Hinojosa, A
Bezrukov, SM
Zimmerberg, J
AF Ravin, Rea
Blank, Paul S.
Steinkamp, Alex
Rappaport, Shay M.
Ravin, Nitay
Bezrukov, Ludmila
Guerrero-Cazares, Hugo
Quinones-Hinojosa, Alfredo
Bezrukov, Sergey M.
Zimmerberg, Joshua
TI Shear Forces during Blast, Not Abrupt Changes in Pressure Alone,
Generate Calcium Activity in Human Brain Cells
SO PLOS ONE
LA English
DT Article
ID IN-VITRO; INJURY; MODEL; MECHANISMS; WAVE; RESPONSES
AB Blast-Induced Traumatic Brain Injury (bTBI) describes a spectrum of injuries caused by an explosive force that results in changes in brain function. The mechanism responsible for primary bTBI following a blast shockwave remains unknown. We have developed a pneumatic device that delivers shockwaves, similar to those known to induce bTBI, within a chamber optimal for fluorescence microscopy. Abrupt changes in pressure can be created with and without the presence of shear forces at the surface of cells. In primary cultures of human central nervous system cells, the cellular calcium response to shockwaves alone was negligible. Even when the applied pressure reached 15 atm, there was no damage or excitation, unless concomitant shear forces, peaking between 0.3 to 0.7 Pa, were present at the cell surface. The probability of cellular injury in response to a shockwave was low and cell survival was unaffected 20 hours after shockwave exposure.
C1 [Ravin, Rea; Blank, Paul S.; Steinkamp, Alex; Rappaport, Shay M.; Ravin, Nitay; Bezrukov, Ludmila; Bezrukov, Sergey M.; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
[Blank, Paul S.; Rappaport, Shay M.; Bezrukov, Sergey M.; Zimmerberg, Joshua] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Guerrero-Cazares, Hugo; Quinones-Hinojosa, Alfredo] Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD USA.
RP Ravin, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
EM zimmerbj@mail.nih.gov
FU Department of Defense in the Center for Neuroscience and Regenerative
Medicine (CNRM); Eunice Kennedy Shriver National Institute of Child
Health & Human Development (NICHD), National Institutes of Health (NIH)
FX Support for this work included funding from Department of Defense in the
Center for Neuroscience and Regenerative Medicine (CNRM) and the
Intramural Program of the Eunice Kennedy Shriver National Institute of
Child Health & Human Development (NICHD), National Institutes of Health
(NIH). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 27
TC 17
Z9 17
U1 1
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 29
PY 2012
VL 7
IS 6
AR e39421
DI 10.1371/journal.pone.0039421
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 967FO
UT WOS:000305892100049
PM 22768078
ER
PT J
AU Brautigam, CA
Deka, RK
Schuck, P
Tomchick, DR
Norgard, MV
AF Brautigam, Chad A.
Deka, Ranjit K.
Schuck, Peter
Tomchick, Diana R.
Norgard, Michael V.
TI Structural and Thermodynamic Characterization of the Interaction between
Two Periplasmic Treponema pallidum Lipoproteins that are Components of a
TPR-Protein-Associated TRAP Transporter (TPAT)
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE TRAP transporter; syphilis; Treponema pallidum; TPR motif; protein
interactions
ID BACTERIUM ALCANIVORAX-BORKUMENSIS; SIZE-DISTRIBUTION ANALYSIS; NEGATIVE
OUTER-MEMBRANE; CRYSTAL-STRUCTURE; ANALYTICAL ULTRACENTRIFUGATION;
MALTOSE TRANSPORTER; SYPHILIS SPIROCHETE; IMMUNE-RESPONSES; ABC
TRANSPORTERS; GENOME SEQUENCE
AB Tripartite ATP-independent periplasmic transporters (TRAP-Ts) are bacterial transport systems that have been implicated in the import of small molecules into the cytoplasm. A newly discovered subfamily of TRAP-Ts [tetratricopeptide repeat-protein associated TRAP transporters (TPATs)] has four components. Three are common to both TRAP-Ts and TPATs: the P component, a ligand-binding protein, and a transmembrane symporter apparatus comprising the M and Q components (M and Q are sometimes fused to form a single polypeptide). TPATs are distinguished from TRAP-Ts by the presence of a unique protein called the "T component". In Treponema pallidum, this protein (TatT) is a water-soluble trimer whose protomers are each perforated by a pore. Its respective P component (TatP(T)) interacts with the TatT in vitro and in vivo. In this work, we further characterized this interaction. Co-crystal structures of two complexes between the two proteins confirm that up to three monomers of TatP(T) can bind to the TatT trimer. A putative ligand-binding cleft of TatP(T) aligns with the pore of TatT, strongly suggesting ligand transfer between T and P-T. We used a combination of site-directed mutagenesis and analytical ultracentrifugation to derive thermodynamic parameters for the interactions. These observations confirm that the observed crystallographic interface is recapitulated in solution. These results prompt a hypothesis of the molecular mechanism(s) of hydrophobic ligand transport by the TPATs. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Deka, Ranjit K.; Norgard, Michael V.] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA.
[Brautigam, Chad A.; Tomchick, Diana R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
[Schuck, Peter] NIBIB, Dynam Mol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Norgard, MV (reprint author), Univ Texas SW Med Ctr Dallas, Dept Microbiol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Michael.Norgard@UTSouthwestern.edu
OI Schuck, Peter/0000-0002-8859-6966; Tomchick, Diana/0000-0002-7529-4643
FU National Institutes of Health [AI056305]; National Institute of
Biomedical Imaging and Bioengineering; U.S. Department of Energy, Office
of Biological and Environmental Research [DE-AC02-06CH11357]
FX We thank Martin Goldberg for technical assistance and the scientists in
the University of Texas Southwestern Protein Chemistry Core for protein
sequence and mass analyses. This research was supported by a National
Institutes of Health grant (AI056305) to M.V.N. This work was also
supported in part by the Intramural Research Program of the National
Institute of Biomedical Imaging and Bioengineering (P.S.). Results in
this report were derived from work performed at Argonne National
Laboratory, Structural Biology Center at the Advanced Photon Source.
Argonne is operated by UChicago Argonne, LLC, for the U.S. Department of
Energy, Office of Biological and Environmental Research under contract
DE-AC02-06CH11357.
NR 67
TC 11
Z9 11
U1 0
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD JUN 29
PY 2012
VL 420
IS 1-2
BP 70
EP 86
DI 10.1016/j.jmb.2012.04.001
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 964TB
UT WOS:000305718500007
PM 22504226
ER
PT J
AU Dever, TE
AF Dever, Thomas E.
TI A New Start for Protein Synthesis
SO SCIENCE
LA English
DT Editorial Material
ID TRANSLATION INITIATION; MAMMALIAN-CELLS; AUG; RIBOSOME; SITE
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Dever, TE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
EM tdever@nih.gov
NR 13
TC 3
Z9 3
U1 0
U2 7
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUN 29
PY 2012
VL 336
IS 6089
BP 1645
EP 1646
DI 10.1126/science.1224439
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965VD
UT WOS:000305794500027
PM 22745408
ER
PT J
AU Nabel, GJ
Wolinsky, SM
Haynes, BF
AF Nabel, Gary J.
Wolinsky, Steven M.
Haynes, Barton F.
TI Norman L. Letvin (1949-2012)
SO SCIENCE
LA English
DT Biographical-Item
C1 [Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Wolinsky, Steven M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Haynes, Barton F.] Duke Univ, Med Ctr, Durham, NC 27705 USA.
RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
EM gnabel@nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUN 29
PY 2012
VL 336
IS 6089
BP 1653
EP 1653
DI 10.1126/science.1225947
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965VD
UT WOS:000305794500033
PM 22745414
ER
PT J
AU Germain, RN
Robey, EA
Cahalan, MD
AF Germain, Ronald N.
Robey, Ellen A.
Cahalan, Michael D.
TI A Decade of Imaging Cellular Motility and Interaction Dynamics in the
Immune System
SO SCIENCE
LA English
DT Review
ID SUBCAPSULAR SINUS MACROPHAGES; BEARING DENDRITIC CELLS; CD8(+) T-CELLS;
NODE B-CELLS; IN-VIVO; LYMPH-NODES; 2-PHOTON MICROSCOPY; STOP SIGNAL;
MYCOBACTERIAL GRANULOMAS; PATHOGEN INTERACTIONS
AB To mount an immune response, lymphocytes must recirculate between the blood and lymph nodes, recognize antigens upon contact with specialized presenting cells, proliferate to expand a small number of clonally relevant lymphocytes, differentiate to antibody-producing plasma cells or effector T cells, exit from lymph nodes, migrate to tissues, and engage in host-protective activities. All of these processes involve motility and cellular interactions-events that were hidden from view until recently. Introduced to immunology by three papers in this journal in 2002, in vivo live-cell imaging studies are revealing the behavior of cells mediating adaptive and innate immunity in diverse tissue environments, providing quantitative measurement of cellular motility, interactions, and response dynamics. Here, we review themes emerging from such studies and speculate on the future of immunoimaging.
C1 [Germain, Ronald N.] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Robey, Ellen A.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Cahalan, Michael D.] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA.
RP Germain, RN (reprint author), NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
EM rgermain@nih.gov; erobey@berkeley.edu; mcahalan@uci.edu
FU National Institute of Allergy and Infectious Diseases, NIH; NIH
[GM-41514]; [AI-065537]; [AI-064227]
FX We would like to thank members of our laboratory groups for their
contributions to the research described here and for comments on the
manuscript. We apologize to the many authors who contributed importantly
to the field of imaging the immune response but whose work could not be
included in the references for lack of space. This research was
supported by the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases, NIH (R.N.G.); AI-065537 and
AI-064227 (E.A.R.); and NIH RO1 grant GM-41514 (M.D.C.).
NR 91
TC 123
Z9 125
U1 6
U2 44
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUN 29
PY 2012
VL 336
IS 6089
BP 1676
EP 1681
DI 10.1126/science.1221063
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965VD
UT WOS:000305794500042
PM 22745423
ER
PT J
AU Ghanouni, P
Behera, D
Xie, J
Chen, XY
Moseley, M
Biswal, S
AF Ghanouni, Pejman
Behera, Deepak
Xie, Jin
Chen, Xiaoyuan
Moseley, Michael
Biswal, Sandip
TI In vivo USPIO magnetic resonance imaging shows that minocycline
mitigates macrophage recruitment to a peripheral nerve injury
SO MOLECULAR PAIN
LA English
DT Article
DE Neuropathic pain; Macrophages; Magnetic resonance imaging; Iron-oxide
nanoparticles; Spared-nerve injury model
ID NEUROPATHIC PAIN; ALLOGRAFT-REJECTION; CELLS; IMMUNE; INFILTRATION;
INFLAMMATION; NEURONS; MODEL
AB Background: Minocycline has proven anti-nociceptive effects, but the mechanism by which minocycline delays the development of allodynia and hyperalgesia after peripheral nerve injury remains unclear. Inflammatory cells, in particular macrophages, are critical components of the response to nerve injury. Using ultrasmall superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI) to monitor macrophage trafficking, the purpose of this project is to determine whether minocycline modulates macrophage trafficking to the site of nerve injury in vivo and, in turn, results in altered pain thresholds.
Results: Animal experiments were approved by Stanford IACUC. A model of neuropathic pain was created using the Spared Nerve Injury (SNI) model that involves ligation of the left sciatic nerve in the left thigh of adult Sprague-Dawley rats. Animals with SNI and uninjured animals were then injected with/without USPIOs (300 mu mol/kg IV) and with/without minocycline (50 mg/kg IP). Bilateral sciatic nerves were scanned with a volume coil in a 7 T magnet 7 days after USPIO administration. Fluid-sensitive MR images were obtained, and ROIs were placed on bilateral sciatic nerves to quantify signal intensity. Pain behavior modulation by minocycline was measured using the Von Frey filament test. Sciatic nerves were ultimately harvested at day 7, fixed in 10% buffered formalin and stained for the presence of iron oxide-laden macrophages. Behavioral measurements confirmed the presence of allodynia in the neuropathic pain model while the uninjured and minocycline-treated injured group had significantly higher paw withdrawal thresholds (p < 0.011). Decreased MR signal is observed in the SNI group that received USPIOs (3.3+/-0.5%) compared to the minocycline-treated SNI group that received USPIOs (15.2+/-4.5%) and minocycline-treated group that did not receive USPIOs (41.2+/-2.3%) (p < 0.04). Histology of harvested sciatic nerve specimens confirmed the presence USPIOs at the nerve injury site in the SNI group without minocycline treatment.
Conclusion: Animals with neuropathic pain in the left hindpaw show increased trafficking of USPIO-laden macrophages to the site of sciatic nerve injury. Minocycline to retards the migration of macrophages to the nerve injury site, which may partly explain its anti-nociceptive effects. USPIO-MRI is an effective in vivo imaging tool to study the role of macrophages in the development of neuropathic pain.
C1 [Ghanouni, Pejman; Behera, Deepak; Moseley, Michael; Biswal, Sandip] Stanford Univ, Sch Med, Mol Imaging Program Stanford, Dept Radiol, Stanford, CA 94305 USA.
[Xie, Jin] Univ Georgia, Dept Chem & Bioimaging, Res Ctr, Athens, GA 30602 USA.
[Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, Bethesda, MD USA.
RP Biswal, S (reprint author), Stanford Univ, Sch Med, Mol Imaging Program Stanford, Dept Radiol, Stanford, CA 94305 USA.
EM biswal@stanford.edu
RI Behera, Deepak/D-2914-2011
OI Behera, Deepak/0000-0002-0294-7260
FU NCI NIH HHS [R00 CA153772]
NR 16
TC 8
Z9 8
U1 1
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1744-8069
J9 MOL PAIN
JI Mol. Pain
PD JUN 28
PY 2012
VL 8
AR 49
DI 10.1186/1744-8069-8-49
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 020UE
UT WOS:000309839300001
PM 22742763
ER
PT J
AU Yewdell, JW
Princiotta, MF
AF Yewdell, Jonathan W.
Princiotta, Michael F.
TI All roads lead to "ome": defining the DRiPome
SO BLOOD
LA English
DT Editorial Material
ID CLASS-I MOLECULES; ANTIGENIC PEPTIDES; MAJOR SOURCE
C1 [Yewdell, Jonathan W.; Princiotta, Michael F.] Suny Upstate Med Univ, NIAID, New York, NY USA.
RP Yewdell, JW (reprint author), Suny Upstate Med Univ, NIAID, New York, NY USA.
NR 11
TC 1
Z9 1
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 28
PY 2012
VL 119
IS 26
BP 6179
EP 6180
DI 10.1182/blood-2012-04-420810
PG 4
WC Hematology
SC Hematology
GA 987FA
UT WOS:000307400700004
PM 22745294
ER
PT J
AU Busch, MP
Murthy, KK
Kleinman, SH
Hirschkorn, DF
Herring, BL
Delwart, EL
Racanelli, V
Yoon, JC
Rehermann, B
Alter, HJ
AF Busch, Michael P.
Murthy, Krishna K.
Kleinman, Steven H.
Hirschkorn, Dale F.
Herring, Belinda L.
Delwart, Eric L.
Racanelli, Vito
Yoon, Joo Chun
Rehermann, Barbara
Alter, Harvey J.
TI Infectivity in chimpanzees (Pan troglodytes) of plasma collected before
HCV RNA detectability by FDA-licensed assays: implications for
transfusion safety and HCV infection outcomes
SO BLOOD
LA English
DT Article
ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; CELLULAR
IMMUNE-RESPONSES; ANTI-D IMMUNOGLOBULIN; LOW-LEVEL VIREMIA; ANTIVIRAL
THERAPY; BLOOD-DONORS; PERIOD MODEL; TRANSMISSION; VACCINE
AB Serial plasma aliquots (50 mL) obtained from 10 commercial donors who converted from hepatitis C virus (HCV) RNA negative to positive were transfused into 2 chimpanzees to assess infectivity during early HCV infection. Plasma, obtained 4 days before HCV RNA detectability by licensed assays, transmitted HCV infection to chimpanzee X355. The infectious PCR-negative plasma was subsequently shown to be positive in 2 of 23 replicates using a sensitive transcription-mediated amplification (TMA) assay, and estimated to contain 1.2 HCV RNA copies/mL (60 copies/50 mL transfused). Plasma units obtained up to 8 weeks earlier were not infectious in a second susceptible chimp, even when from donors with low-level, intermittent HCV RNA detection. Chimp x355 developed acute viremia with subsequent seroconversion, but cleared both virus and Ab in 17 weeks. When rechallenged 38 months later with 6000 RNA copies/mL from the same donor, X355 was transiently reinfected and again rapidly lost all HCV markers. We conclude that: (1) transfusions can transmit HCV infection before RNA detection, but the interval of test-negative infectivity is very brief; (2) early "blips" of HCV RNA appear noninfectious and can be ignored when calculating residual transfusion risk; and (3) markers of HCV infection can be lost rapidly after exposure to low-dose inocula. (Blood. 2012;119(26):6326-6334)
C1 [Busch, Michael P.; Kleinman, Steven H.; Hirschkorn, Dale F.; Herring, Belinda L.; Delwart, Eric L.] Blood Syst Res Inst, San Francisco, CA 94118 USA.
[Busch, Michael P.; Delwart, Eric L.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Murthy, Krishna K.] Texas Biomed Res Inst, San Antonio, TX USA.
[Murthy, Krishna K.] SW Natl Primate Res Ctr, San Antonio, TX USA.
[Kleinman, Steven H.] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada.
[Racanelli, Vito; Yoon, Joo Chun; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD USA.
[Alter, Harvey J.] NIH, Infect Dis Sect, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Busch, MP (reprint author), Blood Syst Res Inst, 270 Masonic Ave, San Francisco, CA 94118 USA.
EM mbusch@bloodsystems.org
RI Herring, Belinda/M-7252-2015; Yoon, Joo Chun/D-3675-2012;
OI Yoon, Joo Chun/0000-0001-9395-8418; RACANELLI, Vito/0000-0002-8639-1940;
Delwart, Eric/0000-0002-6296-4484
FU National Heart, Lung, and Blood Institute [R01 HL-076902, N01-HB-27091]
FX This work was supported in part by National Heart, Lung, and Blood
Institute grant R01 HL-076902 and contract N01-HB-27091.
NR 36
TC 9
Z9 9
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 28
PY 2012
VL 119
IS 26
BP 6326
EP 6334
DI 10.1182/blood-2011-12-393637
PG 9
WC Hematology
SC Hematology
GA 987FA
UT WOS:000307400700024
PM 22498743
ER
PT J
AU Hajjo, R
Setola, V
Roth, BL
Tropsha, A
AF Hajjo, Rima
Setola, Vincent
Roth, Bryan L.
Tropsha, Alexander
TI Chemocentric Informatics Approach to Drug Discovery: Identification and
Experimental Validation of Selective Estrogen Receptor Modulators as
Ligands of 5-Hydroxytryptamine-6 Receptors and as Potential Cognition
Enhancers
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID GENE-EXPRESSION OMNIBUS; CONVERGENT FUNCTIONAL GENOMICS; RANDOMIZED
CONTROLLED-TRIAL; HEALTH INITIATIVE MEMORY; MICROARRAY DATA-ANALYSIS;
ALZHEIMERS-DISEASE; CHEMICAL GENOMICS; CONNECTIVITY MAP; POSTMENOPAUSAL
WOMEN; HUMAN METABOLOME
AB We have devised a chemocentric informatics methodology for drug discovery integrating independent approaches to mining biomolecular databases. As a proof of concept, we have searched for novel putative cognition enhancers. First, we generated Quantitative Structure-Activity Relationship (QSAR) models of compounds binding to 5-hydroxytryptamine-6 receptor (5-HT6R), a known target for cognition enhancers, and employed these models for virtual screening to identify putative 5-HT6R actives. Second, we queried chemogenomics data from the Connectivity Map (http://www.broad.mit.edu/cmap/) with the gene expression profile signatures of Alzheimer's disease patients to identify compounds putatively linked to the disease. Thirteen common hits were tested in 5-HT6R radioligand binding assays and ten were confirmed as actives. Four of them were known selective estrogen receptor modulators that were never reported as 5-HT6R ligands. Furthermore, nine of the confirmed actives were reported elsewhere to have memory-enhancing effects. The approaches discussed herein can be used broadly to identify novel drug-target-disease associations.
C1 [Hajjo, Rima; Roth, Bryan L.; Tropsha, Alexander] Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA.
[Setola, Vincent; Roth, Bryan L.] Univ N Carolina, Sch Med, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Dept Pharmacol, Chapel Hill, NC 27599 USA.
RP Tropsha, A (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, CB 7360,Beard Hall, Chapel Hill, NC 27599 USA.
EM alex_tropsha@unc.edu
RI Tropsha, Alexander/G-6245-2014; Roth, Bryan/F-3928-2010
FU NIH research grant [GM066940]; NIH contract; Michael Hooker Chair in
Protein Therapeutics and Translational Proteomics; University of Jordan
scholarship; Tripos; Chemical Computing Group; eduSoft; [RO1MH61887];
[U19MH82441]
FX We thank Tripos, Chemical Computing Group, and eduSoft for software
grants. We also thank Ms. Xin Chin from the Center for Integrative
Chemical Biology and Drug Discovery at UNC-Chapel Hill for performing
the purity control tests. Finally, we acknowledge the access to the
computing facilities at the ITS Research Computing Division of the
University of North Carolina at Chapel Hill. The studies reported in
this article were supported in part by the NIH research grant GM066940
(awarded to A.T.); RO1MH61887, U19MH82441, an NIH contract which
supports the NIMH Psychoactive Drug Screening Program, and the Michael
Hooker Chair in Protein Therapeutics and Translational Proteomics
(awarded to B.R.); and the University of Jordan scholarship (awarded to
R.H.).
NR 112
TC 18
Z9 18
U1 0
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD JUN 28
PY 2012
VL 55
IS 12
BP 5704
EP 5719
DI 10.1021/jm2011657
PG 16
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 965LP
UT WOS:000305769600003
PM 22537153
ER
PT J
AU Patnaik, S
Zheng, W
Choi, JH
Motabar, O
Southall, N
Westbroek, W
Lea, WA
Velayati, A
Goldin, E
Sidransky, E
Leister, W
Marugan, JJ
AF Patnaik, Samarjit
Zheng, Wei
Choi, Jae H.
Motabar, Omid
Southall, Noel
Westbroek, Wendy
Lea, Wendy A.
Velayati, Arash
Goldin, Ehud
Sidransky, Ellen
Leister, William
Marugan, Juan J.
TI Discovery, Structure-Activity Relationship, and Biological Evaluation of
Noninhibitory Small Molecule Chaperones of Glucocerebrosidase
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID LYSOSOMAL STORAGE DISORDERS; ACID ALPHA-GLUCOSIDASE; GLYCOGENOSIS
TYPE-II; GAUCHER-DISEASE; PHARMACOLOGICAL CHAPERONES; BETA-GLUCOSIDASE;
CHEMICAL CHAPERONES; HIGHLY POTENT; THERAPY; ENZYME
AB A major challenge in the field of Gaucher disease has been the development of new therapeutic strategies including molecular chaperones. All previously described chaperones of glucocerebrosidase are enzyme inhibitors, which complicates their clinical development because their chaperone activity must be balanced against the functional inhibition of the enzyme. Using a novel high throughput screening methodology, we identified a chemical series that does not inhibit the enzyme but can still facilitate its translocation to the lysosome as measured by immunostaining of glucocerebrosidase in patient fibroblasts. These compounds provide the basis for the development of a novel approach toward small molecule treatment for patients with Gaucher disease.
C1 [Patnaik, Samarjit; Zheng, Wei; Motabar, Omid; Southall, Noel; Lea, Wendy A.; Leister, William; Marugan, Juan J.] Natl Ctr Adv Translat Sci, NIH Chem Genom Ctr, Natl Inst Hlth, Rockville, MD 20850 USA.
[Choi, Jae H.; Motabar, Omid; Westbroek, Wendy; Velayati, Arash; Goldin, Ehud; Sidransky, Ellen] Natl Human Genome Res Inst, Natl Inst Hlth, Med Genet Branch, Bethesda, MD 20892 USA.
RP Marugan, JJ (reprint author), Natl Ctr Adv Translat Sci, NIH Chem Genom Ctr, Natl Inst Hlth, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM maruganj@mail.nih.gov
RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014
OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757
FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research;
Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health
FX This research was supported by the Molecular Libraries Initiative of the
NIH Roadmap for Medical Research and the Intramural Research Program of
the National Human Genome Research Institute, National Institutes of
Health. We thank Jim Bougie, Thomas Daniel Paul Shinn, Danielle van
Leer, and Christopher Leclair at the NCGC compound management and
analytical groups for assistance in compound handling, plating, and
purification.
NR 51
TC 48
Z9 48
U1 2
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD JUN 28
PY 2012
VL 55
IS 12
BP 5734
EP 5748
DI 10.1021/jm300063b
PG 15
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 965LP
UT WOS:000305769600005
PM 22646221
ER
PT J
AU Nunez, LE
Nybo, SE
Gonzalez-Sabin, J
Perez, M
Menendez, N
Brana, AF
Shaaban, KA
He, M
Moris, F
Salas, JA
Rohr, J
Mendez, C
AF Nunez, Luz E.
Nybo, Stephen E.
Gonzalez-Sabin, Javier
Perez, Maria
Menendez, Nuria
Brana, Alfredo F.
Shaaban, Khaled A.
He, Min
Moris, Francisco
Salas, Jose A.
Rohr, Juergen
Mendez, Carmen
TI A Novel Mithramycin Analogue with High Antitumor Activity and Less
Toxicity Generated by Combinatorial Biosynthesis
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PRODUCER STREPTOMYCES-ARGILLACEUS; CHROMOMYCIN A(3); CANCER-THERAPY;
ANTIBIOTIC MITHRAMYCIN; TRANSCRIPTION FACTOR; SUGAR BIOSYNTHESIS;
PANCREATIC-CANCER; DRUG MITHRAMYCIN; GENE-CLUSTER; IN-VITRO
AB Mithramycin is an antitumor compound produced by Streptomyces argillaceus that has been used for the treatment of several types of tumors and hypercalcaemia processes. However, its use in humans has been limited because of its side effects. Using combinatorial biosynthesis approaches, we have generated seven new mithramycin derivatives, which differ from the parental compound in the sugar profile or in both the sugar profile and the 3-side chain. From these studies three novel derivatives were OH 14,0 identified, demycarosyl-3D-beta-D-digitoxosylmithramycin SK, demycarosylmithramycin SDK, and demycarosyl-3D-beta-D-digitoxosylmithramycin SDK, which show high antitumor activity. The first one, which combines two structural features previously found to improve pharmacological behavior, was generated following two different strategies, and it showed less toxicity than mithramycin. Preliminary in vivo evaluation of its antitumor activity through hollow fiber assays, and in subcutaneous colon and melanoma cancers xenografts models, suggests that demycarosyl-3D-beta-D-digitoxosylmithramycin SK could be a promising antitumor agent worthy of further investigation.
C1 [Nybo, Stephen E.; Shaaban, Khaled A.; Rohr, Juergen] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA.
[Perez, Maria; Brana, Alfredo F.; Salas, Jose A.; Mendez, Carmen] Univ Oviedo, Dept Biol Func, E-33006 Oviedo, Spain.
[Nunez, Luz E.; Gonzalez-Sabin, Javier; Menendez, Nuria; Moris, Francisco] EntreChem SL, Oviedo, Spain.
[He, Min] Natl Canc Inst, Dev Therapeut Program, Div Canc Treatment & Diag, Natl Inst Hlth, Rockville, MD USA.
[Perez, Maria; Brana, Alfredo F.; Salas, Jose A.; Mendez, Carmen] Univ Oviedo, IUOPA, E-33006 Oviedo, Spain.
RP Rohr, J (reprint author), Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, 789 S Limestone St, Lexington, KY 40536 USA.
EM jrohr2@email.uky.edu; cmendezf@uniovi.es
RI Rohr, Jurgen/G-5375-2014; Brana, Alfredo/M-1836-2014;
OI Rohr, Jurgen/0000-0001-6447-5951; Brana, Alfredo/0000-0002-3277-9085;
Mendez-Fernandez, Maria del Carmen/0000-0003-2729-841X
FU National Institutes of Health [CA091901]; Spanish Ministry of Science
and Innovation [BIO2005-04115, BIO2008-00269, PET2005-0401]; Spanish
Ministry of Science and Innovation; Torres-Quevedo Program Funding from
the Spanish Ministry of Science and Innovation [PTQ04-3-0487];
University of Kentucky graduate school
FX This work was supported by grants from the National Institutes of Health
(Grant CA091901 to J.R.) and the Spanish Ministry of Science and
Innovation (Grants BIO2005-04115 and BIO2008-00269 to C.M. and Grant
PET2005-0401 to C.M. and F.M.). M.P. was the recipient of a predoctoral
fellowship from the Spanish Ministry of Science and Innovation. L.E.N.
was the recipient of Torres-Quevedo Program Funding (Grant PTQ04-3-0487)
from the Spanish Ministry of Science and Innovation. S.E.N. was
partially supported by a graduate fellowship from the University of
Kentucky graduate school.
NR 51
TC 27
Z9 29
U1 0
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD JUN 28
PY 2012
VL 55
IS 12
BP 5813
EP 5825
DI 10.1021/jm300234t
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 965LP
UT WOS:000305769600011
PM 22578073
ER
PT J
AU Ayele, FT
Hailu, E
Finan, C
Aseffa, A
Davey, G
Newport, MJ
Rotimi, CN
Adeyemo, A
AF Ayele, Fasil Tekola
Hailu, Elena
Finan, Chris
Aseffa, Abraham
Davey, Gail
Newport, Melanie J.
Rotimi, Charles N.
Adeyemo, Adebowale
TI Prediction of HLA Class II Alleles Using SNPs in an African Population
SO PLOS ONE
LA English
DT Article
ID MAJOR HISTOCOMPATIBILITY COMPLEX; SYMPATRIC ETHNIC-GROUPS; TYPING
IDENTIFIED 2; EXTENDED HUMAN MHC; ASSOCIATION ANALYSIS; KENYAN
POPULATION; GENOME-WIDE; GENE MAP; PODOCONIOSIS; SEQUENCE
AB Background: Despite the importance of the human leukocyte antigen (HLA) gene locus in research and clinical practice, direct HLA typing is laborious and expensive. Furthermore, the analysis requires specialized software and expertise which are unavailable in most developing country settings. Recently, in silico methods have been developed for predicting HLA alleles using single nucleotide polymorphisms (SNPs). However, the utility of these methods in African populations has not been systematically evaluated.
Methodology/Principal Findings: In the present study, we investigate prediction of HLA class II (HLA-DRB1 and HLA-DQB1) alleles using SNPs in the Wolaita population, southern Ethiopia. The subjects comprised 297 Ethiopians with genome-wide SNP data, of whom 188 had also been HLA typed and were used for training and testing the model. The 109 subjects with SNP data alone were used for empirical prediction using the multi-allelic gene prediction method. We evaluated accuracy of the prediction, agreement between predicted and HLA typed alleles, and discriminative ability of the prediction probability supplied by the model. We found that the model predicted intermediate (two-digit) resolution for HLA-DRB1 and HLA-DQB1 alleles at accuracy levels of 96% and 87%, respectively. All measures of performance showed high accuracy and reliability for prediction. The distribution of the majority of HLA alleles in the study was similar to that previously reported for the Oromo and Amhara ethnic groups from Ethiopia.
Conclusions/Significance: We demonstrate that HLA class II alleles can be predicted from SNP genotype data with a high level of accuracy at intermediate (two-digit) resolution in an African population. This finding offers new opportunities for HLA studies of disease epidemiology and population genetics in developing countries.
C1 [Ayele, Fasil Tekola; Rotimi, Charles N.; Adeyemo, Adebowale] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Hailu, Elena; Aseffa, Abraham] Armauer Hansen Res Inst, Addis Ababa, Ethiopia.
[Finan, Chris; Davey, Gail; Newport, Melanie J.] Brighton & Sussex Med Sch, Brighton, E Sussex, England.
RP Ayele, FT (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
EM ayeleft@mail.nih.gov
RI Aseffa, Abraham/J-3248-2016;
OI Aseffa, Abraham/0000-0002-8028-1150; Adeyemo,
Adebowale/0000-0002-3105-3231; Davey, Gail/0000-0003-2796-7468;
Tekola-Ayele, Fasil/0000-0003-4194-9370
FU Wellcome Trust [079791]; National Human Genome Research Institute,
National Institutes of Health, in the Center for Research on Genomics
and Global Health
FX This work was supported by the Wellcome Trust [grant number 079791]; and
the Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health, in the Center for Research on
Genomics and Global Health. The funders had no role in the study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 47
TC 4
Z9 4
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 28
PY 2012
VL 7
IS 6
AR e40206
DI 10.1371/journal.pone.0040206
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 966GR
UT WOS:000305826400061
ER
PT J
AU Flores, R
Shi, JX
Gail, MH
Gajer, P
Ravel, J
Goedert, JJ
AF Flores, Roberto
Shi, Jianxin
Gail, Mitchell H.
Gajer, Pawel
Ravel, Jacques
Goedert, James J.
TI Association of Fecal Microbial Diversity and Taxonomy with Selected
Enzymatic Functions
SO PLOS ONE
LA English
DT Article
ID BETA-GLUCURONIDASE; GUT MICROBIOME; HUMAN FECES; GLUCOSIDASE;
EXPRESSION; BACTERIA; ENZYMES
AB Few microbial functions have been compared to a comprehensive survey of the human fecal microbiome. We evaluated determinants of fecal microbial beta-glucuronidase and beta-glucosidase activities, focusing especially on associations with microbial alpha and beta diversity and taxonomy. We enrolled 51 healthy volunteers (26 female, mean age 39) who provided questionnaire data and multiple aliquots of a stool, from which proteins were extracted to quantify beta-glucuronidase and beta-glucosidase activities, and DNA was extracted to amplify and pyrosequence 16S rRNA gene sequences to classify and quantify microbiome diversity and taxonomy. Fecal beta-glucuronidase was elevated with weight loss of at least 5 lb. (P = 0.03), whereas beta-glucosidase was marginally reduced in the four vegetarians (P = 0.06). Both enzymes were correlated directly with microbiome richness and alpha diversity measures, directly with the abundance of four Firmicutes Clostridia genera, and inversely with the abundance of two other genera (Firmicutes Lactobacillales Streptococcus and Bacteroidetes Rikenellaceae Alistipes) (all P = 0.05-0.0001). Beta diversity reflected the taxonomic associations. These observations suggest that these enzymatic functions are performed by particular taxa and that diversity indices may serve as surrogates of bacterial functions. Independent validation and deeper understanding of these associations are needed, particularly to characterize functions and pathways that may be amenable to manipulation.
C1 [Flores, Roberto; Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Flores, Roberto] NCI, Canc Prevent Fellowship Program, Rockville, MD USA.
[Shi, Jianxin; Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Gajer, Pawel; Ravel, Jacques] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
RP Flores, R (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
EM floresr2@mail.nih.gov
OI Ravel, Jacques/0000-0002-0851-2233
FU National Cancer Institute, National Institutes of Health [Z01-CP010214]
FX This project (Z01-CP010214) was funded by the Intramural Research
Program of the National Cancer Institute, National Institutes of Health.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 22
TC 9
Z9 10
U1 3
U2 31
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 28
PY 2012
VL 7
IS 6
AR e39745
DI 10.1371/journal.pone.0039745
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 966GR
UT WOS:000305826400034
PM 22761886
ER
PT J
AU Rodriguez, V
Vasudevan, S
Noma, A
Carlson, BA
Green, JE
Suzuki, T
Chandrasekharappa, SC
AF Rodriguez, Virginia
Vasudevan, Sona
Noma, Akiko
Carlson, Bradley A.
Green, Jeffrey E.
Suzuki, Tsutomu
Chandrasekharappa, Settara C.
TI Structure-Function Analysis of Human TYW2 Enzyme Required for the
Biosynthesis of a Highly Modified Wybutosine (yW) Base in
Phenylalanine-tRNA
SO PLOS ONE
LA English
DT Article
ID TRANSGENIC MICE; GENE-EXPRESSION; MAMMARY-TUMORS; CANCER; LIVER; RAT;
SELENOCYSTEINE; CLASSIFICATION; CHROMOSOME-8; POSITION-37
AB Posttranscriptional modifications are critical for structure and function of tRNAs. Wybutosine (yW) and its derivatives are hyper-modified guanosines found at the position 37 of eukaryotic and archaeal tRNA(Phe). TYW2 is an enzyme that catalyzes a-amino-a-carboxypropyl transfer activity at the third step of yW biogenesis. Using complementation of a Delta TYW2 strain, we demonstrate here that human TYW2 (hTYW2) is active in yeast and can synthesize the yW of yeast tRNA(Phe). Structure-guided analysis identified several conserved residues in hTYW2 that interact with S-adenosyl-methionine (AdoMet), and mutation studies revealed that K225 and E265 are critical residues for the enzymatic activity. We previously reported that the human TYW2 is overexpressed in breast cancer. However, no difference in the tRNA(Phe) modification status was observed in either normal mouse tissue or a mouse tumor model that overexpresses Tyw2, indicating that hTYW2 may have a role in tumorigenesis unrelated to yW biogenesis.
C1 [Rodriguez, Virginia; Chandrasekharappa, Settara C.] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA.
[Vasudevan, Sona] Georgetown Univ, Med Ctr, Dept Biochem & Mol Cellular Biol, Washington, DC 20007 USA.
[Noma, Akiko; Suzuki, Tsutomu] Univ Tokyo, Grad Sch Engn, Dept Chem & Biotechnol, Tokyo, Japan.
[Carlson, Bradley A.] NCI, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA.
[Green, Jeffrey E.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
RP Rodriguez, V (reprint author), NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA.
EM chandra@mail.nih.gov
RI Suzuki, Tsutomu/J-1776-2015
OI Suzuki, Tsutomu/0000-0002-9731-1731
FU National Human Genome Research Institute; Center for Cancer Research,
National Cancer Institute, National Institutes of Health; JSPS
FX This work was supported by the Intramural Research Programs of the
National Human Genome Research Institute, and the Center for Cancer
Research, National Cancer Institute, National Institutes of Health. A.N.
thanks the JSPS Fellowship for Japanese Junior Scientists. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 35
TC 2
Z9 3
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 28
PY 2012
VL 7
IS 6
AR e39297
DI 10.1371/journal.pone.0039297
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 966GR
UT WOS:000305826400012
PM 22761755
ER
PT J
AU Prufer, K
Munch, K
Hellmann, I
Akagi, K
Miller, JR
Walenz, B
Koren, S
Sutton, G
Kodira, C
Winer, R
Knight, JR
Mullikin, JC
Meader, SJ
Ponting, CP
Lunter, G
Higashino, S
Hobolth, A
Dutheil, J
Karakoc, E
Alkan, C
Sajjadian, S
Catacchio, CR
Ventura, M
Marques-Bonet, T
Eichler, EE
Andre, C
Atencia, R
Mugisha, L
Junhold, J
Patterson, N
Siebauer, M
Good, JM
Fischer, A
Ptak, SE
Lachmann, M
Symer, DE
Mailund, T
Schierup, MH
Andres, AM
Kelso, J
Paabo, S
AF Pruefer, Kay
Munch, Kasper
Hellmann, Ines
Akagi, Keiko
Miller, Jason R.
Walenz, Brian
Koren, Sergey
Sutton, Granger
Kodira, Chinnappa
Winer, Roger
Knight, James R.
Mullikin, James C.
Meader, Stephen J.
Ponting, Chris P.
Lunter, Gerton
Higashino, Saneyuki
Hobolth, Asger
Dutheil, Julien
Karakoc, Emre
Alkan, Can
Sajjadian, Saba
Catacchio, Claudia Rita
Ventura, Mario
Marques-Bonet, Tomas
Eichler, Evan E.
Andre, Claudine
Atencia, Rebeca
Mugisha, Lawrence
Junhold, Joerg
Patterson, Nick
Siebauer, Michael
Good, Jeffrey M.
Fischer, Anne
Ptak, Susan E.
Lachmann, Michael
Symer, David E.
Mailund, Thomas
Schierup, Mikkel H.
Andres, Aida M.
Kelso, Janet
Paeaebo, Svante
TI The bonobo genome compared with the chimpanzee and human genomes
SO NATURE
LA English
DT Article
ID RETROTRANSPOSITION; LANDSCAPE; SEQUENCE; PRIMATES
AB Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours(1-4), and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other.
C1 [Pruefer, Kay; Siebauer, Michael; Good, Jeffrey M.; Fischer, Anne; Ptak, Susan E.; Lachmann, Michael; Andres, Aida M.; Kelso, Janet; Paeaebo, Svante] Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany.
[Munch, Kasper; Hobolth, Asger; Dutheil, Julien; Mailund, Thomas; Schierup, Mikkel H.] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus C, Denmark.
[Hellmann, Ines] Univ Vienna, Max F Perutz Labs, A-1030 Vienna, Austria.
[Akagi, Keiko; Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA.
[Akagi, Keiko; Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Miller, Jason R.; Walenz, Brian; Sutton, Granger] J Craig Venter Inst, Rockville, MD 20850 USA.
[Koren, Sergey] Univ Maryland, College Pk, MD 20742 USA.
[Kodira, Chinnappa; Winer, Roger; Knight, James R.] 454 Life Sci, Branford, CT 06405 USA.
[Mullikin, James C.] NHGRI, Genome Technol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Meader, Stephen J.; Ponting, Chris P.] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford OX1 3QX, England.
[Lunter, Gerton] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Higashino, Saneyuki] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Kanagawa 2268503, Japan.
[Karakoc, Emre; Alkan, Can; Sajjadian, Saba; Ventura, Mario; Marques-Bonet, Tomas; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Karakoc, Emre; Alkan, Can; Sajjadian, Saba; Ventura, Mario; Marques-Bonet, Tomas; Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA.
[Catacchio, Claudia Rita; Ventura, Mario] Univ Bari, Dipartimento Anat Patol & Genet, Sez Genet, I-70125 Bari, Italy.
[Marques-Bonet, Tomas] UPF CSIC, Inst Biol Evolutiva, ICREA, Barcelona 08003, Catalonia, Spain.
[Atencia, Rebeca] Jane Goodall Inst, Pointe Noire, Zaire.
[Mugisha, Lawrence] CSWCT, Entebbe, Uganda.
[Junhold, Joerg] Zoo Leipzig, D-04105 Leipzig, Germany.
[Patterson, Nick] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Good, Jeffrey M.] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA.
[Fischer, Anne] Int Ctr Insect Physiol & Ecol, Nairobi 00100, Kenya.
[Schierup, Mikkel H.] Aarhus Univ, Dept Biosci, DK-8000 Aarhus C, Denmark.
RP Prufer, K (reprint author), Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany.
EM pruefer@eva.mpg.de; paabo@eva.mpg.de
RI Andres, Aida/B-4088-2014; Marques-Bonet, Tomas/I-4618-2014; Schierup,
Mikkel/F-1675-2010; Catacchio, Claudia/P-8898-2015; Lunter,
Gerton/H-4939-2016; Dutheil, Julien/K-5479-2016; Ventura,
Mario/E-6420-2011; Munch, Kasper/A-1434-2010; Alkan, Can/D-2982-2009;
Symer, David/E-4173-2011
OI Ponting, Chris/0000-0003-0202-7816; Hobolth, Asger/0000-0003-4056-1286;
Lunter, Gerton/0000-0002-3798-2058; Andres, Aida/0000-0002-8590-9672;
Marques-Bonet, Tomas/0000-0002-5597-3075; Schierup,
Mikkel/0000-0002-5028-1790; Catacchio, Claudia/0000-0002-2166-723X;
Dutheil, Julien/0000-0001-7753-4121; Mailund,
Thomas/0000-0001-6206-9239; Ventura, Mario/0000-0001-7762-8777; Munch,
Kasper/0000-0003-2880-6252; Alkan, Can/0000-0002-5443-0706;
FU ERC [233297, StG_20091118]; National Institutes of Health
[2R01GM077117-04A1, HG002385]; Ramon y Cajal grant (MICINN-RYC); Ohio
State University Comprehensive Cancer Center; Ohio Supercomputer Center
[PAS0425]; Ohio Cancer Research Associates [GRT00024299]; Wellcome Trust
[090532/Z/09/Z]; US National Science Foundation [OISE-0754461]; Danish
Council for Independent Research \ Natural Sciences [09-062535]
FX The sequencing effort was made possible by the ERC (grant 233297,
TWOPAN) and the Max Planck Society. We thank D. Reich and L. Vigilant
for comments; the 454 Sequencing Center, the MPI-EVA sequencing group,
M. Kircher, M. Rampp and M. Halbwax for technical support; the staff of
Zoo Leipzig (Germany), the Ngamba Island Chimpanzee Sanctuary (Entebbe,
Uganda), the Tchimpounga Chimpanzee Rehabilitation Center (Pointe-Noire,
Republic of Congo) and the Lola ya Bonobo bonobo sanctuary (Kinshasa,
Democratic Republic of Congo) for providing samples; and A. Navarro, E.
Gazave and C. Baker for performing the ArrayCGH hybridizations. The ape
distribution layers for Fig. 1a were provided by UNEP-WCMC and IUCN.2008
(IUCN Red List of Threatened Species, Version 2011.2,
http://www.iucnredlist.org). The National Institutes of Health provided
funding for J.R.M., B. W., S. K., G. S. (2R01GM077117-04A1), J.C.M.
(Intramural Research Program of the National Human Genome Research
Institute) and E. E. E. (HG002385). E. E. E is an Investigator of the
Howard Hughes Medical Institute. T.M.-B. was supported by a Ramon y
Cajal grant (MICINN-RYC 2010) and an ERC Starting Grant (StG_20091118);
D. E. S., K. A. and S. H. were supported by the Ohio State University
Comprehensive Cancer Center, the Ohio Supercomputer Center (#PAS0425)
and the Ohio Cancer Research Associates (GRT00024299); and G. L. was
supported by a Wellcome Trust grant (090532/Z/09/Z). The US National
Science Foundation provided an International Postdoctoral Fellowship
(OISE-0754461) to J.M.G. The Danish Council for Independent Research
vertical bar Natural Sciences (grant no. 09-062535) provided funding for
K.M. and M.H.S.
NR 30
TC 136
Z9 141
U1 9
U2 169
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUN 28
PY 2012
VL 486
IS 7404
BP 527
EP 531
DI 10.1038/nature11128
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600042
PM 22722832
ER
PT J
AU Marini, JC
Forlino, A
AF Marini, Joan C.
Forlino, Antonella
TI Replenishing Cartilage from Endogenous Stem Cells
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Marini, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA.
[Forlino, Antonella] Univ Pavia, Dept Mol Med, Biochem Sect, I-27100 Pavia, Italy.
RP Marini, JC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA.
RI Forlino, Antonella/H-5385-2015
OI Forlino, Antonella/0000-0002-6385-1182
NR 5
TC 7
Z9 9
U1 2
U2 19
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 28
PY 2012
VL 366
IS 26
BP 2522
EP 2524
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 965DP
UT WOS:000305747000015
PM 22738103
ER
PT J
AU Park, SS
Wu, WW
Zhou, Y
Shen, RF
Martin, B
Maudsley, S
AF Park, Sung-Soo
Wu, Wells W.
Zhou, Yu
Shen, Rong-Fong
Martin, Bronwen
Maudsley, Stuart
TI Effective correction of experimental errors in quantitative proteomics
using stable isotope labeling by amino acids in cell culture (SILAC)
SO JOURNAL OF PROTEOMICS
LA English
DT Article
DE SILAC; Incomplete isotope labeling; Arginine-to-proline conversion;
Label-swap replication; Receptor
ID COMPLEX PROTEIN MIXTURES; GROWTH-FACTOR RECEPTOR; MUSCARINIC RECEPTOR;
KINASE; PHOSPHORYLATION; ARGININE; ACTIVATION; CONVERSION;
QUANTIFICATION; ASSOCIATION
AB Accurate and reliable quantitative proteomics in cell culture has been considerably facilitated by the introduction of the stable isotope labeling by amino acids in cell culture (SILAC), combined with high resolution mass spectrometry. There are however several major sources of quantification errors that commonly occur with SILAC techniques, i.e. incomplete incorporation of isotopic amino acids, arginine-to-proline conversion, and experimental errors in final sample mixing. Dataset normalization is a widely adopted solution to such errors, however this may not completely prevent introducing incorrect expression ratios. Here we demonstrate that a label-swap replication of SILAC experiments was able to effectively correct experimental errors by averaging ratios measured in individual replicates using quantitative proteomics and phosphoproteomics of ligand treatment of neural cell cultures. Furthermore, this strategy was successfully applied to a SILAC triplet experiment, which presents a much more complicated experimental matrix, affected by both incomplete labeling and arginine-to-proline conversion. Based on our results, we suggest that SILAC experiments should be designed to incorporate label-swap replications for enhanced reliability in expression ratios. Published by Elsevier B.V.
C1 [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Wu, Wells W.; Shen, Rong-Fong; Martin, Bronwen] NIA, Metab Unit, NIH, Baltimore, MD 21224 USA.
RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM maudsleyst@mail.nih.gov
RI Zhou, Yu/M-7975-2014
FU Intramural Research Program of the National Institutes of Health
FX This work was carried out entirely with the support of the Intramural
Research Program of the National Institutes of Health.
NR 33
TC 15
Z9 15
U1 4
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-3919
J9 J PROTEOMICS
JI J. Proteomics
PD JUN 27
PY 2012
VL 75
IS 12
BP 3720
EP 3732
DI 10.1016/j.jprot.2012.04.035
PG 13
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 982ZU
UT WOS:000307086500028
PM 22575385
ER
PT J
AU Anzalone, A
Lizardi-Ortiz, JE
Ramos, M
De Mei, C
Hopf, FW
Iaccarino, C
Halbout, B
Jacobsen, J
Kinoshita, C
Welter, M
Caron, MG
Bonci, A
Sulzer, D
Borrelli, E
AF Anzalone, Andrea
Lizardi-Ortiz, Jose E.
Ramos, Maria
De Mei, Claudia
Hopf, F. Woodward
Iaccarino, Ciro
Halbout, Briac
Jacobsen, Jacob
Kinoshita, Chisato
Welter, Marc
Caron, Marc G.
Bonci, Antonello
Sulzer, David
Borrelli, Emiliana
TI Dual Control of Dopamine Synthesis and Release by Presynaptic and
Postsynaptic Dopamine D2 Receptors
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID TYROSINE-HYDROXYLASE ACTIVITY; MICE LACKING DOPAMINE-D-2; KNOCK-OUT
MICE; IN-VIVO; DEFICIENT MICE; BASAL GANGLIA; CORTICOSTRIATAL TERMINALS;
STRIATAL SYNAPTOSOMES; INHIBITORY CONTROL; NUCLEUS-ACCUMBENS
AB Dysfunctions of dopaminergic homeostasis leading to either low or high dopamine (DA) levels are causally linked to Parkinson's disease, schizophrenia, and addiction. Major sites of DA synthesis are the mesencephalic neurons originating in the substantia nigra and ventral tegmental area; these structures send major projections to the dorsal striatum (DSt) and nucleus accumbens (NAcc), respectively. DA finely tunes its own synthesis and release by activating DAD2 receptors (D2R). To date, this critical D2R-dependent function was thought to be solely due to activation of D2Rs on dopaminergic neurons (D2 autoreceptors); instead, using site-specific D2R knock-out mice, we uncover that D2 heteroreceptors located on non-DAergic medium spiny neurons participate in the control of DA levels. This D2 heteroreceptor-mediated mechanism is more efficient in the DSt than in NAcc, indicating that D2R signaling differentially regulates mesolimbic-versus nigrostriatal-mediated functions. This study reveals previously unappreciated control of DA signaling, shedding new light on region-specific regulation of DA-mediated effects.
C1 [Anzalone, Andrea; Ramos, Maria; De Mei, Claudia; Iaccarino, Ciro; Halbout, Briac; Kinoshita, Chisato; Welter, Marc; Borrelli, Emiliana] Univ Calif Irvine, INSERM, U904, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA.
[Lizardi-Ortiz, Jose E.; Sulzer, David] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
[Bonci, Antonello] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA.
[Jacobsen, Jacob; Caron, Marc G.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
[Bonci, Antonello] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA.
[Sulzer, David] Columbia Univ, Dept Neurol, New York, NY 10032 USA.
[Sulzer, David] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.
RP Borrelli, E (reprint author), Univ Calif Irvine, INSERM, U904, Dept Microbiol & Mol Genet, 308 Sprague Hall, Irvine, CA 92697 USA.
EM borrelli@uci.edu
FU NIH Grant [DA024689]; European Community Grant EC [LSHM-CT-2004-005166];
[INSERM-44790]
FX This work was supported by INSERM-44790, NIH Grant DA024689, and
European Community Grant EC LSHM-CT-2004-005166 (to E.B.). We are
grateful to Drs. G. Schutz and W. Wurst for the generous gift of the
D1CRE mice and En1Cre mice, respectively. We thank Andree Dierich and
members of the IGBMC mouse facility for generating
D2Rfloxflox mice; N. Tognazzi, A. Usiello, E. Erbs, R.
Lutzing, C. Paparo for the initial interest in this work; E. Chen and A.
Nasamran for technical assistance.
NR 58
TC 71
Z9 72
U1 0
U2 23
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 27
PY 2012
VL 32
IS 26
BP 9023
EP 9034
DI 10.1523/JNEUROSCI.0918-12.2012
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 967FB
UT WOS:000305890700025
PM 22745501
ER
PT J
AU Gold, PW
Pavlatou, MG
Carlson, PJ
Luckenbaugh, DA
Costello, R
Bonne, O
Csako, G
Drevets, WC
Remaley, AT
Charney, DS
Neumeister, A
Kling, MA
AF Gold, Philip W.
Pavlatou, Maria G.
Carlson, Paul J.
Luckenbaugh, David A.
Costello, Rene
Bonne, Omer
Csako, Gyorgy
Drevets, Wayne C.
Remaley, Alan T.
Charney, Dennis S.
Neumeister, Alexander
Kling, Mitchel A.
TI Unmedicated, remitted patients with major depression have decreased
serum immunoglobulin A
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Major depression; Immunoglobulin IgA; Proinflammatory state
ID IGA DEFICIENCY; BODY-COMPOSITION; DISEASE; CELLS; INTERLEUKIN-6;
CYTOKINES; DISORDER; CHILDREN; IMMUNITY; MARKERS
AB Patents with major depression have evidence of a proinflammatory state with consistent elevations in acute phase proteins and in the levels of inflammatory mediators such as interleukin-6 and tumor necrosis factor-alpha. We report here a study of the serum levels of immunoglobulin A (IgA) in medication-free patients with major depression in the remitted state (ruMDD). Selective IgA deficiency is the most common form of immunoglobulin abnormality, and is often associated with a higher than expected incidence of proinflammatory and autoimmune phenomena. We measured serum IgG, IgM, and IgA in 28 ruMDD patients and 27 healthy subjects (Ctrl) at 0 (pretreatment), 7, and 24 h following sham depletion and tryptophan (TrpD) depletion conducted at least 8 days apart under balanced, randomized, blinded conditions. Immunoglobulins were measured by automated immunonephelometry. Data were analyzed by repeated measures ANOVA with diagnosis as a fixed effect and drug (TrpD vs. sham), and time as repeated measures factors. Serum IgA was consistently lower in ruMDD patients vs. Ctrl at all time points examined (p < 0.04 for main effect of diagnosis). Serum IgG and IgM levels did not show significant differences by diagnosis. Medication-free patients with major depression in the remitted state have a significant reduction in serum IgA levels measured on multiple occasions. In the light of the fact that IgA serves many immunomodulatory, anti-inflammatory roles, this finding supports the concept that major depressive illness represents a proinflammatory state. Published by Elsevier Ireland Ltd.
C1 [Gold, Philip W.; Pavlatou, Maria G.; Kling, Mitchel A.] NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA.
[Carlson, Paul J.] Univ Utah, Dept Psychiat, Sch Med, Salt Lake City, UT 84132 USA.
[Carlson, Paul J.] Salt Lake VA Med Ctr, Salt Lake City, UT 84132 USA.
[Luckenbaugh, David A.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
[Costello, Rene; Csako, Gyorgy; Remaley, Alan T.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Bonne, Omer] Hadassah Hebrew Univ Med Ctr, Dept Psychiat, IL-91120 Jerusalem, Israel.
[Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK 74136 USA.
[Charney, Dennis S.] Mt Sinai Sch Med, Off Dean, New York, NY 10029 USA.
[Neumeister, Alexander] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[Kling, Mitchel A.] Philadelphia VA Med Ctr, Behav Hlth Serv, Philadelphia, PA USA.
[Kling, Mitchel A.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
RP Gold, PW (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, Bldg 10-2D-46-12824,10 Ctr Dr, Bethesda, MD 20892 USA.
EM philipgold@mail.nih.gov; pavlatom@mail.nih.gov;
paul.carlson@hsc.utah.edu; luckenbd@mail.nih.gov;
rcostello@mail.nih.gov; BONNE@hadassah.org.il; LMCSJ@aol.com;
wdrevets@laureateinstitute.org; aremaley1@cc.nih.gov;
dennis.charney@mssm.edu; alexander.neumeister@mssm.edu;
Mitchel.Kling@uphs.upenn.edu
OI Kling, Mitchel/0000-0002-2232-1409
FU NIMH DIRP
FX Dr. Philip W. Gold, Dr. Maria G. Pavlatou, Dr. Paul J. Carlson, Dr.
David A. Luckenbaughc, Mr. Rene Costello, Dr. Omer Bonne, Dr.
Gyorgy Csako, Dr. Alan Remaley, Dr. Alexander Neumeister, and Dr.
Mitchel A. King have no conflicts to disclose. Dr. Wayne C. Drevets has
reported that the research support for this project was provided
entirely by the NIMH DIRP. Although Dr. Drevets has no financial
conflicts that are relevant to the subject matter of the manuscript,
during the past two years he has served as a consultant for the
following companies: Pfizer, Eisai, Rules Based Medicine, Johnson and
Johnson. Dr. Drevets also is named as co-inventor for a Use Patent filed
by the NIMH for Scopolamine in the Treatment of Depression. Dr. Dennis
S. Charney has reported that he and Mount Sinai School of Medicine have
been named on a use patent of Ketamine for the treatment of depression.
If Ketamine were shown to be effective in the treatment of depression
and received approval from the Food and Drug Administration (FDA) for
this indication, Dr. Charney and Mount Sinai School of Medicine could
benefit financially. Dr. Charney has also disclosed that he is not
currently engaged in any consulting activity and has had no activity for
the past three years.
NR 32
TC 7
Z9 7
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD JUN 27
PY 2012
VL 520
IS 1
BP 1
EP 5
DI 10.1016/j.neulet.2012.04.072
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 969AE
UT WOS:000306027300001
PM 22579817
ER
PT J
AU Cao, D
Jiao, XD
Liu, X
Hennis, A
Leske, MC
Nemesure, B
Hejtmancik, JF
AF Cao, Dan
Jiao, Xiaodong
Liu, Xing
Hennis, Anselm
Leske, M. Cristina
Nemesure, Barbara
Hejtmancik, J. Fielding
TI CDKN2B Polymorphism Is Associated with Primary Open-Glaucoma (POAG) in
the Afro-Caribbean Population of Barbados, West Indies
SO PLOS ONE
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; GENOME-WIDE ASSOCIATION; TO-DISC RATIO; COMMON
VARIANTS; RISK-FACTORS; OPTIC DISC; SUSCEPTIBILITY LOCI; GENE
POLYMORPHISMS; AFRICAN DESCENT; EYE
AB The purpose of this study was to confirm previously reported associations of common variants in or near CDC7/TGFBR3, ZP4, SRBD1, ELOVL5, CAV1/CAV2, TLR4, CDKN2B, CDKN2B-AS1, ATOH7, PLXDC2, TMTC2, SIX1, and CARD10, with primary open angle glaucoma (POAG) in the Afro-Caribbean population of Barbados, West Indies. A total of 437 unrelated subjects from the Barbados Family Study of Open Angle Glaucoma (BFSG), including 272 with POAG and 165 unaffected individuals were included in this study. Eighteen SNPs were genotyped by using the multiplex SNaPshot method. Allelic, genotypic and model-based (dominant, recessive, and additive) associations of the SNPs with POAG were analyzed using Chi-squared tests and logistic regression. SNP rs1063192 (near CDKN2B) was found to be significantly associated with POAG (allelic P = 0.0008, genotypic P = 0.0029), and the minor allele C of rs1063192 was protective against POAG (OR = 0.39; 95% CI = 0.22-0.69). Suggestive association was also noted for rs7916697 (near ATHO7, allelic P = 0.0096, genotypic P = 0.01) with the minor allele being protective (OR = 0.67; 95% CI = 0.50-0.91), although this finding did not withstand correction for multiple testing. However, a significant interactive effect on POAG risk was identified between rs1063192 and rs7916697 (P-interaction = 2.80x10(-5)). Individuals with the rs1063192 protective genotype CC or CT and also rs7916697 genotypes GG or GA show a significantly decreased risk of POAG (OR = 0.17, 95% CI: 0.07-0.41). Our study confirms the significant association between SNP rs1063192 (CDKN2B, previously shown to influence vertical cup-to-disc ratio and POAG at 9p21) and POAG in the Afro-Caribbean population of Barbados. The minor allele of rs1063192 interacts with that of rs7916697 (ATOH7)) to reduce POAG risk. Our results also suggest that rs1063912 is a common protective variant for POAG in populations of African as well as European descent.
C1 [Cao, Dan; Jiao, Xiaodong; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Cao, Dan; Liu, Xing] Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China.
[Hennis, Anselm] Univ W Indies, Bridgetown, Barbados.
[Hennis, Anselm] Minist Hlth, Bridgetown, Barbados.
[Leske, M. Cristina; Nemesure, Barbara] Stony Brook Med, Dept Prevent Med, Stony Brook, NY USA.
RP Cao, D (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
EM f3h@helix.nih.gov
FU National Eye Institute (NEI)
FX There are no current external funding sources for this study other than
the intramural program of the National Eye Institute (NEI).
NR 41
TC 34
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U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2012
VL 7
IS 6
AR e39278
DI 10.1371/journal.pone.0039278
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 966GL
UT WOS:000305825800028
PM 22761751
ER
PT J
AU Standley, S
Petralia, RS
Gravell, M
Hamilton, R
Wang, YX
Schubert, M
Wenthold, RJ
AF Standley, Steve
Petralia, Ronald S.
Gravell, Manneth
Hamilton, Rebecca
Wang, Ya-Xian
Schubert, Manfred
Wenthold, Robert J.
TI Trafficking of the NMDAR2B Receptor Subunit Distal Cytoplasmic Tail from
Endoplasmic Reticulum to the Synapse
SO PLOS ONE
LA English
DT Article
ID DENSITY PROTEIN PSD-95; ER RETENTION SIGNAL; TRANS-GOLGI NETWORK;
VESICULAR STOMATITIS-VIRUS; PRESYNAPTIC ACTIVE ZONES;
HIPPOCAMPAL-NEURONS; SECRETORY PATHWAY; CELL-SURFACE; PDZ PROTEINS;
CORTICAL-NEURONS
AB NMDA receptor NR2A/B subunits have PDZ-binding domains on their extreme C-termini that are known to interact with the PSD-95 family and other PDZ proteins. We explore the interactions between PSD-95 family proteins and the NR2A/B cytoplasmic tails, and the consequences of these interactions, from the endoplasmic reticulum (ER) through delivery to the synapse in primary rat hippocampal and cortical cultured neurons. We find that the NR2A/B cytoplasmic tails cluster very early in the secretory pathway and interact serially with SAP102 beginning at the intermediate compartment, and then PSD-95. We further establish that colocalization of the distal C-terminus of NR2B and PSD-95 begins at the trans-Golgi Network (TGN). Formation of NR2B/PSD-95/SAP102 complexes is dependent on the PDZ binding domain of NR2B subunits, but association with SAP102 and PSD-95 plays no distinguishable role in cluster pre-formation or initial targeting to the vicinity of the synapse. Instead the PDZ binding domain plays a role in restricting cell-surface clusters to postsynaptic targets.
C1 [Standley, Steve] Western Univ Hlth Sci, Grad Coll Biomed Sci, Pomona, CA USA.
[Petralia, Ronald S.; Wang, Ya-Xian; Wenthold, Robert J.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD USA.
[Gravell, Manneth; Hamilton, Rebecca; Schubert, Manfred] NINDS, Mol Virol & Neurogenet Sect, NIH, Bethesda, MD 20892 USA.
RP Standley, S (reprint author), Western Univ Hlth Sci, Grad Coll Biomed Sci, Pomona, CA USA.
EM sstandley@westernu.edu
FU National Institute on Deafness and Other Communication Disorders
(NIDCD); National Institutes on Neurological Diseases and Stroke (NINDS)
FX This study was funded by the Intramural programs of the National
Institute on Deafness and Other Communication Disorders (NIDCD) and the
National Institutes on Neurological Diseases and Stroke (NINDS). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 76
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U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2012
VL 7
IS 6
AR e39585
DI 10.1371/journal.pone.0039585
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 966GL
UT WOS:000305825800046
PM 22761831
ER
PT J
AU Verhagen, JH
Munster, VJ
Majoor, F
Lexmond, P
Vuong, O
Stumpel, JBG
Rimmelzwaan, GF
Osterhaus, ADME
Schutten, M
Slaterus, R
Fouchier, RAM
AF Verhagen, Josanne H.
Munster, Vincent J.
Majoor, Frank
Lexmond, Pascal
Oanh Vuong
Stumpel, Job B. G.
Rimmelzwaan, Guus F.
Osterhaus, Albert D. M. E.
Schutten, Martin
Slaterus, Roy
Fouchier, Ron A. M.
TI Avian Influenza A Virus in Wild Birds in Highly Urbanized Areas
SO PLOS ONE
LA English
DT Article
ID DUCKS; HEMAGGLUTININ; SURVEILLANCE
AB Avian influenza virus (AIV) surveillance studies in wild birds are usually conducted in rural areas and nature reserves. Less is known of avian influenza virus prevalence in wild birds located in densely populated urban areas, while these birds are more likely to be in close contact with humans. Influenza virus prevalence was investigated in 6059 wild birds sampled in cities in the Netherlands between 2006 and 2009, and compared with parallel AIV surveillance data from low urbanized areas in the Netherlands. Viral prevalence varied with the level of urbanization, with highest prevalence in low urbanized areas. Within cities virus was detected in 0.5% of birds, while seroprevalence exceeded 50%. Ring recoveries of urban wild birds sampled for virus detection demonstrated that most birds were sighted within the same city, while few were sighted in other cities or migrated up to 2659 km away from the sample location in the Netherlands. Here we show that urban birds were infected with AIVs and that urban birds were not separated completely from populations of long-distance migrants. The latter suggests that wild birds in cities may play a role in the introduction of AIVs into cities. Thus, urban bird populations should not be excluded as a human-animal interface for influenza viruses.
C1 [Verhagen, Josanne H.; Lexmond, Pascal; Oanh Vuong; Stumpel, Job B. G.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Schutten, Martin; Fouchier, Ron A. M.] Erasmus MC, Natl Influenza Ctr, Rotterdam, Netherlands.
[Verhagen, Josanne H.; Lexmond, Pascal; Oanh Vuong; Stumpel, Job B. G.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Schutten, Martin; Fouchier, Ron A. M.] Erasmus MC, Dept Virol, Rotterdam, Netherlands.
[Munster, Vincent J.] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Majoor, Frank; Slaterus, Roy] Sovon Dutch Ctr Field Ornithol, Nijmegen, Netherlands.
RP Verhagen, JH (reprint author), Erasmus MC, Natl Influenza Ctr, Rotterdam, Netherlands.
EM r.fouchier@erasmusmc.nl
RI Fouchier, Ron/A-1911-2014;
OI Fouchier, Ron/0000-0001-8095-2869; Osterhaus,
Albert/0000-0002-6074-1172; Munster, Vincent/0000-0002-2288-3196
FU Dutch Ministry of Agriculture; EU DG; EU [044490]; NIAID NIH
[HHSN266200700010C]; Division of Intramural Research, National Institute
of Allergy and Infectious Diseases, National Institutes of Health
FX This work was sponsored by grants from the Dutch Ministry of
Agriculture, the EU DG Sanco monitoring program, EU Framework six
program NewFluBird (044490), and contract NIAID NIH HHSN266200700010C.
VJM is currently supported by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 16
TC 9
Z9 10
U1 3
U2 24
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2012
VL 7
IS 6
AR e38256
DI 10.1371/journal.pone.0038256
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 966GL
UT WOS:000305825800010
PM 22761671
ER
PT J
AU Yanpallewar, SU
Barrick, CA
Buckley, H
Becker, J
Tessarollo, L
AF Yanpallewar, Sudhirkumar U.
Barrick, Colleen A.
Buckley, Hannah
Becker, Jodi
Tessarollo, Lino
TI Deletion of the BDNF Truncated Receptor TrkB.T1 Delays Disease Onset in
a Mouse Model of Amyotrophic Lateral Sclerosis
SO PLOS ONE
LA English
DT Article
ID MOTOR-NEURON DEGENERATION; NEUROTROPHIN RECEPTOR; IN-VIVO; TRANSGENIC
MICE; NERVOUS-SYSTEM; SPINAL-CORDS; FULL-LENGTH; CELL-DEATH; EXPRESSION;
GENE
AB Brain Derived Neurotrophic Factor (BDNF) exerts strong pro-survival effects on developing and injured motoneurons. However, in clinical trials, BDNF has failed to benefit patients with amyotrophic lateral sclerosis (ALS). To date, the cause of this failure remains unclear. Motoneurons express the TrkB kinase receptor but also high levels of the truncated TrkB. T1 receptor isoform. Thus, we investigated whether the presence of this receptor may affect the response of diseased motoneurons to endogenous BDNF. We deleted TrkB. T1 in the hSOD1(G93A) ALS mouse model and evaluated the impact of this mutation on motoneuron death, muscle weakness and disease progression. We found that TrkB. T1 deletion significantly slowed the onset of motor neuron degeneration. Moreover, it delayed the development of muscle weakness by 33 days. Although the life span of the animals was not affected we observed an overall improvement in the neurological score at the late stage of the disease. To investigate the effectiveness of strategies aimed at bypassing the TrkB. T1 limit to BDNF signaling we treated SOD1 mutant mice with the adenosine A2A receptor agonist CGS21680, which can activate motoneuron TrkB receptor signaling independent of neurotrophins. We found that CGS21680 treatment slowed the onset of motor neuron degeneration and muscle weakness similarly to TrkB. T1 removal. Together, our data provide evidence that endogenous TrkB. T1 limits motoneuron responsiveness to BDNF in vivo and suggest that new strategies such as Trk receptor transactivation may be used for therapeutic intervention in ALS or other neurodegenerative disorders.
C1 [Yanpallewar, Sudhirkumar U.; Barrick, Colleen A.; Buckley, Hannah; Becker, Jodi; Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
RP Yanpallewar, SU (reprint author), NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
EM tessarol@mail.nih.gov
FU National Cancer Institute, Center for Cancer Research, NIH
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research, NIH. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 48
TC 23
Z9 23
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2012
VL 7
IS 6
AR e39946
DI 10.1371/journal.pone.0039946
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 966GL
UT WOS:000305825800080
PM 22761934
ER
PT J
AU Yong, ST
Wang, XF
AF Yong, Sheila T.
Wang, Xiao-Fan
TI A Novel, Non-Apoptotic Role for Scythe/BAT3: A Functional Switch between
the Pro- and Anti-Proliferative Roles of p21 during the Cell Cycle
SO PLOS ONE
LA English
DT Article
ID UBIQUITIN LIGASE COMPLEX; DNA-DAMAGE; LUNG-CANCER; CYTOPLASMIC
LOCALIZATION; INDUCED PHOSPHORYLATION; NUCLEAR ACCUMULATION; MEDIATED
DEGRADATION; PROTEASOMAL TURNOVER; BREAST-CANCER; P21(CIP1)
AB Background: Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investigated whether BAT3 is also involved in cell-cycle progression.
Methods/Principal Findings: Using a stable-inducible Bat3-knockdown cellular system, we demonstrated that reduced BAT3 protein level causes a delay in both G1/S transition and G2/M progression. Concurrent with these changes in cell-cycle progression, we observed a reduction in the turnover and phosphorylation of the CDK inhibitor p21, which is best known as an inhibitor of DNA replication; however, phosphorylated p21 has also been shown to promote G2/M progression. Our findings indicate that in Bat3-knockdown cells, p21 continues to be synthesized during cell-cycle phases that do not normally require p21, resulting in p21 protein accumulation and a subsequent delay in cell-cycle progression. Finally, we showed that BAT3 co-localizes with p21 during the cell cycle and is required for the translocation of p21 from the cytoplasm to the nucleus during the G1/S transition and G2/M progression.
Conclusion:: Our study reveals a novel, non-apoptotic role for BAT3 in cell-cycle regulation. By maintaining a low p21 protein level during the G1/S transition, BAT3 counteracts the inhibitory effect of p21 on DNA replication and thus enables the cells to progress from G1 to S phase. Conversely, during G2/M progression, BAT3 facilitates p21 phosphorylation by cyclin A/Cdk2, an event required for G2/M progression. BAT3 modulates these pro- and anti-proliferative roles of p21 at least in part by regulating cyclin A abundance, as well as p21 translocation between the cytoplasm and the nucleus to ensure that it functions in the appropriate intracellular compartment during each phase of the cell cycle.
C1 [Yong, Sheila T.; Wang, Xiao-Fan] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA.
RP Yong, ST (reprint author), Natl Inst Environm Hlth Sci, Inositol Signaling Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC USA.
EM xiao.fan.wang@duke.edu
FU National Institutes of Health [CA123250, GM83000]
FX This study was supported by National Institutes of Health CA123250 and
GM83000 to XFW. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 67
TC 11
Z9 11
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2012
VL 7
IS 6
AR e38085
DI 10.1371/journal.pone.0038085
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 966GL
UT WOS:000305825800008
PM 22761665
ER
PT J
AU Rich, AM
Bombarda, E
Schenk, AD
Lee, PE
Cox, EH
Spuches, AM
Hudson, LD
Kieffer, B
Wilcox, DE
AF Rich, Anne M.
Bombarda, Elisa
Schenk, Austin D.
Lee, Paul E.
Cox, Elizabeth H.
Spuches, Anne M.
Hudson, Lynn D.
Kieffer, Bruno
Wilcox, Dean E.
TI Thermodynamics of Zn2+ Binding to Cys(2)His(2) and Cys(2)HisCys Zinc
Fingers and a Cys(4) Transcription Factor Site
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID ISOTHERMAL TITRATION CALORIMETRY; RECEPTOR DNA-BINDING; HIV-1
NUCLEOCAPSID PROTEIN; GLUCOCORTICOID-RECEPTOR; METAL-BINDING; HIDDEN
THERMODYNAMICS; DEPENDENT STRUCTURE; REDOX REACTIONS; LIGAND-BINDING;
FACTOR-IIIA
AB The thermodynamics of Zn2+ binding to three peptides corresponding to naturally occurring Zn-binding sequences in transcription factors have been quantified with isothermal titration calorimetry (ITC). These peptides, the third zinc finger of Sp1 (Sp1-3), the second zinc finger of myelin transcription factor 1 (MyT1-2), and the second Zn-binding sequence of the DNA-binding domain of glucocorticoid receptor (GR-2), bind Zn2+ with Cys(2)His(2), Cys(2)HisCys, and Cys(4) coordination, respectively. Circular dichroism confirms that Sp1-3 and MyT1-2 have considerable and negligible Zn-stabilized secondary structure, respectively, and indicate only a small amount for GR-2. The pK(a)'s of the Sp1-3 cysteines and histidines were determined by NMR and used to estimate the number of protons displaced by Zn2+ at pH 7.4. ITC was also used to determine this number, and the two methods agree. Subtraction of buffer contributions to the calorimetric data reveals that all three peptides have a similar affinity for Zn2+, which has equal enthalpy and entropy components for Sp1-3 but is more enthalpically disfavored and entropically favored with increasing Cys ligands. The resulting enthalpy-entropy compensation originates from the Zn-Cys coordination, as subtraction of the cysteine deprotonation enthalpy results in a similar Zn2+-binding enthalpy for all three peptides, and the binding entropy tracks with the number of displaced protons. Metal and protein components of the binding enthalpy and entropy have been estimated. While dominated by Zn2+ coordination to the cysteines and histidines, other residues in the sequence affect the protein contributions that modulate the stability of these motifs.
C1 [Rich, Anne M.; Schenk, Austin D.; Lee, Paul E.; Cox, Elizabeth H.; Spuches, Anne M.; Wilcox, Dean E.] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA.
[Bombarda, Elisa] Univ Strasbourg 1, Lab Pharmacol & Physiochim Interact Cellulaires &, F-67401 Illkirch Graffenstaden, France.
[Hudson, Lynn D.] NINDS, Sect Dev Genet, Bethesda, MD 20892 USA.
[Kieffer, Bruno] Inst Genet & Biol Mol & Cellulaire, Dept Biol Struct & Genom, F-67404 Illkirch Graffenstaden, France.
RP Wilcox, DE (reprint author), Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA.
EM dwilcox@dartmouth.edu
RI Cox, Elizabeth/O-9044-2015
OI Cox, Elizabeth/0000-0003-0467-6609
FU NIH [P42-ES007373]; NSF [CHE-0910746]
FX We thank Yin Xu for the CD spectra of Sp1-3, Harriet Kruszyna for
Specfit analysis of Sp1-3 and MyT1-2 optical titrations, Jane Merkel and
Brian Hill for preliminary results on GR-2, Margaret Carpenter for help
with Figure 1, and Nick Grossoehme and Jean-Marc Latour for useful
discussions. We are grateful to NIH (P42-ES007373) and NSF (CHE-0910746)
for support of this research. This paper is dedicated to Lutetia Anne
Ward and Johannes Konrad Ullmann.
NR 67
TC 31
Z9 31
U1 4
U2 58
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JUN 27
PY 2012
VL 134
IS 25
BP 10405
EP 10418
DI 10.1021/ja211417g
PG 14
WC Chemistry, Multidisciplinary
SC Chemistry
GA 964SJ
UT WOS:000305716700025
PM 22591173
ER
PT J
AU Ketkar, A
Zafar, MK
Banerjee, S
Marquez, VE
Egli, M
Eoff, RL
AF Ketkar, Amit
Zafar, Maroof K.
Banerjee, Surajit
Marquez, Victor E.
Egli, Martin
Eoff, Robert L.
TI A Nucleotide-Analogue-Induced Gain of Function Corrects the Error-Prone
Nature of Human DNA Polymerase iota
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID CONFORMATION NUCLEOSIDE ANALOGS; NUCLEIC-ACID STRUCTURES;
SULFOLOBUS-SOLFATARICUS; N-METHANOCARBATHYMIDINE; STRUCTURAL BASIS;
LESION-BYPASS; SUGAR PUCKER; POL-ETA; REPLICATION; TEMPLATE
AB Y-family DNA polymerases participate in replication stress and DNA damage tolerance mechanisms. The properties that allow these enzymes to copy past bulky adducts or distorted template DNA can result in a greater propensity for them to make mistakes. Of the four human Y-family members, human DNA polymerase iota (hpol t) is the most error-prone. In the current study, we elucidate the molecular basis for improving the fidelity of hpol t through use of the fixed-conformation nucleotide North-methanocarba-2'-deoxyadenosine triphosphate (N-MC-dATP). Three crystal structures were solved of hpol t in complex with DNA containing a template 2'-deoxythymidine (dT) paired with an incoming dNTP or modified nucleotide triphosphate. The ternary complex of hpol t inserting N-MC-dATP opposite dT reveals that the adenine ring is stabilized in the anti orientation about the pseudo-glycosyl torsion angle, which mimics precisely the mutagenic arrangement of dGTP:dT normally preferred by hpol t. The stabilized anti conformation occurs without notable contacts from the protein but likely results from constraints imposed by the bicyclo[3.1.0]hexane scaffold of the modified nucleotide. Unmodified dATP and South-MC-dATP each adopt syn glycosyl orientations to form Hoogsteen base pairs with dT. The Hoogsteen orientation exhibits weaker base-stacking interactions and is less catalytically favorable than anti N-MC-dATP. Thus, N-MC-dATP corrects the error-prone nature of hpol t by preventing the Hoogsteen base-pairing mode normally observed for hpol t-catalyzed insertion of dATP opposite dT. These results provide a previously unrecognized means of altering the efficiency and the fidelity of a human translesion DNA polymerase.
C1 [Ketkar, Amit; Zafar, Maroof K.; Eoff, Robert L.] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA.
[Banerjee, Surajit] Cornell Univ, Dept Chem & Chem Biol, Argonne Natl Lab, Argonne, IL 60439 USA.
[Banerjee, Surajit] Cornell Univ, Argonne Natl Lab, NE Collaborat Access Team, Argonne, IL 60439 USA.
[Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Egli, Martin] Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA.
RP Eoff, RL (reprint author), Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA.
EM rleoff@uams.edu
OI Banerjee, Surajit/0000-0002-9414-7163
FU National Institutes of Health [R00 GM084460, R01 GM055237]; NIH,
National Cancer Institute, Center for Cancer Research; National Center
for Research Resources [5P41RR015301-10]; National Institute of General
Medical Sciences from the National Institutes of Health [8 P41
GM103403-10]; U.S. DOE [DE-AC02-06CH11357]
FX This work was supported in part by National Institutes of Health grants
R00 GM084460 (R.L.E.) and R01 GM055237 (M.E.). Supported in part by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. This work is based upon research conducted
at the Advanced Photon Source on the Northeastern Collaborative Access
Team beamlines, which are supported by grants from the National Center
for Research Resources (5P41RR015301-10) and the National Institute of
General Medical Sciences (8 P41 GM103403-10) from the National
Institutes of Health. Use of the Advanced Photon Source, an Office of
Science User Facility operated for the U.S. Department of Energy (DOE)
Office of Science by Argonne National Laboratory, was supported by the
U.S. DOE under Contract No. DE-AC02-06CH11357).
NR 51
TC 4
Z9 4
U1 0
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JUN 27
PY 2012
VL 134
IS 25
BP 10698
EP 10705
DI 10.1021/ja304176q
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA 964SJ
UT WOS:000305716700056
PM 22632140
ER
PT J
AU Grontved, L
Bandle, R
John, S
Baek, S
Chung, HJ
Liu, Y
Aguilera, G
Oberholtzer, C
Hager, GL
Levens, D
AF Grontved, Lars
Bandle, Russell
John, Sam
Baek, Songjoon
Chung, Hye-Jung
Liu, Ying
Aguilera, Greti
Oberholtzer, Carl
Hager, Gordon L.
Levens, David
TI Rapid genome-scale mapping of chromatin accessibility in tissue
SO EPIGENETICS & CHROMATIN
LA English
DT Article
DE Chromatin accessibility; Tissue; TACh; Benzonase; Cyanase; DNase I
ID GLUCOCORTICOID-RECEPTOR BINDING; REGULATORY ELEMENTS; IN-VIVO; DNASE-I;
TRANSCRIPTION; SEQUENCE; LIVER; NUCLEASE; PREDICTS; ISLETS
AB Background: The challenge in extracting genome-wide chromatin features from limiting clinical samples poses a significant hurdle in identification of regulatory marks that impact the physiological or pathological state. Current methods that identify nuclease accessible chromatin are reliant on large amounts of purified nuclei as starting material. This complicates analysis of trace clinical tissue samples that are often stored frozen. We have developed an alternative nuclease based procedure to bypass nuclear preparation to interrogate nuclease accessible regions in frozen tissue samples.
Results: Here we introduce a novel technique that specifically identifies Tissue Accessible Chromatin (TACh). The TACh method uses pulverized frozen tissue as starting material and employs one of the two robust endonucleases, Benzonase or Cyansase, which are fully active under a range of stringent conditions such as high levels of detergent and DTT. As a proof of principle we applied TACh to frozen mouse liver tissue. Combined with massive parallel sequencing TACh identifies accessible regions that are associated with euchromatic features and accessibility at transcriptional start sites correlates positively with levels of gene transcription. Accessible chromatin identified by TACh overlaps to a large extend with accessible chromatin identified by DNase I using nuclei purified from freshly isolated liver tissue as starting material. The similarities are most pronounced at highly accessible regions, whereas identification of less accessible regions tends to be more divergence between nucleases. Interestingly, we show that some of the differences between DNase I and Benzonase relate to their intrinsic sequence biases and accordingly accessibility of CpG islands is probed more efficiently using TACh.
Conclusion: The TACh methodology identifies accessible chromatin derived from frozen tissue samples. We propose that this simple, robust approach can be applied across a broad range of clinically relevant samples to allow demarcation of regulatory elements of considerable prognostic significance.
C1 [Bandle, Russell; Chung, Hye-Jung; Oberholtzer, Carl; Levens, David] NCI, Gene Regulat Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Grontved, Lars; John, Sam; Baek, Songjoon; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA.
[Liu, Ying; Aguilera, Greti] NICHD, Sect Endocrine Physiol, NIH, Bethesda, MD 20892 USA.
RP Oberholtzer, C (reprint author), NCI, Gene Regulat Sect, Pathol Lab, NIH, Bldg 10,Room 2 N212, Bethesda, MD 20892 USA.
EM oberholtzerc@mail.nih.gov; hagerg@exchange.nih.gov; levensd@mail.nih.gov
RI Levens, David/C-9216-2009;
OI Levens, David/0000-0002-7616-922X; Grontved, Lars/0000-0002-6735-8483
FU Lundbeck Foundation; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX LG was supported by a research grant from the Lundbeck Foundation. This
work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 32
TC 14
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U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-8935
J9 EPIGENET CHROMATIN
JI Epigenetics Chromatin
PD JUN 26
PY 2012
VL 5
AR 10
DI 10.1186/1756-8935-5-10
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 005HL
UT WOS:000308741400001
PM 22734930
ER
PT J
AU Ray, DM
Myers, PH
Painter, JT
Hoenerhoff, MJ
Olden, K
Roberts, JD
AF Ray, D. M.
Myers, P. H.
Painter, J. T.
Hoenerhoff, M. J.
Olden, K.
Roberts, J. D.
TI Inhibition of transforming growth factor-beta-activated kinase-1 blocks
cancer cell adhesion, invasion, and metastasis
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE adhesion; invasion; metastasis; fatty acid; TGF-beta-activated kinase-1;
breast cancer
ID BREAST-CARCINOMA CELLS; SIGNALING PATHWAY; FATTY-ACIDS; DIETARY-FAT; IV
COLLAGEN; NUDE-MICE; P38 MAPK; TAK1; LINE; MATRIGEL
AB BACKGROUND: Tumour cell metastasis involves cell adhesion and invasion, processes that depend on signal transduction, which can be influenced by the tumour microenvironment. N-6 polyunsaturated fatty acids, found both in the diet and in response to inflammatory responses, are important components of this microenvironment.
METHODS: We used short hairpin RNA (shRNA) knockdown of TGF-beta-activated kinase-1 (TAK1) in human tumour cells to examine its involvement in fatty acid-stimulated cell adhesion and invasion in vitro. An in vivo model of metastasis was developed in which cells, stably expressing firefly luciferase and either a control shRNA or a TAK1-specific shRNA, were injected into the mammary fat pads of mice fed diets, rich in n-6 polyunsaturated fatty acids. Tumour growth and spontaneous metastasis were monitored with in vivo and in situ imaging of bioluminescence.
RESULTS: Arachidonic acid activated TAK1 and downstream kinases in MDA-MB-435 breast cancer cells and led to increased adhesion and invasion. Knockdown of TAK1 blocked this activation and inhibited both cell adhesion and invasion in vitro. Tumour growth at the site of injection was not affected by TAK1 knockdown, but both the incidence and extent of metastasis to the lung were significantly reduced in mice injected with TAK1 knockdown cells compared with mice carrying control tumour cells.
CONCLUSION: These data demonstrate the importance of TAK1 signalling in tumour metastasis in vivo and suggest an opportunity for antimetastatic therapies. British Journal of Cancer (2012) 107, 129-136. doi: 10.1038/bjc.2012.214 www.bjcancer.com Published online 29 May 2012 (C) 2012 Cancer Research UK
C1 [Ray, D. M.; Olden, K.; Roberts, J. D.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Myers, P. H.] NIEHS, Comparat Med Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Painter, J. T.] Integrated Lab Syst Inc, Comparat & Mol Pathol Div, Durham, NC 27709 USA.
[Hoenerhoff, M. J.] NIEHS, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Roberts, JD (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Mail Drop D2-05,Room D248A,Rall Bldg,111T W Alexa, Res Triangle Pk, NC 27709 USA.
EM roberts1@niehs.nih.gov
FU NIEHS; NIH
FX We thank Dr Ron Herbert for the pathology analysis, Dr Shyamal Peddada
for statistical analysis, Norris Flagler for image analysis, and the
Histology Core Facility at NIEHS for help with necropsy and tissue
preparation. We thank Drs Darlene Dixon and Robert Langenbach for a
careful reading of the manuscript. This work has been supported in part,
or in whole, by the Intramural Research Program of the NIEHS and the
NIH.
NR 24
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U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD JUN 26
PY 2012
VL 107
IS 1
BP 129
EP 136
DI 10.1038/bjc.2012.214
PG 8
WC Oncology
SC Oncology
GA 967EE
UT WOS:000305888400019
PM 22644295
ER
PT J
AU Persson, EC
Quraishi, SM
Welzel, TM
Carreon, JD
Gridley, G
Graubard, BI
McGlynn, KA
AF Persson, E. C.
Quraishi, S. M.
Welzel, T. M.
Carreon, J. D.
Gridley, G.
Graubard, B. I.
McGlynn, K. A.
TI Risk of liver cancer among US male veterans with cirrhosis, 1969-1996
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE liver cancer; cirrhosis; epidemiology; cohort; US Veterans Affairs
ID HEPATOCELLULAR-CARCINOMA; UNITED-STATES; ESOPHAGEAL-VARICES;
RANDOMIZED-TRIAL; SURVIVAL; PREVENTION; AFFAIRS; RACE; CARE;
SURVEILLANCE
AB BACKGROUND: Liver cancer incidence rates in the United States have increased for several decades for reasons that are not entirely clear. Regardless of aetiology, cirrhosis is a strong risk factor for liver cancer. As mortality from cirrhosis has been declining in recent decades, it is possible that the risk of liver cancer among persons with cirrhosis has been affected.
METHODS: Data from the US Veterans Affairs medical records database were analysed after adjustment for attained age, race, number of hospital visits, obesity, diabetes, and chronic obstructive pulmonary disease. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated using Cox proportional hazards modelling. Survival analyses were conducted using age as the time metric and incidence of cirrhosis as a time-dependent covariate.
RESULTS: Among 103 257 men with incident cirrhosis, 788 liver cancers developed. The HR of liver cancer was highest among men with viral-related cirrhosis (HR = 37.59, 95% CI: 22.57-62.61), lowest among men with alcohol-related cirrhosis (HR = 8.20, 95% CI: 7.55-8.91) and intermediate among men with idiopathic cirrhosis (HR = 10.45, 95% CI: 8.52-12.81), when compared with those without cirrhosis. Regardless of cirrhosis type, white men had higher HRs than black men. The HR of developing liver cancer increased from 6.40 (95% CI: 4.40-9.33) in 1969-1973 to 34.71 (95% CI: 23.10-52.16) in 1992-1996 for those with cirrhosis compared with those without.
CONCLUSION: In conclusion, the significantly increased HR of developing liver cancer among men with cirrhosis compared with men without cirrhosis in the United States may be contributing to the increasing incidence of liver cancer. British Journal of Cancer (2012) 107, 195-200. doi:10.1038/bjc.2012.193 www.bjcancer.com Published online 15 May 2012 (C) 2012 Cancer Research UK
C1 [Persson, E. C.; Quraishi, S. M.; Carreon, J. D.; Gridley, G.; Graubard, B. I.; McGlynn, K. A.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20852 USA.
[Welzel, T. M.] Klinikum JW Goethe Univ Frankfurt Main, Med Klin 1, D-60590 Frankfurt, Germany.
RP Persson, EC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20852 USA.
EM christina.persson@nih.gov
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services
FX We thank the Medical Administration Service of the US Veterans Health
Services and Research Administration for providing the data on which
this study is based, and Eric Boyd and Dave S Campbell of Information
Management Services Inc. for programming support. This research was
supported by the Intramural Research Program of the National Cancer
Institute, National Institutes of Health, Department of Health and Human
Services.
NR 29
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U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD JUN 26
PY 2012
VL 107
IS 1
BP 195
EP 200
DI 10.1038/bjc.2012.193
PG 6
WC Oncology
SC Oncology
GA 967EE
UT WOS:000305888400030
PM 22588556
ER
PT J
AU Shebl, FM
Sakoda, LC
Black, A
Koshiol, J
Andriole, GL
Grubb, R
Church, TR
Chia, D
Zhou, C
Chu, LW
Huang, WY
Peters, U
Kirsh, VA
Chatterjee, N
Leitzmann, MF
Hayes, RB
Hsing, AW
AF Shebl, F. M.
Sakoda, L. C.
Black, A.
Koshiol, J.
Andriole, G. L.
Grubb, R.
Church, T. R.
Chia, D.
Zhou, C.
Chu, L. W.
Huang, W-Y
Peters, U.
Kirsh, V. A.
Chatterjee, N.
Leitzmann, M. F.
Hayes, R. B.
Hsing, A. W.
TI Aspirin but not ibuprofen use is associated with reduced risk of
prostate cancer: a PLCO Study
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE prostate cancer; non-steroidal anti-inflammatory drugs; cyclooxgenase
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LARGE COHORT; SCREENING TRIAL;
CYCLOOXYGENASE-2 INHIBITOR; OVER-EXPRESSION; POPULATION; METAANALYSIS;
CELLS; LUNG; PREVENTION
AB BACKGROUND: Although most epidemiological studies suggest that non-steroidal anti-inflammatory drug use is inversely associated with prostate cancer risk, the magnitude and specificity of this association remain unclear.
METHODS: We examined self-reported aspirin and ibuprofen use in relation to prostate cancer risk among 29 450 men ages 55-74 who were initially screened for prostate cancer from 1993 to 2001 in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Men were followed from their first screening exam until 31 December 2009, during which 3575 cases of prostate cancer were identified.
RESULTS: After adjusting for potential confounders, the hazard ratios (HRs) of prostate cancer associated with < 1 and >= 1 pill of aspirin daily were 0.98 (95% confidence interval (CI), 0.90-1.07) and 0.92 (95% CI: 0.85-0.99), respectively, compared with never use (P for trend 0.04). The effect of taking at least one aspirin daily was more pronounced when restricting the analyses to men older than age 65 or men who had a history of cardiovascular-related diseases or arthritis (HR (95% CI); 0.87 (0.78-0.97), 0.89 (0.80-0.99), and 0.88 (0.78-1.00), respectively). The data did not support an association between ibuprofen use and prostate cancer risk.
CONCLUSION: Daily aspirin use, but not ibuprofen use, was associated with lower risk of prostate cancer risk. British Journal of Cancer (2012) 107, 207-214. doi:10.1038/bjc.2012.227 www.bjcancer.com Published online 21 June 2012 (C) 2012 Cancer Research UK
C1 [Shebl, F. M.; Sakoda, L. C.; Black, A.; Koshiol, J.; Zhou, C.; Huang, W-Y; Chatterjee, N.; Hsing, A. W.] NCI, Dept Human Hlth & Serv, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Shebl, F. M.] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT USA.
[Sakoda, L. C.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Andriole, G. L.; Grubb, R.] Washington Univ, Sch Med, St Louis, MO USA.
[Church, T. R.] Univ Minnesota, Minneapolis, MN USA.
[Chia, D.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Zhou, C.] George Washington Univ, Sch Publ Hlth, Washington, DC USA.
[Chu, L. W.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Div Canc Prevent,NIH,Dept Hlth & Human Serv,Div E, Rockville, MD USA.
[Peters, U.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Kirsh, V. A.] Canc Care Ontario, Div Prevent Oncol, Res Unit, Toronto, ON, Canada.
[Leitzmann, M. F.] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany.
[Leitzmann, M. F.; Hayes, R. B.] NYU, Dept Environm Med, Sch Med, Div Epidemiol, New York, NY 10016 USA.
RP Shebl, FM (reprint author), NCI, Dept Human Hlth & Serv, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
EM fatma.shebl@yale.edu
RI Zhou, Cindy /H-2165-2015;
OI Zhou, Cindy /0000-0003-4814-4305; Church, Timothy
R./0000-0003-3292-5035; Hayes, Richard/0000-0002-0918-661X
FU NIH, National Cancer Institute
FX We thank Drs Philip Prorok and Christine Berg at the Division of Cancer
Prevention, National Cancer Institute, the Screening Centre
investigators and staff of the PLCO Cancer Screening Trial, Tom Riley
and staff (Information Management Services, Inc.), and Barbara O'Brien
and staff (Westat, Inc.) for their contributions to making this study
possible. This research was supported by the Intramural Research Program
of the NIH, National Cancer Institute.
NR 64
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U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD JUN 26
PY 2012
VL 107
IS 1
BP 207
EP 214
DI 10.1038/bjc.2012.227
PG 8
WC Oncology
SC Oncology
GA 967EE
UT WOS:000305888400032
PM 22722313
ER
PT J
AU Baker, CM
Comrie, WA
Hyun, YM
Chung, HL
Fedorchuk, CA
Lim, K
Brakebusch, C
McGrath, JL
Waugh, RE
Meier-Schellersheim, M
Kim, M
AF Baker, Christina M.
Comrie, William A.
Hyun, Young-Min
Chung, Hung-Li
Fedorchuk, Christine A.
Lim, Kihong
Brakebusch, Cord
McGrath, James L.
Waugh, Richard E.
Meier-Schellersheim, Martin
Kim, Minsoo
TI Opposing roles for RhoH GTPase during T-cell migration and activation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID HEMATOPOIETIC PROGENITOR CELLS; IMMUNOLOGICAL SYNAPSE; GENE-EXPRESSION;
DENDRITIC CELLS; INTEGRIN LFA-1; CUTTING EDGE; RECEPTOR; PROLIFERATION;
ADHESION; PROTEIN
AB T cells spend the majority of their time perusing lymphoid organs in search of cognate antigen presented by antigen presenting cells (APCs) and then quickly recirculate through the bloodstream to another lymph node. Therefore, regulation of a T-cell response is dependent upon the ability of cells to arrive in the correct location following chemokine gradients ("go" signal) as well as to receive appropriate T-cell receptor (TCR) activation signals upon cognate antigen recognition ("stop" signal). However, the mechanisms by which T cells regulate these go and stop signals remain unclear. We found that overexpression of the hematopoietic-specific RhoH protein in the presence of chemokine signals resulted in decreased Rap1-GTP and LFA-1 adhesiveness to ICAM-1, thus impairing T-cell chemotaxis; while in the presence of TCR signals, there were enhanced and sustained Rap1-GTP and LFA-1 activation as well as prolonged T:APC conjugates. RT-PCR analyses of activated CD4(+) T cells and live images of T-cell migration and immunological synapse (IS) formation revealed that functions of RhoH took place primarily at the levels of transcription and intracellular distribution. Thus, we conclude that RhoH expression provides a key molecular determinant that allows T cells to switch between sensing chemokine-mediated go signals and TCR-dependent stop signals.
C1 [Baker, Christina M.; Comrie, William A.; Hyun, Young-Min; Fedorchuk, Christine A.; Lim, Kihong; Kim, Minsoo] Univ Rochester, David H Smith Ctr Vaccine Biol & Immunol, Dept Microbiol & Immunol, Rochester, NY 14642 USA.
[Brakebusch, Cord] Univ Copenhagen, Dept Mol Pathol, DK-2200 Copenhagen N, Denmark.
[Chung, Hung-Li; McGrath, James L.; Waugh, Richard E.] Univ Rochester, Dept Biomed Engn, Rochester, NY 14642 USA.
[Meier-Schellersheim, Martin] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Kim, M (reprint author), Univ Rochester, David H Smith Ctr Vaccine Biol & Immunol, Dept Microbiol & Immunol, 601 Elmwood Ave, Rochester, NY 14642 USA.
EM Minsoo_Kim@urmc.rochester.edu
OI Comrie, William/0000-0003-1173-1127
FU National Institutes of Health [HL087088, HL018208]
FX We thank Rachel Spoonhower, Pranita Sarangi, and Nicole Morin for
technical assistance; Dr. Jim Miller for reagents and manuscript
comments; Dr. Andrea Sant for the Mel-14 hybridoma; and Nathan Laniewski
for cell sorting. This project was supported by National Institutes of
Health Grants HL087088 and HL018208 (to M.K.).
NR 34
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U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 26
PY 2012
VL 109
IS 26
BP 10474
EP 10479
DI 10.1073/pnas.1114214109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972QE
UT WOS:000306291400077
PM 22689994
ER
PT J
AU Sarkar, K
Cai, ZQ
Gupta, R
Parajuli, N
Fox-Talbot, K
Darshan, MS
Gonzalez, FJ
Semenza, GL
AF Sarkar, Kakali
Cai, Zheqing
Gupta, Rigu
Parajuli, Nirmal
Fox-Talbot, Karen
Darshan, Medha S.
Gonzalez, Frank J.
Semenza, Gregg L.
TI Hypoxia-inducible factor 1 transcriptional activity in endothelial cells
is required for acute phase cardioprotection induced by ischemic
preconditioning
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE CD39; CD73; coronary artery disease; myocardial infarction; oxygen
ID INTERMITTENT HYPOXIA; MYOCARDIAL-ISCHEMIA; FACTOR-I;
ECTO-5'-NUCLEOTIDASE CD73; CARDIAC METABOLISM; REPERFUSION INJURY;
FACTOR 1-ALPHA; TUMOR-GROWTH; ARNT GENE; HIF-1-ALPHA
AB Infarction occurs when myocardial perfusion is interrupted for prolonged periods of time. Short episodes of ischemia and reperfusion protect against tissue injury when the heart is subjected to a subsequent prolonged ischemic episode, a phenomenon known as ischemic preconditioning (IPC). Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates adaptive responses to hypoxia/ischemia and is required for IPC. In this study, we performed a cellular and molecular characterization of the role of HIF-1 in IPC. We analyzed mice with knockout of HIF-1 alpha or HIF-1 beta in Tie2(+) lineage cells, which include bone marrow (BM) and vascular endothelial cells, compared with control littermates. Hearts were subjected to 30 min of ischemia and 120 min of reperfusion, either as ex vivo Langendorff preparations or by in situ occlusion of the left anterior descending artery. The IPC stimulus consisted of two cycles of 5-min ischemia and 5-min reperfusion. Mice lacking HIF-1 alpha or HIF-1 beta in Tie2(+) lineage cells showed complete absence of protection induced by IPC, whereas significant protection was induced by adenosine infusion. Treatment of mice with a HIF-1 inhibitor (digoxin or acriflavine) 4 h before Langendorff perfusion resulted in loss of IPC, as did administration of acriflavine directly into the perfusate immediately before IPC. We conclude that HIF-1 activity in endothelial cells is required for acute IPC. Expression and dimerization of the HIF-1 alpha and HIF-1 beta subunits is required, suggesting that the heterodimer is functioning as a transcriptional activator, despite the acute nature of the response.
C1 [Sarkar, Kakali; Gupta, Rigu; Darshan, Medha S.; Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Vasc Program, Inst Cell Engn, Baltimore, MD 21205 USA.
[Sarkar, Kakali; Cai, Zheqing; Gupta, Rigu; Parajuli, Nirmal; Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Fox-Talbot, Karen] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol, Baltimore, MD 21205 USA.
[Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
[Darshan, Medha S.; Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20814 USA.
RP Semenza, GL (reprint author), Johns Hopkins Univ, Sch Med, Vasc Program, Inst Cell Engn, Baltimore, MD 21205 USA.
EM gsemenza@jhmi.edu
RI Parajuli, Nirmal/E-2536-2016
FU National Institutes of Health [P01-HL65608]; Johns Hopkins Institute for
Cell Engineering
FX We thank Amanda Cardona for technical assistance with genotyping and
Karen Padgett of Novus Biologicals for generously providing anti-HIF-1
beta antibody. G. L. S. is the C. Michael Armstrong Professor at The
Johns Hopkins University School of Medicine. This work was supported by
Grant P01-HL65608 from the National Institutes of Health and by funds
from the Johns Hopkins Institute for Cell Engineering.
NR 51
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 26
PY 2012
VL 109
IS 26
BP 10504
EP 10509
DI 10.1073/pnas.1208314109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972QE
UT WOS:000306291400082
PM 22699503
ER
PT J
AU Tang, YY
Lu, QL
Fan, M
Yang, YH
Posner, MI
AF Tang, Yi-Yuan
Lu, Qilin
Fan, Ming
Yang, Yihong
Posner, Michael I.
TI Mechanisms of white matter changes induced by meditation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE attention network test; anterior corona radiata; profile of mood states
ID SHORT-TERM MEDITATION; ANTERIOR CINGULATE; RADIAL DIFFUSIVITY; BRAIN;
ATTENTION; WATER; PLASTICITY; INTEGRITY; TRACTS; CORTEX
AB Using diffusion tensor imaging, several recent studies have shown that training results in changes in white matter efficiency as measured by fractional anisotropy (FA). In our work, we found that a form of mindfulness meditation, integrative body-mind training (IBMT), improved FA in areas surrounding the anterior cingulate cortex after 4-wk training more than controls given relaxation training. Reductions in radial diffusivity (RD) have been interpreted as improved myelin but reductions in axial diffusivity (AD) involve other mechanisms, such as axonal density. We now report that after 4-wk training with IBMT, both RD and AD decrease accompanied by increased FA, indicating improved efficiency of white matter involves increased myelin as well as other axonal changes. However, 2-wk IBMT reduced AD, but not RD or FA, and improved moods. Our results demonstrate the time-course of white matter neuroplasticity in short-term meditation. This dynamic pattern of white matter change involving the anterior cingulate cortex, a part of the brain network related to self-regulation, could provide a means for intervention to improve or prevent mental disorders.
C1 [Tang, Yi-Yuan] Texas Tech Univ, Dept Psychol, Texas Tech Neuroimaging Inst, Lubbock, TX 79409 USA.
[Tang, Yi-Yuan; Lu, Qilin] Dalian Univ Technol, Inst Neuroinformat, Dalian 116024, Peoples R China.
[Tang, Yi-Yuan; Lu, Qilin] Dalian Univ Technol, Lab Body & Mind, Dalian 116024, Peoples R China.
[Tang, Yi-Yuan; Posner, Michael I.] Univ Oregon, Dept Psychol, Eugene, OR 97403 USA.
[Fan, Ming] Inst Basic Med Sci, Beijing 100850, Peoples R China.
[Yang, Yihong] NIDA, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD 21224 USA.
RP Tang, YY (reprint author), Texas Tech Univ, Dept Psychol, Texas Tech Neuroimaging Inst, Lubbock, TX 79409 USA.
EM yiyuan.tang@ttu.edu; mposner@uoregon.edu
FU 973 Program [2012CB518200, R21DA030066]; Office of Naval Research;
National Institute on Drug Abuse, National Institutes of Health
FX We thank the Institute of Neuroinformatics and the Lewis Center for
Neuroimaging for data collection and Rongxiang Tang for manuscript
preparation. This study is supported by 973 Program 2012CB518200,
R21DA030066, the Office of Naval Research, and the Intramural Research
Program of the National Institute on Drug Abuse, National Institutes of
Health.
NR 43
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U1 9
U2 74
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 26
PY 2012
VL 109
IS 26
BP 10570
EP 10574
DI 10.1073/pnas.1207817109
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972QE
UT WOS:000306291400093
PM 22689998
ER
PT J
AU Maltsev, AS
Ying, JF
Bax, A
AF Maltsev, Alexander S.
Ying, Jinfa
Bax, Ad
TI Impact of N-Terminal Acetylation of alpha-Synuclein on Its Random Coil
and Lipid Binding Properties
SO BIOCHEMISTRY
LA English
DT Article
ID SOLUTION NMR-SPECTROSCOPY; SECONDARY STRUCTURE; PARKINSONS-DISEASE;
PHOSPHOLIPID-BINDING; HELIX; FIBRILLATION; VESICLES; STATES;
PHOSPHORYLATION; QUANTIFICATION
AB N-Terminal acetylation of alpha-synuclein (aS), a protein implicated in the etiology of Parkinson's disease, is common in mammals. The impact of this modification on the protein's structure and dynamics in free solution and on its membrane binding properties has been evaluated by high-resolution nuclear magnetic resonance and circular dichroism (CD) spectroscopy. While no tetrameric form of acetylated aS could be isolated, N-terminal acetylation resulted in chemical shift perturbations of the first 12 residues of the protein that progressively decreased with the distance from the N-terminus. The directions of the chemical shift changes and small changes in backbone (3)J(HH) couplings are consistent with an increase in the alpha-helicity of the first six residues of aS, although a high degree of dynamic conformational disorder remains and the helical structure is sampled < 20% of the time. Chemical shift and (3)J(HH) data for the intact protein are virtually indistinguishable from those recorded for the corresponding N-terminally acetylated and nonacetylated 15-residue synthetic peptides. An increase in alpha-helicity at the N-terminus of aS is supported by CD data on the acetylated peptide and by weak medium-range nuclear Overhauser effect contacts indicative of alpha-helical character. The remainder of the protein has chemical shift values that are very close to random coil values and indistinguishable between the two forms of the protein. No significant differences in the fibrillation kinetics were observed between acetylated and nonacetylated aS. However, the lipid binding properties of aS are strongly impacted by acetylation and exhibit distinct behavior for the first 12 residues, indicative of an initiation role for the N-terminal residues in an "initiation-elongation" process of binding to the membrane.
C1 [Maltsev, Alexander S.; Ying, Jinfa; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), 5 Mem Dr, Bethesda, MD 20892 USA.
EM bax@nih.gov
RI Maltsev, Alexander/A-8175-2012
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; National Institutes of Health (NIH);
Intramural AIDS-Targeted Antiviral Program of the Office of the
Director, NIH
FX This work was funded by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health (NIH), and the Intramural AIDS-Targeted Antiviral
Program of the Office of the Director, NIH.
NR 47
TC 65
Z9 65
U1 1
U2 47
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUN 26
PY 2012
VL 51
IS 25
BP 5004
EP 5013
DI 10.1021/bi300642h
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 963YV
UT WOS:000305661800003
PM 22694188
ER
PT J
AU Jeang, KT
AF Jeang, Kuan-Teh
TI RNAi in the regulation of mammalian viral infections
SO BMC BIOLOGY
LA English
DT Editorial Material
ID SILENCING SUPPRESSOR ACTIVITY; SMALL NONCODING RNAS; VIRUS-INFECTION;
ENDOGENOUS RETROVIRUSES; HIV-1-INFECTED CELLS; ANTIVIRAL DEFENSE; HIV-1
REPLICATION; HUMAN MICRORNAS; EXPRESSION; INTERFERENCE
AB Although RNA interference (RNAi) is known to play an important part in defense against viruses of invertebrates, its contribution to mammalian antiviral defense has been a matter of dispute. This is surprising because all components of the RNAi machinery necessary for robust RNAi-mediated restriction of viruses are conserved in mammals, and the introduction of synthetic small interfering RNAs (siRNAs) into cells efficiently silences the replication of viruses that contain siRNA complementary sequences in those cells. Here, I discuss the reasons for the dispute, and review the evidence that RNAi is a part of the physiological defense of mammalian cells against viral infections.
C1 NIH, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM KJEANG@niaid.nih.gov
FU Intramural NIH HHS
NR 58
TC 31
Z9 33
U1 1
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7007
J9 BMC BIOL
JI BMC Biol.
PD JUN 26
PY 2012
VL 10
AR 58
DI 10.1186/1741-7007-10-58
PG 6
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 964LK
UT WOS:000305696500001
PM 22734679
ER
PT J
AU Feiglin, A
Moult, J
Lee, B
Ofran, Y
Unger, R
AF Feiglin, Ariel
Moult, John
Lee, Byungkook
Ofran, Yanay
Unger, Ron
TI Neighbor Overlap Is Enriched in the Yeast Interaction Network: Analysis
and Implications
SO PLOS ONE
LA English
DT Article
ID PROTEIN-INTERACTION NETWORKS; SACCHAROMYCES-CEREVISIAE; COMPLEX
NETWORKS; GENETIC INTERACTIONS; MATING PHEROMONE; INVASIVE GROWTH; MAP;
PATHWAY; ORGANIZATION; MKK2
AB The yeast protein-protein interaction network has been shown to have distinct topological features such as a scale free degree distribution and a high level of clustering. Here we analyze an additional feature which is called Neighbor Overlap. This feature reflects the number of shared neighbors between a pair of proteins. We show that Neighbor Overlap is enriched in the yeast protein-protein interaction network compared with control networks carefully designed to match the characteristics of the yeast network in terms of degree distribution and clustering coefficient. Our analysis also reveals that pairs of proteins with high Neighbor Overlap have higher sequence similarity, more similar GO annotations and stronger genetic interactions than pairs with low ones. Finally, we demonstrate that pairs of proteins with redundant functions tend to have high Neighbor Overlap. We suggest that a combination of three mechanisms is the basis for this feature: The abundance of protein complexes, selection for backup of function, and the need to allow functional variation.
C1 [Feiglin, Ariel; Ofran, Yanay; Unger, Ron] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Ramat Gan, Israel.
[Moult, John] Univ Maryland, Inst Biosci & Biotechnol, Rockville, MD USA.
[Lee, Byungkook] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Feiglin, A (reprint author), Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Ramat Gan, Israel.
EM ron@biomodel.os.biu.ac.il
OI Moult, John/0000-0002-3012-2282
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; National Institute of Health [LM007174]; Israeli
Science Foundation [1339/08]
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, by National Institute of Health grant LM007174 to
JM and Israeli Science Foundation grant 1339/08 to RU. No additional
external funding was received for this study. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 49
TC 1
Z9 1
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 26
PY 2012
VL 7
IS 6
AR e39662
DI 10.1371/journal.pone.0039662
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 966AK
UT WOS:000305808700044
PM 22761860
ER
PT J
AU Orlov, M
Vaida, F
Finney, OC
Smith, DM
Talley, AK
Wang, RB
Kappe, SH
Deng, QQ
Schooley, RT
Duffy, PE
AF Orlov, Marika
Vaida, Florin
Finney, Olivia C.
Smith, David M.
Talley, Angela K.
Wang, Ruobing
Kappe, Stefan H.
Deng, Qianqian
Schooley, Robert T.
Duffy, Patrick E.
TI P. falciparum Enhances HIV Replication in an Experimental Malaria
Challenge System
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; SUB-SAHARAN AFRICA;
PLASMODIUM-FALCIPARUM; INTERFERON-GAMMA; IFN-GAMMA; TNF-ALPHA; NK CELLS;
INFECTION; BLOOD
AB Co-infection with HIV and P. falciparum worsens the prognosis of both infections; however, the mechanisms driving this adverse interaction are not fully delineated. To evaluate this, we studied HIV-1 and P. falciparum interactions in vitro using peripheral blood mononuclear cells (PBMCs) from human malaria naive volunteers experimentally infected with P. falciparum in a malaria challenge trial. PBMCs collected before the malaria challenge and at several time points post-infection were infected with HIV-1 and co-cultured with either P. falciparum infected (iRBCs) or uninfected (uRBCs) red blood cells. HIV p24Ag and TNF-alpha, IFN-gamma, IL-4, IL-6, IL-10, IL-17, and MIP-1 alpha were quantified in the co-culture supernatants. In general, iRBCs stimulated more HIV p24Ag production by PBMCs than did uRBCs. HIV p24Ag production by PBMCs in the presence of iRBCs (but not uRBCs) further increased during convalescence (days 35, 56, and 90 post-challenge). In parallel, iRBCs induced higher secretion of pro-inflammatory cytokines (TNF-alpha, IFN-gamma, and MIP-1 alpha) than uRBCs, and production increased further during convalescence. Because the increase in p24Ag production occurred after parasitemia and generalized immune activation had resolved, our results suggest that enhanced HIV production is related to the development of anti-malaria immunity and may be mediated by pro-inflammatory cytokines.
C1 [Orlov, Marika; Finney, Olivia C.; Talley, Angela K.; Wang, Ruobing; Kappe, Stefan H.; Duffy, Patrick E.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Orlov, Marika; Smith, David M.; Deng, Qianqian; Schooley, Robert T.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Vaida, Florin] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Duffy, Patrick E.] NIAID, Lab Malaria Immunol, NIH, Rockville, MD USA.
RP Orlov, M (reprint author), Seattle Biomed Res Inst, 4 Nickerson St, Seattle, WA 98109 USA.
EM rschooley@ucsd.edu
FU Translational Virology Core at the UC San Diego Center for AIDS Research
[AI36214]; Gilead Sciences; Foundation for the National Institutes of
Health through the Grand Challenges in Global Health Initiative; U.S.
National Institutes of Health [U19 AI065664]; Gilead's SAB
FX This work was performed with the support of the Translational Virology
Core at the UC San Diego Center for AIDS Research (AI36214), Gilead
Sciences, and funded in part by a Grant from the Foundation for the
National Institutes of Health through the Grand Challenges in Global
Health Initiative and from the U.S. National Institutes of Health (Grant
U19 AI065664). No additional external funding was received. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.; Robert T. Schooley is a
member of the Scientific Advisory Board for Gilead Sciences. A
consulting fee from Gilead Sciences was sent on to the University of
California to be used in an unrestricted fashion for research and
educational activities that are not covered by other sources. Ms. Orlov
is a graduate student, and Dr. Schooley has used, in part, the funds
from his role as a member of Gilead's SAB to pay for her stipend and for
some of the laboratory resources used for this work. This does not alter
the authors' adherence to all the PLoS ONE policies on sharing data and
materials.
NR 35
TC 6
Z9 6
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 26
PY 2012
VL 7
IS 6
AR e39000
DI 10.1371/journal.pone.0039000
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 966AK
UT WOS:000305808700015
PM 22745697
ER
PT J
AU Zhang, DP
de Souza, RF
Anantharaman, V
Iyer, LM
Aravind, L
AF Zhang, Dapeng
de Souza, Robson F.
Anantharaman, Vivek
Iyer, Lakshminarayan M.
Aravind, L.
TI Polymorphic toxin systems: Comprehensive characterization of trafficking
modes, processing, mechanisms of action, immunity and ecology using
comparative genomics
SO BIOLOGY DIRECT
LA English
DT Article
ID HORIZONTAL GENE-TRANSFER; PORE-FORMING TOXINS; NF-KAPPA-B;
RESTRICTION-MODIFICATION SYSTEMS; CYSTEINE PROTEASE DOMAIN; PROGRAMMED
CELL-DEATH; VI SECRETION SYSTEM; LACTIS GAMMA-TOXIN; CLASS-III REGION;
CRYSTAL-STRUCTURE
AB Background: Proteinaceous toxins are observed across all levels of inter-organismal and intra-genomic conflicts. These include recently discovered prokaryotic polymorphic toxin systems implicated in intra-specific conflicts. They are characterized by a remarkable diversity of C-terminal toxin domains generated by recombination with standalone toxin-coding cassettes. Prior analysis revealed a striking diversity of nuclease and deaminase domains among the toxin modules. We systematically investigated polymorphic toxin systems using comparative genomics, sequence and structure analysis.
Results: Polymorphic toxin systems are distributed across all major bacterial lineages and are delivered by at least eight distinct secretory systems. In addition to type-II, these include type-V, VI, VII (ESX), and the poorly characterized "Photorhabdus virulence cassettes (PVC)", PrsW-dependent and MuF phage-capsid-like systems. We present evidence that trafficking of these toxins is often accompanied by autoproteolytic processing catalyzed by HINT, ZU5, PrsW, caspase-like, papain-like, and a novel metallopeptidase associated with the PVC system. We identified over 150 distinct toxin domains in these systems. These span an extraordinary catalytic spectrum to include 23 distinct clades of peptidases, numerous previously unrecognized versions of nucleases and deaminases, ADP-ribosyltransferases, ADP ribosyl cyclases, RelA/SpoT-like nucleotidyltransferases, glycosyltranferases and other enzymes predicted to modify lipids and carbohydrates, and a pore-forming toxin domain. Several of these toxin domains are shared with host-directed effectors of pathogenic bacteria. Over 90 families of immunity proteins might neutralize anywhere between a single to at least 27 distinct types of toxin domains. In some organisms multiple tandem immunity genes or immunity protein domains are organized into polyimmunity loci or polyimmunity proteins. Gene-neighborhood-analysis of polymorphic toxin systems predicts the presence of novel trafficking-related components, and also the organizational logic that allows toxin diversification through recombination. Domain architecture and protein-length analysis revealed that these toxins might be deployed as secreted factors, through directed injection, or via inter-cellular contact facilitated by filamentous structures formed by RHS/YD, filamentous hemagglutinin and other repeats. Phyletic pattern and life-style analysis indicate that polymorphic toxins and polyimmunity loci participate in cooperative behavior and facultative 'cheating' in several ecosystems such as the human oral cavity and soil. Multiple domains from these systems have also been repeatedly transferred to eukaryotes and their viruses, such as the nucleo-cytoplasmic large DNA viruses.
Conclusions: Along with a comprehensive inventory of toxins and immunity proteins, we present several testable predictions regarding active sites and catalytic mechanisms of toxins, their processing and trafficking and their role in intra-specific and inter-specific interactions between bacteria. These systems provide insights regarding the emergence of key systems at different points in eukaryotic evolution, such as ADP ribosylation, interaction of myosin VI with cargo proteins, mediation of apoptosis, hyphal heteroincompatibility, hedgehog signaling, arthropod toxins, cell-cell interaction molecules like teneurins and different signaling messengers.
C1 [Zhang, Dapeng; de Souza, Robson F.; Anantharaman, Vivek; Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[de Souza, Robson F.] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508 Sao Paulo, Brazil.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM aravind@ncbi.nlm.nih.gov
OI Anantharaman, Vivek/0000-0001-8395-0009
FU intramural funds of the US Department of Health and Human Services
(National Library of Medicine, NIH)
FX The authors' research is supported by the intramural funds of the US
Department of Health and Human Services (National Library of Medicine,
NIH).
NR 230
TC 100
Z9 100
U1 1
U2 18
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD JUN 25
PY 2012
VL 7
AR 18
DI 10.1186/1745-6150-7-18
PG 76
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 031EV
UT WOS:000310622700001
PM 22731697
ER
PT J
AU Baibakov, B
Boggs, NA
Yauger, B
Baibakov, G
Dean, J
AF Baibakov, Boris
Boggs, Nathan A.
Yauger, Belinda
Baibakov, Galina
Dean, Jurrien
TI Human sperm bind to the N-terminal domain of ZP2 in humanized zonae
pellucidae in transgenic mice
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID EGG VITELLINE ENVELOPE; HUMAN-SPERMATOZOA; MOUSE SPERM; XENOPUS-LAEVIS;
MONOCLONAL-ANTIBODIES; RECEPTOR ACTIVITY; FERTILIZATION; GLYCOPROTEINS;
PROTEIN; IDENTIFICATION
AB Fertilization requires taxon-specific gamete recognition, and human sperm do not bind to zonae pellucidae (ZP1-3) surrounding mouse eggs. Using transgenesis to replace endogenous mouse proteins with human homologues, gain-of-function sperm-binding assays were established to evaluate human gamete recognition. Human sperm bound only to zonae pellucidae containing human ZP2, either alone or coexpressed with other human zona proteins. Binding to the humanized matrix was a dominant effect that resulted in human sperm penetration of the zona pellucida and accumulation in the perivitelline space, where they were unable to fuse with mouse eggs. Using recombinant peptides, the site of gamete recognition was located to a defined domain in the N terminus of ZP2. These results provide experimental evidence for the role of ZP2 in mediating sperm binding to the zona pellucida and support a model in which human sperm-egg recognition is dependent on an N-terminal domain of ZP2, which is degraded after fertilization to provide a definitive block to polyspermy.
C1 [Baibakov, Boris; Boggs, Nathan A.; Yauger, Belinda; Baibakov, Galina; Dean, Jurrien] NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Dean, J (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
EM jurrien@helix.nih.gov
FU National Institutes of Health, National Institutes of Diabetes and
Digestive and Kidney Diseases
FX This research was support by the Intramural Research Program of the
National Institutes of Health, National Institutes of Diabetes and
Digestive and Kidney Diseases.
NR 57
TC 24
Z9 27
U1 3
U2 20
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD JUN 25
PY 2012
VL 197
IS 7
BP 897
EP 905
DI 10.1083/jcb.201203062
PG 9
WC Cell Biology
SC Cell Biology
GA 965ZT
UT WOS:000305807000007
PM 22734000
ER
PT J
AU Grontved, L
Hager, GL
AF Grontved, Lars
Hager, Gordon L.
TI Impact of chromatin structure on PR signaling: Transition from local to
global analysis
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE Progesterone; Receptor; Steroid; Chromatin; Dynamics; Nuclear
architecture
ID GLUCOCORTICOID-RECEPTOR-BINDING; LONG-RANGE INTERACTIONS; TUMOR VIRUS
PROMOTER; MMTV PROMOTER; PROGESTERONE-RECEPTOR; GENE-REGULATION; HISTONE
H1; TRANSCRIPTION FACTORS; MOLECULAR CHAPERONES; INDUCIBLE PROMOTER
AB The progesterone receptor (PR) interacts with chromatin in a highly dynamic manner that requires ongoing chromatin remodeling, interaction with chaparones and activity of the proteasome. Here we discuss dynamic interaction of steroid receptor with chromatin, with special attention not only to PR but also to the glucocorticoid receptor (GR), as these receptors share many similarities regarding interaction with, and remodeling of, chromatin. Both receptors can bind nucleosomal DNA and have accordingly been described as pioneering factors. However recent genomic approaches (ChIP-seq and DHS-seq) show that a large fraction of receptor binding events occur at pre-accessible chromatin. Thus factors which generate and maintain accessible chromatin during development, and in fully differentiated tissue, contribute a major fraction of receptor tissue specificity. In addition, chromosome conformation capture techniques suggest that steroid receptors preferentially sequester within distinct nuclear hubs. We will integrate dynamic studies from single cells and genomic studies from cell populations, and discuss how genomic approaches have reshaped our current understanding of mechanisms that control steroid receptor interaction with chromatin. Published by Elsevier Ireland Ltd.
C1 [Grontved, Lars; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602,41 Lib Dr, Bethesda, MD 20892 USA.
EM hagerg@exchange.nih.gov
OI Grontved, Lars/0000-0002-6735-8483
FU Lundbeck Foundation; NIH, National Cancer Institute, Center for Cancer
Research
FX L.G. was supported by a research grant from the Lundbeck Foundation.
This work was supported by the intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 85
TC 10
Z9 10
U1 0
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD JUN 24
PY 2012
VL 357
IS 1-2
SI SI
BP 30
EP 36
DI 10.1016/j.mce.2011.09.006
PG 7
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 950GX
UT WOS:000304638700004
PM 21958695
ER
PT J
AU Neuwald, AF
Lanczycki, CJ
Marchler-Bauer, A
AF Neuwald, Andrew F.
Lanczycki, Christopher J.
Marchler-Bauer, Aron
TI Automated hierarchical classification of protein domain subfamilies
based on functionally-divergent residue signatures
SO BMC BIOINFORMATICS
LA English
DT Article
ID SPECIFICITY-DETERMINING RESIDUES; SEQUENCE ALIGNMENTS; PHYLOGENETIC
TREES; NEW-GENERATION; RAN GTPASES; FAMILIES; IDENTIFICATION;
MECHANISMS; DATABASE; PREDICTION
AB Background: The NCBI Conserved Domain Database (CDD) consists of a collection of multiple sequence alignments of protein domains that are at various stages of being manually curated into evolutionary hierarchies based on conserved and divergent sequence and structural features. These domain models are annotated to provide insights into the relationships between sequence, structure and function via web-based BLAST searches.
Results: Here we automate the generation of conserved domain (CD) hierarchies using a combination of heuristic and Markov chain Monte Carlo (MCMC) sampling procedures and starting from a (typically very large) multiple sequence alignment. This procedure relies on statistical criteria to define each hierarchy based on the conserved and divergent sequence patterns associated with protein functional-specialization. At the same time this facilitates the sequence and structural annotation of residues that are functionally important. These statistical criteria also provide a means to objectively assess the quality of CD hierarchies, a non-trivial task considering that the protein subgroups are often very distantly related-a situation in which standard phylogenetic methods can be unreliable. Our aim here is to automatically generate (typically sub-optimal) hierarchies that, based on statistical criteria and visual comparisons, are comparable to manually curated hierarchies; this serves as the first step toward the ultimate goal of obtaining optimal hierarchical classifications. A plot of runtimes for the most time-intensive (non-parallelizable) part of the algorithm indicates a nearly linear time complexity so that, even for the extremely large Rossmann fold protein class, results were obtained in about a day.
Conclusions: This approach automates the rapid creation of protein domain hierarchies and thus will eliminate one of the most time consuming aspects of conserved domain database curation. At the same time, it also facilitates protein domain annotation by identifying those pattern residues that most distinguish each protein domain subgroup from other related subgroups.
C1 [Neuwald, Andrew F.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
[Neuwald, Andrew F.] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
[Lanczycki, Christopher J.; Marchler-Bauer, Aron] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Neuwald, AF (reprint author), Univ Maryland, Sch Med, Inst Genome Sci, BioPk 2,Room 617,801 West Baltimore St, Baltimore, MD 21201 USA.
EM aneuwald@som.umaryland.edu
OI Marchler-Bauer, Aron/0000-0003-1516-0712
FU University of Maryland; NIH Division of General Medicine Grant
[GM078541]; National Library of Medicine at National Institutes of
Health/DHHS
FX We thank Art Delcher for critical reading of the manuscript. Funding for
AFN provided by the University of Maryland and the NIH Division of
General Medicine Grant GM078541. Funding for CL and AMB provided by the
Intramural Research Program of the National Library of Medicine at
National Institutes of Health/DHHS. Funding to pay the Open Access
publication charges for this article was provided, in part, by the
Intramural Research Program of the National Library of Medicine at the
National Institutes of Health/DHHS.
NR 62
TC 8
Z9 8
U1 0
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JUN 22
PY 2012
VL 13
AR 144
DI 10.1186/1471-2105-13-144
PG 21
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 106YH
UT WOS:000316181000001
PM 22726767
ER
PT J
AU Pfister, RH
Bingham, P
Edwards, EM
Horbar, JD
Kenny, MJ
Inder, T
Nelson, KB
Raju, T
Soll, RF
AF Pfister, Robert H.
Bingham, Peter
Edwards, Erika M.
Horbar, Jeffrey D.
Kenny, Michael J.
Inder, Terrie
Nelson, Karin B.
Raju, Tonse
Soll, Roger F.
TI The Vermont oxford neonatal encephalopathy registry: rationale, methods,
and initial results
SO BMC PEDIATRICS
LA English
DT Article
DE Hypoxic ischemic encephalopathy; Neonatal encephalopathy; HIE;
Therapeutic hypothermia; Asphyxia; Cooling; Neuroprotection; Neonatal
encephalopathy; Registry
ID PERINATAL ASPHYXIAL ENCEPHALOPATHY; HYPOXIC-ISCHEMIC ENCEPHALOPATHY;
WHOLE-BODY HYPOTHERMIA; NEWBORN ENCEPHALOPATHY; POSTISCHEMIC SEIZURES;
MODERATE HYPOTHERMIA; RISK-FACTORS; FETAL SHEEP; INFANTS; TRIAL
AB Background: In 2006, the Vermont Oxford Network (VON) established the Neonatal Encephalopathy Registry (NER) to characterize infants born with neonatal encephalopathy, describe evaluations and medical treatments, monitor hypothermic therapy (HT) dissemination, define clinical research questions, and identify opportunities for improved care.
Methods: Eligible infants were >= 36 weeks with seizures, altered consciousness (stupor, coma) during the first 72 hours of life, a 5 minute Apgar score of <= 3, or receiving HT. Infants with central nervous system birth defects were excluded.
Results: From 2006-2010, 95 centers registered 4232 infants. Of those, 59% suffered a seizure, 50% had a 5 minute Apgar score of <= 3, 38% received HT, and 18% had stupor/coma documented on neurologic exam. Some infants experienced more than one eligibility criterion. Only 53% had a cord gas obtained and only 63% had a blood gas obtained within 24 hours of birth, important components for determining HT eligibility. Sixty-four percent received ventilator support, 65% received anticonvulsants, 66% had a head MRI, 23% had a cranial CT, 67% had a full channel encephalogram (EEG) and 33% amplitude integrated EEG. Of all infants, 87% survived.
Conclusions: The VON NER describes the heterogeneous population of infants with NE, the subset that received HT, their patterns of care, and outcomes. The optimal routine care of infants with neonatal encephalopathy is unknown. The registry method is well suited to identify opportunities for improvement in the care of infants affected by NE and study interventions such as HT as they are implemented in clinical practice.
C1 [Pfister, Robert H.; Bingham, Peter; Edwards, Erika M.; Horbar, Jeffrey D.; Kenny, Michael J.; Soll, Roger F.] Univ Vermont, Burlington, VT 05405 USA.
[Pfister, Robert H.; Edwards, Erika M.; Horbar, Jeffrey D.; Kenny, Michael J.; Soll, Roger F.] Vermont Oxford Network, Burlington, VT USA.
[Inder, Terrie] Washington Univ, St Louis, MO USA.
[Nelson, Karin B.] NINDS, Bethesda, MD 20892 USA.
[Nelson, Karin B.] Natl Childrens Hosp, Med Ctr, Washington, DC USA.
[Raju, Tonse] NICHHD, Bethesda, MD 20892 USA.
RP Pfister, RH (reprint author), Univ Vermont, Burlington, VT 05405 USA.
EM robert.pfister@vtmednet.org
RI Kenny, Michael/N-3244-2013
OI Kenny, Michael/0000-0002-7750-654X
FU Vermont Oxford Network
FX The VON NER is funded solely by the Vermont Oxford Network. The Vermont
Oxford Network will pay the article processing charge. Drs. Horbar and
Soll are employees of Vermont Oxford Network. The Vermont Oxford Network
nor any of the authors will receive reimbursements, fees, funding, or
salary as a result of the publication of this manuscript. On December
20, 2006 the Food and Drug Administration (FDA) approved the Olympic
Cool-Cap (R) device to provide selective head cooling in infants with
clinical evidence of moderate to severe hypoxic ischemic encephalopathy.
The FDA has required that Olympic Medical Corporation provide Cool-Cap
(R) users the opportunity to enroll cooled infants in a registry.
Olympic Medical Corporation contracted with the Vermont Oxford Network
to make its Registry available to Cool-Cap (R) users who are members of
the Network. The Vermont Oxford Network provides Olympic Medical
Corporation with special de-identified reports for these infants which
Olympic Medical Corporation may choose to submit to the FDA for post
marketing surveillance.
NR 27
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U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2431
J9 BMC PEDIATR
JI BMC Pediatr.
PD JUN 22
PY 2012
VL 12
AR 84
DI 10.1186/1471-2431-12-84
PG 10
WC Pediatrics
SC Pediatrics
GA 040QZ
UT WOS:000311339300001
PM 22726296
ER
PT J
AU Taylor, CE
Cobb, BA
Rittenhouse-Olson, K
Paulson, JC
Schreiber, JR
AF Taylor, Christopher E.
Cobb, Brian A.
Rittenhouse-Olson, Kate
Paulson, James C.
Schreiber, John R.
TI Carbohydrate moieties as vaccine candidates: Targeting the sweet spot in
the immune response
SO VACCINE
LA English
DT Article
DE Carbohydrate moieties; Vaccine; Glycans; Immune response; Glycomics;
Adjuvants
ID GLYCAN; OLIGOSACCHARIDES; ANTIBODIES
AB Advances in the use of carbohydrates as vaccine candidates for the prevention of infectious and malignant diseases was the topic for a meeting in Rockville, MD, sponsored by the National Institute of Allergy and Infectious Diseases involving a diverse group of scientists. Participants included research scientists and clinicians from academia and industry, and representatives from the National Institutes of Health and US Food and Drug Administration. This workshop was the third in a series of meetings designed to address issues relating to the immune response to carbohydrate antigens and how this information is used in the development of vaccines. Participants also identified roadblocks, research opportunities and resource needs. The meeting was organized into sessions that focused on recent advances in the immune response to microbial and cancer carbohydrate antigens, glycomics, novel vaccine approaches, novel adjuvants and delivery systems.
C1 [Taylor, Christopher E.] NIAID, Resp Dis Branch, Div Microbiol & Infect Dis, Bethesda, MD 20852 USA.
[Cobb, Brian A.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Rittenhouse-Olson, Kate] SUNY Buffalo, Buffalo, NY 14260 USA.
[Paulson, James C.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Schreiber, John R.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Schreiber, John R.] Floating Hosp Children, Tufts Med Ctr, Boston, MA USA.
RP Taylor, CE (reprint author), NIAID, Resp Dis Branch, Div Microbiol & Infect Dis, 6610 Rockledge Dr,Room 3202, Bethesda, MD 20852 USA.
EM ctaylor@niaid.nih.gov
FU Respiratory Diseases Branch, Division of Microbiology and Infectious
Diseases, NIAID
FX This summary is based on presentations made at the "Carbohydrate
Moieties as Vaccine Targets" meeting held in Rockville, MD on October
3-4, 2011. We wish to acknowledge the valuable contributions of the
speakers and meeting participants The meeting was sponsored by the
Respiratory Diseases Branch, Division of Microbiology and Infectious
Diseases, NIAID.
NR 22
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U1 2
U2 21
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD JUN 22
PY 2012
VL 30
IS 30
BP 4409
EP 4413
DI 10.1016/j.vaccine.2012.04.090
PG 5
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 024NY
UT WOS:000310117100002
PM 22575168
ER
PT J
AU Reynolds, MR
Weiler, AM
Piaskowski, SM
Piatak, M
Robertson, HT
Allison, DB
Bett, AJ
Casimiro, DR
Shiver, JW
Wilson, NA
Lifson, JD
Koff, WC
Watkins, DI
AF Reynolds, Matthew R.
Weiler, Andrea M.
Piaskowski, Shari M.
Piatak, Michael, Jr.
Robertson, Henry T.
Allison, David B.
Bett, Andrew J.
Casimiro, Danilo R.
Shiver, John W.
Wilson, Nancy A.
Lifson, Jeffrey D.
Koff, Wayne C.
Watkins, David I.
TI A trivalent recombinant Ad5 gag/pol/nef vaccine fails to protect rhesus
macaques from infection or control virus replication after a
limiting-dose heterologous SIV challenge
SO VACCINE
LA English
DT Article
DE HIV vaccine; Adenovirus serotype 5; Simian immunodeficiency virus;
CD8(+) T cells; CD4(+) T cells; Step trial
ID SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL RESPONSES; HIV-1 VACCINE; STEP
TRIAL; VIRAL LOAD; MEDIATED-IMMUNITY; DOUBLE-BLIND; AIDS; MONKEYS;
ACQUISITION
AB It has been suggested that poor immunogenicity may explain the lack of vaccine efficacy in preventing or controlling HIV infection in the Step trial. To investigate this issue we vaccinated eight Indian rhesus macaques with a trivalent replication-incompetent adenovirus serotype 5 vaccine expressing SIV Gag, Pol, and Nef using a regimen similar to that employed in the Step trial. We detected broad vaccine-induced CD8(+) (2-7 pool-specific responses) and CD4(+) (5-19 pool-specific responses) T-cell responses in IFN-gamma ELISPOT assays at one week post-boost using fresh PBMC. However, using cryopreserved cells at one and four weeks post-boost we observed a reduction in both the number and magnitude of most vaccine-induced responses. This demonstrates that the time points and conditions chosen to perform immune assays may influence the observed breadth and frequency of vaccine-induced T-cell responses. To evaluate protective efficacy, we challenged the immunized macaques, along with naive controls, with repeated, limiting doses of the heterologous swarm isolate SIVsmE660. Vaccination did not significantly affect acquisition or control of virus replication in vaccinees compared to naive controls. Post-infection we observed an average of only two anamnestic CD8(+) T-cell responses per animal, which may not have been sufficiently broad to control heterologous virus replication. While the trivalent vaccine regimen induced relatively broad T-cell responses in rhesus macaques, it failed to protect against infection or control viral replication. Our results are consistent with those observed in the Step trial and indicate that SIV immunization and challenge studies in macaque models of HIV infection can be informative in assessing pre-clinical HIV vaccines. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Reynolds, Matthew R.; Weiler, Andrea M.; Piaskowski, Shari M.; Wilson, Nancy A.; Watkins, David I.] AIDS Vaccine Res Lab, Madison, WI 53711 USA.
[Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Robertson, Henry T.; Allison, David B.] Univ Alabama Birmingham, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA.
[Bett, Andrew J.; Casimiro, Danilo R.; Shiver, John W.] Merck Res Labs, Dept Vaccine Basic Res, West Point, PA 19486 USA.
[Koff, Wayne C.] Int AIDS Vaccine Initiat, New York, NY 10038 USA.
[Watkins, David I.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA.
RP Reynolds, MR (reprint author), AIDS Vaccine Res Lab, 555 Sci Dr, Madison, WI 53711 USA.
EM mrreynol@wisc.edu; amweiler@wisc.edu; sharip@primate.wisc.edu;
Michael.Piatak2@nih.gov; HRobertson@ms.soph.uab.edu;
DAllison@ms.soph.uab.edu; andrew_bett@merck.com;
danilo_casimiro@merck.com; john_shiver@merck.com;
nwilson@primate.wisc.edu; Jeffrey.Lifson@nih.gov; WKoff@iavi.org;
DWatkins@med.miami.edu
OI Allison, David/0000-0003-3566-9399
FU International AIDS Vaccine Initiative; National Institutes of Health
(NIH) [RO1 AI049120, R24 RR016038, R24 RR015371, HHSN266200400088C,
HHSN261200800001E]; National Center for Research Resources (NCRR) [P51
RR000167]; National Cancer Institute; Research Facilities Improvement
Program [RR15459-01, RR020141-01]
FX This research was supported by funds from the International AIDS Vaccine
Initiative, National Institutes of Health (NIH) Grants RO1 AI049120, R24
RR016038, R24 RR015371, and contract HHSN266200400088C to D.I.W., P51
RR000167 to the WNPRC from the National Center for Research Resources
(NCRR), a component of the NIH, and in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
No. HHSN261200800001E. Additionally, this research was conducted at a
facility constructed with support from Research Facilities Improvement
Program Grant numbers RR15459-01 and RR020141-01. This publication's
contents are solely the responsibility of the authors and do not
necessarily represent the official views of NCRR or NIH. Employees of
the International AIDS Vaccine Initiative contributed to the study
design and preparation of the manuscript.
NR 68
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U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD JUN 22
PY 2012
VL 30
IS 30
BP 4465
EP 4475
DI 10.1016/j.vaccine.2012.04.082
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 024NY
UT WOS:000310117100009
PM 22569124
ER
PT J
AU Fernandez-Medina, RD
Ribeiro, JMC
Carareto, CMA
Velasque, L
Struchiner, CJ
AF Fernandez-Medina, Rita D.
Ribeiro, Jose M. C.
Carareto, Claudia M. A.
Velasque, Luciane
Struchiner, Claudio J.
TI Losing identity: structural diversity of transposable elements belonging
to different classes in the genome of Anopheles gambiae
SO BMC GENOMICS
LA English
DT Article
DE Transposable elements; LTR; Non-LTR; Class II; Deterioration; Anopheles
gambiae
ID NON-LTR RETROTRANSPOSONS; LINE-LIKE ELEMENT; DNA LOSS;
DROSOPHILA-MELANOGASTER; SACCHAROMYCES-CEREVISIAE; EVOLUTIONARY
DYNAMICS; REGULATORY SEQUENCES; MALARIA MOSQUITO; MOBILE ELEMENTS;
TY3/GYPSY GROUP
AB Background: Transposable elements (TEs), both DNA transposons and retrotransposons, are genetic elements with the main characteristic of being able to mobilize and amplify their own representation within genomes, utilizing different mechanisms of transposition. An almost universal feature of TEs in eukaryotic genomes is their inability to transpose by themselves, mainly as the result of sequence degeneration (by either mutations or deletions). Most of the elements are thus either inactive or non-autonomous. Considering that the bulk of some eukaryotic genomes derive from TEs, they have been conceived as "TE graveyards." It has been shown that once an element has been inactivated, it progressively accumulates mutations and deletions at neutral rates until completely losing its identity or being lost from the host genome; however, it has also been shown that these "neutral sequences" might serve as raw material for domestication by host genomes.
Results: We have analyzed the sequence structural variations, nucleotide divergence, and pattern of insertions and deletions of several superfamilies of TEs belonging to both class I (long terminal repeats [LTRs] and non-LTRs [NLTRs]) and II in the genome of Anopheles gambiae, aiming at describing the landscape of deterioration of these elements in this particular genome. Our results describe a great diversity in patterns of deterioration, indicating lineage-specific differences including the presence of Solo-LTRs in the LTR lineage, 5'-deleted NLTRs, and several non-autonomous and MITEs in the class II families. Interestingly, we found fragments of NLTRs corresponding to the RT domain, which preserves high identity among them, suggesting a possible remaining genomic role for these domains.
Conclusions: We show here that the TEs in the An. gambiae genome deteriorate in different ways according to the class to which they belong. This diversity certainly has implications not only at the host genomic level but also at the amplification dynamic and evolution of the TE families themselves.
C1 [Fernandez-Medina, Rita D.; Struchiner, Claudio J.] Fundacao Oswaldo Cruz, Escola Nacl Saude Publ Sergio Arouca, Rio De Janeiro, Brazil.
[Ribeiro, Jose M. C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Carareto, Claudia M. A.] Univ Estadual Paulista, UNESP, Dept Biol, Lab Evolucao Mol, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil.
[Velasque, Luciane] Univ Fed Estado Rio de Janeiro, Dept Matemat & Estat, Rio De Janeiro, Brazil.
[Struchiner, Claudio J.] Univ Estado Rio de Janeiro, Inst Med Social, BR-20550011 Rio De Janeiro, Brazil.
RP Fernandez-Medina, RD (reprint author), Fundacao Oswaldo Cruz, Escola Nacl Saude Publ Sergio Arouca, Rio De Janeiro, Brazil.
EM dfernandezmedina@gmail.com
RI Struchiner, Claudio/M-9360-2013; Carareto, Claudia/D-2814-2012; Ribeiro,
Jose/J-7011-2015;
OI Ribeiro, Jose/0000-0002-9107-0818
FU Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health; FAPERJ (Fundacao de Amparo a Pesquisa do Estado de
Rio de Janeiro); CNPq (Conselho Nacional de Pesquisa); CNPq
FX This work was supported in part by the Intramural Research Program of
the Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. We thank Brenda Rae
Marshall, DPSS, NIAID, for editing. RDFM and CJS were funded by FAPERJ
(Fundacao de Amparo a Pesquisa do Estado de Rio de Janeiro) and CNPq
(Conselho Nacional de Pesquisa). CMCA was funded by CNPq.
NR 81
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U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUN 22
PY 2012
VL 13
AR 272
DI 10.1186/1471-2164-13-272
PG 15
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 008CK
UT WOS:000308934700001
PM 22726298
ER
PT J
AU Fleming, JM
Ginsburg, E
Oliver, SD
Goldsmith, P
Vonderhaar, BK
AF Fleming, Jodie M.
Ginsburg, Erika
Oliver, Shannon D.
Goldsmith, Paul
Vonderhaar, Barbara K.
TI Hornerin, an S100 family protein, is functional in breast cells and
aberrantly expressed in breast cancer
SO BMC CANCER
LA English
DT Article
DE Hornerin; S100 protein; Mammary gland; Breast cancer; Apoptosis; Protein
fragmentation
ID MASS-SPECTROMETRY; TUMOR-SUPPRESSOR; EPITHELIAL-CELLS; MAMMARY-GLAND;
EXOSOMES; LINES; PSORIASIN; DISEASE; BINDING; SKIN
AB Background: Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca2+ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin's potential role in normal breast cells and breast cancer.
Methods: The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H2O2 to detect changes in hornerin expression during induction of apoptosis/necrosis.
Results: Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization.
Conclusions: Our data opens new possibilities for hornerin and its proteolytic fragments in the control of mammary cell function and breast cancer.
C1 [Fleming, Jodie M.; Oliver, Shannon D.] N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA.
[Goldsmith, Paul] NCI, Antibody Prod & Purificat Unit, NIH, Bethesda, MD 20892 USA.
[Fleming, Jodie M.; Ginsburg, Erika; Vonderhaar, Barbara K.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Fleming, JM (reprint author), N Carolina Cent Univ, Dept Biol, 1801 Fayetteville St,Mary Townes Sci Complex,Rm 2, Durham, NC 27707 USA.
EM jodie.fleming@nccu.edu
FU Center for Cancer Research, an Intramural Research Program of the
National Cancer Institute; Breast Cancer Research Stamp proceeds awarded
FX This research was supported by the Center for Cancer Research, an
Intramural Research Program of the National Cancer Institute, and by
Breast Cancer Research Stamp proceeds awarded through competitive peer
review. The authors would like to thank Dr D. Esposito in the Laboratory
of Proteomics and Analytical Technologies SAIC-Frederick Inc., NCI, for
the attempts at hornerin overexpression and Dr. K. Nagashima of the
Advanced Technology Program, SAIC-Frederick Inc., NCI, for the
processing and TEM imaging of the exosomes.
NR 49
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U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD JUN 22
PY 2012
VL 12
AR 266
DI 10.1186/1471-2407-12-266
PG 12
WC Oncology
SC Oncology
GA 999ZA
UT WOS:000308353500001
PM 22727333
ER
PT J
AU Stone, CL
McMahon, MB
Fortis, LL
Nunez, A
Smythers, GW
Luster, DG
Frederick, RD
AF Stone, Christine L.
McMahon, Michael B.
Fortis, Laurie L.
Nunez, Alberto
Smythers, Gary W.
Luster, Douglas G.
Frederick, Reid D.
TI Gene expression and proteomic analysis of the formation of Phakopsora
pachyrhizi appressoria
SO BMC GENOMICS
LA English
DT Article
ID RICE BLAST FUNGUS; MEDIATED PLANT INFECTION; SUPPRESSION SUBTRACTIVE
HYBRIDIZATION; POLYMERASE-CHAIN-REACTION; ASIAN SOYBEAN RUST;
MAGNAPORTHE-GRISEA; COLLETOTRICHUM-LAGENARIUM; SUBCELLULAR-LOCALIZATION;
CELLULAR-DIFFERENTIATION; PHYTOPHTHORA-INFESTANS
AB Background: Phakopsora pachyrhizi is an obligate fungal pathogen causing Asian soybean rust (ASR). A dual approach was taken to examine the molecular and biochemical processes occurring during the development of appressoria, specialized infection structures by which P. pachyrhizi invades a host plant. Suppression subtractive hybridization (SSH) was utilized to generate a cDNA library enriched for transcripts expressed during appressoria formation. Two-dimensional gel electrophoresis and mass spectroscopy analysis were used to generate a partial proteome of proteins present during appressoria formation.
Results: Sequence analysis of 1133 expressed sequence tags (ESTs) revealed 238 non-redundant ESTs, of which 53% had putative identities assigned. Twenty-nine of the non-redundant ESTs were found to be specific to the appressoria-enriched cDNA library, and did not occur in a previously constructed germinated urediniospore cDNA library. Analysis of proteins against a custom database of the appressoria-enriched ESTs plus Basidiomycota EST sequences available from NCBI revealed 256 proteins. Fifty-nine of these proteins were not previously identified in a partial proteome of P. pachyrhizi germinated urediniospores. Genes and proteins identified fell into functional categories of metabolism, cell cycle and DNA processing, protein fate, cellular transport, cellular communication and signal transduction, and cell rescue. However, 38% of ESTs and 24% of proteins matched only to hypothetical proteins of unknown function, or showed no similarity to sequences in the current NCBI database. Three novel Phakopsora genes were identified from the cDNA library along with six potentially rust-specific genes. Protein analysis revealed eight proteins of unknown function, which possessed classic secretion signals. Two of the extracellular proteins are reported as potential effector proteins.
Conclusions: Several genes and proteins were identified that are expressed in P. pachyrhizi during appressoria formation. Understanding the role that these genes and proteins play in the molecular and biochemical processes in the infection process may provide insight for developing targeted control measures and novel methods of disease management.
C1 [Stone, Christine L.; McMahon, Michael B.; Luster, Douglas G.; Frederick, Reid D.] Agr Res Serv, USDA, Foreign Dis Weed Sci Res Unit, Ft Detrick, MD 21702 USA.
[Fortis, Laurie L.; Nunez, Alberto] Agr Res Serv, USDA, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA.
[Smythers, Gary W.] NCI, Adv Biomed Comp Ctr, Ft Detrick, MD 21702 USA.
RP Frederick, RD (reprint author), Agr Res Serv, USDA, Foreign Dis Weed Sci Res Unit, 1301 Ditto Ave, Ft Detrick, MD 21702 USA.
EM reid.frederick@ars.usda.gov
FU USDA CRIS project [1920-22000-035-00D]
FX This research was supported by USDA CRIS project 1920-22000-035-00D.
Mention of trade names or commercial products in this publication is
solely for the purpose of providing specific information and does not
imply recommendation or endorsement by the U.S. Department of
Agriculture. The U.S. Department of Agriculture (USDA) prohibits
discrimination in all its programs and activities on the basis of race,
color, national origin, age, disability, and where applicable, sex,
marital status, familial status, parental status, religion, sexual
orientation, genetic information, political beliefs, reprisal, or
because all or part of an individual's income is derived from any public
assistance program. (Not all prohibited bases apply to all programs.)
Persons with disabilities who require alternative means for
communication of program information (Braille, large print, audiotape,
etc.) should contact USDA's TARGET Center at (202) 720-2600 (voice and
TDD). To file a complaint of discrimination, write to USDA, Director,
Office of Civil Rights, 1400 Independence Avenue, S.W., Washington, D.C.
20250-9410, or call (800) 795-3272 (voice) or (202) 720-6382 (TDD). USDA
is an equal opportunity provider and employer.
NR 79
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U1 2
U2 25
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUN 22
PY 2012
VL 13
AR 269
DI 10.1186/1471-2164-13-269
PG 21
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 000CW
UT WOS:000308365100001
PM 22727213
ER
PT J
AU Spivak, CE
Kim, W
Liu, QR
Lupica, CR
Doyle, ME
AF Spivak, Charles E.
Kim, Wook
Liu, Qing-Rong
Lupica, Carl R.
Doyle, Maire E.
TI Blockade of beta-cell K-ATP channels by the endocannabinoid,
2-arachidonoylglycerol
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE beta-Cell; Endocannabinoid; Receptor independent effects; Insulinoma
cell line; Low glucose
ID CANNABINOID RECEPTORS; INSULIN-SECRETION; ANANDAMIDE; IDENTIFICATION;
ANTAGONISTS; MEMBRANES; AGONISTS; BINDING; SYSTEM; ISLETS
AB The endocannabinoid system has been demonstrated to be active in the pancreatic beta-cell. However the effects of the endocannabinoids (ECs) on insulin secretion are not well defined and may vary depending on the metabolic state of the beta-cell. Specifically it is not known whether the effects of the ECs occur by activation of the cannabinoid receptors or via their direct interaction with the ion channels of the beta-cell. To begin to delineate the effects of ECs on beta-cell function, we examined how the EC, 2-AG influences beta-cell ion channels in the absence of glucose stimulation. The mouse insulinoma cell line R7T1 was used to survey the effects of 2-AG on the high voltage activated (HVA) calcium, the delayed rectifier (K-v), and the ATP-sensitive K (K-ATP) channels by whole cell patch clamp recording. At 2 mM glucose, 2-AG inhibited the HVA calcium (the majority of which are L-type channels), K-v, and K-ATP channels. The channel exhibiting the most sensitivity to 2-AG blockade was the K-ATP channel, where the IC50 for 2-AG was 1 mu M. Pharmacological agents revealed that the blockade of all these channels was independent of cannabinoid receptors. Our results provide a mechanism for the previous observations that CB1R agonists increase insulin secretion at low glucose concentrations through CB1R independent blockade of the K-ATP channel. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Doyle, Maire E.] Johns Hopkins Med Inst, Div Endocrinol, Dept Med, JHBMC, Baltimore, MD 21224 USA.
[Spivak, Charles E.; Lupica, Carl R.] NIDA, Cellular Neurobiol Branch, Elect Res Sect, NIH, Baltimore, MD 21224 USA.
[Liu, Qing-Rong] NIDA, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA.
[Kim, Wook] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA.
RP Doyle, ME (reprint author), Johns Hopkins Med Inst, Div Endocrinol, Dept Med, JHBMC, 5200 Eastern Ave,MFL Bldg,Ctr Tower,4th Fl,Rm 430, Baltimore, MD 21224 USA.
EM mdoylel@jhmi.edu
RI Liu, Qing-Rong/A-3059-2012
OI Liu, Qing-Rong/0000-0001-8477-6452
FU Juvenile Diabetes Research Foundation (JDRF) [26-2008-864]; Sanford
Project for Type 1 Diabetes, Sioux Falls SD; Autoimmunity Fund at Johns
Hopkins, Division of Endocrinology; National Institute of Drug Abuse
(NIDA)/NIH; National Institute on Aging (NIA)/NIH
FX M.E.D. was the recipient of the Sanford Career Award granted by the
Juvenile Diabetes Research Foundation (JDRF) in collaboration with the
Sanford Project for Type 1 Diabetes, Sioux Falls SD. M.E.D. was also
funded by JDRF innovative award # 26-2008-864 and by a special Grant
from Autoimmunity Fund at Johns Hopkins, Division of Endocrinology. This
work was supported in part by the Intramural Research Program of the
National Institute of Drug Abuse (NIDA)/NIH and Intramural Research
Program of the National Institute on Aging (NIA)/NIH.
NR 22
TC 3
Z9 3
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUN 22
PY 2012
VL 423
IS 1
BP 13
EP 18
DI 10.1016/j.bbrc.2012.05.042
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 983AE
UT WOS:000307087700003
PM 22609205
ER
PT J
AU Alvarez-Downing, MM
Inchauste, SM
Dudley, ME
White, DE
Wunderlich, JR
Rosenberg, SA
Kammula, US
AF Alvarez-Downing, Melissa M.
Inchauste, Suzanne M.
Dudley, Mark E.
White, Donald E.
Wunderlich, John R.
Rosenberg, Steven A.
Kammula, Udai S.
TI Minimally invasive liver resection to obtain tumor-infiltrating
lymphocytes for adoptive cell therapy in patients with metastatic
melanoma
SO WORLD JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Article
DE adoptive cell therapy; advanced melanoma; hepatobiliary; laparoscopy;
tumor infiltrating lymphocytes
ID OPEN HEPATIC RESECTION; CANCER-IMMUNOTHERAPY; SINGLE-INSTITUTION;
COMPLETE RESPONSES; PHASE-III; INTERLEUKIN-2; EXPERIENCE; CHEMOTHERAPY;
DACARBAZINE; OUTCOMES
AB Background: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) in patients with metastatic melanoma has been reported to have a 56% overall response rate with 20% complete responders. To increase the availability of this promising therapy in patients with advanced melanoma, a minimally invasive approach to procure tumor for TIL generation is warranted.
Methods: A feasibility study was performed to determine the safety and efficacy of laparoscopic liver resection to generate TIL for ACT. Retrospective review of a prospectively maintained database identified 22 patients with advanced melanoma and visceral metastasis (AJCC Stage M1c) who underwent laparoscopic liver resection between 1 October 2005 and 31 July 2011. The indication for resection in all patients was to receive postoperative ACT with TIL.
Results: Twenty patients (91%) underwent resection utilizing a closed laparoscopic technique, one required hand-assistance and another required conversion to open resection. Median intraoperative blood loss was 100 mL with most cases performed without a Pringle maneuver. Median hospital stay was 3 days. Three (14%) patients experienced a complication from resection with no mortality. TIL were generated from 18 of 22 (82%) patients. Twelve of 15 (80%) TIL tested were found to have in vitro tumor reactivity. Eleven patients (50%) received the intended ACT. Two patients were rendered no evidence of disease after surgical resection, with one undergoing delayed ACT with generated TIL after relapse. Objective tumor response was seen in 5 of 11 patients (45%) who received TIL, with one patient experiencing an ongoing complete response (32+ months).
Conclusions: Laparoscopic liver resection can be performed with minimal morbidity and serve as an effective means to procure tumor to generate therapeutic TIL for ACT to patients with metastatic melanoma.
C1 [Alvarez-Downing, Melissa M.; Inchauste, Suzanne M.; Dudley, Mark E.; White, Donald E.; Wunderlich, John R.; Rosenberg, Steven A.; Kammula, Udai S.] NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Kammula, US (reprint author), NCI, Surg Branch, Ctr Canc Res, 10 Ctr Dr,Bldg 10 Hatfield CRC,Room 3-5930, Bethesda, MD 20892 USA.
EM udai_kammula@nih.gov
NR 39
TC 1
Z9 1
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1477-7819
J9 WORLD J SURG ONCOL
JI World J. Surg. Oncol.
PD JUN 22
PY 2012
VL 10
AR 113
DI 10.1186/1477-7819-10-113
PG 9
WC Oncology; Surgery
SC Oncology; Surgery
GA 985RM
UT WOS:000307286900001
PM 22726267
ER
PT J
AU Wu, YL
Sommers, JA
Loiland, JA
Kitao, H
Kuper, J
Kisker, C
Brosh, RM
AF Wu, Yuliang
Sommers, Joshua A.
Loiland, Jason A.
Kitao, Hiroyuki
Kuper, Jochen
Kisker, Caroline
Brosh, Robert M., Jr.
TI The Q Motif of Fanconi Anemia Group J Protein (FANCJ) DNA Helicase
Regulates Its Dimerization, DNA Binding, and DNA Repair Function
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BLOOMS-SYNDROME; BREAST-CANCER; ATP BINDING; HOMOLOGOUS RECOMBINATION;
INACTIVATING MUTATIONS; STRUCTURAL BASIS; RECQ HELICASES; GENE-PRODUCT;
MECHANISMS; BACH1
AB The Q motif, conserved in a number of RNA and DNA helicases, is proposed to be important for ATP binding based on structural data, but its precise biochemical functions are less certain. FANCJ encodes a Q motif DEAH box DNA helicase implicated in Fanconi anemia and breast cancer. A Q25A mutation of the invariant glutamine in the Q motif abolished its ability to complement cisplatin or telomestatin sensitivity of a fancj null cell line and exerted a dominant negative effect. Biochemical characterization of the purified recombinant FANCJ-Q25A protein showed that the mutation disabled FANCJ helicase activity and the ability to disrupt protein-DNA interactions. FANCJ-Q25A showed impaired DNA binding and ATPase activity but displayed ATP binding and temperature-induced unfolding transition similar to FANCJ-WT. Size exclusion chromatography and sedimentation velocity analyses revealed that FANCJ-WT existed as molecular weight species corresponding to a monomer and a dimer, and the dimeric form displayed a higher specific activity for ATPase and helicase, as well as greater DNA binding. In contrast, FANCJ-Q25A existed only as a monomer, devoid of helicase activity. Thus, the Q motif is essential for FANCJ enzymatic activity in vitro and DNA repair function in vivo.
C1 [Wu, Yuliang; Sommers, Joshua A.; Loiland, Jason A.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Kitao, Hiroyuki] Kyushu Univ, Dept Mol Oncol, Grad Sch Med Sci, Fukuoka 8128582, Japan.
[Kuper, Jochen; Kisker, Caroline] Univ Wurzburg, Rudolf Virchow Ctr Expt Biomed, Inst Biol Struct, D-97080 Wurzburg, Germany.
RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM broshr@mail.nih.gov
FU National Institutes of Health Intramural Research Program, NIA; Fanconi
Anemia Research Fund; Deutsche Forschungsgemeinschaft [Forschungszentrum
FZ82]
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program, NIA. This work was also supported by
the Fanconi Anemia Research Fund (to R. M. B.) and Deutsche
Forschungsgemeinschaft Grant Forschungszentrum FZ82 (to C. K.).
NR 59
TC 13
Z9 13
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 22
PY 2012
VL 287
IS 26
BP 21699
EP 21716
DI 10.1074/jbc.M112.351338
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 974GH
UT WOS:000306418600012
PM 22582397
ER
PT J
AU Mertz, EL
Facchini, M
Pham, AT
Gualeni, B
De Leonardis, F
Rossi, A
Forlino, A
AF Mertz, Edward L.
Facchini, Marcella
Pham, Anna T.
Gualeni, Benedetta
De Leonardis, Fabio
Rossi, Antonio
Forlino, Antonella
TI Matrix Disruptions, Growth, and Degradation of Cartilage with Impaired
Sulfation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN ARTICULAR-CARTILAGE; AMINO-ACID SULFUR; DIASTROPHIC DYSPLASIA;
CHONDROITIN SULFATE; INDIAN HEDGEHOG; BIOCHEMICAL-CHARACTERIZATION;
CHONDROCYTE DIFFERENTIATION; PROTEOGLYCAN SULFATION; SKELETAL
DEVELOPMENT; CHOLESTEROL SULFATE
AB Diastrophic dysplasia (DTD) is an incurable recessive chondrodysplasia caused by mutations in the SLC26A2 transporter responsible for sulfate uptake by chondrocytes. The mutations cause undersulfation of glycosaminoglycans in cartilage. Studies of dtd mice with a knock-in Slc26a2 mutation showed an unusual progression of the disorder: net undersulfation is mild and normalizing with age, but the articular cartilage degrades with age and bones develop abnormally. To understand underlying mechanisms, we studied newborn dtd mice. We developed, verified and used high-definition infrared hyperspectral imaging of cartilage sections at physiological conditions, to quantify collagen and its orientation, noncollagenous proteins, and chondroitin chains, and their sulfation with 6-mu m spatial resolution and without labeling. We found that chondroitin sulfation across the proximal femur cartilage varied dramatically in dtd, but not in the wild type. Corresponding undersulfation of dtd was mild in most regions, but strong in narrow articular and growth plate regions crucial for bone development. This undersulfation correlated with the chondroitin synthesis rate measured via radioactive sulfate incorporation, explaining the sulfation normalization with age. Collagen orientation was reduced, and the reduction correlated with chondroitin undersulfation. Such disorientation involved the layer of collagen covering the articular surface and protecting cartilage from degradation. Malformation of this layer may contribute to the degradation progression with age and to collagen and proteoglycan depletion from the articular region, which we observed in mice already at birth. The results provide clues to in vivo sulfation, DTD treatment, and cartilage growth.
C1 [Mertz, Edward L.; Pham, Anna T.] Eunice Kennedy Shriver NICHD, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA.
[Facchini, Marcella; Gualeni, Benedetta; De Leonardis, Fabio; Rossi, Antonio; Forlino, Antonella] Univ Pavia, Biochem Sect, Dept Mol Med, I-27100 Pavia, Italy.
RP Mertz, EL (reprint author), Eunice Kennedy Shriver NICHD, Sect Phys Biochem, NIH, 9000 Rockville Pike,Bldg 9,Rm 1E125, Bethesda, MD 20892 USA.
EM mertze@mail.nih.gov
RI Rossi, Antonio/E-9935-2012; Forlino, Antonella/H-5385-2015
OI Forlino, Antonella/0000-0002-6385-1182
FU National Institutes of Health Director's Challenge Fund; NICHD
Intramural Research Program; PRIN [20094C2H2M]; Regione Lombardia
[REGLOM16]; European Community FP6 EuroGrow Grant [LSHM-CT-2007-037471]
FX This work was supported, in whole or in part, by the National Institutes
of Health Director's Challenge Fund, the NICHD Intramural Research
Program, PRIN 20094C2H2M, Regione Lombardia REGLOM16, and European
Community FP6 EuroGrow Grant LSHM-CT-2007-037471.
NR 75
TC 9
Z9 10
U1 2
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 22
PY 2012
VL 287
IS 26
BP 22030
EP 22042
DI 10.1074/jbc.M110.116467
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 974GH
UT WOS:000306418600041
PM 22556422
ER
PT J
AU Cerna, D
Li, HY
Flaherty, S
Takebe, N
Coleman, CN
Yoo, SS
AF Cerna, David
Li, Hongyun
Flaherty, Siobhan
Takebe, Naoko
Coleman, C. Norman
Yoo, Stephen S.
TI Inhibition of Nicotinamide Phosphoribosyltransferase (NAMPT) Activity by
Small Molecule GMX1778 Regulates Reactive Oxygen Species (ROS)-mediated
Cytotoxicity in a p53-and Nicotinic Acid Phosphoribosyltransferase1
(NAPRT1)-dependent Manner
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CANCER STEM-CELLS; OXIDATIVE STRESS; TUMOR-CELLS; P53; APOPTOSIS; ROS;
ANTIOXIDANT; SURVIVAL; DAMAGE; ACTIVATION
AB Cancer cells undergo mitosis more frequently than normal cells and thus have increased metabolic needs, which in turn lead to higher than normal reactive oxygen species (ROS) production. Higher ROS production increases cancer cell dependence on ROS scavenging systems to balance the increased ROS. Selectively modulating intracellular ROS in cancers by exploiting cancer dependence on ROS scavenging systems provides a useful therapeutic approach. Essential to developing these therapeutic strategies is to maintain physiologically low ROS levels in normal tissues while inducing ROS in cancer cells. GMX1778 is a specific inhibitor of nicotinamide phosphoribosyltransferase, a rate-limiting enzyme required for the regeneration of NAD(+) from nicotinamide. We show that GMX1778 increases intracellular ROS in cancer cells by elevating the superoxide level while decreasing the intracellular NAD(+) level. Notably, GMX1778 treatment does not induce ROS in normal cells. GMX1778-induced ROS can be diminished by adding nicotinic acid (NA) in a NA phosphoribosyltransferase 1 (NAPRT1)-dependent manner, but NAPRT1 is lost in a high frequency of glioblastomas, neuroblastomas, and sarcomas. In NAPRT1-deficient cancer cells, ROS induced by GMX1778 was not susceptible to treatment with NA. GMX1778-mediated ROS induction is p53-dependent, suggesting that the status of both p53 and NAPRT1 might affect tumor apoptosis, as determined by annexin-V staining. However, as determined by colony formation, GMX1778 long term cytotoxicity in cancer cells was only prevented by the addition of NA to NAPRT1-expressing cells. Exposure to GMX1778 may be a novel way including ROS selectively in NAPRT1-negative tumors without inducing cytotoxic ROS in normal tissue.
C1 [Cerna, David; Li, Hongyun; Flaherty, Siobhan; Yoo, Stephen S.] NIH, Mol Radiat Therapeut Branch Support, SAIC Frederick, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Takebe, Naoko] NCI, Mol Radiat Therapeut Branch, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA.
[Coleman, C. Norman] NCI, Mol Radiat Therapeut Branch, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Yoo, SS (reprint author), NCI, Mol Radiat Therapeut Branch, Div Canc Treatment & Diag, 6130 Execut Blvd,Rm 6012, Rockville, MD USA.
EM yoosu@mail.nih.gov
FU National Institutes of Health Grant from NCI [HHSN261200800001E]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant HHSN261200800001E from NCI.
NR 40
TC 29
Z9 31
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 22
PY 2012
VL 287
IS 26
BP 22408
EP 22417
DI 10.1074/jbc.M112.357301
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 974GH
UT WOS:000306418600077
PM 22570471
ER
PT J
AU Hu, LL
Cui, WR
He, ZS
Shi, XH
Feng, KY
Ma, BY
Cai, YD
AF Hu, Lele
Cui, Weiren
He, Zhisong
Shi, Xiaohe
Feng, Kaiyan
Ma, Buyong
Cai, Yu-Dong
TI Cooperativity among Short Amyloid Stretches in Long Amyloidogenic
Sequences
SO PLOS ONE
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTIONS; SCORING MATRICES; AGGREGATION RATES;
RIBONUCLEASE-A; HUMAN-DISEASE; PREDICTION; FIBRILS; POLYPEPTIDE;
SEGMENTS; IDENTIFICATION
AB Amyloid fibrillar aggregates of polypeptides are associated with many neurodegenerative diseases. Short peptide segments in protein sequences may trigger aggregation. Identifying these stretches and examining their behavior in longer protein segments is critical for understanding these diseases and obtaining potential therapies. In this study, we combined machine learning and structure-based energy evaluation to examine and predict amyloidogenic segments. Our feature selection method discovered that windows consisting of long amino acid segments of similar to 30 residues, instead of the commonly used short hexapeptides, provided the highest accuracy. Weighted contributions of an amino acid at each position in a 27 residue window revealed three cooperative regions of short stretch, resemble the beta-strand-turn-beta-strand motif in A-beta peptide amyloid and beta-solenoid structure of HET-s(218-289) prion (C). Using an in-house energy evaluation algorithm, the interaction energy between two short stretches in long segment is computed and incorporated as an additional feature. The algorithm successfully predicted and classified amyloid segments with an overall accuracy of 75%. Our study revealed that genome-wide amyloid segments are not only dependent on short high propensity stretches, but also on nearby residues.
C1 [Hu, Lele; Cai, Yu-Dong] Shanghai Univ, Inst Syst Biol, Shanghai, Peoples R China.
[Cui, Weiren; He, Zhisong] Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Shanghai, Peoples R China.
[Hu, Lele] Shanghai Univ, Coll Sci, Dept Chem, Shanghai, Peoples R China.
[Shi, Xiaohe] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China.
[Shi, Xiaohe] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China.
[Feng, Kaiyan] Shanghai Ctr Bioinformat Technol, Shanghai, Peoples R China.
[Ma, Buyong] NCI, Basic Sci Program, SAIC Frederick, Ctr Canc Res Nanobiol Program,NIH, Frederick, MD 21701 USA.
RP Hu, LL (reprint author), Shanghai Univ, Inst Syst Biol, Shanghai, Peoples R China.
EM mabuyong@mail.nih.gov; cai_yud@yahoo.com.cn
RI Ma, Buyong/F-9491-2011;
OI Ma, Buyong/0000-0002-7383-719X; cai, yudong/0000-0001-5664-7979
FU National Basic Research Program of China [2011CB510102, 2011CB510101];
Shanghai Municipal Education Commission [12ZZ087]; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]
FX This project has been funded in whole or in part with funds from the
National Basic Research Program of China (2011CB510102, 2011CB510101),
Innovation Program of Shanghai Municipal Education Commission (12ZZ087),
and Federal funds from National Cancer Institute, National Institutes of
Health, under contract number HHSN261200800001E. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 58
TC 7
Z9 7
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 22
PY 2012
VL 7
IS 6
AR e39369
DI 10.1371/journal.pone.0039369
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 964XV
UT WOS:000305730900052
PM 22761773
ER
PT J
AU Hu, ZH
Yu, DN
Almeida-Suhett, C
Tu, K
Marini, AM
Eiden, L
Braga, MF
Zhu, J
Li, Z
AF Hu, Zhonghua
Yu, Danni
Almeida-Suhett, Camila
Tu, Kang
Marini, Ann M.
Eiden, Lee
Braga, Maria F.
Zhu, Jun
Li, Zheng
TI Expression of miRNAs and Their Cooperative Regulation of the
Pathophysiology in Traumatic Brain Injury
SO PLOS ONE
LA English
DT Article
ID GENE-EXPRESSION; MICRORNA; IMPACT; RAT; NEUROPROTECTION; MECHANISMS;
GENOME; MEMORY
AB Traumatic brain injury (TBI) is a leading cause of injury-related death and disability worldwide. Effective treatment for TBI is limited and many TBI patients suffer from neuropsychiatric sequelae. The molecular and cellular mechanisms underlying the neuronal damage and impairment of mental abilities following TBI are largely unknown. Here we used the next generation sequencing platform to delineate miRNA transcriptome changes in the hippocampus at 24 hours and 7 days following TBI in the rat controlled cortical impact injury (CCI) model, and developed a bioinformatic analysis to identify cellular activities that are regulated by miRNAs differentially expressed in the CCI brains. The results of our study indicate that distinct sets of miRNAs are regulated at different post-traumatic times, and suggest that multiple miRNA species cooperatively regulate cellular pathways for the pathological changes and management of brain injury. The distinctive miRNAs expression profiles at different post-CCI times may be used as molecular signatures to assess TBI progression. In addition to known pathophysiological changes, our study identifies many other cellular pathways that are subjected to modification by differentially expressed miRNAs in TBI brains. These pathways can potentially be targeted for development of novel TBI treatment.
C1 [Hu, Zhonghua; Li, Zheng] NIMH, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA.
[Eiden, Lee] NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA.
[Tu, Kang; Zhu, Jun] NHLBI, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Yu, Danni] Purdue Univ, Dept Stat, W Lafayette, IN 47907 USA.
[Almeida-Suhett, Camila; Braga, Maria F.] Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA.
[Marini, Ann M.] Uniformed Serv Univ Hlth Sci, Sch Med, Dept Neurol, Bethesda, MD 20814 USA.
RP Hu, ZH (reprint author), NIMH, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA.
EM lizheng2@mail.nih.gov
RI Hu, Zhonghua/F-9493-2014; Li, Zheng/I-8016-2014; Hu,
Zhonghua/J-1169-2016;
OI Li, Zheng/0000-0002-2978-2531; Hu, Zhonghua/0000-0002-0117-7081; Eiden,
Lee/0000-0001-7524-944X
FU NIMH; Department of Defense in the Center for Neuroscience and
Regenerative Medicine
FX Support for this work includes funding from the Intramural Research
Program of the NIMH and Department of Defense in the Center for
Neuroscience and Regenerative Medicine. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 35
TC 23
Z9 25
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 22
PY 2012
VL 7
IS 6
AR e39357
DI 10.1371/journal.pone.0039357
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 964XV
UT WOS:000305730900050
PM 22761770
ER
PT J
AU Unlu, S
Tang, SW
Wang, EN
Martinez, I
Tang, DL
Bianchi, ME
Zeh, HJ
Lotze, MT
AF Unlu, Sebnem
Tang, Siuwah
Wang, E. Na
Martinez, Ivan
Tang, Daolin
Bianchi, Marco E.
Zeh, Herbert J., III
Lotze, Michael T.
TI Damage Associated Molecular Pattern Molecule-Induced microRNAs
(DAMPmiRs) in Human Peripheral Blood Mononuclear Cells
SO PLOS ONE
LA English
DT Article
ID DENDRITIC CELLS; EXPRESSION; CANCER; GROWTH; METASTASIS; SIGNATURE;
AUTOPHAGY; PATHWAY; DANGER; DEATH
AB Endogenous damage associated molecular pattern molecules (DAMPs) released from necrotic, damaged or stressed cells are associated with an inflammatory response. Whether the microRNA (miR) expression signature of this response is different from that of a pathogen associated molecular pattern (PAMP)-stimulated inflammatory response is unknown. We report here that miR-34c and miR-214 are significantly expressed in fresh human peripheral blood mononuclear cells (PBMCs) exposed to DAMP-containing freeze-thaw lysates, or to conditioned media from serum-starved and glucose-deprived cells (p<6x10(-4) and p<3.7x10(-3)), respectively. Interestingly, only miR-34c expression was differentially expressed in PBMCs exposed to freeze-thaw lysates or conditioned media from wildtype High Mobility Group B1 (HMGB1(+/+)) mouse embryonic fibroblast (MEF) cells, when compared to cultures exposed to lysates or conditioned media from HMGB1(-/-) MEFs. miR-155 expression in these cultures was negligible, but was significantly expressed in PBMCs stimulated with Lipopolysaccahride (LPS) or most other Toll-like receptor (TLR) ligands, making it the prototypic "PAMPmiR". Exposure to a damaged human colorectal carcinoma cell line lysate (HCT116) similarly resulted in increased miR-34c and miR-214 levels. When PBMCs were pre-transfected with anti-miR-34c and then exposed to lysate, expression levels of IKK gamma mRNA, a putative target of miR-34c, increased, while protein levels of IKK gamma in cultures transfected with a pre-miR-34c were abrogated. Levels of miR-34c expression (as well as pro-inflammatory cytokines, IL-1 beta and TNF alpha) decreased when PBMC cultures were briefly pre-incubated with the K+ channel (inflammasome) inhibitor, glybenclamide, suggesting that inflammasome activation is upstream of miR-34c expression in response to DAMPs. Our findings demonstrate that a specific microRNA expression signature is associated with the inflammatory response to damaged/injured cells and carries implications for many acute and chronic inflammatory disorders.
C1 [Unlu, Sebnem; Tang, Siuwah; Tang, Daolin; Zeh, Herbert J., III; Lotze, Michael T.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15260 USA.
[Wang, E. Na] NIH, Dept Transfus Med, Infect Dis & Immunogenet Lab, Bethesda, MD 20892 USA.
[Bianchi, Marco E.] San Raffaele Univ, Dept Mol Biol & Funct Genom, Milan, Italy.
[Bianchi, Marco E.] Ist Sci San Raffaele, I-20132 Milan, Italy.
[Martinez, Ivan] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
RP Unlu, S (reprint author), Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15260 USA.
EM unlus@upmc.edu; lotzemt@upmc.edu
RI Tang, Daolin/B-2905-2010;
OI Bianchi, Marco Emilio/0000-0002-5329-6445
FU National Institutes of Health [P01 CA 101944-04]; National Cancer
Institute; Clinical and Translational Research award
[1U54RR023506-01-PI]
FX This project was funded by the National Institutes of Health (P01 CA
101944-04, PI: Michael T. Lotze, MD), the National Cancer Institute
("Integrating NK and DC into Cancer Therapy") and a Clinical and
Translational Research award to Herbert J. Zeh and Bino John. (from
1U54RR023506-01-PI: Steven Reis, MD). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 33
TC 18
Z9 19
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 22
PY 2012
VL 7
IS 6
AR e38899
DI 10.1371/journal.pone.0038899
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 964XV
UT WOS:000305730900022
PM 22745684
ER
PT J
AU Field, JJ
Pera, B
Calvo, E
Canales, A
Zurwerra, D
Trigili, C
Rodriguez-Salarichs, J
Matesanz, R
Kanakkanthara, A
Wakefield, S
Singh, AJ
Jimenez-Barbero, J
Northcote, P
Miller, JH
Lopez, JA
Hamel, E
Barasoain, I
Altmann, KH
Diaz, JF
AF Field, Jessica J.
Pera, Benet
Calvo, Enrique
Canales, Angeles
Zurwerra, Didier
Trigili, Chiara
Rodriguez-Salarichs, Javier
Matesanz, Ruth
Kanakkanthara, Arun
Wakefield, St John
Singh, A. Jonathan
Jimenez-Barbero, Jesus
Northcote, Peter
Miller, John H.
Antonio Lopez, Juan
Hamel, Ernest
Barasoain, Isabel
Altmann, Karl-Heinz
Fernando Diaz, Jose
TI Zampanolide, a Potent New Microtubule-Stabilizing Agent, Covalently
Reacts with the Taxane Luminal Site in Tubulin alpha,beta-Heterodimers
and Microtubules
SO CHEMISTRY & BIOLOGY
LA English
DT Article
ID HIGH-AFFINITY; MOLECULAR RECOGNITION; CYTOTOXIC MACROLIDE; BOUND
CONFORMATION; BINDING-SITES; TAXOID SITE; NMR; PACLITAXEL; EPOTHILONE;
LIGAND
AB Zampanolide and its less active analog dactylolide compete with paclitaxel for binding to microtubules and represent a new class of microtubule-stabilizing agent (MSA). Mass spectrometry demonstrated that the mechanism of action of both compounds involved covalent binding to beta-tubulin at residues N228 and H229 in the taxane site of the microtubule. Alkylation of N228 and H229 was also detected in alpha,beta-tubulin dimers. However, unlike cyclostreptin, the other known MSA that alkylates beta-tubulin, zampanolide was a strong MSA. Modeling the structure of the adducts, using the NMR-derived dactylolide conformation, indicated that the stabilizing activity of zampanolide is likely due to interactions with the M-loop. Our results strongly support the existence of the luminal taxane site of microtubules in tubulin dimers and suggest that microtubule nucleation induction by MSAs may proceed through an allosteric mechanism.
C1 [Pera, Benet; Canales, Angeles; Trigili, Chiara; Rodriguez-Salarichs, Javier; Matesanz, Ruth; Jimenez-Barbero, Jesus; Barasoain, Isabel; Fernando Diaz, Jose] CSIC, Ctr Invest Biol, Madrid 28040, Spain.
[Field, Jessica J.; Kanakkanthara, Arun; Miller, John H.] Victoria Univ Wellington, Sch Biol Sci, Wellington 6012, New Zealand.
[Singh, A. Jonathan; Northcote, Peter] Victoria Univ Wellington, Sch Chem & Phys Sci, Wellington 6012, New Zealand.
[Calvo, Enrique; Antonio Lopez, Juan] Ctr Nacl Invest Cardiovasc, Unidad Prote, Madrid 28029, Spain.
[Canales, Angeles] Univ Complutense Madrid, Fac Ciencias Quim, E-28040 Madrid, Spain.
[Zurwerra, Didier; Altmann, Karl-Heinz] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Inst Pharmaceut Sci, Zurich, Switzerland.
[Rodriguez-Salarichs, Javier] Ctr Estudios Avanzados Cuba, Havana, Cuba.
[Wakefield, St John] Wellington Sch Med & Hlth Sci, Dept Pathol, Wellington 6021, New Zealand.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
RP Diaz, JF (reprint author), CSIC, Ctr Invest Biol, Madrid 28040, Spain.
EM fer@cib.csic.es
RI Field, Jessica/I-6711-2012; JESUS, JIMENEZ-BARBERO/D-4431-2014;
Rodriguez-Salarichs, Javier/C-1123-2015; Lopez, Juan
Antonio/G-7750-2015; Canales, Angeles/K-7499-2015
OI JESUS, JIMENEZ-BARBERO/0000-0001-5421-8513; Lopez, Juan
Antonio/0000-0002-9097-6060; Canales, Angeles/0000-0003-0542-3080
FU EMBO; Genesis Oncology Trust; Ministerio de Economia y Competitividad
[BIO2010-16351, CTQ2009-08536]; Comunidad Autonoma de Madrid
[S2010/BMD-2457 BIPEDD2]; Cancer Society of New Zealand; Wellington
Medical Research Foundation; Fundacion Pro CNIC; Programs de Cooperacion
Cientifica entre el Ministerio de Ciencia, Tecnologias y Medio Ambiente
de la Republica de Cuba (CITMA) y el CSIC
FX We thank Rhone Poulenc Rorer Aventis for DCX and Matadero Municipal
Vicente de Lucas de Segovia for the calf brains for tubulin
purification. JRS was supported by a fellowship from Programs de
Cooperacion Cientifica entre el Ministerio de Ciencia, Tecnologias y
Medio Ambiente de la Republica de Cuba (CITMA) y el CSIC. J.F. received
a short-term fellowship from EMBO and a Professional Development Grant
from the Genesis Oncology Trust. This work was supported in part by
grants BIO2010-16351 and CTQ2009-08536 from Ministerio de Economia y
Competitividad to J.F.D. and J.J.B., respectively, and grant
S2010/BMD-2457 BIPEDD2 from Comunidad Autonoma de Madrid to J.F.D., the
Cancer Society of New Zealand, and the Wellington Medical Research
Foundation (J.M.). The CNIC is supported by the Ministerio de Economia y
Competitividad and the Fundacion Pro CNIC.
NR 45
TC 32
Z9 32
U1 3
U2 31
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
J9 CHEM BIOL
JI Chem. Biol.
PD JUN 22
PY 2012
VL 19
IS 6
BP 686
EP 698
DI 10.1016/j.chembiol.2012.05.008
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 969AW
UT WOS:000306029100009
PM 22726683
ER
PT J
AU Fauci, AS
Collins, FS
AF Fauci, Anthony S.
Collins, Francis S.
TI Benefits and Risks of Influenza Research: Lessons Learned
SO SCIENCE
LA English
DT Editorial Material
AB Given the yearly challenge of seasonal influenza and the potential catastrophic consequences of future pandemics, the need for intensive basic and clinical influenza research is unquestionable. Although the fruits of decades of research have enabled dramatic improvements in our ability to prevent and treat influenza, many fundamental questions remain, including those related to the complex factors associated with host switching and transmission of influenza viruses. Recent public concern over two H5N1 influenza manuscripts that studied the transmissibility of influenza viruses has triggered intense discussion on dual-use research and the way forward.
C1 [Fauci, Anthony S.; Collins, Francis S.] NIH, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM afauci@niaid.nih.gov
NR 7
TC 24
Z9 25
U1 1
U2 22
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUN 22
PY 2012
VL 336
IS 6088
BP 1522
EP 1523
DI 10.1126/science.1224305
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961ZE
UT WOS:000305507500041
PM 22723407
ER
PT J
AU Herfst, S
Schrauwen, EJA
Linster, M
Chutinimitkul, S
de Wit, E
Munster, VJ
Sorrell, EM
Bestebroer, TM
Burke, DF
Smith, DJ
Rimmelzwaan, GF
Osterhaus, ADME
Fouchier, RAM
AF Herfst, Sander
Schrauwen, Eefje J. A.
Linster, Martin
Chutinimitkul, Salin
de Wit, Emmie
Munster, Vincent J.
Sorrell, Erin M.
Bestebroer, Theo M.
Burke, David F.
Smith, Derek J.
Rimmelzwaan, Guus F.
Osterhaus, Albert D. M. E.
Fouchier, Ron A. M.
TI Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets
SO SCIENCE
LA English
DT Article
ID PATHOGENIC AVIAN INFLUENZA; TO-PERSON TRANSMISSION; A VIRUS; H5N1 VIRUS;
RECEPTOR SPECIFICITY; MEDIATED SELECTION; HEMAGGLUTININ; HOST;
INFECTION; MODEL
AB Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza.
C1 [Herfst, Sander; Schrauwen, Eefje J. A.; Linster, Martin; Chutinimitkul, Salin; de Wit, Emmie; Munster, Vincent J.; Sorrell, Erin M.; Bestebroer, Theo M.; Smith, Derek J.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.] Erasmus MC, Dept Virol, Rotterdam, Netherlands.
[Burke, David F.; Smith, Derek J.] Univ Cambridge, Dept Zool, Cambridge, England.
[Smith, Derek J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Fouchier, RAM (reprint author), Erasmus MC, Dept Virol, Rotterdam, Netherlands.
EM r.fouchier@erasmusmc.nl
RI burke, david/C-2091-2013; Wei, Jianjian/F-7788-2011; Fouchier,
Ron/A-1911-2014;
OI Wei, Jianjian/0000-0001-8859-8462; Fouchier, Ron/0000-0001-8095-2869;
burke, david/0000-0001-8830-3951; Osterhaus, Albert/0000-0002-6074-1172;
de Wit, Emmie/0000-0002-9763-7758; Munster, Vincent/0000-0002-2288-3196
FU NIAID-NIH [HHSN266200700010C]; NIH Director's Pioneer Award
[DP1-OD000490-01]; Nederlandse Organisatie voor Wetenschappelijk
Onderzoek VICI grant; European Union FP7 program EMPERIE [223498]; Human
Frontier Science Program [P0050/2008]
FX We thank D. de Meulder, G. van Amerongen, and D. Akkermans for technical
assistance. M. Peiris, Univ. of Hong Kong, provided A/Indonesia/5/2005
with permission from I. Kandun of the Indonesian government. This work
was financed through NIAID-NIH contract HHSN266200700010C. D.J.S. and
D.F.B. were supported in part by NIH Director's Pioneer Award
DP1-OD000490-01. We acknowledge a Nederlandse Organisatie voor
Wetenschappelijk Onderzoek VICI grant, European Union FP7 program
EMPERIE (223498), and Human Frontier Science Program grant P0050/2008.
D.F.B. and D.J.S. acknowledge the use of the CamGrid distributed
computing resource. Sequence data generated from this study were
deposited in GenBank with accession numbers CY116643 to CY116698.
Special arrangements are in place with the NIH and the contractor at
Mount Sinai School of Medicine, New York, for sharing the viruses (and
plasmids) in the present paper; please contact R.A.M.F. A.D.M. E.O. and
G.F.R. are CSO and part-time employee of ViroClinics Biosciences BV.
A.D.M.E.O. has advisory affiliations on behalf of Viroclinics
Biosciences BV with GlaxoSmithKline, Novartis, and Roche. A.D.M.E.O. and
R.A.M.F. are holders of certificates of shares in ViroClinics
Biosciences B.V. To avoid any possible conflict of interests, Erasmus MC
policy dictates that the shares as such are held by the Stichting
Administratiekantoor Erasmus Personeelsparticipaties. The board of this
foundation is appointed by the Board of Governors of the Erasmus MC and
exercises all voting rights with regard to these shares.
NR 56
TC 661
Z9 688
U1 26
U2 258
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUN 22
PY 2012
VL 336
IS 6088
BP 1534
EP 1541
DI 10.1126/science.1213362
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961ZE
UT WOS:000305507500047
PM 22723413
ER
PT J
AU Russell, CA
Fonville, JM
Brown, AEX
Burke, DF
Smith, DL
James, SL
Herfst, S
van Boheemen, S
Linster, M
Schrauwen, EJ
Katzelnick, L
Mosterin, A
Kuiken, T
Maher, E
Neumann, G
Osterhaus, ADME
Kawaoka, Y
Fouchier, RAM
Smith, DJ
AF Russell, Colin A.
Fonville, Judith M.
Brown, Andre E. X.
Burke, David F.
Smith, David L.
James, Sarah L.
Herfst, Sander
van Boheemen, Sander
Linster, Martin
Schrauwen, Eefje J.
Katzelnick, Leah
Mosterin, Ana
Kuiken, Thijs
Maher, Eileen
Neumann, Gabriele
Osterhaus, Albert D. M. E.
Kawaoka, Yoshihiro
Fouchier, Ron A. M.
Smith, Derek J.
TI The Potential for Respiratory Droplet-Transmissible A/H5N1 Influenza
Virus to Evolve in a Mammalian Host
SO SCIENCE
LA English
DT Article
ID A H5N1; RECEPTOR SPECIFICITY; PANDEMIC INFLUENZA; MODEL; REPLICATION;
RESISTANCE; INFECTION; SELECTION; DYNAMICS
AB Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, we found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals. We used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat. These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat.
C1 [Russell, Colin A.; Fonville, Judith M.; Burke, David F.; James, Sarah L.; Katzelnick, Leah; Mosterin, Ana; Smith, Derek J.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
[Russell, Colin A.; Fonville, Judith M.; Burke, David F.; James, Sarah L.; Katzelnick, Leah; Mosterin, Ana; Smith, Derek J.] World Hlth Org WHO Collaborating Ctr Modeling Evo, Cambridge CB2 3EJ, England.
[Russell, Colin A.; Smith, David L.; Smith, Derek J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Brown, Andre E. X.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD 21205 USA.
[Herfst, Sander; van Boheemen, Sander; Linster, Martin; Schrauwen, Eefje J.; Kuiken, Thijs; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.; Smith, Derek J.] Erasmus MC, Dept Virol, NL-3015 CE Rotterdam, Netherlands.
[Mosterin, Ana] Univ Pompeu Fabra, Ctr Res Hlth & Econ, Barcelona 08005, Spain.
[Maher, Eileen; Neumann, Gabriele; Kawaoka, Yoshihiro] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA.
[Kawaoka, Yoshihiro] Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Dept Special Pathogens,Minato Ku, Tokyo 1088639, Japan.
[Kawaoka, Yoshihiro] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Virol,Minato Ku, Tokyo 1088639, Japan.
[Kawaoka, Yoshihiro] Japan Sci & Technol Agcy, Exploratory Res Adv Technol ERATO Infect Induced, Saitama 1020076, Japan.
RP Smith, DJ (reprint author), Univ Cambridge, Dept Zool, Downing St, Cambridge CB2 3EJ, England.
EM dsmith@zoo.cam.ac.uk
RI burke, david/C-2091-2013; Smith, David/L-8850-2013; Fouchier,
Ron/A-1911-2014;
OI Smith, David/0000-0003-4367-3849; Fouchier, Ron/0000-0001-8095-2869;
burke, david/0000-0001-8830-3951; Osterhaus, Albert/0000-0002-6074-1172;
Russell, Colin/0000-0002-2113-162X; Brown, Andre/0000-0002-1324-8764
FU University Research Fellowship from the Royal Society; Nederlandse
Organisatie voor Wetenschappelijk Onderzoek (NWO) VICI grant; European
Union (EU) FP7 program EMPERIE [223498]; European Union (EU) FP7 program
ANTIGONE [278976]; Human Frontier Science Program (HFSP) program
[P0050/2008]; Wellcome [087982AIA]; Bill and Melinda Gates Foundation
[OPPGH5383]; NIH Director's Pioneer Award [DP1-OD000490-01]; National
Institute of Allergy and Infectious Diseases (NIAID)-NIH
[HHSN266200700010C.]; NIAID-NIH [R01 AI 069274]; Ministry of Education,
Culture, Sports, Science, and Technology of Japan; ERATO
FX C.A.R. was supported by a University Research Fellowship from the Royal
Society. The authors acknowledge an Nederlandse Organisatie voor
Wetenschappelijk Onderzoek (NWO) VICI grant, European Union (EU) FP7
programs EMPERIE (223498) and ANTIGONE (278976), Human Frontier Science
Program (HFSP) program grant P0050/2008, Wellcome 087982AIA, the Bill
and Melinda Gates Foundation (OPPGH5383), and NIH Director's Pioneer
Award DP1-OD000490-01. R. A. M. F was supported by National Institute of
Allergy and Infectious Diseases (NIAID)-NIH contract HHSN266200700010C.
A. E. X. B. was supported by a long-term fellowship from the HFSP. E.
M., G.N., and Y.K. are supported by the Bill and Melinda Gates
Foundation (OPPGH5383) and NIAID-NIH grant R01 AI 069274; in addition,
Y.K. was supported by a Grant-in-Aid for Specially Promoted Research
from the Ministry of Education, Culture, Sports, Science, and Technology
of Japan and by ERATO. Y.K. and G.N. have a financial interest as
founders of FluGen and hold a patent on influenza virus reverse
genetics. Y.K and G.N. have a paid consulting relationship with
Theraclone; Y.K. also has a paid consulting relationship with Crucell.
Y.K. has received speaker's honoraria from Chugai Pharmaceuticals,
Novartis, Daiichi-Sankyo Pharmaceutical, Toyama Chemical, Wyeth,
GlaxoSmithKline, and Astellas and grant support from Chugai
Pharmaceuticals, Daiichi Sankyo Pharmaceutical, Toyama Chemical, Otsuka
Pharmaceutical Company A.D.M.E.O. (on behalf of Viroclinics Biosciences
BV) has advisory affiliations with GlaxoSmithKline, Novartis, and Roche.
A.D.M.E.O. is Chief Scientific Officer of Viroclinics Biosciences BV. We
thank S. Cornell, E. Ghedin, R. Johnstone, L. Reperant, and D. M. Smith
for helpful discussions and the reviewers for their detailed and
thoughtful comments.
NR 37
TC 171
Z9 177
U1 7
U2 64
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUN 22
PY 2012
VL 336
IS 6088
BP 1541
EP 1547
DI 10.1126/science.1222526
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961ZE
UT WOS:000305507500048
PM 22723414
ER
PT J
AU Sonmez, M
Saikus, CE
Bell, JA
Franson, DN
Halabi, M
Faranesh, AZ
Ozturk, C
Lederman, RJ
Kocaturk, O
AF Sonmez, Merdim
Saikus, Christina E.
Bell, Jamie A.
Franson, Dominique N.
Halabi, Majdi
Faranesh, Anthony Z.
Ozturk, Cengizhan
Lederman, Robert J.
Kocaturk, Ozgur
TI MRI active guidewire with an embedded temperature probe and providing a
distinct tip signal to enhance clinical safety
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
ID INTERVENTIONAL MRI; CATHETERS; WIRES; SENSITIVITY; ANTENNA
AB Background: The field of interventional cardiovascular MRI is hampered by the unavailability of active guidewires that are both safe and conspicuous. Heating of conductive guidewires is difficult to predict in vivo and disruptive to measure using external probes. We describe a clinical-grade 0.035 '' (0.89 mm) guidewire for MRI right and left heart catheterization at 1.5 T that has an internal probe to monitor temperature in real-time, and that has both tip and shaft visibility as well as suitable flexibility.
Methods: The design has an internal fiberoptic temperature probe, as well as a distal solenoid to enhance tip visibility on a loopless antenna. We tested different tip-solenoid configurations to balance heating and signal profiles. We tested mechanical performance in vitro and in vivo in comparison with a popular clinical nitinol guidewire.
Results: The solenoid displaced the point of maximal heating ("hot spot") from the tip to a more proximal location where it can be measured without impairing guidewire flexion. Probe pullback allowed creation of lengthwise guidewire temperature maps that allowed rapid evaluation of design prototypes. Distal-only solenoid attachment offered the best compromise between tip visibility and heating among design candidates. When fixed at the hot spot, the internal probe consistently reflected the maximum temperature compared external probes. Real-time temperature monitoring was performed during porcine left heart catheterization. Heating was negligible using normal operating parameters (flip angle, 45 degrees; SAR, 1.01 W/kg); the temperature increased by 4.2 degrees C only during high RF power mode (flip angle, 90 degrees; SAR, 3.96 W/kg) and only when the guidewire was isolated from blood cooling effects by an introducer sheath. The tip flexibility and in vivo performance of the final guidewire design were similar to a popular commercial guidewire.
Conclusions: We integrated a fiberoptic temperature probe inside a 0.035 '' MRI guidewire. Real-time monitoring helps detect deleterious heating during use, without impairing mechanical guidewire operation, and without impairing MRI visibility. We therefore need not rely on prediction to ensure safe clinical operation. Future implementations may modulate specific absorption rate (SAR) based on temperature feedback.
C1 [Sonmez, Merdim; Saikus, Christina E.; Bell, Jamie A.; Franson, Dominique N.; Halabi, Majdi; Faranesh, Anthony Z.; Lederman, Robert J.; Kocaturk, Ozgur] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Sonmez, Merdim; Ozturk, Cengizhan] Bogazici Univ, Inst Biomed Engn, Istanbul, Turkey.
RP Lederman, RJ (reprint author), NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
EM lederman@nih.gov
RI Kocaturk, Ozgur/A-1419-2016; Ozturk, Cengizhan/A-6177-2016;
OI Ozturk, Cengizhan/0000-0002-6966-0774; lederman,
robert/0000-0003-1202-6673
FU Division of Intramural Research, National Heart Lung and Blood
Institute, National Institutes of Health USA [Z01-HL006041-01, Z01
HL005062-08]
FX Supported by the Division of Intramural Research, National Heart Lung
and Blood Institute, National Institutes of Health USA, Z01-HL006041-01
and Z01 HL005062-08.
NR 19
TC 13
Z9 13
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD JUN 21
PY 2012
VL 14
AR 38
DI 10.1186/1532-429X-14-38
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 993SD
UT WOS:000307879000001
PM 22720758
ER
PT J
AU Oakley, K
Han, YF
Vishwakarma, BA
Chu, S
Bhatia, R
Gudmundsson, KO
Keller, J
Chen, XF
Vasko, V
Jenkins, NA
Copeland, NG
Du, Y
AF Oakley, Kevin
Han, Yufen
Vishwakarma, Bandana A.
Chu, Su
Bhatia, Ravi
Gudmundsson, Kristbjorn O.
Keller, Jonathan
Chen, Xiongfong
Vasko, Vasyl
Jenkins, Nancy A.
Copeland, Neal G.
Du, Yang
TI Setbp1 promotes the self-renewal of murine myeloid progenitors via
activation of Hoxa9 and Hoxa10
SO BLOOD
LA English
DT Article
ID LEUKEMIA STEM-CELLS; BLAST-CRISIS CML; ACUTE UNDIFFERENTIATED LEUKEMIA;
CHRONIC MYELOGENOUS LEUKEMIA; DNA-BINDING DOMAIN; GENE-EXPRESSION;
PROTEIN SET; HEMATOPOIETIC PROGENITORS; RAPID INDUCTION; HMGA PROTEINS
AB Acquisition of self-renewal capability by myeloid progenitors to become leukemic stem cells during myeloid leukemia development is poorly understood. Here, we show that Setbp1 overexpression efficiently confers self-renewal capability to myeloid progenitors in vitro, causing their immortalization in the presence of stem cell factor and IL-3. Self-renewal after immortalization requires continuous Setbp1 expression. We also found that Hoxa9 and Hoxa10 mRNA are present at dramatically higher levels in Setbp1-immortalized cells compared with other immortalized cells, and are induced shortly after Setbp1 expression in primary myeloid progenitors. Suppression of either gene in Setbp1-immortalized cells drastically reduces their colony-forming capability. Interestingly, Setbp1 protein associates with Hoxa9 and Hoxa10 promoters in chromatin immunoprecipitation assays in these cells, suggesting that both are direct transcriptional targets of Setbp1. Setbp1 also promotes self-renewal of myeloid progenitors in vivo as its coexpression with BCR/ABL transforms primary mouse myeloid progenitors, generating aggressive leukemias in recipient mice resembling chronic myelogenous leukemia (CML) myeloid blast crisis. Increased SETBP1 mRNA levels were also detected in a subset of CML advanced phase/blast crisis patients with high levels of HOXA9 and HOXA10 expression. Thus, Setbp1 activation represents a novel mechanism conferring self-renewal capability to myeloid progenitors in myeloid leukemia development. (Blood. 2012;119(25):6099-6108)
C1 [Oakley, Kevin; Han, Yufen; Vishwakarma, Bandana A.; Vasko, Vasyl; Du, Yang] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA.
[Chu, Su; Bhatia, Ravi] City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplant, Duarte, CA 91010 USA.
[Gudmundsson, Kristbjorn O.; Keller, Jonathan; Chen, Xiongfong] NCI, Frederick, MD 21701 USA.
[Jenkins, Nancy A.; Copeland, Neal G.] Inst Mol & Cell Biol, Canc Genet Lab, Proteos, Singapore.
RP Du, Y (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pediat, Bldg A,Rm 3042B,4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM yang.du@usuhs.edu
RI ASTAR, IMCB/E-2320-2012;
OI Vishwakarma, Bandana/0000-0002-3233-684X
FU National Cancer Institute grant [CA143193]; Department of Pediatrics at
USUHS
FX This work was supported by National Cancer Institute grant CA143193 (to
Y.D.) and the Department of Pediatrics at USUHS.
NR 49
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U1 1
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 21
PY 2012
VL 119
IS 25
BP 6099
EP 6108
DI 10.1182/blood-2011-10-388710
PG 10
WC Hematology
SC Hematology
GA 987EG
UT WOS:000307398700025
PM 22566606
ER
PT J
AU Wu, M
Kwoh, CK
Przytycka, TM
Li, J
Zheng, J
AF Wu, Min
Kwoh, Chee-Keong
Przytycka, Teresa M.
Li, Jing
Zheng, Jie
TI Epigenetic functions enriched in transcription factors binding to mouse
recombination hotspots
SO PROTEOME SCIENCE
LA English
DT Article
ID MEIOTIC RECOMBINATION; HUMANS; GENOME; PRDM9; PROFILES; COMMON; DRIVE;
RATES; MOTIF
AB The regulatory mechanism of recombination is a fundamental problem in genomics, with wide applications in genome-wide association studies, birth-defect diseases, molecular evolution, cancer research, etc. In mammalian genomes, recombination events cluster into short genomic regions called "recombination hotspots". Recently, a 13-mer motif enriched in hotspots is identified as a candidate cis-regulatory element of human recombination hotspots; moreover, a zinc finger protein, PRDM9, binds to this motif and is associated with variation of recombination phenotype in human and mouse genomes, thus is a trans-acting regulator of recombination hotspots. However, this pair of cis and trans-regulators covers only a fraction of hotspots, thus other regulators of recombination hotspots remain to be discovered. In this paper, we propose an approach to predicting additional trans-regulators from DNA-binding proteins by comparing their enrichment of binding sites in hotspots. Applying this approach on newly mapped mouse hotspots genome-wide, we confirmed that PRDM9 is a major trans-regulator of hotspots. In addition, a list of top candidate trans-regulators of mouse hotspots is reported. Using GO analysis we observed that the top genes are enriched with function of histone modification, highlighting the epigenetic regulatory mechanisms of recombination hotspots.
C1 [Wu, Min; Kwoh, Chee-Keong; Zheng, Jie] Nanyang Technol Univ, Sch Comp Engn, Singapore, Singapore.
[Przytycka, Teresa M.] NIH, Computat Biol Branch, NCBI, Natl Lib Med, Bethesda, MD 20892 USA.
[Li, Jing] Case Western Reserve Univ, Dept EECS, Cleveland, OH 44106 USA.
RP Zheng, J (reprint author), Nanyang Technol Univ, Sch Comp Engn, Singapore, Singapore.
EM zhengjie@ntu.edu.sg
RI Zheng, Jie/C-1356-2011
OI Zheng, Jie/0000-0001-6774-9786
FU Nanyang Technological University, Singapore [M58020030]; Ministry of
Education, Singapore [MOE2008-T2-1-074]; NIH, National Library of
Medicine, USA
FX We would like to thank Pavel P. Khil from Genetics and Biochemistry
Branch, NIDDK, NIH, USA for helpful discussions and providing motif
information in [8]. This research has been supported by Startup Grant
M58020030 from Nanyang Technological University, Singapore, and Tier 2
AcRF Grant MOE2008-T2-1-074 from Ministry of Education, Singapore. This
work was also supported by the Intramural Research Program of NIH,
National Library of Medicine, USA.
NR 24
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U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1477-5956
J9 PROTEOME SCI
JI Proteome Sci.
PD JUN 21
PY 2012
VL 10
SU 1
AR S11
DI 10.1186/1477-5956-10-S1-S11
PG 11
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 970XX
UT WOS:000306166700011
PM 22759569
ER
PT J
AU Aldrich, MC
Kumar, R
Colangelo, LA
Williams, LK
Sen, S
Kritchevsky, SB
Meibohm, B
Galanter, J
Hu, DL
Gignoux, CR
Liu, YM
Harris, TB
Ziv, E
Zmuda, J
Garcia, M
Leak, TS
Foreman, MG
Smith, LJ
Fornage, M
Liu, K
Burchard, EG
AF Aldrich, Melinda C.
Kumar, Rajesh
Colangelo, Laura A.
Williams, L. Keoki
Sen, Saunak
Kritchevsky, Stephen B.
Meibohm, Bernd
Galanter, Joshua
Hu, Donglei
Gignoux, Christopher R.
Liu, Yongmei
Harris, Tamara B.
Ziv, Elad
Zmuda, Joseph
Garcia, Melissa
Leak, Tennille S.
Foreman, Marilyn G.
Smith, Lewis J.
Fornage, Myriam
Liu, Kiang
Burchard, Esteban G.
CA Hlth ABC CARDIA Studies
TI Genetic Ancestry-Smoking Interactions and Lung Function in African
Americans: A Cohort Study
SO PLOS ONE
LA English
DT Article
ID FORCED EXPIRATORY VOLUME; PULMONARY-FUNCTION; CARDIOVASCULAR-DISEASE;
LONGITUDINAL CHANGE; GENDER-DIFFERENCES; UNITED-STATES; POPULATION;
MORTALITY; HEALTH; SCAN
AB Background: Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans.
Methodology/Principal Findings: We evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA) Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV1) per pack-year of smoking (-5.7 ml FEV1/smoking pack-year) compared with smokers with lower African ancestry (-4.6 ml in FEV1/smoking pack-year) (interaction P value = 0.17). Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV1 decline in Health ABC and independently replicated in CARDIA.
Conclusions/Significance: African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking.
C1 [Aldrich, Melinda C.] Vanderbilt Univ, Div Epidemiol, Dept Thorac Surg, Nashville, TN USA.
[Aldrich, Melinda C.; Galanter, Joshua; Hu, Donglei; Gignoux, Christopher R.; Ziv, Elad; Burchard, Esteban G.] Univ Calif San Francisco, Dept Med Sci, San Francisco, CA 94143 USA.
[Aldrich, Melinda C.; Galanter, Joshua; Hu, Donglei; Gignoux, Christopher R.; Ziv, Elad; Burchard, Esteban G.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Kumar, Rajesh] Northwestern Univ, Childrens Mem Hosp, Dept Pediat, Feinberg Sch Med, Chicago, IL 60614 USA.
[Colangelo, Laura A.; Liu, Kiang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Williams, L. Keoki] Henry Ford Hlth Syst, Dept Internal Med, Detroit, MI USA.
[Williams, L. Keoki] Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Detroit, MI USA.
[Sen, Saunak] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Meibohm, Bernd] Univ Tennessee, Ctr Hlth Sci, Coll Pharm, Memphis, TN 38163 USA.
[Liu, Yongmei] Wake Forest Univ, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA.
[Harris, Tamara B.; Garcia, Melissa] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Zmuda, Joseph; Leak, Tennille S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Foreman, Marilyn G.] Morehouse Sch Med, Div Pulm & Crit Care Med, Atlanta, GA 30310 USA.
[Smith, Lewis J.] Northwestern Univ, Dept Med, Div Pulm & Crit Care, Feinberg Sch Med, Chicago, IL 60611 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Div Epidemiol, Houston, TX USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Inst Mol Med, Houston, TX USA.
RP Aldrich, MC (reprint author), Vanderbilt Univ, Div Epidemiol, Dept Thorac Surg, Nashville, TN USA.
EM melinda.aldrich@vanderbilt.edu
RI Ziv, Elad/L-5396-2014;
OI Smith, Lewis J/0000-0002-4728-1562; Kritchevsky,
Stephen/0000-0003-3336-6781; Foreman, Marilyn/0000-0002-9405-7475;
Galanter, Joshua/0000-0002-2561-6384
FU National Institutes of Health [HL078885, AI077439, HL088133, R01
HL74104, AI079139, AI061774, HL079055, DK064695, K23HL093023, HL092601,
N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, N01-HC-48047, 48050,
N01-HC-95095]; Vanderbilt Clinical and Translational Research Scholars
Program; Flight Attendant Medical Research Institute (FAMRI); American
Asthma Foundation; Sandler Foundation; National Heart, Lung, and Blood
Institute (NHLBI); Karmel-Sonix; Merck Co
FX Supported by the National Institutes of Health (HL078885, AI077439,
HL088133, R01 HL74104, AI079139, AI061774, HL079055, DK064695,
K23HL093023, HL092601, contracts N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, N01-HC-48047 through 48050, and N01-HC-95095), the
Vanderbilt Clinical and Translational Research Scholars Program, the
Flight Attendant Medical Research Institute (FAMRI), the American Asthma
Foundation and the Sandler Foundation. The funders had no role in study
design, data collection and analysis, or preparation of the manuscript.
The NIA had final responsibility for the decision to submit for
publication for Health ABC. The Coronary Artery Risk Development in
Young Adults Study (CARDIA) is conducted and supported by the National
Heart, Lung, and Blood Institute (NHLBI) in collaboration with the
University of Alabama at Birmingham, University of Minnesota,
Northwestern University, and Kaiser Foundation Research Institute. This
manuscript has been reviewed by CARDIA for scientific content and
consistency of data interpretation with previous CARDIA publications.;
The authors have read the journal's policy and have the following
conflicts: Dr. Aldrich has served as a Guest Editor for PLoS ONE.
Christopher R. Gignoux holds stock with 23andMe, Inc. Dr. Smith received
consultancy funds from Karmel-Sonix. Dr. Williams has received funding
from Merck & Co for speaking engagements and travel. No other
disclosures were reported. This does not alter the authors' adherence to
all the PLoS ONE policies on sharing data and materials.
NR 46
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U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 21
PY 2012
VL 7
IS 6
AR e39541
DI 10.1371/journal.pone.0039541
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 964KY
UT WOS:000305695100043
PM 22737244
ER
PT J
AU Kim, BM
Thier, MC
Oh, S
Sherwood, R
Kanellopoulou, C
Edenhofer, F
Choi, MY
AF Kim, Byeong-Moo
Thier, Marc-Christian
Oh, Sangnam
Sherwood, Richard
Kanellopoulou, Chryssa
Edenhofer, Frank
Choi, Michael Y.
TI MicroRNAs Are Indispensable for Reprogramming Mouse Embryonic
Fibroblasts into Induced Stem Cell-Like Cells
SO PLOS ONE
LA English
DT Article
ID MICROPROCESSOR COMPLEX; RNA INTERFERENCE; NUCLEAR EXPORT; ENZYME DICER;
BIOGENESIS; PLURIPOTENCY; EXPRESSION; GENERATION; DIFFERENTIATION;
MIR-302
AB MicroRNAs play a pivotal role in cellular maintenance, proliferation, and differentiation. They have also been implicated to play a key role in disease pathogenesis, and more recently, cellular reprogramming. Certain microRNA clusters can enhance or even directly induce reprogramming, while repressing key proteins involved in microRNA processing decreases reprogramming efficiency. Although microRNAs clearly play important roles in cellular reprogramming, it remains unknown whether microRNAs are absolutely necessary. We endeavored to answer this fundamental question by attempting to reprogram Dicer-null mouse embryonic fibroblasts (MEFs) that lack almost all functional microRNAs using a defined set of transcription factors. Transduction of reprogramming factors using either lentiviral or piggyBac transposon vector into two, independently derived lines of Dicer-null MEFs failed to produce cells resembling embryonic stem cells (ESCs). However, expression of human Dicer in the Dicer-null MEFs restored their reprogramming potential. Our study demonstrates for the first time that microRNAs are indispensable for dedifferentiation reprogramming.
C1 [Kim, Byeong-Moo; Oh, Sangnam; Choi, Michael Y.] Massachusetts Gen Hosp, Dept Med, GI Unit, Boston, MA 02114 USA.
[Kim, Byeong-Moo; Oh, Sangnam; Sherwood, Richard; Choi, Michael Y.] Harvard Univ, Sch Med, Boston, MA USA.
[Thier, Marc-Christian; Edenhofer, Frank] Univ Bonn, Life & Brain Ctr, Inst Reconstruct Neurobiol, Bonn, Germany.
[Sherwood, Richard] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Kanellopoulou, Chryssa] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Kim, BM (reprint author), Massachusetts Gen Hosp, Dept Med, GI Unit, Boston, MA 02114 USA.
EM mchoi@partners.org
OI Edenhofer, Frank/0000-0002-6489-714X
FU NIH [K08 DK078641]
FX The research was supported by NIH grants to M.Y.C. (K08 DK078641). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 39
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U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 21
PY 2012
VL 7
IS 6
AR e39239
DI 10.1371/journal.pone.0039239
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 964KY
UT WOS:000305695100029
PM 22737231
ER
PT J
AU Kim, H
Phung, Y
Ho, M
AF Kim, Heungnam
Phung, Yen
Ho, Mitchell
TI Changes in Global Gene Expression Associated with 3D Structure of
Tumors: An Ex Vivo Matrix-Free Mesothelioma Spheroid Model
SO PLOS ONE
LA English
DT Article
ID MULTICELLULAR SPHEROIDS; APOPTOTIC RESISTANCE; SOLID TUMORS;
LUNG-CANCER; CELL-LINES; INHIBITORS; CYTOKINES; PATHWAY; KINASE; APRIL
AB Tumor microenvironments present significant barriers to anti-tumor agents. Molecules involved in multicellular tumor microenvironments, however, are difficult to study ex vivo. Here, we generated a matrix-free tumor spheroid model using the NCI-H226 mesothelioma cell line and compared the gene expression profiles of spheroids and monolayers using microarray analysis. Microarray analysis revealed that 142 probe sets were differentially expressed between tumor spheroids and monolayers. Gene ontology analysis revealed that upregulated genes were primarily related to immune response, wound response, lymphocyte stimulation and response to cytokine stimulation, whereas downregulated genes were primarily associated with apoptosis. Among the 142 genes, 27 are located in the membrane and related to biologic processes of cellular movement, cell-to-cell signaling, cellular growth and proliferation and morphology. Western blot analysis validated elevation of MMP2, BAFF/BLyS/TNFSF13B, RANTES/CCL5 and TNFAIP6/TSG-6 protein expression in spheroids as compared to monolayers. Thus, we have reported the first large scale comparison of the transcriptional profiles using an ex vivo matrix-free spheroid model to identify genes specific to the three-dimensional biological structure of tumors. The method described here can be used for gene expression profiling of tumors other than mesothelioma.
C1 [Kim, Heungnam; Phung, Yen; Ho, Mitchell] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Kim, H (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM homi@mail.nih.gov
RI Ho, Mitchell/F-5059-2015
FU National Institutes of Health (NIH), National Cancer Institute (NCI);
Center for Cancer Research; NCI; Mesothelioma Applied Research
Foundation
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute (NCI),
and Center for Cancer Research and by a NCI Director's Intramural
Innovation Principal Investigator Award to MH. This work was also
possible because of a Mesothelioma Applied Research Foundation Craig
Kozicki Memorial Grant to MH. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 25
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Z9 14
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 21
PY 2012
VL 7
IS 6
AR e39556
DI 10.1371/journal.pone.0039556
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 964KY
UT WOS:000305695100045
PM 22737246
ER
PT J
AU Papp, D
Lenti, K
Modos, D
Fazekas, D
Dul, Z
Turei, D
Foldvari-Nagy, L
Nussinov, R
Csermely, P
Korcsmaros, T
AF Papp, Diana
Lenti, Katalin
Modos, Dezso
Fazekas, David
Dul, Zoltan
Tuerei, Denes
Foeldvari-Nagy, Laszlo
Nussinov, Ruth
Csermely, Peter
Korcsmaros, Tamas
TI The NRF2-related interactome and regulome contain multifunctional
proteins and fine-tuned autoregulatory loops
SO FEBS LETTERS
LA English
DT Article
DE NRF2; Protein-protein interaction; Interaction prediction; Regulatory
loops; Signaling network; Double-edged sword
ID BZIP TRANSCRIPTION FACTOR; STRESS-RESPONSE; TARGETED DISRUPTION;
EMBRYONIC LETHALITY; CELLULAR NETWORKS; MULTITARGET DRUGS; NRF2;
BINDING; ACTIVATION; DATABASE
AB NRF2 is a well-known, master transcription factor (TF) of oxidative and xenobiotic stress responses. Recent studies uncovered an even wider regulatory role of NRF2 influencing carcinogenesis, inflammation and neurodegeneration. Prompted by these advances here we present a systems-level resource for NRF2 interactome and regulome that includes 289 protein-protein, 7469 TF-DNA and 85 miRNA interactions. As systems-level examples of NRF2-related signaling we identified regulatory loops of NRF2 interacting proteins (e. g., JNK1 and CBP) and a fine-tuned regulatory system, where 35 TFs regulated by NRF2 influence 63 miRNAs that down-regulate NRF2. The presented network and the uncovered regulatory loops may facilitate the development of efficient, NRF2-based therapeutic agents. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
C1 [Papp, Diana; Modos, Dezso; Fazekas, David; Dul, Zoltan; Tuerei, Denes; Foeldvari-Nagy, Laszlo; Korcsmaros, Tamas] Eotvos Lorand Univ, Dept Genet, Budapest, Hungary.
[Papp, Diana; Modos, Dezso; Tuerei, Denes; Csermely, Peter; Korcsmaros, Tamas] Semmelweis Univ, Fac Med, Dept Med Chem, H-1085 Budapest, Hungary.
[Lenti, Katalin; Modos, Dezso] Semmelweis Univ, Fac Hlth Sci, Dept Morphol & Physiol, H-1085 Budapest, Hungary.
[Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, Sci Applicat Int Corp SAIC Frederick, Frederick Natl Lab, Frederick, MD 21701 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Korcsmaros, T (reprint author), Eotvos Lorand Univ, Dept Genet, Budapest, Hungary.
EM korcsmaros@netbiol.elte.hu
RI Korcsmaros, Tamas/C-3526-2015; Papp, Diana/K-3921-2015;
OI Korcsmaros, Tamas/0000-0003-1717-996X; Papp, Diana/0000-0001-5001-5719;
Fazekas, David/0000-0001-7605-592X; Dul, Zoltan/0000-0002-9523-3450;
Foldvari-Nagy, Laszlo/0000-0002-3954-721X; Modos,
Dezso/0000-0001-9412-6867; Turei, Denes/0000-0002-7249-9379
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; EU-ESF grant [TAMOP 4.2.1./B-09/1/KMR-2010-0003,
TAMOP-4.2.2/B-10/1-2010-0013]; Hungarian Scientific Research Fund [OTKA
K83314]; Hungarian Research and Technology Office [5LET-08-2-2009-0041];
NIH, National Cancer Institute, Center for Cancer Research
FX We thank the anonymous reviewers for their advice and G. Szuromi for
technical help. This project has been funded in whole or in part with
Federal funds from the National Cancer Institute, National Institutes of
Health, under contract number HHSN261200800001E, by the EU-ESF grant
TAMOP 4.2.1./B-09/1/KMR-2010-0003 and TAMOP-4.2.2/B-10/1-2010-0013, the
Hungarian Scientific Research Fund (OTKA K83314), the Hungarian Research
and Technology Office (5LET-08-2-2009-0041) and by a residence at the
Rockefeller Foundation Bellagio Center for PC. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the U.
S. Government. This research was supported (in part) by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 55
TC 29
Z9 29
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD JUN 21
PY 2012
VL 586
IS 13
BP 1795
EP 1802
DI 10.1016/j.febslet.2012.05.016
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 960RC
UT WOS:000305405000009
PM 22641035
ER
PT J
AU Morens, DM
Subbarao, K
Taubenberger, JK
AF Morens, David M.
Subbarao, Kanta
Taubenberger, Jeffery K.
TI Engineering H5N1 avian influenza viruses to study human adaptation
SO NATURE
LA English
DT Article
ID A VIRUSES; RECEPTOR SPECIFICITY; MOUSE MODEL; VIRULENCE DETERMINANTS;
SWINE INFLUENZA; CLEAVAGE SITE; TRANSMISSION; HEMAGGLUTININ; FERRETS;
REPLICATION
AB Two studies of H5N1 avian influenza viruses that had been genetically engineered to render them transmissible between ferrets have proved highly controversial. Divergent opinions exist about the importance of these studies of influenza transmission and about potential 'dual use' research implications. No consensus has developed yet about how to balance these concerns. After not recommending immediate full publication of earlier, less complete versions of the studies, the United States National Science Advisory Board for Biosecurity subsequently recommended full publication of more complete manuscripts; however, controversy about this and similar research remains.
C1 [Morens, David M.; Subbarao, Kanta; Taubenberger, Jeffery K.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dm270q@nih.gov
FU National Institutes of Health; National Institute of Allergy and
Infectious Diseases
FX This work was supported by the National Institutes of Health and the
National Institute of Allergy and Infectious Diseases. The authors
declare no competing financial interests. We thank L. Qi for translation
and discussion of a Chinese language publication.
NR 101
TC 23
Z9 24
U1 1
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUN 21
PY 2012
VL 486
IS 7403
BP 335
EP 340
DI 10.1038/nature11170
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800031
PM 22722191
ER
PT J
AU Schoen, RE
Pinsky, PF
Weissfeld, JL
Yokochi, LA
Church, T
Laiyemo, AO
Bresalier, R
Andriole, GL
Buys, SS
Crawford, ED
Fouad, MN
Isaacs, C
Johnson, CC
Reding, DJ
O'Brien, B
Carrick, DM
Wright, P
Riley, TL
Purdue, MP
Izmirlian, G
Kramer, BS
Miller, AB
Gohagan, JK
Prorok, PC
Berg, CD
AF Schoen, Robert E.
Pinsky, Paul F.
Weissfeld, Joel L.
Yokochi, Lance A.
Church, Timothy
Laiyemo, Adeyinka O.
Bresalier, Robert
Andriole, Gerald L.
Buys, Saundra S.
Crawford, E. David
Fouad, Mona N.
Isaacs, Claudine
Johnson, Christine C.
Reding, Douglas J.
O'Brien, Barbara
Carrick, Danielle M.
Wright, Patrick
Riley, Thomas L.
Purdue, Mark P.
Izmirlian, Grant
Kramer, Barnett S.
Miller, Anthony B.
Gohagan, John K.
Prorok, Philip C.
Berg, Christine D.
CA PLCO Project Team
TI Colorectal-Cancer Incidence and Mortality with Screening Flexible
Sigmoidoscopy
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID FECAL-OCCULT-BLOOD; RANDOMIZED CONTROLLED-TRIAL; SURVEILLANCE
COLONOSCOPY; NEGATIVE COLONOSCOPY; PROSTATE; LUNG; ASSOCIATION;
PROFILES; DEATH; YIELD
AB BACKGROUND
The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality.
METHODS
From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care. Cases of colorectal cancer and deaths from the disease were ascertained.
RESULTS
Of the 77,445 participants randomly assigned to screening (intervention group), 83.5% underwent baseline flexible sigmoidoscopy and 54.0% were screened at 3 or 5 years. The incidence of colorectal cancer after a median follow-up of 11.9 years was 11.9 cases per 10,000 person-years in the intervention group (1012 cases), as compared with 15.2 cases per 10,000 person-years in the usual-care group (1287 cases), which represents a 21% reduction (relative risk, 0.79; 95% confidence interval [CI], 0.72 to 0.85; P < 0.001). Significant reductions were observed in the incidence of both distal colorectal cancer (479 cases in the intervention group vs. 669 cases in the usual-care group; relative risk, 0.71; 95% CI, 0.64 to 0.80; P < 0.001) and proximal colorectal cancer (512 cases vs. 595 cases; relative risk, 0.86; 95% CI, 0.76 to 0.97; P = 0.01). There were 2.9 deaths from colorectal cancer per 10,000 person-years in the intervention group (252 deaths), as compared with 3.9 per 10,000 person-years in the usual-care group (341 deaths), which represents a 26% reduction (relative risk, 0.74; 95% CI, 0.63 to 0.87; P < 0.001). Mortality from distal colorectal cancer was reduced by 50% (87 deaths in the intervention group vs. 175 in the usual-care group; relative risk, 0.50; 95% CI, 0.38 to 0.64; P < 0.001); mortality from proximal colorectal cancer was unaffected (143 and 147 deaths, respectively; relative risk, 0.97; 95% CI, 0.77 to 1.22; P = 0.81).
CONCLUSIONS
Screening with flexible sigmoidoscopy was associated with a significant decrease in colorectal-cancer incidence (in both the distal and proximal colon) and mortality (distal colon only). (Funded by the National Cancer Institute; PLCO ClinicalTrials.gov number, NCT00002540.)
C1 [Schoen, Robert E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA.
[Schoen, Robert E.; Weissfeld, Joel L.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Schoen, Robert E.; Weissfeld, Joel L.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Pinsky, Paul F.; Izmirlian, Grant; Kramer, Barnett S.; Prorok, Philip C.; Berg, Christine D.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Gohagan, John K.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
[O'Brien, Barbara; Carrick, Danielle M.] Westat Corp, Rockville, MD USA.
[Wright, Patrick; Riley, Thomas L.] Informat Management Serv Inc, Rockville, MD USA.
[Yokochi, Lance A.] Pacific Hlth Res & Educ Inst, Rockville, MD USA.
[Church, Timothy] Univ Minnesota, Dept Hlth Studies & Environm Hlth Sci, Minneapolis, MN USA.
[Laiyemo, Adeyinka O.] Howard Univ, Dept Med, Washington, DC 20059 USA.
[Isaacs, Claudine] Georgetown Univ, Washington, DC USA.
[Bresalier, Robert] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Andriole, Gerald L.] Washington Univ, St Louis, MO 63130 USA.
[Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Crawford, E. David] Univ Colorado, Anschutz Canc Pavil, Denver, CO 80202 USA.
[Fouad, Mona N.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA.
[Johnson, Christine C.] Henry Ford Hlth Syst, Detroit, MI USA.
[Reding, Douglas J.] Marshfield Clin Res Fdn, Marshfield, WI USA.
[Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
RP Schoen, RE (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA.
RI Berg , Christine/K-1047-2014; Purdue, Mark/C-9228-2016;
OI Purdue, Mark/0000-0003-1177-3108; Johnson, Christine
Cole/0000-0002-6864-6604; Church, Timothy R./0000-0003-3292-5035
FU Division of Cancer Prevention, National Cancer Institute [N01-CN-25476,
N01-CN-25511, N01-CN-25512, N01-CN-25513, N01-CN-25514, N01-CN-25515,
N01-CN-25516, N01-CN-25518, N01-CN-25522, N01-CN-25524, N01-CN-75022];
Amgen; Augmenix; Bayer; Bristol-Myers Squibb; Cambridge Endo; Caris;
GlaxoSmithKline; Janssen Biotech; Myriad Genetics; Steba Biotech; Ortho
Clinical Diagnostics; UpToDate; Year Book of Urology; Johnson Johnson;
Medivation; Wilex; Viking Medical
FX Supported by contracts from the Division of Cancer Prevention, National
Cancer Institute, to the 10 screening centers and to the coordinating
center (N01-CN-25476, to Westat; N01-CN-25511, to the University of
Pittsburgh Cancer Institute; N01-CN-25512, to Henry Ford Health System;
N01-CN-25513, to the University of Minnesota School of Public Health;
N01-CN-25514, to the University of Colorado; N01-CN-25515, to Pacific
Health Research and Education Institute; N01-CN-25516, to Washington
University; N01-CN-25518, to Marshfield Clinic Research Foundation;
N01-CN-25522, to Georgetown University Medical Center; N01-CN-25524, to
the University of Utah; and N01-CN-75022, to the University of Alabama
at Birmingham).; Dr. Andriole reports receiving consulting fees, payment
for the development of presentations, and payment for travel,
accommodation, and meeting expenses from Amgen; consulting fees, stock
options, and payment for travel, accommodation, and meeting expenses
from Augmenix; consulting fees and payment for travel, accommodation,
and meeting expenses from Bayer; consulting fees and payment for travel,
accommodation, and meeting expenses from Bristol-Myers Squibb;
consulting fees, stock options, and payment for travel, accommodation,
and meeting expenses from Cambridge Endo; consulting fees and payment
for travel, accommodation, and meeting expenses from Caris; consulting
fees and payment for travel, accommodation, and meeting expenses from
GlaxoSmithKline; consulting fees and payment for travel, accommodation,
and meeting expenses from Janssen Biotech; consulting fees and payment
for travel, accommodation, and meeting expenses from Myriad Genetics;
consulting fees and payment for travel, accommodation, and meeting
expenses from Steba Biotech; consulting fees and payment for travel,
accommodation, and meeting expenses from Ortho Clinical Diagnostics;
consulting fees and stock options from Viking Medical; royalties from
UpToDate and Year Book of Urology; stock options from Envisioneering
Medical; and grant support to his institution from Johnson & Johnson,
Medivation, and Wilex; and being a member of an independent data
monitoring committee for Amarex. Dr. Schoen reports receiving stock
options from Onconome. No other potential conflict of interest relevant
to this article was reported.
NR 42
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U1 5
U2 52
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 21
PY 2012
VL 366
IS 25
BP 2345
EP 2357
DI 10.1056/NEJMoa1114635
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 961GH
UT WOS:000305451700004
PM 22612596
ER
PT J
AU Wei, JT
Nygaard, I
Richter, HE
Nager, CW
Barber, MD
Kenton, K
Amundsen, CL
Schaffer, J
Meikle, SF
Spino, C
AF Wei, John T.
Nygaard, Ingrid
Richter, Holly E.
Nager, Charles W.
Barber, Matthew D.
Kenton, Kim
Amundsen, Cindy L.
Schaffer, Joseph
Meikle, Susan F.
Spino, Cathie
CA Pelvic Floor Disorders Network
TI A Midurethral Sling to Reduce Incontinence after Vaginal Prolapse Repair
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PELVIC ORGAN PROLAPSE; URINARY-INCONTINENCE; STRESS-INCONTINENCE; WOMEN;
OUTCOMES; SURGERY; RISK; TAPE
AB BACKGROUND
Women without stress urinary incontinence undergoing vaginal surgery for pelvicorgan prolapse are at risk for postoperative urinary incontinence. A midurethral sling may be placed at the time of prolapse repair to reduce this risk.
METHODS
We performed a multicenter trial involving women without symptoms of stress incontinence and with anterior prolapse (of stage 2 or higher on a Pelvic Organ Prolapse Quantification system examination) who were planning to undergo vaginal prolapse surgery. Women were randomly assigned to receive either a midurethral sling or sham incisions during surgery. One primary end point was urinary incontinence or treatment for this condition at 3 months. The second primary end point was the presence of incontinence at 12 months, allowing for subsequent treatment for incontinence.
RESULTS
Of the 337 women who underwent randomization, 327 (97%) completed follow-up at 1 year. At 3 months, the rate of urinary incontinence (or treatment) was 23.6% in the sling group and 49.4% in the sham group (P < 0.001). At 12 months, urinary incontinence (allowing for subsequent treatment of incontinence) was present in 27.3% and 43.0% of patients in the sling and sham groups, respectively (P = 0.002). The number needed to treat with a sling to prevent one case of urinary incontinence at 12 months was 6.3. The rate of bladder perforation was higher in the sling group than in the sham group (6.7% vs. 0%), as were rates of urinary tract infection (31.0% vs. 18.3%), major bleeding complications (3.1% vs. 0%), and incomplete bladder emptying 6 weeks after surgery (3.7% vs. 0%) (P <= 0.05 for all comparisons).
CONCLUSIONS
A prophylactic midurethral sling inserted during vaginal prolapse surgery resulted in a lower rate of urinary incontinence at 3 and 12 months but higher rates of adverse events. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health; OPUS ClinicalTrials.gov number, NCT00460434.)
C1 [Wei, John T.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
[Nygaard, Ingrid] Univ Utah, Salt Lake City, UT USA.
[Richter, Holly E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Nager, Charles W.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Barber, Matthew D.] Cleveland Clin, Cleveland, OH USA.
[Kenton, Kim] Loyola Univ, Chicago, IL 60611 USA.
[Amundsen, Cindy L.] Duke Univ, Durham, NC USA.
[Schaffer, Joseph] Univ Texas SW, Dallas, TX USA.
[Meikle, Susan F.] Natl Inst Child Hlth & Human Dev, Bethesda, MD USA.
RP Wei, JT (reprint author), Univ Michigan, Dept Urol, 2800 Plymouth Rd,Bldg 520,Rm 3192, Ann Arbor, MI 48109 USA.
EM jtwei@umich.edu
RI Wei, John/E-8967-2012
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [2U01 HD41249, 2U10 HD41250, 2U10 HD41261, 2U10 HD41267,
1U10 HD54136, 1U10 HD54214, 1U10 HD54215, 1U10 HD54241]; National
Institutes of Health Office of Research on Women's Health
FX Supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (2U01 HD41249, 2U10 HD41250, 2U10
HD41261, 2U10 HD41267, 1U10 HD54136, 1U10 HD54214, 1U10 HD54215, and
1U10 HD54241) and the National Institutes of Health Office of Research
on Women's Health.
NR 16
TC 76
Z9 80
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 21
PY 2012
VL 366
IS 25
BP 2358
EP 2367
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 961GH
UT WOS:000305451700005
PM 22716974
ER
PT J
AU Nielsen-Saines, K
Watts, H
Veloso, VG
Bryson, YJ
Joao, EC
Pilotto, JH
Gray, G
Theron, G
Santos, B
Fonseca, R
Kreitchmann, R
Pinto, J
Mussi-Pinhata, MM
Ceriotto, M
Machado, D
Bethel, J
Morgado, MG
Dickover, R
Camarca, M
Mirochnick, M
Siberry, G
Grinsztejn, B
Moreira, RI
Bastos, FI
Xu, JH
Moye, J
Mofenson, LM
AF Nielsen-Saines, Karin
Watts, Heather
Veloso, Valdilea G.
Bryson, Yvonne J.
Joao, Esau C.
Pilotto, Jose Henrique
Gray, Glenda
Theron, Gerhard
Santos, Breno
Fonseca, Rosana
Kreitchmann, Regis
Pinto, Jorge
Mussi-Pinhata, Marisa M.
Ceriotto, Mariana
Machado, Daisy
Bethel, James
Morgado, Marisa G.
Dickover, Ruth
Camarca, Margaret
Mirochnick, Mark
Siberry, George
Grinsztejn, Beatriz
Moreira, Ronaldo I.
Bastos, Francisco I.
Xu, Jiahong
Moye, Jack
Mofenson, Lynne M.
CA NICHD HPTN 040 PACTG Protocol Team
TI Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV
Infection
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; MATERNAL-INFANT
TRANSMISSION; PERINATAL TRANSMISSION; POSTEXPOSURE PROPHYLAXIS;
ZIDOVUDINE TREATMENT; RANDOMIZED-TRIAL; VIRAL LOAD; NEVIRAPINE;
RESISTANCE
AB BACKGROUND
The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants.
METHODS
Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth.
RESULTS A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two-and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P < 0.001 for both comparisons with the other groups).
CONCLUSIONS In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two-or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.)
C1 [Nielsen-Saines, Karin] Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USA.
[Gray, Glenda; Moye, Jack; Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Bethel, James; Camarca, Margaret; Xu, Jiahong] Westat Corp, Rockville, MD USA.
[Veloso, Valdilea G.; Grinsztejn, Beatriz] Fundacao Oswaldo Cruz Fiocruz, Lab Pesquisa Clin DST & AIDS, Inst Pesquisa Clin Evandro Chagas, Rio De Janeiro, Brazil.
[Pilotto, Jose Henrique; Morgado, Marisa G.] Fundacao Oswaldo Cruz Fiocruz, Lab AIDS & Imunol Mol, Inst Oswaldo Cruz, Rio De Janeiro, Brazil.
[Moreira, Ronaldo I.; Bastos, Francisco I.] Fundacao Oswaldo Cruz Fiocruz, Lab Informacoes Saude, Inst Informacao Cient & Tecnol Saude, Rio De Janeiro, Brazil.
[Joao, Esau C.] Hosp Fed Servidores Estado, Rio De Janeiro, Brazil.
[Pilotto, Jose Henrique] Hosp Geral Nova Iguacu, Rio De Janeiro, Brazil.
[Gray, Glenda] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa.
[Gray, Glenda] Chris Hani Baragwanath Hosp, Johannesburg, South Africa.
[Theron, Gerhard] Univ Stellenbosch, Cape Town, South Africa.
[Theron, Gerhard] Tygerberg Hosp, Cape Town, South Africa.
[Santos, Breno] Hosp Conceicao, Porto Alegre, RS, Brazil.
[Fonseca, Rosana] Hosp Femina, Porto Alegre, RS, Brazil.
[Kreitchmann, Regis] Irmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, Brazil.
[Pinto, Jorge] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil.
[Mussi-Pinhata, Marisa M.] Univ Sao Paulo, BR-14049 Ribeirao Preto, SP, Brazil.
[Machado, Daisy] Univ Fed Sao Paulo, Sao Paulo, Brazil.
[Dickover, Ruth] Univ Calif Davis, Davis, CA 95616 USA.
[Ceriotto, Mariana] Fdn Maternal & Infant Hlth, Buenos Aires, DF, Argentina.
[Mirochnick, Mark] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Nielsen-Saines, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, MDCC 22-442 10833 LeConte Ave, Los Angeles, CA 90095 USA.
EM knielsen@mednet.ucla.edu
RI Goncalves Veloso, Valdilea/J-6189-2012; Mussi-Pinhata,
Marisa/G-6568-2012;
OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586
FU NICHD [HHSN267200800001C, N01-HD-8-0001]; HIV Prevention Trials Network;
National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI047986, U01 AI068632]; National Institute of Mental Health [AI068632]
FX Supported by the NICHD (HHSN267200800001C, N01-HD-8-0001) and by a grant
from the HIV Prevention Trials Network, which is funded by the National
Institute of Allergy and Infectious Diseases (NIAID), to the Brazilian
AIDS Prevention Trials International Network at the University of
California, Los Angeles (U01 AI047986). Overall support for IMPAACT,
which endorsed the study, was provided by grants from the NIAID (U01
AI068632), the NICHD, and the National Institute of Mental Health
(AI068632).
NR 37
TC 58
Z9 61
U1 0
U2 5
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 21
PY 2012
VL 366
IS 25
BP 2368
EP 2379
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 961GH
UT WOS:000305451700006
PM 22716975
ER
PT J
AU Violari, A
Lindsey, JC
Hughes, MD
Mujuru, HA
Barlow-Mosha, L
Kamthunzi, P
Chi, BH
Cotton, MF
Moultrie, H
Khadse, S
Schimana, W
Bobat, R
Purdue, L
Eshleman, SH
Abrams, EJ
Millar, L
Petzold, E
Mofenson, LM
Jean-Philippe, P
Palumbo, P
AF Violari, Avy
Lindsey, Jane C.
Hughes, Michael D.
Mujuru, Hilda A.
Barlow-Mosha, Linda
Kamthunzi, Portia
Chi, Benjamin H.
Cotton, Mark F.
Moultrie, Harry
Khadse, Sandhya
Schimana, Werner
Bobat, Raziya
Purdue, Lynette
Eshleman, Susan H.
Abrams, Elaine J.
Millar, Linda
Petzold, Elizabeth
Mofenson, Lynne M.
Jean-Philippe, Patrick
Palumbo, Paul
TI Nevirapine versus Ritonavir-Boosted Lopinavir for HIV-Infected Children
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID SINGLE-DOSE NEVIRAPINE; RANDOMIZED CONTROLLED-TRIAL; ANTIRETROVIRAL
THERAPY; PROTEASE INHIBITOR; DRUG-RESISTANCE; GROWTH; INITIATION;
DYNAMICS; EXPOSURE; FAILURE
AB BACKGROUND
Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus (HIV) transmission is common, a problem that has led to the recommendation of ritonavir-boosted lopinavir in such settings. Regardless of whether there has been prior exposure to nevirapine, the performance of nevirapine versus ritonavir-boosted lopinavir in young children has not been rigorously established.
METHODS
In a randomized trial conducted in six African countries and India, we compared the initiation of HIV treatment with zidovudine, lamivudine, and either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 2 to 36 months of age who had no prior exposure to nevirapine. The primary end point was virologic failure or discontinuation of treatment by study week 24.
RESULTS
A total of 288 children were enrolled; the median percentage of CD4+ T cells was 15%, and the median plasma HIV type 1 (HIV-1) RNA level was 5.7 log(10) copies per milliliter. The percentage of children who reached the primary end point was significantly higher in the nevirapine group than in the ritonavir-boosted lopinavir group (40.8% vs. 19.3%; P < 0.001). Among the nevirapine-treated children with virologic failure for whom data on resistance were available, more than half (19 of 32) had resistance at the time of virologic failure. In addition, the time to a protocol-defined toxicity end point was shorter in the nevirapine group (P=0.04), as was the time to death (P=0.06).
CONCLUSIONS
Outcomes were superior with ritonavir-boosted lopinavir among young children with no prior exposure to nevirapine. Factors that may have contributed to the suboptimal results with nevirapine include elevated viral load at baseline, selection for nevirapine resistance, background regimen of nucleoside reverse-transcriptase inhibitors, and the standard ramp-up dosing strategy. The results of this trial present policymakers with difficult choices. (Funded by the National Institute of Allergy and Infectious Diseases and others; P1060 ClinicalTrials.gov number, NCT00307151.)
C1 [Violari, Avy] Univ Witwatersrand, Perinatal HIV Res Unit, ZA-2050 Johannesburg, South Africa.
[Mujuru, Hilda A.] Univ Witwatersrand, Reprod Hlth & HIV Inst, Fac Hlth Sci, Johannesburg, South Africa.
[Cotton, Mark F.] Univ Stellenbosch, Tygerberg Childrens Hosp, ZA-7505 Tygerberg, South Africa.
[Bobat, Raziya] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Durban, South Africa.
[Lindsey, Jane C.; Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Mujuru, Hilda A.] Univ Zimbabwe, Coll Hlth Sci, Dept Paediat & Child Hlth, Harare, Zimbabwe.
[Barlow-Mosha, Linda] Johns Hopkins Univ, Res Collaborat, Makerere Univ, Kampala, Uganda.
[Kamthunzi, Portia] Univ N Carolina Project, Lilongwe, Malawi.
[Chi, Benjamin H.] Ctr Infect Dis Res Zambia, Lusaka, Zambia.
[Khadse, Sandhya] BJ Med Coll & Sassoon Gen Hosp, Dept Pediat, Pune, Maharashtra, India.
[Schimana, Werner] Duke Univ, Kilimanjaro Christian Med Ctr Collaborat, Moshi, Tanzania.
[Purdue, Lynette] NIAID, NIH, Div Aids, Pharmaceut Affairs Branch, Bethesda, MD 20892 USA.
[Jean-Philippe, Patrick] NIAID, NIH, Div Aids, Henry Jackson Fdn, Bethesda, MD 20892 USA.
[Petzold, Elizabeth] Social & Sci Syst, Silver Spring, MD USA.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA.
[Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Abrams, Elaine J.] Columbia Univ, Sch Publ Hlth, Int Ctr AIDS Care Program, New York, NY USA.
[Abrams, Elaine J.] Columbia Univ, Sch Publ Hlth, Treatment Program, New York, NY USA.
[Abrams, Elaine J.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Millar, Linda] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Palumbo, Paul] Dartmouth Med Sch, Lebanon, NH USA.
RP Palumbo, P (reprint author), Dartmouth Hitchcock Med Ctr, Int Pediat HIV Program, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
EM paul.e.palumbo@dartmouth.edu
OI Mofenson, Lynne/0000-0002-2818-9808
FU National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI068632]; Eunice Kennedy Shriver National Institute of Child Health and
Human Development; National Institute of Mental Health [U01 AI068632, 5
U01 AI41110, 1 U01 AI068616]; NIAID [HHSN272200800014C]; Abbott;
Tibotec; Boehringer Ingelheim; Pfizer; Medicines Development;
GlaxoSmithKline; ViiV Healthcare
FX Supported by a grant [U01 AI068632] from the National Institute of
Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, and the
National Institute of Mental Health to the Pediatric AIDS Clinical
Trials Group (PACTG) and the International Maternal Pediatric Adolescent
AIDS Clinical Trials (IMPAACT) Group; the Statistical and Data Analysis
Center at Harvard School of Public Health under NIAID cooperative
agreements (5 U01 AI41110 with the PACTG and 1 U01 AI068616 and U01
AI068632 with the IMPAACT Group); and by a contract from the NIAID
(HHSN272200800014C).; Dr. Avy Violari reports receiving lecture fees
from Abbott, consulting fees from Tibotec, and trial drugs from
GlaxoSmithKline; Dr. Hughes, consulting fees from Boehringer Ingelheim,
Pfizer, Medicines Development, and Tibotec and support for a scientific
workshop from Merck; Dr. Cotton, lecture fees from Abbott; and Dr.
Moultrie, grants from GlaxoSmithKline, ViiV Healthcare, and Tibotec. No
other potential conflict of interest relevant to this article was
reported.
NR 16
TC 80
Z9 82
U1 0
U2 6
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 21
PY 2012
VL 366
IS 25
BP 2380
EP 2389
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 961GH
UT WOS:000305451700007
PM 22716976
ER
PT J
AU Oler, AJ
Traina-Dorge, S
Derbes, RS
Canella, D
Cairns, BR
Roy-Engel, AM
AF Oler, Andrew J.
Traina-Dorge, Stephen
Derbes, Rebecca S.
Canella, Donatella
Cairns, Brad R.
Roy-Engel, Astrid M.
TI Alu expression in human cell lines and their retrotranspositional
potential
SO MOBILE DNA
LA English
DT Article
DE Alu source elements; Alu expression; RT-PCR; ChIP-seq;
Retrotransposition; SINE
ID HUMAN GENOME; TRANSCRIPTION; SEQUENCES; CHROMATIN; ELEMENTS
AB Background: The vast majority of the 1.1 million Alu elements are retrotranspositionally inactive, where only a few loci referred to as 'source elements' can generate new Alu insertions. The first step in identifying the active Alu sources is to determine the loci transcribed by RNA polymerase III (pol III). Previous genome-wide analyses from normal and transformed cell lines identified multiple Alu loci occupied by pol III factors, making them candidate source elements.
Findings: Analysis of the data from these genome-wide studies determined that the majority of pol III-bound Alus belonged to the older subfamilies Alu S and Alu J, which varied between cell lines from 62.5% to 98.7% of the identified loci. The pol III-bound Alus were further scored for estimated retrotransposition potential (ERP) based on the absence or presence of selected sequence features associated with Alu retrotransposition capability. Our analyses indicate that most of the pol III-bound Alu loci candidates identified lack the sequence characteristics important for retrotransposition.
Conclusions: These data suggest that Alu expression likely varies by cell type, growth conditions and transformation state. This variation could extend to where the same cell lines in different laboratories present different Alu expression patterns. The vast majority of Alu loci potentially transcribed by RNA pol III lack important sequence features for retrotransposition and the majority of potentially active Alu loci in the genome (scored high ERP) belong to young Alu subfamilies. Our observations suggest that in an in vivo scenario, the contribution of Alu activity on somatic genetic damage may significantly vary between individuals and tissues.
C1 [Traina-Dorge, Stephen; Derbes, Rebecca S.; Roy-Engel, Astrid M.] Tulane Univ, Tulane Canc Ctr SL 66, Dept Epidemiol, New Orleans, LA 70112 USA.
[Oler, Andrew J.; Cairns, Brad R.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA.
[Oler, Andrew J.; Cairns, Brad R.] Univ Utah, Sch Med, Howard Hughes Med Inst, Salt Lake City, UT USA.
[Canella, Donatella] Univ Lausanne, Fac Biol & Med, CIG, CH-1015 Lausanne, Switzerland.
[Oler, Andrew J.] NIAID, NIH, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, Bethesda, MD 20892 USA.
RP Roy-Engel, AM (reprint author), Tulane Univ, Tulane Canc Ctr SL 66, Dept Epidemiol, 1430 Tulane Ave, New Orleans, LA 70112 USA.
EM aengel@tulane.edu
RI Oler, Andrew/B-5053-2013;
OI Oler, Andrew/0000-0002-6310-0434; Engel, Astrid/0000-0002-8884-4544
FU National Institutes of Health (NIH) [GM45668, P20GM103518/P20RR020152,
R01GM079709A]; Howard Hughes Medical Institute; [P30 CA042014]
FX This publication was made possible by Grants Number GM45668 (PD) and
P20GM103518/P20RR020152, plus R01GM079709A (to AMR-E) from the National
Institutes of Health (NIH) and the Howard Hughes Medical Institute
(AJO). An allocation of resources from the Center for High Performance
Computing at the University of Utah is gratefully acknowledged. Huntsman
Cancer Institute Biostatistics Core Facility supported by grant P30
CA042014 also participated in this work. The contents are solely the
responsibility of the authors and do not necessarily represent the
official views of NCRR or NIH. We would like to thank Prescott Deininger
for his helpful comments on the manuscript.
NR 24
TC 14
Z9 14
U1 3
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1759-8753
J9 MOBILE DNA-UK
JI Mob. DNA
PD JUN 20
PY 2012
VL 3
AR 11
DI 10.1186/1759-8753-3-11
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 135NL
UT WOS:000318294800001
PM 22716230
ER
PT J
AU Dallmeier, D
Larson, MG
Vasan, RS
Keaney, JF
Fontes, JD
Meigs, JB
Fox, CS
Benjamin, EJ
AF Dallmeier, Dhayana
Larson, Martin G.
Vasan, Ramachandran S.
Keaney, John F., Jr.
Fontes, Joao D.
Meigs, James B.
Fox, Caroline S.
Benjamin, Emelia J.
TI Metabolic syndrome and inflammatory biomarkers: a community-based
cross-sectional study at the Framingham Heart Study
SO DIABETOLOGY & METABOLIC SYNDROME
LA English
DT Article
DE Metabolic syndrome; Inflammatory biomarkers; Body mass index; Insulin
resistance
ID CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; ADIPOSE-TISSUE; P-SELECTIN;
US ADULTS; MARKERS; ASSOCIATION; RISK; PREVALENCE; OBESITY
AB Background: Prior studies reported conflicting findings on the association between metabolic syndrome and inflammatory biomarkers. We tested the cross-sectional associations between metabolic syndrome and nine inflammatory markers.
Methods: We measured C-reactive protein, CD40 ligand, interleukin-6, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, osteoprotegerin, P-selectin, tumor necrosis factor-alpha, and tumor necrosis factor receptor-2 in 2570 Framingham Offspring Study participants free of diabetes and cardiovascular disease at examination 7. Metabolic syndrome was defined by National Cholesterol Education Program criteria. We performed multivariable linear regressions for each biomarker with metabolic syndrome as the exposure adjusting for age, sex, smoking, aspirin use, and hormone replacement. We subsequently added to the models components of the metabolic syndrome as continuous traits plus lipid lowering and hypertension treatments. We considered P < 0.05 as statistically significant.
Results: Metabolic syndrome was present in 984 (38%) participants and was statistically significantly associated with each biomarker (all P < 0.02) except osteoprotegerin. After adjusting for its component variables, the metabolic syndrome was associated only with P-selectin (1.06 fold higher in metabolic syndrome, 95% CI 1.02, 1.10, p = 0.005).
Conclusions: Metabolic syndrome was associated with multiple inflammatory biomarkers. However, adjusting for each of its components eliminated the association with most inflammatory markers, except P-selectin. Our results suggest that the relation between metabolic syndrome and inflammation is largely accounted for by its components.
C1 [Dallmeier, Dhayana] Boston Univ, Sch Med, Div Gen Internal Med, Boston, MA 02118 USA.
[Dallmeier, Dhayana; Larson, Martin G.; Vasan, Ramachandran S.; Fontes, Joao D.; Fox, Caroline S.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Dallmeier, Dhayana; Larson, Martin G.; Vasan, Ramachandran S.; Fontes, Joao D.; Fox, Caroline S.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Div Prevent Med, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Diabet Endocrinol & Metab, Boston, MA 02115 USA.
RP Benjamin, EJ (reprint author), NHLBI, Framingham, MA USA.
EM emelia@bu.edu
OI Larson, Martin/0000-0002-9631-1254; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]; National Institutes of Health, National Center for
Research Resources, General Clinical Research Centers Program
[RO1-HL076784, RO1-HL064753, R01-AG028321]; American Diabetes
Association; NIDDK [K24 DK080140]
FX This study was funded by the National Heart, Lung, and Blood Institute's
Framingham Heart Study N01-HC-25195; and by RO1-HL076784, RO1-HL064753,
and R01-AG028321, the National Institutes of Health, National Center for
Research Resources, General Clinical Research Centers Program, and by a
Career Development Award from the American Diabetes Association (Dr.
Meigs) Dr. Meigs was supported by NIDDK K24 DK080140. No other potential
conflict of interest was reported. The authors declare that there is no
duality of interest associated with this manuscript. An earlier version
of this paper has been presented as an abstract at the 50th
Cardiovascular Disease Epidemiology and Prevention Conference 2010, San
Francisco, USA.
NR 29
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Z9 17
U1 2
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-5996
J9 DIABETOL METAB SYNDR
JI Diabetol. Metab. Syndr.
PD JUN 20
PY 2012
VL 4
AR 28
DI 10.1186/1758-5996-4-28
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 071UG
UT WOS:000313620100001
PM 22716219
ER
PT J
AU Banerjee, A
Berezhkovskii, A
Nossal, R
AF Banerjee, Anand
Berezhkovskii, Alexander
Nossal, Ralph
TI Stochastic Model of Clathrin-Coated Pit Assembly
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID MEDIATED ENDOCYTOSIS; MEMBRANES; DYNAMICS; CELLS
AB In recent years, fluorescence microscopy has enabled researchers to observe the dynamics of clathrin-coated pit (CCP) assembly in real time. The assembly dynamics of CCPs shows striking heterogeneity. Some CCPs are long-lived (productive CCPs); they bind cargo and grow in size to form clathrin-coated vesicles. In contrast, other CCPs (abortive CCPs) are relatively short-lived and disassemble well before reaching vesicle size. Within both populations there is significant variance in CCP lifetime. We propose a stochastic biophysical model that links these observations with the energetics of CCPs and kinetics of their assembly. We show that without cargo, CCP assembly faces a high energy barrier that is difficult to overcome. As a consequence, CCPs without cargo are almost always abortive. We suggest a mechanism by which cargo binding stabilizes CCPs and facilitates their growth. The lifetime distribution of abortive pits calculated from our model agrees well with published experimental data. We also estimate the lifetimes of productive CCPs and show that the stochastic nature of CCP assembly plays a crucial role in causing their observed wide distribution.
C1 [Banerjee, Anand; Nossal, Ralph] Eunice Kennedy Shriver Inst Child Hlth & Human De, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Berezhkovskii, Alexander] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Banerjee, A (reprint author), Eunice Kennedy Shriver Inst Child Hlth & Human De, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
EM banerjeea3@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; Center for Information Technology
FX This study was supported by the Intramural Research Program of the
National Institutes of Health Eunice Kennedy Shriver National Institute
of Child Health and Human Development, and the Center for Information
Technology.
NR 25
TC 10
Z9 10
U1 1
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD JUN 20
PY 2012
VL 102
IS 12
BP 2725
EP 2730
DI 10.1016/j.bpj.2012.05.010
PG 6
WC Biophysics
SC Biophysics
GA 962LL
UT WOS:000305546500006
PM 22735522
ER
PT J
AU Barouki, R
Gluckman, PD
Grandjean, P
Hanson, M
Heindel, JJ
AF Barouki, Robert
Gluckman, Peter D.
Grandjean, Philippe
Hanson, Mark
Heindel, Jerrold J.
TI Developmental origins of non-communicable disease: Implications for
research and public health
SO ENVIRONMENTAL HEALTH
LA English
DT Review
DE Environmental exposure; Fetal development; Non-communicable disease;
Nutritional requirements; Prenatal exposure delayed effects
ID ENDOCRINE-DISRUPTING CHEMICALS
AB This White Paper highlights the developmental period as a plastic phase, which allows the organism to adapt to changes in the environment to maintain or improve reproductive capability in part through sustained health. Plasticity is more prominent prenatally and during early postnatal life, i.e., during the time of cell differentiation and specific tissue formation. These developmental periods are highly sensitive to environmental factors, such as nutrients, environmental chemicals, drugs, infections and other stressors. Nutrient and toxicant effects share many of the same characteristics and reflect two sides of the same coin. In both cases, alterations in physiological functions can be induced and may lead to the development of non-communicable conditions. Many of the major diseases - and dysfunctions - that have increased substantially in prevalence over the last 40 years seem to be related in part to developmental factors associated with either nutritional imbalance or exposures to environmental chemicals. The Developmental Origins of Health and Disease (DOHaD) concept provides significant insight into new strategies for research and disease prevention and is sufficiently robust and repeatable across species, including humans, to require a policy and public health response. This White Paper therefore concludes that, as early development (in utero and during the first years of postnatal life) is particularly sensitive to developmental disruption by nutritional factors or environmental chemical exposures, with potentially adverse consequences for health later in life, both research and disease prevention strategies should focus more on these vulnerable life stages.
C1 [Barouki, Robert] Univ Paris 06, INSERM, UMR S 747, F-75270 Paris 06, France.
[Gluckman, Peter D.] Univ Auckland, Auckland 01142, New Zealand.
[Grandjean, Philippe] Univ So Denmark, DK-5000 Odense, Denmark.
[Grandjean, Philippe] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Hanson, Mark] Univ Southampton, Southampton Gen Hosp, Southampton SO16 6YD, Hants, England.
[Heindel, Jerrold J.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Barouki, R (reprint author), Univ Paris 06, INSERM, UMR S 747, F-75270 Paris 06, France.
EM robert.barouki@parisdescartes.fr
FU British Heart Foundation
FX The PPTOX conference was supported by the Agency for Food Safety,
Environment and Work (France); European Environment Agency; Health,
Environment and Toxicology of the Ile-de France Region; Forsythia
Foundation; International Society for Developmental Origins of Health
and Disease; National Alliance for Life Sciences and Health (Aviesan,
France); the Institut de Recherche en Sante Publique (IRESP, France),
National Center for Toxicological Research (FDA, USA); National
Institute for Environmental Studies (Japan); National Institute of
Environmental health Sciences, and Eunice Kennedy Shriver National
Institute of Child Health & Human Development (NIH, USA); Oak
Foundation; Society of Toxicology and its endowment fund; Superfund
Research Program (USA); Universite Paris Descartes; and World Health
Organization. MAH is supported by the British Heart Foundation. The
contents of this paper do not necessarily represent the official views
of the sponsors.
NR 8
TC 168
Z9 171
U1 6
U2 52
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-069X
J9 ENVIRON HEALTH-GLOB
JI Environ. Health
PD JUN 20
PY 2012
VL 11
AR 42
DI 10.1186/1476-069X-11-42
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 965CY
UT WOS:000305745000001
PM 22715989
ER
PT J
AU Koonin, EV
Dolja, VV
AF Koonin, Eugene V.
Dolja, Valerian V.
TI Expanding networks of RNA virus evolution
SO BMC BIOLOGY
LA English
DT Editorial Material
ID GENOME
AB In a recent BMC Evolutionary Biology article, Huiquan Liu and colleagues report two new genomes of double-stranded RNA (dsRNA) viruses from fungi and use these as a springboard to perform an extensive phylogenomic analysis of dsRNA viruses. The results support the old scenario of polyphyletic origin of dsRNA viruses from different groups of positive-strand RNA viruses and additionally reveal extensive horizontal gene transfer between diverse viruses consistent with the network-like rather than tree-like mode of viral evolution. Together with the unexpected discoveries of the first putative archaeal RNA virus and a RNA-DNA virus hybrid, this work shows that RNA viral genomics has major surprises to deliver.
C1 [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Dolja, Valerian V.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA.
[Dolja, Valerian V.] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
NR 12
TC 9
Z9 10
U1 0
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7007
J9 BMC BIOL
JI BMC Biol.
PD JUN 20
PY 2012
VL 10
AR 54
DI 10.1186/1741-7007-10-54
PG 4
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 962VR
UT WOS:000305576000001
PM 22715894
ER
PT J
AU Burstein, HJ
Piccart-Gebhart, MJ
Perez, EA
Hortobagyi, GN
Wolmark, N
Albain, KS
Norton, L
Winer, EP
Hudis, CA
AF Burstein, Harold J.
Piccart-Gebhart, Martine J.
Perez, Edith A.
Hortobagyi, Gabriel N.
Wolmark, Norman
Albain, Kathy S.
Norton, Larry
Winer, Eric P.
Hudis, Clifford A.
TI Choosing the Best Trastuzumab-Based Adjuvant Chemotherapy Regimen:
Should We Abandon Anthracyclines?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID HER2-POSITIVE BREAST-CANCER; NSABP B-31; PACLITAXEL; CONCURRENT;
EFFICACY; THERAPY; TRIAL; HER2
C1 [Burstein, Harold J.; Winer, Eric P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Piccart-Gebhart, Martine J.] Inst Jules Bordet, B-1000 Brussels, Belgium.
[Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA.
[Hortobagyi, Gabriel N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Wolmark, Norman] Allegheny Gen Hosp, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA.
[Albain, Kathy S.] Loyola Univ, Chicago Stritch Sch Med, Maywood, IL 60153 USA.
[Norton, Larry; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
OI Norton, Larry/0000-0003-3701-9250
NR 19
TC 22
Z9 22
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 20
PY 2012
VL 30
IS 18
BP 2179
EP 2182
DI 10.1200/JCO.2012.42.0695
PG 4
WC Oncology
SC Oncology
GA 960TJ
UT WOS:000305413200008
PM 22614986
ER
PT J
AU Cifani, C
Koya, E
Navarre, BM
Calu, DJ
Baumann, MH
Marchant, NJ
Liu, QR
Khuc, T
Pickel, J
Lupica, CR
Shaham, Y
Hope, BT
AF Cifani, Carlo
Koya, Eisuke
Navarre, Brittany M.
Calu, Donna J.
Baumann, Michael H.
Marchant, Nathan J.
Liu, Qing-Rong
Khuc, Thi
Pickel, James
Lupica, Carl R.
Shaham, Yavin
Hope, Bruce T.
TI Medial Prefrontal Cortex Neuronal Activation and Synaptic Alterations
after Stress-Induced Reinstatement of Palatable Food Seeking: A Study
Using c-fos-GFP Transgenic Female Rats
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ANXIOGENIC DRUG YOHIMBINE; NUCLEUS-ACCUMBENS NEURONS; AMPA RECEPTOR
PLASTICITY; SEX-DIFFERENCES; COCAINE-SEEKING; HEROIN-SEEKING;
NORADRENERGIC MECHANISMS; INDUCED RELAPSE; ESTROUS-CYCLE; ADDICTION
AB Relapse to maladaptive eating habits during dieting is often provoked by stress and there is evidence for a role of ovarian hormones in stress responses and feeding. We studied the role of these hormones in stress-induced reinstatement of food seeking and medial prefrontal cortex (mPFC) neuronal activation in c-fos-GFP transgenic female rats, which express GFP in strongly activated neurons. Food-restricted ovariectomized or sham-operated c-fos-GFP rats were trained to lever-press for palatable food pellets. Subsequently, lever-pressing was extinguished and reinstatement of food seeking and mPFC neuronal activation was assessed after injections of the pharmacological stressor yohimbine (0.5-2 mg/kg) or pellet priming (1-4 noncontingent pellets). Estrous cycle effects on reinstatement were also assessed in wild-type rats. Yohimbine-and pellet-priming-induced reinstatement was associated with Fos and GFP induction in mPFC; both reinstatement and neuronal activation were minimally affected by ovarian hormones in both c-fos-GFP and wild-type rats. c-fos-GFP transgenic rats were then used to assess glutamatergic synaptic alterations within activated GFP-positive and nonactivated GFP-negative mPFC neurons following yohimbine-induced reinstatement of food seeking. This reinstatement was associated with reduced AMPA receptor/NMDA receptor current ratios and increased paired-pulse facilitation in activated GFP-positive but not GFP-negative neurons. While ovarian hormones do not appear to play a role in stress-induced relapse of food seeking in our rat model, this reinstatement was associated with unique synaptic alterations in strongly activated mPFC neurons. Our paper introduces the c-fos-GFP transgenic rat as a new tool to study unique synaptic changes in activated neurons during behavior.
C1 [Hope, Bruce T.] NIDA, NIH, Biomed Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA.
[Pickel, James] NIMH, NIH, Bethesda, MD 20892 USA.
RP Hope, BT (reprint author), NIDA, NIH, Biomed Res Ctr, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM yshaham@intra.nida.nih.gov; bhope@intra.nida.nih.gov
RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014; Liu,
Qing-Rong/A-3059-2012;
OI Hope, Bruce/0000-0001-5804-7061; Liu, Qing-Rong/0000-0001-8477-6452;
Cifani, Carlo/0000-0001-6180-828X; Marchant, Nathan/0000-0001-8269-0532
FU Intramural Research Program of the National Institute on Drug Abuse
FX The work was supported by the Intramural Research Program of the
National Institute on Drug Abuse. We thank Dr. Fabio Cruz for technical
assistance.
NR 66
TC 30
Z9 31
U1 1
U2 7
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 20
PY 2012
VL 32
IS 25
BP 8480
EP 8490
DI 10.1523/JNEUROSCI.5895-11.2012
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 964FD
UT WOS:000305678500007
PM 22723688
ER
PT J
AU Mur, M
Ruff, DA
Bodurka, J
De Weerd, P
Bandettini, PA
Kriegeskorte, N
AF Mur, Marieke
Ruff, Douglas A.
Bodurka, Jerzy
De Weerd, Peter
Bandettini, Peter A.
Kriegeskorte, Nikolaus
TI Categorical, Yet Graded - Single-Image Activation Profiles of Human
Category-Selective Cortical Regions
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID FUSIFORM FACE AREA; INFERIOR TEMPORAL CORTEX; OBJECT REPRESENTATIONS;
INFEROTEMPORAL CORTEX; RESPONSE PATTERNS; VISUAL-CORTEX; FMRI;
ATTENTION; INFORMATION; PERCEPTION
AB Human inferior temporal cortex contains category-selective visual regions, including the fusiform face area (FFA) and the parahippocampal place area (PPA). These regions are defined by their greater category-average activation to the preferred category (faces and places, respectively) relative to nonpreferred categories. The approach of investigating category-average activation has left unclear to what extent category selectivity holds for individual object images. Here we investigate single-image activation profiles to address (1) whether each image from the preferred category elicits greater activation than any image outside the preferred category (categorical ranking), (2) whether there are activation differences within and outside the preferred category (gradedness), and (3) whether the activation profile falls off continuously across the category boundary or exhibits a discontinuity at the boundary (category step). We used functional magnetic resonance imaging to measure the activation elicited in the FFA and PPA by each of 96 object images from a wide range of categories, including faces and places, but also humans and animals, and natural and manmade objects. Results suggest that responses in FFA and PPA exhibit almost perfect categorical ranking, are graded within and outside the preferred category, and exhibit a category step. The gradedness within the preferred category was more pronounced in FFA; the category step was more pronounced in PPA. These findings support the idea that these regions have category-specific functions, but are also consistent with a distributed object representation emphasizing categories while still distinguishing individual images.
C1 [Mur, Marieke; Ruff, Douglas A.; Bandettini, Peter A.; Kriegeskorte, Nikolaus] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Bodurka, Jerzy; Bandettini, Peter A.] NIMH, Funct Magnet Resonance Imaging Facil, NIH, Bethesda, MD 20892 USA.
[Mur, Marieke; De Weerd, Peter] Maastricht Univ, Fac Psychol & Neurosci, Dept Cognit Neurosci, NL-6200 MD Maastricht, Netherlands.
RP Mur, M (reprint author), MRC Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 7EF, England.
EM marieke.mur@mrc-cbu.cam.ac.uk; nikolaus.kriegeskorte@mrc-cbu.cam.ac.uk
OI Ruff, Douglas/0000-0001-7228-8822; Kriegeskorte,
Nikolaus/0000-0001-7433-9005
FU Intramural Research Program of the U.S. National Institutes of Mental
Health (Bethesda, Maryland); Maastricht University (Maastricht, The
Netherlands)
FX This work was supported by the Intramural Research Program of the U.S.
National Institutes of Mental Health (Bethesda, Maryland) and Maastricht
University (Maastricht, The Netherlands).
NR 38
TC 31
Z9 32
U1 1
U2 7
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 20
PY 2012
VL 32
IS 25
BP 8649
EP 8662
DI 10.1523/JNEUROSCI.2334-11.2012
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 964FD
UT WOS:000305678500024
PM 22723705
ER
PT J
AU Mishra, SK
Holzman, S
Hoon, MA
AF Mishra, Santosh K.
Holzman, Sarah
Hoon, Mark A.
TI A Nociceptive Signaling Role for Neuromedin B
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID DORSAL-HORN NEURONS; MAMMALIAN TASTE RECEPTORS; CAT SPINAL-CORD;
SUBSTANCE-P; SENSORY NEURONS; NERVOUS-SYSTEM; ITCH SENSATION;
MESSENGER-RNAS; DEFICIENT MICE; ROOT GANGLIA
AB Here we used an array-based differential screen to uncover the expression of the neuropeptide neuromedin B (NMB) in the trigeminal ganglia of mice. Double-labeling experiments reveal NMB is expressed in a subset of sensory neurons that colabel with calcitonin gene-related peptide and TRPV1 suggestive of a role for NMB in nociception. Indeed, administration of NMB antagonist greatly attenuates edema and nerve sensitization following stimulation of peripheral nerves with mustard oil, demonstrating that NMB contributes to neurogenic inflammation. Moreover, direct injection of NMB causes local swelling and nociceptive sensitization. Interestingly, we also find that the receptor for NMB is expressed in interneurons in the superficial layers of the dorsal horn. We used NMB-saporin to specifically eliminate NMBR-expressing neurons and determined they are required in responses to noxious heat, but not for reaction to mechanical and pruritic stimuli. Thus, NMB may be a neurotransmitter that is selectively involved in the perception of thermal stimuli.
C1 [Mishra, Santosh K.; Holzman, Sarah; Hoon, Mark A.] Natl Inst Dent & Craniofacial Hlth, Mol Genet Unit, Lab Sensory Biol, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Hoon, MA (reprint author), Natl Inst Dent & Craniofacial Hlth, Mol Genet Unit, Lab Sensory Biol, Natl Inst Hlth, Bldg 49,Room 1A16,49 Convent Dr, Bethesda, MD 20892 USA.
EM mark.hoon@nih.gov
FU National Institutes of Health-National Institute of Dental and
Craniofacial Health; National Center for Research Resources-NIH;
National Institute of Neurological Disorders and Stroke
FX This research was supported by the intramural research program of the
National Institutes of Health-National Institute of Dental and
Craniofacial Health (M.A.H.) The mouse strain used for this research
project, STOCK Tg(NmbrEGFP), was obtained from the Mutant Mouse Regional
Resource Center (MMRRC), a National Center for Research
Resources-NIH-funded strain repository, and was donated to the MMRRC by
the National Institute of Neurological Disorders and Stroke funded
GENSAT BAC transgenic project. We are grateful to Nick Ryba for
encouragement and helpful advice and Dr. Siraganian and the Hoon lab for
valuable suggestions.
NR 54
TC 16
Z9 16
U1 1
U2 5
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUN 20
PY 2012
VL 32
IS 25
BP 8686
EP 8695
DI 10.1523/JNEUROSCI.1533-12.2012
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 964FD
UT WOS:000305678500027
PM 22723708
ER
PT J
AU Siddiqua, A
Luo, Y
Meyer, V
Swanson, MA
Yu, X
Wei, GH
Zheng, J
Eaton, GR
Ma, BY
Nussinov, R
Eaton, SS
Margittai, M
AF Siddiqua, Ayisha
Luo, Yin
Meyer, Virginia
Swanson, Michael A.
Yu, Xiang
Wei, Guanghong
Zheng, Jie
Eaton, Gareth R.
Ma, Buyong
Nussinov, Ruth
Eaton, Sandra S.
Margittai, Martin
TI Conformational Basis for Asymmetric Seeding Barrier in Filaments of
Three- and Four-Repeat Tau
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PAIRED HELICAL FILAMENTS; PARAMAGNETIC-RESONANCE SPECTROSCOPY;
ELECTRON-ELECTRON RESONANCE; AMYLOID FIBRILS; ALZHEIMERS-DISEASE;
ALPHA-SYNUCLEIN; MOLECULAR-DYNAMICS; STRAIN VARIATION; BETA-STRUCTURE;
PRION STRAINS
AB Tau pathology in Alzheimer's disease is intimately linked to the deposition of proteinacious filaments, which akin to infectious prions, have been proposed to spread via seeded conversion. Here we use double electron electron resonance (DEER) spectroscopy in combination with extensive computational analysis to show that filaments of three- (3R) and four-repeat (4R) tau are conformationally distinct. Distance measurements between spin labels in the third repeat, reveal tau amyloid filaments as ensembles of known beta-strand-turn-beta-strand U-turn motifs. Whereas filaments seeded with 3R tau are structurally homogeneous, filaments seeded with 4R tau are heterogeneous, composed of at least three distinct conformers. These findings establish a molecular basis for the seeding barrier between different tau isoforms and offer a new powerful approach for investigating the composition and dynamics of amyloid fibril ensembles.
C1 [Siddiqua, Ayisha; Meyer, Virginia; Swanson, Michael A.; Eaton, Gareth R.; Eaton, Sandra S.; Margittai, Martin] Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA.
[Luo, Yin; Wei, Guanghong] Fudan Univ, State Key Lab Surface Phys, Key Lab Computat Phys Sci MOE, Shanghai 200433, Peoples R China.
[Luo, Yin; Wei, Guanghong] Fudan Univ, Dept Phys, Shanghai 200433, Peoples R China.
[Yu, Xiang; Zheng, Jie] Univ Akron, Dept Chem & Biomol Engn, Akron, OH 44325 USA.
[Ma, Buyong; Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program,Frederick Natl Lab, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Dept Human Genet & Mol Med, Sackler Inst Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
RP Margittai, M (reprint author), Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA.
EM martin.margittai@du.edu
RI Ma, Buyong/F-9491-2011; Zheng, Jie/B-5057-2013; Margittai,
Martin/D-5039-2014; Yu, Xiang/A-9765-2012;
OI Eaton, Sandra S/0000-0002-2731-7986; Ma, Buyong/0000-0002-7383-719X;
Zheng, Jie/0000-0003-1547-3612; Margittai, Martin/0000-0003-1903-5927;
Yu, Xiang/0000-0002-0486-1110; Eaton, Gareth R/0000-0001-7429-8469
FU National Institute of Neurological Disorders and Stroke [R01NS076619];
National Cancer Institute [HHSN261200800001E]; intramural research
program of the National Cancer Institute Center for Cancer Research;
National Science Foundation CAREER Award [CBET-0952624]; 3M nontenured
faculty award; National Natural Science [11074047]; Research Fund for
the Doctoral Program of Higher Education of China [RFDP-20100071110006]
FX This project was supported by National Institute of Neurological
Disorders and Stroke Grant R01NS076619 (to KM.). This work was also
supported by National Cancer Institute contract HHSN261200800001E, the
intramural research program of the National Cancer Institute Center for
Cancer Research, National Science Foundation CAREER Award CBET-0952624
(to J.Z.), a 3M nontenured faculty award (to J.Z.), National Natural
Science Foundation of China Grant 11074047 (to G.W.), and Research Fund
for the Doctoral Program of Higher Education of China Grant
RFDP-20100071110006 (to G.W.).
NR 63
TC 27
Z9 27
U1 1
U2 36
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JUN 20
PY 2012
VL 134
IS 24
BP 10271
EP 10278
DI 10.1021/ja303498q
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA 959ZX
UT WOS:000305358900069
PM 22656332
ER
PT J
AU Thomas, HE
Mercer, CA
Carnevalli, LS
Park, J
Andersen, JB
Conner, EA
Tanaka, K
Matsutani, T
Iwanami, A
Aronow, BJ
Manway, L
Maira, SM
Thorgeirsson, SS
Mischel, PS
Thomas, G
Kozma, SC
AF Thomas, Hala Elnakat
Mercer, Carol A.
Carnevalli, Larissa S.
Park, Jongsun
Andersen, Jesper B.
Conner, Elizabeth A.
Tanaka, Kazuhiro
Matsutani, Tomoo
Iwanami, Akio
Aronow, Bruce J.
Manway, Liu
Maira, S. Michel
Thorgeirsson, Snorri S.
Mischel, Paul S.
Thomas, George
Kozma, Sara C.
TI mTOR Inhibitors Synergize on Regression, Reversal of Gene Expression,
and Autophagy in Hepatocellular Carcinoma
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID ENDOPLASMIC-RETICULUM; CELL-PROLIFERATION; INSULIN-RESISTANCE; MAMMALIAN
TARGET; CANCER; RAPAMYCIN; PROTEIN; ACTIVATION; MICE; PHOSPHORYLATION
AB Hepatocellular carcinoma (HCC) affects more than half a million people worldwide and is the third most common cause of cancer deaths. Because mammalian target of rapamycin (mTOR) signaling is up-regulated in 50% of HCCs, we compared the effects of the U.S. Food and Drug Administration-approved mTOR-allosteric inhibitor, RAD001, with a new-generation phosphatidylinositol 3-kinase/mTOR adenosine triphosphate-site competitive inhibitor, BEZ235. Unexpectedly, the two drugs acted synergistically in inhibiting the proliferation of cultured HCC cells. The synergistic effect closely paralleled eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) dephosphorylation, which is implicated in the suppression of tumor cell proliferation. In a mouse model approximating human HCC, the drugs in combination, but not singly, induced a marked regression in tumor burden. However, in the tumor, BEZ235 alone was as effective as the combination in inhibiting 4E-BP1 phosphorylation, which suggests that additional target(s) may also be involved. Microarray analyses revealed a large number of genes that reverted to normal liver tissue expression in mice treated with both drugs, but not either drug alone. These analyses also revealed the down-regulation of autophagy genes in tumors compared to normal liver. Moreover, in HCC patients, altered expression of autophagy genes was associated with poor prognosis. Consistent with these findings, the drug combination had a profound effect on UNC51-like kinase 1 (ULK1) dephosphorylation and autophagy in culture, independent of 4E-BP1, and in parallel induced tumor mitophagy, a tumor suppressor process in liver. These observations have led to an investigator-initiated phase 1B-2 dose escalation trial with RAD001 combined with BEZ235 in patients with HCC and other advanced solid tumors.
C1 [Thomas, Hala Elnakat; Carnevalli, Larissa S.; Park, Jongsun; Thomas, George; Kozma, Sara C.] Univ Cincinnati, Dept Canc & Cell Biol, Cincinnati, OH 45215 USA.
[Thomas, Hala Elnakat; Mercer, Carol A.; Park, Jongsun; Thomas, George; Kozma, Sara C.] Univ Cincinnati, Div Hematol Oncol, Dept Internal Med, Cincinnati, OH 45215 USA.
[Andersen, Jesper B.; Conner, Elizabeth A.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Tanaka, Kazuhiro; Matsutani, Tomoo; Iwanami, Akio; Mischel, Paul S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA.
[Tanaka, Kazuhiro; Matsutani, Tomoo; Iwanami, Akio; Mischel, Paul S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Lab Med, Los Angeles, CA 90095 USA.
[Aronow, Bruce J.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA.
[Manway, Liu] Novartis Inst Biomed Res Inc, Cambridge, MA 02139 USA.
[Maira, S. Michel] Novartis Inst Biomed Res Inc, CH-4002 Basel, Switzerland.
[Thomas, George; Kozma, Sara C.] Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol, Barcelona 08908, Spain.
RP Kozma, SC (reprint author), Univ Cincinnati, Dept Canc & Cell Biol, Cincinnati, OH 45215 USA.
EM sara.kozma@uc.edu
RI Thomas, George/K-9235-2014; Park, Jongsun/E-7465-2010;
OI Thomas, George/0000-0003-3518-8149; Park, Jongsun/0000-0002-4690-1854;
Carnevalli, Larissa/0000-0001-7432-0195; Andersen , Jesper
B/0000-0003-1760-5244
FU National Cancer Institute [U01CA120475, U01CA120475-S1, U01CA141464];
Department of Defense [W81XWH-10-0325]; Novartis; [U54 RR-25216]
FX Supported by National Cancer Institute grants U01CA120475 and
U01CA120475-S1 to S.C.K. and U01CA141464 to G.T. B.J.A. is funded by
W81XWH-10-0325 (Department of Defense) and U54 RR-25216.; S.M.M. and
L.M. are Novartis employees. P.S.M. has served on an advisory board for
Celgene, and G.T. has received consultancy fees from Novartis. All other
authors declare that they have no competing interests.
NR 57
TC 22
Z9 22
U1 2
U2 6
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JUN 20
PY 2012
VL 4
IS 139
AR 139ra84
DI 10.1126/scitranslmed.3003923
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 963NZ
UT WOS:000305629600006
PM 22539746
ER
PT J
AU O'Grady, NP
Murray, PR
Ames, N
AF O'Grady, Naomi P.
Murray, Patrick R.
Ames, Nancy
TI Preventing Ventilator-Associated Pneumonia Does the Evidence Support the
Practice?
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID INTENSIVE-CARE-UNIT; BACTERIAL-COLONIZATION; ENDOTRACHEAL-TUBE;
SELECTIVE DECONTAMINATION; MECHANICAL VENTILATION; SUBGLOTTIC
SECRETIONS; CONTINUOUS ASPIRATION; NOSOCOMIAL PNEUMONIA;
RANDOMIZED-TRIAL; DIGESTIVE-TRACT
AB Ventilator-associated pneumonia (VAP) is among the most common infections in patients requiring endotracheal tubes with mechanical ventilation. Ventilator-associated pneumonia is associated with increased hospital costs, a greater number of days in the intensive care unit, longer duration of mechanical ventilation, and higher mortality. Despite widely accepted recommendations for interventions designed to reduce rates of VAP, few studies have assessed the ability of these interventions to improve patient outcomes. As the understanding of VAP advances and new technologies to reduce VAP become available, studies should directly assess patient outcomes before the health care community implements specific prevention approaches in clinical practice. JAMA. 2012; 307(23):2534-2539 www.jama.com
C1 [O'Grady, Naomi P.] NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Murray, Patrick R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Ames, Nancy] NIH, Dept Nursing & Patient Care Serv, Ctr Clin, Bethesda, MD 20892 USA.
RP O'Grady, NP (reprint author), NIH, Crit Care Med Dept, Ctr Clin, Bldg 10 Room 2C142,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA.
EM nogrady@mail.cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 53
TC 26
Z9 33
U1 1
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 20
PY 2012
VL 307
IS 23
BP 2534
EP 2539
DI 10.1001/jama.2012.6445
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 960MB
UT WOS:000305391400030
PM 22797453
ER
PT J
AU Memoli, MJ
Bristol, T
Proudfoot, KE
Davis, AS
Dunham, EJ
Taubenberger, JK
AF Memoli, Matthew J.
Bristol, Tyler
Proudfoot, Kathleen E.
Davis, A. Sally
Dunham, Eleca J.
Taubenberger, Jeffery K.
TI In vivo evaluation of pathogenicity and transmissibility of influenza
A(H1N1)pdm09 hemagglutinin receptor binding domain 222 intrahost
variants isolated from a single immunocompromised patient
SO VIROLOGY
LA English
DT Article
DE Influenza A; A(H1N1)pdm09; Pathogenesis; D222G; Hemagglutinin;
Immunocompromised; Pandemic; Ferrets
ID H1N1 VIRUS-INFECTION; SUBSTITUTION; VIRULENCE; D222G
AB The influenza A(H1N1)pdm09 virus has circulated worldwide and continued to cause complicated infections and deaths. Reports have identified an increased prevalence of the hemagglutinin receptor binding domain D222G mutation in viruses isolated from individuals who have suffered such severe infections, but this association is still unclear. Virus isolated from a nasopharyngeal wash of a severely ill immunocompromised patient at the time of diagnosis contained the D222, but isolates collected later in his course from a bronchoalveolar lavage contained primarily the G222 mutation and was mixed with a minor population of D222. These clinical isolates were compared to a G222 plaque purified virus in the ferret model. The G222 predominant clinical isolate was the most pathogenic in ferrets and developed the most diversity at the 222 amino acid position during infection, suggesting that increased diversity and not a specific polymorphism at HA 222 may be important in predicting pathogenic potential. Published by Elsevier Inc.
C1 [Memoli, Matthew J.; Bristol, Tyler; Proudfoot, Kathleen E.; Davis, A. Sally; Dunham, Eleca J.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Memoli, MJ (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, MSC 3203,33 North Dr, Bethesda, MD 20892 USA.
EM memolim@niaid.nih.gov
OI Davis, Anne/0000-0001-5711-3936
FU NIH; NIAID
FX This work was supported by the Intramural funds of the NIH and the
NIAID. We thank the Comparative Medicine Branch (NIAID, NIH) for
assistance with animal studies. We also thank the Histopathology
Laboratory at the College of Veterinary Medicine, North Carolina State
University for assistance with the immunohistochemical analysis.
NR 32
TC 10
Z9 10
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 0042-6822
J9 VIROLOGY
JI Virology
PD JUN 20
PY 2012
VL 428
IS 1
BP 21
EP 29
DI 10.1016/j.virol.2012.02.018
PG 9
WC Virology
SC Virology
GA 950IA
UT WOS:000304641600003
PM 22575875
ER
PT J
AU Pilz, IH
Di Pasquale, G
Rzadzinska, A
Leppla, SH
Chiorini, JA
AF Pilz, Ingo H.
Di Pasquale, Giovanni
Rzadzinska, Agnieszka
Leppla, Stephen H.
Chiorini, John A.
TI Mutation in the platelet-derived growth factor receptor alpha inhibits
adeno-associated virus type 5 transduction
SO VIROLOGY
LA English
DT Article
DE Forward genetics; AAV5; Furin; Toxin; CHO cells; Anthrax
ID ZAIRE-EBOLAVIRUS; TYROSINE KINASE; CELLS; PROTEIN; FURIN; PDGFR; AAV5;
GLYCOSYLATION; SPECIFICITY; EPITHELIA
AB Due to its non-pathogenic lifecycle, little is known about the cellular determinants of infection by adeno-associated virus (AAV). To identify these critical cellular factors, we took advantage of the gene transfer abilities of AAV in combination with a forward genetic selection to identify proteins critical for transduction by this virus. AAV serotype 5 (AAV5) vectors encoding the furin gene were used to transduce furin-deficient cells followed by selection with furin-dependent toxins. A population of cells specifically resistant to AAV5 transduction was identified and sequence analysis suggested all had a single amino acid mutation in the leader sequence of the platelet-derived growth factor receptor alpha (PDGFR alpha) gene. Characterization of this mutation suggested it inhibited PDGFR alpha trafficking resulting in limited expression on the plasma membrane. Mutagenesis and transfection experiments confirmed the effect of this mutation on PDGFR alpha trafficking, and the AAV5 resistant phenotype could be rescued by transfection with wild type PDGFR alpha. Published by Elsevier Inc.
C1 [Pilz, Ingo H.; Di Pasquale, Giovanni; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Rzadzinska, Agnieszka] Addenbrookes Hosp, Cambridge, England.
[Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
RP Chiorini, JA (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, 16,Bldg 10,Rm 1N113,10 Ctr Dr,17 MSC1190, Bethesda, MD 20892 USA.
EM ingo.hinrich.pilz@uniklinik-freiburg.de; gdipasqu@nidcr.nih.gov;
agnieszka.rzadzinska@addenbrookes.nhs.uk; sleppla@nih.gov;
jchiorini@dir.nidcr.nih.gov
FU National Institute of Health, National Institute of Dental and
Craniofacial Research; Molecular Physiology and Therapeutics Branch,
National Institute of Dental and Craniofacial Research; National
Institute of Allergy and Infectious Diseases
FX This work was supported by a National Institute of Health, National
Institute of Dental and Craniofacial Research intramural research grant
to JAC, by funds of the Molecular Physiology and Therapeutics Branch,
National Institute of Dental and Craniofacial Research, and by the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases.
NR 26
TC 8
Z9 8
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD JUN 20
PY 2012
VL 428
IS 1
BP 58
EP 63
DI 10.1016/j.virol.2012.03.004
PG 6
WC Virology
SC Virology
GA 950IA
UT WOS:000304641600007
PM 22520943
ER
PT J
AU Bailey-Wilson, JE
Childs, EJ
Cropp, CD
Schaid, DJ
Xu, JF
Camp, NJ
Cannon-Albright, LA
Farnham, JM
George, A
Powell, I
Carpten, JD
Giles, GG
Hopper, JL
Severi, G
English, DR
Foulkes, WD
Maehle, L
Moller, P
Eeles, R
Easton, D
Guy, M
Edwards, S
Badzioch, MD
Whittemore, AS
Oakley-Girvan, I
Hsieh, CL
Dimitrov, L
Stanford, JL
Karyadi, DM
Deutsch, K
McIntosh, L
Ostrander, EA
Wiley, KE
Isaacs, SD
Walsh, PC
Thibodeau, SN
McDonnell, SK
Hebbring, S
Lange, EM
Cooney, KA
Tammela, TLJ
Schleutker, J
Maier, C
Bochum, S
Hoegel, J
Gronberg, H
Wiklund, F
Emanuelsson, M
Cancel-Tassin, G
Valeri, A
Cussenot, O
Isaacs, WB
AF Bailey-Wilson, Joan E.
Childs, Erica J.
Cropp, Cheryl D.
Schaid, Daniel J.
Xu, Jianfeng
Camp, Nicola J.
Cannon-Albright, Lisa A.
Farnham, James M.
George, Asha
Powell, Isaac
Carpten, John D.
Giles, Graham G.
Hopper, John L.
Severi, Gianluca
English, Dallas R.
Foulkes, William D.
Maehle, Lovise
Moller, Pal
Eeles, Rosalind
Easton, Douglas
Guy, Michelle
Edwards, Steve
Badzioch, Michael D.
Whittemore, Alice S.
Oakley-Girvan, Ingrid
Hsieh, Chih-Lin
Dimitrov, Latchezar
Stanford, Janet L.
Karyadi, Danielle M.
Deutsch, Kerry
McIntosh, Laura
Ostrander, Elaine A.
Wiley, Kathleen E.
Isaacs, Sarah D.
Walsh, Patrick C.
Thibodeau, Stephen N.
McDonnell, Shannon K.
Hebbring, Scott
Lange, Ethan M.
Cooney, Kathleen A.
Tammela, Teuvo L. J.
Schleutker, Johanna
Maier, Christiane
Bochum, Sylvia
Hoegel, Josef
Gronberg, Henrik
Wiklund, Fredrik
Emanuelsson, Monica
Cancel-Tassin, Geraldine
Valeri, Antoine
Cussenot, Olivier
Isaacs, William B.
CA Int Consortium Prostate Canc Genet
TI Analysis of Xq27-28 linkage in the international consortium for prostate
cancer genetics (ICPCG) families
SO BMC MEDICAL GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCUS HPCX; RIBONUCLEASE-L GENE;
AGGRESSIVENESS LOCUS; ALLELIC IMBALANCE; CHROMOSOME; RISK; SCAN;
CONFIRMATION; VARIANTS
AB Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive.
Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed.
Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded.
Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.
C1 [Bailey-Wilson, Joan E.; Childs, Erica J.; Cropp, Cheryl D.; George, Asha] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA.
[Childs, Erica J.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Schaid, Daniel J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Xu, Jianfeng; Dimitrov, Latchezar] Wake Forest Univ, Bowman Gray Sch Med, Data Coordinating Ctr ICPCG, Winston Salem, NC 27157 USA.
[Xu, Jianfeng; Dimitrov, Latchezar] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC 27157 USA.
[Camp, Nicola J.; Cannon-Albright, Lisa A.; Farnham, James M.] Univ Utah, Sch Med, ICPCG Grp, Salt Lake City, UT USA.
[Camp, Nicola J.; Cannon-Albright, Lisa A.; Farnham, James M.] Univ Utah, Sch Med, Div Genet Epidemiol, Salt Lake City, UT USA.
[Cannon-Albright, Lisa A.] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA.
[Bailey-Wilson, Joan E.; George, Asha; Powell, Isaac; Carpten, John D.] African Amer Hereditary Prostate Canc ICPCG Grp, Phoenix, AZ USA.
[George, Asha] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Powell, Isaac] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Carpten, John D.] Translat Genom Res Inst, Genet Basis Human Dis Res Div, Phoenix, AZ USA.
[Giles, Graham G.; Hopper, John L.; Severi, Gianluca; English, Dallas R.; Foulkes, William D.; Maehle, Lovise; Moller, Pal; Eeles, Rosalind; Easton, Douglas; Guy, Michelle; Edwards, Steve; Badzioch, Michael D.] ACTANE Consortium, Melbourne, Vic, Australia.
[Giles, Graham G.; Severi, Gianluca; English, Dallas R.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham G.; Hopper, John L.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Sch Populat Hlth, Melbourne, Vic, Australia.
[Foulkes, William D.] McGill Univ, Program Canc Genet, Montreal, PQ, Canada.
[Maehle, Lovise; Moller, Pal] Norwegian Radium Hosp, Oslo Univ Hosp, Dept Med Genet, Oslo, Norway.
[Eeles, Rosalind; Guy, Michelle; Edwards, Steve] Inst Canc Res, Surrey, England.
[Eeles, Rosalind; Guy, Michelle; Edwards, Steve] Royal Marsden NHS Fdn Trust, Surrey, England.
[Easton, Douglas] Canc Res UK Genet Epidemiol Unit, Cambridge, England.
[Badzioch, Michael D.] Univ Washington, Med Ctr, Div Med Genet, Seattle, WA 98195 USA.
[Whittemore, Alice S.; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin] BC CA HI ICPCG Grp, Stanford, CA USA.
[Whittemore, Alice S.; Oakley-Girvan, Ingrid] Stanford Sch Med, Dept Hlth Res & Policy, Stanford, CA USA.
[Whittemore, Alice S.; Oakley-Girvan, Ingrid] Stanford Sch Med, Stanford Canc Inst, Stanford, CA USA.
[Hsieh, Chih-Lin] Univ So Calif, Dept Urol, Los Angeles, CA USA.
[Hsieh, Chih-Lin] Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA USA.
[Stanford, Janet L.; Karyadi, Danielle M.; Deutsch, Kerry; McIntosh, Laura; Ostrander, Elaine A.] FHCRC ICPCG Grp, Seattle, WA USA.
[Stanford, Janet L.; McIntosh, Laura] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Karyadi, Danielle M.; Ostrander, Elaine A.] NHGRI, Canc Gene Branch, NIH, Bethesda, MD 20892 USA.
[Deutsch, Kerry] Inst Syst Biol, Seattle, WA USA.
[Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.] Johns Hopkins Univ, ICPCG Grp, Baltimore, MD USA.
[Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA.
[Thibodeau, Stephen N.; McDonnell, Shannon K.; Hebbring, Scott] Mayo Clin, Rochester, MN USA.
[Lange, Ethan M.] Univ Michigan, ICPCG Grp, Ann Arbor, MI 48109 USA.
[Lange, Ethan M.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Cooney, Kathleen A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Bailey-Wilson, Joan E.; Tammela, Teuvo L. J.; Schleutker, Johanna] Univ Tampere, ICPCG Grp, FIN-33101 Tampere, Finland.
[Tammela, Teuvo L. J.; Schleutker, Johanna] Univ Tampere, Inst Biomed Technol, FIN-33101 Tampere, Finland.
[Tammela, Teuvo L. J.; Schleutker, Johanna] Tampere Univ Hosp, Ctr Lab Med, Tampere, Finland.
[Tammela, Teuvo L. J.; Schleutker, Johanna] Tampere Univ Hosp, Dept Urol, Tampere, Finland.
[Maier, Christiane; Bochum, Sylvia; Hoegel, Josef] Univ Ulm, ICPCG Grp, Ulm, Germany.
[Maier, Christiane] Univ Ulm, Dept Urol, Ulm, Germany.
[Maier, Christiane; Bochum, Sylvia; Hoegel, Josef] Univ Ulm, Inst Human Genet, Ulm, Germany.
[Gronberg, Henrik; Wiklund, Fredrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Emanuelsson, Monica] Umea Univ, Ctr Oncol, Umea, Sweden.
[Cancel-Tassin, Geraldine; Valeri, Antoine; Cussenot, Olivier] CeRePP ICPCG Grp, F-75020 Paris, France.
[Cussenot, Olivier] Hop Tenon, AP HP, F-75020 Paris, France.
RP Bailey-Wilson, JE (reprint author), NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA.
EM jebw@mail.nih.gov
RI Whittemore, Alice/F-9925-2014;
OI Bailey-Wilson, Joan/0000-0002-9153-2920; Eeles,
Rosalind/0000-0002-3698-6241; Farnham, James/0000-0002-8213-949X;
albright, lisa/0000-0003-2602-3668; foulkes,
william/0000-0001-7427-4651; Heimdal, Ketil/0000-0002-8911-3508; Giles,
Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188;
Ostrander, Elaine/0000-0001-6075-9738; Cancel-Tassin,
Geraldine/0000-0002-9583-6382
FU National Institutes of Health [U01 CA89600]; Intramural Research
Programs of the National Human Genome Research Institute; National
Cancer Institute, National Institutes of Health; ACTANE Group; Cancer
Research U.K (CR-UK); Prostate Cancer Research Foundation; Times
Christmas Appeal; Institute of Cancer Research; BREAKTHROUGH Breast
Cancer [328323]; The Cancer Council Victoria; National Health and
Medical Research Council [940934, 251533, 209057, 126402, 396407];
Tattersall's; Whitten Foundation; NCI Post-doctoral Fellowship in Cancer
Prevention [R25]; Department of Defense; Fred Hutchingson Cancer
Research Center; USPHS [CA80122, CA78836, CA106523, CA95052]; Fred
Hutchinson Cancer Research Center; Pirkanmaa Hospital District; Reino
Lahtikari Foundation; Finnish Cancer Organisations; Sigrid Juselius
Foundation; Academy of Finland [118413]; University of Ulm Group:
Deutsche Krebshilfe [70-3111-V03]; Swedish Cancer Society; Umea
University Hospital, Umea, Sweden; National Cancer Institute's
Surveillance, Epidemiology, [HHSN261201000026C]; Utah State Department
of Health; University of Utah; University of Utah Huntsman Cancer
Institute; National Center for Research Resources [USPHS M01-RR00064];
Association pour la Recherche sur le Cancer [5441]; [USPHS CA90752]
FX We would like to express our gratitude to the many families who
participated in the many studies involved in the International
Consortium for Prostate Cancer Genetics (ICPCG). The ICPCG, including
the consortium's Data Coordinating Center (DCC), is made possible by a
grant from the National Institutes of Health U01 CA89600 (to W.B.I.).
This project was supported in part by the Intramural Research Programs
of the National Human Genome Research Institute and the National Cancer
Institute, National Institutes of Health (J.E. B-W, E.L.C., C.D.C.,
E.A.O., D.M.K.). Additional support to participating groups, or members
within groups, is as follows: ACTANE Group: Genotyping and statistical
analysis for this study, and recruitment of U.K. families, was supported
by Cancer Research U.K (CR-UK). Additional support was provided by The
Prostate Cancer Research Foundation, The Times Christmas Appeal and the
Institute of Cancer Research. Genotyping was conducted in the 'Jean Rook
Gene Cloning Laboratory' which is supported by BREAKTHROUGH Breast
Cancer - Charity No. 328323. The funds for the ABI 377 used in this
study were generously provided by the legacy of the late Marion Silcock.
We thank S. Seal and A. Hall for kindly storing and logging the samples
that were provided. D.F.E is a Principal Research Fellow of CR-UK.
Funding in Australia was obtained from The Cancer Council Victoria, The
National Health and Medical Research Council (grants 940934, 251533,
209057, 126402, 396407), Tattersall's and The Whitten Foundation. We
would like to acknowledge the work of the study coordinator M. Staples
and the Research Team B. McCudden, J. Connal, R. Thorowgood, C. Costa,
M. Kevan, and S. Palmer, and to J. Karpowicz for DNA extractions. The
Texas study of familial prostate cancer was initiated by the Department
of Epidemiology, M. D. Anderson Cancer Center. M. B. was supported by an
NCI Post-doctoral Fellowship in Cancer Prevention (R25). BC/CA/HI Group:
USPHS CA67044. Research carried out by WDF was supported by the
Department of Defense. Fred Hutchingson Cancer Research Center Group:
USPHS CA80122 (to J.L.S.) which supports the family collection; USPHS
CA78836 (to E.A.O), with additional support from the Fred Hutchinson
Cancer Research Center. JHU Group: Genotyping for the JHU, University of
Michigan, University of Tampere, and University of Umea groups'
pedigrees was provided by NHGRI genotyping staff including E.
Gillanders, MP Jones, D. Gildea, D. Freas-Lutz, C. Markey, J. Carpten
and J. Trent. Mayo Clinic Group: USPHS CA72818. Michigan Group: USPHS
CA079596. University of Tampere Group: The Competitive Research Funding
of the Pirkanmaa Hospital District, Reino Lahtikari Foundation, Finnish
Cancer Organisations, Sigrid Juselius Foundation, and Academy of Finland
grant 118413. University of Ulm Group: Deutsche Krebshilfe, grant number
70-3111-V03. University of Umea Group: Work was supported by the Swedish
Cancer Society and a Spear grant from the Umea University Hospital,
Umea, Sweden. University of Utah Group: Data collection was supported by
USPHS CA90752 (to L.A.C.-A.) and by the Utah Cancer Registry, which is
funded by Contract HHSN261201000026C from the National Cancer
Institute's Surveillance, Epidemiology, and End-Results Program with
additional support from the Utah State Department of Health and the
University of Utah. Partial support for all datasets within the Utah
Population Database was provided by the University of Utah Huntsman
Cancer Institute and also by the USPHS M01-RR00064 from the National
Center for Research Resources.; Genotyping services were provided by the
Center for Inherited Disease Research (N01-HG-65403). CeRePP Group: work
was supported by the Association pour la Recherche sur le Cancer, grant
number 5441. DCC: The study is partially supported by USPHS CA106523 (to
J.X.), USPHS CA95052 (to J.X.), and Department of Defense grant PC051264
(to J.X.). The funding bodies did not play a role in study design, in
the collection, analysis, and interpretation of data, in the writing of
the manuscript or in the decision to submit the manuscript for
publication.
NR 64
TC 4
Z9 4
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD JUN 19
PY 2012
VL 13
AR 46
DI 10.1186/1471-2350-13-46
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 037YT
UT WOS:000311143100001
PM 22712434
ER
PT J
AU Tarca, AL
Draghici, S
Bhatti, G
Romero, R
AF Tarca, Adi Laurentiu
Draghici, Sorin
Bhatti, Gaurav
Romero, Roberto
TI Down-weighting overlapping genes improves gene set analysis
SO BMC BIOINFORMATICS
LA English
DT Article
DE Gene expression; Gene set analysis; Pathway analysis; Overlapping gene
sets
ID MICROARRAY DATA; EXPRESSION PROFILES; ENRICHMENT ANALYSIS; SIGNALING
PATHWAYS; PROBE LEVEL; DISEASE; CANCER; IDENTIFICATION; NORMALIZATION;
CARCINOMA
AB Background: The identification of gene sets that are significantly impacted in a given condition based on microarray data is a crucial step in current life science research. Most gene set analysis methods treat genes equally, regardless how specific they are to a given gene set.
Results: In this work we propose a new gene set analysis method that computes a gene set score as the mean of absolute values of weighted moderated gene t-scores. The gene weights are designed to emphasize the genes appearing in few gene sets, versus genes that appear in many gene sets. We demonstrate the usefulness of the method when analyzing gene sets that correspond to the KEGG pathways, and hence we called our method Pathway Analysis with Down-weighting of Overlapping Genes (PADOG). Unlike most gene set analysis methods which are validated through the analysis of 2-3 data sets followed by a human interpretation of the results, the validation employed here uses 24 different data sets and a completely objective assessment scheme that makes minimal assumptions and eliminates the need for possibly biased human assessments of the analysis results.
Conclusions: PADOG significantly improves gene set ranking and boosts sensitivity of analysis using information already available in the gene expression profiles and the collection of gene sets to be analyzed. The advantages of PADOG over other existing approaches are shown to be stable to changes in the database of gene sets to be analyzed. PADOG was implemented as an R package available at: http://bioinformaticsprb.med.wayne.edu/PADOG/ or www.bioconductor.org.
C1 [Tarca, Adi Laurentiu; Bhatti, Gaurav; Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Bethesda, MD USA.
[Tarca, Adi Laurentiu; Bhatti, Gaurav; Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA.
[Tarca, Adi Laurentiu; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA.
[Tarca, Adi Laurentiu] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48202 USA.
[Draghici, Sorin] Wayne State Univ, Dept Clin & Translat Sci, Detroit, MI USA.
RP Tarca, AL (reprint author), NICHD, NIH, DHHS, Perinatol Res Branch, Bethesda, MD USA.
EM atarca@med.wayne.edu
RI Draghici, Sorin/B-3074-2013
OI Draghici, Sorin/0000-0002-0786-8377
FU Intramural Research Program of the National Institute of Child Health
and Human Development, NIH/DHHS; NIH [RO1 RDK089167-01]; NSF
[DBI-0965741]; Robert J. Sokol Endowment in Systems Biology
FX This research was supported, in part, by the Intramural Research Program
of the National Institute of Child Health and Human Development,
NIH/DHHS. SD was also supported by the following grants: NIH RO1
RDK089167-01 and NSF DBI-0965741 (to S.D.), and by the Robert J. Sokol
Endowment in Systems Biology. Any opinions, findings, and conclusions or
recommendations expressed in this material are those of the authors and
do not necessarily reflect the views of any of the funding agencies.
NR 47
TC 23
Z9 24
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JUN 19
PY 2012
VL 13
AR 136
DI 10.1186/1471-2105-13-136
PG 14
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 006DV
UT WOS:000308800600001
PM 22713124
ER
EF