FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Rappaport, SM
Kim, S
Lan, Q
Li, GL
Vermeulen, R
Waidyanatha, S
Zhang, LP
Yin, SN
Smith, MT
Rothman, N
AF Rappaport, Stephen M.
Kim, Sungkyoon
Lan, Qing
Li, Guilan
Vermeulen, Roel
Waidyanatha, Suramya
Zhang, Luoping
Yin, Songnian
Smith, Martyn T.
Rothman, Nathaniel
TI Human benzene metabolism following occupational and environmental
exposures
SO CHEMICO-BIOLOGICAL INTERACTIONS
LA English
DT Article
DE Benzene; Metabolism; Toxicokinetics; Biomonitoring
ID GENETIC POLYMORPHISMS; URINARY BIOMARKERS; UNEXPOSED SUBJECTS; LEUKEMIA;
WORKERS; HYDROQUINONE; HYPOTHESIS; EXCRETION; ADDUCTS; PHENOL
AB We previously reported evidence that humans metabolize benzene via two enzymes, including a hitherto unrecognized high-affinity enzyme that was responsible for an estimated 73% of total urinary metabolites [sum of phenol (PH), hydroquinone (HQ), catechol (CA), E,E-muconic acid (MA), and S-phenylmercapturic acid (SPMA)] in nonsmoking females exposed to benzene at sub-saturating (ppb) air concentrations. Here, we used the same Michaelis-Menten-like kinetic models to individually analyze urinary levels of PH, HQ CA and MA from 263 nonsmoking Chinese women (179 benzene-exposed workers and 84 control workers) with estimated benzene air concentrations ranging from less than 0.001-299 ppm. One model depicted benzene metabolism as a single enzymatic process (1-enzyme model) and the other as two enzymatic processes which competed for access to benzene (2-enzyme model). We evaluated model fits based upon the difference in values of Akaike's Information Criterion (Delta AIC), and we gauged the weights of evidence favoring the two models based upon the associated Akaike weights and Evidence Ratios. For each metabolite, the 2-enzyme model provided a better fit than the 1-enzyme model with Delta AIC values decreasing in the order 9.511 for MA, 7.379 for PH, 1.417 for CA, and 0.193 for HQ. The corresponding weights of evidence favoring the 2-enzyme model (Evidence Ratios) were: 116.2:1 for MA, 40.0:1 for PH, 2.0:1 for CA and 1.1:1 for HQ. These results indicate that our earlier findings from models of total metabolites were driven largely by MA, representing the ring-opening pathway, and by PH, representing the ring-hydroxylation pathway. The predicted percentage of benzene metabolized by the putative high-affinity enzyme at an air concentration of 0.001 ppm was 88% based upon urinary MA and was 80% based upon urinary PH. As benzene concentrations increased, the respective percentages of benzene metabolized to MA and PH by the high-affinity enzyme decreased successively to 66 and 77% at 0.1 ppm, 20 and 58% at 1 ppm, and 2.7 and 17% at 10 ppm. This indicates that the putative high-affinity enzyme was active primarily below 1 ppm and favored the ring-opening pathway. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Rappaport, Stephen M.; Zhang, Luoping; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Kim, Sungkyoon] Seoul Natl Univ, Sch Publ Hlth, Seoul, South Korea.
[Lan, Qing] NCI, NIH, DHHS, Bethesda, MD 20892 USA.
[Li, Guilan; Yin, Songnian] Chinese Ctr Dis Control & Prevent, Inst Occupat Hlth & Poison Control, Beijing, Peoples R China.
[Vermeulen, Roel; Rothman, Nathaniel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Waidyanatha, Suramya] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
RP Rappaport, SM (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
EM srappaport@berkeley.edu
RI Vermeulen, Roel/F-8037-2011
OI Vermeulen, Roel/0000-0003-4082-8163
FU American Petroleum Institute; American Chemistry Council; National
Institute for Environmental Health Sciences [P42ES05948, P30ES10126,
R01ES06721, P42ES04705]; NIH, National Cancer Institute
FX S.M.R. has received consulting and expert testimony fees from law firms
representing plaintiffs' cases involving exposure to benzene and has
received research support from the American Petroleum Institute and the
American Chemistry Council. G.L. has received funds from the American
Petroleum Institute for consulting on benzene-related health research.
M.T.S. has received consulting and expert testimony fees from law firms
representing both plaintiffs and defendants in cases involving exposure
to benzene.; Funding sources: This research was supported by the
National Institute for Environmental Health Sciences through grants
P42ES05948 and P30ES10126 (S.M.R.) and R01ES06721 and P42ES04705
(M.T.S.) and by funds from the intramural research program of the NIH,
National Cancer Institute.
NR 30
TC 19
Z9 21
U1 4
U2 15
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0009-2797
J9 CHEM-BIOL INTERACT
JI Chem.-Biol. Interact.
PD MAR 19
PY 2010
VL 184
IS 1-2
SI SI
BP 189
EP 195
DI 10.1016/j.cbi.2009.12.017
PG 7
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA 586CD
UT WOS:000276877800024
PM 20026321
ER
PT J
AU Zarbl, H
Gallo, MA
Glick, J
Yeung, KY
Vouros, P
AF Zarbl, Helmut
Gallo, Michael A.
Glick, James
Yeung, Ka Yee
Vouros, Paul
TI The vanishing zero revisited: Thresholds in the age of genomics
SO CHEMICO-BIOLOGICAL INTERACTIONS
LA English
DT Article
DE No observable transcriptional effect level; Low dose-response; Risk
assessment; Toxicogenomics
ID TRANSCRIPTIONAL-EFFECT-LEVEL; DOSE-RESPONSE RELATIONSHIPS;
GENE-EXPRESSION; RISK-ASSESSMENT; BONE-MARROW; CHRONIC EXPOSURE; INHALED
BENZENE; ETHYLENE-OXIDE; DNA-ADDUCTS; TOXICITY
AB The concept of the vanishing zero, which was first discussed 50 years ago in relation to pesticide residues in foods and food crops, focused on the unintended regulatory consequences created by ever-increasing sensitivity and selectivity of analytical methods, in conjunction with the ambiguous wording of legislation meant to protect public health. In the interim, the ability to detect xenobiotics in most substrates has increased from tens of parts per million to parts per trillion or less, challenging our ability to interpret the biological significance of exposures at the lowest detectable levels. As a result the focus of risk assessment, especially for potential carcinogens, has shifted from defining an acceptable level, to extrapolating from the best available analytical results. Analysis of gene expression profiles in exposed target cells using genomic technologies can identify biological pathways induced or repressed by the exposure as a function of dose and time. This treatise explores how toxicogenomic responses at low doses may inform risk assessment and risk management by defining thresholds for cellular responses linked to modes or mechanisms of toxicity at the molecular level. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Zarbl, Helmut] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Environm & Occupat Hlth Sci Inst, NIEHS Ctr Environm Exposures & Dis, Piscataway, NJ 08854 USA.
[Glick, James; Vouros, Paul] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA.
[Glick, James; Vouros, Paul] Northeastern Univ, Barnett Inst, Boston, MA 02115 USA.
[Yeung, Ka Yee] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
RP Zarbl, H (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Environm & Occupat Hlth Sci Inst, NIEHS Ctr Environm Exposures & Dis, 170 Frelinghuysen Rd,Room 426, Piscataway, NJ 08854 USA.
EM zarbl@eohsi.rutgers.edu
OI Yeung, Ka Yee/0000-0002-1754-7577
FU NIH [RO1CA112231, U19ES011387, P30ES005022, 3R01GM084163, 5K25CA106988]
FX This work was supported by Public Health Services Grants (NIH):
RO1CA112231 (P. Vouros, P.I.), U19ES011387 (H. Zarbl, P.I), P30ES005022
(H. Zarbl, P.I.), 3R01GM084163 (K.A. Yeung, PI) and 5K25CA106988 (K.A.
Yeung, P.I).
NR 50
TC 8
Z9 8
U1 0
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0009-2797
J9 CHEM-BIOL INTERACT
JI Chem.-Biol. Interact.
PD MAR 19
PY 2010
VL 184
IS 1-2
SI SI
BP 273
EP 278
DI 10.1016/j.cbi.2010.01.031
PG 6
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA 586CD
UT WOS:000276877800038
PM 20109442
ER
PT J
AU Patino-Lopez, G
Aravind, L
Dong, XY
Kruhlak, MJ
Ostap, EM
Shaw, S
AF Patino-Lopez, Genaro
Aravind, L.
Dong, Xiaoyun
Kruhlak, Michael J.
Ostap, E. Michael
Shaw, Stephen
TI Myosin 1G Is an Abundant Class I Myosin in Lymphocytes Whose
Localization at the Plasma Membrane Depends on Its Ancient Divergent
Pleckstrin Homology (PH) Domain (Myo1PH)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BRUSH-BORDER; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; TISSUE
DISTRIBUTION; STRUCTURAL BASIS; L-SELECTIN; BINDING; TAIL; PROTEIN;
CELLS; PHOSPHOINOSITIDES
AB Class I myosins, which link F-actin to membrane, are largely undefined in lymphocytes. Mass spectrometric analysis of lymphocytes identified two short tail forms: (Myo1G and Myo1C) and one long tail (Myo1F). We investigated Myo1G, the most abundant in T-lymphocytes, and compared key findings with Myo1C and Myo1F. Myo1G localizes to the plasma membrane and associates in an ATP-releasable manner to the actin-containing insoluble pellet. The IQ + tail region of Myo1G (Myo1C and Myo1F) is sufficient for membrane localization, but membrane localization is augmented by the motor domain. The minimal region lacks IQ motifs but includes: 1) a PH-like domain; 2) a "Pre-PH" region; and 3) a "Post-PH" region. The Pre-PH predicted alpha helices may contribute electrostatically, because two conserved basic residues on one face are required for optimal membrane localization. Our sequence analysis characterizes the divergent PH domain family, Myo1PH, present also in long tail myosins, in eukaryotic proteins unrelated to myosins, and in a probable ancestral protein in prokaryotes. The Myo1GMyo1PH domain utilizes the classic lipid binding site for membrane association, because mutating either of two basic residues in the "signature motif" destroys membrane localization. Mutation of each basic residue of the Myo1G Myo1PH domain reveals another critical basic residue in the beta 3 strand, which is shared only by Myo1D. Myo1G differs from Myo1C in its phosphatidylinositol 4,5-bisphosphate dependence for membrane association, because membrane localization of phosphoinositide 5-phosphatase releases Myo1C from the membrane but not Myo1G. Thus Myo1PH domains likely play universal roles in myosin I membrane association, but different isoforms have diverged in their binding specificity.
C1 [Patino-Lopez, Genaro; Dong, Xiaoyun; Kruhlak, Michael J.; Shaw, Stephen] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Ostap, E. Michael] Univ Penn, Sch Med, Penn Muscle Inst, Philadelphia, PA 19104 USA.
[Ostap, E. Michael] Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA.
RP Shaw, S (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B36,10 Ctr Dr,MSC 1360, Bethesda, MD 20892 USA.
EM shaws@mail.nih.gov
OI Patino-Lopez, Genaro/0000-0002-8716-722X
FU National Institutes of Health [GM57247]; NCI; National Library of
Medicine
FX This work was supported, in whole or in part, by National Institutes of
Health Grant GM57247 and the Intramural Research Program of the National
Institutes of Health, NCI. This work was also supported by the National
Library of Medicine.
NR 44
TC 33
Z9 35
U1 1
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 MAR 19
PY 2010
VL 285
IS 12
BP 8675
EP 8686
DI 10.1074/jbc.M109.086959
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 568VZ
UT WOS:000275553700020
PM 20071333
ER
PT J
AU Zhang, M
Wang, MN
Tan, XH
Li, TF
Zhang, YE
Chen, D
AF Zhang, Ming
Wang, Meina
Tan, Xiaohong
Li, Tian-Fang
Zhang, Ying E.
Chen, Di
TI Smad3 Prevents beta-Catenin Degradation and Facilitates beta-Catenin
Nuclear Translocation in Chondrocytes
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GROWTH-FACTOR-BETA; MESENCHYMAL STEM-CELLS; F-BOX PROTEIN; SIGNALING
CROSS-TALK; TGF-BETA; UBIQUITIN LIGASE; CARCINOMA CELLS; WNT PATHWAYS;
DIFFERENTIATION; BONE
AB Our previous study demonstrated that transforming growth factor (TGF)-beta activates beta-catenin signaling through Smad3 interaction with beta-catenin in chondrocytes. In the present studies, we further investigated the detailed molecular mechanism of the cross-talk between TGF-beta/Smad3 and Wnt/beta-catenin signaling pathways. We found that C-terminal Smad3 interacted with both the N-terminal region and the middle region of beta-catenin protein in a TGF-beta-dependent manner. Both Smad3 and Smad4 were required for the interaction with beta-catenin and protected beta-catenin from an ubiquitin-proteasome-dependent degradation. In addition, the formation of the Smad3-Smad4-beta-catenin protein complex also mediated beta-catenin nuclear translocation. This Smad3-mediated regulatory mechanism of beta-catenin protein stability enhanced the activity of beta-catenin to activate downstream target genes during chondrogenesis. Our findings demonstrate a novel mechanism between TGF-beta and Wnt/beta-catenin signaling pathways during chondrocyte development.
C1 [Zhang, Ming; Wang, Meina; Tan, Xiaohong; Li, Tian-Fang; Chen, Di] Univ Rochester, Med Ctr, Ctr Musculoskeletal Res, Dept Orthopaed & Rehabil, Rochester, NY 14642 USA.
[Zhang, Ying E.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Chen, D (reprint author), Univ Rochester, Med Ctr, Ctr Musculoskeletal Res, Dept Orthopaed & Rehabil, Rochester, NY 14642 USA.
EM di_chen@urmc.rochester.edu
RI Zhang, Ming/H-6467-2011; Wang, Meina/K-8915-2012; Zhang,
Ying/G-3657-2015
OI Zhang, Ying/0000-0003-2753-7601
FU National Institutes of Health [R01 AR051189, R01 AR054465, K02 AR052411,
R01 AR055915]; New York State Department of Health [N08G-070]; Empire
State Stem Cell Board
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01 AR051189, R01 AR054465, K02 AR052411, and R01 AR055915
(to D. C.). This work was also supported by Grant N08G-070 (to D. C.)
from the New York State Department of Health and the Empire State Stem
Cell Board.
NR 42
TC 40
Z9 41
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 MAR 19
PY 2010
VL 285
IS 12
BP 8703
EP 8710
DI 10.1074/jbc.M109.093526
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 568VZ
UT WOS:000275553700023
PM 20097766
ER
PT J
AU De Donatis, GM
Singh, SK
Viswanathan, S
Maurizi, MR
AF De Donatis, Gian Marco
Singh, Satyendra K.
Viswanathan, Sarada
Maurizi, Michael R.
TI A Single ClpS Monomer Is Sufficient to Direct the Activity of the ClpA
Hexamer
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID N-END RULE; ADAPTER PROTEIN CLPS; SUBSTRATE-BINDING DOMAIN;
ATP-DEPENDENT PROTEASES; SSRA-TAGGED PROTEINS; ESCHERICHIA-COLI;
CRYSTAL-STRUCTURE; CHAPERONE CLPA; PORE LOOPS; DEGRADATION
AB ClpS is an adaptor protein that interacts with ClpA and promotes degradation of proteins with N-end rule degradation motifs (N-degrons) by ClpAP while blocking degradation of substrates with other motifs. Although monomeric ClpS forms a 1: 1 complex with an isolated N-domain of ClpA, only one molecule of ClpS binds with high affinity to ClpA hexamers (ClpA(6)). One or two additional molecules per hexamer bind with lower affinity. Tightly bound ClpS dissociates slowly from ClpA(6) with a t(1/2) of similar to 3 min at 37 degrees C. Maximum activation of degradation of the N-end rule substrate, LR-GFP(Venus), occurs with a single ClpS bound per ClpA(6); one ClpS is also sufficient to inhibit degradation of proteins without N-degrons. ClpS competitively inhibits degradation of unfolded substrates that interact with ClpA N-domains and is a non-competitive inhibitor with substrates that depend on internal binding sites in ClpA. ClpS inhibition of substrate binding is dependent on the order of addition. When added first, ClpS blocks binding of both high and low affinity substrates; however, when substrates first form committed complexes with ClpA(6), ClpS cannot displace them or block their degradation by ClpP. We propose that the first molecule of ClpS binds to the N-domain and to an additional functional binding site, sterically blocking binding of non-N-end rule substrates as well as additional ClpS molecules to ClpA(6). Limiting ClpS-mediated substrate delivery to one per ClpA(6) avoids congestion at the axial channel and allows facile transfer of proteins to the unfolding and translocation apparatus.
C1 [De Donatis, Gian Marco; Singh, Satyendra K.; Viswanathan, Sarada; Maurizi, Michael R.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Maurizi, MR (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37 Rm 2128,37 Convent Dr MSC4256, Bethesda, MD 20892 USA.
EM mmaurizi@helix.nih.gov
FU National Institutes of Health, NCI, Center for Cancer Research
FX This work was supported, in whole or in part, by the National Institutes
of Health, NCI, Center for Cancer Research, Intramural Research Program.
NR 47
TC 16
Z9 16
U1 0
U2 1
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 MAR 19
PY 2010
VL 285
IS 12
BP 8771
EP 8781
DI 10.1074/jbc.M109.053736
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 568VZ
UT WOS:000275553700029
PM 20068042
ER
PT J
AU Yang, RQ
Zhan, M
Nalabothula, NR
Yang, QY
Indig, FE
Carrier, F
AF Yang, Ruiqing
Zhan, Ming
Nalabothula, Narasimha Rao
Yang, Qingyuan
Indig, Fred E.
Carrier, France
TI Functional Significance for a Heterogenous Ribonucleoprotein A18
Signature RNA Motif in the 3 '-Untranslated Region of Ataxia
Telangiectasia Mutated and Rad3-related (ATR) Transcript
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DAMAGE-INDUCIBLE TRANSCRIPTS; TARGET MESSENGER-RNAS; BINDING PROTEIN;
POSTTRANSCRIPTIONAL REGULATION; GENOME INTEGRITY; KINASE;
IDENTIFICATION; THIOREDOXIN; TRANSLATION; INHIBITION
AB The predominantly nuclear heterogenous ribonucleoprotein A18 (hnRNP A18) translocates to the cytosol in response to cellular stress and increases translation by specifically binding to the 3'-untranslated region (UTR) of several mRNA transcripts and the eukaryotic initiation factor 4G. Here, we identified a 51-nucleotide motif that is present 11.49 times more often in the 3'-UTR of hnRNP A18 mRNA targets than in the UniGene data base. This motif was identified by computational analysis of primary sequences and secondary structures of hnRNP A18 mRNA targets against the unaligned sequences. Band shift analyses indicate that the motif is sufficient to confer binding to hnRNP A18. A search of the entire UniGene data base indicates that the hnRNP A18 motif is also present in the 3'-UTR of the ataxia telangiectasia mutated and Rad3-related (ATR) mRNA. Validation of the predicted hnRNP A18 motif is provided by amplification of endogenous ATR transcript on polysomal fractions immunoprecipitated with hnRNP A18. Moreover, overexpression of hnRNP A18 results in increased ATR protein levels and increased phosphorylation of Chk1, a preferred ATR substrate, in response to UV radiation. In addition, our data indicate that inhibition of casein kinase II or GSK3 beta significantly reduced hnRNP A18 cytosolic translocation in response to UV radiation. To our knowledge, this constitutes the first demonstration of a post-transcriptional regulatory mechanism for ATR activity. hnRNP A18 could thus become a new target to trigger ATR activity as back-up stress response mechanisms to functionally compensate for absent or defective responders.
C1 [Yang, Ruiqing; Nalabothula, Narasimha Rao; Yang, Qingyuan; Carrier, France] Univ Maryland, Dept Radiat Oncol, Marlene & Stewart Greenebaum Canc Ctr, Sch Med, Baltimore, MD 21201 USA.
[Zhan, Ming] NIA, Res Resources Branch, Intramural Res Program, Baltimore, MD 21224 USA.
[Indig, Fred E.] NIA, NIH, Baltimore, MD 21224 USA.
RP Carrier, F (reprint author), 655 W Baltimore St, Baltimore, MD 21201 USA.
EM fcarr001@umaryland.edu
FU National Institutes of Health [RO1 GM57827, RO1 1CA116491-01];
University of Maryland, Baltimore
FX This work was supported in part by National Institutes of Health Grants
RO1 GM57827 and RO1 1CA116491-01 (to F. C.). This work was also
supported by funds from the graduate program in biochemistry of the
University of Maryland, Baltimore (to R. Y.).
NR 33
TC 13
Z9 13
U1 0
U2 0
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 MAR 19
PY 2010
VL 285
IS 12
BP 8887
EP 8893
DI 10.1074/jbc.M109.013128
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 568VZ
UT WOS:000275553700040
PM 20103595
ER
PT J
AU Navath, RS
Wang, B
Kannan, S
Romero, R
Kannan, RM
AF Navath, Raghavendra S.
Wang, Bing
Kannan, Sujatha
Romero, Roberto
Kannan, Rangaramanujam M.
TI Stimuli-responsive star poly(ethylene glycol) drug conjugates for
improved intracellular delivery of the drug in neuroinflammation
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE PEG; Polyethylene glycol-drug conjugates; Intracellular delivery;
N-acetyl cysteine; Neuroinflammation; Microglial cells
ID POLYMERIC ANTICANCER DRUGS; PH-CONTROLLED ACTIVATION; N-ACETYLCYSTEINE;
L-CYSTEINE; IN-VITRO; RELEASE; PRODRUGS; THERAPEUTICS; SYSTEMS; CANCER
AB N-Acetyl cysteine (NAC) is a vital drug currently under clinical trials for the treatment of neuroinflammation in maternal-fetal applications. The free sulfhydryl groups in NAG lead to high plasma protein binding, resulting in low bioavailability. Preparation and activity of conjugates of NAC with thiol terminated multi-arm (6 and 8) poly(ethylene-glycol) (PEG) with disulfide linkages involving sulfhydryls of NAC are reported. Multiple copies (5 and 7) of NAC were conjugated on 6 and 8-arm-PEG respectively. Both the conjugates released 74% of NAG within 2 h by thiol exchange reactions in the redox environment provided by glutathione (GSH) intracellularly (2-10 mM). At physiological extracellular glutathione concentration (2 mu M) both the conjugates were stable and did not release NAC. MTT assay showed comparable cell viability for unmodified PEGs and both the PEG-S-S-NAG conjugates. The conjugates were readily endocytosed by cells, as confirmed by flow cytometry and confocal microscopy. Efficacy of 6 and 8-arm-PEG-S-S-NAC conjugates was evaluated on activated microglial cells (the target cells, ill vivo) by monitoring cytokine release in lipopolysaccharide (LPS) induced inflammatory response in microglial cells using the reactive oxygen species (ROS), free radical nitrile (NO), anti-inflammatory activity and GSH depletion. The conjugates showed significant increase in antioxidant activity (more than a factor of 2) compared to free drug as seen from the inhibition of LPS induced ROS, NO, GSH and tumor necrosis factor-alpha (TNF-alpha) release in microglial cells. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Navath, Raghavendra S.; Kannan, Rangaramanujam M.] Wayne State Univ, Dept Chem Engn & Mat Sci & Biomed Engn, Detroit, MI 48202 USA.
[Navath, Raghavendra S.; Wang, Bing; Kannan, Sujatha; Romero, Roberto; Kannan, Rangaramanujam M.] NICHD, Perinatol Res Branch, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH,DHHS, Bethesda, MD USA.
[Wang, Bing; Kannan, Sujatha] Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Crit Care Med, Detroit, MI 48202 USA.
RP Kannan, RM (reprint author), Wayne State Univ, Dept Chem Engn & Mat Sci & Biomed Engn, Detroit, MI 48202 USA.
EM rkannan@eng.wayne.edu
FU National Institute of Child Health and Human Development, NIH, DHHS
FX This study was supported by the Intramural Research Program of the
National Institute of Child Health and Human Development, NIH, DHHS.
NR 34
TC 33
Z9 38
U1 2
U2 31
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
J9 J CONTROL RELEASE
JI J. Control. Release
PD MAR 19
PY 2010
VL 142
IS 3
BP 447
EP 456
DI 10.1016/j.jconrel.2009.10.035
PG 10
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 582ER
UT WOS:000276579500022
PM 19896998
ER
PT J
AU Xu, YM
Lorieau, J
McDermott, AE
AF Xu, Yimin
Lorieau, Justin
McDermott, Ann E.
TI Triosephosphate Isomerase: N-15 and C-13 Chemical Shift Assignments and
Conformational Change upon Ligand Binding by Magic-Angle Spinning
Solid-State NMR Spectroscopy
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE triosephosphate isomerase; solid-state NMR; sequential assignment;
crystal packing; conformational change
ID TRIOSE PHOSPHATE ISOMERASE; SITE LOOP MOTION; ACTIVE-SITE; CATALYTIC
MECHANISM; PROTON-TRANSFER; MICROCRYSTALLINE UBIQUITIN; RESOLUTION
ENHANCEMENT; COMPUTER-SIMULATION; CRYSTAL-STRUCTURES; SPECTRAL-ANALYSIS
AB Microcrystalline uniformly C-13, N-15-enriched yeast triosephosphate isomerase (TIM) is sequentially assigned by high-resolution solid-state NMR (SSNMR). Assignments are based on intraresidue and interresidue correlations, using dipolar polarization transfer methods, and guided by solution NMR assignments of the same protein. We obtained information on most of the active-site residues involved in chemistry, including sonic that were not reported in a previous solution NMR study, such as the side-chain carbons of His95 Chemical shift differences comparing the microcrystalline environment to the aqueous environment appear to be mainly due to crystal packing interactions. Site-specific perturbations of the enzyme's chemical shifts upon ligand binding are studied by SSNMR for the first time. These changes monitor protemwide conformational adjustment upon ligand binding, including many of the sites probed by solution NMR and X-ray studies Changes in Gln119, Ala163, and Gly210 were observed in our SSNM.R studies, but were not reported in solution NMR studies (chicken or yeast). These studies identify a number of new sites with particularly clear markers for ligand binding, paving the way for future studies of triosephosphate isomerase dynamics and mechanism. (C) 2009 Published by Elsevier Ltd
C1 [Xu, Yimin; McDermott, Ann E.] Columbia Univ, Dept Chem, New York, NY 10027 USA.
[Lorieau, Justin] NIH, Bethesda, MD 20892 USA.
RP McDermott, AE (reprint author), Columbia Univ, Dept Chem, New York, NY 10027 USA.
EM aem5@columbia.edu
FU New York State Office of Science, Technology, and Academic Research;
National Institutes of Health
FX We thank Ivan Sergeyev for his program ACCEPTN M R (http:
//mcdermott.chem/software/) used for crystal contact calculations. We
thank previous and current McDermott group members for technical
assistance. A.E.M. is a member of the New York Structural Biology
Center. The New York Structural Biology Center is a STAR center
supported by the New York State Office of Science, Technology, and
Academic Research. This work was supported by funds from the National
Institutes of Health.
NR 66
TC 11
Z9 11
U1 0
U2 10
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 MAR 19
PY 2010
VL 397
IS 1
BP 233
EP 248
DI 10.1016/j.jmb.2010.10.043
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 571WC
UT WOS:000275785600016
PM 19854202
ER
PT J
AU Zeng, X
Yin, BL
Hu, Z
Liao, CZ
Liu, JL
Li, S
Li, Z
Nicklaus, MC
Zhou, GB
Jiang, S
AF Zeng, Xin
Yin, Biaolin
Hu, Zheng
Liao, Chenzhong
Liu, Jinglei
Li, Shang
Li, Zheng
Nicklaus, Marc C.
Zhou, Guangbiao
Jiang, Sheng
TI Total Synthesis and Biological Evaluation of Largazole and Derivatives
with Promising Selectivity for Cancers Cells
SO ORGANIC LETTERS
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITOR; NATURAL-PRODUCTS; ANALOGS; DRUGS
AB The efficient total synthesis of the natural substance largazole is described. Using this strategy, a small library of largazole analogs was developed. Structure-activity relationship studies suggested that the geometry of the alkene In the side chain is critical. While the largazole's analogues with trans-alkene are potent for the anti proliferative effect, those with cls-alkene are completely inactive. Most importantly, replacement of valine with tyrosine in largazole increased selectivity toward human cancer cells over human normal cells more than 100-fold.
C1 [Zeng, Xin; Hu, Zheng; Liu, Jinglei; Li, Shang; Zhou, Guangbiao; Jiang, Sheng] CAS, Guangzhou Inst Biomed & Hlth, Guangzhou 510663, Guangdong, Peoples R China.
[Hu, Zheng; Liu, Jinglei; Zhou, Guangbiao] CAS, Lab Mol Carcinogenesis & Targeted Therapy Canc, State Key Lab Biomembrane & Membrane Biotechnol, Inst Zool, Beijing 100101, Peoples R China.
[Yin, Biaolin] S China Univ Technol, Guangzhou 510640, Peoples R China.
[Liao, Chenzhong; Nicklaus, Marc C.] NCI, NIH, Frederick, MD 21702 USA.
[Hu, Zheng; Liu, Jinglei; Zhou, Guangbiao] Univ Sci & Technol China, Hefei 230027, Peoples R China.
[Li, Zheng] Methodist Hosp, Res Inst, Houston, TX 77030 USA.
RP Zhou, GB (reprint author), CAS, Guangzhou Inst Biomed & Hlth, Guangzhou 510663, Guangdong, Peoples R China.
EM gbzhou@ioz.ac.cn; jiang_sheng@gibh.ac.cn
RI Nicklaus, Marc/N-4183-2014;
OI Zhou, Guangbiao/0000-0001-6778-7133; Nicklaus, Marc/0000-0002-4775-7030
FU National Natural Science Foundation [20802078, 20972160, 30871110]; 973
Program [2009CB940900, 2010CB529201]
FX This project was supported by the National Natural Science Foundation
(20802078, 20972160, 30871110), and 973 Program (2009CB940900,
2010CB529201). Dr. Nadya I. Tarasova at NO is thanked for correcting the
English.
NR 25
TC 53
Z9 54
U1 1
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1523-7060
J9 ORG LETT
JI Org. Lett.
PD MAR 19
PY 2010
VL 12
IS 6
BP 1368
EP 1371
DI 10.1021/ol100308a
PG 4
WC Chemistry, Organic
SC Chemistry
GA 566NL
UT WOS:000275379100057
PM 20184338
ER
PT J
AU Ruiz, MO
Chaves, LF
Hamer, GL
Sun, T
Brown, WM
Walker, ED
Haramis, L
Goldberg, TL
Kitron, UD
AF Ruiz, Marilyn O.
Chaves, Luis F.
Hamer, Gabriel L.
Sun, Ting
Brown, William M.
Walker, Edward D.
Haramis, Linn
Goldberg, Tony L.
Kitron, Uriel D.
TI Local impact of temperature and precipitation on West Nile virus
infection in Culex species mosquitoes in northeast Illinois, USA
SO PARASITES & VECTORS
LA English
DT Article
ID SPATIAL INTERPOLATION METHODS; DROUGHT-INDUCED AMPLIFICATION; PIPIENS
DIPTERA; UNITED-STATES; TARSALIS DIPTERA; LAND-USE; SEASONAL ABUNDANCE;
BRIDGE VECTOR; CULICIDAE; TRANSMISSION
AB Background: Models of the effects of environmental factors on West Nile virus disease risk have yielded conflicting outcomes. The role of precipitation has been especially difficult to discern from existing studies, due in part to habitat and behavior characteristics of specific vector species and because of differences in the temporal and spatial scales of the published studies. We used spatial and statistical modeling techniques to analyze and forecast fine scale spatial (2000 m grid) and temporal (weekly) patterns of West Nile virus mosquito infection relative to changing weather conditions in the urban landscape of the greater Chicago, Illinois, region for the years from 2004 to 2008.
Results: Increased air temperature was the strongest temporal predictor of increased infection in Culex pipiens and Culex restuans mosquitoes, with cumulative high temperature differences being a key factor distinguishing years with higher mosquito infection and higher human illness rates from those with lower rates. Drier conditions in the spring followed by wetter conditions just prior to an increase in infection were factors in some but not all years. Overall, 80% of the weekly variation in mosquito infection was explained by prior weather conditions. Spatially, lower precipitation was the most important variable predicting stronger mosquito infection; precipitation and temperature alone could explain the pattern of spatial variability better than could other environmental variables (79% explained in the best model). Variables related to impervious surfaces and elevation differences were of modest importance in the spatial model.
Conclusion: Finely grained temporal and spatial patterns of precipitation and air temperature have a consistent and significant impact on the timing and location of increased mosquito infection in the northeastern Illinois study area. The use of local weather data at multiple monitoring locations and the integration of mosquito infection data from numerous sources across several years are important to the strength of the models presented. The other spatial environmental factors that tended to be important, including impervious surfaces and elevation measures, would mediate the effect of rainfall on soils and in urban catch basins. Changes in weather patterns with global climate change make it especially important to improve our ability to predict how inter-related local weather and environmental factors affect vectors and vector-borne disease risk.
Local impact of temperature and precipitation on West Nile virus infection in Culex species mosquitoes in northeast Illinois, USA.
C1 [Ruiz, Marilyn O.; Sun, Ting; Brown, William M.] Univ Illinois, Dept Pathol, Urbana, IL 61801 USA.
[Chaves, Luis F.; Kitron, Uriel D.] Emory Univ, Dept Environm Studies, Atlanta, GA 30322 USA.
[Hamer, Gabriel L.; Goldberg, Tony L.] Univ Wisconsin, Dept Pathol Sci, Madison, WI USA.
[Walker, Edward D.] Michigan State Univ, Dept Microbiol & Mol Genet, Lansing, MI USA.
[Haramis, Linn] Illinois Dept Publ Hlth, Vector Control Program, Springfield, IL 62761 USA.
[Kitron, Uriel D.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Ruiz, MO (reprint author), Univ Illinois, Dept Pathol, Urbana, IL 61801 USA.
EM moruiz@illinois.edu
RI Chaves, Luis Fernando/F-3448-2010
OI Chaves, Luis Fernando/0000-0002-5301-2764
FU NSF [0429124, 0840403]; University of Illinois Adaptive Infrastructure
Information Systems Initiative; Village of Oak Lawn
FX This project was funded through NSF Ecology of Infectious Disease Grants
0429124 (West Nile Virus: Eco-Epidemiology of Disease Emergence in Urban
Areas) and 0840403 (Eco-epidemiology of Disease Emergence in Urban Areas
II) and through funding from the University of Illinois Adaptive
Infrastructure Information Systems Initiative. We thank the Village of
Oak Lawn for ongoing support of this project. Kenneth Kunkel contributed
to early discussions on this topic. Jane Messina, Julie Clennon and
Joanna Ganning helped with geocoding and organization of spatial
mosquito data. LFC and UK also thank the Research and Policy for
Infectious Disease Dynamics (RAPIDD) program of the Science and
Technology Directorate and the Fogarty International Center, National
Institutes of Health program on mosquito borne diseases, for helpful
discussions in the context of this manuscript. We thank Tavis Anderson
and two anonymous reviewers for helpful suggestions for revisions, which
have greatly improved the paper.
NR 73
TC 78
Z9 81
U1 3
U2 45
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-3305
J9 PARASITE VECTOR
JI Parasites Vectors
PD MAR 19
PY 2010
VL 3
AR 19
DI 10.1186/1756-3305-3-19
PG 16
WC Parasitology
SC Parasitology
GA 586DN
UT WOS:000276882100001
PM 20302617
ER
PT J
AU Fauriat, C
Long, EO
Ljunggren, HG
Bryceson, YT
AF Fauriat, Cyril
Long, Eric O.
Ljunggren, Hans-Gustaf
Bryceson, Yenan T.
TI Regulation of human NK-cell cytokine and chemokine production by target
cell recognition
SO BLOOD
LA English
DT Article
ID NATURAL-KILLER-CELLS; MHC CLASS-I; INTERFERON-GAMMA; INHIBITORY
RECEPTORS; LYMPHOCYTE SUBSETS; GENE-EXPRESSION; CUTTING EDGE;
ACTIVATION; CD56(BRIGHT); CYTOTOXICITY
AB Natural killer (NK)-cell recognition of infected or neoplastic cells can induce cytotoxicity and cytokine secretion. So far, it has been difficult to assess the relative contribution of multiple NK-cell activation receptors to cytokine and chemokine production upon target cell recognition. Using Drosophila cells expressing ligands for the NK-cell receptors LFA-1, NKG2D, DNAM-1, 2B4, and CD16, we studied the minimal requirements for secretion by freshly isolated, human NK cells. Target cell stimulation induced secretion of predominately proinflammatory cytokines and chemokines. Release of chemokines MIP-1 alpha, MIP-1 beta, and RANTES was induced within 1 hour of stimulation, whereas release of TNF-alpha and IFN-gamma occurred later. Engagement of CD16, 2B4, or NKG2D sufficed for chemokine release, whereas induction of TNF-alpha and IFN-gamma required engagement of additional receptors. Remarkably, our results revealed that, upon target cell recognition, CD56(dim) NK cells were more prominent cytokine and chemokine producers than CD56(bright) NK cells. The present data demonstrate how specific target cell ligands dictate qualitative and temporal aspects of NK-cell cytokine and chemokine responses. Conceptually, the results point to CD56(dim) NK cells as an important source of cytokines and chemokines upon recognition of aberrant cells, producing graded responses depending on the multiplicity of activating receptors engaged. (Blood. 2010;115:2167-2176)
C1 [Fauriat, Cyril; Ljunggren, Hans-Gustaf; Bryceson, Yenan T.] Karolinska Univ, Huddinge Hosp, Ctr Infect Med, Dept Med,Karolinska Inst, S-14186 Stockholm, Sweden.
[Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Fauriat, C (reprint author), Karolinska Univ, Huddinge Hosp, Ctr Infect Med, Dept Med,Karolinska Inst, S-14186 Stockholm, Sweden.
EM cfauriat@wanadoo.fr; yenan.bryceson@ki.se
RI Long, Eric/G-5475-2011; Fauriat, Cyril/D-4285-2017;
OI Long, Eric/0000-0002-7793-3728; Bryceson, Yenan/0000-0002-7783-9934
FU Swedish Foundation for Strategic Research; Research Council, and Cancer
Society; Intramural Research Program at National Institutes of Health;
National Institute of Allergy and Infectious Diseases; Mary Beve's
Foundation; David & Astrid Hagelen's Foundation; Karolinska Institute
Research Foundation
FX This work was supported by grants from the Swedish Foundation for
Strategic Research, Research Council, and Cancer Society (C.F., H.-
G.L., and Y.T.B.), by the Intramural Research Program at National
Institutes of Health, National Institute of Allergy and Infectious
Diseases (E.O.L.), and Mary Beve's Foundation, David & Astrid Hagelen's
Foundation, the Karolinska Institute Research Foundation, and Jonas
Soderquist's Stipend (Y.T.B.).
NR 57
TC 237
Z9 245
U1 1
U2 11
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 MAR 18
PY 2010
VL 115
IS 11
BP 2167
EP 2176
DI 10.1182/blood-2009-08-238469
PG 10
WC Hematology
SC Hematology
GA 571KT
UT WOS:000275751400012
PM 19965656
ER
PT J
AU McDermott, DH
Conway, SE
Wang, T
Ricklefs, SM
Agovi, MA
Porcella, SF
Tran, HTB
Milford, E
Spellman, S
Abdi, R
AF McDermott, David H.
Conway, Susan E.
Wang, Tao
Ricklefs, Stacy M.
Agovi, Manza A.
Porcella, Stephen F.
Tran, Huong Thi Bich
Milford, Edgar
Spellman, Stephen
Abdi, Reza
TI Donor and recipient chemokine receptor CCR5 genotype is associated with
survival after bone marrow transplantation
SO BLOOD
LA English
DT Article
ID VERSUS-HOST-DISEASE; STEM-CELL TRANSPLANTATION; ALLOGENEIC
TRANSPLANTATION; PROMOTER POLYMORPHISM; CHRONIC GRAFT; T-CELLS;
PROGRESSION; RISK; REACTIVATION; EXPRESSION
AB Despite continual improvement, morbidity and mortality after hematopoietic stem cell transplantation (HSCT) remain high. The importance of chemokines in HSCT lies in their regulation of immune responses that determine transplantation outcomes. We investigated the role of recipient and donor chemokine system gene polymorphisms by using a candidate gene approach on the incidence of graft-versus-host disease and posttransplantation outcomes in 1370 extensively human leukocyte antigen-matched, unrelated donor-recipient pairs by using multivariate Cox regression models. Our analysis identified that recipients homozygous for a common CCR5 haplotype (H1/H1) had better disease-free survival (DFS; P = .005) and overall survival (P = .021). When the same genotype of both the donor and recipient were considered in the models, a highly significant association with DFS and overall survival was noted (P < .001 and P = .007, respectively) with absolute differences in survival of up to 20% seen between the groups at 3 years after transplantation (50% DFS for pairs with recipient CCR5 H1/H1 vs 30% for pairs with donor CCR5 H1/H1). This finding suggests that donor and/or recipient CCR5 genotypes may be associated with HSCT outcome and suggests new diagnostic and therapeutic strategies for optimizing therapy. (Blood. 2010; 115: 2311- 2318)
C1 [Abdi, Reza] Harvard Univ, Sch Med, Brigham & Womens Hosp, Transplantat Res Ctr,Renal Div, Boston, MA 02115 USA.
[Conway, Susan E.; Tran, Huong Thi Bich; Milford, Edgar; Abdi, Reza] Childrens Hosp, Boston, MA 02115 USA.
[McDermott, David H.] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Wang, Tao] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Ricklefs, Stacy M.; Porcella, Stephen F.] NIAID, Genom Core Unit, Res Technol Sect, Res Technol Branch,NIH, Hamilton, MO USA.
[Agovi, Manza A.] CIBMTR, Minneapolis, MN USA.
[Spellman, Stephen] NMDP, Minneapolis, MN USA.
RP Abdi, R (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Transplantat Res Ctr,Renal Div, 221 Longwood Ave, Boston, MA 02115 USA.
EM rabdi@rics.bwh.harvard.edu
OI McDermott, David/0000-0001-6978-0867
FU Intramural Division of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health; National Marrow Donor Program
(NMDP); National Cancer Institute (NCI) [U24-CA76518]; National Heart,
Lung, and Blood Institute (NHLBI) [5U01HL069294]; National Institute of
Allergy and Infectious Diseases (NIAID); Health Resources and Services
Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research
[N00014-06-1-0704, N00014-08-1-0058]; AABB; Aetna; American Society for
Blood and Marrow Transplantation; Amgen Inc
FX This work was supported by the Intramural Division of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, and a grant to R. A. by the National Marrow Donor Program
(NMDP).; The CIBMTR is supported by Public Health Service
Grant/Cooperative Agreement U24-CA76518 from the National Cancer
Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI),
and the National Institute of Allergy and Infectious Diseases (NIAID); a
Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract
HHSH234200637015C with Health Resources and Services Administration
(HRSA/DHHS); grants N00014-06-1-0704 and N00014-08-1-0058 from the
Office of Naval Research; and grants from AABB; Aetna; American Society
for Blood and Marrow Transplantation; Amgen Inc; anonymous donation to
the Medical College of Wisconsin; Astellas Pharma US Inc; Baxter
International Inc; Bayer HealthCare Pharmaceuticals; Be the Match
Foundation; Biogen IDEC; BioMarin Pharmaceutical Inc; Biovitrum AB;
BloodCenter ofWisconsin; Blue Cross and Blue Shield Association; Bone
Marrow Foundation; Canadian Blood and Marrow Transplant Group;
CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease
Control and Prevention; Children's Leukemia Research Association;
ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist
Pharmaceuticals; Cylex Inc; CytoTherm; DOR BioPharma Inc; Dynal Biotech,
an Invitrogen Company; Eisai Inc; Enzon Pharmaceuticals Inc; European
Group for Blood and
NR 29
TC 13
Z9 13
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 MAR 18
PY 2010
VL 115
IS 11
BP 2311
EP 2318
DI 10.1182/blood-2009-08-237768
PG 8
WC Hematology
SC Hematology
GA 571KT
UT WOS:000275751400028
PM 20068218
ER
PT J
AU Lee, K
Ambrose, Z
Martin, TD
Oztop, I
Mulky, A
Julias, JG
Vandegraaff, N
Baumann, JG
Wang, R
Yuen, W
Takemura, T
Shelton, K
Taniuchi, I
Li, Y
Sodroski, J
Littman, DR
Coffin, JM
Hughes, SH
Unutmaz, D
Engelman, A
KewalRamani, VN
AF Lee, KyeongEun
Ambrose, Zandrea
Martin, Thomas D.
Oztop, Ilker
Mulky, Alok
Julias, John G.
Vandegraaff, Nick
Baumann, Joerg G.
Wang, Rui
Yuen, Wendy
Takemura, Taichiro
Shelton, Kenneth
Taniuchi, Ichiro
Li, Yuan
Sodroski, Joseph
Littman, Dan R.
Coffin, John M.
Hughes, Stephen H.
Unutmaz, Derya
Engelman, Alan
KewalRamani, Vineet N.
TI Flexible Use of Nuclear Import Pathways by HIV-1
SO CELL HOST & MICROBE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL DNA FLAP; FACTOR-I-M; NONDIVIDING
CELLS; PREINTEGRATION COMPLEX; MATRIX PROTEIN; PORE COMPLEX; INFECTION;
TYPE-1; LOCALIZATION
AB HIV-1 replication requires transport of nascent viral DNA and associated virion proteins, the retroviral preintegration complex (PIG), into the nucleus. Too large for passive diffusion through nuclear pore complexes (NPCs), PICs use cellular nuclear transport mechanisms and nucleoporins (NUPs), the NPC components that permit selective nuclear-cytoplasmic exchange, but the details remain unclear. Here we identify a fragment of the cleavage and polyadenylation factor 6, CPSF6, as a potent inhibitor of HIV-1 infection. When enriched in the cytoplasm, CPSF6 prevents HIV-1 nuclear entry by targeting the viral capsid (CA). HIV-1 harboring the N74D mutation in CA fails to interact with CPSF6 and evades the nuclear import restriction. Interestingly, whereas wild-type HIV-1 requires NUP153, N74D HIV-1 mimics feline immunodeficiency virus nuclear import requirements and is more sensitive to NUP155 depletion. These findings reveal a remarkable flexibility in HIV-1 nuclear transport and highlight a single residue in CA as essential in regulating interactions with NUPs.
C1 [Lee, KyeongEun; Ambrose, Zandrea; Martin, Thomas D.; Mulky, Alok; Baumann, Joerg G.; Yuen, Wendy; Takemura, Taichiro; Shelton, Kenneth; Hughes, Stephen H.; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Oztop, Ilker; Vandegraaff, Nick; Li, Yuan; Sodroski, Joseph; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Julias, John G.] SAIC Frederick, Frederick, MD 21702 USA.
[Wang, Rui; Unutmaz, Derya] NYU, Sch Med, Dept Pathol & Microbiol, New York, NY 10016 USA.
[Littman, Dan R.] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
[Littman, Dan R.] NYU, Sch Med, Mol Pathogenesis Program, Skirball Inst Biomol Med, New York, NY 10016 USA.
[Taniuchi, Ichiro] Riken Res Ctr Allergy & Immunol, Lab Transcript Regulat, Yokohama, Kanagawa 2300045, Japan.
[Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Sackler Sch Biomed Sci, Boston, MA 02111 USA.
RP KewalRamani, VN (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM vineet@mail.nih.gov
RI Li, Yuan/B-4098-2013; Taniuchi, Ichiro/N-6399-2015
OI Taniuchi, Ichiro/0000-0002-9853-9068
FU National Cancer Institute's intramural Center for Cancer Research; HIV
Drug Resistance Program; National Institutes of Health [A152014,
A1033303, A1033856, A149131, CA0894, A1063987, A107609441]; American
Foundation for AIDS Research postdoctoral fellowship [106404-33-RFMC];
George Kirby Foundation
FX We thank Eric Freed for manuscript comments; Paul Bieniasz, Michael
Emerman, Eric Freed, and Masahiro Yamashita for discussions; Julie Tang
for assistance; and Sabine Dettwiler, Michael Emerman, Eric Freed, John
Kappes, Walter Keller, Ned Landau, Eric Poeschla, Wes Sundquist, and Uta
von Schwedler for reagents. This work was supported by the National
Cancer Institute's intramural Center for Cancer Research, which supports
the HIV Drug Resistance Program (S.H.H., V.N.K.); National Institutes of
Health (NH) grants to A.E. (A152014), D.R.L. (A1033303; A1033856), D.U.
(A149131), J.M.C. (CA089441), and J.S. (A1063987; A1076094); and an
American Foundation for AIDS Research postdoctoral fellowship to Z.A.
(106404-33-RFMC). J.M.C. was a Research Professor of the American Cancer
Society, with support from the George Kirby Foundation. The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. government.
NR 51
TC 167
Z9 169
U1 1
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD MAR 18
PY 2010
VL 7
IS 3
BP 221
EP 233
DI 10.1016/j.chom.2010.02.007
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 573XA
UT WOS:000275947500007
PM 20227665
ER
PT J
AU Wacholder, S
Hartge, P
Prentice, R
Garcia-Closas, M
Feigelson, HS
Diver, WR
Thun, MJ
Cox, DG
Hankinson, SE
Kraft, P
Rosner, B
Berg, CD
Brinton, LA
Lissowska, J
Sherman, ME
Chlebowski, R
Kooperberg, C
Jackson, RD
Buckman, DW
Hui, P
Pfeiffer, R
Jacobs, KB
Thomas, GD
Hoover, RN
Gail, MH
Chanock, SJ
Hunter, DJ
AF Wacholder, Sholom
Hartge, Patricia
Prentice, Ross
Garcia-Closas, Montserrat
Feigelson, Heather Spencer
Diver, W. Ryan
Thun, Michael J.
Cox, David G.
Hankinson, Susan E.
Kraft, Peter
Rosner, Bernard
Berg, Christine D.
Brinton, Louise A.
Lissowska, Jolanta
Sherman, Mark E.
Chlebowski, Rowan
Kooperberg, Charles
Jackson, Rebecca D.
Buckman, Dennis W.
Hui, Peter
Pfeiffer, Ruth
Jacobs, Kevin B.
Thomas, Gilles D.
Hoover, Robert N.
Gail, Mitchell H.
Chanock, Stephen J.
Hunter, David J.
TI Performance of Common Genetic Variants in Breast-Cancer Risk Models.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BASE-LINE CHARACTERISTICS; SUSCEPTIBILITY LOCI;
POLYMORPHISMS; RECLASSIFICATION; PREVENTION; ALLELES; DISEASE; MARKER
AB Background: Genomewide association studies have identified multiple genetic variants associated with breast cancer. The extent to which these variants add to existing risk-assessment models is unknown.
Methods: We used information on traditional risk factors and 10 common genetic variants associated with breast cancer in 5590 case subjects and 5998 control subjects, 50 to 79 years of age, from four U.S. cohort studies and one case-control study from Poland to fit models of the absolute risk of breast cancer. With the use of receiver-operating-characteristic curve analysis, we calculated the area under the curve (AUC) as a measure of discrimination. By definition, random classification of case and control subjects provides an AUC of 50%; perfect classification provides an AUC of 100%. We calculated the fraction of case subjects in quintiles of estimated absolute risk after the addition of genetic variants to the traditional risk model.
Results: The AUC for a risk model with age, study and entry year, and four traditional risk factors was 58.0%; with the addition of 10 genetic variants, the AUC was 61.8%. About half the case subjects (47.2%) were in the same quintile of risk as in a model without genetic variants; 32.5% were in a higher quintile, and 20.4% were in a lower quintile.
Conclusions: The inclusion of newly discovered genetic factors modestly improved the performance of risk models for breast cancer. The level of predicted breast-cancer risk among most women changed little after the addition of currently available genetic information.
N Engl J Med 2010;362:986-93.
C1 [Wacholder, Sholom; Hartge, Patricia; Garcia-Closas, Montserrat; Brinton, Louise A.; Sherman, Mark E.; Pfeiffer, Ruth; Jacobs, Kevin B.; Thomas, Gilles D.; Hoover, Robert N.; Gail, Mitchell H.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Berg, Christine D.] NCI, Early Detect Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Prentice, Ross; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Feigelson, Heather Spencer; Diver, W. Ryan; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA.
[Feigelson, Heather Spencer] Kaiser Permanente, Inst Hlth Res, Denver, CO USA.
[Cox, David G.] INSERM, F-69008 Lyon, France.
[Cox, David G.; Hankinson, Susan E.; Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Rosner, Bernard] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Hankinson, Susan E.; Rosner, Bernard; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Hankinson, Susan E.; Rosner, Bernard; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Chlebowski, Rowan] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Hematol & Med Oncol, Torrance, CA 90509 USA.
[Jackson, Rebecca D.] Ohio State Univ, Columbus, OH 43210 USA.
[Buckman, Dennis W.; Hui, Peter] Informat Management Serv Inc, Silver Spring, MD USA.
RP Wacholder, S (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 5050,MSC 7244, Bethesda, MD 20892 USA.
EM wacholds@mail.nih.gov
RI Cox, David/A-2023-2009; Pfeiffer, Ruth /F-4748-2011; Garcia-Closas,
Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015;
OI Cox, David/0000-0002-2152-9259; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska,
Jolanta/0000-0003-2695-5799
FU Division of Cancer Epidemiology and Genetics of the National Cancer
Institute; National Institutes of Health [N01WH22110, P01 CA87969, P01
CA53996, R01 CA49449, U01CA098233, U01CA098710]
FX Supported in part by the Intramural Research Program of the Division of
Cancer Epidemiology and Genetics of the National Cancer Institute and by
grants from the National Institutes of Health (N01WH22110, P01 CA87969,
P01 CA53996, R01 CA49449, U01CA098233, and U01CA098710).
NR 32
TC 251
Z9 258
U1 0
U2 20
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 MAR 18
PY 2010
VL 362
IS 11
BP 986
EP 993
DI 10.1056/NEJMoa0907727
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 570CY
UT WOS:000275650400009
PM 20237344
ER
PT J
AU Komiya, T
Coxon, A
Park, Y
Chen, WD
Zajac-Kaye, M
Meltzer, P
Karpova, T
Kaye, FJ
AF Komiya, T.
Coxon, A.
Park, Y.
Chen, W-D
Zajac-Kaye, M.
Meltzer, P.
Karpova, T.
Kaye, F. J.
TI Enhanced activity of the CREB co-activator Crtc1 in LKB1 null lung
cancer
SO ONCOGENE
LA English
DT Article
DE Crtc1; LKB1; lung cancer; Mect1/Torc1; NR4A2
ID SENSITIVE COINCIDENCE DETECTOR; PEUTZ-JEGHERS-SYNDROME; MUCOEPIDERMOID
CARCINOMA; SALIVARY-GLAND; MAMMALIAN-CELLS; WARTHINS TUMORS;
GENE-EXPRESSION; RECEPTOR NR4A2; FUSION; ACTIVATION
AB Activation of Crtc1 (also known as Mect1/Torc1) by a t(11; 19) chromosomal rearrangement underlies the etiology of malignant salivary gland tumors. As LKB1 is a target for mutational inactivation in lung cancer and was recently shown to regulate hepatic Crtc2/CREB transcriptional activity in mice, we now present evidence suggesting disruption of an LKB1/Crtc pathway in cancer. Although Crtc1 is preferentially expressed in adult brain tissues, we observed elevated levels of steady-state Crtc1 in thoracic tumors. In addition, we show that somatic loss of LKB1 is associated with underphosphorylation of endogenous Crtc1, enhanced Crtc1 nuclear localization and enhanced expression of the Crtc prototypic target gene, NR4A2/Nurr1. Inhibition of NR4A2 was associated with growth suppression of LKB1 null tumors, but showed little effect on LKB1-wildtype cells. These data strengthen the role of dysregulated Crtc as a bona. de cancer gene, present a new element to the complex LKB1 tumorigenic axis, and suggest that Crtc genes may be aberrantly activated in a wider range of common adult malignancies. Oncogene (2010) 29, 1672-1680; doi:10.1038/onc.2009.453; published online 14 December 2009
C1 [Komiya, T.; Coxon, A.; Park, Y.; Chen, W-D; Meltzer, P.; Kaye, F. J.] NCI, Genet Branch, Bethesda, MD 20892 USA.
[Komiya, T.; Coxon, A.; Park, Y.; Chen, W-D; Zajac-Kaye, M.; Meltzer, P.; Karpova, T.; Kaye, F. J.] Natl Naval Med Ctr, Bethesda, MD USA.
[Zajac-Kaye, M.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Karpova, T.] NCI, Lab Receptor Biol, Bethesda, MD 20892 USA.
RP Kaye, FJ (reprint author), Univ Florida Coll, Canc Genet Res Ctr, Dept Med, Rm 364,1376 Mowry Rd, Gainesville, FL 32610 USA.
EM fkaye@ufl.edu
RI kaye, frederic/E-2437-2011; CHEN, WEI-DONG/F-4521-2014
OI CHEN, WEI-DONG/0000-0003-2264-5515
NR 48
TC 22
Z9 23
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR 18
PY 2010
VL 29
IS 11
BP 1672
EP 1680
DI 10.1038/onc.2009.453
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 570RC
UT WOS:000275694700012
PM 20010869
ER
PT J
AU Ryan, BC
Young, NB
Crawley, JN
Bodfish, JW
Moy, SS
AF Ryan, Bryce C.
Young, Nancy B.
Crawley, Jacqueline N.
Bodfish, James W.
Moy, Sheryl S.
TI Social deficits, stereotypy and early emergence of repetitive behavior
in the C58/J inbred mouse strain
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Autism; Social transmission of food preference; Maternal behavior;
Neonatal development; Olfaction; Repetitive behavior; Social approach;
Stereotypy
ID AUTISM SPECTRUM DISORDERS; KNOCKOUT MICE; CORPUS-CALLOSUM; OLFACTORY
FINGERPRINTS; FOOD PREFERENCE; LOW SOCIABILITY; MUTANT MICE; BODY ODORS;
RELEVANT; TRANSMISSION
AB Mouse lines with behavioral phenotypes relevant to symptoms in neurodevelopmental disorders may provide models to test hypotheses about disease etiology and to evaluate potential treatments. The present studies were designed to confirm and expand earlier work on the intriguing behavioral profile of the C58/J inbred strain, including low social approach and aberrant repetitive movements. Additional tests were selected to reflect aspects of autism, a severe neurodevelopmental disorder characterized by emergence of symptoms early in life, higher prevalence in males, social deficits and abnormal repetitive behavior. Mice from the C57BL/6J inbred strain, which has a similar genetic lineage and physical appearance to C58/J, served as a comparison group. Our results revealed that C58/J mice display elevated activity levels by postnatal day 6, which persist into adulthood. Despite normal olfactory ability, young adult male C58/J mice showed deficits in social approach in the three-chambered choice assay and failed to demonstrate social transmission of food preference. In contrast, female C58/J mice performed similarly to female C57BL/6J mice in both social tests. C58/J mice of both sexes demonstrated abnormal repetitive behaviors, displaying excessive Jumping and back flipping in both social and non-social situations. These stereotypies were clearly evident in C58/J pups by postnatal days 20-21, and were also observed in C58/J dams during a test for maternal behavior. Overall, the strain profile for C58/J, including spontaneously developing motor stereotypies emerging early in the developmental trajectory, and social deficits primarily in males, models multiple components of the autism phenotype. (C) 2009 ElsevierB.V. All rights reserved.
C1 [Ryan, Bryce C.] Univ Redlands, Dept Biol, Redlands, CA 92373 USA.
[Ryan, Bryce C.; Young, Nancy B.; Crawley, Jacqueline N.; Bodfish, James W.; Moy, Sheryl S.] Univ N Carolina, Sch Med, Neurodev Disorders Res Ctr, Chapel Hill, NC 27599 USA.
[Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA.
[Bodfish, James W.] Univ N Carolina, Sch Med, Clin Ctr Study Dev & Learning, Chapel Hill, NC 27599 USA.
[Bodfish, James W.; Moy, Sheryl S.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA.
RP Ryan, BC (reprint author), 1200 E Colton Ave,POB 3080, Redlands, CA 92373 USA.
EM bryce_ryan@redlands.edu
FU NIMH [R21 MH084132, R01 MH73402]; NICHD [T32 HD40127, P30 HD03110];
National Institute of Mental Health Intrarmural Research Program
FX The authors would like to thank Randal Nonneman, Joe Piven and Steve
Reznick for their valuable assistance and insight throughout this
project. This work was supported by NIMH grants R21 MH084132 and R01
MH73402, and NICHD grants T32 HD40127 and P30 HD03110 and the National
Institute of Mental Health Intrarmural Research Program.
NR 57
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Z9 54
U1 1
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD MAR 17
PY 2010
VL 208
IS 1
BP 178
EP 188
DI 10.1016/j.bbr.2009.11.031
PG 11
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 569TQ
UT WOS:000275625100025
PM 19941908
ER
PT J
AU Ren, XF
Hurley, JH
AF Ren, Xuefeng
Hurley, James H.
TI VHS domains of ESCRT-0 cooperate in high-avidity binding to
polyubiquitinated cargo
SO EMBO JOURNAL
LA English
DT Article
DE Cps1; crystal structure; protein structure; vacuole; yeast genetics
ID MULTIVESICULAR BODY PATHWAY; UBIQUITIN-INTERACTING MOTIF; TRANS-GOLGI
NETWORK; EARLY ENDOSOMES; GGA PROTEINS; MEMBRANE TRAFFICKING; SORTING
MACHINERY; STRUCTURAL BASIS; EGF RECEPTOR; COMPLEX
AB VHS (Vps27, Hrs, and STAM) domains occur in ESCRT-0 subunits Hrs and STAM, GGA adapters, and other trafficking proteins. The structure of the STAM VHS domain-ubiquitin complex was solved at 2.6 angstrom resolution, revealing that determinants for ubiquitin recognition are conserved in nearly all VHS domains. VHS domains from all classes of VHS-domain containing proteins in yeast and humans, including both subunits of ESCRT-0, bound ubiquitin in vitro. ESCRTs have been implicated in the sorting of Lys63-linked polyubiquitinated cargo. Intact human ESCRT-0 binds Lys63-linked tetraubiquitin 50-fold more tightly than monoubiquitin, though only 2-fold more tightly than Lys48-linked tetraubiquitin. The gain in affinity is attributed to the cooperation of flexibly connected VHS and UIM motifs of ESCRT-0 in avid binding to the polyubiquitin chain. Mutational analysis of all the five ubiquitin-binding sites in yeast ESCRT-0 shows that cooperation between them is required for the sorting of the Lys63-linked polyubiquitinated cargo Cps1 to the vacuole. The EMBO Journal (2010) 29, 1045-1054. doi: 10.1038/emboj.2010.6; Published online 11 February 2010
C1 [Ren, Xuefeng; Hurley, James H.] NIDDKD, Mol Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, US Dept HHS, Bldg 50 Rm 4517, Bethesda, MD 20892 USA.
EM hurley@helix.nih.gov
FU US DOE, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]; NIH
FX We thank D Kloer for assistance with crystallographic analysis, B
Baibokov and Y Im for assistance with microscopy, L Saidi for cell
culture support, J Dean for microscope access, K Iwai, C Wolberger, S
Misra, Y Ye, and A Weissman for reagents and advice on polyUb chain
synthesis, C Philpott, J Bonifacino, and R Puertollano for cDNAs, and W
Prinz for yeast strains. Use of the APS was supported by the US DOE,
Basic Energy Sciences, Office of Science, under Contract No.
W-31-109-Eng-38. This work was supported by the NIDDK and IATAP programs
of the NIH intramural research program. Crystallographic coordinates
have been deposited in the Protein Data Bank with the accession code
3LDZ.
NR 51
TC 76
Z9 78
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD MAR 17
PY 2010
VL 29
IS 6
BP 1045
EP 1054
DI 10.1038/emboj.2010.6
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 570NP
UT WOS:000275685300004
PM 20150893
ER
PT J
AU Schiffman, M
Solomon, D
AF Schiffman, Mark
Solomon, Diane
TI Liquid-Based Cytology vs Conventional Cytology in Detecting Cervical
Cancer Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Solomon, Diane] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Schiffman, M (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM schiffman@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 17
PY 2010
VL 303
IS 11
BP 1034
EP 1035
DI 10.1001/jama.2010.278
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 569KC
UT WOS:000275594100012
ER
PT J
AU Hui, D
Elsayem, A
De La Cruz, M
Berger, A
Zhukovsky, DS
Palla, S
Evans, A
Fadul, N
Palmer, JL
Bruera, E
AF Hui, David
Elsayem, Ahmed
De La Cruz, Maxine
Berger, Ann
Zhukovsky, Donna S.
Palla, Shana
Evans, Avery
Fadul, Nada
Palmer, J. Lynn
Bruera, Eduardo
TI Availability and Integration of Palliative Care at US Cancer Centers
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID UNITED-STATES; SUPPORTIVE CARE; MEDICAL-CARE; DATA-BASE; LIFE; ONCOLOGY;
QUALITY; END; HOSPITALS; SOCIETY
AB Context The current state of palliative care in cancer centers is not known.
Objectives To determine the availability and degree of integration of palliative care services and to compare between National Cancer Institute (NCI) and non-NCI cancer centers in the United States.
Design, Setting, and Participants A survey of 71 NCI-designated cancer centers and a random sample of 71 non-NCI cancer centers of both executives and palliative care clinical program leaders, where applicable, regarding their palliative care services between June and October 2009. Survey questions were generated after a comprehensive literature search, review of guidelines from the National Quality Forum, and discussions among 7 physicians with research interest in palliative oncology. Executives were also asked about their attitudes toward palliative care.
Main Outcome Measure Availability of palliative care services in the cancer center, defined as the presence of at least 1 palliative care physician.
Results A total of 142 and 120 surveys were sent to executives and program leaders, with response rates of 71% and 82%, respectively. National Cancer Institute cancer centers were significantly more likely to have a palliative care program (50/51 [98%] vs 39/50 [78%]; P=.002), at least 1 palliative care physician (46/50 [92%] vs 28/38 [74%]; P=.04), an inpatient palliative care consultation team (47/51 [92%] vs 28/50 [56%]; P<.001), and an outpatient palliative care clinic (30/51 [59%] vs 11/50 [22%]; P<.001). Few centers had dedicated palliative care beds (23/101 [23%]) or an institution-operated hospice (37/101 [37%]). The median (interquartile range) reported durations from referral to death were 7 (4-16), 7 (5-10), and 90 (30-120) days for inpatient consultation teams, inpatient units, and outpatient clinics, respectively. Research programs, palliative care fellowships, and mandatory rotations for oncology fellows were uncommon. Executives were supportive of stronger integration and increasing palliative care resources.
Conclusion Most cancer centers reported a palliative care program, although the scope of services and the degree of integration varied widely. JAMA. 2010; 303(11): 1054-1061
C1 [Hui, David; Elsayem, Ahmed; De La Cruz, Maxine; Zhukovsky, Donna S.; Evans, Avery; Fadul, Nada; Bruera, Eduardo] Univ Texas MD Anderson Canc Ctr, Dept Palliat Care & Rehabil Med, Houston, TX 77030 USA.
[Palla, Shana; Palmer, J. Lynn] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Berger, Ann] NCI, Dept Palliat Care, Ctr Clin Canc, Bethesda, MD 20892 USA.
RP Elsayem, A (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Palliat Care & Rehabil Med, Unit 1414,1515 Holcombe Blvd, Houston, TX 77030 USA.
EM aelsayem@mdanderson.org
FU National Institutes of Health [RO1NR010162-01A1, RO1CA122292-01,
RO1CA124481-01]; National Cancer Institute [CA16672]; Royal College of
Physicians and Surgeons of Canada
FX Funding/Support: This work was supported in part by grants
RO1NR010162-01A1, RO1CA122292-01, and RO1CA124481-01 from the National
Institutes of Health (Dr Bruera); grant CA16672 from the National Cancer
Institute (Patient- Reported Outcomes, Survey and Population Research
Shared Resources); and the Clinician Investigator Program, Royal College
of Physicians and Surgeons of Canada (Dr Hui).
NR 33
TC 171
Z9 173
U1 1
U2 14
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 MAR 17
PY 2010
VL 303
IS 11
BP 1054
EP 1061
DI 10.1001/jama.2010.258
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 569KC
UT WOS:000275594100018
PM 20233823
ER
PT J
AU Niederhuber, JE
AF Niederhuber, John E.
TI Translating Discovery to Patient Care
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID TUMOR MICROENVIRONMENT; CANCER
C1 NCI, Bethesda, MD 20892 USA.
RP Niederhuber, JE (reprint author), NCI, 31 Ctr Dr,Room 11A48, Bethesda, MD 20892 USA.
EM niederj@mail.nih.gov
NR 9
TC 6
Z9 6
U1 0
U2 0
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 MAR 17
PY 2010
VL 303
IS 11
BP 1088
EP 1089
DI 10.1001/jama.2010.281
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 569KC
UT WOS:000275594100024
PM 20233829
ER
PT J
AU Conant, K
Wang, Y
Szklarczyk, A
Dudak, A
Mattson, MP
Lim, ST
AF Conant, K.
Wang, Y.
Szklarczyk, A.
Dudak, A.
Mattson, M. P.
Lim, S. T.
TI MATRIX METALLOPROTEINASE-DEPENDENT SHEDDING OF INTERCELLULAR ADHESION
MOLECULE-5 OCCURS WITH LONG-TERM POTENTIATION
SO NEUROSCIENCE
LA English
DT Article
DE telencephalin; NMDA; MMPs; dendrite; plasticity; shedding
ID SYNAPTIC PLASTICITY; EXTRACELLULAR-MATRIX; HIPPOCAMPAL-NEURONS;
DENDRITIC SPINES; TISSUE INHIBITOR; ERM PROTEINS;
MATRIX-METALLOPROTEINASE-9; TELENCEPHALIN; INVOLVEMENT; ACTIVATION
AB Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that can be released or activated in a neuronal activity dependent manner. Although pathologically elevated levels of MMPs may be synaptotoxic, physiologically appropriate levels of MMPs may instead enhance synaptic transmission. MMP inhibitors can block long term potentiation (LTP), and at least one family member can affect an increase in the volume of dendritic spines. While the mechanism by which MMPs affect these changes is not completely understood, one possibility is that the cleavage of specific synaptic cell adhesion molecules plays a role. In the present study, we have examined the ability of neuronal activity to stimulate rapid MMP dependent shedding of the intercellular adhesion molecule-5 (ICAM-5), a synaptic adhesion molecule that is thought to inhibit the maturation and enlargement of dendritic spines. Since such cleavage would likely occur within minutes if it were relevant to a process such as LTP, we focused on post stimulus time points of 30 min or less. We show that NMDA can stimulate rapid shedding of ICAM-5 from cortical neurons in dissociated cell cultures and that such shedding is diminished by pretreatment of cultures with inhibitors that target MMP-3 and -9, proteases thought to influence synaptic plasticity. Additional studies suggest that MMP mediated cleavage of ICAM-5 occurs at amino acid 780, so that the major portion of the ectodomain is released. Since reductions in ICAM-5 have been linked to changes in dendritic spine morphology that are associated with LTP, we also examined the possibility that MMP dependent ICAM-5 shedding occurs following high frequency tetanic stimulation of murine hippocampal slices. Results show that the shedding of ICAM-5 occurs in association with LTP, and that both LTP and the associated ICAM-5 shedding are reduced when slices are pretreated with an MMP inhibitor. Together, these findings suggest that neuronal activity is linked to the shedding of a molecule that may inhibit dendritic spine enlargement and that MMPs can affect this change. While further studies will be necessary to determine the extent to which cleavage of ICAM-5 in particular contributes to MMP dependent LTP, our data support an emerging body of literature suggesting that MMPs are critical mediators of synaptic plasticity. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Conant, K.; Szklarczyk, A.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Conant, K.; Dudak, A.; Lim, S. T.] Georgetown Univ, Dept Neurosci, Washington, DC USA.
[Wang, Y.; Mattson, M. P.] NIA, Neurosci Lab, Baltimore, MD 21224 USA.
RP Conant, K (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
EM kec84@georgetown.edu; ls379@georgetown.edu
RI Mattson, Mark/F-6038-2012
FU Alzheimer's Association; National Institutes of Drug Abuse [DA024447];
National Multiple Sclerosis Society; National Institutes of Aging
[AG029806]
FX This work was supported in part by the Alzheimer's Association, the
National Institutes of Drug Abuse (DA024447), the National Multiple
Sclerosis Society, and the National Institutes of Aging (Intramural
Program and AG029806).
NR 59
TC 53
Z9 55
U1 1
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD MAR 17
PY 2010
VL 166
IS 2
BP 508
EP 521
DI 10.1016/j.neuroscience.2009.12.061
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 560PJ
UT WOS:000274914300019
PM 20045450
ER
PT J
AU Jett, DA
AF Jett, David A.
TI Finding New Cures for Neurological Disorders: A Possible Fringe Benefit
of Biodefense Research?
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID STATUS EPILEPTICUS; ENZYME EVOLUTION; X-RAY; SARIN;
ACETYLCHOLINESTERASE; RECOGNITION; MECHANISMS; ZEBRAFISH; RECEPTORS;
DYNAMICS
AB The National Institutes of Health (NIH) supports research about and the development of better therapies for treating exposure to toxic chemicals that could be used in a terrorist attack or released during an industrial accident. A review of recent research published by NIH investigators working in this field indicates that scientific advances in this area also have implications for reducing the burden of other neurological diseases and disorders. Some key examples discussed include studies on the development of therapeutic drugs to treat seizures and the neuropathology caused by chemical nerve agents, which may help find better cures for epilepsy, stroke, and neurodegenerative diseases.
C1 NINDS, NIH CounterACT Res, NIH, Bethesda, MD 20892 USA.
RP Jett, DA (reprint author), NINDS, NIH CounterACT Res, NIH, Bethesda, MD 20892 USA.
EM jettd@ninds.nih.gov
NR 35
TC 3
Z9 3
U1 0
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 MAR 17
PY 2010
VL 2
IS 23
AR 23ps12
DI 10.1126/scitranslmed.3000752
PG 4
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 591ME
UT WOS:000277304000002
PM 20375001
ER
PT J
AU Goldfine, AB
Fonseca, V
Jablonski, KA
Pyle, L
Staten, MA
Shoelson, SE
AF Goldfine, Allison B.
Fonseca, Vivian
Jablonski, Kathleen A.
Pyle, Laura
Staten, Myrlene A.
Shoelson, Steven E.
CA TINSAL-T2D Targeting Inflammation
TI The Effects of Salsalate on Glycemic Control in Patients With Type 2
Diabetes A Randomized Trial
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID NF-KAPPA-B; GLOMERULAR-FILTRATION-RATE; INDUCED INSULIN-RESISTANCE;
SODIUM-SALICYLATE; IKK-BETA; NONACETYLATED SALICYLATE; CYSTATIN-C;
URIC-ACID; ASPIRIN; INFLAMMATION
AB Background: Salsalate, a nonacetylated prodrug of salicylate, has been shown to decrease blood glucose concentration in small studies.
Objective: To compare the efficacy and safety of salsalate at different doses in patients with type 2 diabetes.
Design: Parallel randomized trial with computer-generated randomization and centralized allocation. Patients and investigators, including those assessing outcomes and performing analyses, were masked to group assignment. (ClinicalTrials.gov registration number: NCT00392678)
Setting: 3 private practices and 14 universities in the United States.
Patients: Persons aged 18 to 75 years with fasting plasma glucose concentrations of 12.5 mmol/L or less (<= 225 mg/dL) and hemoglobin A(1c) (HbA(1c)) levels of 7.0% to 9.5% treated by diet, exercise, and oral medication at stable doses for at least 8 weeks.
Intervention: After a 4-week, single-masked run-in period, patients were randomly assigned to receive placebo or salsalate in dosages of 3.0, 3.5, or 4.0 g/d for 14 weeks (27 patients each) in addition to their current therapy.
Measurements: Change in HbA(1c) was the primary outcome. Adverse effects and changes in measures of coronary risk and renal function were secondary outcomes.
Results: Higher proportions of patients in the 3 salsalate treatment groups experienced decreases in HbA(1c) levels of 0.5% or more from baseline (P = 0.009). Mean HbA(1c) changes were -0.36% (P = 0.02) at 3.0 g/d, -0.34% (P = 0.02) at 3.5 g/d, and -0.49% (P = 0.001) at 4.0 g/d compared with placebo. Other markers of glycemic control also improved in the 3 salsalate groups, as did circulating triglyceride and adiponectin concentrations. Mild hypoglycemia was more common with salsalate; documented events occurred only in patients taking sulfonylureas. Urine albumin concentrations increased in all salsalate groups compared with placebo. The drug was otherwise well tolerated.
Limitation: The number of patients studied and the trial duration were insufficient to warrant recommending the use of salsalate for type 2 diabetes at this time.
Conclusion: Salsalate lowers HbA(1c) levels and improves other markers of glycemic control in patients with type 2 diabetes and may therefore provide a new avenue for treatment. Renal and cardiac safety of the drug require further evaluation.
C1 [Shoelson, Steven E.] Joslin Diabet Ctr, Boston, MA 02215 USA.
Tulane Univ, New Orleans, LA 70118 USA.
George Washington Univ, Rockville, MD USA.
NIDDKD, Washington, DC USA.
RP Shoelson, SE (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA.
EM steven.shoelson@joslin.harvard.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health; National Institutes of Health [U01
DK74556, P50 HL83813]; National Institutes of Health General Clinical
Research Center; Clinical and Translational Science
FX National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.; By National Institutes of Health grants
U01 DK74556 and P50 HL83813, National Institutes of Health General
Clinical Research Center and Clinical and Translational Science Award
grants at multiple sites, and the Tullis-Tulane (Dr. Fonseca) and Helen
and Morton Adler (Dr. Shoelson) Chairs. Caraco Pharmaceuticals (Detroit,
Michigan) supplied drug and placebo, Lifescan (Miltipas, California; a
division of Johnson & Johnson) supplied home glucose-monitoring kits,
and Mercodia (Uppsala, Sweden) supplied insulin assay kits.
NR 37
TC 198
Z9 201
U1 0
U2 13
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 16
PY 2010
VL 152
IS 6
BP 346
EP +
DI 10.7326/0003-4819-152-6-201003160-00004
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA 573IF
UT WOS:000275905200002
PM 20231565
ER
PT J
AU Polgar, O
Ierano, C
Tamaki, A
Stanley, B
Ward, Y
Xia, D
Tarasova, N
Robey, RW
Bates, SE
AF Polgar, Orsolya
Ierano, Caterina
Tamaki, Akina
Stanley, Bradford
Ward, Yvona
Xia, Di
Tarasova, Nadya
Robey, Robert W.
Bates, Susan E.
TI Mutational Analysis of Threonine 402 Adjacent to the GXXXG Dimerization
Motif in Transmembrane Segment 1 of ABCG2
SO BIOCHEMISTRY
LA English
DT Article
ID MULTIDRUG-RESISTANCE TRANSPORTER; BREAST-CANCER CELLS; GLYCOPHORIN-A;
PHARMACOLOGICAL CHAPERONES; BIOLOGICAL MEMBRANE; ACQUIRED MUTATIONS;
HELIX INTERACTIONS; CYSTIC-FIBROSIS; DIMER; GENE
AB ABCG2 is an ATP-binding cassette half-transporter important in normal tissue protection, drug distribution, and excretion. ABCG2 requires homodimerization for function, though the mechanism for dimerization has not been elucidated. We conducted mutational analysis of threonine 402, three residues from the GXXXG motif in TM1, to study its potential role in ABCG2 dimerization (TXXXGXXXG). Single Mutations to leucine (T402L) or arginine (T402R) did not have a significant impact oil the ABCG2 protein. On the other hand, combining the T402 Mutations with the GXXXG glycine to leucine mutations (T402L/G406L/G410L and T402R/G406L/G410L) resulted in a substantially reduced level of expression, altered glycosylation, degradation by it proteosome-independent pathway, and partial retention in the endoplasmic reticulum as suggested by immunostaining, Endo H sensitivity, and MG132 and bafilomycin failed effect. The T402L/G406L/G410L Mutant when incubated with the ABCG2 substrate NIX showed it shift oil immunoblot analysis to the band representing the fully Mature glycoprotein. The T402R/G406L/G410L mutant carrying the more drastic substitution Was found to primarily localize intracellularly. The same set of mutations also displayed impaired dimerization in the TOXCAT assay for TM1 compared to that of the wild type. Homology modeling of ABCG2 places the TXXXGXXXG motif at the dimer interface. These Studies are consistent with a role for the extended TXXXGXXXG motif in ABCG2 folding, processing, and/or dimerization.
C1 [Polgar, Orsolya; Ierano, Caterina; Tamaki, Akina; Robey, Robert W.; Bates, Susan E.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Xia, Di] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Stanley, Bradford] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
[Tarasova, Nadya] NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21702 USA.
[Ward, Yvona] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Bates, SE (reprint author), NCI, Med Oncol Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA.
EM sebates@helix.nih.gov
RI Ierano, Caterina/K-1676-2016
OI Ierano, Caterina/0000-0003-3138-1873
FU 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.
NR 54
TC 26
Z9 26
U1 0
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 16
PY 2010
VL 49
IS 10
BP 2235
EP 2245
DI 10.1021/bi902085q
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 564PH
UT WOS:000275227000016
PM 20088606
ER
PT J
AU McCormack, T
Petrovich, RM
Mercier, KA
DeRose, EF
Cuneo, MJ
Williams, J
Johnson, KL
Lamb, PW
London, RE
Yakel, JL
AF McCormack, Thomas
Petrovich, Robert M.
Mercier, Kelly A.
DeRose, Eugene F.
Cuneo, Matthew J.
Williams, Jason
Johnson, Katina L.
Lamb, Patricia W.
London, Robert E.
Yakel, Jerrel L.
TI Identification and Functional Characterization of a Novel
Acetylcholine-Binding Protein from the Marine Annelid Capitella teleta
SO BIOCHEMISTRY
LA English
DT Article
ID RAY SOLUTION SCATTERING; CRYSTAL-STRUCTURE; NICOTINIC RECEPTORS;
ESCHERICHIA-COLI; HIGH-RESOLUTION; LIGAND-BINDING; DOMAIN; NMR;
TRANSITIONS; REVEALS
AB We identified it homologue of the molluscan acetylcholine-binding protein (AChBP) in the marine polychaete Capitella teleta, from the annelid phylum. The amino acid sequence of C. teleta AChBP (ct-AChBP) is 21-30% identical with those of known molluscan AMPS. Sequence alignments Indicate that ct-AChBP has a shortened Cys loop compared to other Cys loop receptors, and a variation on a conserved Cys loop triad, which is associated with ligand binding in other AChBPs and nicotinic ACh receptor (nAChR) alpha subunits. Within the D loop of ct-AChBP, a conserved aromatic residue (Tyr or Trp) in nAChRs and molluscan AChBPs. which has been implicated directly in ligand binding, is substituted with an isoleucine. Mass spectrometry results that Asn 122 and Asn216 of ct-AChBP are glycosylated expressed using HEK293 cells. Small-angle X-ray scattering data suggest that the overall shape of ct-AChBP in the apo of unliganded state is similar to that of homologous with known pentameric crystal Structures. NMR experiments show that acetylcholine, nicotine, and alpha-bungarotoxin bind to ct-AChBP with high affinity, with K(D) values of 28.7 mu M, 209 nM, and 110 nM, respectively. Choline bound with a lower affinity (K(D) = 163 mu M). Our finding of a functional AChBP in it marine annelid demonstrates that AChBPs may exhibit variations in hallmark motifs such its ligand-binding residues and Cys loop length and shows conclusively that this neurotransmitter binding, protein is not limited to the phyllum Mollusca.
C1 [McCormack, Thomas; Lamb, Patricia W.; Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Petrovich, Robert M.; Mercier, Kelly A.; DeRose, Eugene F.; Cuneo, Matthew J.; Williams, Jason; Johnson, Katina L.; London, Robert E.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM yakel@niehs.nih.gov
OI Cuneo, Matthew/0000-0002-1475-6656
FU National Institutes of Health, National Institute of Environmental
Health Sciences [HHSN273200700046U]
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Institute of Environmental Health Sciences. E.F.D's
contribution was funded in whole with federal funds from the National
Institutes of Health, National Institute of Environmental Health
Sciences, under Delivery Order HHSN273200700046U to SRA International,
Inc.
NR 27
TC 14
Z9 14
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 16
PY 2010
VL 49
IS 10
BP 2279
EP 2287
DI 10.1021/bi902023y
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 564PH
UT WOS:000275227000020
PM 20136097
ER
PT J
AU Huang, J
Chen, K
Chen, J
Gong, W
Dunlop, NM
Howard, OMZ
Gao, Y
Bian, XW
Wang, JM
AF Huang, J.
Chen, K.
Chen, J.
Gong, W.
Dunlop, N. M.
Howard, O. M. Z.
Gao, Y.
Bian, X-W
Wang, J. M.
TI The G-protein-coupled formylpeptide receptor FPR confers a more invasive
phenotype on human glioblastoma cells
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE formylpeptide receptor; invasion; glioblastoma; cancer
ID FORMYL PEPTIDE-RECEPTOR; METHIONYL-LEUCYL-PHENYLALANINE; ENDOTHELIAL
GROWTH-FACTOR; MALIGNANT GLIOMA-CELLS; LISTERIA-MONOCYTOGENES;
N-FORMYLPEPTIDE; CYCLOSPORINE-H; ANNEXIN-I; ACTIVATION; IDENTIFICATION
AB BACKGROUND: The G-protein-coupled formylpeptide receptor (FPR) that mediates chemotaxis of phagocytic leucocytes induced by bacterial and host-derived chemotactic peptides is selectively expressed by highly malignant human gliomas and contributes to tumour growth and angiogenesis. As invasion of surrounding normal tissues is one of the important features of tumour malignancy, we investigated the function of FPR in the invasive behaviour of human glioblastoma cells.
METHODS: Cells (FPR(+) and FPR(-)) were isolated by single-cell cloning from a human glioblastoma cell line U-87MG. The FPR expression was assayed by flow cytometry and reverse transcription PCR. The function of FPR was investigated by chemotaxis and calcium flux induced by FPR agonist fMLF. Tumour cell motility was assayed by a wound-healing model in vitro. The growth and invasive phenotype were observed with subcutaneous implantation of tumour cells in nude mice. Over-expression of FPR in FPR(-) cells was performed by transfection of a plasmid vector-containing human FPR gene.
RESULTS: One of the glioma clones F9 that expressed high level of FPR showed a more 'motile' phenotype in vitro as compared with a clone G3 without FPR expression. Although F9 and G3 clones both formed subcutaneous tumours in nude mice, only F9 tumours invaded surrounding mouse connective tissues. Over-expression of FPR in G3 clone (G3F) increased the cell motility in vitro and the capacity of the cells to form more rapidly growing and invasive tumours in nude mice. We further found that, in addition to supernatant of necrotic tumour cells, foetal calf serum and human serum used in culture media contained FPR agonist activity and increased the motility of FPR-expressing glioblastoma cells.
CONCLUSION: The expression of FPR is responsible for increased motility of human glioblastoma cells and their formation of highly invasive tumours. British Journal of Cancer (2010) 102, 1052-1060. doi:10.1038/sj.bjc.6605591 www.bjcancer.com Published online 2 March 2010 (C) 2010 Cancer Research UK
C1 [Huang, J.; Gao, Y.] Third Mil Med Univ, Coll High Altitude Mil Med, Dept Pathophysiol, Chongqing 400038, Peoples R China.
[Huang, J.; Chen, K.; Dunlop, N. M.; Howard, O. M. Z.; Wang, J. M.] NCI Frederick, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Chen, J.; Bian, X-W] Third Mil Med Univ, Inst Pathol, Chongqing 400038, Peoples R China.
[Chen, J.; Bian, X-W] Third Mil Med Univ, SW Canc Ctr, Southwest Hosp, Chongqing 400038, Peoples R China.
[Gong, W.] NCI Frederick, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA.
RP Huang, J (reprint author), Third Mil Med Univ, Coll High Altitude Mil Med, Dept Pathophysiol, Chongqing 400038, Peoples R China.
EM hj3red@gmail.com; wangji@mail.nih.gov
RI Bian, Xiuwu/F-1569-2011; Howard, O M Zack/B-6117-2012; Bian,
Xiu-wu/D-4736-2017
OI Howard, O M Zack/0000-0002-0505-7052; Bian, Xiu-wu/0000-0003-4383-0197
FU National Cancer Institutes, National Institutes of Health
[NO1-CO-12400]; National Natural Science foundation of China [30973446]
FX We thank Dr Joost J Oppenheim for reviewing the manuscript and Ms Cheryl
N Magers and Ms Cheryl F Lamb for secretarial assistance. 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 organisations implies endorsement by the
US Government. This project has been funded in part with federal funds
from the National Cancer Institutes, National Institutes of Health,
under Contract No. NO1-CO-12400. The research was also supported in part
by the Intramural Research Program of the NCI, NIH and National Natural
Science foundation of China (NSFC, No. 30973446). Animal care was
provided in accordance with the procedures outlined in the 'Guide for
Care and Use of Laboratory Animals' (National Research Council; 1996;
National Academy Press; Washington, D. C.).
NR 32
TC 31
Z9 34
U1 1
U2 12
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 MAR 16
PY 2010
VL 102
IS 6
BP 1052
EP 1060
DI 10.1038/sj.bjc.6605591
PG 9
WC Oncology
SC Oncology
GA 569XK
UT WOS:000275635900017
PM 20197768
ER
PT J
AU Burgos, PV
Mardones, GA
Rojas, AL
daSilva, LLP
Prabhu, Y
Hurley, JH
Bonifacino, JS
AF Burgos, Patricia V.
Mardones, Gonzalo A.
Rojas, Adriana L.
daSilva, Luis L. P.
Prabhu, Yogikala
Hurley, James H.
Bonifacino, Juan S.
TI Sorting of the Alzheimer's Disease Amyloid Precursor Protein Mediated by
the AP-4 Complex
SO DEVELOPMENTAL CELL
LA English
DT Article
ID TRANS-GOLGI NETWORK; BETA-PROTEIN; AP2 COMPLEX; STRUCTURAL EXPLANATION;
SECRETASE CLEAVAGE; MEDIUM CHAINS; CELL-SURFACE; SIGNALS; ADAPTER;
GENERATION
AB Adaptor protein 4 (AP-4) is the most recently discovered and least well-characterized member of the family of heterotetrameric adaptor protein (AP) complexes that mediate sorting of transmembrane cargo in post-Golgi compartments. Herein, we report the interaction of an YKFFE sequence from the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) with the mu 4 subunit of AP-4. Biochemical and X-ray crystallographic analyses reveal that the properties of the APP sequence and the location of the binding site on mu 4 are distinct from those of other signal-adaptor interactions. Disruption of the APP-AP-4 interaction decreases localization of APP to endosomes and enhances gamma-secretase-catalyzed cleavage of APP to the pathogenic amyloid-beta peptide. These findings demonstrate that APP and AP-4 engage in a distinct type of signal-adaptor interaction that mediates transport of APP from the trans-Golgi network (TGN) to endosomes, thereby reducing amyloidogenic processing of the protein.
C1 [Burgos, Patricia V.; Mardones, Gonzalo A.; daSilva, Luis L. P.; Prabhu, Yogikala; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Rojas, Adriana L.; Hurley, James H.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM juan@helix.nih.gov
RI LP daSilva, Luis/A-9949-2010; Rojas, Adriana/G-2403-2011;
OI LP daSilva, Luis/0000-0003-3558-0087; Rojas,
Adriana/0000-0002-7358-3505; Bonifacino, Juan S./0000-0002-5673-6370
FU National Cancer Institute [Y1-C0-1020]; National Institute of General
Medical Science [Y1-GM-1104]; U.S. Department of Energy, Basic Energy
Sciences, Office of Science [DE-AC02-06CH11357]; NICHD; NIDDK; NIH
FX We thank X. Zhu, and N. Tsai for excellent technical assistance; R.
Doms, C. Dotti, A. Gonzalez, C. Haass, R. Hegde, M. S. Robinson, and W.
Smith for gifts of reagents; J. Sayer, J. Louis, and G. M. Clore for use
of the iTC200 microcalorimeter; N. Noinaj for collecting the
native data set; and the staffs of the SER-CAT and GM/CA-CAT beamlines
at the APS, Argonne National Laboratory, for assistance with X-ray data
collection. GM/CA-CAT has been funded in whole or in part with funds
from the National Cancer Institute (Y1-C0-1020) and the National
Institute of General Medical Science (Y1-GM-1104). Use of the APS was
supported by the U.S. Department of Energy, Basic Energy Sciences,
Office of Science, under contract no. DE-AC02-06CH11357. This work was
funded by the Intramural Programs of NICHD and NIDDK, NIH.
NR 46
TC 115
Z9 119
U1 1
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD MAR 16
PY 2010
VL 18
IS 3
BP 425
EP 436
DI 10.1016/j.devcel.2010.01.015
PG 12
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 575HP
UT WOS:000276058400013
PM 20230749
ER
PT J
AU Chen, H
Huang, X
Guo, X
Mailman, RB
Park, Y
Kamel, F
Umbach, DM
Xu, Q
Hollenbeck, A
Schatzkin, A
Blair, A
AF Chen, H.
Huang, X.
Guo, X.
Mailman, R. B.
Park, Y.
Kamel, F.
Umbach, D. M.
Xu, Q.
Hollenbeck, A.
Schatzkin, A.
Blair, A.
TI Smoking duration, intensity, and risk of Parkinson disease
SO NEUROLOGY
LA English
DT Article
ID CIGARETTE-SMOKING; TRANSDERMAL NICOTINE; PROGRESSION; SURVIVAL; COHORT;
HEALTH; MOTOR; TWINS; DIET
AB Objective: To evaluate the relative importance of smoking duration vs intensity in reducing the risk of Parkinson disease (PD). Methods: The study included 305,468 participants of the NIH-AARP Diet and Health cohort, of whom 1,662 had a PD diagnosis after 1995. We estimated odds ratios (OR) and 95% confidence intervals from multivariate logistic regression models.
Results: Compared with never smokers, the multivariate ORs were 0.78 for past smokers and 0.56 for current smokers. Among past smokers, a monotonic trend toward lower PD risk was observed for all indicators of more smoking. Stratified analyses indicated that smoking duration was associated with lower PD risk within fixed intensities of smoking. For example, compared with never smokers, the ORs among past smokers who smoked >20 cigarettes/day were 0.96 for 1-9 years of smoking, 0.78 for 10-19 years, 0.64 for 20-29 years, and 0.59 for 30 years or more (p for trend = 0.001). In contrast, at fixed duration, the typical number of cigarettes smoked per day in general was not related to PD risk. Close examination of smoking behaviors in early life showed that patients with PD were less likely to be smokers at each age period, but if they smoked, they smoked similar numbers of cigarettes per day as individuals without PD.
Conclusions: This large study suggests that long-term smoking is more important than smoking intensity in the smoking-Parkinson disease relationship. Neurology (R) 2010; 74: 878-884
C1 [Chen, H.; Kamel, F.; Xu, Q.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Umbach, D. M.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Huang, X.; Mailman, R. B.] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
[Huang, X.] Penn State Univ, Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA 17033 USA.
[Huang, X.] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA.
[Huang, X.; Mailman, R. B.] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA.
[Huang, X.] Penn State Univ, Milton S Hershey Med Ctr, Dept Kinesiol, Hershey, PA 17033 USA.
[Huang, X.] Penn State Univ, Milton S Hershey Med Ctr, Dept Bioengn, Hershey, PA 17033 USA.
[Guo, X.] Westat Corp, Res Triangle Pk, NC USA.
[Park, Y.; Schatzkin, A.] NCI, Nutr Epidemiol Branch, Rockville, MD USA.
[Blair, A.] NCI, Occupat & Environm Epidemiol Branch, Rockville, MD USA.
[Hollenbeck, A.] AARP, Washington, DC USA.
RP Chen, H (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM chenh2@niehs.nih.gov
OI Kamel, Freya/0000-0001-5052-6615; Mailman, Richard/0000-0003-1353-2738;
Chen, Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X
FU Intramural NIH HHS; NCI NIH HHS [Z01 CP010196-02]; NIEHS NIH HHS
[Z01-ES-101986]
NR 27
TC 86
Z9 89
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD MAR 16
PY 2010
VL 74
IS 11
BP 878
EP 884
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 569LO
UT WOS:000275598700005
PM 20220126
ER
PT J
AU Segal, BH
Han, W
Bushey, JJ
Joo, M
Bhatti, Z
Feminella, J
Dennis, CG
Vethanayagam, RR
Yull, FE
Capitano, M
Wallace, PK
Minderman, H
Christman, JW
Sporn, MB
Chan, J
Vinh, DC
Holland, SM
Romani, LR
Gaffen, SL
Freeman, ML
Blackwell, TS
AF Segal, Brahm H.
Han, Wei
Bushey, Jennifer J.
Joo, Myungsoo
Bhatti, Zahida
Feminella, Joy
Dennis, Carly G.
Vethanayagam, R. Robert
Yull, Fiona E.
Capitano, Maegan
Wallace, Paul K.
Minderman, Hans
Christman, John W.
Sporn, Michael B.
Chan, Jefferson
Vinh, Donald C.
Holland, Steven M.
Romani, Luigina R.
Gaffen, Sarah L.
Freeman, Michael L.
Blackwell, Timothy S.
TI NADPH Oxidase Limits Innate Immune Responses in the Lungs in Mice
SO PLOS ONE
LA English
DT Article
ID CHRONIC GRANULOMATOUS-DISEASE; NF-KAPPA-B; SMOKE-INDUCED EMPHYSEMA;
CUL3-BASED E3 LIGASE; CDDO-IMIDAZOLIDE; HOST-DEFENSE; DEFICIENT MICE;
ENHANCES SUSCEPTIBILITY; SYNTHETIC TRITERPENOIDS; INFLAMMATORY RESPONSES
AB Background: Chronic granulomatous disease (CGD), an inherited disorder of the NADPH oxidase in which phagocytes are defective in generating superoxide anion and downstream reactive oxidant intermediates (ROIs), is characterized by recurrent bacterial and fungal infections and by excessive inflammation (e. g., inflammatory bowel disease). The mechanisms by which NADPH oxidase regulates inflammation are not well understood.
Methodology/Principal Findings: We found that NADPH oxidase restrains inflammation by modulating redox-sensitive innate immune pathways. When challenged with either intratracheal zymosan or LPS, NADPH oxidase-deficient p47(phox-/-) mice and gp91(phox)-deficient mice developed exaggerated and progressive lung inflammation, augmented NF-kappa B activation, and elevated downstream pro-inflammatory cytokines (TNF-alpha, IL-17, and G-CSF) compared to wildtype mice. Replacement of functional NADPH oxidase in bone marrow-derived cells restored the normal lung inflammatory response. Studies in vivo and in isolated macrophages demonstrated that in the absence of functional NADPH oxidase, zymosan failed to activate Nrf2, a key redox-sensitive anti-inflammatory regulator. The triterpenoid, CDDO-Im, activated Nrf2 independently of NADPH oxidase and reduced zymosan-induced lung inflammation in CGD mice. Consistent with these findings, zymosan-treated peripheral blood mononuclear cells from X-linked CGD patients showed impaired Nrf2 activity and increased NF-kB activation.
Conclusions/Significance: These studies support a model in which NADPH oxidase-dependent, redox-mediated signaling is critical for termination of lung inflammation and suggest new potential therapeutic targets for CGD.
C1 [Segal, Brahm H.; Bushey, Jennifer J.; Feminella, Joy; Dennis, Carly G.; Vethanayagam, R. Robert; Minderman, Hans] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA.
[Segal, Brahm H.; Capitano, Maegan] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA.
[Segal, Brahm H.; Bhatti, Zahida] Univ Buffalo, Sch Med & Biomed Sci, Buffalo, NY USA.
[Han, Wei; Blackwell, Timothy S.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.
[Joo, Myungsoo] Pusan Natl Univ, Sch Oriental Med, Div Appl Med, Yangsan, South Korea.
[Yull, Fiona E.; Blackwell, Timothy S.] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA.
[Wallace, Paul K.; Minderman, Hans] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA.
[Christman, John W.] Univ Illinois, Sect Pulm Crit Care & Sleep Med, Chicago, IL USA.
[Sporn, Michael B.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03756 USA.
[Chan, Jefferson] Univ So Calif, Sch Med, Dept Pathol, Irvine, CA USA.
[Vinh, Donald C.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Romani, Luigina R.] Univ Perugia, Dept Expt Med, I-06100 Perugia, Italy.
[Gaffen, Sarah L.] Univ Pittsburgh, Div Rheumatol & Clin Immunol, Pittsburgh, PA USA.
[Freeman, Michael L.] Vanderbilt Univ, Sch Med, Dept Radiat Oncol, Nashville, TN 37212 USA.
[Blackwell, Timothy S.] Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37212 USA.
[Blackwell, Timothy S.] Dept Vet Affairs, Nashville, TN USA.
RP Segal, BH (reprint author), Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA.
EM brahm.segal@roswellpark.org
OI VINH, DONALD/0000-0003-1347-7767; Freeman, Michael/0000-0003-1881-366X;
Romani, Luigina/0000-0002-1356-525X
FU Chronic Granulomatous Disorder Research Trust; NIH/NIAID [R01AI079253];
NIH/NCI [CA115556]; NIH [HL61419]; U.S. Department of Veterans Affairs
(TSB); Korea Healthcare Technology RD [A084891]; NCI Cancer Center
[CA016056]
FX This work was supported by Chronic Granulomatous Disorder Research Trust
and NIH/NIAID R01AI079253 (BHS), NIH/NCI CA115556 (MLF), NIH HL61419
(TSB), the U.S. Department of Veterans Affairs (TSB), and Korea
Healthcare Technology R&D Project A084891 (MJ). This research was
supported, in part, by the NCI Cancer Center Support Grant to Roswell
Park Cancer Institute (CA016056). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 65
TC 83
Z9 84
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 16
PY 2010
VL 5
IS 3
AR e9631
DI 10.1371/journal.pone.0009631
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570ZC
UT WOS:000275716400001
PM 20300512
ER
PT J
AU Auld, DS
Lovell, S
Thorne, N
Lea, WA
Maloney, DJ
Shen, M
Rai, G
Battaile, KP
Thomas, CJ
Simeonov, A
Hanzlik, RP
Inglese, J
AF Auld, Douglas S.
Lovell, Scott
Thorne, Natasha
Lea, Wendy A.
Maloney, David J.
Shen, Min
Rai, Ganesha
Battaile, Kevin P.
Thomas, Craig J.
Simeonov, Anton
Hanzlik, Robert P.
Inglese, James
TI Molecular basis for the high-affinity binding and stabilization of
firefly luciferase by PTC124
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Ataluren; multisubstrate adduct inhibitor; protein stability; reporter
gene assay; X-ray crystallography
ID MULTISUBSTRATE ADDUCT INHIBITOR; CRYSTAL-STRUCTURE; BIOLUMINESCENCE;
MECHANISM; REPORTER; ENZYME; ASSAYS; TRANSFORMYLASE; IDENTIFICATION;
SPECIFICITY
AB Firefly luciferase (FLuc), an ATP-dependent bioluminescent reporter enzyme, is broadly used in chemical biology and drug discovery assays. PTC124 (Ataluren; (3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl] benzoic acid) discovered in an FLuc-based assay targeting nonsense codon suppression, is an unusually potent FLuc-inhibitor. Paradoxically, PTC124 and related analogs increase cellular FLuc activity levels by posttranslational stabilization. In this study, we show that FLuc inhibition and stabilization is the result of an inhibitory product formed during the FLuc-catalyzed reaction between its natural substrate, ATP, and PTC124. A 2.0 angstrom cocrystal structure revealed the inhibitor to be the acyl-AMP mixed-anhydride adduct PTC124-AMP, which was subsequently synthesized and shown to be a high-affinity multisubstrate adduct inhibitor (MAI; K(D) = 120 pM) of FLuc. Biochemical assays, liquid chromatography/mass spectrometry, and near-attack conformer modeling demonstrate that formation of this novel MAI is absolutely dependent upon the precise positioning and reactivity of a key meta-carboxylate of PTC124 within the FLuc active site. We also demonstrate that the inhibitory activity of PTC124-AMP is relieved by free coenzyme A, a component present at high concentrations in luciferase detection reagents used for cell-based assays. This explains why PTC124 can appear to increase, instead of inhibit, FLuc activity in cell-based reporter gene assays. To our knowledge, this is an unusual example in which the "off-target" effect of a small molecule is mediated by an MAI mechanism.
C1 [Auld, Douglas S.; Thorne, Natasha; Lea, Wendy A.; Maloney, David J.; Shen, Min; Rai, Ganesha; Thomas, Craig J.; Simeonov, Anton; Inglese, James] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Lovell, Scott; Hanzlik, Robert P.] Univ Kansas, Struct Biol Ctr, Lawrence, KS 66047 USA.
[Battaile, Kevin P.] Argonne Natl Lab, Adv Photon Source, Ind Macromol Crystallog Assoc Collaborat Access T, Argonne, IL 60439 USA.
RP Inglese, J (reprint author), NIH, Chem Genom Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM jinglese@mail.nih.gov
OI Battaile, Kevin/0000-0003-0833-3259
FU Molecular Libraries Initiative of the National Institutes of Health
(NIH) Roadmap for Medical Research; NIH Center of Biomedical Research
[5P20 RR17708]
FX This research was supported by the Molecular Libraries Initiative of the
National Institutes of Health (NIH) Roadmap for Medical Research, and an
NIH Center of Biomedical Research Excellence Award (5P20 RR17708) to the
University of Kansas (KU). We thank Nadya Galeva from the KU Mass
Spectrometry Laboratory for her assistance with the Matrix Assisted
Laser Desorption-Ionization-Mass Spectrometry analysis, and Bill Leister
of the NIH Chemical Genomics Center for analytical chemistry support.
NR 31
TC 89
Z9 93
U1 0
U2 24
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 MAR 16
PY 2010
VL 107
IS 11
BP 4878
EP 4883
DI 10.1073/pnas.0909141107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570YI
UT WOS:000275714300017
PM 20194791
ER
PT J
AU McElhinny, SAN
Watts, BE
Kumar, D
Watt, DL
Lundstrom, EB
Burgers, PMJ
Johansson, E
Chabes, A
Kunkel, TA
AF McElhinny, Stephanie A. Nick
Watts, Brian E.
Kumar, Dinesh
Watt, Danielle L.
Lundstrom, Else-Britt
Burgers, Peter M. J.
Johansson, Erik
Chabes, Andrei
Kunkel, Thomas A.
TI Abundant ribonucleotide incorporation into DNA by yeast replicative
polymerases
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE DNA replication; nucleotide precursors; nucleotide selectivity
ID SACCHAROMYCES-CEREVISIAE; SUBSTRATE-SPECIFICITY; REVERSE-TRANSCRIPTASE;
CRYSTAL-STRUCTURE; RESIDUE; EPSILON; REPAIR; FIDELITY; DAMAGE; SUGAR
AB Measurements of nucleoside triphosphate levels in Saccharomyces cerevisiae reveal that the four rNTPs are in 36- to 190-fold molar excess over their corresponding dNTPs. During DNA synthesis in vitro using the physiological nucleoside triphosphate concentrations, yeast DNA polymerase epsilon, which is implicated in leading strand replication, incorporates one rNMP for every 1,250 dNMPs. Pol delta and Pol alpha, which conduct lagging strand replication, incorporate one rNMP for every 5,000 or 625 dNMPs, respectively. Discrimination against rNMP incorporation varies widely, in some cases by more than 100-fold, depending on the identity of the base and the template sequence context in which it is located. Given estimates of the amount of replication catalyzed by Pols alpha, delta, and epsilon, the results are consistent with the possibility that more than 10,000 rNMPs may be incorporated into the nuclear genome during each round of replication in yeast. Thus, rNMPs may be the most common noncanonical nucleotides introduced into the eukaryotic genome. Potential beneficial and negative consequences of abundant ribonucleotide incorporation into DNA are discussed, including the possibility that unrepaired rNMPs in DNA could be problematic because yeast DNA polymerase epsilon has difficulty bypassing a single rNMP present within a DNA template.
C1 [McElhinny, Stephanie A. Nick; Watts, Brian E.; Watt, Danielle L.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[McElhinny, Stephanie A. Nick; Watts, Brian E.; Watt, Danielle L.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Kumar, Dinesh; Lundstrom, Else-Britt; Johansson, Erik; Chabes, Andrei] Umea Univ, Dept Med Biochem & Biophys, SE-90187 Umea, Sweden.
[Burgers, Peter M. J.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
[Chabes, Andrei] Umea Univ, Lab Mol Infect Med Sweden MIMS, SE-90187 Umea, Sweden.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
OI Chabes, Andrei/0000-0003-1708-8259
FU National Institutes of Health, National Institute on Environmental
Health Sciences [Z01 ES065070]; Swedish Foundation for Strategic
Research; Swedish Research Council; Swedish Cancer Society; Swedish
Cancer Society, Smartafonden; Basic Science-oriented Biotechnology,
Medical Faculty of Umea University; National Institutes of Health
[GM032431]
FX We thank A. Clark and M. Murray for helpful comments on the manuscript.
This work was supported in part by Project Z01 ES065070 ( to T. A. K.)
from the Division of Intramural Research of the National Institutes of
Health, National Institute on Environmental Health Sciences; by the
Swedish Foundation for Strategic Research, the Swedish Research Council
and the Swedish Cancer Society ( to A. C.); by the Swedish Research
Council, the Swedish Cancer Society, Smartafonden and the fund for Basic
Science-oriented Biotechnology, Medical Faculty of Umea University ( to
E.J.); and by National Institutes of Health Grant GM032431 ( to P. M.
B.).
NR 50
TC 154
Z9 155
U1 1
U2 15
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 MAR 16
PY 2010
VL 107
IS 11
BP 4949
EP 4954
DI 10.1073/pnas.0914857107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570YI
UT WOS:000275714300029
ER
PT J
AU Dail, M
Li, Q
McDaniel, A
Wong, J
Akagi, K
Huang, B
Kang, HC
Kogan, SC
Shokat, K
Wolff, L
Braun, BS
Shannon, K
AF Dail, Monique
Li, Qing
McDaniel, Andrew
Wong, Jason
Akagi, Keiko
Huang, Ben
Kang, Hio Chung
Kogan, Scott C.
Shokat, Kevan
Wolff, Linda
Braun, Benjamin S.
Shannon, Kevin
TI Mutant Ikzf1, Kras(G12D), and Notch1 cooperate in T lineage
leukemogenesis and modulate responses to targeted agents
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE K-ras; retroviral insertional mutagenesis; T cell leukemia; targeted
therapeutics; Ikaros
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; PROVIRUS INSERTIONAL MUTAGENESIS; K-RAS;
CELL LEUKEMOGENESIS; MOLECULAR-GENETICS; SOMATIC ACTIVATION; TRANSGENIC
MICE; ONCOGENIC KRAS; C-MYC; MUTATIONS
AB Mice that accurately model the genetic diversity found in human cancer are valuable tools for interrogating disease mechanisms and investigating novel therapeutic strategies. We performed insertional mutagenesis with the MOL4070LTR retrovirus in Mx1-Cre, Kras(G12D) mice and generated a large cohort of T lineage acute lymphoblastic leukemias (T-ALLs). Molecular analysis infers that retroviral integration within Ikzf1 is an early event in leukemogenesis that precedes KrasG12D expression and later acquisition of somatic Notch1 mutations. Importantly, biochemical analysis uncovered unexpected heterogeneity, which suggests that Ras signaling networks are remodeled during multistep tumorigenesis. We tested tumor-derived cell lines to identify biomarkers of therapeutic response to targeted inhibitors. Whereas all T-ALLs tested were sensitive to a dual-specificity phosphoinosityl 3-kinase/mammalian target of rapamycin inhibitor, biochemical evidence of Notch1 activation correlated with sensitivity to gamma-secretase inhibition. In addition, Kras(G12D) T-ALLs were more responsive to a MAP/ERK kinase inhibitor in vitro and in vivo. Together, these studies identify a genetic pathway involving Ikzf1, Kras(G12D), and Notch1 in T lineage leukemogenesis, reveal unexpected diversity in Ras-regulated signaling networks, and define biomarkers of drug responses that may inform treatment strategies.
C1 [Dail, Monique; McDaniel, Andrew; Wong, Jason; Huang, Ben; Kang, Hio Chung; Braun, Benjamin S.; Shannon, Kevin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Li, Qing] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Kogan, Scott C.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Shokat, Kevan] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA.
[Akagi, Keiko] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Wolff, Linda] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
RP Shannon, K (reprint author), Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
EM shannonk@peds.ucsf.edu
FU National Institutes of Health [U01 CA84221, R37 CA72614, K08 CA119105];
Leukemia and Lymphoma Society of America [7019-04]; William Lawrence and
Blanche Hughes Foundation; Jeffrey and Karen Peterson Family Foundation;
Frank A. Campini Foundation; LLSA
FX We thank Judith Leopold (Pfizer) for providing PD0325901 and David
Tuveson and Tyler Jacks for providing KrasG12D mice; Charles Mullighan
for the Murine Stem Cell Virus Ik6 construct and for helpful comments
and suggestions; Jon Aster and Michelle Hermison for insightful
comments; and Michelle Kang for technical guidance. This work was
supported by National Institutes of Health Grants U01 CA84221, R37
CA72614, and K08 CA119105, by a Specialized Center of Research award
from the Leukemia and Lymphoma Society of America (LLSA 7019-04), by the
William Lawrence and Blanche Hughes Foundation, the Jeffrey and Karen
Peterson Family Foundation, and by the Frank A. Campini Foundation. S.
C. K. is an LLSA Scholar, and M. D. is a supported by an LLSA
Fellowship. The Intramural Research Program of the National Cancer
Institute Center for Cancer Research supports research in the laboratory
of L. W. at the National Institutes of Health.
NR 41
TC 30
Z9 32
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 16
PY 2010
VL 107
IS 11
BP 5106
EP 5111
DI 10.1073/pnas.1001064107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570YI
UT WOS:000275714300056
PM 20194733
ER
PT J
AU Lee, J
Shmueli, K
Fukunaga, M
van Gelderen, P
Merkle, H
Silva, AC
Duyn, JH
AF Lee, Jongho
Shmueli, Karin
Fukunaga, Masaki
van Gelderen, Peter
Merkle, Hellmut
Silva, Afonso C.
Duyn, Jeff H.
TI Sensitivity of MRI resonance frequency to the orientation of brain
tissue microstructure
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE MRI phase contrast; resonance frequency shift; anisotropic
susceptibility; magnetic susceptibility tensor; white matter fiber
tracking
ID HIGH-FIELD MRI; IN-VIVO; MAGNETIC-SUSCEPTIBILITY; WHITE-MATTER; LECITHIN
MEMBRANES; PHASE-CONTRAST; ANISOTROPY; RELAXATION; PROTEINS; BILAYERS
AB Recent advances in high-field (>= 7 T) MRI have made it possible to study the fine structure of the human brain at the level of fiber bundles and cortical layers. In particular, techniques aimed at detecting MRI resonance frequency shifts originating from local variation in magnetic susceptibility and other sources have greatly improved the visualization of these structures. A recent theoretical study [He X, Yablonskiy DA (2009) Proc Natl Acad Sci USA 106:13558-13563] suggests that MRI resonance frequency may report not only on tissue composition, but also on microscopic compartmentalization of susceptibility inclusions and their orientation relative to the magnetic field. The proposed sensitivity to tissue structure may greatly expand the information available with conventional MRI techniques. To investigate this possibility, we studied postmortem tissue samples from human corpus callosum with an experimental design that allowed separation of microstructural effects from confounding macrostructural effects. The results show that MRI resonance frequency does depend on microstructural orientation. Furthermore, the spatial distribution of the resonance frequency shift suggests an origin related to anisotropic susceptibility effects rather than microscopic compartmentalization. This anisotropy, which has been shown to depend on molecular ordering, may provide valuable information about tissue molecular structure.
C1 [Lee, Jongho; Shmueli, Karin; Fukunaga, Masaki; van Gelderen, Peter; Merkle, Hellmut; Duyn, Jeff H.] NINDS, Adv MRI Sect, NIH, Bethesda, MD 20892 USA.
[Silva, Afonso C.] NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Lee, J (reprint author), NINDS, Adv MRI Sect, NIH, Bethesda, MD 20892 USA.
EM jonghoyi@mail.nih.gov
RI Duyn, Jozef/F-2483-2010; Silva, Afonso/A-7129-2009; Fukunaga,
Masaki/F-6441-2013; Shmueli, Karin/B-9432-2017
OI Fukunaga, Masaki/0000-0003-1010-2644;
FU National Institutes of Health; National Institute of Neurological
Disorders and Stroke
FX We thank Dr. Ara Kocharyan and Dr. Kant M. Matsuda for tissue
preparation. This research was supported by the Intramural Research
Program of the National Institutes of Health, National Institute of
Neurological Disorders and Stroke.
NR 40
TC 108
Z9 110
U1 0
U2 13
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 MAR 16
PY 2010
VL 107
IS 11
BP 5130
EP 5135
DI 10.1073/pnas.0910222107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570YI
UT WOS:000275714300060
PM 20202922
ER
PT J
AU Reimann, F
Cox, JJ
Belfer, I
Diatchenko, L
Zaykin, DV
McHale, DP
Drenth, JPH
Dai, F
Wheeler, J
Sanders, F
Wood, L
Wu, TX
Karppinen, J
Nikolajsen, L
Mannikko, M
Max, MB
Kiselycznyk, C
Poddar, M
Morsche, RHMT
Smith, S
Gibson, D
Kelempisioti, A
Maixner, W
Gribble, FM
Woods, CG
AF Reimann, Frank
Cox, James J.
Belfer, Inna
Diatchenko, Luda
Zaykin, Dmitri V.
McHale, Duncan P.
Drenth, Joost P. H.
Dai, Feng
Wheeler, Jerry
Sanders, Frances
Wood, Linda
Wu, Tian-Xia
Karppinen, Jaro
Nikolajsen, Lone
Mannikko, Minna
Max, Mitchell B.
Kiselycznyk, Carly
Poddar, Minakshi
Morsche, Rene H. M. Te
Smith, Shad
Gibson, Dustin
Kelempisioti, Anthi
Maixner, William
Gribble, Fiona M.
Woods, C. Geoffrey
TI Pain perception is altered by a nucleotide polymorphism in SCN9A
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Na(v)1.7; nociception; pain; SCN9A; single nucleotide polymorphisms
ID CHANNEL ALPHA-SUBUNIT; OF-FUNCTION MUTATIONS; SODIUM-CHANNEL; PRIMARY
ERYTHERMALGIA; ERYTHROMELALGIA; DISORDER; SENSITIVITY; NOCICEPTION;
MANAGEMENT
AB The gene SCN9A is responsible for three human pain disorders. Nonsense mutations cause a complete absence of pain, whereas activating mutations cause severe episodic pain in paroxysmal extreme pain disorder and primary erythermalgia. This led us to investigate whether single nucleotide polymorphisms (SNPs) in SCN9A were associated with differing pain perception in the general population. We first genotyped 27 SCN9A SNPs in 578 individuals with a radiographic diagnosis of osteoarthritis and a pain score assessment. A significant association was found between pain score and SNP rs6746030; the rarer A allele was associated with increased pain scores compared to the commoner G allele (P = 0.016). This SNP was then further genotyped in 195 pain-assessed people with sciatica, 100 amputees with phantom pain, 179 individuals after lumbar discectomy, and 205 individuals with pancreatitis. The combined P value for increased A allele pain was 0.0001 in the five cohorts tested (1277 people in total). The two alleles of the SNP rs6746030 alter the coding sequence of the sodium channel Nav1.7. Each was separately transfected into HEK293 cells and electrophysiologically assessed by patch-clamping. The two alleles showed a difference in the voltage-dependent slow inactivation (P = 0.042) where the Aallele would be predicted to increase Nav1.7 activity. Finally, we genotyped 186 healthy females characterized by their responses to a diverse set of noxious stimuli. The A allele of rs6746030 was associated with an altered pain threshold and the effect mediated through C-fiber activation. We conclude that individuals experience differing amounts of pain, per nociceptive stimulus, on the basis of their SCN9A rs6746030 genotype.
C1 [Reimann, Frank; Gribble, Fiona M.] Addenbrookes Hosp, Cambridge Inst Med Res, Dept Clin Biochem, Cambridge CB2 0XY, England.
[Cox, James J.; Woods, C. Geoffrey] Addenbrookes Hosp, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 0XY, England.
[Belfer, Inna; Dai, Feng; Max, Mitchell B.; Poddar, Minakshi] Univ Pittsburgh, Dept Anaesthesiol, Mol Epidemiol Pain Program, Pittsburgh, PA 15261 USA.
[Diatchenko, Luda; Smith, Shad; Gibson, Dustin; Maixner, William] Univ N Carolina, Sch Dent, Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA.
[Zaykin, Dmitri V.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[McHale, Duncan P.; Wheeler, Jerry; Sanders, Frances] Pfizer Global Res & Dev, Sandwich Labs, Sandwich CT13 9NJ, Kent, England.
[Drenth, Joost P. H.; Morsche, Rene H. M. Te] Radboud Univ Nijmegen, Ctr Med, Dept Gastroenterol & Hepatol, NL-6500 HB Nijmegen, Netherlands.
[Dai, Feng] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA.
[Dai, Feng] Univ Pittsburgh, Sch Med, Dept Biostat & Human Genet, Pittsburgh, PA 15261 USA.
[Wood, Linda] Pfizer Global Res & Dev, Groton Labs, Groton, CT 06340 USA.
[Wu, Tian-Xia; Kiselycznyk, Carly] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Karppinen, Jaro; Mannikko, Minna; Kelempisioti, Anthi] Univ Oulu, Oulu Ctr Cell Matrix Res, Bioctr, FIN-90014 Oulu, Finland.
[Karppinen, Jaro; Mannikko, Minna; Kelempisioti, Anthi] Univ Oulu, Dept Med Biochem & Mol Biol, FIN-90014 Oulu, Finland.
[Nikolajsen, Lone] Univ Oulu, Finnish Inst Occupat Hlth, Musculoskeletal Ctr, FI-90220 Oulu, Finland.
[Nikolajsen, Lone] Univ Oulu, Dept Phys Med & Rehabil, Inst Clin Sci, FI-90220 Oulu, Finland.
RP Gribble, FM (reprint author), Addenbrookes Hosp, Cambridge Inst Med Res, Dept Clin Biochem, Cambridge CB2 0XY, England.
EM fmg23@cam.ac.uk; cw347@cam.ac.uk
RI woods, christopher/A-1361-2010; Drenth, J.P.H./H-8025-2014; te Morsche,
Rene/P-9143-2015; Cox, James/R-1910-2016;
OI Gibson, Dustin/0000-0002-9073-3376
FU National Institutes of Health; National Institute of Environmental
Health Sciences; Wellcome Trust; Pfizer
FX We thank Adeline Nicholas, Gemma Thornton, Baljinder Matharu, and John
Yates for help in preparing this manuscript. We also thank Steven J.
Atlas and Robert B. Keller, the principal clinical investigators of the
Maine Lumbar Spine Study, for allowing us to investigate their patients;
and Monique H. M. Derikx for clinical data collection. St John's College
in Cambridge, United Kingdom, the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences, the Wellcome Trust, and Pfizer contributed to the
funding of this project.
NR 34
TC 132
Z9 137
U1 2
U2 28
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 MAR 16
PY 2010
VL 107
IS 11
BP 5148
EP 5153
DI 10.1073/pnas.0913181107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 570YI
UT WOS:000275714300062
PM 20212137
ER
PT J
AU Anstrom, KJ
Kaner, RJ
Loyd, JE
Roman, J
Brown, KK
King, TE
Lasky, JA
Martinez, FJ
Noth, I
Deandrade, J
Raghu, G
Ryu, JH
Lynch, JP
Hunninghake, GW
Reynolds, HY
AF Anstrom, Kevin J.
Kaner, Robert J.
Loyd, James E.
Roman, Jesse
Brown, Kevin K.
King, Talmadge E., Jr.
Lasky, Joseph A.
Martinez, Fernando J.
Noth, Imre
Deandrade, Joao
Raghu, Ganesh
Ryu, Jay H.
Lynch, Joseph P., III
Hunninghake, Gary W.
Reynolds, Herbert Y.
CA IPFnet Investigators
TI The IPFnet Strategy Creating a Comprehensive Approach in the Treatment
of Idiopathic Pulmonary Fibrosis
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID LUNG; TELOMERASE; MUTATIONS; ORIGIN; CELLS
C1 [Anstrom, Kevin J.] Duke Univ, Durham, NC 27706 USA.
[Kaner, Robert J.] Weill Cornell Med Coll, New York, NY USA.
[Loyd, James E.] Vanderbilt Univ, Nashville, TN USA.
[Roman, Jesse] Univ Louisville, Louisville, KY 40292 USA.
[Brown, Kevin K.] Natl Jewish Med & Res Ctr, Denver, CO USA.
[King, Talmadge E., Jr.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Lasky, Joseph A.] Tulane Univ, New Orleans, LA 70118 USA.
[Martinez, Fernando J.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Noth, Imre] Univ Chicago, Chicago, IL 60637 USA.
[Deandrade, Joao] Univ Alabama, Birmingham, AL USA.
[Raghu, Ganesh] Univ Washington, Seattle, WA 98195 USA.
[Ryu, Jay H.] Mayo Clin, Rochester, MN USA.
[Lynch, Joseph P., III] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Hunninghake, Gary W.] Univ Iowa, Iowa City, IA USA.
[Reynolds, Herbert Y.] NHLBI, Bethesda, MD 20892 USA.
RP Anstrom, KJ (reprint author), Duke Univ, Durham, NC 27706 USA.
NR 14
TC 5
Z9 5
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD MAR 15
PY 2010
VL 181
IS 6
BP 527
EP 528
DI 10.1164/rccm.200903-0483ED
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 632RX
UT WOS:000280446500001
ER
PT J
AU Mularski, RA
Campbell, ML
Asch, SM
Reeve, BB
Basch, E
Maxwell, TL
Hoverman, JR
Cuny, J
Clauser, SB
Snyder, C
Seow, H
Wu, AW
Dy, S
AF Mularski, Richard A.
Campbell, Margaret L.
Asch, Steven M.
Reeve, Bryce B.
Basch, Ethan
Maxwell, Terri L.
Hoverman, J. Russell
Cuny, Joanne
Clauser, Steve B.
Snyder, Claire
Seow, Hsien
Wu, Albert W.
Dy, Sydney
TI A Review of Quality of Care Evaluation for the Palliation of Dyspnea
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE dyspnea; quality of health care; quality indicators; health care;
assessment
ID CLINICAL METHODS; LIFE CARE; DISEASE; BREATHLESSNESS; QUESTIONNAIRE;
END; INDICATORS; CANCER; DESCRIPTORS; SHORTNESS
AB Assessment and management of dyspnea has emerged as a priority topic for quality evaluation and improvement. Evaluating dyspnea quality of care requires valid, reliable, and responsive measures of the care provided to patients across settings and diseases. As part of an Agency for Healthcare Research and Quality Symposium, we reviewed quality of care measures for dyspnea by compiling quality measures identified in systematic searches and reviews. Systematic reviews identified only three existing quality measurement sets that included quality measures for dyspnea care. The existing dyspnea quality measures reported by retrospective evaluations of care assess only four aspects: dyspnea assessment within 48 hours of hospital admission, use of objective scales to rate dyspnea severity, identification of management plans, and evidence of dyspnea reduction. To begin to improve care, clinicians need to assess and regularly document patient's experiences of dyspnea. There is no consensus on how dyspnea should be characterized for quality measurement, and although over 40 tools exist to assess dyspnea, no rating scale or instrument is ideal for palliative care. The panel recommended that dyspnea assessment should include a measure of intensity and some inquiry into the associated bother or distress experienced by the patient. A simple question into the presence or absence of dyspnea would be unlikely to help guide therapy, as complete relief of dyspnea in advanced disease would not be anticipated. Additional knowledge gaps include standards for clinical dyspnea care, assessment in the cognitively impaired, and evaluation of effectiveness of dyspnea care for patients with advanced disease.
C1 [Mularski, Richard A.] Oregon Hlth & Sci Univ, Ctr Hlth Res, Portland, OR 97227 USA.
[Campbell, Margaret L.] Wayne State Univ, Detroit Receiving Hosp Ctr Hlth Res, Detroit, MI USA.
[Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA.
[Reeve, Bryce B.; Clauser, Steve B.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Basch, Ethan] Mem Sloan Kettering Canc Ctr, Hlth Outcomes Grp, New York, NY 10021 USA.
[Maxwell, Terri L.] ExcelleRx Inc, Philadelphia, PA USA.
[Hoverman, J. Russell] Texas Oncol, Dallas, TX USA.
[Cuny, Joanne] Univ HealthSyst Consortium, Oak Brook, IL USA.
[Snyder, Claire; Dy, Sydney] Johns Hopkins Sch Publ Hlth, Dept Hlth Policy & Management, Johns Hopkins Sch Med, Div Gen Internal Med, Baltimore, MD USA.
[Seow, Hsien] McMaster Univ, Dept Oncol, Hamilton, ON, Canada.
RP Mularski, RA (reprint author), Oregon Hlth & Sci Univ, Ctr Hlth Res, 3800 N Interstate,WIN 1060, Portland, OR 97227 USA.
EM Richard.A.Mularski@kpchr.org
OI Campbell, Margaret/0000-0003-4517-690X
FU Agency for Healthcare Research and Quality, U.S. Department of Health
and Human Services [290-2005-00341]; Spiration, Inc.; Novartis; Amgen;
Wyeth Pharmaceuticals; United Healthcare
FX Supported by Contract No. 290-2005-00341 from the Agency for Healthcare
Research and Quality, U.S. Department of Health and Human Services as
part of the Developing Evidence to Inform Decisions about Effectiveness
(DEcIDE) program. The Symposium on Developing a Framework to Assess
Cancer Quality Indicators for End-of-Life Care was held in Baltimore, MD
on April 28, 2008. The authors of this manuscript are responsible for
its content. Statements in the manuscript should not be construed as
endorsement by the Agency for Healthcare Research and Quality or the
U.S. Department of Health and Human Services.; R.A.M. received
850,001-$100,000 from Spiration, Inc., and 850,001-8100,001 from
Novartis in industry-sponsored grants. M.L.C. does not have a financial
relationship with a commercial entity that has an interest in the
subject of this manuscript. S.M.A. received more than 8100,001 from
Amgen in grants. B.B.R. does not have a financial relationship with a
commercial entity that has an interest in the subject of this
manuscript. E.B. does not have a financial relationship with a
commercial entity that has an interest in the subject of this
manuscript. T.L.M. is a full-time employee of excelleRx, Inc., and
received S10,001-850,000 from Wyeth Pharmaceuticals in
industry-sponsored grants for database analysis related to constipation
prevalence at the end of life. J.R.H. received $1,001-85,000 from United
Healthcare in advisory board fees. j.C. does not have a financial
relationship with a commercial entity that has an interest in the
subject of this manuscript. S.B.C. does not have a financial
relationship with a commercial entity that has an interest in the
subject of this manuscript. C.S. does not have a financial relationship
with a commercial I. entity that has an interest in the subject of this
manuscript. H.S. does not
NR 50
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U1 1
U2 3
PU AMER THORACIC SOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD MAR 15
PY 2010
VL 181
IS 6
BP 534
EP 538
DI 10.1164/rccm.200903-0462PP
PG 5
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 632RX
UT WOS:000280446500005
PM 20056904
ER
PT J
AU Wang, PY
Rao, JN
Zou, TT
Liu, L
Xiao, L
Yu, TX
Turner, DJ
Gorospe, M
Wang, JY
AF Wang, Peng-Yuan
Rao, Jaladanki N.
Zou, Tongtong
Liu, Lan
Xiao, Lan
Yu, Ting-Xi
Turner, Douglas J.
Gorospe, Myriam
Wang, Jian-Ying
TI Post-transcriptional regulation of MEK-1 by polyamines through the
RNA-binding protein HuR modulating intestinal epithelial apoptosis
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE mitogen-activated protein kinase kinase-1 (MEK-1); mRNA stability;
ornithine decarboxylase; polyamine; ribonucleoprotein; translational
regulation; 3 '-untranslated region (3 '-UTR)
ID AU-RICH ELEMENTS; MESSENGER-RNA; BARRIER FUNCTION; GENE-EXPRESSION;
HEAT-SHOCK; CELLS; KINASE; PHOSPHORYLATION; DEPLETION; STABILIZATION
AB MEK-1 [MAPK (mitogen-activated protein kinase) kinase-1] is all important signal transducing enzyme that is implicated ill many aspects Of Cellular functions. In the present paper, we report that cellular polyamines regulate MEK-1 expression at the post-transcriptional level through the RNA-binding protein HuR (Hu-antigen R) in IECs (intestinal epithelial cells). Decreasing the levels of cellular polyamines by inhibiting ODC (ornithine decarboxylase) stabilized MEK-1 mRNA and promoted its translation through enhancement of the interaction between HuR and the 3'-untranslated region of MEK-1 mRNA, whereas increasing polyamine levels by ectopic ODC overexpression destabilized the MEK-1 transcript and repressed its translation by reducing the abundance of HuR-MEK-1 mRNA complex, neither intervention changed MEK-1 gene transcription via its promoter. HuR silencing rendered the MEK-1 mRNA unstable and inhibited its translation, thus preventing increases in MEK-1 mRNA and protein in polyamine-deficient cells. Conversely, HuR overexpression increased MEK-1 mRNA stability and promoted its translation. Inhibition of Mill expression by MEK-1 silencing or HuR silencing prevented the increased resistance of polyamine-deficient cells to apoptosis. Moreover. HuR overexpression did not protect against apoptosis if MEK-1 expression vas silenced. These results indicate that polyamines destabilize the Mill mRNA and repress its translation by inhibiting the association between HuR and the MEK-1 transcript. Our findings indicate that MEK-1 is a key effector of the HuR-elicited anti-apoptotic programme in IECs.
C1 [Wang, Peng-Yuan; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Xiao, Lan; Yu, Ting-Xi; Turner, Douglas J.; Wang, Jian-Ying] Univ Maryland, Sch Med, Cell Biol Grp, Dept Surg, Baltimore, MD 21201 USA.
[Wang, Peng-Yuan; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Yu, Ting-Xi; Turner, Douglas J.] Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA.
[Xiao, Lan; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Wang, JY (reprint author), Univ Maryland, Sch Med, Cell Biol Grp, Dept Surg, Baltimore, MD 21201 USA.
EM jwang@smail.umaryland.edu
FU Department of Veterans Affairs, U.S.A.; National Institutes of Health
[DK-57819, DK-61972, DK-68461]; National Institute on Aging
FX This work was supported by the Department of Veterans Affairs, U.S.A.
[Merit Review Grant (to J.-Y W.)] the National Institutes of Health
[grant numbers DK-57819, DK-61972 and DK-68461 (to J.-Y. W.)]. P.-YW. is
a visiting scientist from Peking University First Hospital, Beijing,
China J.-Y. W. is a Research Career Scientist, Medical Research Service,
Department of Veterans Affairs. M. G. is supported by the National
Institute on Aging Intramural Research Program.
NR 59
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Z9 29
U1 0
U2 0
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0264-6021
J9 BIOCHEM J
JI Biochem. J.
PD MAR 15
PY 2010
VL 426
BP 293
EP 306
DI 10.1042/BJ20091459
PN 3
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 572OU
UT WOS:000275843300005
PM 20001965
ER
PT J
AU Gao, ZG
Ding, Y
Jacobson, KA
AF Gao, Zhan-Guo
Ding, Yi
Jacobson, Kenneth A.
TI UDP-glucose acting at P2Y(14) receptors is a mediator of mast cell
degranulation
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Nucleotide; P2Y receptor; Mast cell; Allergy; Inflammation; G
protein-coupled receptor
ID PROTEIN-COUPLED RECEPTOR; A(3) ADENOSINE RECEPTOR; FUNCTIONAL
EXPRESSION; DENDRITIC CELLS; LEUKEMIA-CELLS; P2Y14 RECEPTOR; ACTIVATION;
RELEASE; MECHANISMS; ENHANCEMENT
AB UDP-glucose (UDPG), a glycosyl donor in the biosynthesis of carbohydrates, is an endogenous agonist of the G protein-coupled P2Y(14) receptor. RBL-2H3 mast cells endogenously express a P2Y(14) receptor at which UDPG mediates degranulation as indicated by beta-hexosaminidase (HEX) release. Both UDPG and a more potent, selective 2-thio-modified UDPG analog, MRS2690 (diphosphoric acid 1-alpha-D-glucopyranosyl ester 2-[(2-thio)uridin-5 ''-yl] ester), caused a substantial calcium transient in RBL-2H3 cells, which was blocked by pertussis toxin, indicating the presence of the G(i)-coupled P2Y(14) receptor, supported also by quantitative detection of abundant mRNA. Expression of the closely related P2Y(6) receptor was over 100 times lower than the P2Y(14) receptor, and the P2Y(6) agonist 3-phenacyl-UDP was inactive in RBL-2H3 cells. P2Y(14) receptor agonists also induced [S-35]GTP gamma S binding to RBL-2H3 cell membranes, and phosphorylation of ERK1/2, P38 and JNK. UDPG and MRS2690 concentration-dependently enhanced HEX release with EC50 values of 1150 +/- 320 and 103 +/- 18 nM, respectively. The enhancement was completely blocked by pertussis toxin and significantly diminished by P2Y(14) receptor-specific siRNA. Thus, mast cells express an endogenous P2Y(14) receptor, which mediates G(i)-dependent degranulation and is therefore a potential novel therapeutic target for allergic conditions. Published by Elsevier Inc.
C1 [Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
[Ding, Yi] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Gao, ZG (reprint author), NIDDK, Mol Recognit Sect, NIH, LBC, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM ZhanguoG@niddk.nih.gov; kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU National Institutes of Health
FX Supported by the NIDDK Intramural Research Program, National Institutes
of Health.
NR 33
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U1 1
U2 6
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 MAR 15
PY 2010
VL 79
IS 6
BP 873
EP 879
DI 10.1016/j.bcp.2009.10.024
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 550WZ
UT WOS:000274165500008
PM 19896471
ER
PT J
AU Das, U
Doroudi, A
Gul, HI
Pati, HN
Kawase, M
Sakagami, H
Chu, Q
Stables, JP
Dimmock, JR
AF Das, Umashankar
Doroudi, Alireza
Gul, H. Inci
Pati, Hari N.
Kawase, Masami
Sakagami, Hiroshi
Chu, Qing
Stables, James P.
Dimmock, Jonathan R.
TI Cytotoxic 2-benzylidene-6-(nitrobenzylidene)cyclohexanones which display
substantially greater toxicity for neoplasms than non-malignant cells
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Unsaturated ketones; Selective cytotoxicity; Structure-activity
relationships; Murine toxicity
ID MANNICH-BASES; MULTIDRUG-RESISTANCE; SELECTIVE TOXICITY; STYRYL KETONES;
REVERSAL; GLUTATHIONE; ANTITUMOR
AB Various 2-benzylidene-6-(nitrobenzylidene)cyclohexanones were prepared as candidate cytotoxins in which the nitro group was located in the ortho, meta and para positions leading to series 1-3, respectively. The CC(50) values towards human HSC-2 and HSC-4 oral squamous cell carcinomas as well as human HL-60 promyelocytic leukemic cells are in the low micromolar range in general. On the other hand, most of the compounds afforded clear evidence of being far less toxic towards human HGF gingival fibroblasts, HPC pulp cells and HPLF periodontal ligament. broblasts which are non-malignant cells. Selectivity index (SI) figures were generated which are the ratios of the average CC(50) values towards normal cells and the CC(50) figure towards a malignant cell line. Huge SI values were obtained for many of the compounds. In particular 1c, 2f, 3c and 3g which have average SI values of >76, >38, 124 and 341, respectively, are clearly lead molecules affording direction for amplification of this area of study. A lead compound 1c caused internucleosomal DNA fragmentation and activation of caspase-3 in HL-60 cells but not in HSC-2 carcinomas. In a short-term toxicity study, doses up to and including 300 mg/kg of the majority of the compounds prepared in this study did not cause any mortalities to mice. Some guidelines for development of these tumor-selective cytotoxins are presented. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Das, Umashankar; Doroudi, Alireza; Gul, H. Inci; Pati, Hari N.; Dimmock, Jonathan R.] Univ Saskatchewan, Drug Design & Discovery Res Grp, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada.
[Kawase, Masami] Matsuyama Univ, Fac Pharmaceut Sci, Maysuyama, Ehime 7908578, Japan.
[Sakagami, Hiroshi; Chu, Qing] Meikai Univ, Sch Dent, Div Pharmacol, Dept Diagnost & Therapeut Sci, Saitama 3500238, Japan.
[Stables, James P.] Natl Inst Neurol Disorders & Stroke, Rockville, MD 20852 USA.
RP Dimmock, JR (reprint author), Univ Saskatchewan, Drug Design & Discovery Res Grp, Coll Pharm & Nutr, 110 Sci Pl, Saskatoon, SK S7N 5C9, Canada.
EM jr.dimmock@usask.ca
FU Canadian Institutes of Health Research; Ministry of Education, Science,
Sports and Culture of Japan [19592156]; National Institute of
Neurological Disorders and Stroke, USA; Iranian Ministry of Health and
Medical Education; Scientific and Technical Research Council of Turkey
(TUBITAK) [NATO-B2]
FX The authors thank the Canadian Institutes of Health Research for an
operating grant to J. R. Dimmock and the Ministry of Education, Science,
Sports and Culture of Japan for a Grant-in-Aid (No. 19592156) to H.
Sakagami. The National Institute of Neurological Disorders and Stroke,
USA undertook the in vivo experimentation with mice which is recorded
with gratitude. Our appreciation is extended to the Iranian Ministry of
Health and Medical Education who provided financial support for A.
Doroudi while H. I. Gul was supported by a visiting scholar grant
(NATO-B2) distributed by the Scientific and Technical Research Council
of Turkey (TUBITAK).
NR 27
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U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD MAR 15
PY 2010
VL 18
IS 6
BP 2219
EP 2224
DI 10.1016/j.bmc.2010.01.069
PG 6
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 568HR
UT WOS:000275513700018
PM 20189402
ER
PT J
AU Weidlich, IE
Dexheimer, T
Marchand, C
Antony, S
Pommier, Y
Nicklaus, MC
AF Weidlich, Iwona E.
Dexheimer, Thomas
Marchand, Christophe
Antony, Smitha
Pommier, Yves
Nicklaus, Marc C.
TI Inhibitors of human tyrosyl-DNA phospodiesterase (hTdp1) developed by
virtual screening using ligand-based pharmacophores (vol 18, pg 182,
2010)
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Correction
C1 [Weidlich, Iwona E.; Nicklaus, Marc C.] NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA.
[Dexheimer, Thomas; Marchand, Christophe; Antony, Smitha; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA.
RP Nicklaus, MC (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA.
EM iweidlic@helix.nih.gov; mn1@helix.nih.gov
RI Nicklaus, Marc/N-4183-2014
NR 1
TC 2
Z9 2
U1 1
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD MAR 15
PY 2010
VL 18
IS 6
BP 2346
EP 2346
DI 10.1016/j.bmc.2010.02.008
PG 1
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 568HR
UT WOS:000275513700031
ER
PT J
AU Jagadeeswaran, P
Lin, S
Weinstein, B
Hutson, A
Kim, S
AF Jagadeeswaran, Pudur
Lin, Shuo
Weinstein, Brant
Hutson, Angela
Kim, Seongcheol
TI Loss of GATA1 and gain of FLI1 expression during thrombocyte maturation
SO BLOOD CELLS MOLECULES AND DISEASES
LA English
DT Article
DE Zebrafish; Thrombocyte; Transcription; Maturation; GFP; FLI1; GATA1
ID ZEBRAFISH THROMBOCYTES; TRANSGENIC ZEBRAFISH; FAMILY; GENE
AB In this paper, we characterized expression of GATA1 and FLI1 gene promoters in thrombocytes of zebrafish transgenic lines, G1-GM2 and TG(fli1:EGFP)y1 that carry transgenes of GATA1 and FLI1 gene promoters driving GFR We found two discrete populations of thrombocytes verified by morphology, labeled with GFP in both G1-GM2 and TG(fli1:EGFP)y1 lines: (1) the more intensely labeled GFP+ thrombocyte. and (2) the less intensely labeled GFP+ thrombocytes. The more intensely labeled GFP+ thrombocyte in G1-GM2 line and the less intensely labeled GFP+ thrombocytes in the TG(fli1:EGFP)y1 line corresponded to young thrombocytes. These results showed that young thrombocytes have higher GATA1 promoter activity, while mature thrombocytes have more FLI1 gene promoter transcription. This finding suggests that there is a gradual loss of GATA1 and gain of FLI1 expression as the thrombocytes mature, and this overexpression of FLI1 may help maintain the thrombocyte lineage. Furthermore, the presence of transcriptional factors similar to those found in megakaryocytes raises the possibility that vertebrate thrombocytes may be the forerunners of mammalian megakaryocytes and, therefore, could serve as a model to study megakaryocyte maturation. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Jagadeeswaran, Pudur; Hutson, Angela; Kim, Seongcheol] Univ N Texas, Dept Biol Sci, Denton, TX 76203 USA.
[Lin, Shuo] Univ Calif Los Angeles, Dept Mol Cellular & Dev Biol, Los Angeles, CA 90095 USA.
[Weinstein, Brant] NICD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
RP Jagadeeswaran, P (reprint author), Univ N Texas, Dept Biol Sci, 1510 Chestnut Ave, Denton, TX 76203 USA.
EM jag@unt.edu
FU National Institutes of Health [HL077910]
FX This research was supported by a grant from the National Institutes of
Health, HL077910 (to P.J.).
NR 11
TC 12
Z9 12
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 1079-9796
J9 BLOOD CELL MOL DIS
JI Blood Cells Mol. Dis.
PD MAR 15
PY 2010
VL 44
IS 3
BP 175
EP 180
DI 10.1016/j.bcmd.2009.12.012
PG 6
WC Hematology
SC Hematology
GA 564MC
UT WOS:000275217800010
PM 20110178
ER
PT J
AU Sarosy, GA
Hussain, MM
Seiden, MV
Fuller, AF
Nikrui, N
Goodman, A
Minasian, L
Reed, E
Steinberg, SM
Kohn, EC
AF Sarosy, Gisele A.
Hussain, Mahrukh M.
Seiden, Michael V.
Fuller, Arlan F.
Nikrui, Najmosama
Goodman, Annekathryn
Minasian, Lori
Reed, Eddie
Steinberg, Seth M.
Kohn, Elise C.
TI Ten-Year Follow-Up of a Phase 2 Study of Dose-Intense Paclitaxel With
Cisplatin and Cyclophosphamide as Initial Therapy for Poor-Prognosis,
Advanced-Stage Epithelial Ovarian Cancer
SO CANCER
LA English
DT Article
DE ovarian neoplasms; paclitaxel; cyclophosphamide; cisplatin;
antineoplastic combined chemotherapy protocols; filgrastim; drug
dose-response relation
ID GYNECOLOGIC-ONCOLOGY-GROUP; CARCINOMA CELL-LINES; 1ST-LINE TREATMENT;
IV; PACLITAXEL/CARBOPLATIN; CYTOTOXICITY
AB BACKGROUND: The objective of this study was to assess activity and toxicity in patients with newly diagnosed, advanced-stage epithelial ovarian cancer (EOC) who were receiving dose-intense paclitaxel, cyclophosphamide, cisplatin, and filgrastim delivered with a flexible dosing schedule. METHODS: Patients with stage III/IV EOC received cyclophosphamide 750 mg/m(2), followed by a 24-hour infusion of paclitaxel 250 mg/m(2) and cisplatin 75 mg/m(2) on Day 2. Filgrastim began on Day 3 at 10 mu g/kg daily for 9 days. Patients received 6 cycles of all drugs. Those who achieved a pathologic complete response or had microscopic residual disease at the conclusion of 6 cycles of therapy received an additional 2 to 4 cycles of paclitaxel with cyclophosphamide. Patients who had an objective response continued on cyclophosphamide and paclitaxel. RESULTS: Sixty-two patients were enrolled. Thirty-two of 62 patients had stage IIIC disease, and 26 of 62 patients had stage IV disease. According to an intent-to-treat analysis, 55 patients (89%) experienced a clinical complete remission. At a median potential follow-up of 11.4 years, the median progression-free survival was 18.9 months, and the median survival was 5.4 years. The most serious toxicity was grade 3/4 neutropenic fever (35%). Although all participants developed peripheral neuropathy, improvement in neuropathic symptoms began with the decrease or cessation of paclitaxel. CONCLUSIONS: The studied regimen yielded a high response rate and encouraging overall survival. The current data and those reported by the Japanese Gynecologic Cincology Group suggest that further study is warranted of dose-dense or dose-intense paclitaxel regimens in women with newly diagnosed, advanced-stage EOC. Cancer 2010;116:1476-84. (C) 2070 American Cancer Society.
C1 [Sarosy, Gisele A.; Hussain, Mahrukh M.; Minasian, Lori; Reed, Eddie; Kohn, Elise C.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Seiden, Michael V.] Massachusetts Gen Hosp, Div Canc Biol, Boston, MA 02114 USA.
[Fuller, Arlan F.; Nikrui, Najmosama; Goodman, Annekathryn] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Kohn, EC (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 10 Ctr Dr,MSC 1906, Bethesda, MD 20892 USA.
EM kohne@mail.nih.gov
FU National Institutes of Health; National Cancer Institute, Center for
Cancer Research; Amgen Corporation
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research.
Patient care Support was provided to the Massachusetts General Hospital
investigators from Amgen Corporation.
NR 24
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U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2010
VL 116
IS 6
BP 1476
EP 1484
DI 10.1002/cncr.24861
PG 9
WC Oncology
SC Oncology
GA 564SY
UT WOS:000275238800015
PM 20091841
ER
PT J
AU Freedman, ND
Lacey, JV
Hollenbeck, AR
Leitzmann, MF
Schatzkin, A
Abnet, CC
AF Freedman, Neal D.
Lacey, James V., Jr.
Hollenbeck, Albert R.
Leitzmann, Michael F.
Schatzkin, Arthur
Abnet, Christian C.
TI The Association of Menstrual and Reproductive Factors With Upper
Gastrointestinal Tract Cancers in the NIH-AARP Cohort
SO CANCER
LA English
DT Article
DE head and neck neoplasms; stomach neoplasms; esophageal neoplasms;
estrogen replacement therapy
ID HORMONE-REPLACEMENT THERAPY; CONJUGATED EQUINE ESTROGENS;
GASTRIC-CANCER; POSTMENOPAUSAL WOMEN; RISK-FACTORS; NECK-CANCER;
NATIONAL-INSTITUTES; ENDOMETRIAL CANCER; COLORECTAL-CANCER; ESOPHAGEAL
CANCER
AB BACKGROUND: In most populations, incidence rates of upper gastrointestinal (UGI) tract cancers (head and neck, esophagus, and stomach) are higher among men than among women. Established risk factors do not appear to explain these differences, suggesting a possible role for sex hormones. METHODS: 201,506 women of the NIH-AARP Diet and Health cohort completed a questionnaire in 1995-1996. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models. RESULTS: During follow-up through 2003, 162 incident adenocarcinomas (ACs; esophagus, N = 25, and stomach, N = 137) and 353 incident squamous cell carcinomas (SCCs; head and neck, n = 297, and esophagus, N = 56) occurred. Among examined exposures, older age at menopause was associated inversely with SCC (P(trend) across categories = .013) but not AC (P(trend) = .501). Use of menopausal hormone therapy (MHT) was significantly associated with lower risk of SCC (hazard ratio [HR] = 0.77, 0.62-0.96) and nonsignificantly associated with lower risk of AC (HR = 0.81, 0.59-1.12). A subset (N = 127,386) of the cohort completed a more detailed MHT questionnaire a year after baseline. In 74,372 women with intact uteri, ever use of estrogen-progestin MHT conferred 0.47 (0.30-0.75) times the risk for SCC and 0.52 (0.26-1.07) times the risk for ACC. In 51,515 women with a hysterectomy before baseline, we found no associations between use of estrogen MHT and AC or SCC. CONCLUSIONS: Higher estrogen and progesterone levels may be related inversely to UGI cancers and in this way help explain lower incidence rates in women compared with men. Cancer 2010;116:1572-81. (C) 2070 American Cancer Society.
C1 [Freedman, Neal D.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
[Leitzmann, Michael F.] Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany.
RP Freedman, ND (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS-320,MSC 7232, Rockville, MD 20852 USA.
EM freedmanne@mail.nih.gov
RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015
OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098
FU National Institutes of Health, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute.
NR 34
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U1 3
U2 7
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2010
VL 116
IS 6
BP 1572
EP 1581
DI 10.1002/cncr.24880
PG 10
WC Oncology
SC Oncology
GA 564SY
UT WOS:000275238800026
PM 20186831
ER
PT J
AU Maity, A
Bernhard, EJ
AF Maity, Amit
Bernhard, Eric J.
TI Modulating Tumor Vasculature through Signaling Inhibition to Improve
Cytotoxic Therapy
SO CANCER RESEARCH
LA English
DT Review
ID IONIZING-RADIATION; ENDOTHELIAL-CELLS; FLUID PRESSURE; UP-REGULATION;
GROWTH; HYPOXIA; ANGIOGENESIS; NORMALIZATION; CANCER; RAS
AB The tumor microenvironment is a key factor in cancer treatment response. Recent work has shown that changes in the tumor vasculature can be achieved by inhibiting tumor cell signaling, resulting in enhanced tumor oxygenation. These changes could promote responses to both chemo- and radiation therapy. Cancer Res; 70( 6); 2141-5. (C) 2010 AACR.
C1 [Bernhard, Eric J.] NCI, Radiotherapy Dev Branch, Radiat Res Program, Div Canc Treatment & Diag,NIH, Rockville, MD 20892 USA.
[Maity, Amit] Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
RP Bernhard, EJ (reprint author), NCI, Radiotherapy Dev Branch, Radiat Res Program, Div Canc Treatment & Diag,NIH, 6130 Execut Blvd,Rm 6010,MSC 7440, Rockville, MD 20892 USA.
EM bernhardej@mail.nih.gov
FU National Institutes of Health (NIH) [CA093638, CA73820]; MRC
FX Grant Support; Grants from the National Institutes of Health (NIH):
CA093638 (A. Maity), CA73820 (E.J. Bernhard), and MRC (E.J. Bernhard)
during the studies described in this report.
NR 36
TC 23
Z9 24
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2010
VL 70
IS 6
BP 2141
EP 2145
DI 10.1158/0008-5472.CAN-09-3615
PG 5
WC Oncology
SC Oncology
GA 607GA
UT WOS:000278485900001
PM 20179191
ER
PT J
AU Reinhold, WC
Mergny, JL
Liu, HF
Ryan, M
Pfister, TD
Kinders, R
Parchment, R
Doroshow, J
Weinstein, JN
Pommier, Y
AF Reinhold, William C.
Mergny, Jean-Louis
Liu, Hongfang
Ryan, Michael
Pfister, Thomas D.
Kinders, Robert
Parchment, Ralph
Doroshow, James
Weinstein, John N.
Pommier, Yves
TI Exon Array Analyses across the NCI-60 Reveal Potential Regulation of
TOP1 by Transcription Pausing at Guanosine Quartets in the First Intron
SO CANCER RESEARCH
LA English
DT Article
ID CANCER-CELL LINES; TOPOISOMERASE-I INHIBITORS; RNA-POLYMERASE-II; DNA
TOPOISOMERASES; PROMOTER; EXPRESSION; GENE; MICROARRAY; PANEL;
CAMPTOTHECIN
AB Because topoisomerase 1 (TOP1) is critical for the relaxation of DNA supercoils and because it is the target for the anticancer activity of camptothecins, we assessed TOP1 transcript levels in the 60 cell line panel (the NCI-60) of the National Cancer Institute's anticancer drug screen. TOP1 expression levels varied over a 5.7-fold range across the NCI-60. HCT116 colon and MCF-7 breast cancer cells were the highest expressers; SK-MEL-28 melanoma and HS578T breast carcinoma cells were the lowest. TOP1 mRNA expression was highly correlated with Top1 protein levels, indicating that TOP1 transcripts could be conveniently used to monitor Top1 protein levels and activity in tissues. Assessment of the TOP1 locus by array comparative genomic hybridization across the NCI-60 showed copy numbers ranging from 1.71 to 4.13 and a statistically significant correlation with TOP1 transcript levels (P < 0.01). Further analyses of TOP1 expression on an exon-specific basis revealed that exon 1 expression was generally higher and less variable than expression of the other exons, suggesting some form of transcriptional pausing regulation between exons 1 and 2. Accordingly, we found the presence of multiple evolutionarily conserved potential G-quadruplex-forming sequences in the first TOP1 intron. Physicochemical tests for actual quadruplex formation by several of those sequences yielded quadruplex formation for two of them and duplex formation for one. The observations reported here suggest the hypothesis that there is a conserved negative transcription regulator within intron 1 of the TOP1 gene associated with a quadruplex-prone region. Cancer Res; 70(6); 2191-203. (C) 2010 AACR.
C1 [Reinhold, William C.; Liu, Hongfang; Doroshow, James; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20894 USA.
[Doroshow, James] NCI, Dev Therapeut Program, Ctr Canc Res, NIH, Bethesda, MD 20894 USA.
[Mergny, Jean-Louis] Museum Natl Hist Nat USM 503, Inst Natl Sante & Rech Med U565, Regulat & Dynam Genomes Lab Biophys, Paris, France.
[Liu, Hongfang] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Ryan, Michael] Tiger Team Consulting, Fairfax, VA USA.
[Pfister, Thomas D.; Kinders, Robert; Parchment, Ralph] NCI, Lab Human Toxicol & Pharmacol, Appl Dev Res Support Directorate, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA.
[Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
RP Reinhold, WC (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 37,Room 5056, Bethesda, MD 20894 USA.
EM wcr@mail.nih.gov
RI Mergny, Jean-Louis/E-2860-2013
OI Mergny, Jean-Louis/0000-0003-3043-8401
FU National Cancer Institute, Center for Cancer Research
FX Grant Support; Intramural Program of National Cancer Institute, Center
for Cancer Research.
NR 42
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U1 1
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2010
VL 70
IS 6
BP 2191
EP 2203
DI 10.1158/0008-5472.CAN-09-3528
PG 13
WC Oncology
SC Oncology
GA 607GA
UT WOS:000278485900007
PM 20215517
ER
PT J
AU Amos, CI
Pinney, SM
Li, YF
Kupert, E
Lee, J
de Andrade, MA
Yang, P
Schwartz, AG
Fain, PR
Gazdar, A
Minna, J
Wiest, JS
Zeng, D
Rothschild, H
Mandal, D
You, M
Coons, T
Gaba, C
Bailey-Wilson, JE
Anderson, MW
AF Amos, Christopher I.
Pinney, Susan M.
Li, Yafang
Kupert, Elena
Lee, Juwon
de Andrade, Mariza A.
Yang, Ping
Schwartz, Ann G.
Fain, Pam R.
Gazdar, Adi
Minna, John
Wiest, Jonathan S.
Zeng, Dong
Rothschild, Henry
Mandal, Diptasri
You, Ming
Coons, Teresa
Gaba, Colette
Bailey-Wilson, Joan E.
Anderson, Marshall W.
TI A Susceptibility Locus on Chromosome 6q Greatly Increases Lung Cancer
Risk among Light and Never Smokers
SO CANCER RESEARCH
LA English
DT Article
ID FAMILIAL RISK; RELATIVES; GENE; POPULATION; VALIDITY; 6Q23-25
AB Cigarette smoking is the major cause for lung cancer, but genetic factors also affect susceptibility. We studied families that included multiple relatives affected by lung cancer. Results from linkage analysis showed strong evidence that a region of chromosome 6q affects lung cancer risk. To characterize the effects that this region of chromosome 6q region has on lung cancer risk, we identified a haplotype that segregated with lung cancer. We then performed Cox regression analysis to estimate the differential effects that smoking behaviors have on lung cancer risk according to whether each individual carried a risk-associated haplotype or could not be classified and was assigned unknown haplotypic status. We divided smoking exposures into never smokers, light smokers (<20 pack-years), moderate smokers (20 to <40 pack-years), and heavy smokers (>= 40 pack-years). Comparing results according to smoking behavior stratified by carrier status, compared with never smokers, there was weakly increasing risk for increasing smoking behaviors, with the hazards ratios being 3.44, 4.91, and 5.18, respectively, for light, moderate, or heavy smokers, whereas among the individuals from families without the risk haplotype, the risks associated with smoking increased strongly with exposure, the hazards ratios being, respectively, 4.25, 9.17, and 11.89 for light, moderate, and heavy smokers. The never smoking carriers had a 4.71-fold higher risk than the never smoking individuals without known risk haplotypes. These results identify a region of chromosome 6q that increases risk for lung cancer and that confers particularly higher risks to never and light smokers. Cancer Res; 70(6); 2359-67. (C) 2010 AACR.
C1 [Amos, Christopher I.; Li, Yafang; Zeng, Dong] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77005 USA.
[Pinney, Susan M.; Kupert, Elena; Lee, Juwon; Anderson, Marshall W.] Univ Cincinnati, Cincinnati, OH USA.
[de Andrade, Mariza A.; Yang, Ping] Mayo Clin, Coll Med, Rochester, MN USA.
[Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Fain, Pam R.] Univ Colorado, Denver, CO 80202 USA.
[Gazdar, Adi; Minna, John] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Wiest, Jonathan S.] NCI, NIH, Bethesda, MD 20892 USA.
[Rothschild, Henry; Mandal, Diptasri] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA.
[You, Ming] Washington Univ, St Louis, MO USA.
[Coons, Teresa] Saccomanno Res Inst, Grand Junction, CO USA.
[Gaba, Colette] Med Coll Ohio, Toledo, OH 43699 USA.
[Bailey-Wilson, Joan E.] NHGRI, Baltimore, MD USA.
RP Amos, CI (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, 1155 Pressler St,Unit 1340, Houston, TX 77005 USA.
EM camos@mdanderson.org
OI Bailey-Wilson, Joan/0000-0002-9153-2920
FU NIH [UO1CA076293, P30ES06096, P30CA016772, R01CA133996, RO1CA060691,
RO1CA87895, P30ES007789, P50CA70907, NO1PC35145]; National Cancer
Institute; National Human Genome Research Institute, NIH
FX Grant Support; NIH grants UO1CA076293, P30ES06096, P30CA016772,
R01CA133996, RO1CA060691, RO1CA87895, P30ES007789, P50CA70907, and
NO1PC35145 and the intramural programs of the National Cancer Institute
and the National Human Genome Research Institute, NIH.
NR 30
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Z9 24
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2010
VL 70
IS 6
BP 2359
EP 2367
DI 10.1158/0008-5472.CAN-09-3096
PG 9
WC Oncology
SC Oncology
GA 607GA
UT WOS:000278485900023
PM 20215501
ER
PT J
AU Koutros, S
Schumacher, FR
Hayes, RB
Ma, J
Huang, WY
Albanes, D
Canzian, F
Chanock, SJ
Crawford, ED
Diver, WR
Feigelson, HS
Giovanucci, E
Haiman, CA
Henderson, BE
Hunter, DJ
Kaaks, R
Kolonel, LN
Kraft, P
Le Marchand, L
Riboli, E
Siddiq, A
Stampfer, MJ
Stram, DO
Thomas, G
Travis, RC
Thun, MJ
Yeager, M
Berndt, SI
AF Koutros, Stella
Schumacher, Fredrick R.
Hayes, Richard B.
Ma, Jing
Huang, Wen-Yi
Albanes, Demetrius
Canzian, Federico
Chanock, Stephen J.
Crawford, E. David
Diver, W. Ryan
Feigelson, Heather Spencer
Giovanucci, Edward
Haiman, Christopher A.
Henderson, Brian E.
Hunter, David J.
Kaaks, Rudolf
Kolonel, Laurence N.
Kraft, Peter
Le Marchand, Loic
Riboli, Elio
Siddiq, Afshan
Stampfer, Mier J.
Stram, Daniel O.
Thomas, Gilles
Travis, Ruth C.
Thun, Michael J.
Yeager, Meredith
Berndt, Sonja I.
TI Pooled Analysis of Phosphatidylinositol 3-Kinase Pathway Variants and
Risk of Prostate Cancer
SO CANCER RESEARCH
LA English
DT Article
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GROWTH-FACTOR-I; PHOSPHOINOSITIDE
3-KINASE; FAMILY-HISTORY; GENETIC ASSOCIATION; REGULATORY SUBUNIT;
BINDING PROTEIN-3; CELL-MIGRATION; OVARIAN-CANCER; FACTOR (IGF)-I
AB The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and intracellular trafficking, and may affect prostate carcinogenesis. Thus, we explored the association between single-nucleotide polymorphisms (SNP) in PI3K genes and prostate cancer. Pooled data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium were examined for associations between 89 SNPs in PI3K genes (PIK3C2B, PIK3AP1, PIK3C2A, PIK3CD, and PIK3R3) and prostate cancer risk in 8,309 cases and 9,286 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. SNP rs7556371 in PIK3C2B was significantly associated with prostate cancer risk [OR(per) (allele), 1.08 (95% CI, 1.03-1.14); P(trend) = 0.0017] after adjustment for multiple testing (P(adj) = 0.024). Simultaneous adjustment of rs7556371 for nearby SNPs strengthened the association [OR(per) (allele), 1.21 (95% CI, 1.09-1.34); P(trend) = 0.0003]. The adjusted association was stronger for men who were diagnosed before the age of 65 years [OR(per) (allele), 1.47 (95% CI, 1.20-1.79); P(trend) = 0.0001] or had a family history [OR(per) (allele) = 1.57 (95% CI, 1.11-2.23); P(trend) = 0.0114], and was strongest in those with both characteristics [OR(per) (allele) = 2.31 (95% CI, 1.07-5.07), P-interaction = 0.005]. Increased risks were observed among men in the top tertile of circulating insulin-like growth factor-I (IGF-I) levels [OR(per) (allele) = 1.46 (95% CI, 1.04-2.06); P(trend) = 0.075]. No differences were observed with disease aggressiveness (Gleason grade = 8 or stage T(3)/T(4) or fatal). In conclusion, we observed a significant association between PIK3C2B and prostate cancer risk, especially for familial, early-onset disease, which may be attributable to IGF-dependent PI3K signaling. Cancer Res; 70(6); 2389-96. (C)2010 AACR.
C1 [Koutros, Stella] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Schumacher, Fredrick R.; Haiman, Christopher A.; Henderson, Brian E.; Stram, Daniel O.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Hayes, Richard B.] NYU, Sch Med, New York, NY USA.
[Ma, Jing; Stampfer, Mier J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Ma, Jing; Stampfer, Mier J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Giovanucci, Edward; Kraft, Peter; Stampfer, Mier J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Canzian, Federico; Kaaks, Rudolf] German Canc Res Ctr, Heidelberg, Germany.
[Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Dept Urol, Aurora, CO USA.
[Diver, W. Ryan; Feigelson, Heather Spencer; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA.
[Feigelson, Heather Spencer; Hunter, David J.] Kaiser Permanente, Denver, CO USA.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA.
[Riboli, Elio; Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, London, England.
[Travis, Ruth C.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
RP Koutros, S (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8115,MSC 7240, Rockville, MD 20852 USA.
EM KoutrosS@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015;
OI Hayes, Richard/0000-0002-0918-661X
FU National Cancer Institute [CA98233, CA98710, CA98216, CA98758]; National
Cancer Institute, NIH
FX Grant Support; National Cancer Institute under UO1 grants CA98233,
CA98710, CA98216, and CA98758 and the Intramural Research Program of the
National Cancer Institute, NIH.
NR 45
TC 28
Z9 29
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2010
VL 70
IS 6
BP 2389
EP 2396
DI 10.1158/0008-5472.CAN-09-3575
PG 8
WC Oncology
SC Oncology
GA 607GA
UT WOS:000278485900026
PM 20197460
ER
PT J
AU Cross, AJ
Ferrucci, LM
Risch, A
Graubard, BI
Ward, MH
Park, Y
Hollenbeck, AR
Schatzkin, A
Sinha, R
AF Cross, Amanda J.
Ferrucci, Leah M.
Risch, Adam
Graubard, Barry I.
Ward, Mary H.
Park, Yikyung
Hollenbeck, Albert R.
Schatzkin, Arthur
Sinha, Rashmi
TI A Large Prospective Study of Meat Consumption and Colorectal Cancer
Risk: An Investigation of Potential Mechanisms Underlying this
Association
SO CANCER RESEARCH
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRES; HETEROCYCLIC AMINE CONTENT; PUBLIC
WATER-SUPPLIES; RED MEAT; COLON-CANCER; GENETIC POLYMORPHISMS; VARYING
DEGREES; DIETARY HEME; EXPOSURE; ADENOMA
AB Although the relation between red and processed meat intake and colorectal cancer has been reported in several epidemiologic studies, very few investigated the potential mechanisms. This study examined multiple potential mechanisms in a large U. S. prospective cohort with a detailed questionnaire on meat type and meat cooking methods linked to databases for estimating intake of mutagens formed in meats cooked at high temperatures (heterocyclic amines, polycyclic aromatic hydrocarbons), heme iron, nitrate, and nitrite. During 7 years of follow-up, 2,719 colorectal cancer cases were ascertained from a cohort of 300,948 men and women. The hazard ratios (HR) and 95% confidence intervals (95% CI) comparing the fifth to the first quintile for both red (HR, 1.24; 95% CI, 1.09-1.42; P-trend < 0.001) and processed meat (HR, 1.16; 95% CI, 1.01-1.32; P-trend = 0.017) intakes indicated an elevated risk for colorectal cancer. The potential mechanisms for this relation include heme iron (HR, 1.13; 95% CI, 0.99-1.29; P-trend = 0.022), nitrate from processed meats (HR, 1.16; 95% CI, 1.02-1.32; P-trend = 0.001), and heterocyclic amine intake [HR, 1.19; 95% CI, 1.05-1.34; P-trend < 0.001 for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and HR, 1.17; 95% CI, 1.05-1.29; P-trend < 0.001 for 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)]. In general, the elevated risks were higher for rectal cancer than for colon cancer, with the exception of MeIQx and DiMeIQx, which were only associated with colon cancer. In conclusion, we found a positive association for red and processed meat intake and colorectal cancer; heme iron, nitrate/nitrite, and heterocyclic amines from meat may explain these associations. Cancer Res; 70(6); 2406-14. (C)2010 AACR.
C1 [Cross, Amanda J.; Ferrucci, Leah M.; Park, Yikyung; Schatzkin, Arthur; Sinha, Rashmi] NCI, Nutr Epidemiol Branch, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
[Graubard, Barry I.] NCI, Biostat Branch, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
[Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA.
[Risch, Adam] Informat Management Serv Inc, Silver Spring, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Cross, AJ (reprint author), 6120 Execut Blvd, Rockville, MD 20852 USA.
EM crossa@mail.nih.gov
RI Sinha, Rashmi/G-7446-2015;
OI Sinha, Rashmi/0000-0002-2466-7462; Park, Yikyung/0000-0002-6281-489X
FU National Cancer Institute, NIH
FX Grant Support; Intramural Research Program of National Cancer Institute,
NIH.
NR 42
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U2 57
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2010
VL 70
IS 6
BP 2406
EP 2414
DI 10.1158/0008-5472.CAN-09-3929
PG 9
WC Oncology
SC Oncology
GA 607GA
UT WOS:000278485900028
PM 20215514
ER
PT J
AU Ivy, SP
Siu, LL
Garrett-Mayer, E
Rubinstein, L
AF Ivy, S. Percy
Siu, Lillian L.
Garrett-Mayer, Elizabeth
Rubinstein, Larry
TI Approaches to Phase 1 Clinical Trial Design Focused on Safety,
Efficiency, and Selected Patient Populations: A Report from the Clinical
Trial Design Task Force of the National Cancer Institute Investigational
Drug Steering Committee
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CONTINUAL REASSESSMENT METHOD; LATE-ONSET TOXICITIES; ONCOLOGY TRIALS; I
TRIALS; BIOMARKERS; BENEFITS; AGENTS; RISKS; RATES; CRM
AB The goals and objectives of phase 1 clinical trials are changing to include further evaluation of end-points such as molecular targeted effects, in addition to dose-toxicity profile of the investigational agent. Because of these changes in focus, the National Cancer Institute and Investigational Drug Steering Committee's Task Force on Clinical Trial Design met to evaluate the most efficient ways to design and implement early clinical trials with novel therapeutics. Clinical approaches discussed included the conventional 3 + 3 cohort expansion phase 1 design, multi-institutional phase 1 studies, accelerated titration designs, continual reassessment methods, the study of specific target patient populations, and phase 0 studies. Each of these approaches uniquely contributes to some aspect of the phase 1 study, with all focused on dose and schedule determination, patient safety, and limited patient exposure to ineffective doses of investigational agent. The benefit of labor-intensive generation of preliminary biomarker evidence of target inhibition, as well as the value of molecular profiling of the study population, is considered. New drug development is expensive and the failure rate remains high. By identifying patient populations expected to respond to the study agent and tailoring the treatment with a novel drug, investigators will be one step closer to personalizing cancer treatment. The "fail early and fast" approach is acceptable if the appropriate patient population is evaluated in the phase 1 trial. The approaches outlined in this overview address the merits, advantages, disadvantages, and obstacles encountered during first in human studies. Clin Cancer Res; 16(6); 1726-36. (C) 2010 AACR.
C1 [Ivy, S. Percy; Rubinstein, Larry] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA.
[Ivy, S. Percy; Rubinstein, Larry] NCI, Biometr Res Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA.
[Siu, Lillian L.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Garrett-Mayer, Elizabeth] Med Univ S Carolina, Charleston, SC 29425 USA.
RP Ivy, SP (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, 6130 Execut Blvd,Suite 7131, Rockville, MD 20852 USA.
EM ivyp@ctep.nci.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 46
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U1 1
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2010
VL 16
IS 6
BP 1726
EP 1736
DI 10.1158/1078-0432.CCR-09-1961
PG 11
WC Oncology
SC Oncology
GA 608OT
UT WOS:000278595600006
PM 20215542
ER
PT J
AU Dancey, JE
Dobbin, KK
Groshen, S
Jessup, JM
Hruszkewycz, AH
Koehler, M
Parchment, R
Ratain, MJ
Shankar, LK
Stadler, WM
True, LD
Gravell, A
Grever, MR
AF Dancey, Janet E.
Dobbin, Kevin K.
Groshen, Susan
Jessup, J. Milburn
Hruszkewycz, Andrew H.
Koehler, Maria
Parchment, Ralph
Ratain, Mark J.
Shankar, Lalitha K.
Stadler, Walter M.
True, Lawrence D.
Gravell, Amy
Grever, Michael R.
CA Biomarkers Task Force NCI Invest
TI Guidelines for the Development and Incorporation of Biomarker Studies in
Early Clinical Trials of Novel Agents
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SURROGATE END-POINTS; DRUG DEVELOPMENT; ASSESSMENT MODALITIES;
DIAGNOSTIC-ACCURACY; VALIDATION; RECOMMENDATIONS; PATHWAY; TUMOR
AB The National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) charged the Biomarker Task Force to develop recommendations to improve the decisions about incorporation of biomarker studies in early investigational drug trials. The Task Force members reviewed biomarker trials, the peer-reviewed literature, NCI and U. S. Food and Drug Administration (FDA) guidance documents, and conducted a survey of investigators to determine practices and challenges to executing biomarker studies in clinical trials of new drugs in early development. This document provides standard definitions and categories of biomarkers, and lists recommendations to sponsors and investigators for biomarker incorporation into such trials. Our recommendations for sponsors focus on the identification and prioritization of biomarkers and assays, the coordination of activities for the development and use of assays, and for operational activities. We also provide recommendations for investigators developing clinical trials with biomarker studies for scientific rationale, assay criteria, trial design, and analysis. The incorporation of biomarker studies into early drug trials is complex. Thus the decision to proceed with studies of biomarkers should be based on balancing the strength of science, assay robustness, feasibility, and resources with the burden of proper sample collection on the patient and potential impact of the results on drug development. The Task Force provides these guidelines in the hopes that improvements in biomarker studies will enhance the efficiency of investigational drug development. Clin Cancer Res; 16(6); 1745-55. (C) 2010 AACR.
C1 [Grever, Michael R.] Ohio State Univ, Columbus, OH 43210 USA.
[Groshen, Susan] Univ So Calif, Los Angeles, CA USA.
[Dancey, Janet E.; Dobbin, Kevin K.; Jessup, J. Milburn; Hruszkewycz, Andrew H.; Shankar, Lalitha K.] NCI, Bethesda, MD 20892 USA.
[Koehler, Maria] GlaxoSmithKline Inc, Narberth, PA USA.
[Parchment, Ralph] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Ratain, Mark J.; Stadler, Walter M.] Univ Chicago, Chicago, IL 60637 USA.
[True, Lawrence D.] Univ Washington, Seattle, WA 98195 USA.
[Gravell, Amy] Emmes Corp, Rockville, MD USA.
RP Dancey, JE (reprint author), MaRS Ctr, Ontario Inst Canc Res, S Tower,101 Coll St,Suite 800, Toronto, ON M5G 0A3, Canada.
EM janet.dancey@oicr.on.ca
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part by federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E.
NR 30
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PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2010
VL 16
IS 6
BP 1745
EP 1755
DI 10.1158/1078-0432.CCR-09-2167
PG 11
WC Oncology
SC Oncology
GA 608OT
UT WOS:000278595600008
PM 20215558
ER
PT J
AU Seymour, L
Ivy, SP
Sargent, D
Spriggs, D
Baker, L
Rubinstein, L
Ratain, MJ
Le Blanc, M
Stewart, D
Crowley, J
Groshen, S
Humphrey, JS
West, P
Berry, D
AF Seymour, Lesley
Ivy, S. Percy
Sargent, Daniel
Spriggs, David
Baker, Laurence
Rubinstein, Larry
Ratain, Mark J.
Le Blanc, Michael
Stewart, David
Crowley, John
Groshen, Susan
Humphrey, Jeffrey S.
West, Pamela
Berry, Donald
TI The Design of Phase II Clinical Trials Testing Cancer Therapeutics:
Consensus Recommendations from the Clinical Trial Design Task Force of
the National Cancer Institute Investigational Drug Steering Committee
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PROGRESSION-FREE SURVIVAL; FUTURE-DIRECTIONS; END-POINTS; ONCOLOGY;
PROPOSAL; OUTCOMES; ISSUES; AGENTS
AB The optimal design of phase II studies continues to be the subject of vigorous debate, especially studies of newer molecularly targeted agents. The observations that many new therapeutics "fail" in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials, further emphasize the critical importance of robust and efficient phase II design. The Clinical Trial Design Task Force (CTD-TF) of the National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) has published a series of discussion papers on phase II trial design in Clinical Cancer Research. The IDSC has developed formal recommendations about aspects of phase II trial design that are the subject of frequent debate, such as endpoints (response versus progression-free survival), randomization (single-arm designs versus randomization), inclusion of biomarkers, biomarker-based patient enrichment strategies, and statistical design (e. g., two-stage designs versus multiple-group adaptive designs). Although these recommendations in general encourage the use of progression-free survival as the primary endpoint, randomization, inclusion of biomarkers, and incorporation of newer designs, we acknowledge that objective response as an endpoint and single-arm designs remain relevant in certain situations. The design of any clinical trial should always be carefully evaluated and justified based on characteristic specific to the situation. Clin Cancer Res; 16(6); 1764-9. (C) 2010 AACR.
C1 [Seymour, Lesley] NCIC Clin Trials Grp, Kingston, ON K7L 3N6, Canada.
[Ivy, S. Percy; Rubinstein, Larry] NCI, Bethesda, MD 20892 USA.
[Sargent, Daniel] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Spriggs, David] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Baker, Laurence] Univ Michigan, Dept Med & Pharmacol, Ann Arbor, MI 48109 USA.
[Ratain, Mark J.] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Le Blanc, Michael; Crowley, John] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Stewart, David; Berry, Donald] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Groshen, Susan] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Los Angeles, CA USA.
[Humphrey, Jeffrey S.] Bristol Myers Squibb Co, Plainsboro, NJ USA.
[West, Pamela] Emmes Corp, Rockville, MD USA.
RP Seymour, L (reprint author), NCIC Clin Trials Grp, 10 Stuart St, Kingston, ON K7L 3N6, Canada.
EM lseymour@ctg.queensu.ca
OI Sargent, Daniel/0000-0002-2684-4741
FU NCI; IDSC
FX The Clinical Trial Design Task Force would like to acknowledge the
support of the NCI and the IDSC members and chairs, Amy Gravell, LeeAnn
Jensen, the attendees of the original Phase II Workshop, as well as all
Task Force members, past and present, especially Drs. Alex Adjei and
Michaele Christian who originally led the Task Force (Table 2).
NR 23
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PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2010
VL 16
IS 6
BP 1764
EP 1769
DI 10.1158/1078-0432.CCR-09-3287
PG 6
WC Oncology
SC Oncology
GA 608OT
UT WOS:000278595600010
PM 20215557
ER
PT J
AU Wayne, AS
Kreitman, RJ
Findley, HW
Lew, G
Delbrook, C
Steinberg, SM
Stetler-Stevenson, M
FitzGerald, DJ
Pastan, I
AF Wayne, Alan S.
Kreitman, Robert J.
Findley, Harry W.
Lew, Glen
Delbrook, Cynthia
Steinberg, Seth M.
Stetler-Stevenson, Maryalice
FitzGerald, David J.
Pastan, Ira
TI Anti-CD22 Immunotoxin RFB4(dsFv)-PE38 (BL22) for CD22-Positive
Hematologic Malignancies of Childhood: Preclinical Studies and Phase I
Clinical Trial
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HAIRY-CELL LEUKEMIA; CYTOTOXIC ACTIVITY;
PEDIATRIC-PATIENTS; RESPONSE CRITERIA; CANCER; STANDARDS; DIAGNOSIS;
SURVIVORS; LYMPHOMA
AB Purpose: Although most children with B-lineage acute lymphoblastic leukemia (ALL) and non Hodgkin lymphoma are cured, new agents are needed to overcome drug resistance and reduce toxicities of chemotherapy. We hypothesized that the novel anti-CD22 immunotoxin, RFB4(dsFv)-PE38 (BL22, CAT-3888), would be active and have limited nonspecific side effects in children with CD22-expressing hematologic malignancies. We conducted the first preclinical and phase I clinical studies of BL22 in that setting.
Experimental Design: Lymphoblasts from children with B-lineage ALL were assessed for CD22 expression by flow cytometry and for BL22 sensitivity by in vitro cytotoxicity assay. BL22 was evaluated in a human ALL murine xenograft model. A phase I clinical trial was conducted for pediatric subjects with CD22+ ALL and non-Hodgkin lymphoma.
Results: All samples screened were CD22+. BL22 was cytotoxic to blasts in vitro (median IC(50), 9.8 ng/mL) and prolonged the leukemia-free survival of murine xenografts. Phase I trial cohorts were treated at escalating doses and schedules ranging from 10 to 40 mu g/kg every other day for three or six doses repeated every 21 or 28 days. Treatment was associated with an acceptable safety profile, adverse events were rapidly reversible, and no maximum tolerated dose was defined. Pharmacokinetics were influenced by disease burden consistent with rapid drug binding by CD22+ blasts. Although no responses were observed, transient clinical activity was seen in most subjects.
Conclusions: CD22 represents an excellent target and anti-CD22 immunotoxins offer therapeutic promise in B-lineage hematologic malignancies of childhood. Clin Cancer Res; 16(6); 1894-903. (C) 2010 AACR.
C1 [Wayne, Alan S.; Delbrook, Cynthia] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kreitman, Robert J.; FitzGerald, David J.; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Findley, Harry W.; Lew, Glen] Emory Univ, Sch Med Childrens Healthcare Atlanta, Aflac Canc Ctr, Atlanta, GA 30322 USA.
[Findley, Harry W.; Lew, Glen] Emory Univ, Sch Med Childrens Healthcare Atlanta, Blood Disorders Serv, Atlanta, GA 30322 USA.
RP Wayne, AS (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 1-3750,9000 Rockville Pike,MSC 1104, Bethesda, MD 20892 USA.
EM waynea@mail.nih.gov
FU NIH, National Cancer Institute; Center for Cancer Research; Cooperative
Research and Development Agreement; MedImmune, LLC
FX Intramural Research Program of the NIH, National Cancer Institute, the
Center for Cancer Research, and a Cooperative Research and Development
Agreement between the NIH, National Cancer Institute, and MedImmune,
LLC.
NR 32
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U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2010
VL 16
IS 6
BP 1894
EP 1903
DI 10.1158/1078-0432.CCR-09-2980
PG 10
WC Oncology
SC Oncology
GA 608OT
UT WOS:000278595600023
PM 20215554
ER
PT J
AU McMahon, D
Jones, J
Wiegand, A
Gange, SJ
Kearney, M
Palmer, S
McNulty, S
Metcalf, JA
Acosta, E
Rehm, C
Coffin, JM
Mellors, JW
Maldarelli, F
AF McMahon, D.
Jones, J.
Wiegand, A.
Gange, S. J.
Kearney, M.
Palmer, S.
McNulty, S.
Metcalf, J. A.
Acosta, E.
Rehm, C.
Coffin, J. M.
Mellors, J. W.
Maldarelli, F.
TI Short-Course Raltegravir Intensification Does Not Reduce Persistent
Low-Level Viremia in Patients with HIV-1 Suppression during Receipt of
Combination Antiretroviral Therapy
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID INTEGRASE INHIBITOR RALTEGRAVIR; CENTRAL-NERVOUS-SYSTEM; VIRUS TYPE-1
RNA; INFECTED INDIVIDUALS; CEREBROSPINAL-FLUID; RESIDUAL VIREMIA;
EXTENDED PERIODS; LATENT RESERVOIR; VIRAL RESERVOIR; P-GLYCOPROTEIN
AB Background. Combination antiretroviral therapy suppresses but does not eradicate human immunodeficiency virus type 1 (HIV-1) in infected persons, and low-level viremia can be detected despite years of suppressive antiretroviral therapy. Short-course (28-day) intensification of standard antiretroviral combination therapy is a useful approach to determine whether complete rounds of HIV-1 replication in rapidly cycling cells contribute to persistent viremia. We investigated whether intensification with the integrase inhibitor raltegravir decreases plasma HIV-1 RNA levels in patients receiving suppressive antiretroviral therapy.
Methods. Subjects (n=10) with long-term HIV-1 suppression receiving combination antiretroviral regimens had their regimens intensified for 4 weeks with raltegravir. Plasma HIV-1 RNA level was determined before, during, and after the 4-week intensification period, using a sensitive assay (limit of detection, 0.2 copies of HIV-1 RNA/mL of plasma). A 4-week intensification course was chosen to investigate potential HIV-1 replication in cells with relatively short (similar to 1-14-day) half-lives.
Results. There was no evidence in any subject of a decline in HIV-1 RNA level during the period of raltegravir intensification or of rebound after discontinuation. Median levels of HIV-1 RNA before (0.17 log(10) copies/mL), during (0.04 log(10) copies/mL), and after (0.04 log(10) copies/mL) raltegravir intensification were not significantly different (P>.1 for all comparisons in parametric analyses). High-performance liquid chromatography and mass spectroscopy experiments confirmed that therapeutic levels of raltegravir were achieved in plasma during intensification.
Conclusions. Intensification of antiretroviral therapy with a potent HIV-1 integrase inhibitor did not decrease persistent viremia in subjects receiving suppressive regimens, indicating that rapidly cycling cells infected with HIV-1 were not present. Eradication of HIV-1 from infected persons will require new therapeutic approaches.
C1 [McMahon, D.; Jones, J.; McNulty, S.; Mellors, J. W.] Univ Pittsburgh, Dept Infect Dis, Pittsburgh, PA USA.
[Wiegand, A.; Kearney, M.; Palmer, S.; Coffin, J. M.; Maldarelli, F.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA.
[Gange, S. J.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Metcalf, J. A.; Rehm, C.] NIAID, Clin Res Sect, NIH, Bethesda, MD 20892 USA.
[Acosta, E.] Univ Alabama, Dept Pharmacol, Birmingham, AL USA.
RP Maldarelli, F (reprint author), NCI, NIH, Bldg 10,Rm 5A06, Bethesda, MD 20892 USA.
EM fmalli@mail.nih.gov
OI Gange, Stephen/0000-0001-7842-512X
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health [HHSN261200800001E]; SAIC [20XS190A]; George Kirby
Foundation
FX National Institute of Allergy and Infectious Diseases, National
Institutes of Health (contract HHSN261200800001E to D. M.), and SAIC
(contract 20XS190A to J. W. M.). J. W. M. is a research professor of the
American Cancer Society with support from the George Kirby Foundation.
NR 42
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U1 2
U2 5
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAR 15
PY 2010
VL 50
IS 6
BP 912
EP 919
DI 10.1086/650749
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 557FW
UT WOS:000274656000019
PM 20156060
ER
PT J
AU Hohmann, C
Kang, EM
Jancel, T
AF Hohmann, Carina
Kang, Elizabeth M.
Jancel, Timothy
TI Rifampin and Posaconazole Coadministration Leads to Decreased Serum
Posaconazole Concentrations
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Letter
ID PHARMACOKINETICS; ITRACONAZOLE; METABOLISM
C1 [Jancel, Timothy] NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA.
[Hohmann, Carina] Klinikum Fulda gAG, Dept Pharm, Fulda, Germany.
[Kang, Elizabeth M.] NIAID, Host Def Lab, Bethesda, MD 20892 USA.
RP Jancel, T (reprint author), NIH, Ctr Clin, Dept Pharm, Bldg 10,Rm 1N257,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jancelt@mail.nih.gov
NR 14
TC 13
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U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAR 15
PY 2010
VL 50
IS 6
BP 939
EP 940
DI 10.1086/650740
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 557FW
UT WOS:000274656000028
PM 20166829
ER
PT J
AU Li, L
Zheng, P
Dean, J
AF Li, Lei
Zheng, Ping
Dean, Jurrien
TI Maternal control of early mouse development
SO DEVELOPMENT
LA English
DT Review
DE Maternal-effect genes; Mater (Nlrp5); Floped (Ooep); Padi6; Tle6; Filia;
Embryonic cell lineage; Cleavage-stage arrest; Embryonic gene
activation; Preimplantation development; Subcortical maternal complex
ID EARLY EMBRYONIC-DEVELOPMENT; PRE-IMPLANTATION DEVELOPMENT; DE-NOVO
METHYLATION; EFFECT GENE; PREIMPLANTATION DEVELOPMENT; DROSOPHILA
EMBRYO; SELECTIVE DEGRADATION; MAMMALIAN DEVELOPMENT; SIGNALING
PATHWAYS; FEMALE FERTILITY
AB The hiatus between oocyte and embryonic gene transcription dictates a role for stored maternal factors in early mammalian development. Encoded by maternal-effect genes, these factors accumulate during oogenesis and enable the activation of the embryonic genome, the subsequent cleavage stages of embryogenesis and the initial establishment of embryonic cell lineages. Recent studies in mice have yielded new findings on the role of maternally provided proteins and multi-component complexes in preimplantation development. Nevertheless, significant gaps remain in our mechanistic understanding of the networks that regulate early mammalian embryogenesis, which provide an impetus and opportunities for future investigations.
C1 [Li, Lei; Zheng, Ping; Dean, Jurrien] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Li, L (reprint author), Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China.
EM lil@ioz.ac.cn; jurrien@helix.nih.gov
OI Li, Lei/0000-0001-5478-5681
FU National Institutes of Health, NIDDK
FX We appreciate the critical review of the manuscript by Dr Scott Coonrod
and the expert insight provided during the review process. The authors
are funded by the Intramural Research Program of the National Institutes
of Health, NIDDK. Deposited in PMC for release after 12 months.
NR 122
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U1 3
U2 42
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD MAR 15
PY 2010
VL 137
IS 6
BP 859
EP 870
DI 10.1242/dev.039487
PG 12
WC Developmental Biology
SC Developmental Biology
GA 560FK
UT WOS:000274887300002
PM 20179092
ER
PT J
AU Joseph, DS
Malik, M
Nurudeen, S
Catherino, WH
AF Joseph, Doina S.
Malik, Minnie
Nurudeen, Sahadat
Catherino, William H.
TI Myometrial cells undergo fibrotic transformation under the influence of
transforming growth factor beta-3
SO FERTILITY AND STERILITY
LA English
DT Article
DE Transforming growth factor beta 3; extracellular matrix; leiomyoma;
myometrium; collagen; fibronectin; connective tissue growth factor;
matrix metalloproteinases
ID SMOOTH-MUSCLE-CELLS; GONADOTROPIN-RELEASING-HORMONE; MATRIX
METALLOPROTEINASE INDUCER; UTERINE LEIOMYOMA CELLS; TGF-BETA; TISSUE
INHIBITORS; GENE-EXPRESSION; DIFFERENTIAL EXPRESSION; HUMAN
STROMELYSIN-3; REPERFUSION INJURY
AB Objective: To examine the effect of transforming growth factor (TGF) beta 3 on immortalized myometrial and leiomyoma cell lines cloned from primary cell cultures of surgical specimens, and to determine whether such treatment alters myometrial cell extracellular matrix (ECM) expression.
Design: Laboratory study.
Setting: University hospital.
Patient(s): Immortalized myometrial and leiomyoma cells from patients with symptomatic leiomyomata.
Intervention(s): Tissue culture, followed by cellular, RNA, and protein analysis.
Main Outcome Measure(s): Cell proliferation, alteration in ECM component expression.
Result(s): Immortalized leiomyoma and myometrial cells demonstrate increased mRNA and protein production of the ECM proteins, collagen 1 A 1(15.0-fold), fibronectin 1 (2.93 fold), and connective tissue growth factor (9.40-fold) with exogenous TGF-beta 3 stimulation. Notably, the expression of collagen 1 A 1, fibronectin 1, and connective tissue growth factor in myometrial cells increase to similar expression levels as those found in leiomyoma cells. In addition, TGF-beta 3 decreased production of genes involved in matrix resorption, including matrix metalloproteinase 2 (0.65-fold) and -11 (0.68-fold).
Conclusion(s): TGF-beta 3 induced a molecular phenotype in myometrial cells that was similar to leiomyoma cells, with elevated production of ECM-related genes and decreased production of ECM degradation related genes. (Fertil Steril (R) 2010;93:1500-8. (C)2010 by American Society for Reproductive Medicine.)
C1 [Joseph, Doina S.; Malik, Minnie; Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
[Nurudeen, Sahadat] Georgetown Univ Hosp, Dept Obstet & Gynecol, Washington, DC 20007 USA.
[Catherino, William H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, NIH, Bethesda, MD USA.
RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM wcatherino@usuhs.mil
FU Berlex Foundation; Reproductive Biology and Medicine Branch, National
Institute of Child Health and Human Development, National Institutes of
Health
FX Supported by the Berlex Foundation and by the intramural research
program of the Reproductive Biology and Medicine Branch, National
Institute of Child Health and Human Development, National Institutes of
Health.
NR 61
TC 27
Z9 29
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD MAR 15
PY 2010
VL 93
IS 5
BP 1500
EP 1508
DI 10.1016/j.fertnstert.2009.01.081
PG 9
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 575BM
UT WOS:000276038700016
PM 19328471
ER
PT J
AU Kaneko, KJ
Kohn, MJ
Liu, CY
DePamphilis, ML
AF Kaneko, Kotaro J.
Kohn, Matthew J.
Liu, Chengyu
DePamphilis, Melvin L.
TI The acrosomal protein Dickkopf-like 1 (DKKL1) is not essential for
fertility
SO FERTILITY AND STERILITY
LA English
DT Article
DE Fertilization; acrosome; sperm; DKKL1; conditional knock-out
ID MOUSE DEVELOPMENT; GENE-EXPRESSION; FAMILY; SOGGY
AB Objective: To determine the role of Dkkl1 on mouse development, viability, and fertility.
Design: Prospective experimental study. Setting: Government research institution.
Animal(s): Mice of C57BL/6 and 129X1/SvJ strains, as well as transgenic mice of mixed C57BL/6 and 129X1/SvJ strains were used for the studies.
Intervention(s): Mice were constructed that lacked a functional Dkkl1 gene.
Main Outcome Measure(s): Deletion of the gene was confirmed by DNA, RNA, and protein analyses; in vivo fertility was examined by continuous mating scheme.
Result(s): Previous studies have shown that Dkkl1, a gene unique to mammals, is expressed predominantly, if not exclusively, in developing spermatocytes, and the DKKL1 protein accumulates in the acrosome of mature sperm. Subsequent studies (reported in the accompanying article) demonstrate that Dkkl1 also is expressed in the trophectoderm/placental lineage. Taken together, these results strongly suggested that DKKL1 protein is required for terminal differentiation either of trophoblast giant cells or of sperm, both of which are directly involved in fertility. To challenge this hypothesis, conditional targeted mutagenesis was used to ablate the Dkkl1 gene in mice. Surprisingly, Dkkl1 nullizygous embryos developed into viable, fertile adults, despite the fact that they failed to produce any portion of the DKKL1 protein.
Conclusion(s): DKKL1 is a mammalian-specific acrosomal protein that is not essential either for development or fertility. (Fertil Steril (R) 2010;93:1526-32. (C)2010 by American Society for Reproductive Medicine.)
C1 [Kaneko, Kotaro J.; Kohn, Matthew J.; DePamphilis, Melvin L.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Liu, Chengyu] NHLBI, NIH, Bethesda, MD 20892 USA.
RP DePamphilis, ML (reprint author), NICHHD, NIH, Bldg 6,Room 3A-15,9000 Rockville Pike,6 Ctr Dr MS, Bethesda, MD 20892 USA.
EM depamphm@mail.nih.gov
FU National Institute of Child Health and Human Development
FX Supported by the intramural program of the National Institute of Child
Health and Human Development. Animals were treated according to the
Guide for the Care and Use of Laboratory Animals, Institute of
Laboratory Animal Research, National Academy of Sciences, USA. The
present address for Matthew J. Kohn is NYSTEM, New York State Department
of Health, Albany, NY.
NR 13
TC 2
Z9 2
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 MAR 15
PY 2010
VL 93
IS 5
BP 1526
EP 1532
DI 10.1016/j.fertnstert.2009.06.011
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 575BM
UT WOS:000276038700019
PM 19596310
ER
PT J
AU Kohn, MJ
Sztein, J
Yagi, R
DePamphilis, ML
Kaneko, KJ
AF Kohn, Matthew J.
Sztein, Jorge
Yagi, Rieko
DePamphilis, Melvin L.
Kaneko, Kotaro J.
TI The acrosomal protein Dickkopf-like 1 (DKKL1) facilitates sperm
penetration of the zona pellucida
SO FERTILITY AND STERILITY
LA English
DT Article
DE Fertilization; acrosome; sperm; zona pellucida; DKKL1; IVF
ID MOUSE SPERM; MALE-MICE; MAMMALIAN FERTILIZATION; GENE-EXPRESSION;
SPERMATOZOA; ASTHENOZOOSPERMIA; HYALURONIDASE; CAPACITATION; FERTILITY;
CELLS
AB Objective: To determine the role of Dkkl1 in mouse development, viability, and fertility.
Design: Prospective experimental study.
Setting: Government research institution.
Animal(s): Mice of C57BL/6. B6D2F1/J, and 129X1/SvJ strains, as well as transgenic mice of mixed C57BL/6 and 129X1/SvJ strains were used for the studies.
Intervention(s): Expression of the Dkkl1 gene was characterized during early mouse development, and the effects of Dkkl1 ablation on reproduction and fertility were characterized in vitro and in vivo.
Main Outcome Measure(s): Dkkl1 RNA expression was determined by Northern blotting hybridization as well as quantitative reverse transcriptase-polymerase chain reaction assays. In vitro fertilization assays were used to assess fertility of sperm from male mice lacking functional Dkkl1.
Result(s): Dkkl1 is a gene unique to mammals that is expressed primarily in developing spermatocytes and its product localized in the acrosome of mature sperm. Here we show that Dkkl1 also is expressed in the trophectoderm/placental lineage. Surprisingly, embryos lacking DKKL1 protein developed into viable, fertile adults. Nevertheless, the ability of sperm that lacked DKKL1 protein to fertilize wild-type eggs was severely compromised in vitro. Because this defect could be overcome either by removal of the zona pellucida or by the presence of wild-type sperm. Dkkl1, either directly or indirectly, facilitates the ability of sperm to penetrate the zona pellucida. Penetration of the zona pellucida by Dkkl1 sperm was delayed in vivo as well as in vitro, but the delay in vivo was compensated by other factors during preimplantation development. Accordingly, Dkkl1 I males offer an in vitro fertilization model for identifying factors that may contribute to infertility.
Conclusion(s): DKKL1 is a mammalian-specific, acrosomal protein that strongly affects in vitro fertilization, although the effect is attenuated in vivo. (Fertil Steril (R) 2010;93:1533-7. (C)2010 by American Society for Reproductive Medicine.)
C1 [Kohn, Matthew J.; Yagi, Rieko; DePamphilis, Melvin L.; Kaneko, Kotaro J.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Sztein, Jorge] NEI, Genet Engn Core Facil, NIH, Bethesda, MD 20892 USA.
RP Kaneko, KJ (reprint author), NICHHD, NIH, Bldg 6,Room 3A-04,9000 Rockville Pike,6 Ctr Dr MS, Bethesda, MD 20892 USA.
EM KanekoK@mail.nih.gov
RI Sztein, Jorge/B-7165-2012;
OI Sztein, Jorge Mario/0000-0001-7047-2634
FU National Institute of Child Health and Human Development
FX This work was funded by the intramural program of the National Institute
of Child Health and Human Development. Animals were treated according to
the Guide for the Care and Use of Laboratory Animals, Institute of
Laboratory Animal Research, National Academy of Sciences, USA.
NR 36
TC 10
Z9 12
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 MAR 15
PY 2010
VL 93
IS 5
BP 1533
EP 1537
DI 10.1016/j.fertnstert.2009.06.010
PG 5
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 575BM
UT WOS:000276038700020
PM 19596312
ER
PT J
AU Taylor, JE
Miller, BT
Gray, KD
Scott, RT
Catherino, WH
Segars, JH
AF Taylor, Joelle E.
Miller, Bradley T.
Gray, Karen D.
Scott, Richard T., Jr.
Catherino, William H.
Segars, James H.
TI The mechanism responsible for the supraphysiologic gonadotropin surge in
females treated with gonadotropin-releasing hormone (GnRH) agonist and
primed with GnRH antagonist
SO FERTILITY AND STERILITY
LA English
DT Article
DE LH-RH; GnRH receptor; ovulation induction; LH surge; OHSS; ovarian
hyperstimulation syndrome; pituitary
ID FINAL OOCYTE MATURATION; IN-VITRO FERTILIZATION; OVARIAN
HYPERSTIMULATION SYNDROME; FOLLICLE-STIMULATING-HORMONE; HUMAN
CHORIONIC-GONADOTROPIN; MESSENGER-RIBONUCLEIC-ACID; PITUITARY LHRH
RECEPTORS; LONG-TERM TREATMENT; LUTEINIZING-HORMONE; DOWN-REGULATION
AB Objective: To elucidate the physiologic mechanism responsible for the supraphysiologic gonadotropin release from the pituitary induced by gonadotropin-releasing hormone (GnRH) agonist in female rats primed with GnRH antagonist.
Design: Controlled experimental intervention.
Setting: Government research facility.
Animal(s): Forty 8-week-old Sprague-Dawley rats.
Intervention(s): Forty oophorectomized rats were randomized into four treatment groups of 10: group A. control vehicles; group B. GnRH agonist (leuprolide acetate; 1.7 mu g/kg twice a day) on day 4; group C. GnRH antagonist (Nal-Lys; 3 mg/kg each day) days 1 to 4; or group D, GnRH antagonist (Nal-Lys; 3 mg/kg each day) days 1 to 4 plus GnRH agonist (1.7 mu g/kg twice a day) on day 4.
Main Outcome Measure(s): Immunohistochemical methods, Northern and in situ hybridization to quantitate pituitary follicle-stimulating hormone beta (FSH-beta), luteinizing hormone beta (LH-beta), and GnRH receptor (GnRH-R) messenger RNA (mRNA), and receptor protein levels in all treatment groups.
Result(s): Treatment with GnRH antagonist was associated with increased storage of gonadotropin in the pituitary for FSH-beta and LH-beta, but mRNA levels were unchanged. The GnRH-R mRNA decreased after GnRH-agonist treatment but remained stable in the GnRH-antagonist treatment groups. Levels of GnRH-R were decreased after GnRH-antagonist treatment.
Conclusion(s): These data indicate that the in vivo mechanism responsible for the exaggerated release of gonadotropins in rats primed with GnRH antagonist and treated with GnRH agonist was an increase in releasable gonadotropin pools coupled with a reduction in GnRH-R, but receptor function was preserved. (Fertil Steril (R) 2010;93:1668-75. (C)2010 by American Society for Reproductive Medicine.)
C1 [Taylor, Joelle E.; Miller, Bradley T.; Segars, James H.] NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA.
[Taylor, Joelle E.] Wake Forest Univ, Bowman Gray Sch Med, Dept Obstet & Gynecol, Winston Salem, NC 27103 USA.
[Miller, Bradley T.; Catherino, William H.; Segars, James H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
[Gray, Karen D.] NCI, NIH, Frederick, MD 21701 USA.
[Scott, Richard T., Jr.] Reprod Med Associates New Jersey, Morristown, NJ USA.
RP Segars, JH (reprint author), NICHD, Program Reprod & Adult Endocrinol, Bldg CRC,Room 1E3140,10 Ctr Dr, Bethesda, MD 20814 USA.
EM segarsj@mail.nih.gov
FU Intramural Research Program of the Reproductive Biology and Medicine
Branch; NICHD; NIH
FX Supported in part by the Intramural Research Program of the Reproductive
Biology and Medicine Branch, NICHD, NIH.
NR 43
TC 5
Z9 5
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 MAR 15
PY 2010
VL 93
IS 5
BP 1668
EP 1675
DI 10.1016/j.fertnstert.2008.12.047
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 575BM
UT WOS:000276038700037
PM 19200975
ER
PT J
AU Bertoia, M
Albanes, D
Mayne, ST
Mannisto, S
Virtamo, J
Wright, ME
AF Bertoia, Monica
Albanes, Demetrius
Mayne, Susan T.
Mannisto, Satu
Virtamo, Jarmo
Wright, Margaret E.
TI No association between fruit, vegetables, antioxidant nutrients and risk
of renal cell carcinoma
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE antioxidants; cohort study; diet; fruit; renal cell cancer; vegetables
ID CANCER-RISK; SWEDISH WOMEN; DIET; COHORT; VITAMIN; QUESTIONNAIRE;
CONSUMPTION; NUTRITION; PATTERNS; ETIOLOGY
AB Previous epidemiologic studies that have examined the relationship between renal cell carcinoma (RCC) risk and intakes of plant foods and antioxidant nutrients have yielded inconsistent results. We therefore examined the associations between intakes of fruit, vegetables, carotenoids, flavonoids, vitamin E and vitamin C and RCC risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort. At baseline, 27,062 male Finnish smokers aged 50-69 years completed a 276-item dietary questionnaire that included questions on frequency of consumption and portion size. During up to 19 years of follow-up, 255 men developed RCC. Cox proportional hazards models were utilized to estimate relative risks (RR) and 95% confidence intervals (CI). Despite a large range in intake, no association was observed between fruit, vegetables or antioxidant nutrients and RCC risk. For example, multivariate RRs and 95% CIs for the highest versus the lowest quartile of intake were 0.79 (0.55-1.14), 1.23 (0.85-1.79), 1.09 (0.74-1.60), 0.83 (0.57-1.21), 1.09 (0.73-1.64) and 0.99 (0.67-1.46) for fruit, vegetables, total carotenoids, total flavonoids, total vitamin E and vitamin C, respectively (all p values for trend > 0.05). Our results indicate that diet may not play a large role in the etiology of RCC in male smokers, although further examination of these associations in nonsmokers, women and diverse racial populations is warranted.
C1 [Wright, Margaret E.] Univ Illinois, Dept Pathol, Chicago, IL 60612 USA.
[Bertoia, Monica; Mayne, Susan T.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Bertoia, Monica; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Mannisto, Satu; Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland.
RP Wright, ME (reprint author), Univ Illinois, Dept Pathol MC 847, Coll Med, 840 S Wood St,CSN 130, Chicago, IL 60612 USA.
EM mewright@uic.edu
RI Albanes, Demetrius/B-9749-2015;
OI Mannisto, Satu/0000-0002-8668-3046
FU NIH; DHHS
FX The Intramural Research Program of the National Cancer Institute, NIH,
DHHS
NR 37
TC 19
Z9 19
U1 0
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 15
PY 2010
VL 126
IS 6
BP 1504
EP 1512
DI 10.1002/ijc.24829
PG 9
WC Oncology
SC Oncology
GA 567GU
UT WOS:000275434100021
PM 19685494
ER
PT J
AU Numaga, T
Nishida, M
Kiyonaka, S
Kato, K
Katano, M
Mori, E
Kurosaki, T
Inoue, R
Hikida, M
Putney, JW
Mori, Y
AF Numaga, Takuro
Nishida, Motohiro
Kiyonaka, Shigeki
Kato, Kenta
Katano, Masahiro
Mori, Emiko
Kurosaki, Tomohiro
Inoue, Ryuji
Hikida, Masaki
Putney, James W., Jr.
Mori, Yasuo
TI Ca2+ influx and protein scaffolding via TRPC3 sustain PKC beta and ERK
activation in B cells
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE B-cell receptor; Ca2+ signaling; Diacylglycerol; PKC beta; TRP channels
ID RECEPTOR POTENTIAL CHANNELS; CA2+-PERMEABLE CATION CHANNEL; KINASE-C;
TRANSIENT RECEPTOR; ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION;
CALCIUM-CHANNELS; T-LYMPHOCYTES; ENTRY; MEMBRANE
AB Ca2+ signaling mediated by phospholipase C that produces inositol 1,4,5-trisphosphate [Ins(1,4,5) P-3] and diacylglycerol (DAG) controls lymphocyte activation. In contrast to store-operated Ca2+ entry activated by Ins(1,4,5)P-3-induced Ca2+ release from endoplasmic reticulum, the importance of DAG-activated Ca2+ entry remains elusive. Here, we describe the physiological role of DAG-activated Ca2+ entry channels in B-cell receptor (BCR) signaling. In avian DT40 B cells, deficiency of transient receptor potential TRPC3 at the plasma membrane (PM) impaired DAG-activated cation currents and, upon BCR stimulation, the sustained translocation to the PM of protein kinase C beta (PKC beta) that activated extracellular signal-regulated kinase (ERK). Notably, TRPC3 showed direct association with PKC beta that maintained localization of PKC beta at the PM. Thus, TRPC3 functions as both a Ca2+-permeable channel and a protein scaffold at the PM for downstream PKC beta activation in B cells.
C1 [Numaga, Takuro; Kiyonaka, Shigeki; Kato, Kenta; Katano, Masahiro; Mori, Emiko; Mori, Yasuo] Kyoto Univ, Grad Sch Engn, Dept Synthet Chem & Biol Chem, Kyoto 6158510, Japan.
[Numaga, Takuro; Putney, James W., Jr.] NIEHS, Lab Signal Transduct, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Nishida, Motohiro] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol & Toxicol, Higashi Ku, Fukuoka 8128582, Japan.
[Kiyonaka, Shigeki; Mori, Yasuo] JST, CREST, Chiyoda Ku, Tokyo 1020075, Japan.
[Kurosaki, Tomohiro] RIKEN Res Ctr Allergy & Immunol, Lab Lymphocyte Differentiat, Tsurumi Ku, Kanagawa 2300045, Japan.
[Inoue, Ryuji] Fukuoka Univ, Sch Med, Dept Physiol, Jonan Ku, Fukuoka 8140180, Japan.
[Hikida, Masaki] Kyoto Univ, Grad Sch Med, Ctr Innovat Immunoregulat Technol & Therapeut, Kyoto 6068501, Japan.
RP Mori, Y (reprint author), Kyoto Univ, Grad Sch Engn, Dept Synthet Chem & Biol Chem, Kyoto 6158510, Japan.
EM mori@sbchem.kyoto-u.ac.jp
RI Kurosaki, Tomohiro/D-1306-2009
OI Kurosaki, Tomohiro/0000-0002-6352-304X
FU Ministry of Education, Culture, Sports, Science and Technology of Japan;
Japan Society for the Promotion of Sciences; NIH; National Institute of
Environmental Health Sciences
FX We thank Y. Aiba and S. Yamamoto for much technical advice and helpful
discussions, and R. Y. Tsien for mCherry and mStrawberry. This study was
supported by research grants from Ministry of Education, Culture,
Sports, Science and Technology of Japan and the Japan Society for the
Promotion of Sciences, and in part by the Intramural Program of the NIH,
National Institute of Environmental Health Sciences. Deposited in PMC
for release after 12 months.
NR 63
TC 29
Z9 30
U1 0
U2 1
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD MAR 15
PY 2010
VL 123
IS 6
BP 927
EP 938
DI 10.1242/jcs.061051
PG 12
WC Cell Biology
SC Cell Biology
GA 563UQ
UT WOS:000275160800013
PM 20179100
ER
PT J
AU Liao, XH
Buggey, J
Kimmel, AR
AF Liao, Xin-Hua
Buggey, Jonathan
Kimmel, Alan R.
TI Chemotactic activation of Dictyostelium AGC-family kinases AKT and PKBR1
requires separate but coordinated functions of PDK1 and TORC2
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE PDK1; Chemotaxis; PI3K/PtdIns(3,4,5)P(3); BAR domains; PH domains; TORC2
ID RICTOR-MTOR COMPLEX; SUBSTRATE-SPECIFICITY; AKT/PKB; PROTEIN;
IDENTIFICATION; DISCOIDEUM; DOMAIN; BAR; PHOSPHORYLATION; RESPONSES
AB Protein kinases AKT and PKBR1 of Dictyostelium belong to the AGC protein kinase superfamily. AKT and PKBR1 are phosphorylated at similar sites by phosphoinositide-dependent kinase 1 (PDK1) and TORC2 kinases; however, they have different subcellular localizing domains. AKT has a phosphoinositide 3-kinase (PI3K)/phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P(3)]-regulated PH (pleckstrin homology) domain whereas PKBR1 is myristoylated and persistently membrane localized. Using strains defective for PI3K/PtdIns(3,4,5)P(3)-, PDK1- and TORC2-signaling or strains that express phospho-site mutants of AKT and PKBR1, we dissect the different roles of PI3K/PtdIns(3,4,5)P(3), PDK1 and TORC2. We show that activation of AKT and PKBR1 requires PDK1-site phosphorylation, but that phosphorylation by TORC2 is insufficient for AKT or PKBR1 activation. However, PDK1-site phosphorylation is dependent on phosphorylation by TORC2, which suggests that there is regulatory coordination among PDK1, TORC2 and their phospho-site targets. This defines a separate input for signaling in control of chemotaxis and dependency on PDK1 function. We also demonstrate that PDK1 in Dictyostelium functions independently of PI3K/PtdIns(3,4,5)P(3). Finally, we show that AKT and PKBR1 exhibit substrate selectivity and identify two novel lipid-interacting proteins preferentially phosphorylated by AKT. Despite certain similarities, AKT and PKBR1 have distinct regulatory paths that impact activation and effector targeting, with PDK1 serving a central role.
C1 [Liao, Xin-Hua; Buggey, Jonathan; Kimmel, Alan R.] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Kimmel, AR (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM ark1@helix.nih.gov
FU National Institutes of Health; National Institute of Diabetes and
Digestive and Kidney Diseases
FX We thank Xiuli Huang, Marielle Young and Colette Young for assistance in
gene targeting experiments. David Eric Anderson was invaluable for mass
spectrometric analyses. Finally, we thank Dictybase and colleagues for
various strains. This research was supported by the Intramural Research
Program of the National Institutes of Health, the National Institute of
Diabetes and Digestive and Kidney Diseases. Deposited in PMC for release
after 12 months.
NR 35
TC 26
Z9 27
U1 1
U2 1
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD MAR 15
PY 2010
VL 123
IS 6
BP 983
EP 992
DI 10.1242/jcs.064022
PG 10
WC Cell Biology
SC Cell Biology
GA 563UQ
UT WOS:000275160800018
PM 20200230
ER
PT J
AU Wilson, MS
Madala, SK
Ramalingam, TR
Gochuico, BR
Rosas, IO
Cheever, AW
Wynn, TA
AF Wilson, Mark S.
Madala, Satish K.
Ramalingam, Thirumalai R.
Gochuico, Bernadette R.
Rosas, Ivan O.
Cheever, Allen W.
Wynn, Thomas A.
TI Bleomycin and IL-1 beta-mediated pulmonary fibrosis is IL-17A dependent
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID CELL-MEDIATED PATHOLOGY; IL-17-PRODUCING T-CELLS; INDUCED LUNG INJURY;
NF-KAPPA-B; TGF-BETA; IN-VIVO; INTERFERON-GAMMA; INTRATRACHEAL
BLEOMYCIN; AUTOIMMUNE INFLAMMATION; NEUTROPHIL RECRUITMENT
AB Idiopathic pulmonary fibrosis (IPF) is a destructive inflammatory disease with limited therapeutic options. To better understand the inflammatory responses that precede and concur with collagen deposition, we used three models of pulmonary fibrosis and identify a critical mechanistic role for IL-17A. After exposure to bleomycin (BLM), but not Schistosoma mansoni eggs, IL-17A produced by CD4(+) and gamma delta(+) T cells induced significant neutrophilia and pulmonary fibrosis. Studies conducted with C57BL/6 il17a(-/-) mice confirmed an essential role for IL-17A. Mechanistically, using ifn gamma(-/-), il10(-/-), il10(-/-) il12p40(-/-), and il10(-/-) il17a(-/-) mice and TGF-beta blockade, we demonstrate that IL-17A-driven fibrosis is suppressed by IL-10 and facilitated by IFN-gamma and IL-12/23p40. BLM-induced IL-17A production was also TGF-beta dependent, and recombinant IL-17A-mediated fibrosis required TGF-beta, suggesting cooperative roles for IL-17A and TGF-beta in the development of fibrosis. Finally, we show that fibrosis induced by IL-1 beta, which mimics BLM-induced fibrosis, is also highly dependent on IL-17A. IL-17A and IL-1 beta were also increased in the bronchoalveolar lavage fluid of patients with IPF. Together, these studies identify a critical role for IL-17A in fibrosis, illustrating the potential utility of targeting IL-17A in the treatment of drug and inflammation-induced fibrosis.
C1 [Wilson, Mark S.; Madala, Satish K.; Ramalingam, Thirumalai R.; Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Gochuico, Bernadette R.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Rosas, Ivan O.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Cheever, Allen W.] Biomed Res Inst, Rockville, MD 20852 USA.
RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
EM twynn@niaid.nih.gov
RI Wynn, Thomas/C-2797-2011
FU National Institutes of Health; National Institute of Allergy and
Infectious Disease; National Human Genome Research Institute
FX We are very grateful to the Intramural Research Program of the National
Institutes of Health, National Institute of Allergy and Infectious
Disease, and National Human Genome Research Institute, who supported
this research.
NR 79
TC 193
Z9 215
U1 6
U2 21
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD MAR 15
PY 2010
VL 207
IS 3
BP 535
EP 552
DI 10.1084/jem.20092121
PG 18
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 569KB
UT WOS:000275593900009
PM 20176803
ER
PT J
AU Quezada, SA
Simpson, TR
Peggs, KS
Merghoub, T
Vider, J
Fan, XZ
Blasberg, R
Yagita, H
Muranski, P
Antony, PA
Restifo, NP
Allison, JP
AF Quezada, Sergio A.
Simpson, Tyler R.
Peggs, Karl S.
Merghoub, Taha
Vider, Jelena
Fan, Xiaozhou
Blasberg, Ronald
Yagita, Hideo
Muranski, Pawel
Antony, Paul A.
Restifo, Nicholas P.
Allison, James P.
TI Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate
large established melanoma after transfer into lymphopenic hosts
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID ANTITUMOR IMMUNE-RESPONSE; MINOR HISTOCOMPATIBILITY ANTIGEN; NEGATIVE
CANCER-CELLS; METASTATIC MELANOMA; TH1 CELLS; IN-VIVO; ADOPTIVE
IMMUNOTHERAPY; EFFECTOR-CELLS; CD4+T CELLS; THERAPY
AB Adoptive transfer of large numbers of tumor-reactive CD8(+) cytotoxic T lymphocytes (CTLs) expanded and differentiated in vitro has shown promising clinical activity against cancer. However, such protocols are complicated by extensive ex vivo manipulations of tumor-reactive cells and have largely focused on CD8(+) CTLs, with much less emphasis on the role and contribution of CD4(+) T cells. Using a mouse model of advanced melanoma, we found that transfer of small numbers of naive tumor-reactive CD4(+) T cells into lymphopenic recipients induces substantial T cell expansion, differentiation, and regression of large established tumors without the need for in vitro manipulation. Surprisingly, CD4(+) T cells developed cytotoxic activity, and tumor rejection was dependent on class II-restricted recognition of tumors by tumor-reactive CD4(+) T cells. Furthermore, blockade of the co-inhibitory receptor CTL-associated antigen 4 (CTLA-4) on the transferred CD4(+) T cells resulted in greater expansion of effector T cells, diminished accumulation of tumor-reactive regulatory T cells, and superior antitumor activity capable of inducing regression of spontaneous mouse melanoma. These findings suggest a novel potential therapeutic role for cytotoxic CD4(+) T cells and CTLA-4 blockade in cancer immunotherapy, and demonstrate the potential advantages of differentiating tumor-reactive CD4(+) cells in vivo over current protocols favoring in vitro expansion and differentiation.
C1 [Quezada, Sergio A.; Simpson, Tyler R.; Peggs, Karl S.; Fan, Xiaozhou; Allison, James P.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, Ludwig Ctr Canc Immunotherapy, New York, NY 10021 USA.
[Quezada, Sergio A.; Simpson, Tyler R.; Peggs, Karl S.; Merghoub, Taha; Fan, Xiaozhou; Allison, James P.] Mem Sloan Kettering Canc Ctr, Dept Immunol, New York, NY 10021 USA.
[Vider, Jelena; Blasberg, Ronald] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA.
[Yagita, Hideo] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 1138421, Japan.
[Muranski, Pawel; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Antony, Paul A.] Univ Maryland, Sch Med, Program Mol Microbiol & Immunol, Dept Pathol, Baltimore, MD 21201 USA.
RP Allison, JP (reprint author), Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, Ludwig Ctr Canc Immunotherapy, New York, NY 10021 USA.
EM allisonj@mskcc.org
RI PEGGS, Karl/B-3869-2009; Restifo, Nicholas/A-5713-2008; Muranski,
Pawel/E-5572-2010; Vider, Jelena/B-9663-2011;
OI Vider, Jelena/0000-0003-1696-9812; Restifo, Nicholas
P./0000-0003-4229-4580
FU Irvington Institute Fellowship Program of the Cancer Research Institute;
Millennium Nucleus on Immunology and Immunotherapy; Pontificia
Universidad Catolica de Chile; Canadian Institutes of Health; Leukaemia
Research Fund; Experimental Therapeutics Center of Memorial
Sloan-Kettering Cancer Center; Swim Across America Foundation
FX S. A. Quezada is a Research Fellow funded by the Irvington Institute
Fellowship Program of the Cancer Research Institute and a junior member
of the Millennium Nucleus on Immunology and Immunotherapy, Pontificia
Universidad Catolica de Chile. T. R. Simpson is supported by a Canadian
Institutes of Health Doctoral Research Award. K. S. Peggs is currently
an investigator at the Department of Haematology, University College
London Cancer Institute, University College London, and receives funding
from the Leukaemia Research Fund. J.P. Allison is an investigator of the
Howard Hughes Medical Institute and holds the David H. Koch Chair in
Immunological Studies at the Memorial Sloan-Kettering Cancer Center.
This work was also supported by the Experimental Therapeutics Center of
Memorial Sloan-Kettering Cancer Center funded by W. H. Goodwin and A.
Goodwin, and the Swim Across America Foundation.
NR 49
TC 263
Z9 273
U1 1
U2 19
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD MAR 15
PY 2010
VL 207
IS 3
BP 637
EP 650
DI 10.1084/jem.20091918
PG 14
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 569KB
UT WOS:000275593900016
PM 20156971
ER
PT J
AU Xie, Y
Akpinarli, A
Maris, C
Hipkiss, EL
Lane, M
Kwon, EKM
Muranski, P
Restifo, NP
Antony, PA
AF Xie, Ying
Akpinarli, Akguel
Maris, Charles
Hipkiss, Edward L.
Lane, Malcolm
Kwon, Eun-Kyung M.
Muranski, Pawel
Restifo, Nicholas P.
Antony, Paul Andrew
TI Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate
established melanoma
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID SUPERIOR ANTITUMOR IMMUNITY; DENDRITIC CELLS; METASTATIC MELANOMA;
CANCER REGRESSION; LYMPH-NODES; IFN-GAMMA; CLASS-II; HOMEOSTATIC
PROLIFERATION; SECONDARY EXPANSION; STEM-CELLS
AB In vitro differentiated CD8(+) T cells have been the primary focus of immunotherapy of cancer with little focus on CD4(+) T cells. Immunotherapy involving in vitro differentiated T cells given after lymphodepleting regimens significantly augments antitumor immunity in animals and human patients with cancer. However, the mechanisms by which lymphopenia augments adoptive cell therapy and the means of properly differentiating T cells in vitro are still emerging. We demonstrate that naive tumor/self-specific CD4(+) T cells naturally differentiated into T helper type 1 cytotoxic T cells in vivo and caused the regression of established tumors and depigmentation in lymphopenic hosts. Therapy was independent of vaccination, exogenous cytokine support, CD8(+), B, natural killer (NK), and NKT cells. Proper activation of CD4(+) T cells in vivo was important for tumor clearance, as naive tumor-specific CD4(+) T cells could not completely treat tumor in lymphopenic common gamma chain (gamma(c))-deficient hosts.. c signaling in the tumor-bearing host was important for survival and proper differentiation of adoptively transferred tumor-specific CD4(+) T cells. Thus, these data provide a platform for designing immunotherapies that incorporate tumor/self-reactive CD4(+) T cells.
C1 [Antony, Paul Andrew] Univ Maryland, Sch Med, Program Mol Microbiol & Immunol, Baltimore, MD 21201 USA.
[Xie, Ying; Kwon, Eun-Kyung M.; Antony, Paul Andrew] Univ Maryland, Sch Med, Lab Immunol & Canc Immunotherapy, Dept Pathol, Baltimore, MD 21201 USA.
[Lane, Malcolm] Univ Maryland, Sch Med, Dept Epidemiol & Preventat Med, Baltimore, MD 21201 USA.
[Antony, Paul Andrew] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Tumor Immunol & Immunotherapy Program, Baltimore, MD 21201 USA.
[Antony, Paul Andrew] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Program Oncol, Baltimore, MD 21201 USA.
[Akpinarli, Akguel] NIAID, Cellular & Mol Immunol Lab, Bethesda, MD 20892 USA.
[Maris, Charles; Hipkiss, Edward L.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA.
[Muranski, Pawel; Restifo, Nicholas P.] Ctr Canc Res, Surg Branch, Bethesda, MD 20892 USA.
RP Antony, PA (reprint author), Univ Maryland, Sch Med, Program Mol Microbiol & Immunol, Baltimore, MD 21201 USA.
EM pantony@som.umaryland.edu
RI Restifo, Nicholas/A-5713-2008; Muranski, Pawel/E-5572-2010;
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Center for Cancer Research; K22 NCI [5K22CA125200]; Melanoma Research
Foundation
FX This research was initiated at the Surgery Branch of the National Cancer
Institute and was supported by the Center for Cancer Research. The work
was further supported by a K22 NCI career transition award (5K22CA125200
to P. A. Antony) and the Melanoma Research Foundation (P. A. Antony).
NR 86
TC 166
Z9 171
U1 0
U2 10
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD MAR 15
PY 2010
VL 207
IS 3
BP 651
EP 667
DI 10.1084/jem.20091921
PG 17
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 569KB
UT WOS:000275593900017
PM 20156973
ER
PT J
AU Guimond, M
Freud, AG
Mao, HC
Yu, JH
Blaser, BW
Leong, JW
Vandeusen, JB
Dorrance, A
Zhang, JY
Mackall, CL
Caligiuri, MA
AF Guimond, Martin
Freud, Aharon G.
Mao, Hsiaoyin C.
Yu, Jianhua
Blaser, Bradley W.
Leong, Jeffrey W.
Vandeusen, Jeffrey B.
Dorrance, Adrienne
Zhang, Jianying
Mackall, Crystal L.
Caligiuri, Michael A.
TI In Vivo Role of Flt3 Ligand and Dendritic Cells in NK Cell Homeostasis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; HEMATOPOIETIC PROGENITOR CELLS; CD8(+) T-CELLS;
TRANS PRESENTATION; MESSENGER-RNA; CUTTING EDGE; IL-15; INTERLEUKIN-15;
IL-15R-ALPHA; EXPRESSION
AB IL-15 is required for NK cell development and homeostasis in vivo. Because IL-15 is presented in traits via its high-affinity IL-15R alpha-chain to cells expressing the IL-15R beta gamma complex, we postulated that certain IL-15-bearing cells must be required for NK cell homeostasis. Using IL-15(WT/WT) and IL-15(-/-) mice, bone marrow chimeras with normal cellularity, and a selective depletion of CD11c(hi) dendritic cells (DCs), we demonstrate that ablation of the resting CD11c(hi) DC population results in a highly significant decrease in the absolute number of mature NK cells. In contrast, administration of Flt3 ligand increases the CD11c(hi) DC population, which, when expressing IL-15, significantly expands mature NK cells via enhanced survival and proliferation. In summary, a CD11c(hi) DC population expressing IL-15 is required to maintain NK cell homeostasis under conditions of normal cellularity and also is required to mediate Flt3 ligand-induced NK cell expansion in vivo. The Journal of Immunology, 2010, 184: 2769-2775.
C1 [Caligiuri, Michael A.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Guimond, Martin; Mao, Hsiaoyin C.; Yu, Jianhua; Dorrance, Adrienne; Caligiuri, Michael A.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Freud, Aharon G.; Blaser, Bradley W.; Vandeusen, Jeffrey B.] Ohio State Univ, Med Sci Program, Columbus, OH 43210 USA.
[Freud, Aharon G.; Blaser, Bradley W.; Vandeusen, Jeffrey B.] Ohio State Univ, Integrated Biomed Sci Grad Program, Columbus, OH 43210 USA.
[Zhang, Jianying] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA.
[Caligiuri, Michael A.] Ohio State Univ, Div Hematol & Oncol, Dept Internal Med, Columbus, OH 43210 USA.
[Leong, Jeffrey W.; Mackall, Crystal L.] NCI, NIH, Bethesda, MD 20892 USA.
RP Caligiuri, MA (reprint author), Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
EM Michael.Caligiuri@osumc.edu
FU National Cancer Institute [CA95426, CA68458]; Ohio State University;
James Cancer Hospital; Solove Research Institute
FX This work was supported by National Cancer Institute Grants CA95426 and
CA68458 (to M.A.C.) and the Intramural Program of the National Cancer
Institute (to C.L.M.). M.G. is the recipient of the Up on The Roof
fellowship award from The Ohio State University Comprehensive Cancer
Center, James Cancer Hospital, and Solove Research Institute.
NR 42
TC 26
Z9 27
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2010
VL 184
IS 6
BP 2769
EP 2775
DI 10.4049/jimmunol.0900685
PG 7
WC Immunology
SC Immunology
GA 566QW
UT WOS:000275389000005
PM 20142363
ER
PT J
AU Dalet, A
Vigneron, N
Stroobant, V
Hanada, K
Van den Eynde, BJ
AF Dalet, Alexandre
Vigneron, Nathalie
Stroobant, Vincent
Hanada, Ken-ichi
Van den Eynde, Benoit J.
TI Splicing of Distant Peptide Fragments Occurs in the Proteasome by
Transpeptidation and Produces the Spliced Antigenic Peptide Derived from
Fibroblast Growth Factor-5
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID 20S PROTEASOME; THERMOPLASMA-ACIDOPHILUM; DEGRADATION; ACTIVATION;
RESOLUTION; PROTEINS
AB Peptide splicing is a newly described mode of production of antigenic peptides presented by MHC class I molecules, whereby two noncontiguous fragments of the parental protein are joined together after excision of the intervening segment. Three spliced peptides have been described. In two cases, splicing involved the excision of a short intervening segment of 4 or 6 aa and was shown to occur in the proteasome by transpeptidation resulting from the nucleophilic attack of an acyl-enzyme intermediate by the N terminus of the other peptide fragment. For the third peptide, which is derived from fibroblast growth factor-5 (FGF-5), the splicing mechanism remains unknown. In this case, the intervening segment is 40 aa long. This much greater length made the transpeptidation model more difficult to envision. Therefore, we evaluated the role of the proteasome in the splicing of this peptide. We observed that the spliced FGF-5 peptide was produced in vitro after incubation of proteasomes with a 49-aa-long precursor peptide. We evaluated the catalytic mechanism by incubating proteasomes with various precursor peptides. The results confirmed the transpeptidation model of splicing. By transfecting a series of mutant FGF-5 constructs, we observed that reducing the length of the intervening segment increased the production of the spliced peptide, as predicted by the transpeptidation model. Finally, we observed that traits-splicing (i.e., splicing of fragments from two distinct proteins) can occur in the cell, but with a much lower efficacy than splicing of fragments from the same protein. The Journal of Immunology, 2010, 184: 3016-3024.
C1 [Van den Eynde, Benoit J.] Catholic Univ Louvain, Ludwig Inst Canc Res, Duve Inst, Brussels Branch, B-1200 Brussels, Belgium.
[Hanada, Ken-ichi] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Van den Eynde, BJ (reprint author), Catholic Univ Louvain, Ludwig Inst Canc Res, Duve Inst, Brussels Branch, Ave Hippocrate 74,UCL 7459, B-1200 Brussels, Belgium.
EM benoit.vandeneynde@bru.licr.org
RI Hanada, Ken-ichi/L-2481-2013
OI Hanada, Ken-ichi/0000-0003-2959-1257
FU European Community [LSHC-2006-518234]; Fonds J. Maisin (Belgium);
Fondation contre le Cancer (Belgium); Fonds National de la Recherche
Scientifique (Belgium); Fonds National de la Recherche Scientifique
FX This work was supported by the European Community under the Sixth
Framework Programme (Grant LSHC-2006-518234: CancerImmunotherapy); by
the Belgian Programme on Interuniversity Poles of Attraction initiated
by the Belgian State, Prime Ministre's Office, Science Policy
Programming: and by grants from the Fonds J. Maisin (Belgium), the
Fondation contre le Cancer (Belgium), and the Fonds National de la
Recherche Scientifique (Belgium). A.D. is supported by a Televie
fellowship from the Fonds National de la Recherche Scientifique. and
N.V. is a postdoctoral researcher with the Fonds National de la
Recherche Scientifique.
NR 24
TC 27
Z9 27
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2010
VL 184
IS 6
BP 3016
EP 3024
DI 10.4049/jimmunol.0901277
PG 9
WC Immunology
SC Immunology
GA 566QW
UT WOS:000275389000030
PM 20154207
ER
PT J
AU Motiwala, AS
Dai, Y
Jones-Lopez, EC
Hwang, SH
Lee, JS
Cho, SN
Via, LE
Barry, CE
Alland, D
AF Motiwala, Alifiya S.
Dai, Yang
Jones-Lopez, Edward C.
Hwang, Soo-Hee
Lee, Jong Seok
Cho, Sang Nae
Via, Laura E.
Barry, Clifton E., III
Alland, David
TI Mutations in Extensively Drug-Resistant Mycobacterium tuberculosis That
Do Not Code for Known Drug-Resistance Mechanisms
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID ETHAMBUTOL; VIRULENCE; EVOLUTION; STRAINS; COST
AB Background. Highly lethal outbreaks of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are increasing. Whole-genome sequencing of KwaZulu-Natal MDR and XDR outbreak strains prevalent in human immunodeficiency virus (HIV)-infected patients by the Broad Institute identified 22 novel mutations which were unique to the XDR genome or shared only by the MDR and XDR genomes and not already known to be associated with drug resistance.
Methods. We studied the 12 novel mutations which were not located in highly-repetitive genes to identify mutations that were truly associated with drug resistance or were likely to confer a specific fitness advantage.
Results. None of these mutations could be found in a phylogenetically and geographically diverse set of drug-resistant and drug-susceptible Mycobacterium tuberculosis isolates, suggesting that these mutations are unique to the KZN clone. Examination of the 600-basepair region flanking each mutation revealed 26 new mutations. We searched for a convergent evolutionary signal in the new mutations for evidence that they emerged under selective pressure, consistent with increased fitness. However, all but 1 rare mutation were monophyletic, indicating that the mutations were markers of strain phylogeny rather than fitness or drug resistance.
Conclusions. Our results suggest that virulent XDR tuberculosis in immunocompromised HIV-infected patients can evolve without generalizable fitness changes or other XDR-specific mutations.
C1 [Motiwala, Alifiya S.; Dai, Yang; Jones-Lopez, Edward C.; Alland, David] Univ Med & Dent New Jersey, New Jersey Med Sch, Div Infect Dis, Dept Med, Newark, NJ 07103 USA.
[Motiwala, Alifiya S.; Dai, Yang; Jones-Lopez, Edward C.; Alland, David] Univ Med & Dent New Jersey, New Jersey Med Sch, Ruy V Lourenco Ctr Study Emerging & Reemerging Pa, Newark, NJ 07103 USA.
[Hwang, Soo-Hee] Natl Masan TB Hosp, Masan, South Korea.
[Lee, Jong Seok] Int TB Res Ctr, Masan, South Korea.
[Cho, Sang Nae] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea.
[Via, Laura E.; Barry, Clifton E., III] NIH, Bethesda, MD 20892 USA.
RP Alland, D (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Div Infect Dis, Dept Med, 185 S Orange Ave,MSB A920C, Newark, NJ 07103 USA.
EM allandda@umdnj.edu
RI Barry, III, Clifton/H-3839-2012;
OI Via, Laura/0000-0001-6074-9521
FU National Institutes of Health [AI065663]; National Institutes of Health,
National Institute of Allergy and Infectious Disease
FX Financial support: National Institutes of Health grant AI065663 and the
intramural research program of the National Institutes of Health,
National Institute of Allergy and Infectious Disease.
NR 15
TC 13
Z9 14
U1 3
U2 9
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 15
PY 2010
VL 201
IS 6
BP 881
EP 888
DI 10.1086/650999
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 557JH
UT WOS:000274664900011
PM 20136412
ER
PT J
AU Rockx, B
Donaldson, E
Frieman, M
Sheahan, T
Corti, D
Lanzavecchia, A
Baric, RS
AF Rockx, Barry
Donaldson, Eric
Frieman, Matthew
Sheahan, Timothy
Corti, Davide
Lanzavecchia, Antonio
Baric, Ralph S.
TI Escape from Human Monoclonal Antibody Neutralization Affects In Vitro
and In Vivo Fitness of Severe Acute Respiratory Syndrome Coronavirus
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID RECEPTOR-BINDING DOMAIN; SARS-CORONAVIRUS; STRUCTURAL BASIS; COV;
DETERMINANTS; MUTANTS; SUBUNIT; DISEASE; EPITOPE; MICE
AB Background. Severe acute respiratory syndrome (SARS) emerged as a human disease in 2002. Detailed phylogenetic analysis and epidemiologic studies have suggested that the SARS coronavirus (SARS-CoV) originated from animals. The spike (S) glycoprotein has been identified as a major target of protective immunity and contains >= 3 regions that are targeted by neutralizing antibodies in the S1 and S2 domains. We previously characterized a panel of neutralizing human monoclonal antibodies (MAbs), but the majority of epitopes recognized by the MAbs remain unknown.
Methods. In the present study, we generated neutralization escape mutants and studied the effect of these neutralization escape mutations on human and animal receptor usage as well as on in vitro and in vivo fitness.
Results. Distinct but partially overlapping sets of amino acids were identified that are critical to the binding of MAbs with differential neutralization profiles. We also identified possible interactions between the S1 and S2 domains of the SARS-CoV S glycoprotein. Finally, we showed that escape from neutralization usually attenuates SARS-CoV infection.
Conclusions. These data provide a mechanism for overcoming neutralization escape by use of broadly cross-reactive cocktails of cross-neutralizing MAbs that recognize residues within the receptor-binding domain that are critical for virus replication and virulence.
C1 [Rockx, Barry; Donaldson, Eric; Frieman, Matthew; Sheahan, Timothy; Baric, Ralph S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Baric, Ralph S.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
[Rockx, Barry] NIAID, Rocky Mt Lab, NIH, Hamilton, MT 59840 USA.
[Corti, Davide; Lanzavecchia, Antonio] Biomed Res Inst, Bellinzona, Switzerland.
RP Baric, RS (reprint author), Univ N Carolina, Dept Epidemiol, Campus Box 7435, Chapel Hill, NC 27599 USA.
EM rbaric@email.unc.edu
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [P01-AI059443, AI059136]; European Union
[N.SP22.CT.2004.511065]
FX Financial support: National Institute of Allergy and Infectious
Diseases, National Institutes of Health (grants P01-AI059443 and
AI059136 to R.B.); and European Union (SARSVAC grant
N.SP22.CT.2004.511065 to A.L.).
NR 28
TC 24
Z9 26
U1 0
U2 2
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 15
PY 2010
VL 201
IS 6
BP 946
EP 955
DI 10.1086/651022
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 557JH
UT WOS:000274664900018
PM 20144042
ER
PT J
AU Otto, M
Wardenburg, JB
Deleo, FR
AF Otto, Michael
Wardenburg, Juliane Bubeck
DeLeo, Frank R.
TI The Panton-Valentine Leukocidin Is a Virulence Factor in a Murine Model
of Necrotizing Pneumonia Reply
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Letter
ID STAPHYLOCOCCUS-AUREUS; EXPRESSION; MUTATION
C1 [Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
[Wardenburg, Juliane Bubeck] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA.
[DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT USA.
RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, 9000 Rockville Pike,Bldg 33, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
OI Otto, Michael/0000-0002-2222-4115
NR 11
TC 0
Z9 0
U1 0
U2 2
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 15
PY 2010
VL 201
IS 6
BP 969
EP 970
DI 10.1086/651027
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 557JH
UT WOS:000274664900021
ER
PT J
AU Luo, QF
Lu, H
Lu, HB
Yang, YH
Gao, JH
AF Luo, Qingfei
Lu, Huo
Lu, Hanbing
Yang, Yihong
Gao, Jia-Hong
TI Comparison of visually evoked local field potentials in isolated turtle
brain: Patterned versus blank stimulation
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Turtle; Preparation; Local field potential; Visual; Cortex; Tectum
ID NEURONAL CURRENTS; PYRAMIDAL NEURONS; RECEPTIVE FIELDS; STRIATE CORTEX;
LIGHT-FLASHES; MRI; RESPONSES; CELLS; POPULATIONS; DIFFUSE
AB Isolated turtle brain/eye preparation has recently been used as a bloodless animal model for detecting the magnetic resonance imaging (MRI) signal changes produced by visually evoked neuronal currents. The present work aims to determine whether checkerboard-patterned or full field flash (blank) stimulation should be used in order to achieve stronger neuronal responses in turtle brain/eye preparation. The knowledge gained in this study is essential for optimizing the visual stimulation methods in functional neuroimaging studies using turtle brain/eye preparation. In this study, visually evoked local field potentials (LFPs) were measured and compared in turtle visual cortex and optic tectum elicited by checkerboard and full field flash stimuli with three different inter-stimulus intervals (ISIs = 5, 10, and 16 s). It was found that the behavior of neuronal adaptation in the cortical and tectal LFP signals for checkerboard stimulation was comparable to flash stimulation. In addition, there was no significant difference in the LFP peak amplitudes (ISI = 16 s) between these two stimuli. These results indicate that the intensity of neuronal responses to checkerboard is comparable to flash stimulation. These two stimulation methods should be equivalent in functional neuroimaging studies using turtle brain/eye preparation. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Luo, Qingfei; Gao, Jia-Hong] Univ Chicago, Brain Res Imaging Ctr, Chicago, IL 60637 USA.
[Luo, Qingfei; Gao, Jia-Hong] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA.
[Lu, Huo] Philadelphia Coll Osteopath Med, Dept Basic Sci, Suwanee, GA 30024 USA.
[Lu, Hanbing; Yang, Yihong] NIDA, NIH, Baltimore, MD 21224 USA.
[Gao, Jia-Hong] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
RP Gao, JH (reprint author), Univ Chicago, Brain Res Imaging Ctr, 5841 S Maryland Ave,MC 2026, Chicago, IL 60637 USA.
EM jgao@uchicago.edu
OI Luo, Qingfei/0000-0002-1078-799X
FU NIH [RO1 EB004753]; NIH/NIDA
FX We thank D. Senseman for helping with the experimental setup and
valuable advice and comments. We also thank P. Ulinski for useful
discussion. This work was supported by a NIH grant (RO1 EB004753 to JHG)
and the Intramural Research Program of the NIH/NIDA.
NR 28
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD MAR 15
PY 2010
VL 187
IS 1
BP 26
EP 32
DI 10.1016/j.jneumeth.2009.12.005
PG 7
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 571QP
UT WOS:000275769900004
PM 20034520
ER
PT J
AU Thangavel, S
Mendoza-Maldonado, R
Tissino, E
Sidorova, JM
Yin, JH
Wang, WD
Monnat, RJ
Falaschi, A
Vindigni, A
AF Thangavel, Saravanabhavan
Mendoza-Maldonado, Ramiro
Tissino, Erika
Sidorova, Julia M.
Yin, Jinhu
Wang, Weidong
Monnat, Raymond J., Jr.
Falaschi, Arturo
Vindigni, Alessandro
TI Human RECQ1 and RECQ4 Helicases Play Distinct Roles in DNA Replication
Initiation
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID ROTHMUND-THOMSON-SYNDROME; ORIGIN RECOGNITION COMPLEX; WERNER-SYNDROME
PROTEIN; BLOOM-SYNDROME PROTEIN; CELL-CYCLE; SYNDROME GENE; S-PHASE; BLM
HELICASE; FORK; ACTIVATION
AB Cellular and biochemical studies support a role for all five human RecQ helicases in DNA replication; however, their specific functions during this process are unclear. Here we investigate the in vivo association of the five human RecQ helicases with three well-characterized human replication origins. We show that only RECQ1 (also called RECQL or RECQL1) and RECQ4 (also called RECQL4) associate with replication origins in a cell cycle-regulated fashion in unperturbed cells. RECQ4 is recruited to origins at late G(1), after ORC and MCM complex assembly, while RECQ1 and additional RECQ4 are loaded at origins at the onset of S phase, when licensed origins begin firing. Both proteins are lost from origins after DNA replication initiation, indicating either disassembly or tracking with the newly formed replisome. Nascent-origin DNA synthesis and the frequency of origin firing are reduced after RECQ1 depletion and, to a greater extent, after RECQ4 depletion. Depletion of RECQ1, though not that of RECQ4, also suppresses replication fork rates in otherwise unperturbed cells. These results indicate that RECQ1 and RECQ4 are integral components of the human replication complex and play distinct roles in DNA replication initiation and replication fork progression in vivo.
C1 [Thangavel, Saravanabhavan; Mendoza-Maldonado, Ramiro; Tissino, Erika; Falaschi, Arturo; Vindigni, Alessandro] Int Ctr Genet Engn & Biotechnol, I-34149 Trieste, Italy.
[Thangavel, Saravanabhavan; Falaschi, Arturo] Scuola Normale Super Pisa, Mol Biol Lab, I-56124 Pisa, Italy.
[Sidorova, Julia M.; Monnat, Raymond J., Jr.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Monnat, Raymond J., Jr.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Yin, Jinhu; Wang, Weidong] NIA, Genet Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Falaschi, Arturo] CNR, Ist Fisiol Clin, I-56124 Pisa, Italy.
RP Vindigni, A (reprint author), Int Ctr Genet Engn & Biotechnol, Padriciano 99, I-34149 Trieste, Italy.
EM vindigni@icgeb.org
OI Sidorova, Julia/0000-0001-5502-4323
FU Associazione Italiana per la Ricerca sul Cancro (AIRC); NCI [PO1
CA77852]; National Institute on Aging [AG000661-06]; National Institutes
of Health
FX This work was supported by a grant from the Associazione Italiana per la
Ricerca sul Cancro (AIRC) to A.V., by NCI grant PO1 CA77852 to R.J.M.,
by grants from the AIRC and the Instituto Toscano dei Tumori to A.F.,
and by the Intramural Research Program of the National Institute on
Aging (grant AG000661-06), National Institutes of Health, to W.W.
NR 71
TC 75
Z9 75
U1 0
U2 8
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 MAR 15
PY 2010
VL 30
IS 6
BP 1382
EP 1396
DI 10.1128/MCB.01290-09
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 562NH
UT WOS:000275058100008
PM 20065033
ER
PT J
AU Penmatsa, H
Zhang, WQ
Yarlagadda, S
Li, CY
Conoley, VG
Yue, JM
Bahouth, SW
Buddington, RK
Zhang, GP
Nelson, DJ
Sonecha, MD
Manganiello, V
Wine, JJ
Naren, AP
AF Penmatsa, Himabindu
Zhang, Weiqiang
Yarlagadda, Sunitha
Li, Chunying
Conoley, Veronica G.
Yue, Junming
Bahouth, Suleiman W.
Buddington, Randal K.
Zhang, Guangping
Nelson, Deborah J.
Sonecha, Monal D.
Manganiello, Vincent
Wine, Jeffrey J.
Naren, Anjaparavanda P.
TI Compartmentalized Cyclic Adenosine 3 ',5 '-Monophosphate at the Plasma
Membrane Clusters PDE3A and Cystic Fibrosis Transmembrane Conductance
Regulator into Microdomains
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID AIRWAY EPITHELIAL-CELLS; PHOSPHODIESTERASE INHIBITORS; PROTEIN-KINASE;
CHLORIDE CHANNEL; APICAL MEMBRANE; CL-SECRETION; CFTR; CAMP; DIFFUSION;
AMP
AB Formation of multiple-protein macromolecular complexes at specialized subcellular microdomains increases the specificity and efficiency of signaling in cells. In this study, we demonstrate that phosphodiesterase type 3A (PDE3A) physically and functionally interacts with cystic fibrosis transmembrane conductance regulator (CFTR) channel. PDE3A inhibition generates compartmentalized cyclic adenosine 3',5'-monophosphate (cAMP), which further clusters PDE3A and CFTR into microdomains at the plasma membrane and potentiates CFTR channel function. Actin skeleton disruption reduces PDE3A-CFTR interaction and segregates PDE3A from its interacting partners, thus compromising the integrity of the CFTR-PDE3A-containing macromolecular complex. Consequently, compartmentalized cAMP signaling is lost. PDE3A inhibition no longer activates CFTR channel function in a compartmentalized manner. The physiological relevance of PDE3A-CFTR interaction was investigated using pig trachea submucosal gland secretion model. Our data show that PDE3A inhibition augments CFTR-dependent submucosal gland secretion and actin skeleton disruption decreases secretion.
C1 [Penmatsa, Himabindu; Zhang, Weiqiang; Yarlagadda, Sunitha; Conoley, Veronica G.; Yue, Junming; Naren, Anjaparavanda P.] Univ Tennessee, Hlth Sci Ctr, Dept Physiol, Memphis, TN 38163 USA.
[Li, Chunying] Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI 48201 USA.
[Bahouth, Suleiman W.] Univ Tennessee, Hlth Sci Ctr, Dept Pharmacol, Memphis, TN 38163 USA.
[Buddington, Randal K.] Univ Memphis, Dept Hlth & Sports Sci, Memphis, TN 38152 USA.
[Zhang, Guangping; Nelson, Deborah J.] Univ Chicago, Dept Neurobiol Pharmacol & Physiol, Chicago, IL 60637 USA.
[Sonecha, Monal D.; Wine, Jeffrey J.] Stanford Univ, Cyst Fibrosis Res Lab, Stanford, CA 94305 USA.
[Manganiello, Vincent] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Naren, AP (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Physiol, Memphis, TN 38163 USA.
EM anaren@uthsc.edu
FU National Institutes of Health [DK074996, DK080834]; American Heart
Association [R079008141]
FX We thank Dr. David Armbruster for critically editing the manuscript; Dr.
Richard A. Heil-Chapdelaine for technical support with imaging; Dr.
Bakhram K. Berdiev (Department of Cell Biology, University of Alabama at
Birmingham, Birmingham, AL) for providing pcDNA3.1(-)-CFP and YFP-CFTR
constructs; and Dr. Juan P. Ianowski for help with data analysis. This
work was supported by grants from National Institutes of Health Grant
DK074996 and DK080834 to A.P.N. and American Heart Association
predoctoral fellowship R079008141 to H. P.
NR 61
TC 45
Z9 45
U1 0
U2 3
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD MAR 15
PY 2010
VL 21
IS 6
BP 1097
EP 1110
DI 10.1091/mbc.E09-08-0655
PG 14
WC Cell Biology
SC Cell Biology
GA 567GQ
UT WOS:000275433500023
PM 20089840
ER
PT J
AU Fan, JS
Zeller, K
Chen, YC
Watkins, T
Barnes, KC
Becker, KG
Dang, CV
Cheadle, C
AF Fan, JinShui
Zeller, Karen
Chen, Yu-Chi
Watkins, Tonya
Barnes, Kathleen C.
Becker, Kevin G.
Dang, Chi V.
Cheadle, Chris
TI Time-Dependent c-Myc Transactomes Mapped by Array-Based Nuclear Run-On
Reveal Transcriptional Modules in Human B Cells
SO PLOS ONE
LA English
DT Article
ID GENE-EXPRESSION; GENOMIC TARGETS; RNA; ACTIVATION; NETWORK; CLUSTER;
LINE
AB Background: The definition of transcriptional networks through measurements of changes in gene expression profiles and mapping of transcription factor binding sites is limited by the moderate overlap between binding and gene expression changes and the inability to directly measure global nuclear transcription (coined ``transactome'').
Methodology/Principal Findings: We developed a method to measure nascent nuclear gene transcription with an Arraybased Nuclear Run-On (ANRO) assay using commercial microarray platforms. This strategy provides the missing component, the transactome, to fully map transcriptional networks. ANRO measurements in an inducible c-Myc expressing human P4936 B cell model reveals time-dependent waves of transcription, with a transactome early after c-Myc induction that does not persist at a late, steady-state phase, when genes that are regulated by c-Myc and E2F predominate. Gene set matrix analysis further uncovers functionally related groups of genes putatively regulated by waves of transcription factor motifs following Myc induction, starting with AP1 and CREB that are followed by EGR1, NFkB and STAT, and ending with E2F, Myc and ARNT/HIF motifs.
Conclusions/Significance: By coupling ANRO with previous global mapping of c-Myc binding sites by chromatin immunoprecipitation (ChIP) in P493-6 cells, we define a set of transcriptionally regulated direct c-Myc target genes and pave the way for the use of ANRO to comprehensively map any transcriptional network.
C1 [Fan, JinShui; Chen, Yu-Chi; Watkins, Tonya; Barnes, Kathleen C.; Cheadle, Chris] Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Immunol & Allergy,Lowe Family Genom Core, Baltimore, MD 21205 USA.
[Zeller, Karen; Dang, Chi V.] Johns Hopkins Univ, Sch Med, Dept Med, Div Hematol, Baltimore, MD 21205 USA.
[Dang, Chi V.] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA.
[Dang, Chi V.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Becker, Kevin G.] NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
RP Fan, JS (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Immunol & Allergy,Lowe Family Genom Core, Baltimore, MD 21205 USA.
EM cvdang@jhmi.edu; ccheadl1@jhmi.edu
OI Becker, Kevin/0000-0002-6794-6656
FU National Institute on Aging, NIH [R01CA57341, R01CA51497]; Maryland Stem
Cell Research Fund [2007-MSCRFE-0167-00, 2008-MSCRFE-0156-00]; Mary
Beryl Patch Turnbull Scholar Program
FX This work was partially supported in part by the Intramural Research
Program of the NIH, National Institute on Aging, NIH grants R01CA57341
and R01CA51497 and Maryland Stem Cell Research Fund grants
2007-MSCRFE-0167-00 and 2008-MSCRFE-0156-00. KCB was supported in part
by the Mary Beryl Patch Turnbull Scholar Program. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 27
TC 21
Z9 21
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 15
PY 2010
VL 5
IS 3
AR e9691
DI 10.1371/journal.pone.0009691
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 569SM
UT WOS:000275621000009
PM 20300622
ER
PT J
AU Auerbach, SS
Shah, RR
Mav, D
Smith, CS
Walker, NJ
Vallant, MK
Boorman, GA
Irwin, RD
AF Auerbach, Scott S.
Shah, Ruchir R.
Mav, Deepak
Smith, Cynthia S.
Walker, Nigel J.
Vallant, Molly K.
Boorman, Gary A.
Irwin, Richard D.
TI Predicting the hepatocarcinogenic potential of alkenylbenzene flavoring
agents using toxicogenomics and machine learning
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Toxicogenomics; Cancer; Liver; Prediction; Alkenylbenzene; Rat
ID NATIONAL-TOXICOLOGY-PROGRAM; CHRONIC TOXICITY CARCINOGENICITY; SUPPORT
VECTOR MACHINES; AVAILABLE DATA; CANCER CLASSIFICATION; EXPRESSION
PROFILES; RISK-EVALUATION; LIVER-TUMORS; IN-VIVO; GENE
AB Identification of carcinogenic activity is the primary goal of the 2-year bioassay. The expense of these studies limits the number of chemicals that can be studied and therefore chemicals need to be prioritized based on a variety of parameters. We have developed an ensemble of support vector machine classification models based on male F344 rat liver gene expression following 2, 14 OF 90 days of exposure to a collection of hepatocarcinogens (aflatoxin B1, 1-amino-2,4-dibromoanthraquinone, N-nitrosodimethylamine, methyleugenol) and non-hepatocarcinogens (acetaminophen, ascorbic acid, tryptophan). Seven models were generated based on individual exposure durations (2, 14 or 90 days) or a combination of exposures (2 + 14, 2 + 90, 14 + 90 and 2 + 14 + 90 days). All sets of data, with the exception of one yielded models with 0% cross-validation error. Independent validation of the models was performed using expression data from the liver of rats exposed at 2 dose levels to a collection of alkenylbenzene flavoring agents. Depending on the model Used and the exposure duration of the test data, independent validation error rates ranged from 47% to 10%. The variable with the most notable effect on independent validation accuracy was exposure duration of the alkenylbenzene test data. All models generally exhibited improved performance as the exposure duration of the alkenylbenzene data increased. The models differentiated between hepatocarcinogenic (estragole and safrole) and non-hepatocarcinogenic (anethole, eugenol and isoeugenol) alkenylbenzenes previously studied in a carcinogenicity bioassay. In the case of safrole the models correctly differentiated between carcinogenic and non-carcinogenic dose levels. The models predict that two alkenylbenzenes not previously assessed in a carcinogenicity bioassay, myristicin and isosafrole, would be weakly hepatocarcinogenic if studied at a dose level of 2 mmol/kg bw/day for 2 years in male F344 rats; therefore suggesting that these chemicals should be a higher priority relative to other untested alkenylbenzenes for evaluation in the carcinogenicity bioassay. The results of the Study indicate that gene expression-based predictive models are an effective tool for identifying hepatocarcinogens. Furthermore, we find that exposure duration is a critical variable in the success or failure of such an approach, particularly when evaluating chemicals with unknown carcinogenic potency. Published by Elsevier Inc.
C1 [Auerbach, Scott S.; Smith, Cynthia S.; Walker, Nigel J.; Vallant, Molly K.; Boorman, Gary A.; Irwin, Richard D.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Shah, Ruchir R.; Mav, Deepak] SRA Int, Res Triangle Pk, NC 27709 USA.
RP Irwin, RD (reprint author), NIEHS, Natl Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM irwin@niehs.nih.gov
RI Walker, Nigel/D-6583-2012
OI Walker, Nigel/0000-0002-9111-6855
FU NIH; National Institute of Environmental Health Sciences [1 Z01
ESO45004-11]
FX Funding: T is research was supported [in part] by the Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences under Research Project Number 1 Z01 ESO45004-11 BB. The authors
would like to thank Drs. Julia Gohlke and Rick Paules to critical review
of the article.
NR 77
TC 42
Z9 45
U1 0
U2 10
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 MAR 15
PY 2010
VL 243
IS 3
BP 300
EP 314
DI 10.1016/j.taap.2009.11.021
PG 15
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 567IZ
UT WOS:000275441600004
PM 20004213
ER
PT J
AU Minor, RK
Smith, DL
Sossong, AM
Kaushik, S
Poosala, S
Spangler, EL
Roth, GS
Lane, M
Allison, DB
de Cabo, R
Ingram, DK
Mattison, JA
AF Minor, Robin K.
Smith, Daniel L., Jr.
Sossong, Alex M.
Kaushik, Susmita
Poosala, Suresh
Spangler, Edward L.
Roth, George S.
Lane, Mark
Allison, David B.
de Cabo, Rafael
Ingram, Donald K.
Mattison, Julie A.
TI Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and
increases mortality in rats
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Deoxyglucose; Calorie restriction; Lifespan; Mortality; Cardiac
vacuolarization
ID CALORIE RESTRICTION; DIETARY RESTRICTION; OXIDATIVE STRESS;
CONTROLLED-TRIAL; RISK-FACTORS; CELL-GROWTH; IN-VIVO; 2-DEOXYGLUCOSE;
GLUCOSE; EXERCISE
AB Calorie restriction (CR). the Purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway Fats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG Sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolarization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound. Published by Elsevier Inc.
C1 [Minor, Robin K.; Sossong, Alex M.; Spangler, Edward L.; de Cabo, Rafael; Mattison, Julie A.] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Smith, Daniel L., Jr.] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Kaushik, Susmita] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Dept Dev & Mol Biol, Bronx, NY 10461 USA.
[Kaushik, Susmita] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Dept Anat & Struct Biol, Bronx, NY 10461 USA.
[Poosala, Suresh] NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
[Roth, George S.] GeroScience Inc, Pylesville, MD 21132 USA.
[Lane, Mark] Medimmune LLC, Gaithersburg, MD 20878 USA.
[Allison, David B.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA.
[Ingram, Donald K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA.
RP Mattison, JA (reprint author), NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
EM donald.ingram@pbrc.edu; mattisonj@mail.nih.gov
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; Allison, David/0000-0003-3566-9399;
, rafael/0000-0003-2830-5693
FU National Institute on Aging; National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health. We would
like to acknowledge the generous gift of 2DG from Regent Chemical
Products and we also want to thank Dr. Deborah A. Banas of the
Experimental Pathology Laboratories, Inc., for her careful pathological
analysis of the rats in the survival study. None of the authors have any
conflict of interest to disclose.
NR 38
TC 47
Z9 48
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD MAR 15
PY 2010
VL 243
IS 3
BP 332
EP 339
DI 10.1016/j.taap.2009.11.025
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 567IZ
UT WOS:000275441600007
PM 20026095
ER
PT J
AU Pecon-Slattery, J
AF Pecon-Slattery, Jill
TI Special Issue 9th International Feline Retrovirus Research Symposium
2008 Preface
SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
LA English
DT Editorial Material
C1 NCI, Lab Genom Divers, NIH, Frederick, MD 21701 USA.
RP Pecon-Slattery, J (reprint author), NCI, Lab Genom Divers, NIH, Frederick, MD 21701 USA.
EM SlatterJ@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2427
J9 VET IMMUNOL IMMUNOP
JI Vet. Immunol. Immunopathol.
PD MAR 15
PY 2010
VL 134
IS 1-2
SI SI
BP 1
EP 2
DI 10.1016/j.vetimm.2009.10.002
PG 2
WC Immunology; Veterinary Sciences
SC Immunology; Veterinary Sciences
GA 569TV
UT WOS:000275625700001
PM 19931187
ER
PT J
AU Luttge, BG
Freed, EO
AF Luttge, Benjamin G.
Freed, Eric O.
TI FIV Gag: Virus assembly and host-cell interactions
SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
LA English
DT Article; Proceedings Paper
CT 9th International Feline Retrovirus Research Symposium
CY AUG 24-27, 2008
CL Vienna, AUSTRIA
DE FIV; HIV-1; Gag; Viral late domains; ESCRT; Virus-cell interactions
ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP41 CYTOPLASMIC TAIL; ROUS-SARCOMA-VIRUS;
STABLE MICROTUBULE FORMATION; LATE-BUDDING DOMAINS; YPXL LATE DOMAINS;
CYCLOPHILIN-A; TYPE-1 GAG; MATRIX PROTEIN; NUCLEOCAPSID PROTEIN
AB Infection of domestic cats with virulent strains of the feline immunodeficiency virus (FIV) leads to an acquired immunodeficiency syndrome (AIDS), similar to the pathogenesis induced in humans by infection with human immunodeficiency virus type I (HIV-1). Thus, FIV is a highly relevant model for anti-HIV therapy and vaccine development. FIV is not infectious in humans, so it is also a potentially effective non-toxic gene therapy vector. To make better use of this model, it is important to define the cellular machinery utilized by each virus to produce virus particles so that relevant similarities can be identified. It is well understood that all replication-competent retroviruses encode gag, pol, and env genes, which provide core elements for virus replication. As a result, most antiretroviral therapy targets pol-derived enzymes (protease, reverse transcriptase, and integrase) or env-derived glycoproteins that mediate virus attachment and entry. However, resistance to drugs against these targets is a persistent problem, and novel targets must be identified to produce more effective drugs that can either substitute or be combined with current therapy. Elements of the gag gene (matrix, capsid, nucleocapsid, and "late" domains) have yet to be exploited as antiviral targets, even though the Gag precursor polyprotein is self-sufficient for the assembly and release of virus particles from cells. This process is far better understood in primate lentiviruses, especially HIV-1. However, there has been significant progress in recent years in defining how FIV Gag is targeted to the cellular plasma membrane, assembles into virions, incorporates FIV Env glycoproteins, and utilizes host cell machinery to complete virus release. Recent discoveries of intracellular restriction factors that target HIV-1 and FIV capsids after virus entry have also opened exciting new areas of research. This review summarizes currently known interactions involving HIV-1 and FIV Gag that affect virus release, infectivity, and replication. Published by Elsevier B.V.
C1 [Luttge, Benjamin G.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Bldg 535-Rm 108,1050 Boyles St, Frederick, MD 21702 USA.
EM efreed@nih.gov
FU Intramural NIH HHS [Z01 BC010776-01]
NR 143
TC 9
Z9 9
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2427
J9 VET IMMUNOL IMMUNOP
JI Vet. Immunol. Immunopathol.
PD MAR 15
PY 2010
VL 134
IS 1-2
SI SI
BP 3
EP 13
DI 10.1016/j.vetimm.2009.10.003
PG 11
WC Immunology; Veterinary Sciences
SC Immunology; Veterinary Sciences
GA 569TV
UT WOS:000275625700002
PM 19910057
ER
PT J
AU VandeWoude, S
Troyer, J
Poss, M
AF VandeWoude, Sue
Troyer, Jennifer
Poss, Mary
TI Restrictions to cross-species transmission of lentiviral infection
gleaned from studies of FIV
SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
LA English
DT Article; Proceedings Paper
CT 9th International Feline Retrovirus Research Symposium
CY AUG 24-27, 2008
CL Vienna, AUSTRIA
DE FIV; Cross-species infection; Feline; Lentivirus; Pathogenesis
ID FELINE IMMUNODEFICIENCY VIRUS; POLYMERASE ALPHA-PRIMASE; SMALL RUMINANT
LENTIVIRUSES; MHC CLASS-II; DOMESTIC CAT; PHYLOGENETIC ANALYSIS;
NONHUMAN-PRIMATES; PUMA LENTIVIRUSES; TYPE-1 HIV-1; GAG PROTEINS
AB More than 40 species of primates and over 20 species of cats harbor antibodies that sero-react to lentiviral antigens. In nearly all cases where viral genetic analysis has been conducted, each host species is infected with a unique lentivirus. Though lentivirus clades within a species can be substantially divergent, they are typically monophyletic within that species. A notable significant departure from this observation is apparent cross-species transmission of FIV between bobcats (Lynx rufus) and pumas (Puma concolor) in Southern California that has occurred at least three times; evidence from one bobcat sequence suggests this cross-over may have also occurred in Florida between bobcats and the endangered Florida panther. Several other isolated reports demonstrate cross-species transmission of FIV isolates among captive animals housed in close proximity, and it is well established that HIV-1 and HIV-2 arose from human contact with SIN-infected non-human primates. Using an experimental model, we have determined that domestic cats (Felis catus) are susceptible to FIvs originating from pumas or lions. While infections are initially replicative, and animals seroconvert, within a relatively short period of time circulating virus is reduced to nearly undetectable levels in a majority of animals. This diminution of viral load is proportional to initial viral peak. Although viral reservoirs can be identified in gastrointestinal tissues, most viral genomes recovered peripherally are highly mutated, suggesting that the non-adapted host successfully inhibits normal viral replication, leading to replication incompetent viral progeny. Mechanisms possible for such restriction of cross-species infections in natural settings include: (1) Lack of contact conducive to lentiviral transmission between infected and shedding animals of different species; (2) Lack of suitable receptor repertoire to allow viral entry to susceptible cells of a new species; (3) Cellular machinery in the new host sufficiently divergent from the primary host to support viral replication (i.e. passive unfacilitated viral replication); (4) Intracellular restriction mechanisms present in the new host that is able to limit viral replication (i.e. active interrupted viral replication. These include factors that limit uncoating, replication, packaging, and virion release); (5) Unique ability of new host to raise sterilizing adaptive immunity, resulting in aborted infection and inability to spread infections among con-specifics; or (6) Production of defective or non-infectious viral progeny that lack cellular cofactors to render them infectious to con-specifics (i.e. particles lacking appropriate cellular components in viral Env to render them infectious to other animals of the same species). Data to support or refute the relative importance of each of these possibilities is described in this review. Insights based on our in vivo cross-species model suggest intracellular restriction mechanisms effectively inhibit rapid inter-specific transmission of lentiviruses. Further, limited contact both within and between species in natural populations is highly relevant to limiting the opportunity for spread of FIV strains. Studies of naturally occurring SIV and innate host restriction systems suggest these same two mechanisms are significant factors inhibiting widespread cross-species transmission of lentiviruses among primate species as well. (C) 2009 Elsevier B.V. All rights reserved.
C1 [VandeWoude, Sue] Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA.
[Troyer, Jennifer] NCI, SAIC Frederick, Lab Genom Divers, Frederick, MD 21702 USA.
[Poss, Mary] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
RP VandeWoude, S (reprint author), Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA.
EM suev@lamar.colostate.edu; jtroyer@ncifcrc.gov; mposs@bx.psu.edu
RI Troyer, Jennifer/B-8415-2012
FU NHLBI NIH HHS [R01 HL092791-05A2, R01 HL092791]; NIAID NIH HHS [R01
AI052055, R01 AI052055-04]
NR 75
TC 17
Z9 17
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2427
J9 VET IMMUNOL IMMUNOP
JI Vet. Immunol. Immunopathol.
PD MAR 15
PY 2010
VL 134
IS 1-2
SI SI
BP 25
EP 32
DI 10.1016/j.vetimm.2009.10.005
PG 8
WC Immunology; Veterinary Sciences
SC Immunology; Veterinary Sciences
GA 569TV
UT WOS:000275625700004
PM 19896218
ER
PT J
AU Brown, MA
Munkhtsog, B
Troyer, JL
Ross, S
Sellers, R
Fine, AE
Swanson, WF
Roelke, ME
O'Brien, SJ
AF Brown, Meredith A.
Munkhtsog, Bariushaa
Troyer, Jennifer L.
Ross, Steve
Sellers, Rani
Fine, Amanda E.
Swanson, William F.
Roelke, Melody E.
O'Brien, Stephen J.
TI Feline immunodeficiency virus (FIV) in wild Pallas' cats
SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
LA English
DT Article; Proceedings Paper
CT 9th International Feline Retrovirus Research Symposium
CY AUG 24-27, 2008
CL Vienna, AUSTRIA
DE FIV; Pallas' cat; Evolution; Histopathology; Felidae
ID AFRICAN LIONS; SEQUENCE ALIGNMENT; OTOCOLOBUS-MANUL; DOMESTIC CAT;
DIVERGENCE; INFECTION; TRANSMISSION; ORGANIZATION; POPULATION; PATTERNS
AB Feline immunodeficiency virus (FIV), a feline lentivirus related to HIV, causes immune dysfunction in domestic and wild cats. The Pallas' cat is the only species from Asia known to harbor a species-specific strain of FIV designated FIV(Oma) in natural populations. Here, a 25% seroprevalence of FIV is reported from 28 wild Mongolian Pallas' cats sampled from 2000 to 2008. Phylogenetic analysis of proviral RT-Pol from eight FIV(Oma) isolates from Mongolia, Russia, China and Kazakhstan reveals a unique monophyletic lineage of the virus within the Pallas' cat population, most closely related to the African cheetah and leopard FIV strains. Histopathological examination of lymph node and spleen from infected and uninfected Pallas' cats suggests that FIV(Oma) causes immune depletion in its' native host. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Brown, Meredith A.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA.
[Munkhtsog, Bariushaa] Mongolian Acad Sci, Inst Biol, Ulaanbaatar 51, Bzd, Mongol Peo Rep.
[Troyer, Jennifer L.; Roelke, Melody E.] SAIC Frederick Inc, Lab Genom Divers, Frederick, MD 21702 USA.
[Ross, Steve] Univ Bristol, Sch Biol Sci, Bristol BS8 1UG, Avon, England.
[Sellers, Rani] Yeshiva Univ, Albert Einstein Coll Med, Dept Pathol, Bronx, NY USA.
[Fine, Amanda E.] Mongolia Country Program, Wildlife Conservat Soc, Ulaanbaatar 211238, Mongol Peo Rep.
[Swanson, William F.] Ctr Conservat & Res Endangered Wildlife, Cincinnati, OH 45220 USA.
RP Brown, MA (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA.
EM brownmer@gmail.com
RI Troyer, Jennifer/B-8415-2012
FU Intramural NIH HHS [Z01 BC010537-06]; NCI NIH HHS [N01-CO-12400,
N01CO12400]
NR 25
TC 9
Z9 10
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2427
J9 VET IMMUNOL IMMUNOP
JI Vet. Immunol. Immunopathol.
PD MAR 15
PY 2010
VL 134
IS 1-2
SI SI
BP 90
EP 95
DI 10.1016/j.vetimm.2009.10.014
PG 6
WC Immunology; Veterinary Sciences
SC Immunology; Veterinary Sciences
GA 569TV
UT WOS:000275625700013
PM 19926144
ER
PT J
AU Bisht, H
Brown, E
Moss, B
AF Bisht, Himani
Brown, Erica
Moss, Bernard
TI Kinetics and intracellular location of intramolecular disulfide bond
formation mediated by the cytoplasmic redox system encoded by vaccinia
virus
SO VIROLOGY
LA English
DT Article
DE Protein disulfide bonds; Poxvirus morphogenesis; Viral membrane
ID MEMBRANE-PROTEIN; L1 PROTEIN; MONOCLONAL-ANTIBODIES;
ENDOPLASMIC-RETICULUM; VIRION MORPHOGENESIS; PATHWAY; ENTRY; GENE;
GLUTAREDOXIN; VACCINATION
AB Poxviruses encode a redox system for intramolecular disulfide bond formation in cytoplasmic domains of viral proteins. Our objectives were to determine the kinetics and intracellular location of disulfide bond formation. The vaccinia virus L1 myristoylated membrane protein, used as an example, has three intramolecular disulfide bonds. Reduced and disulfide-bonded forms of L1 were distinguished by electrophoretic mobility and reactivity with monoclonal and polyclonal antibodies. Because disulfide bonds formed during 5 min pulse labeling with radioactive amino acids, a protocol was devised in which dithiothreitol was present at this step. Disulfide bond formation was detected by 2 min after removal of reducing agent and was nearly complete in 10 min. When the penultimate glycine residue was mutated to prevent myristoylation, L1 was mistargeted to the endoplasmic reticulum and disulfide bond formation failed to occur. These data suggested that viral membrane association was required for oxidation of L1, providing specificity for the process. Published by Elsevier Inc.
C1 [Bisht, Himani; Brown, Erica; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20894 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20894 USA.
EM bmoss@nih.gov
FU Division of Intramural Research, MAID, NIH
FX We thank Norman Cooper and Catherine Cotter of NIAID for providing cell
cultures. The research was supported by the Division of Intramural
Research, MAID, NIH.
NR 27
TC 4
Z9 5
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 0042-6822
J9 VIROLOGY
JI Virology
PD MAR 15
PY 2010
VL 398
IS 2
BP 187
EP 193
DI 10.1016/j.virol.2009.11.026
PG 7
WC Virology
SC Virology
GA 557KZ
UT WOS:000274669300005
PM 20042211
ER
PT J
AU Derbala, M
Shebl, FM
Rashid, A
Amer, A
Bener, A
AF Derbala, Moutaz
Shebl, Fatma M.
Rashid, Awad
Amer, Aliaa
Bener, Abdulbari
TI Microalbuminuria in hepatitis C-genotype 4: Effect of pegylated
interferon and ribavirin
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
DE Hepatitis C virus; Genotype; Kidney diseases; Albuminuria; Proteinuria;
Peginterferon alpha-2a; Ribavirin
ID DIABETES-MELLITUS; VIRUS-INFECTION; KIDNEY-DISEASE; RISK-FACTORS;
GLOMERULONEPHRITIS; ASSOCIATION; PREVALENCE; OUTCOMES
AB AIM: To study the relation between hepatitis C virus (HCV) genotype 4 and microalbuminuria and renal impairment in relation to hepatic histology, and viremia in the absence of cryoglobulinemia, and to examine the effect of treatment on microalbuminuria.
METHODS: Three hundred subjects, including 233 HCV genotype-4 infected patients, were tested for cryoglobulinemia, microalbuminuria, albumin creatinine ratio (ACR), urea, creatinine, and estimated glomerular filtration rate (eGFR). The parameters were measured again in the HCV patients after 48 wk of treatment with pegylated interferon and ribavirin.
RESULTS: Significantly higher levels of microalbuminuria were detected in HCV-positive patients compared to HCV-negative controls (median 9.5 vs 5.9, respectively, Kruskal-Wallis P = 0.017). Log microalbuminuria was significantly correlated with hepatic inflammation (r = 0.13, P = 0.036) and fibrosis (r 0.12, P = 0.061), but not with viral load (r = -0.03, P 0.610), or alanine transaminase (r = -0.03, P = 0.617). Diabetes mellitus neither significantly moderated (chi(2) = 0.13, P = 0.720), nor mediated (Sobel test P = 0.49) the HCV effect. HCV status was significantly associated with log microalbuminuria (chi(2) = 4.97, P = 0.026), adjusting for age, gender, diabetes, cryoglobulinemia, urea and creatinine. A positive HCV status was not significantly associated with low eGFR (< 60 mL/min every 1.73 m(2)) [odds ratio (OR): 0.5, 95% confidence interval (CI): 0.2-1.4], nor with high ACR (OR: 1.7, 95% CI: 0.7-4.1). End-of-treatment response (ETR) was achieved in 51.9% of patients. Individuals with ETR had significantly lower microalbuminuria post-treatment (chi(2) = 8.19, P = 0.004).
CONCLUSION: HCV affected the development of microalbuminuria independent of diabetes or cryoglobulinemia. Combination therapy of pegylated interferon-ribavirin had a positive effect in reducing microalbuminuria. (C) 2010 Baishideng. All rights reserved.
C1 [Derbala, Moutaz] Hamad Med Corp, Dept Gastroenterol & Hepatol, Doha 00974, Qatar.
[Derbala, Moutaz] Weill Cornell Med Coll, Dept Med, Doha 00974, Qatar.
[Shebl, Fatma M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Shebl, Fatma M.] Natl Liver Inst, Epidemiol Branch, Menoufia 32511, Egypt.
[Rashid, Awad] Hamad Med Corp, Dept Nephrol, Doha 00974, Qatar.
[Amer, Aliaa] Hamad Med Corp, Dept Lab Med & Histopathol, Hematol Sect, Doha 00974, Qatar.
[Bener, Abdulbari] Hamad Med Corp, Dept Med Stat & Epidemiol, Doha 00974, Qatar.
RP Derbala, M (reprint author), Hamad Med Corp, Dept Gastroenterol & Hepatol, POB 3050, Doha 00974, Qatar.
EM moutazderbala@hotmail.com
NR 21
TC 4
Z9 4
U1 0
U2 1
PU W J G PRESS
PI BEIJING
PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345,
BEIJING 100023, PEOPLES R CHINA
SN 1007-9327
J9 WORLD J GASTROENTERO
JI World J. Gastroenterol.
PD MAR 14
PY 2010
VL 16
IS 10
BP 1226
EP 1231
DI 10.3748/wjg.v16.i10.1226
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 571OS
UT WOS:000275764200008
PM 20222166
ER
PT J
AU Jacobson, DL
Lindsey, JC
Gordon, CM
Moye, J
Hardin, DS
Mulligan, K
Aldrovandi, GM
AF Jacobson, Denise L.
Lindsey, Jane C.
Gordon, Catherine M.
Moye, Jack
Hardin, Dana S.
Mulligan, Kathleen
Aldrovandi, Grace M.
CA Pediat AIDS Clinical Trials Grp P1
TI Total body and spinal bone mineral density across Tanner stage in
perinatally HIV-infected and uninfected children and youth in PACTG 1045
SO AIDS
LA English
DT Article
DE antiretroviral; bone mass; children; DXA; perinatal HIV infection;
Tanner stage
ID QUANTITATIVE COMPUTED-TOMOGRAPHY; IMMUNODEFICIENCY-VIRUS-INFECTION;
PEDIATRIC OFFICIAL POSITIONS; ANTIRETROVIRAL THERAPY; PROTEASE
INHIBITOR; RANDOMIZED-TRIAL; ADOLESCENTS; STRENGTH; DISEASE; PUBERTY
AB Objective: To characterize total body bone mineral content (BMC) and total body and spinal bone mineral density (BMD) in perinatally HIV-infected and uninfected children/youth across puberty.
Design: HIV-infected (7-24 years) were randomly selected from six strata based on Tanner stage/protease inhibitor use. HIV-uninfected were frequency-matched by Tanner group and sociodemographic background to the HIV-infected.
Methods: Dual-energy X-ray absorptiometry (DXA) measured BMC and BMD. Linear regression models tested differences in bone outcomes by HIV and the interaction of HIV by Tanner group (1-2, 3-4, 5). Models were performed separately by sex and adjusted for DXA scanner, race/ethnicity, height, age and lean body mass.
Results: HIV-infected (N = 236) and uninfected (N = 143) were comparable on sex and race/ethnicity. HIV-infected were slightly older (median 12.6 versus 11.9 years). In adjusted models, HIV-infected males had significantly lower total body BMC and total body and spinal BMD at Tanner 5, lower BMC at Tanner 3-4 and similar BMC and BMD at Tanner 1-2, compared to HIV-uninfected males. HIV-infected and uninfected girls did not differ significantly on any bone outcome, but there was a marginally significant interaction of HIV and Tanner group for spinal BMD. Kaletra/ritonavir was associated with lower BMC and total body BMD and nevirapine was associated with higher spinal BMD in a model with all HIV-infected.
Conclusions: Perinatally HIV-infected males showed more evidence of lower bone density especially in the final stage of pubertal development than HIV-infected girls and they may be at increased risk for bone disease during adulthood. (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Jacobson, Denise L.; Lindsey, Jane C.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Gordon, Catherine M.] Childrens Hosp, Dept Adolescent Med, Boston, MA 02115 USA.
[Gordon, Catherine M.] Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA.
[Moye, Jack] NICHHD, Bethesda, MD 20892 USA.
[Hardin, Dana S.] Nationwide Childrens Hosp, Columbus, OH USA.
[Mulligan, Kathleen] Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA USA.
[Aldrovandi, Grace M.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
RP Jacobson, DL (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 651 Huntington Ave, Boston, MA 02115 USA.
EM jacobson@sdac.harvard.edu
OI moye, john/0000-0001-9976-8586
FU National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI068632]; Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD); National Institute of Mental Health (NIMH)
[AI068632]; National Institute of Allergy and Infectious Diseases [5 U01
AI41110]; Pediatric AIDS Clinical Trials Group (PACTG); IMPAACT Group [1
U01 AI068616]; NICHD [N01-DK-9-001/HHSN267200800001C]; National Center
for Research Resources, NIH [MO1 RR00069]; [5U01A1068616]; [1 U01
AI068632-01]
FX All authors were involved in the design phase of the study and
contributed intellectually to writing the manuscript. J.C.L., D.L.J.,G.
M. A. K. M. and C. M. G. participated during the analytic phase. This
work was supported by 5U01A1068616 (D. L. J., J. C. L.) and 1 U01
AI068632-01 (G. M. A.).; Overall support for the International Maternal
Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided
by the National Institute of Allergy and Infectious Diseases (NIAID)
(U01 AI068632), the Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD), and the National Institute of
Mental Health (NIMH) (AI068632). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIH. This work was supported by the Statistical
and Data Analysis Center at Harvard School of Public Health, under the
National Institute of Allergy and Infectious Diseases cooperative
agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group
(PACTG) and #1 U01 AI068616 with the IMPAACT Group. Support of the sites
was provided by the National Institute of Allergy and Infectious
Diseases (NIAID) the NICHD International and Domestic Pediatric and
Maternal HIV Clinical Trials Network funded by NICHD (contract number
N01-DK-9-001/HHSN267200800001C).; The authors would like to thank the
children who participated in this study, their families and the entire
protocol 1045 team for their contributions and support. We would also
like to thank Barb Heckman for outstanding support. The following sites
and individuals have contributed to this study: Children's Hospital of
Chicago; Tulane University School of Medicine, Charity Hospital of New
Orleans: M. Silio, T. Alchediak, C. Borne, S. Bradford; SUNY Health
Science Center, Stony Brook: S. Nachman, D. Ferraro, J. Perillo, S.
Muniz; University of Puerto Rico; Harlem Hospital; NYU Medical
Center/Bellevue; City Hospital at San Juan; New Jersey Medical School;
Jacobi Medical Center; St. Jude Children's Hospital: M. Donohoe, N.
Patel, S. Kaste, J. Utech; Boston Children's Hospital; University of
North Carolina at Chapel Hill; University of South Florida Physicians
Group; The Children's Hospital, University of Colorado, Denver: E. Barr,
J. Maes, B. McFarland, S. Paul, Grant Number MO1 RR00069, GCRC Program,
National Center for Research Resources, NIH; Medical College of Georgia;
Duke University Medical Center: J. Hurwitz, J. Simonetti, M. Donnelly,
C. Mathison; Texas Children's Hospital/Baylor; University of California
San Francisco Medical Center and PCRC (RR001271); Yale University School
of Medicine: W. Andiman, L. Hurst, S. Romano; Los Angeles County
Medical/University of Southern California; Lincoln Medical and Mental
Health; University of Rochester: G. Weinberg, B. Murante, S. Laverty;
Metropolitan Hospital Center; Long Beach Memorial Medical Center; Johns
Hopkins University Hospital; UCSD Medical Center; Children's Hospital at
SUNY Downstate; Bronx- Lebanon Hospital; Harbor General - UCLA Medical
Center; Children's National Medical Center - D. C.: D. Dobbins, T.
Peron, D. Wimbley, H. Spiegel; Children's Diagnostic and Treatment
Center of South Florida; Robert Wood Johnson University Hospital; Howard
University Hospital; University of Florida at Gainesville; Mt. Sinai
Hospital Medical Center, Women's and Children's HIV Program; SUNY Health
Science Center, Syracuse; University of Alabama, Birmingham School of
Medicine: R. Pass, M. Crain, N. Beatty, H. Charlton.
NR 47
TC 34
Z9 34
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD MAR 13
PY 2010
VL 24
IS 5
BP 687
EP 696
DI 10.1097/QAD.0b013e328336095d
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 563QQ
UT WOS:000275148900008
PM 20168204
ER
PT J
AU Negus, SS
Banks, ML
Folk, JE
Rice, KC
AF Negus, S. S.
Banks, M. L.
Folk, J. E.
Rice, K. C.
TI Modulation of delta opioid agonist-induced antinociception by repeated
morphine pretreatment in rhesus monkeys
SO LIFE SCIENCES
LA English
DT Article
DE Delta opioid agonist; Delta opioid receptor; Antinociception; SNC80;
Morphine; Monkey
ID DORSAL-ROOT GANGLIA; CHRONIC INFLAMMATION; THERMAL NOCICEPTION; MU;
RECEPTORS; SNC80; RAT; TRAFFICKING; PAIN; HYPERALGESIA
AB Aims: Repeated treatment with morphine increases antinociceptive effects of delta opioid agonists in rodents by a mechanism that may involve increased cell-surface expression of delta receptors. The present study evaluated effects of repeated morphine treatment on behavioral effects of the delta agonist SNC80 and the mu agonist fentanyl in rhesus monkeys.
Main methods: In an assay of schedule-controlled responding, three monkeys responded for food reinforcement under a fixed-ratio 30 schedule. In an assay of thermal nociception, tail-withdrawal latencies were evaluated in three monkeys using thermal stimulus intensities of 48 and 54 degrees C. In both assays, the effects of SNC80 (0.032-3.2 mg/kg) and fentanyl (0.001-0.056 mg/kg) were evaluated after repeated treatment with saline or a regimen of morphine doses modeled on the regimen that enhanced delta agonist antinociception and apparent delta receptor availability in previous rodent studies.
Key findings: Both SNC80 and fentanyl dose-dependently decreased rates of schedule-controlled responding, and repeated morphine treatment did not significantly alter these effects. In the assay of thermal nociception, SNC80 had little effect on tail-withdrawal latencies from water heated to 48 or 54 degrees C, whereas fentanyl increased tail-withdrawal latencies at both temperatures. Repeated morphine tended to increase the antinociceptive effects of SNC80 and to decrease the antinociceptive effects of fentanyl, but these effects of repeated morphine were small and were significant only at the higher stimulus intensity (54 degrees C).
Significance: These results provide limited support for the proposition that prior stimulation of mu receptors selectively increases the antinociceptive effects of delta agonists in rhesus monkeys. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Negus, S. S.; Banks, M. L.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23220 USA.
[Folk, J. E.; Rice, K. C.] NIDA, Chem Biol Res Branch, Rockville, MD 20852 USA.
[Folk, J. E.; Rice, K. C.] NIAAA, NIH, Rockville, MD 20852 USA.
RP Negus, SS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 N 12th St,POB 980613, Richmond, VA 23298 USA.
EM ssnegus@vcu.edu; mbanks3@vcu.edu; kennerr@mail.nih.gov
RI Banks, Matthew/K-4429-2014
OI Banks, Matthew/0000-0003-4949-5246
FU National Institute on Drug Abuse [R01-DA11460]; National Institutes of
Health; National Institute on Drug Abuse; National Institute on Alcohol
Abuse and Alcoholism
FX This work was supported by Grant R01-DA11460 from the National Institute
on Drug Abuse, National Institutes of Health. 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. These funding sources had no involvement in any aspect of
the study. The authors would like to thank Katrina Schrode and Ember
Morrissey for expert technical assistance.
NR 37
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U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0024-3205
J9 LIFE SCI
JI Life Sci.
PD MAR 13
PY 2010
VL 86
IS 11-12
BP 385
EP 392
DI 10.1016/j.lfs.2010.01.006
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 567ZP
UT WOS:000275489900002
PM 20096291
ER
PT J
AU Hattacharjee, S
Wang, ZM
Ciampa, J
Kraft, P
Chanock, S
Yu, K
Chatterjee, N
AF Hattacharjee, Samsiddhi
Wang, Zhaoming
Ciampa, Julia
Kraft, Peter
Chanock, Stephen
Yu, Kai
Chatterjee, Nilanjan
TI Using Principal Components of Genetic Variation for Robust and Powerful
Detection of Gene-Gene Interactions in Case-Control and Case-Only
Studies
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BREAST-CANCER; POPULATION STRATIFICATION;
ENVIRONMENT INDEPENDENCE; MODELS; SUSCEPTIBILITY; REGRESSION; EPISTASIS;
SELECTION; ALLELES
AB Many popular methods for exploring gene-gene interactions, including the case-only approach, rely on the key assumption that physically distant loci are in linkage equilibrium in the underlying population. These methods utilize the presence of correlation between unlinked loci in a disease-enriched sample as evidence of interactions among the loci in the etiology of the disease. We use data from the CGEMS case-control genome-wide association study of breast cancer to demonstrate empirically that the case-only and related methods have the potential to create large-scale false positives because of the presence Of Population stratification (PS) that creates long-range linkage disequilibrium in the genome. We show that the bias can be removed by considering parametric and nonparametric methods that assume gene-gene independence between unlinked loci, not in the entire population, but only conditional on Population substructure that can be uncovered based on the principal components of a suitably large panel of PS markers. Applications in the CGEMS study as well as simulated data show that the proposed methods are robust to the presence of population stratification and are yet much more powerful, relative to standard logistic regression methods that are also commonly used as robust alternatives to the case-only type methods.
C1 [Hattacharjee, Samsiddhi; Ciampa, Julia; Yu, Kai; Chatterjee, Nilanjan] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Wang, Zhaoming] NCI, Adv Technol Ctr, NIH, Rockville, MD 20852 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Chanock, Stephen] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA.
RP Chatterjee, N (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
EM chattern@mail.nih.gov
FU National Cancer Institute Intramural Program; National Heart, Lung, and
Blood Institute; NIH [P01 CA87969]
FX The authors would like to acknowledge Dr. Jay Sethuraman for helpful
discussions on matching algorithms and Dr. B.J. Stone for proof reading
and editing the manuscript. The research of S.B., J.C., K.Y., S.C., and
N.C. was supported by the National Cancer Institute Intramural Program
and a Gene-Environment Initiative (GEI) grant from the National Heart,
Lung, and Blood Institute. The research of P.K. was Supported by NIH P01
CA87969. We would also like to thank three anonymous reviewers for their
helpful comments to improve the manuscript. This Study utilized the
high-performance Computational capabilities of the StatPro Linux cluster
at the National Cancer Institute and the Bio-wulf Linux cluster at the
National Institutes of Health, Bethesda, MD.
NR 29
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U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD MAR 12
PY 2010
VL 86
IS 3
BP 331
EP 342
DI 10.1016/j.ajhg.2010.01.026
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 570LG
UT WOS:000275678800005
ER
PT J
AU Kennerson, ML
Nicholson, GA
Kaler, SG
Kowalski, B
Mercer, JFB
Tang, JR
Llanos, RM
Chu, SN
Takata, RI
Speck-Martins, CE
Baets, J
Almeida-Souza, L
Fischer, D
Timmerman, V
Taylor, PE
Scherer, SS
Ferguson, TA
Bird, TD
De Jonghe, P
Feely, SME
Shy, ME
Garbern, JY
AF Kennerson, Marina L.
Nicholson, Garth A.
Kaler, Stephen G.
Kowalski, Bartosz
Mercer, Julian F. B.
Tang, Jingrong
Llanos, Roxana M.
Chu, Shannon
Takata, Reinaldo I.
Speck-Martins, Carlos E.
Baets, Jonathan
Almeida-Souza, Leonardo
Fischer, Dirk
Timmerman, Vincent
Taylor, Philip E.
Scherer, Steven S.
Ferguson, Toby A.
Bird, Thomas D.
De Jonghe, Peter
Feely, Shawna M. E.
Shy, Michael E.
Garbern, James Y.
TI Missense Mutations in the Copper Transporter Gene ATP7A Cause X-Linked
Distal Hereditary Motor Neuropathy
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID SPINAL MUSCULAR-ATROPHY; OCCIPITAL-HORN-SYNDROME; MARIE-TOOTH-DISEASE;
MENKES-DISEASE; NEURON DISEASE; CANDIDATE GENE; DEFICIENCY
MYELONEUROPATHY; WILSON-DISEASE; PROTEIN; TRAFFICKING
AB Distal hereditary motor neuropathies comprise a clinically and genetically heterogeneous group of disorders. We recently mapped an X-linked form of this condition to chromosome Xq13.1-q21 in two large unrelated families. The region of genetic linkage included ATP7A, which encodes a copper-transporting P-type ATPase mutated in patients with Menkes disease, a severe infantile-onset neurodegenerative condition. We identified two unique ATP7A missense mutations (p.P1386S and p.T9941) in males with distal motor neuropathy in two families. These molecular alterations impact highly conserved amino acids in the carboxyl half of ATP7A and do not directly involve the copper transporter's known critical functional domains. Studies of p.P1386S revealed normal ATP7A mRNA and protein levels, a defect in ATP7A trafficking, and partial rescue of a S. cerevisiae copper transport knockout. Although ATP7A mutations are typically associated with severe Menkes disease or its milder allelic variant, occipital horn syndrome, we demonstrate here that certain missense mutations at this locus can cause a syndrome restricted to progressive distal motor neuropathy without overt signs of systemic copper deficiency. This previously unrecognized genotype-phenotype correlation suggests an important role of the ATP7A copper transporter in motor-neuron maintenance and function.
C1 [Kennerson, Marina L.; Nicholson, Garth A.; Kowalski, Bartosz; Chu, Shannon] Univ Sydney, ANZAC Res Inst, Northcott Neurosci Lab, Concord, Australia.
[Kennerson, Marina L.; Nicholson, Garth A.] Concord Hosp, Mol Med Lab, Concord, Australia.
[Kaler, Stephen G.; Tang, Jingrong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD USA.
[Mercer, Julian F. B.; Llanos, Roxana M.; Taylor, Philip E.] Deakin Univ, Sch Life & Environm Sci, Ctr Cellular & Mol Biol, Burwood, Australia.
[Takata, Reinaldo I.; Speck-Martins, Carlos E.] Sarah Network Rehabil Hosp, Brasilia, DF, Brazil.
[Baets, Jonathan; Almeida-Souza, Leonardo; Timmerman, Vincent; De Jonghe, Peter] Flanders Inst Biotechnol, Dept Mol Genet, Antwerp, Belgium.
[Baets, Jonathan; Almeida-Souza, Leonardo; Timmerman, Vincent; De Jonghe, Peter] Univ Antwerp, B-2020 Antwerp, Belgium.
[Fischer, Dirk] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland.
[Fischer, Dirk] Univ Childrens Hosp Basel, Dept Neuropediat, Basel, Switzerland.
[Scherer, Steven S.; Ferguson, Toby A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Bird, Thomas D.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA.
[Bird, Thomas D.] Univ Washington, Sch Med, Dept Med Genet, Seattle, WA USA.
[Bird, Thomas D.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Feely, Shawna M. E.; Shy, Michael E.; Garbern, James Y.] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA.
[Feely, Shawna M. E.; Shy, Michael E.; Garbern, James Y.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
RP Kennerson, ML (reprint author), Univ Sydney, ANZAC Res Inst, Northcott Neurosci Lab, Concord, Australia.
EM marinak@anzac.edu.au
RI Almeida-Souza, Leonardo/C-3437-2011; Kennerson, Marina/B-5058-2014
FU Motor Neuron Disease Research Institute of Australia; National Health
and Medical Research Council of Australia; Intramural Research program
of the National Institute of Child Health and Human Development;
Methusalem project of the University of Antwerp; Fund for Scientific
Research (FWO-Flanders); Medical Foundation Queen Elisabeth (GSKE);
Interuniversity Attraction Poles program [P6/43]; Belgian Federal
Science Policy Office (BELSPO)
FX We thank the patients and family members for their participation in this
study. We thank Rabia Chaudhry and Alison Blake for their assistance
with Cell Cultures and Jose Centeno for fibroblast copper measurements.
This work was supported by grants from the Motor Neuron Disease Research
Institute of Australia, the National Health and Medical Research Council
of Australia, the Intramural Research program of the National Institute
of Child Health and Human Development, the Methusalem project of the
University of Antwerp, the Fund for Scientific Research (FWO-Flanders),
the Medical Foundation Queen Elisabeth (GSKE), and the Interuniversity
Attraction Poles program (P6/43) of the Belgian Federal Science Policy
Office (BELSPO). J.B. and L.S. are Supported by PhD fellowships of the
FWO-Flanders and the University of Antwerp, respectively. We thank
Professor David Handelsman for his useful constructive comments on the
manuscript.
NR 47
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U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD MAR 12
PY 2010
VL 86
IS 3
BP 343
EP 352
DI 10.1016/j.ajhg.2010.01.027
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 570LG
UT WOS:000275678800006
PM 20170900
ER
PT J
AU Rehman, AU
Morell, RJ
Belyantseva, IA
Khan, SY
Boger, ET
Shahzad, M
Ahmed, ZM
Riazuddin, S
Khan, SN
Riazuddin, S
Friedman, TB
AF Rehman, Atteeq Ur
Morell, Robert J.
Belyantseva, Inna A.
Khan, Shahid Y.
Boger, Erich T.
Shahzad, Mohsin
Ahmed, Zubair M.
Riazuddin, Saima
Khan, Shaheen N.
Riazuddin, Sheikh
Friedman, Thomas B.
TI Targeted Capture and Next-Generation Sequencing Identifies C9orf75,
Encoding Taperin, as the Mutated Gene in Nonsyndromic Deafness DFNB79
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID AUTOSOMAL RECESSIVE DEAFNESS; COCHLEAR HAIR-CELLS; ANKLE-LINK COMPLEX;
MYOSIN-XVA; GAMMA-ACTIN; PROTEIN; STEREOCILIA; MUTATIONS; DNA; BUNDLE
AB Targeted genome capture combined with next-generation sequencing was used to analyze 2.9 Mb of the DFNB79 interval on chromosome 9q34.3, which includes 108 candidate genes. Genomic DNA from an affected member of a consanguineous family segregating recessive, nonsyndromic hearing loss was used to make a library of fragments covering the DFNB79 linkage interval defined by genetic analyses of four pedigrees. Homozygosity for eight previously unreported variants in transcribed sequences was detected by evaluating a library of 402,554 sequencing reads and was later confirmed by Sanger sequencing. Of these variants, six were determined to be polymorphisms in the Pakistani population, and one was in a noncoding gene that was subsequently excluded genetically from the DFNB79 linkage interval. The remaining variant was a nonsense mutation in a predicted gene, C9orf75, renamed TPRN. Evaluation of the other three DFNB79-linked families identified three additional frameshift Mutations, for a total of four truncating alleles of this gene. Although TPRN is expressed in many tissues, immunolocalization of the protein product in the mouse cochlea shows prominent expression in the taper region of hair cell stereocilia. Consequently, we named the protein taperin.
C1 [Rehman, Atteeq Ur; Morell, Robert J.; Belyantseva, Inna A.; Boger, Erich T.; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA.
[Rehman, Atteeq Ur; Khan, Shahid Y.; Shahzad, Mohsin; Khan, Shaheen N.] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Ahmed, Zubair M.] Cincinnati Childrens Hosp Res Fdn, Div Pediat Ophthalmol, Cincinnati, OH 45229 USA.
[Ahmed, Zubair M.] Univ Cincinnati, Dept Ophthalmol, Cincinnati, OH 45229 USA.
[Riazuddin, Saima] Childrens Hosp Res Fdn, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati, OH 45229 USA.
[Riazuddin, Saima] Childrens Hosp Res Fdn, Div Ophthalmol, Cincinnati, OH 45229 USA.
[Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore 54550, Pakistan.
RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA.
EM friedman@nidcd.nih.gov
RI Nasim Khan, Shaheen/F-2135-2015;
OI Morell, Robert/0000-0003-1537-7356
FU National Institute of Deafness and Other Communication Disorders [1 Z01
DC000039-12]; Higher Education Commission, Islamabad; Ministry of
Science and Technology, Islamabad; International Center for Genetic
Engineering and Biotechnology, Trieste [CRP/PAK08-01, 08/009]
FX We are thankful to the family members who helped make this study
possible. We thank Jonathan Bird, Byung Yoon Choi, Dennis Drayna, Meghan
Drummond, Karen Friderici, Andrew Griffith, Changsoo Kang, Sue Lee, M.
Hashirn Raza, Mary Vendetti, and Barbara Zwiesler. This work was
supported by National Institutes of Health intramural funds from the
National Institute of Deafness and Other Communication Disorders (1 Z01
DC000039-12) to T.B.F; by the Higher Education Commission, Islamabad;
the Ministry of Science and Technology, Islamabad; and by the
International Center for Genetic Engineering and Biotechnology, Trieste,
project CRP/PAK08-01 (contract 08/009), to S.R.
NR 36
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U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD MAR 12
PY 2010
VL 86
IS 3
BP 378
EP 388
DI 10.1016/j.ajhg.2010.01.030
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 570LG
UT WOS:000275678800009
PM 20170899
ER
PT J
AU Woodard, GE
Lopez, JJ
Jardin, I
Salido, GM
Rosado, JA
AF Woodard, Geoffrey E.
Lopez, Jose J.
Jardin, Isaac
Salido, Gines M.
Rosado, Juan A.
TI TRPC3 Regulates Agonist-stimulated Ca2+ Mobilization by Mediating the
Interaction between Type I Inositol 1,4,5-Trisphosphate Receptor, RACK1,
and Orai1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID OPERATED CALCIUM INFLUX; SMOOTH-MUSCLE-CELLS; PLASMA-MEMBRANE; STORE
DEPLETION; CHANNEL FUNCTION; HUMAN PLATELETS; CELLULAR SIGNALS; TRIADIC
PROTEINS; ARC CHANNELS; CRAC CHANNEL
AB There is a body of evidence suggesting that Ca2+ handling proteins assemble into signaling complexes required for a fine regulation of Ca2+ signals, events that regulate a variety of critical cellular processes. Canonical transient receptor potential (TRPC) and Orai proteins have both been proposed to form Ca2+-permeable channels mediating Ca2+ entry upon agonist stimulation. A number of studies have demonstrated that inositol 1,4,5-trisphosphate receptors (IP(3)Rs) interact with plasma membrane TRPC channels; however, at present there is no evidence supporting the interaction between Orai proteins and IP(3)Rs. Here we report that treatment with thapsigargin or cellular agonists results in association of Orai1 with types I and II IP(3)Rs. In addition, we have found that TRPC3, RACK1 (receptor for activated protein kinase C-1), and STIM1 (stromal interaction molecule 1) interact with Orai1 upon stimulation with agonists. TRPC3 expression silencing prevented both the interaction of Orai1 with TRPC3 and, more interestingly, the association of Orai1 with the type I IP3R, but not with the type II IP3R, thus suggesting that TRPC3 selectively mediates interaction between Orai1 and type I IP3R. In addition, TRPC3 expression silencing attenuated ATP- and CCh-stimulated interaction between RACK1 and the type I IP3R, as well as Ca2+ release and entry. In conclusion, our results indicate that agonist stimulation results in the formation of an Orai1-STIM1-TRPC3-RACK1-type I IP3R complex, where TRPC3 plays a central role. This Ca2+ signaling complex might be important for both agonist-induced Ca2+ release and entry.
C1 [Lopez, Jose J.; Jardin, Isaac; Salido, Gines M.; Rosado, Juan A.] Univ Extremadura, Cell Physiol Res Grp, Dept Physiol, Caceres 10071, Spain.
[Woodard, Geoffrey E.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Rosado, JA (reprint author), Univ Extremadura, Cell Physiol Res Grp, Dept Physiol, Caceres 10071, Spain.
EM jarosado@unex.es
RI Woodard, Geoffrey/A-8608-2009; Salido, Gines/A-4292-2009; rosado,
juan/H-3488-2015; Jardin, Isaac/E-8310-2016; LOPEZ, JOSE/F-4602-2016
OI Salido, Gines/0000-0002-8687-2445; rosado, juan/0000-0002-9749-2325;
Jardin, Isaac/0000-0003-4575-8264; LOPEZ, JOSE/0000-0002-5234-1478
FU Spanish Ministry of Science and Innovation [BFI2007-60104]; National
Institutes of Health; Direccion General de Investigation (DGI)
[BES-2005-6899, BFU2007-60104]
FX This work was supported by Spanish Ministry of Science and Innovation
Grant BFI2007-60104. This work was authored, in whole or in part, by
National Institutes of Health staff.; 1Supported by Direccion
General de Investigation (DGI) fellowship BES-2005-6899.;
2Supported by DGI fellowship BFU2007-60104.
NR 60
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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 MAR 12
PY 2010
VL 285
IS 11
BP 8045
EP 8053
DI 10.1074/jbc.M109.033605
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 567AE
UT WOS:000275413800022
PM 20022948
ER
PT J
AU Baranova, IN
Bocharov, AV
Vishnyakova, TG
Kurlander, R
Chen, ZG
Fu, D
Arias, IM
Csako, G
Patterson, AP
Eggerman, TL
AF Baranova, Irina N.
Bocharov, Alexander V.
Vishnyakova, Tatyana G.
Kurlander, Roger
Chen, Zhigang
Fu, Dong
Arias, Irwin M.
Csako, Gyorgy
Patterson, Amy P.
Eggerman, Thomas L.
TI CD36 Is a Novel Serum Amyloid A (SAA) Receptor Mediating SAA Binding and
SAA-induced Signaling in Human and Rodent Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ACUTE-PHASE RESPONSE; C-REACTIVE PROTEIN; INTERLEUKIN-8 GENE-EXPRESSION;
ARTHRITIS SYNOVIAL TISSUE; CORONARY-ARTERY-DISEASE;
LOW-DENSITY-LIPOPROTEIN; B SCAVENGER RECEPTOR; N-TERMINAL KINASE;
RHEUMATOID-ARTHRITIS; A-PROTEIN
AB Serum amyloid A (SAA) is a major acute phase protein involved in multiple physiological and pathological processes. This study provides experimental evidence that CD36, a phagocyte class B scavenger receptor, functions as a novel SAA receptor mediating SAA proinflammatory activity. The uptake of Alexa Fluor (R) 488 SAA as well as of other well established CD36 ligands was increased 5-10-fold in HeLa cells stably transfected with CD36 when compared with mock-transfected cells. Unlike other apolipoproteins that bind to CD36, only SAA induced a 10-50-fold increase of interleukin-8 secretion in CD36-overexpressing HEK293 cells when compared with control cells. SAA-mediated effects were thermolabile, inhibitable by anti-SAA antibody, and also neutralized by association with high density lipoprotein but not by association with bovine serum albumin. SAA-induced cell activation was inhibited by a CD36 peptide based on the CD36 hexarelin-binding site but not by a peptide based on the thrombospondin-1-binding site. A pronounced reduction (up to 60-75%) of SAA- induced pro-inflammatory cytokine secretion was observed in cd36(-/-) rat macrophages and Kupffer cells when compared with wild type rat cells. The results of the MAPK phosphorylation assay as well as of the studies with NF-kappa B and MAPK inhibitors revealed that two MAPKs, JNK and to a lesser extent ERK1/2, primarily contribute to elevated cytokine production in CD36-overexpressing HEK293 cells. In macrophages, four signaling pathways involving NF-kappa B and three MAPKs all appeared to contribute to SAA-induced cytokine release. These observations indicate that CD36 is a receptor mediating SAA binding and SAA- induced pro-inflammatory cytokine secretion predominantly through JNK- and ERK1/2-mediated signaling.
C1 [Baranova, Irina N.; Bocharov, Alexander V.; Vishnyakova, Tatyana G.; Kurlander, Roger; Chen, Zhigang; Csako, Gyorgy; Patterson, Amy P.; Eggerman, Thomas L.] NIDDK, Dept Lab Med, Ctr Clin, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Fu, Dong; Arias, Irwin M.] NIDDK, Cell Biol & Metab Branch, NICHD, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Patterson, Amy P.] NIDDK, Off Biotechnol Activ, Off Sci Policy, Off Director,NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Eggerman, Thomas L.] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Bocharov, AV (reprint author), 9 Mem Dr,Room 1W115,MSC 0919, Bethesda, MD 20892 USA.
EM abocharov@mail.cc.nih.gov; Eggermant@niddk.nih.gov
RI Fu, Dong /J-1426-2012
FU National Institutes of Health Intramural Research Programs of the
Clinical Center; NIDDK; NIAID
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Programs of the Clinical Center, NIDDK, and
NIAID.
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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 MAR 12
PY 2010
VL 285
IS 11
BP 8492
EP 8506
DI 10.1074/jbc.M109.007526
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 567AE
UT WOS:000275413800064
PM 20075072
ER
PT J
AU Liu, J
Nussinov, R
AF Liu, Jin
Nussinov, Ruth
TI Molecular Dynamics Reveal the Essential Role of Linker Motions in the
Function of Cullin-RING E3 Ligases
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE linker; E3 ubiquitin ligase; polyubiquitin; conformational control;
conformational selection
ID SCF UBIQUITIN LIGASES; ALLOSTERIC REGULATION; TUMOR-SUPPRESSOR;
STRUCTURAL BASIS; INTERDOMAIN LINKER; COMPLEX; PROTEIN; DOMAIN;
RECOGNITION; INSIGHTS
AB Tagging proteins by polyubiquitin is a key step in protein degradation. Cullin-RING E3 ubiquitin ligases facilitate ubiquitin transfer from the E2-conjugating enzyme to the substrate, yet crystallography indicates a large distance between the E2 and the substrate, raising the question of how this distance is bridged in the ubiquitin transfer reaction. Here, we demonstrate that the linker motions in the substrate binding proteins can allosterically shorten this distance to facilitate this crucial ubiquitin transfer step and increase this distance to allow polyubiquitination. We performed molecular dynamics simulations for five substrate binding proteins, Skp2, Fbw7, beta-TrCP1, Cdc4, and pVHL, in two forms: bound to their substrates and bound to both substrate and adaptor. The adaptor connects the substrate binding proteins to the cullin. In the bound-to-both forms of all cases, we observed rotations of the substrate binding domain, shortening the gap between the tip of the substrate peptide and the E2 active site by 7-12 angstrom compared with the crystal structures. Overall, together with our earlier simulations of the unbound forms and the bound-to-adaptor forms, the emerging picture is that the maximum distance of 51-73 angstrom between the substrate binding domain and the E2 active site in the modeled unbound forms of these five proteins shrinks to a minimum of 39-49 angstrom in the bound-to-both forms. This large distance range, the result of allosterically controlled linker motions, facilitates ubiquitin transfer and polyubiquitination and as such argues that the cullin-RING E3 ubiquitin ligase is under conformational control. We further observed that substrate binding proteins with multiple substrate acceptor lysines have a larger distance range between the substrate and the E2 as compared with beta-TrCP1, with only one acceptor lysine. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Liu, Jin; Nussinov, Ruth] Natl Canc Inst, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, 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 Nussinov, R (reprint author), Natl Canc Inst, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
EM ruthnu@helix.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
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 number 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 NIH, National Cancer Institute, Center for Cancer Research. This
study used the high-performance computational capabilities of the
Biowulf Linux cluster at the National Institutes of Health (Bethesda,
MD; http://biowulf.nih.gov).
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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 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD MAR 12
PY 2010
VL 396
IS 5
BP 1508
EP 1523
DI 10.1016/j.jmb.2010.01.022
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 570PZ
UT WOS:000275691500024
PM 20083119
ER
PT J
AU Finzi, A
Xiang, SH
Pacheco, B
Wang, LP
Haight, J
Kassa, A
Danek, B
Pancera, M
Kwong, PD
Sodroski, J
AF Finzi, Andres
Xiang, Shi-Hua
Pacheco, Beatriz
Wang, Liping
Haight, Jessica
Kassa, Aemro
Danek, Brenda
Pancera, Marie
Kwong, Peter D.
Sodroski, Joseph
TI Topological Layers in the HIV-1 gp120 Inner Domain Regulate gp41
Interaction and CD4-Triggered Conformational Transitions
SO MOLECULAR CELL
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; EXTERIOR ENVELOPE GLYCOPROTEIN; SOLUBLE
CD4; TRANSMEMBRANE GLYCOPROTEIN; RECEPTOR-BINDING; AIDS PATIENTS; VIRAL
ENTRY; HTLV-III; TYPE-1; NEUTRALIZATION
AB The entry of human immunodeficiency virus (HIV-1) into cells is initiated by binding of the gp120 exterior envelope glycoprotein to the receptor, CD4. How does CD4 binding trigger conformational changes in gp120 that allow the gp41 transmembrane envelope glycoprotein to mediate viral-cell membrane fusion? The transition from the unliganded to the CD4-bound state is regulated by two potentially flexible topological layers (layers 1 and 2) in the gp120 inner domain. Both layers apparently contribute to the noncovalent association of unliganded gp120 with gp41. After CD4 makes initial contact with the gp120 outer domain, layer 1-layer 2 interactions strengthen gp120-CD4 binding by reducing the off rate. Layer 1-layer 2 interactions also destabilize the activated state induced on HIV-1 by treatment with soluble CD4. Thus, despite lack of contact with CD4, the gp120 inner-domain layers govern CD4 triggering by participating in conformational transitions within gp120 and regulating the interaction with gp41.
C1 [Finzi, Andres; Xiang, Shi-Hua; Pacheco, Beatriz; Wang, Liping; Haight, Jessica; Kassa, Aemro; Danek, Brenda; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Pathol,Div AIDS, Dept Canc Immunol & AIDS,Dana Farber Can Inst, Boston, MA 02115 USA.
[Pancera, Marie; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dept Pathol,Div AIDS, Dept Canc Immunol & AIDS,Dana Farber Can Inst, Boston, MA 02115 USA.
FU National Institutes of Health [AI24755, GM56550, AI67854]; International
AIDS Vaccine Initiative
FX We thank Ms Yvette McLaughlin and Ms Elizabeth Carpelan for manuscript
preparation and Dr Lavanya Krishnan for Biacore advice This work was
supported by grants from the National Institutes of Health (AI24755,
GM56550, and AI67854), by the International AIDS Vaccine Initiative, and
by the late William F McCarty-Cooper
NR 58
TC 90
Z9 90
U1 0
U2 14
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 MAR 12
PY 2010
VL 37
IS 5
BP 656
EP 667
DI 10.1016/j.molcel.2010.02.012
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 570UB
UT WOS:000275702500010
PM 20227370
ER
PT J
AU Silliman, CC
Stroncek, D
AF Silliman, Christopher C.
Stroncek, David
TI Identification of the HNA-3a antigen
SO BLOOD
LA English
DT Editorial Material
ID ACUTE LUNG INJURY; ALLOANTIBODIES; NEUTROPHILS; DONORS; TRALI
C1 NIH, Bethesda, MD 20892 USA.
NR 10
TC 2
Z9 4
U1 0
U2 0
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 MAR 11
PY 2010
VL 115
IS 10
BP 1863
EP 1863
PG 1
WC Hematology
SC Hematology
GA 571KS
UT WOS:000275751300005
PM 20223931
ER
PT J
AU Li, XG
Hu, X
Patel, B
Zhou, Z
Liang, S
Ybarra, R
Qiu, Y
Felsenfeld, G
Bungert, J
Huang, SM
AF Li, Xingguo
Hu, Xin
Patel, Bhavita
Zhou, Zhuo
Liang, Shermi
Ybarra, River
Qiu, Yi
Felsenfeld, Gary
Bungert, Joerg
Huang, Suming
TI H4R3 methylation facilitates beta-globin transcription by regulating
histone acetyltransferase binding and H3 acetylation
SO BLOOD
LA English
DT Article
ID LOCUS-CONTROL REGION; ARGININE-METHYLTRANSFERASE; IN-VIVO; MAMMALIAN
CHROMATIN; BARRIER-ELEMENT; GENE-EXPRESSION; ACTIVATION; LYSINE-4;
RECEPTOR; COMPLEX
AB Histone modifications play an important role in the process of transcription. However, in contrast to lysine methylation, the role of arginine methylation in chromatin structure and transcription has been under-explored. The globin genes are regulated by a highly organized chromatin structure that juxtaposes the locus control region (LCR) with downstream globin genes. We report here that the targeted recruitment of asymmetric dimethyl H4R3 catalyzed by PRMT1 (protein arginine methyltransferase 1) facilitates histone H3 acetylation on Lys9/Lys14. Dimethyl H4R3 provides a binding surface for P300/CBP-associated factor (PCAF) and directly enhances histone H3 acetylation in vitro. We show that these active modifications are essential for efficient interactions between the LCR and the beta(maj)-promoter as well as transcription of the beta-globin gene. Furthermore, knockdown (KD) of PRMT1 by RNA interference in erythroid progenitor cells prevents histone acetylation, enhancer and promoter interaction, and recruitment of transcription complexes to the active beta-globin promoter. Reintroducing rat PRMT1 into the PRMT1 KD MEL cells rescues PRMT1 binding, beta-globin transcription, and erythroid differentiation. Taken together, our data suggest that PRMT1-mediated dimethyl H4R3 facilitates histone acetylation and enhancer/promoter communications, which lead to the efficient recruitment of transcription preinitiation complexes to active promoters. (Blood. 2010; 115: 2028-2037)
C1 [Huang, Suming] Univ Florida, Coll Med, Dept Biochem Mol Biol, Gainesville, FL 32610 USA.
[Hu, Xin] Jilin Univ, Coll Life Sci, Edmond H Fischer Signal Transduct Lab, Changchun 130023, Peoples R China.
[Qiu, Yi] Univ Florida, Dept Anat & Cell Biol, Gainesville, FL 32610 USA.
[Felsenfeld, Gary] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Bungert, Joerg; Huang, Suming] Univ Florida, Genet Inst, Gainesville, FL 32610 USA.
[Huang, Suming] Univ Florida, Shands Canc Ctr, Gainesville, FL 32610 USA.
RP Huang, SM (reprint author), Univ Florida, Coll Med, Dept Biochem Mol Biol, POB 103633, Gainesville, FL 32610 USA.
EM sumingh@ufl.edu
FU National Institutes of Health [HL090589, HL091929, HL091929-01A1S1,
DK52356]; Bankhead-Coley Cancer Research; Intramural Research program,
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX This work was supported by grants from the National Institutes of Health
(S. H., HL090589, HL091929, and HL091929-01A1S1- the ARRA Administrative
Supplement; J. B., DK52356) and by grants from the Bankhead-Coley Cancer
Research (Y. Q. and S. H.). G. F. is supported by the Intramural
Research program, National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health.
NR 50
TC 37
Z9 37
U1 2
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 MAR 11
PY 2010
VL 115
IS 10
BP 2028
EP 2037
DI 10.1182/blood-2009-07-236059
PG 10
WC Hematology
SC Hematology
GA 571KS
UT WOS:000275751300027
PM 20068219
ER
PT J
AU Song, YL
Shao, Z
Dexheimer, TS
Scher, ES
Pommier, Y
Cushman, M
AF Song, Yunlong
Shao, Zhiyu
Dexheimer, Thomas S.
Scher, Evan S.
Pommier, Yves
Cushman, Mark
TI Structure-Based Design, Synthesis, and Biological Studies of New
Anticancer Norindenoisoquinoline Topoisomerase I Inhibitors
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID DNA COVALENT COMPLEX; NITRATED INDENOISOQUINOLINES; CELL-LINE;
CAMPTOTHECIN ANALOGS; CURRENT PERSPECTIVES; CANCER; MECHANISM;
IDENTIFICATION; OPTIMIZATION; ORIENTATION
AB On the basis of the superimposition of the crystal structures of norindenoisoquinoline 5 and topotecan (2) bound in the topoisomerase 1-DNA covalent complex, as well as molecular docking and quantum chemical calculations, the Substituted norindenoisoquinoline 14a was designed by transporting the 9-dimethylaminomethyl group of topotecan to the 10-position of the norindenolsoquinoline 5. The desired compound 14a wits synthesized and found to possess topoisomerase I inhibitory activity that was slightly better than that of the starting compound 5. A focused set of 10-substitued norindenoisoquinoline analogues were then synthesized. The imidazole-substituted compound 14c was highly cytotoxic when evaluated in it series of human leukemia, ovarian, and breast cancer cells.
C1 [Song, Yunlong; Shao, Zhiyu; Cushman, Mark] Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA.
[Song, Yunlong; Shao, Zhiyu; Cushman, Mark] Purdue Univ, Ctr Canc Res, W Lafayette, IN 47907 USA.
[Song, Yunlong] Second Mil Med Univ, Sch Pharm, Dept Med Chem, Shanghai 200433, Peoples R China.
[Dexheimer, Thomas S.; Scher, Evan S.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA.
EM cushman@purdue.edu
FU National Institutes of Health (NIH) [UO1 CA89566]; National Institutes
of Health [C06-14499]
FX This work was made possible by the National Institutes of Health (NIH)
through support of this work with Research Grant UO1 CA89566. Some of
this research was conducted in a facility constructed with the financial
support of a Research Facilities Improvement Program Grant C06-14499
from the National Institutes of Health. We thank the Rosen Center for
Advanced Computing (RCAC), Purdue University, for providing computing
facilities.
NR 50
TC 25
Z9 26
U1 0
U2 9
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 MAR 11
PY 2010
VL 53
IS 5
BP 1979
EP 1989
DI 10.1021/jm901649x
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 562WT
UT WOS:000275087000008
PM 20155916
ER
PT J
AU Ziolkowska, NE
Michejda, CJ
Bujacz, GD
AF Ziolkowska, Natasza E.
Michejda, Christopher J.
Bujacz, Grzegorz D.
TI Structural studies of series HIV-1 nonnucleoside reverse transcriptase
inhibitors 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-benzimidazoles
with different 4-substituents
SO JOURNAL OF MOLECULAR STRUCTURE
LA English
DT Article
DE AIDS; HIV-1; Reverse transcriptase inhibitor; Drug design; Crystal
structure
ID HUMAN-IMMUNODEFICIENCY-VIRUS; 2-ARYL-SUBSTITUTED BENZIMIDAZOLES;
ANTIRETROVIRAL THERAPY; BIOLOGICAL-ACTIVITY; HIGHLY POTENT; INFECTION;
BINDING; REPLICATION; DELAVIRDINE; MUTATIONS
AB Over the past 10 years, several anti-viral drugs have become available to fight the HIV infection. Antiretroviral treatment reduces the mortality of AIDS. Nonnucleoside inhibitors of HIV-1 reverse transcriptase are specific and potentially nontoxic drugs against AIDS. The crystal structures of five nonnucleoside inhibitors of HIV-1 reverse transcriptase are presented here. The structural parameters, especially those describing the angular orientation of the pi-electron systems and influencing biological activity, were determined for all of the investigated inhibitors. The chemical character and orientation of the substituent at C4 position of the benzimidazole moiety substantially influences the anti-viral activity. The structural data of the investigated inhibitors is a good basis for modeling enzyme-inhibitor interactions for structure-assisted drug design. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Ziolkowska, Natasza E.; Bujacz, Grzegorz D.] Tech Univ Lodz, Inst Tech Biochem, PL-90924 Lodz, Poland.
[Michejda, Christopher J.] NCI, Mol Aspects Drug Design Sect, Frederick, MD 21702 USA.
RP Bujacz, GD (reprint author), Max Planck Inst Biochem, Klopferspitz 18, D-82152 Martinsried, Germany.
EM gdbujacz@p.lodz.pl
FU Polish Committee for Scientific Research, KBN [4130517 03114]
FX This work was supported by the Polish Committee for Scientific Research,
KBN, Grant No. 4130517 03114. Authors are grateful to Wieslaw Majzner
for his assistance in collecting data on CAD4 diffractometer and to
Jerry Aexandratos for editorial suggestions.
NR 40
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-2860
J9 J MOL STRUCT
JI J. Mol. Struct.
PD MAR 11
PY 2010
VL 966
IS 1-3
BP 53
EP 58
DI 10.1016/j.molstruc.2009.12.006
PG 6
WC Chemistry, Physical
SC Chemistry
GA 571QN
UT WOS:000275769700009
ER
PT J
AU Hergenroeder, GW
Moore, AN
McCoy, JP
Samsel, L
Ward, NH
Clifton, GL
Dash, PK
AF Hergenroeder, Georgene W.
Moore, Anthony N.
McCoy, J. Philip, Jr.
Samsel, Leigh
Ward, Norman H., III
Clifton, Guy L.
Dash, Pramod K.
TI Serum IL-6: a candidate biomarker for intracranial pressure elevation
following isolated traumatic brain injury
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
ID C-REACTIVE PROTEIN; CEREBROSPINAL-FLUID; INTERLEUKIN-6 LEVELS;
TNF-ALPHA; CYTOKINE; DAMAGE; INFLAMMATION; ASSOCIATION; INDUCTION;
CHILDREN
AB Background: Increased intracranial pressure (ICP) is a serious, life-threatening, secondary event following traumatic brain injury (TBI). In many cases, ICP rises in a delayed fashion, reaching a maximal level 48-96 hours after the initial insult. While pressure catheters can be implanted to monitor ICP, there is no clinically proven method for determining a patient's risk for developing this pathology.
Methods: In the present study, we employed antibody array and Luminex-based screening methods to interrogate the levels of inflammatory cytokines in the serum of healthy volunteers and in severe TBI patients (GCS <= 8) with or without incidence of elevated intracranial pressure (ICP). De-identified samples and ELISAs were used to confirm the sensitivity and specificity of IL-6 as a prognostic marker of elevated ICP in both isolated TBI patients, and polytrauma patients with TBI.
Results: Consistent with previous reports, we observed sustained increases in IL-6 levels in TBI patients irrespective of their ICP status. However, the group of patients who subsequently experienced ICP >= 25 mm Hg had significantly higher IL-6 levels within the first 17 hours of injury as compared to the patients whose ICP remained <= 20 mm Hg. When blinded samples (n = 22) were assessed, a serum IL-6 cut-off of <5 pg/ml correctly identified 100% of all the healthy volunteers, a cut-off of >128 pg/ml correctly identified 85% of isolated TBI patients who subsequently developed elevated ICP, and values between these cut-off values correctly identified 75% of all patients whose ICP remained <= 20 mm Hg throughout the study period. In contrast, the marker had no prognostic value in predicting elevated ICP in polytrauma patients with TBI. When the levels of serum IL-6 were assessed in patients with orthopedic injury (n = 7) in the absence of TBI, a significant increase was found in these patients compared to healthy volunteers, albeit lower than that observed in TBI patients.
Conclusions: Our results suggest that serum IL-6 can be used for the differential diagnosis of elevated ICP in isolated TBI.
C1 [Moore, Anthony N.; Dash, Pramod K.] Univ Texas Houston, Sch Med, Dept Neurobiol & Anat, Houston, TX 77225 USA.
[Hergenroeder, Georgene W.; Ward, Norman H., III; Clifton, Guy L.] Univ Texas Houston, Sch Med, Dept Neurosurg, Houston, TX 77225 USA.
[Hergenroeder, Georgene W.] Univ Texas Houston, Sch Med, Vivian L Smith Ctr Neurol Res, Houston, TX 77225 USA.
[McCoy, J. Philip, Jr.; Samsel, Leigh] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Dash, PK (reprint author), Univ Texas Houston, Sch Med, Dept Neurobiol & Anat, Houston, TX 77225 USA.
EM p.dash@uth.tmc.edu
OI Hergenroeder, Georgene/0000-0002-6170-2191
FU Mission Connect/TIRR Foundation; NHLBI
FX The authors thank Dr. Shibani Pati and Dr. Aarif Khakoo for their
assistance in facilitating this project. We would like to thank the
Memorial Hermann Hospital Neurotrauma ICU, and Trauma and EMS coders;
and Elizabeth Jones, MD, Molly S. Bray, PhD, Brian McFarlin, PhD, Ian
Turpin, and Madelene Ottosen, MSN RN for assistance with recruiting
orthopedic patients and healthy volunteers for the study. This work was
supported in part by a grant from Mission Connect/TIRR Foundation and by
the Intramural Research Program of NHLBI. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 49
TC 35
Z9 35
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD MAR 11
PY 2010
VL 7
AR 19
DI 10.1186/1742-2094-7-19
PG 13
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 586BV
UT WOS:000276877000001
PM 20222971
ER
PT J
AU Wang, J
Krishnamoorthi, V
Wang, E
Yang, C
Baptista, D
Wu, XG
Liu, MT
Gardner, M
Elkins, P
Hines, J
Liu, P
AF Wang, Jennie
Krishnamoorthi, Vidhya
Wang, Euphemia
Yang, Chun
Baptista, Diego
Wu, Xiaogang
Liu, Mingtao
Gardner, Michael
Elkins, Phyllis
Hines, John
Liu, Paul
TI LC/MS characterization of impurities and degradation products of a
potent antitumor peptidic dimer, CU201
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE CU201; B201; LC-MS; Impurities characterization; Peptidic dimer;
Bradykinin antagonist
ID BRADYKININ ANTAGONIST DIMER; CANCER CELL-LINES; GROWTH-FACTOR;
CHROMATOGRAPHY; COMBINATION
AB Compound CU201 [SUIM-(D-Arg-Arg-Pro-Hyp-Gly-Igl-Ser-D-Igl-Oic-Arg)(2), where SUIM=suberimidyl; Hyp=trans-4-hydroxyproline; Igl=alpha-(2-indanyl)-glycine; Oic-octahydroindole-2-carboxylic acid], is a dimeric analog of the potent bradykinin antagonist peptide B9430. It blocks the G(alpha q.11) signal of the heterotrimeric G proteins, stimulates c-Jun kinases, and induces apoptosis in lung cancer cells with neuroendocrine features. CU201 shows potent inhibition for small-cell lung cancer cells in vitro (ED(50) = 0.15 mu M), as well as for small-cell lung cancer SHP-77 tumor growth in vivo. An HPLC method was developed, as part of a study supported by the National Cancer Institute's (NCI's) Rapid Access to Interventional Development (RAID) program, to assess the purity and stability of CU201. Impurities and degradation products were characterized by LC/MS. The identity of a major impurity, with I mass unit different from CU201, was confirmed by high resolution LC/MS and the investigation of model compounds. Susceptible linkages in the peptide chains were revealed by the degradation study. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Wang, Jennie; Krishnamoorthi, Vidhya; Wang, Euphemia; Yang, Chun; Baptista, Diego; Wu, Xiaogang; Liu, Mingtao] SRI Int, Analyt Chem, Menlo Pk, CA 94025 USA.
[Gardner, Michael; Elkins, Phyllis; Hines, John] RTI Int, Res Triangle Pk, NC 27709 USA.
[Liu, Paul] NCI, Pharmaceut Resources Branch, DCTD, Bethesda, MD 20892 USA.
RP Wang, J (reprint author), SRI Int, Analyt Chem, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA.
EM jennie.wang@sri.com; hines@rti.org; liup@dtpepn.nci.nih.gov
FU Developmental Therapeutics Program; Division of Cancer Treatment and
Diagnosis; National Cancer Institute; National Institutes of Health;
Department of Health and Human Services [N02-CM-27134, N02-CM-72203]
FX The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government.
NR 13
TC 4
Z9 4
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD MAR 11
PY 2010
VL 51
IS 4
BP 824
EP 833
DI 10.1016/j.jpba.2009.10.004
PG 10
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 542QT
UT WOS:000273510600004
PM 19897331
ER
PT J
AU Craigie, R
AF Craigie, Robert
TI STRUCTURAL BIOLOGY When four become one
SO NATURE
LA English
DT Editorial Material
ID CATALYTIC DOMAIN; HIV-1 INTEGRASE
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 Intramural NIH HHS [Z01 DK036170-01]
NR 7
TC 3
Z9 4
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAR 11
PY 2010
VL 464
IS 7286
BP 167
EP 168
DI 10.1038/464167a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100022
PM 20220826
ER
PT J
AU Chandrashekar, J
Kuhn, C
Oka, Y
Yarmolinsky, DA
Hummler, E
Ryba, NJP
Zuker, CS
AF Chandrashekar, Jayaram
Kuhn, Christina
Oka, Yuki
Yarmolinsky, David A.
Hummler, Edith
Ryba, Nicholas J. P.
Zuker, Charles S.
TI The cells and peripheral representation of sodium taste in mice
SO NATURE
LA English
DT Article
ID SINGLE CHORDA TYMPANI; GLOSSOPHARYNGEAL NERVE; RECEPTOR-CELLS; BITTER
TASTE; SALT TASTE; AMILORIDE; CHANNEL; MOUSE; NACL; RAT
AB Salt taste in mammals can trigger two divergent behavioural responses. In general, concentrated saline solutions elicit robust behavioural aversion, whereas low concentrations of NaCl are typically attractive, particularly after sodium depletion(1-5). Notably, the attractive salt pathway is selectively responsive to sodium and inhibited by amiloride, whereas the aversive one functions as a nonselective detector for a wide range of salts(1-3,6-9). Because amiloride is a potent inhibitor of the epithelial sodium channel (ENaC), ENaC has been proposed to function as a component of the salt-taste-receptor system(1,3,6-14). Previously, we showed that four of the five basic taste qualities-sweet, sour, bitter and umami-are mediated by separate taste-receptor cells (TRCs) each tuned to a single taste modality, and wired to elicit stereotypical behavioural responses(5,15-18). Here we show that sodium sensing is also mediated by a dedicated population of TRCs. These taste cells express the epithelial sodium channel ENaC(19,20), and mediate behavioural attraction to NaCl. We genetically engineered mice lacking ENaC alpha in TRCs, and produced animals exhibiting a complete loss of salt attraction and sodium taste responses. Together, these studies substantiate independent cellular substrates for all five basic taste qualities, and validate the essential role of ENaC for sodium taste in mice.
C1 [Chandrashekar, Jayaram; Oka, Yuki; Yarmolinsky, David A.; Zuker, Charles S.] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
[Chandrashekar, Jayaram; Oka, Yuki; Yarmolinsky, David A.; Zuker, Charles S.] Univ Calif San Diego, Dept Neurobiol, La Jolla, CA 92093 USA.
[Chandrashekar, Jayaram; Oka, Yuki; Yarmolinsky, David A.; Zuker, Charles S.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Kuhn, Christina; Ryba, Nicholas J. P.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
[Hummler, Edith] Univ Lausanne, Fac Biol & Med, Dept Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland.
RP Zuker, CS (reprint author), Columbia Univ, Columbia Coll Phys & Surg, Howard Hughes Med Inst, Dept Biochem, New York, NY 10032 USA.
EM cz2195@columbia.edu
FU NIH, NIDCR
FX We thank W. Guo and A. Becker for generation and maintenance of mouse
lines, and K. Scott and members of our laboratories for valuable
comments. This research was supported in part by the intramural research
program of the NIH, NIDCR (N.J.P.R.). C.S.Z. is an investigator of the
Howard Hughes Medical Institute.
NR 30
TC 203
Z9 206
U1 8
U2 99
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAR 11
PY 2010
VL 464
IS 7286
BP 297
EP U182
DI 10.1038/nature08783
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566JO
UT WOS:000275366100051
PM 20107438
ER
PT J
AU Steidl, C
Lee, T
Shah, SP
Farinha, P
Han, G
Nayar, T
Delaney, A
Jones, SJ
Iqbal, J
Weisenburger, DD
Bast, MA
Rosenwald, A
Muller-Hermelink, HK
Rimsza, LM
Campo, E
Delabie, J
Braziel, RM
Cook, JR
Tubbs, RR
Jaffe, ES
Lenz, G
Connors, JM
Staudt, LM
Chan, WC
Gascoyne, RD
AF Steidl, Christian
Lee, Tang
Shah, Sohrab P.
Farinha, Pedro
Han, Guangming
Nayar, Tarun
Delaney, Allen
Jones, Steven J.
Iqbal, Javeed
Weisenburger, Dennis D.
Bast, Martin A.
Rosenwald, Andreas
Muller-Hermelink, Hans-Konrad
Rimsza, Lisa M.
Campo, Elias
Delabie, Jan
Braziel, Rita M.
Cook, James R.
Tubbs, Ray R.
Jaffe, Elaine S.
Lenz, Georg
Connors, Joseph M.
Staudt, Louis M.
Chan, Wing C.
Gascoyne, Randy D.
TI Tumor-Associated Macrophages and Survival in Classic Hodgkin's Lymphoma
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID REGULATORY T-CELLS; INDEPENDENT PROGNOSTIC-FACTOR; GENE-EXPRESSION;
FOLLICULAR LYMPHOMA; DISEASE; MICROENVIRONMENT; CHEMOTHERAPY;
MICROARRAY; SIGNATURES; PREDICTOR
AB BACKGROUND
Despite advances in treatments for Hodgkin's lymphoma, about 20% of patients still die from progressive disease. Current prognostic models predict the outcome of treatment with imperfect accuracy, and clinically relevant biomarkers have not been established to improve on the International Prognostic Score.
METHODS
Using gene-expression profiling, we analyzed 130 frozen samples obtained from patients with classic Hodgkin's lymphoma during diagnostic lymph-node biopsy to determine which cellular signatures were correlated with treatment outcome. We confirmed our findings in an independent cohort of 166 patients, using immunohistochemical analysis.
RESULTS
Gene-expression profiling identified a gene signature of tumor-associated macrophages that was significantly associated with primary treatment failure (P = 0.02). In an independent cohort of patients, we found that an increased number of CD68+ macrophages was correlated with a shortened progression-free survival (P = 0.03) and with an increased likelihood of relapse after autologous hematopoietic stem-cell transplantation (P = 0.008), resulting in shortened disease-specific survival (P = 0.003). In multivariate analysis, this adverse prognostic factor outperformed the International Prognostic Score for disease-specific survival (P = 0.003 vs. P = 0.03). The absence of an elevated number of CD68+ cells in patients with limited-stage disease defined a subgroup of patients with a long-term disease-specific survival of 100% with the use of current treatment strategies.
CONCLUSIONS
An increased number of tumor-associated macrophages was strongly associated with shortened survival in patients with classic Hodgkin's lymphoma and provides a new biomarker for risk stratification.
C1 [Steidl, Christian; Lee, Tang; Shah, Sohrab P.; Farinha, Pedro; Han, Guangming; Gascoyne, Randy D.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Nayar, Tarun; Delaney, Allen; Jones, Steven J.] Univ British Columbia, Genome Sci Ctr, Vancouver, BC V5Z 1M9, Canada.
[Connors, Joseph M.] Univ British Columbia, Div Med Oncol, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada.
[Shah, Sohrab P.] Univ British Columbia, Dept Comp Sci, Vancouver, BC V6T 1W5, Canada.
[Iqbal, Javeed; Weisenburger, Dennis D.; Bast, Martin A.; Chan, Wing C.] Univ Nebraska Med Ctr, Dept Pathol, Omaha, NE USA.
[Rosenwald, Andreas; Muller-Hermelink, Hans-Konrad] Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany.
[Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ USA.
[Campo, Elias] Univ Barcelona, Hosp Clin, Barcelona, Spain.
[Delabie, Jan] Radium Hosp, Dept Pathol, Oslo, Norway.
[Cook, James R.; Tubbs, Ray R.] Cleveland Clin, Dept Pathol & Lab Med, Cleveland, OH 44106 USA.
[Cook, James R.; Tubbs, Ray R.] Cleveland Clin, Lerner Coll Med, Dept Mol Pathol, Cleveland, OH 44106 USA.
[Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lenz, Georg; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gascoyne, RD (reprint author), British Columbia Canc Agcy, Dept Pathol & Adv Therapeut, 675 W 10th Ave,Rm 5-113, Vancouver, BC V5Z 1L3, Canada.
EM rgascoyn@bccancer.bc.ca
RI Lenz, Georg/I-6844-2012; Tang, Macy/B-9798-2014; Jones,
Steven/C-3621-2009;
OI Delabie, Jan/0000-0001-5023-0689; Farinha, Pedro/0000-0001-9364-9391;
Campo, elias/0000-0001-9850-9793
FU Deutsche Forschungsgemeinschaft; Cancer Research Society; Lymphoma
Research Foundation; Michael Smith Foundation for Health Research; Roche
Molecular Systems; Canadian Institutes of Health Research [178536];
National Cancer Institute [UO1-CA114778-01]; National Cancer Institute
(NCI) [UO1-CA 114778]; Roche Canada
FX Supported by grants from Deutsche Forschungsgemeinschaft, the Cancer
Research Society, and the Lymphoma Research Foundation (to Dr. Steidl),
the Michael Smith Foundation for Health Research (to Drs. Steidl and
Shah), Roche Molecular Systems, the Canadian Institutes of Health
Research (178536, to Dr. Gascoyne), the National Cancer Institute
(UO1-CA114778-01, to Dr. Chan), and the Intramural Research Program of
the National Cancer Institute (NCI) and by an NCI Strategic Partnering
to Evaluate Cancer Signatures (SPECS) grant (UO1-CA 114778) to the
Lymphoma/Leukemia Molecular Profiling Project consortium.; Dr. Gascoyne
reports receiving consulting fees from Genentech, Roche Canada, and Eli
Lilly and research support from Roche Canada. No other potential
conflict of interest relevant to this article was reported.
NR 34
TC 500
Z9 517
U1 2
U2 31
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 MAR 11
PY 2010
VL 362
IS 10
BP 875
EP 885
DI 10.1056/NEJMoa0905680
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 566JM
UT WOS:000275365900008
PM 20220182
ER
PT J
AU Hsieh, MM
Tisdale, JF
AF Hsieh, Matthew M.
Tisdale, John F.
TI Stem-Cell Transplantation for Sickle Cell Disease REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID VERSUS-HOST-DISEASE
C1 [Hsieh, Matthew M.; Tisdale, John F.] NIH, Bethesda, MD 20892 USA.
RP Hsieh, MM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM johntis@mail.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
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 MAR 11
PY 2010
VL 362
IS 10
BP 956
EP 956
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 566JM
UT WOS:000275365900023
ER
PT J
AU Bradford, PT
Freedman, M
Goldstein, AM
Tucker, MA
AF Bradford, Porcia T.
Freedman, Michal
Goldstein, Alisa M.
Tucker, Margaret A.
TI Increased Risk of Second Primary Cancers After a Diagnosis of Melanoma
SO ARCHIVES OF DERMATOLOGY
LA English
DT Article
ID CUTANEOUS MALIGNANT-MELANOMA; MULTIPLE PRIMARY MELANOMAS; GENOME-WIDE
ASSOCIATION; FOLLOW-UP; PROGNOSTIC FACTORS; IMMUNE COMPETENCE; PRONE
FAMILIES; LYMPHOMA; HISTORY; NEVI
AB Objective: To quantify the risk of subsequent primary cancers among patients with primary Cutaneous malignant melanoma.
Design: Population-based registry study.
Setting: We evaluated data from 9 cancer registries of the Surveillance, Epidemiology, and End Results program from 1973-2006.
Participants: We included 89 515 patients who Survived at least 2 months after their initial melanoma diagnosis.
Results: Of the patients with melanoma, 10 857 (12.1%) developed I or more subsequent primary cancers. The overall risk of a subsequent primary cancer increased by 28% (observed to expected [O:E] ratio=1.28). One quarter of the cancers were subsequent primary melanomas (O:E=8.61). Women with head and neck melanoma and patients younger than 30 had markedly increased risks (O:E=13.22 and 13.40, respectively) of developing a subsequent melanoma. Second melanomas were more likely to be thin than were thefirst of multiple primary melanomas (thickness at diagnosis <1.00 mm, 77.9% vs 70.3%, respectively; P<.001). Melanoma survivors had increased risk of developing several cancers; the most common cancers with elevated risks were breast, prostate, and non-Hodgkin lymphoma (O:E=1.10, 1.15, and 1.25, respectively).
Conclusions: Melanoma survivors have an approximately 9-fold increased risk of developing subsequent melanoma compared with the general population. The risk remains elevated more than 20 years after the initial melanoma diagnosis. This increased risk may be owing to behavioral factors, genetic. susceptibility, or medical surveillance. Although the percentage of subsequent primary melanomas thicker than 1 mm is lower than for the first of multiple primary melanomas, it is still substantial. Melanoma survivors should remain under surveillance not only for recurrence but also for future primary melanomas and other cancers.
C1 [Bradford, Porcia T.; Goldstein, Alisa M.; Tucker, Margaret A.] NCI, Genet Epidemiol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Freedman, Michal] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
RP Bradford, PT (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Execut Plaza S,Room 7005, Rockville, MD 20852 USA.
EM bradfordp@mail.nih.gov
RI Tucker, Margaret/B-4297-2015
FU Intramural Research Program of the 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 56
TC 67
Z9 67
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-987X
J9 ARCH DERMATOL
JI Arch. Dermatol.
PD MAR 10
PY 2010
VL 146
IS 3
BP 265
EP 272
PG 8
WC Dermatology
SC Dermatology
GA 569FU
UT WOS:000275582800007
PM 20231496
ER
PT J
AU Miller, DD
Cowen, EW
Nguyen, JC
McCalmont, TH
Fox, LP
AF Miller, Daniel D.
Cowen, Edward W.
Nguyen, Josephine C.
McCalmont, Timothy H.
Fox, Lindy P.
TI Melanoma Associated With Long-term Voriconazole Therapy A New
Manifestation of Chronic Photosensitivity
SO ARCHIVES OF DERMATOLOGY
LA English
DT Article
ID TRIAZOLE ANTIFUNGAL AGENT; XERODERMA-PIGMENTOSUM; SKIN-CANCER;
PSEUDOPORPHYRIA; ASPERGILLOSIS; PREVENTION; CHILDREN; PATIENT
AB Background: Voriconazole is a triazole antifungal agent approved by the US Food and Drug Administration for serious fungal infections, including with Aspergillus, Fusarium, Pseudallescheria, and Scedosporium species. In initial clinical trials, approximately 2% of patients developed cutaneous reactions, including photosensitivity, cheilitis, and xerosis. Subsequent reports have implicated voriconazole as a cause of severe photosensitivity and accelerated photoaging, pseudoporphyria cutanea tarda, and aggressive squamous cell carcinoma.
Observation: We report 5 melanoma in situ lesions in the setting of extreme photosensitivity associated with long-term voriconazole therapy.
Conclusions: We recommend surveillance for skin cancer formation in all patients who require long-term voriconazole treatment, particularly those who manifest signs or symptoms of photosensitivity or chronic photo-damage. Further study of the mechanism underlying voriconazole photosensitivity and oncogenesis is warranted.
C1 [Miller, Daniel D.; McCalmont, Timothy H.; Fox, Lindy P.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[McCalmont, Timothy H.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
[Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD USA.
[Nguyen, Josephine C.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA.
RP Fox, LP (reprint author), Univ Calif San Francisco, Dept Dermatol, 1701 Divisadero St, San Francisco, CA 94143 USA.
EM foxli@derm.ucsf.edu
NR 24
TC 55
Z9 57
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-987X
J9 ARCH DERMATOL
JI Arch. Dermatol.
PD MAR 10
PY 2010
VL 146
IS 3
BP 300
EP 304
PG 5
WC Dermatology
SC Dermatology
GA 569FU
UT WOS:000275582800013
PM 20083676
ER
PT J
AU Turner, MLC
AF Turner, Maria L. Chanco
TI Sun, Drugs, and Skin Cancer A Continuing Saga
SO ARCHIVES OF DERMATOLOGY
LA English
DT Editorial Material
ID ULTRAVIOLET-A; XERODERMA-PIGMENTOSUM; CELL CARCINOMA; P53 MUTATIONS;
MELANOMA; SUNLIGHT; KERATINOCYTES; VORICONAZOLE; PSORIASIS; PSORALEN
C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA.
RP Turner, MLC (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N-238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA.
EM mlturner@mail.nih.gov
NR 23
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-987X
J9 ARCH DERMATOL
JI Arch. Dermatol.
PD MAR 10
PY 2010
VL 146
IS 3
BP 329
EP 331
PG 3
WC Dermatology
SC Dermatology
GA 569FU
UT WOS:000275582800020
PM 20231508
ER
PT J
AU Bae, MA
Dal Rhee, S
Jung, WH
Ahn, JH
Song, BJ
Cheon, HG
AF Bae, Myung-Ae
Dal Rhee, Sang
Jung, Won Hoon
Ahn, Jin Hee
Song, Byoung-Joon
Cheon, Hyae Gyeong
TI Selective Inhibition of Activated Stellate Cells and Protection from
Carbon Tetrachloride-Induced Liver Injury in Rats by a New PPAR gamma
agonist KR62776
SO ARCHIVES OF PHARMACAL RESEARCH
LA English
DT Article
DE PPAR gamma; Stellate cells; Collagen alpha 1(I); alpha-smooth muscle
actin; KR62776
ID ACID-DEFINED DIET; RECEPTOR-GAMMA; IN-VITRO; HEPATIC-FIBROSIS;
APOPTOSIS; PIOGLITAZONE; PROLIFERATION; HALOFUGINONE; METABOLISM;
EXPRESSION
AB Activated hepatic stellate cells (HSC) are the primary source of extracellular matrix proteins found in liver fibrosis/cirrhosis patients. Therefore, the prevention of HSC activation is an important strategy for treating severe liver injury. This study examined the effects of KR62776, a new peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, on the rate of cell proliferation and expression of alpha-smooth muscle actin (alpha-SAM) in rat hepatic stellate HSC-T6 cells. In addition, its effects on the liver damage induced by carbon tetrachloride were investigated. KR62776 caused the apoptosis of activated HSC-T6 cells with the concomitant decrease in the alpha-smooth muscle actin levels in a time- and concentration-dependent manner. However, KR62776 did not cause the apoptosis of human HepG2 and rat McARH7777 hepatoma cells, suggesting that KR62776 has a specific effect on stellate cells. KR62776 increased the levels of Gadd45, p27, p21 and PPAR gamma proteins but decreased the cell cycle-related proteins, such as cdk2, cyclin B and cyclin D1. These changes were reversed by BADGE, a specific PPAR gamma antagonist, indicating that the effects of KR62776 are, at least in part, PPAR gamma-dependent. In addition, KR62776 administration showed some protection against carbon tetrachloride-induced hepatocellular damage in rats. Overall, these results suggest that KR62776 may have potential in the chemoprevention of liver fibrosis/cirrhosis.
C1 [Bae, Myung-Ae] Korea Res Inst Chem Technol, Div Med Sci, Drug Discovery Platform Technol Team, Taejon 305600, South Korea.
[Dal Rhee, Sang; Jung, Won Hoon; Ahn, Jin Hee; Cheon, Hyae Gyeong] Korea Res Inst Chem Technol, Div Med Sci, Ctr Metab Syndrome Therapeut, Taejon 305600, South Korea.
[Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA.
RP Bae, MA (reprint author), Korea Res Inst Chem Technol, Div Med Sci, Drug Discovery Platform Technol Team, Taejon 305600, South Korea.
EM mbae@krict.re.kr; hgcheon@krict.re.kr
FU Ministry of Science and Technology, Korea
FX This study was supported by grant from the Center for Biological
Modulators of the 21th Century Frontier R&D Program, The Ministry of
Science and Technology, Korea.
NR 35
TC 8
Z9 10
U1 0
U2 6
PU PHARMACEUTICAL SOC KOREA
PI SEOUL
PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA
SN 0253-6269
J9 ARCH PHARM RES
JI Arch. Pharm. Res.
PD MAR 10
PY 2010
VL 33
IS 3
BP 433
EP 442
DI 10.1007/s12272-010-0313-3
PG 10
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 572HP
UT WOS:000275819000014
PM 20361309
ER
PT J
AU Legeai, F
Shigenobu, S
Gauthier, JP
Colbourne, J
Rispe, C
Collin, O
Richards, S
Wilson, ACC
Murphy, T
Tagu, D
AF Legeai, F.
Shigenobu, S.
Gauthier, J. -P.
Colbourne, J.
Rispe, C.
Collin, O.
Richards, S.
Wilson, A. C. C.
Murphy, T.
Tagu, D.
TI AphidBase: a centralized bioinformatic resource for annotation of the
pea aphid genome
SO INSECT MOLECULAR BIOLOGY
LA English
DT Article
DE AphidBase; pea aphid genome; annotation; manual curation; GMOD
ID COMMUNITY ANNOTATION; GENE PREDICTION; DATABASE; PROGRAM; SEQUENCES;
MODEL; RNA; TOOLS; DNA
AB AphidBase is a centralized bioinformatic resource that was developed to facilitate community annotation of the pea aphid genome by the International Aphid Genomics Consortium (IAGC). The AphidBase Information System designed to organize and distribute genomic data and annotations for a large international community was constructed using open source software tools from the Generic Model Organism Database (GMOD). The system includes Apollo and GBrowse utilities as well as a wiki, blast search capabilities and a full text search engine. AphidBase strongly supported community cooperation and coordination in the curation of gene models during community annotation of the pea aphid genome. AphidBase can be accessed at http://www.aphidbase.com.
C1 [Legeai, F.] INRIA, Equipe Symbiose, Ctr Rennes Bretagne Atlantique, F-35042 Rennes, France.
[Legeai, F.; Gauthier, J. -P.; Rispe, C.; Tagu, D.] INRA, UMR, Le Rheu, France.
[Shigenobu, S.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Shigenobu, S.] JST, PRESTO, Saitama, Japan.
[Shigenobu, S.] Natl Inst Nat Sci, Okazaki Inst Integrat Biosci, Okazaki, Aichi 4448787, Japan.
[Colbourne, J.] Indiana Univ, Ctr Genom & Bioinformat, Sch Informat, Bloomington, IN 47405 USA.
[Colbourne, J.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
[Richards, S.] Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Wilson, A. C. C.] Univ Miami, Dept Biol, Coral Gables, FL 33124 USA.
[Murphy, T.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Legeai, F (reprint author), INRIA, Equipe Symbiose, Ctr Rennes Bretagne Atlantique, Campus Beaulieu, F-35042 Rennes, France.
EM fabrice.legeai@rennes.inra.fr
RI Shigenobu, Shuji/B-6239-2011; UMR IGEPP, INRA/A-4054-2011; Colbourne,
John/L-7748-2014
OI Shigenobu, Shuji/0000-0003-4640-2323; Tagu, Denis/0000-0002-6320-8648;
Collin, Olivier/0000-0002-8959-8402; Colbourne, John/0000-0002-6966-2972
FU ANR Genoplante 'GnpAnnot'; American Genetic Association; NRI; CSREES;
USDA [2007-04628]; NIH; National Library of Medicine
FX The authors would like to acknowledge the International Aphid Genomics
Consortium and in particular all the curators involved in gene model
improvement. We thank Ed Lee, Olivier Arnaiz, Scott Cain, Dave Clements
and the rest of the GMOD team, Stephanie Sibide-Bocs, Joelle Amselem and
Michael Alaux from ANR GnpAnnot. The assistance of IT staff of
AphidGenomics at Princeton University, and of Phillip Steinbachs for the
establishment of the IAGC Wiki hosted by The Center for Genomics and
Bioinformatics, Indiana University were fully appreciated. AphidBase is
partly funded by ANR Genoplante 'GnpAnnot'. The Pea Aphid Genome
Annotation Workshop I was supported by an American Genetic Association
Special Event Award and an NRI, CSREES, USDA award 2007-04628 to ACCW.
Work at NCBI was supported by the Intramural Research Program of the
NIH, National Library of Medicine.
NR 34
TC 51
Z9 51
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0962-1075
J9 INSECT MOL BIOL
JI Insect Mol. Biol.
PD MAR 10
PY 2010
VL 19
SU 2
BP 5
EP 12
DI 10.1111/j.1365-2583.2009.00930.x
PG 8
WC Biochemistry & Molecular Biology; Entomology
SC Biochemistry & Molecular Biology; Entomology
GA 560NK
UT WOS:000274909200003
PM 20482635
ER
PT J
AU Van Eperen, L
Marincola, FM
Strohm, J
AF Van Eperen, Laura
Marincola, Francesco M.
Strohm, Jennifer
TI Bridging the Divide between Science and Journalism
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
AB There are countless reasons nearly every scientist should learn how to communicate effectively with the media, including increased understanding of critical research findings to attract or sustain funding and build new professional partnerships that will further propel forward research. But where do scientists begin? Bridging the Divide between Science and Journalism offers practical tips for any scientist looking to work with the media. Given the traditional and internet-based sources for medical research and healthcare-related news now available, it is imperative that scientists know how to communicate their latest findings through the appropriate channels. The credible media channels are managed by working journalists, so learning how to package vast, technical research in a form that is appetizing and "bite-sized" in order to get their attention, is an art. Reducing years of research into a headline can be extremely difficult and certainly doesn't come naturally to every scientist, so this article provides suggestions on how to work with the media to communicate your findings.
C1 [Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Van Eperen, Laura; Strohm, Jennifer] Van Eperen & Co, Strateg Commun Consulting, Bethesda, MD 20817 USA.
RP Marincola, FM (reprint author), NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
EM FMarincola@mail.cc.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD MAR 10
PY 2010
VL 8
AR 25
DI 10.1186/1479-5876-8-25
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 579WA
UT WOS:000276406300001
PM 20219123
ER
PT J
AU Lico, DTP
Rosa, JC
Degiorgis, JA
de Vasconcelos, EJR
Casaletti, L
Tauhata, SBF
Baqui, MMA
Fukuda, M
Moreira, JE
Larson, RE
AF Lico, D. T. P.
Rosa, J. C.
Degiorgis, J. A.
de Vasconcelos, E. J. R.
Casaletti, L.
Tauhata, S. B. F.
Baqui, M. M. A.
Fukuda, M.
Moreira, J. E.
Larson, R. E.
TI NOVEL 65 kDa RNA-BINDING PROTEIN IN SQUID PRESYNAPTIC TERMINALS
SO NEUROSCIENCE
LA English
DT Article
DE myosin V; hnRNP complex; RNP motifs; synaptosome; optic lobe; Loligo
ID BRAIN MYOSIN-V; RAT CEREBRAL-CORTEX; MESSENGER-RNAS; GIANT SYNAPSE;
UNCONVENTIONAL MYOSIN; ANTIBODY INJECTION; MOTOR PROTEINS; BUDDING
YEAST; KINASE-II; TRANSPORT
AB A polyclonal antibody (C4), raised against the head domain of chicken myosin Va, reacted strongly towards a 65 kDa polypeptide (p65) on Western blots of extracts from squid optic lobes but did not recognize the heavy chain of squid myosin V. This peptide was not recognized by other myosin Va antibodies, nor by an antibody specific for squid myosin V. In an attempt to identify it, p65 was purified from optic lobes of Loligo plei by cationic exchange and reverse phase chromatography. Several peptide sequences were obtained by mass spectroscopy from p65 cut from sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) gels. BLAST analysis and partial matching with expressed sequence tags (ESTs) from a Loligo pealei data bank indicated that p65 contains consensus signatures for the heterogeneous nuclear ribonucleoprotein (hnRNP) A/B family of RNA-binding proteins. Centrifugation of post mitochondrial extracts from optic lobes on sucrose gradients after treatment with RNase gave biochemical evidence that p65 associates with cytoplasmic RNP complexes in an RNA-dependent manner. Immunohistochemistry and immunofluorescence studies using the C4 antibody showed partial co-labeling with an antibody against squid synaptotagmin in bands within the outer plexiform layer of the optic lobes and at the presynaptic zone of the stellate ganglion. Also, punctate labeling by the C4 antibody was observed within isolated optic lobe synaptosomes. The data indicate that p65 is a novel RNA-binding protein located to the presynaptic terminal within squid neurons and may have a role in synaptic localization of RNA and its translation or processing. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Lico, D. T. P.; Rosa, J. C.; de Vasconcelos, E. J. R.; Casaletti, L.; Tauhata, S. B. F.; Baqui, M. M. A.; Moreira, J. E.; Larson, R. E.] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cellular & Mol Biol, BR-14049900 Sao Paulo, Brazil.
[Degiorgis, J. A.; Moreira, J. E.] Marine Biol Lab, Woods Hole, MA 02543 USA.
[Degiorgis, J. A.] Providence Coll, Dept Biol, Providence, RI 02918 USA.
[Degiorgis, J. A.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
[Fukuda, M.] Tohoku Univ, Grad Sch Life Sci, Dept Dev Biol & Neurosci, Sendai, Miyagi 9808578, Japan.
RP Larson, RE (reprint author), Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cellular & Mol Biol, BR-14049900 Sao Paulo, Brazil.
EM relarson@fmrp.usp.br
RI Rosa, Jose /A-1966-2013; Baqui, Munira/H-5243-2013; Celulas tronco,
Inct/I-1921-2013; Vasconcelos, Elton/O-5593-2014; Fukuda,
MItsunori/I-1511-2015
OI Baqui, Munira/0000-0002-7945-2899;
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Conselho
Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Fundacao de
Apoio ao Ensino, Pesquisa e Assistencia do Hospital das Clinicas da
FMRP-USP (FAEPA); Nation Center for Research Resources, NIH, Bethesda,
MD [P20RR016457]
FX We thank Domingos Pitta, Silvia Regina Andrade Nascimento, Maria Tereza
Picinoto Maglia and Vani Maria Alves Correa for expert technical
assistance. Special thanks to Dr. Thomas Reese, National Institute of
Neurological Disorders and Strokes, NIH, in whose laboratory several
critical experiments on Loligo pealei were first done. Live Loligo plei
were obtained from the Centro de Biologia Marinha da Universidade de Sao
Paulo (CEBIMar). REL, JCR and JEM received financial support from the
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), the
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and
the Fundacao de Apoio ao Ensino, Pesquisa e Assistencia do Hospital das
Clinicas da FMRP-USP (FAEPA). JAD received financial support from the
RI-INBRE Program grant #P20RR016457 from the Nation Center for Research
Resources, NIH, Bethesda, MD. DTPL, LC, SBFT, EJRV and MMAB were
recipients of research fellowships from FAPESP and CNPq. REL and JEM
received Productivity-in-Research fellowships from CNPq. The confocal
work was performed on Leica microscopes in the Laboratorio Multiusuario
de Microscopia Confocal do Departamento de Biologia Celular e Molecular
e Bioagentes Patogenicos-FMRP/USP under the technical supervision of Dr.
Lenaldo Branco Rocha.
NR 56
TC 3
Z9 3
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
EI 1873-7544
J9 NEUROSCIENCE
JI Neuroscience
PD MAR 10
PY 2010
VL 166
IS 1
BP 73
EP 83
DI 10.1016/j.neuroscience.2009.12.005
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 555JT
UT WOS:000274507500009
PM 20004709
ER
PT J
AU Karakasiliotis, I
Vashist, S
Bailey, D
Abente, EJ
Green, KY
Roberts, LO
Sosnovtsev, SV
Goodfellow, IG
AF Karakasiliotis, Ioannis
Vashist, Surender
Bailey, Dalan
Abente, Eugenio J.
Green, Kim Y.
Roberts, Lisa O.
Sosnovtsev, Stanislav V.
Goodfellow, Ian G.
TI Polypyrimidine Tract Binding Protein Functions as a Negative Regulator
of Feline Calicivirus Translation
SO PLOS ONE
LA English
DT Article
ID RIBOSOME ENTRY SITE; NUCLEAR-PORE COMPLEX; VIRUS GENOMIC RNA;
MOUTH-DISEASE VIRUS; CELLULAR-PROTEINS; MAMMALIAN-CELLS; CAPSID PROTEIN;
INFECTED-CELLS; NONSTRUCTURAL POLYPROTEIN; POLY(A)-BINDING PROTEIN
AB Background: Positive strand RNA viruses rely heavily on host cell RNA binding proteins for various aspects of their life cycle. Such proteins interact with sequences usually present at the 59 or 39 extremities of the viral RNA genome, to regulate viral translation and/or replication. We have previously reported that the well characterized host RNA binding protein polypyrimidine tract binding protein (PTB) interacts with the 5'end of the feline calicivirus (FCV) genomic and subgenomic RNAs, playing a role in the FCV life cycle.
Principal Findings: We have demonstrated that PTB interacts with at least two binding sites within the 5'end of the FCV genome. In vitro translation indicated that PTB may function as a negative regulator of FCV translation and this was subsequently confirmed as the translation of the viral subgenomic RNA in PTB siRNA treated cells was stimulated under conditions in which RNA replication could not occur. We also observed that PTB redistributes from the nucleus to the cytoplasm during FCV infection, partially localizing to viral replication complexes, suggesting that PTB binding may be involved in the switch from translation to replication. Reverse genetics studies demonstrated that synonymous mutations in the PTB binding sites result in a cell-type specific defect in FCV replication.
Conclusions: Our data indicates that PTB may function to negatively regulate FCV translation initiation. To reconcile this with efficient virus replication in cells, we propose a putative model for the function of PTB in the FCV life cycle. It is possible that during the early stages of infection, viral RNA is translated in the absence of PTB, however, as the levels of viral proteins increase, the nuclear-cytoplasmic shuttling of PTB is altered, increasing the cytoplasmic levels of PTB, inhibiting viral translation. Whether PTB acts directly to repress translation initiation or via the recruitment of other factors remains to be determined but this may contribute to the stimulation of viral RNA replication via clearance of ribosomes from viral RNA.
C1 [Karakasiliotis, Ioannis; Vashist, Surender; Bailey, Dalan; Goodfellow, Ian G.] Univ London Imperial Coll Sci Technol & Med, Dept Virol, London, England.
[Abente, Eugenio J.; Green, Kim Y.; Sosnovtsev, Stanislav V.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Abente, Eugenio J.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA.
[Roberts, Lisa O.] Univ Surrey, Fac Hlth & Med Sci, Guildford GU2 5XH, Surrey, England.
RP Karakasiliotis, I (reprint author), BSRC Alexander Fleming, Lab Post Transcript Control, Vari, Greece.
EM I.Goodfellow@imperial.ac.uk
RI Roberts, Lisa/E-6365-2010; vashist, surender/H-5879-2013;
OI Bailey, Dalan/0000-0002-5640-2266; Abente, Eugenio/0000-0002-3390-2786;
Goodfellow, Ian/0000-0002-9483-510X
FU Wellcome Trust; Biotechnology and Biological Sciences Research Council
(BBSRC); National Institute of Allergy and Infectious Diseases (NIAID),
National Institutes of Health, US
FX This work was supported by the Wellcome Trust, Biotechnology and
Biological Sciences Research Council (BBSRC) and in part by the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health, US. I.G. is
a Wellcome Senior Fellow. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 64
TC 19
Z9 19
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 10
PY 2010
VL 5
IS 3
AR e9562
DI 10.1371/journal.pone.0009562
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 565XE
UT WOS:000275328800009
PM 20224775
ER
PT J
AU Wang, V
Davis, DA
Veeranna, RP
Haque, M
Yarchoan, R
AF Wang, Victoria
Davis, David A.
Veeranna, Ravindra P.
Haque, Muzammel
Yarchoan, Robert
TI Characterization of the Activation of Protein Tyrosine Phosphatase,
Receptor-Type, Z Polypeptide 1 (PTPRZ1) by Hypoxia Inducible Factor-2
Alpha
SO PLOS ONE
LA English
DT Article
ID RENAL-CELL CARCINOMA; TRANSCRIPTION FACTORS; HIF-2-ALPHA PROMOTES;
ENDOTHELIAL-CELLS; RESPONSE ELEMENTS; BINDING-SITES; BETA-CATENIN;
C-MYC; GENE; EXPRESSION
AB Background: Hypoxia inducible factors (HIFs) are the principal means by which cells upregulate genes in response to hypoxia and certain other stresses. There are two major HIFs, HIF-1 and HIF-2. We previously found that certain genes are preferentially activated by HIF-2. One was protein tyrosine phosphatase, receptor-type, Z polypeptide 1 (PTPRZ1). PTPRZ1 is overexpressed in a number of tumors and has been implicated in glioblastoma pathogenesis.
Methodology/Principal Findings: To understand the preferential activation of PTPRZ1 by HIF-2, we studied the PTPRZ1 promoter in HEK293T cells and Hep3B cells. Through deletion and mutational analysis, we identified the principal hypoxia response element. This element bound to both HIF-1 and HIF-2. We further identified a role for ELK1, an E26 transformation-specific (Ets) factor that can bind to HIF-2 alpha but not HIF-1 alpha, in the HIF-2 responsiveness. Knock-down experiments using siRNA to ELK1 decreased HIF-2 activation by over 50%. Also, a deletion mutation of one of the two Ets binding motifs located near the principal hypoxia response element similarly decreased activation of the PTPRZ1 promoter by HIF-2. Finally, chromatin immunoprecipitation assays showed binding of HIF and ELK1 to the PTPRZ1 promoter region.
Conclusions/Significance: These results identify HIF-binding and Ets-binding motifs on the PTPRZ1 promoter and provide evidence that preferential activation of PTPRZ1 by HIF-2 results at least in part from cooperative binding of HIF-2 and ELK1 to nearby sites on the PTPRZ1 promoter region. These results may have implications in tumor pathogenesis and in understanding neurobiology, and may help inform the development of novel tumor therapy.
C1 [Wang, Victoria] NCI, HIV, NIH, Bethesda, MD 20892 USA.
NCI, AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Wang, V (reprint author), NCI, HIV, NIH, Bethesda, MD 20892 USA.
EM yarchoan@helix.nih.gov
OI Ravindra, P V/0000-0003-4228-1843
FU National Institutes of Heath, National Cancer Institute
FX This project was supported by the Intramural Research Program of the
National Institutes of Heath, National Cancer Institute. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 45
TC 13
Z9 14
U1 3
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 10
PY 2010
VL 5
IS 3
AR e9641
DI 10.1371/journal.pone.0009641
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 565XE
UT WOS:000275328800032
PM 20224786
ER
PT J
AU O'Connor, SL
Lhost, JJ
Becker, EA
Detmer, AM
Johnson, RC
MacNair, CE
Wiseman, RW
Karl, JA
Greene, JM
Burwitz, BJ
Bimber, BN
Lank, SM
Tuscher, JJ
Mee, ET
Rose, NJ
Desrosiers, RC
Hughes, AL
Friedrich, TC
Carrington, M
O'Connor, DH
AF O'Connor, Shelby L.
Lhost, Jennifer J.
Becker, Ericka A.
Detmer, Ann M.
Johnson, Randall C.
MacNair, Caitlin E.
Wiseman, Roger W.
Karl, Julie A.
Greene, Justin M.
Burwitz, Benjamin J.
Bimber, Benjamin N.
Lank, Simon M.
Tuscher, Jennifer J.
Mee, Edward T.
Rose, Nicola J.
Desrosiers, Ronald C.
Hughes, Austin L.
Friedrich, Thomas C.
Carrington, Mary
O'Connor, David H.
TI MHC Heterozygote Advantage in Simian Immunodeficiency Virus-Infected
Mauritian Cynomolgus Macaques
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL RESPONSES; CLASS-I ALLELES;
VIRAL LOAD; HIV-1 EVOLUTION; DISEASE PROGRESSION; LYMPHOCYTE ESCAPE;
RHESUS MACAQUES; VACCINE; HLA
AB The importance of a broad CD8 T lymphocyte (CD8-TL) immune response to HIV is unknown. Ex vivo measurements of immunological activity directed at a limited number of defined epitopes provide an incomplete portrait of the actual immune response. We examined viral loads in simian immunodeficiency virus (SIV)-infected major histocompatibility complex (MHC)-homozygous and MHC-heterozygous Mauritian cynomolgus macaques. Chronic viremia in MHC-homozygous macaques was 80 times that in MHC-heterozygous macaques. Virus from MHC-homozygous macaques accumulated 11 to 14 variants, consistent with escape from CD8-TL responses after 1 year of SIV infection. The pattern of mutations detected in MHC-heterozygous macaques suggests that their epitope-specific CD8-TL responses are a composite of those present in their MHC-homozygous counterparts. These results provide the clearest example of MHC heterozygote advantage among individuals infected with the same immunodeficiency virus strain, suggesting that broad recognition of multiple CD8-TL epitopes should be a key feature of HIV vaccines.
C1 [O'Connor, Shelby L.; Lhost, Jennifer J.; Greene, Justin M.; Burwitz, Benjamin J.; O'Connor, David H.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.
[Becker, Ericka A.; Detmer, Ann M.; MacNair, Caitlin E.; Wiseman, Roger W.; Karl, Julie A.; Bimber, Benjamin N.; Lank, Simon M.; Tuscher, Jennifer J.; Friedrich, Thomas C.; O'Connor, David H.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53706 USA.
[Johnson, Randall C.] NCI, Lab Genom Divers, Sci Applicat Int Corp, Frederick, MD 21702 USA.
[Johnson, Randall C.] Conservatoire Natl Arts & Metiers, Chaire Bioinfromat, F-75003 Paris, France.
[Mee, Edward T.; Rose, Nicola J.] Natl Inst Biol Stand & Controls, Div Retrovirol, Potters Bar EN6 3QG, Herts, England.
[Desrosiers, Ronald C.] Harvard Univ, New England Primate Res Ctr, Sch Med, Southborough, MA 01772 USA.
[Hughes, Austin L.] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA.
[Carrington, Mary] NCI, Canc & Inflammat Program, Sci Applicat Int Corp, Frederick, MD 21702 USA.
[Carrington, Mary] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA.
RP O'Connor, DH (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.
EM doconnor@primate.wisc.edu
RI Johnson, Randall/B-1517-2014;
OI Johnson, Randall/0000-0001-7754-0847; o'connor,
david/0000-0003-2139-470X; Friedrich, Thomas/0000-0001-9831-6895
FU CCR NIH HHS [HHSN261200800001C]; Department of Health; Intramural NIH
HHS; Medical Research Council [G9025730]; NCI NIH HHS
[HHSN261200800001E]; NCRR NIH HHS [C06 RR015459, C06 RR020141, P40
RR019995, P51 RR000167-40, P51 RR000168, RR00168, P51 RR000167, P51
RR000168-430164]; NIAID NIH HHS [R01 AI077376, R01 AI084787, R01
AI084787-01, R21 AI068488, R21 AI082880, R21 AI082880-01, R01
AI077376-02, R21 AI068488-02]; NIGMS NIH HHS [R01 GM043940-11, GM43940,
R01 GM043940]
NR 49
TC 30
Z9 30
U1 0
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 MAR 10
PY 2010
VL 2
IS 22
AR 22ra18
DI 10.1126/scitranslmed.3000524
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 591MD
UT WOS:000277303900002
PM 20375000
ER
PT J
AU Bermejo, GA
Strub, MP
Ho, C
Tjandra, N
AF Bermejo, Guillermo A.
Strub, Marie-Paule
Ho, Chien
Tjandra, Nico
TI Ligand-Free Open-Closed Transitions of Periplasmic Binding Proteins: The
Case of Glutamine-Binding Protein
SO BIOCHEMISTRY
LA English
DT Article
ID PARAMAGNETIC RELAXATION ENHANCEMENT; MOLECULAR-STRUCTURE DETERMINATION;
ESCHERICHIA-COLI; ACTIVE-TRANSPORT; SINORHIZOBIUM-MELILOTI; XPLOR-NIH;
NMR; DYNAMICS; SPECIFICITY; RESOLUTION
AB The ability to undergo large-scale domain rearrangements is essential for the substrate-binding function of periplasmic binding proteins (PBPs). which are indispensable for nutrient uptake in Gram-negative bacteria. Crystal structures Indicate that PBPs typically adopt either an "open" unliganded configuration or a "closed" liganded one. However. it is not clear whether, its a general rule, PBPs remain open until ligand-induced interdomain closure or are in equilibrium with a minor population of unliganded, closed species. Evidence for the latter has been recently reported oil maltose-binding, protein (MBP) in aqueous solution [Tang, C., et al. (2007) Nature 449, 1078-1082] via paramagnetic relaxation enhancement (PRE), a technique able to probe lowly populated regions of conformational spaces. Here, we use PRE to study the unliganded open-closed transition of another PBP: glutamine-binding protein (GlnBP). Through It combination of domain structure knowledge and Intermolecular and concentration dependence PRE experiments, a set of surface residues was found to be involved In intermolecular interactions. Barring such residues, PRE data oil ligand-free GlnBP, paramagnetically labeled at two sites (one at a time), could be appropriately explained by the unliganded, open crystal stricture in that it both yielded a good PRE fit and was not significantly affected by PRE-based refinement. Thus. contrary to MBP, our data did not particularly suggest the coexistence of a minor closed conformer. Several possibilities were explored to explain the observed differences in such Closely structurally related systems; among them, a particularly interesting one arises from close inspection of the interdomain "hinge" region of various PBPs: strong, hydrogen bond Interactions discourage large-scale interdomain dynamics.
C1 [Bermejo, Guillermo A.; Strub, Marie-Paule; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Ho, Chien] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA.
RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 50,Room 3503, Bethesda, MD 20892 USA.
EM tjandran@nhlbi.nih.gov
RI Ho, Chien/O-6112-2016
OI Ho, Chien/0000-0002-4094-9232
FU NIH [GM-084614]; NHLBI
FX This work was supported by NIH Grant GM-084614 to C.H. and by the
Intramural Research program of the NIH, NHLBI, to N.T.
NR 49
TC 34
Z9 35
U1 1
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 9
PY 2010
VL 49
IS 9
BP 1893
EP 1902
DI 10.1021/bi902045p
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 560UK
UT WOS:000274928500010
PM 20141110
ER
PT J
AU Petrik, AF
Strub, MP
Lee, JC
AF Petrik, Amy F.
Strub, Marie-Paule
Lee, Jennifer C.
TI Energy Transfer Ligands of the GluR2 Ligand Binding Core
SO BIOCHEMISTRY
LA English
DT Article
ID IONOTROPIC GLUTAMATE RECEPTORS; TIME-RESOLVED FLUORESCENCE; TRYPTOPHAN
FLUORESCENCE; CONFORMATIONAL DYNAMICS; CRYSTAL-STRUCTURES; ION CHANNELS;
DOMAIN; AMPA; MECHANISMS; PROTEIN
AB Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate excitatory signaling in the central nervous system. When a ligand binds to the extracellular domain of iGluRs, local conformational changes ensue and this motion is translated to the transmembrane domain, inducing channel opening. We have used an isolated ligand binding domain, GluR2-SlS2J (GluR2), as a model system to study the protein-ligand complex by steady-state and time-resolved intrinsic tryptophan fluorescence measurements. Specifically, we determined that the widely used and structurally characterized antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), acts as an efficient fluorescence energy transfer (FET) acceptor for Trp. Consistent with crystallographic data our results indicate that the four native tryptophans are within Forster's radius (R(o) similar to 33 angstrom) of the bound ligand. Additionally, we demonstrate the broader value of this technique by identifying an original FET ligand, 3-nitrotyrosine (3NY), for GluR2 (R(o) similar to 24 angstrom; apparent dissociation constant K(d) similar to 170 mu M). Estimated average donor-acceptor (Trp-ligand) distance extracted from tryptophan excited-state decays are similar for both ligands (similar to 24 angstrom), suggesting that 3NY binds in the structurally characterized ligand binding cleft. Moreover, an alternative competition assay utilizing Trp -> DNQX quenching for detection of ligand binding in GluR2 is described.
C1 [Petrik, Amy F.; Strub, Marie-Paule; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Lee, JC (reprint author), NHLBI, Lab Mol Biophys, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM leej4@mail.nih.gov
FU National Institutes of Health, National Heart, Lung, and Blood Institute
FX This work is supported by the Intramural Research Program of the
National Institutes of Health, National Heart, Lung, and Blood
Institute.
NR 38
TC 1
Z9 1
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 9
PY 2010
VL 49
IS 9
BP 2051
EP 2057
DI 10.1021/bi9020007
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 560UK
UT WOS:000274928500026
PM 20155979
ER
PT J
AU Attardo, GM
Ribeiro, JMC
Wu, YN
Berriman, M
Aksoy, S
AF Attardo, Geoffrey M.
Ribeiro, Jose M. C.
Wu, Yineng
Berriman, Matthew
Aksoy, Serap
TI Transcriptome analysis of reproductive tissue and intrauterine
developmental stages of the tsetse fly (Glossina morsitans morsitans)
SO BMC GENOMICS
LA English
DT Article
ID DROSOPHILA-MELANOGASTER; SEQUENCE ALIGNMENT; MOLECULAR ASPECTS; GENE
ONTOLOGY; YOLK PROTEINS; PSI-BLAST; DATABASE; EXPRESSION; PHYLOGENY;
FAMILIES
AB Background: Tsetse flies, vectors of African trypanosomes, undergo viviparous reproduction (the deposition of live offspring). This reproductive strategy results in a large maternal investment and the deposition of a small number of progeny during a female's lifespan. The reproductive biology of tsetse has been studied on a physiological level; however the molecular analysis of tsetse reproduction requires deeper investigation. To build a foundation from which to base molecular studies of tsetse reproduction, a cDNA library was generated from female tsetse (Glossina morsitans morsitans) reproductive tissues and the intrauterine developmental stages. 3438 expressed sequence tags were sequenced and analyzed.
Results: Analysis of a nonredundant catalogue of 1391 contigs resulted in 520 predicted proteins. 475 of these proteins were full length. We predict that 412 of these represent cytoplasmic proteins while 57 are secreted. Comparison of these proteins with other tissue specific tsetse cDNA libraries (salivary gland, fat body/milk gland, and midgut) identified 51 that are unique to the reproductive/immature cDNA library. 11 unique proteins were homologus to uncharacterized putative proteins within the NR database suggesting the identification of novel genes associated with reproductive functions in other insects (hypothetical conserved). The analysis also yielded seven putative proteins without significant homology to sequences present in the public database (unknown genes). These proteins may represent unique functions associated with tsetse's viviparous reproductive cycle. RTPCR analysis of hypothetical conserved and unknown contigs was performed to determine basic tissue and stage specificity of the expression of these genes.
Conclusion: This paper identifies 51 putative proteins specific to a tsetse reproductive/ immature EST library. 11 of these proteins correspond to hypothetical conserved genes and 7 proteins are tsetse specific.
C1 [Attardo, Geoffrey M.; Wu, Yineng; Aksoy, Serap] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Ribeiro, Jose M. C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Berriman, Matthew] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
RP Aksoy, S (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
EM serap.aksoy@yale.edu
RI Berriman, Matthew/A-7618-2011;
OI Aksoy, Serap/0000-0001-9941-143X; Ribeiro, Jose/0000-0002-9107-0818
FU NIH [AI51584, AI081774, F32 GM077964]; National Institute of Allergy and
Infectious Diseases; Wellcome Trust [WT 085775/Z/08/Z]; WHO/TDR
FX This research was supported by grants from NIH AI51584 and AI081774 to
SA, the NIH Ruth Kirschstein Postdoctoral Training Award F32 GM077964 to
GMA and by the Intramural Research Program of the National Institute of
Allergy and Infectious Diseases to JMCR. 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 organization imply endorsement by the government of the
United States of America.; Because JMCR is a government employee and
this is a government work, the work is in the public domain in the
United States. Notwithstanding any other agreements, the NIH reserves
the right to provide the work to PubMedCentral for display and use by
the public, and PubMedCentral may tag or modify the work consistent with
its customary practices. You can establish rights outside of the U.S.
subject to a government use license. MB is supported by the Wellcome
Trust [grant number WT 085775/Z/08/Z]. This study is part of the
International Glossina Genomics Initiative (IGGI), established in 2004
with support from WHO/TDR to promote knowledge on Glossina biology
including host-pathogen interactions, genetics of vector competence,
olfactory biology and population genetics to support vector control
efforts.
NR 41
TC 17
Z9 17
U1 0
U2 7
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 MAR 9
PY 2010
VL 11
AR 160
DI 10.1186/1471-2164-11-160
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 579IT
UT WOS:000276363700002
PM 20214793
ER
PT J
AU Pemberton, VL
McCrindle, BW
Barkin, S
Daniels, SR
Barlow, SE
Binns, HJ
Cohen, MS
Economos, C
Faith, MS
Gidding, SS
Goldberg, CS
Kavey, RE
Longmuir, P
Rocchini, AP
Van Horn, L
Kaltman, JR
AF Pemberton, Victoria L.
McCrindle, Brian W.
Barkin, Shari
Daniels, Stephen R.
Barlow, Sarah E.
Binns, Helen J.
Cohen, Meryl S.
Economos, Christina
Faith, Myles S.
Gidding, Samuel S.
Goldberg, Caren S.
Kavey, Rae-Ellen
Longmuir, Patricia
Rocchini, Albert P.
Van Horn, Linda
Kaltman, Jonathan R.
TI Report of the National Heart, Lung, and Blood Institute's Working Group
on Obesity and Other Cardiovascular Risk Factors in Congenital Heart
Disease
SO CIRCULATION
LA English
DT Article
DE diet; exercise; heart defects, congenital; obesity; risk factors
ID ARTERIAL SWITCH OPERATION; PHYSICAL-ACTIVITY LEVELS; RANDOMIZED
CONTROLLED-TRIAL; OBSTRUCTIVE SLEEP-APNEA; QUALITY-OF-LIFE; CHILDHOOD
OBESITY; CARDIAC REHABILITATION; SCIENTIFIC STATEMENT; EXERCISE
CAPACITY; PRESSURE RESEARCH
C1 [Pemberton, Victoria L.] NHLBI, NIH, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[McCrindle, Brian W.; Longmuir, Patricia] Univ Toronto, Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada.
[Barkin, Shari] Vanderbilt Univ, Nashville, TN USA.
[Daniels, Stephen R.] Univ Colorado, Boulder, CO 80309 USA.
[Barlow, Sarah E.] Baylor Coll Med, Houston, TX 77030 USA.
[Binns, Helen J.] Childrens Mem Hosp, Chicago, IL 60614 USA.
[Binns, Helen J.; Van Horn, Linda] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Cohen, Meryl S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Economos, Christina] Tufts Univ, Boston, MA 02111 USA.
[Faith, Myles S.] Univ Penn, Philadelphia, PA 19104 USA.
[Gidding, Samuel S.] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Goldberg, Caren S.; Rocchini, Albert P.] Univ Michigan, Ann Arbor, MI 48109 USA.
RP Pemberton, VL (reprint author), NHLBI, NIH, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8102, Bethesda, MD 20892 USA.
EM pembertonv@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute, National Institutes of Health
FX The WG meeting was supported by the National Heart, Lung, and Blood
Institute, National Institutes of Health.
NR 62
TC 37
Z9 38
U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAR 9
PY 2010
VL 121
IS 9
BP 1153
EP 1159
DI 10.1161/CIRCULATIONAHA.109.921544
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 565XR
UT WOS:000275331600012
PM 20212294
ER
PT J
AU Narayan, KMV
Aviles-Santa, L
Oza-Frank, R
Pandey, M
Curb, JD
McNeely, M
Araneta, MRG
Palaniappan, L
Rajpathak, S
Barrett-Connor, E
AF Narayan, K. M. Venkat
Aviles-Santa, Larissa
Oza-Frank, Reena
Pandey, Mona
Curb, J. David
McNeely, Marguerite
Araneta, Maria Rosario G.
Palaniappan, Latha
Rajpathak, Swapnil
Barrett-Connor, Elizabeth
CA Cardiovasc Dis Asian Pacific Islan
TI Report of a National Heart, Lung, and Blood Institute Workshop:
Heterogeneity in Cardiometabolic Risk in Asian Americans in the US
Opportunities for Research
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE cardiovascular disease; type 2 diabetes; Asian Americans; Pacific
Islanders; ethnicity; disparity
ID GESTATIONAL DIABETES-MELLITUS; JAPANESE-AMERICANS;
CARDIOVASCULAR-DISEASE; VISCERAL ADIPOSITY; GLUCOSE-TOLERANCE; WHITE
WOMEN; MULTIETHNIC POPULATION; CORONARY CALCIFICATION; INSULIN
SENSITIVITY; ETHNIC-DIFFERENCES
AB The Asian and Pacific Islander population (Asian Americans) in the U.S. has increased dramatically in the last few decades. Yet, data on cardiovascular disease (CVD) in this population are scarce. The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health conducted an Expert Workshop to: 1) assess the importance of studying CVD in Asian Americans in the U.S.; and 2) consider strategic options for further investigations of CVD in this population. There is considerable geographical, ethnic, cultural, and genetic diversity within this population. Limited data also suggest striking differences in the risk of CVD, obesity, type 2 diabetes mellitus, and other CVD risk factors across the Asian-American population. The Asian-American population is a new diverse pool with less contemporary genetic and cultural admixture relative to groups that have lived in the U.S. for generations, plus it is diverse in lifestyle including culture, diet, and family structure. This diversity provides a window of opportunity for research on genes and gene-environment interactions and also to investigate how acculturation/assimilation to U.S. lifestyles affects health and CVD risk among relatively homogenous groups of recent immigrants. Given the heterogeneity in body weight, body size, and CVD risk, the Asian-American population in the U.S. offers a unique model to study the interaction and relationships between visceral adiposity and adipose tissue distribution and beta cell function, insulin resistance, and atherosclerosis. (J Am Coll Cardiol 2010; 55: 966-73) (C) 2010 by the American College of Cardiology Foundation
C1 [Narayan, K. M. Venkat; Oza-Frank, Reena] Emory Univ, Hubert Dept Global Hlth, Atlanta, GA 30322 USA.
[Aviles-Santa, Larissa; Pandey, Mona] NHLBI, NIH, Bethesda, MD 20892 USA.
[McNeely, Marguerite] Univ Washington, Seattle, WA 98195 USA.
[Araneta, Maria Rosario G.; Barrett-Connor, Elizabeth] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Palaniappan, Latha] Palo Alto Med Fdn Res Inst, Palo Alto, CA USA.
[Rajpathak, Swapnil] Yeshiva Univ, Albert Einstein Coll Med, New York, NY 10033 USA.
RP Narayan, KMV (reprint author), Emory Univ, Hubert Dept Global Hlth, 1518 Clifton Rd, Atlanta, GA 30322 USA.
EM knaraya@emory.edu
RI Narayan, K.M. Venkat /J-9819-2012
OI Narayan, K.M. Venkat /0000-0001-8621-5405
FU National Heart, Lung, and Blood Institute at the National Institutes of
Health; Zymogenetics
FX This paper was a product of a workshop sponsored and conducted by the
National Heart, Lung, and Blood Institute at the National Institutes of
Health. Dr. McNeely has received salary support of <$6,000 from
Zymogenetics for study on risk factors for coagulopathy in post-surgical
patients (October 2008 to May 2009); this support is not directly
related to this article.
NR 65
TC 40
Z9 41
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 9
PY 2010
VL 55
IS 10
BP 966
EP 973
DI 10.1016/j.jacc.2009.07.075
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 563OW
UT WOS:000275143200002
PM 20202512
ER
PT J
AU Bruni, AC
Bernardi, L
Colao, R
Rubino, E
Smirne, N
Frangipane, F
Terni, B
Curcio, SAM
Mirabelli, M
Clodomiro, A
Di Lorenzo, R
Maletta, R
Anfossi, M
Gallo, M
Geracitano, S
Tomaino, C
Muraca, MG
Leotta, A
Lio, SG
Pinessi, L
Rainero, I
Sorbi, S
Nee, L
Milan, G
Pappata, S
Postiglione, A
Abbamondi, N
Forloni, G
Hyslop, PSG
Rogaeva, E
Bugiani, O
Giaccone, G
Foncin, JF
Spillantini, MG
Puccio, G
AF Bruni, A. C.
Bernardi, L.
Colao, R.
Rubino, E.
Smirne, N.
Frangipane, F.
Terni, B.
Curcio, S. A. M.
Mirabelli, M.
Clodomiro, A.
Di Lorenzo, R.
Maletta, R.
Anfossi, M.
Gallo, M.
Geracitano, S.
Tomaino, C.
Muraca, M. G.
Leotta, A.
Lio, S. G.
Pinessi, L.
Rainero, I.
Sorbi, S.
Nee, L.
Milan, G.
Pappata, S.
Postiglione, A.
Abbamondi, N.
Forloni, G.
Hyslop, P. St. George
Rogaeva, E.
Bugiani, O.
Giaccone, G.
Foncin, J. F.
Spillantini, M. G.
Puccio, G.
TI Worldwide distribution of PSEN1 Met146Leu mutation A large variability
for a founder mutation
SO NEUROLOGY
LA English
DT Article
ID ONSET ALZHEIMER-DISEASE; FRONTOTEMPORAL DEMENTIA; PRESENILIN-1 MUTATION;
S182 GENE; FAMILIES; AD; PHENOTYPES
AB Objective: Large kindreds segregating familial Alzheimer disease (FAD) offer the opportunity of studying clinical variability as observed for presenilin 1 (PSEN1) mutations. Two early-onset FAD (EOFAD) Calabrian families with PSEN1 Met146Leu (ATG/CTG) mutation constitute a unique population descending from a remote common ancestor. Recently, several other EOFAD families with the same mutation have been described worldwide.
Methods: We searched for a common founder of the PSEN1 Met146Leu mutation in families with different geographic origins by genealogic and molecular analyses. We also investigated the phenotypic variability at onset in a group of 50 patients (mean age at onset 40.0 +/- 4.8 years) by clinical, neuropsychological, and molecular methodologies.
Results: EOFAD Met146Leu families from around the world resulted to be related and constitute a single kindred originating from Southern Italy before the 17th century. Phenotypic variability at onset is broad: 4 different clinical presentations may be recognized, 2 classic for AD (memory deficits and spatial and temporal disorientation), whereas the others are expressions of frontal impairment. The apathetic and dysexecutive subgroups could be related to orbital-medial prefrontal cortex and dorsolateral prefrontal cortex dysfunction.
Conclusions: Genealogic and molecular findings provided evidence that the PSEN1 Met146Leu families from around the world analyzed in this study are related and represent a single kindred originating from Southern Italy. The marked phenotypic variability might reflect early involvement by the pathologic process of different cortical areas. Although the clinical phenotype is quite variable, the neuropathologic and biochemical characteristics of the lesions account for neurodegenerative processes unmistakably of Alzheimer nature. Neurology (R) 2010; 74: 798-806
C1 [Bruni, A. C.; Bernardi, L.; Colao, R.; Smirne, N.; Frangipane, F.; Curcio, S. A. M.; Mirabelli, M.; Clodomiro, A.; Di Lorenzo, R.; Maletta, R.; Anfossi, M.; Gallo, M.; Geracitano, S.; Tomaino, C.; Muraca, M. G.; Puccio, G.] ASP Catanzaro, Ctr Reg Neurogenet, I-88046 Lamezia Terme, CZ, Italy.
[Leotta, A.; Lio, S. G.] ASP Catanzaro, Dept Pathol, I-88046 Lamezia Terme, CZ, Italy.
[Rubino, E.; Pinessi, L.; Rainero, I.] Univ Turin, Neurol Dept Neurosci 2, I-10124 Turin, Italy.
[Terni, B.; Spillantini, M. G.] Brain Repair Ctr, Cambridge, England.
[Sorbi, S.] Univ Florence, Dept Neurol Sci, I-50121 Florence, Italy.
[Nee, L.] NIH, Bethesda, MD 20892 USA.
[Milan, G.; Postiglione, A.] Univ Naples Federico 2, Dementia Study Ctr, Dept Clin & Expt Dis, Naples, Italy.
[Milan, G.; Abbamondi, N.] ASL Napoli 1, Naples, Italy.
[Pappata, S.] CNR, Inst Biomaging & Biostruct, I-80125 Naples, Italy.
[Forloni, G.] Mario Negri Inst Pharmacol Res, Dept Neurosci, Milan, Italy.
[Hyslop, P. St. George; Rogaeva, E.] Univ Toronto, Dept Med, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada.
[Bugiani, O.; Giaccone, G.] Neurol Inst Carlo Besta, Dept Neuropathol, Neurol Inst, Milan, Italy.
[Foncin, J. F.] Lab Neurohistol EPHE, Brie Comte Robert, France.
RP Bruni, AC (reprint author), ASP Catanzaro, Ctr Reg Neurogenet, Viale A Perugini, I-88046 Lamezia Terme, CZ, Italy.
EM bruni@arn.it
RI Giaccone, Giorgio/J-6212-2012; Rubino, Elisa/K-3282-2016; ,
raffaele/K-4421-2016
OI Rubino, Elisa/0000-0002-7553-7553; sorbi, sandro/0000-0002-0380-6670; ,
raffaele/0000-0002-0758-1835
FU Novartis; Boehringer Ingelheim; Wyeth; Canadian Institutes of Health;
European Union; Medical Research Council UK; Alzheimer's Research Trust;
Parkinson's Diseases Society UK; Multiple Sclerosis Society UK
FX Dr. Bruni, Dr. Bernardi, Dr. Colao, Dr. Rubino, Dr. Smirne, Dr.
Frangipane, Dr. Terni, Dr. Curcio, Dr. Mirabelli, Dr. Clodomiro, Dr. Di
Lorenzo, Dr. Maletta, Dr. Anfossi, Dr. Gallo, Dr. Geracitano, Dr.
Tomaino, Dr. Muraca, Dr. Leotta, Dr. Lio, and Dr. Pinessi report no
disclosures. Dr. Rainero serves as an Associate Editor of the Journal of
Headache and Pain. Dr. Sorbi has received research support from
Novartis, Boehringer Ingelheim, and Wyeth. Dr. Nee, Dr. Milan, Dr.
Pappata, Dr. Postiglione, Dr. Abbamondi, and Dr. Forloni report no
disclosures. Dr. St. George Hyslop receives research support from the
Canadian Institutes of Health. Dr. Rogaeva and Dr. Bugiani report no
disclosures. Dr. Giaccone receives research support from the European
Union. Dr. Foncin reports no disclosures. Dr. Spillantini has
served/serves on scientific advisory boards for Fond de la Recherche and
the Alzheimer's Research Trust; has received travel expenses and/or
honoraria for lectures or educational activities not funded by industry;
serves on the editorial advisory board of Brain Pathology Synapse
Neurodegenerative Diseases; has filed a patent regarding artificial tau
filaments; and receives research support from the Medical Research
Council UK, the European Union, Alzheimer's Research Trust, Parkinson's
Diseases Society UK, and Multiple Sclerosis Society UK. Dr. Puccio
reports no disclosures.
NR 31
TC 19
Z9 19
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD MAR 9
PY 2010
VL 74
IS 10
BP 798
EP 806
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 565XT
UT WOS:000275331900004
PM 20164095
ER
PT J
AU Resnick, SM
Sojkova, J
Zhou, Y
An, Y
Ye, W
Holt, DP
Dannals, RF
Mathis, CA
Klunk, WE
Ferrucci, L
Kraut, MA
Wong, DF
AF Resnick, S. M.
Sojkova, J.
Zhou, Y.
An, Y.
Ye, W.
Holt, D. P.
Dannals, R. F.
Mathis, C. A.
Klunk, W. E.
Ferrucci, L.
Kraut, M. A.
Wong, D. F.
TI Longitudinal cognitive decline is associated with fibrillar amyloid-beta
measured by [C-11]PiB
SO NEUROLOGY
LA English
DT Article
ID PRECLINICAL ALZHEIMERS-DISEASE; REFERENCE TISSUE MODEL; NONDEMENTED
INDIVIDUALS; SPATIAL CONSTRAINT; OLDER-ADULTS; IMPAIRMENT; PET;
DEPOSITION; DEMENTIA; BRAIN
AB Objective: To investigate whether longitudinal declines in cognition are associated with higher fibrillar amyloid-beta (A beta) deposition in vivo in individuals without dementia.
Method: [C-11]PiB images were obtained to measure fibrillar A beta burden in 57 participants without dementia from the Baltimore Longitudinal Study of Aging. Participants (33 men, 24 women) had a mean (SD) age of 78.7 (6.2) years. Six participants (4 men, 2 women) had mild cognitive impairment defined as Clinical Dementia Rating = 0.5. To measure [C-11]PiB retention, distribution volume ratios (DVR) for 15 regions of interest were estimated by fitting a simplified reference tissue model to the measured time activity curves. Mixed effects regression was used to predict cognitive trajectories over time using data before and including time of PiB (mean follow-up 10.8 years), with mean cortical DVR, age at baseline, sex, and education as independent predictors. Voxel-based analysis identified local associations.
Results: [C-11]PiB retention was higher in older individuals. Greater declines over time in mental status and verbal learning and memory, but not visual memory, were associated significantly with higher PiB retention. Voxel-based analysis showed significant associations in frontal and lateral temporal regions.
Conclusions: Higher A beta deposition is associated with greater longitudinal decline in mental status and verbal memory in the preceding years. The differential association for verbal but not visual memory may reflect the greater reliance of verbal word list learning on prefrontal regions, which show early A beta deposition. Prospective imaging may help distinguish between individuals with evolving neuropathology who develop accelerated cognitive decline vs those with normal aging. Neurology (R) 2010; 74: 807-815
C1 [Resnick, S. M.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA.
[Sojkova, J.; Zhou, Y.; Ye, W.; Holt, D. P.; Dannals, R. F.; Kraut, M. A.; Wong, D. F.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
[Wong, D. F.] Johns Hopkins Univ, Dept Psychiat & Neurosci, Baltimore, MD USA.
[An, Y.] MedStar Res Inst, Hyattsville, MD USA.
[Mathis, C. A.] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA.
[Klunk, W. E.] Univ Pittsburgh, Dept Psychiat & Neurol, Pittsburgh, PA 15260 USA.
RP Resnick, SM (reprint author), NIA, Lab Personal & Cognit, NIH, 251 Bayview Blvd BRC Room 4B335, Baltimore, MD 21224 USA.
EM susan.resnick@nih.gov
OI Klunk, William/0000-0001-5512-0251
FU NIH/NIA; Elan Corporation; GE Healthcare; Bayer-Schering Pharma; IBA;
Takeda Pharmaceutical Company Limited; Neuroptix Corporation; NIH
[AG018402, NIA 5 R37 AG025516, NIA 1 P01 AG025204, NIA 1 U01 AG028526,
NIA 5 P50 AG005133, NIA 2 R01 AG018402, NIA 5 U01 AG024904-03S3, NIBIB 1
R01 AG026240, NIA 1 R01 AG031110, NIMH 2 R01 MH085328-05A1, NIMH 1 R01
MH077852-1, NIA 300-N01-AG40012, NIAAA R01AA12839]; US Department of
Energy; Dana Foundation; Elan Corporation/Janssen; Roche; AstraZeneca;
Veterans Administration; Avid Radiopharmaceuticals, Inc.;
AmgenBristol-Myers Squibb; Intra-Cellular Therapies, Inc.; Eli Lilly and
Company; Merck Serono; Orexigen Therapeutics, Inc.; Otsuka
Pharmaceutical Co., Ltd.; sanofi-aventis; Rett Syndrome Research
Foundation
FX GE Healthcare holds a license agreement with the University of
Pittsburgh based on the PiB technology described in this manuscript.
Drs. Klunk and Mathis are co-inventors of PiB and, as such, have a
financial interest in this license agreement. Dr. Resnick serves as
Action Editor for Brain and Cognition; and receives research support
from the NIH/NIA Intramural Research Program. Dr. Sojkova, Dr. Zhou, Mr.
An, Dr. Ye, Dr. Holt report no disclosures. Dr. Dannals serves as editor
of the Journal of Labelled Compounds and Radiopharmaceuticals. Dr.
Mathis serves on a scientific advisory board for Neuroptix Corporation;
has received funding for travel and speaker honoraria from Elan
Corporation, GE Healthcare, Bayer-Schering Pharma, IBA, and Takeda
Pharmaceutical Company Limited; serves on the editorial board of Nuclear
Medicine and Biology; may accrue revenue on over 20 active US and
international patents, 1996present re: amyloid imaging agents; serves as
a consultant for GE Healthcare, Elan Corporation, Wyeth, and Novartis;
estimates that 30% of his academic effort is spent on PiB imaging, which
might benefit the commercial license holder of the technology, GE
Healthcare, and the University of Pittsburgh as the licensor of the
technology; has received/ receives research support from GE Healthcare,
Neuroptix Corporation, the NIH (AG018402 [PI]), the US Department of
Energy, the Dana Foundation, and the Anonymous Foundation; holds stock
options in Neuroptix Corporation; and has received license fees and will
receive future royalties from GE Healthcare (amyloid imaging agents for
brain applications) and Neuroptix Corporation (amyloid imaging agents
for eye applications). Dr. Klunk serves on scientific advisory boards
for GE Healthcare, Neuroptix Corporation, Elan Corporation/ Janssen,
Roche, AstraZeneca; has received funding for travel from Elan
Corporation/Janssen, Roche, AstraZeneca, and for lectures or educational
activities not funded by industry; holds patents US 7,270,800 (plus
related), issued 2007: PiB PET Imaging and US 6,168,776 (plus related),
issued 2001: Chrysamine-G Derivatives for imaging and therapy; has
received honoraria from Cerebrio LLC; receives research support from
Neuroptix Corporation, the NIH (NIA 5 R37 AG025516 [PI], NIA 1 P01
AG025204 [PI], NIA 1 U01 AG028526 [PI], NIA 5 P50 AG005133 [Co-I], NIA 2
R01 AG018402 [Co-I], NIA 5 U01 AG024904-03S3 [Co-I], NIBIB 1 R01
AG026240 [Co-I], NIA 1 R01 AG031110 [Co-I]), and the Anonymous
Foundation; has received license fees and will receive future royalties
from GE Healthcare (PiB PET Imaging) and Neuroptix Corporation
(Chrysamine G Derivatives); and holds stock in Neuroptix Corporation.
Dr. Ferrucci serves as Editor-in-Chief of the Journals of Gerontology
Medical Sciences. Dr. Kraut serves on the editorial board of the Journal
of Magnetic Resonance Imaging; receives royalty from publication of
Neural Basis of Semantic Memory (Cambridge University Press, 2007);
receives research support from the NIH (NIMH 2 R01 MH085328-05A1 [Co-I],
NIMH 1 R01 MH077852-1 [Co-I], NIA 300-N01-AG40012 [Co-I]), and from the
Veterans Administration. Dr. Wong serves on editorial advisory boards
for Neuropsychopharmacology, the Journal of Cerebral Blood Flow and
Metabolism, and Molecular Imaging and Biology; and has received/
receives research support from Avid Radiopharmaceuticals, Inc., Amgen,
Bristol-Myers Squibb, Intra-Cellular Therapies, Inc., Eli Lilly and
Company, Merck Serono, Orexigen Therapeutics, Inc., Otsuka
Pharmaceutical Co., Ltd.; , Roche, sanofi-aventis, the NIH (NIAAA
R01AA12839 [PI], NIA K24, DA00412 [PI], NIMH R01 MH078175 [PI], NIAAA
R01 AA010158 [Co-I], NIDA R21DA020777 [Co-I], NIMH R33 MH079017 [Co-I],
NIMH R01 MH64823 [Co-I], NIMH U01 MH075378 [Co-I], NIDA R21 DA016182
[Co-I], NIDA R01DA022433 [PI on subcontract]), the DANA Foundation, and
the Rett Syndrome Research Foundation.
NR 17
TC 134
Z9 135
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 MAR 9
PY 2010
VL 74
IS 10
BP 807
EP 815
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 565XT
UT WOS:000275331900005
PM 20147655
ER
PT J
AU Davis, M
Auh, S
Riva, M
Richert, ND
Frank, JA
McFarland, HF
Bagnato, F
AF Davis, M.
Auh, S.
Riva, M.
Richert, N. D.
Frank, J. A.
McFarland, H. F.
Bagnato, F.
TI Ring and nodular multiple sclerosis lesions A retrospective natural
history study
SO NEUROLOGY
LA English
DT Article
ID MAGNETIZATION-TRANSFER MR; INTERFERON-BETA; GADOLINIUM ENHANCEMENT;
SPIN-ECHO; SERIAL; EVOLUTION; DEMYELINATION; BREAKDOWN; ATROPHY; MARKER
AB Background: In patients with multiple sclerosis (MS), contrast-enhancing lesions (CELs) on post-contrast MRI are considered markers of the inflammatory responses associated with blood-brain barrier breakdown. Based upon shape, CELs may be defined as nodular (nCEL) or ring (rCEL) lesions. Several short-term studies pointed towards the assumption that rCELs represent areas of a more aggressive inflammatory process.
Methods: In the present long-term (i.e., 2 years) retrospective natural history study, we used monthly imaging to follow rCEL and nCELs evolution in 16 patients with MS during the natural history. New CELs were identified monthly on month 4-9 MRIs, using month 1-3 MRIs to ensure that all CELs were not previously enhancing. Chronic black holes (cBHs) were counted monthly upon CEL disappearance up to the 24th MRI. Generalized estimating equation methods investigated within-patient differences between rCELs and nCELs in volume and likelihood to convert into cBHs. Kaplan-Meier survival curves estimated differences in the length of persistence between cBHs originating from nCELs and cBHs deriving from rCELs.
Results: Fifty-two new rCELs and 281 nCELs were identified. rCELs had larger mean (z = 5.06, p <= 0.0001) volumes than nCELs. The proportion of cBHs from rCELs was similar (z = 1.81, p = 0.0710) to the proportion of cBHs from nCELs. Likewise, the length of persistence of cBHs deriving from rCELs was similar (chi(2)(1) = 2.339, p = 0.1262) to the duration of cBHs from nCELs.
Conclusions: Our data suggest that worse radiologic characteristics associated with the acute phase of ring contrast-enhancing lesions and nodular contrast-enhancing lesions do not necessarily reflect a poorer lesion outcome over time. Neurology (R) 2010; 74: 851-856
C1 [Davis, M.; Riva, M.; Richert, N. D.; McFarland, H. F.; Bagnato, F.] NINDS, NIB, NIH, Bethesda, MD 20892 USA.
[Auh, S.] NINDS, Off Clin Director Biostat Unit, NIH, Bethesda, MD 20892 USA.
[Frank, J. A.] NIH, Lab Radiol & Imaging Sci Clin Canter, Bethesda, MD 20892 USA.
[Frank, J. A.] Natl Inst Biomed Imaging & Bioengn, Intramural Res Program, NIH, Bethesda, MD USA.
RP Bagnato, F (reprint author), NINDS, NIB, NIH, Bldg 10,Room 5C103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bagnatof@ninds.nih.gov
OI Riva, Marco/0000-0003-4643-6451
FU NINDS, NIH
FX Supported by the Intramural Research Program of the NINDS, NIH.
NR 27
TC 6
Z9 6
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 MAR 9
PY 2010
VL 74
IS 10
BP 851
EP 856
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 565XT
UT WOS:000275331900012
PM 20211910
ER
PT J
AU Di Pasquale, G
Kaludov, N
Agbandje-McKenna, M
Chiorini, JA
AF Di Pasquale, Giovanni
Kaludov, Nikola
Agbandje-McKenna, Mavis
Chiorini, John A.
TI BAAV Transcytosis Requires an Interaction with beta-1-4
Linked-Glucosamine and gp96
SO PLOS ONE
LA English
DT Article
ID BOVINE ADENOASSOCIATED VIRUS; GROWTH-FACTOR RECEPTOR;
BLOOD-BRAIN-BARRIER; ESCHERICHIA-COLI; TYPE-2 INFECTION;
EPITHELIAL-CELLS; INNER-EAR; PROTEIN; BINDING; CORECEPTOR
AB Cell surface carbohydrates play an important role in virus entry and intracellular trafficking. Bovine Adeno-Associated Virus (BAAV) uses plasma membrane gangliosides for transduction and infection. In addition, independent of the infectious pathway, BAAV also has the ability to pass through barrier epithelia and endothelia using a transcytosis pathway dependent upon the presence of cell surface carbohydrates. Thus, in order to better define the carbohydrate interactions that are necessary for BAAV infection or transcytosis, a glycan microarray composed of both natural and synthetic carbohydrates was probed with HA-tagged BAAV particles. This identified chitotriose, a trimer of beta-1-4-linked N-acetyl glucosamine, as having an interaction with BAAV. Competition experiments showed that the BAAV interaction with this carbohydrate is not necessary for infection but is instead important in the transcytosis pathway. The beta-1-4-linked N-acetyl glucosamine modification has been reported on gp96, a glycoprotein involved in the transcytosis of bacteria and toxins. Significantly, immunoprecipitation and competition experiments with an anti-gp96 antibody and a soluble form of gp96, respectively, showed this glycoprotein can also interact with BAAV to serve as a receptor for its transcytosis.
C1 [Di Pasquale, Giovanni; Kaludov, Nikola; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Agbandje-McKenna, Mavis] Univ Florida, Coll Med, Dept Biochem & Mol Biol, McKnight Brain Inst, Gainesville, FL 32610 USA.
RP Di Pasquale, G (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
EM jchiorini@dir.nidcr.nih.gov
FU National Institutes of Health [R01 GM082946]; NIH National Institute of
Dental and Craniofacial Research; National Institute of General Medical
Sciences [GM62116]
FX This work is also supported by National Institutes of Health R01
GM082946 to MAM and an NIH National Institute of Dental and Craniofacial
Research intramural grant to JAC. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript. The Consortium for Functional Glycomics
is funded by National Institute of General Medical Sciences grant
GM62116.
NR 40
TC 16
Z9 16
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 9
PY 2010
VL 5
IS 3
AR e9336
DI 10.1371/journal.pone.0009336
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 565XA
UT WOS:000275328300002
PM 20231878
ER
PT J
AU Ferrer-i-Cancho, R
Elvevag, B
AF Ferrer-i-Cancho, Ramon
Elvevag, Brita
TI Random Texts Do Not Exhibit the Real Zipf's Law-Like Rank Distribution
SO PLOS ONE
LA English
DT Article
ID INTERMITTENT SILENCE; POWER LAWS; LANGUAGE
AB Background: Zipf's law states that the relationship between the frequency of a word in a text and its rank ( the most frequent word has rank 1, the 2nd most frequent word has rank 2,...) is approximately linear when plotted on a double logarithmic scale. It has been argued that the law is not a relevant or useful property of language because simple random texts-constructed by concatenating random characters including blanks behaving as word delimiters-exhibit a Zipf's law-like word rank distribution.
Methodology/Principal Findings: In this article, we examine the flaws of such putative good fits of random texts. We demonstrate-by means of three different statistical tests-that ranks derived from random texts and ranks derived from real texts are statistically inconsistent with the parameters employed to argue for such a good fit, even when the parameters are inferred from the target real text. Our findings are valid for both the simplest random texts composed of equally likely characters as well as more elaborate and realistic versions where character probabilities are borrowed from a real text.
Conclusions/Significance: The good fit of random texts to real Zipf's law-like rank distributions has not yet been established. Therefore, we suggest that Zipf's law might in fact be a fundamental law in natural languages.
C1 [Ferrer-i-Cancho, Ramon] Univ Politecn Cataluna, Dept Llenguatges & Sistemes Informat, Barcelona, Catalonia, Spain.
[Elvevag, Brita] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
RP Ferrer-i-Cancho, R (reprint author), Univ Politecn Cataluna, Dept Llenguatges & Sistemes Informat, Barcelona, Catalonia, Spain.
EM rferrericancho@lsi.upc.edu
RI Ferrer-i-Cancho, Ramon/A-5424-2011
OI Ferrer-i-Cancho, Ramon/0000-0002-7820-923X
FU Spanish Ministry of Science [TIN2008-06582-C03-01]; National Institute
of Mental Health Intramural Research Program (NIMH-IRP)
FX This work was partially supported by the project Secuencias Simbolicas:
Analisis, Aprendizaje, Mineria y Evolucion, Barcelona (SESAAME-BAR)
(TIN2008-06582-C03-01) of the Spanish Ministry of Science and
Innovation, http://web.micinn.es/ (RFC); and the National Institute of
Mental Health Intramural Research Program (NIMH-IRP),
http://intramural.nimh.nih.gov/ (BE). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 34
TC 24
Z9 24
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 9
PY 2010
VL 5
IS 3
AR e9411
DI 10.1371/journal.pone.0009411
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 565XA
UT WOS:000275328300004
PM 20231884
ER
PT J
AU Kim, JH
Park, JM
Yea, K
Kim, HW
Suh, PG
Ryu, SH
AF Kim, Jong Hyun
Park, Ji-Man
Yea, Kyungmoo
Kim, Hyun Wook
Suh, Pann-Ghill
Ryu, Sung Ho
TI Phospholipase D1 Mediates AMP-Activated Protein Kinase Signaling for
Glucose Uptake
SO PLOS ONE
LA English
DT Article
ID ADP-RIBOSYLATION FACTOR; RICH TYROSINE KINASE-2; MOUSE SKELETAL-MUSCLE;
PLASMA-MEMBRANE; TRANSPORTER TRANSLOCATION; AS160 PHOSPHORYLATION;
PHOSPHATIDIC-ACID; REGULATED KINASE; MAMMALIAN-CELLS; INSULIN
AB Background: Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK) is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glucose uptake have yet to be elucidated.
Methodology/Principal Findings: Here, we found that AMPK-induced phospholipase D1 (PLD1) activation is required for (14)C-glucose uptake in muscle cells under glucose deprivation conditions. PLD1 activity rather than PLD2 activity is significantly enhanced by glucose deprivation. AMPK-wild type (WT) stimulates PLD activity, while AMPK-dominant negative (DN) inhibits it. AMPK regulates PLD1 activity through phosphorylation of the Ser-505 and this phosphorylation is increased by the presence of AMP. Furthermore, PLD1-S505Q, a phosphorylation-deficient mutant, shows no changes in activity in response to glucose deprivation and does not show a significant increase in (14)C-glucose uptake when compared to PLD1-WT. Taken together, these results suggest that phosphorylation of PLD1 is important for the regulation of (14)C-glucose uptake. In addition, extracellular signal-regulated kinase (ERK) is stimulated by AMPK-induced PLD1 activation through the formation of phosphatidic acid (PA), which is a product of PLD. An ERK pharmacological inhibitor, PD98059, and the PLD inhibitor, 1-BtOH, both attenuate (14)C-glucose uptake in muscle cells. Finally, the extracellular stresses caused by glucose deprivation or aminoimidazole carboxamide ribonucleotide (AICAR; AMPK activator) regulate (14)C-glucose uptake and cell surface glucose transport (GLUT) 4 through ERK stimulation by AMPK-mediated PLD1 activation.
Conclusions/Significance: These results suggest that AMPK-mediated PLD1 activation is required for (14)C-glucose uptake through ERK stimulation. We propose that the AMPK-mediated PLD1 pathway may provide crucial clues to understanding the mechanisms involved in glucose uptake.
C1 [Kim, Jong Hyun; Park, Ji-Man; Yea, Kyungmoo; Kim, Hyun Wook; Suh, Pann-Ghill; Ryu, Sung Ho] Pohang Univ Sci & Technol, Div Mol & Life Sci, Pohang, Kyungbuk, South Korea.
[Kim, Jong Hyun] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
RP Kim, JH (reprint author), Pohang Univ Sci & Technol, Div Mol & Life Sci, Pohang, Kyungbuk, South Korea.
EM sungho@postech.ac.kr
RI Suh, Pann-Ghill/F-3610-2010
FU Ministry of Science and Technology in the Republic of Korea; National
Institutes of Health (NIH) [GM 68849]
FX This work was supported by a grant from the 21st Frontier Proteomics
Research of the Ministry of Science and Technology in the Republic of
Korea and National Institutes of Health (NIH) grant GM 68849 (W. C.).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 45
TC 10
Z9 10
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 9
PY 2010
VL 5
IS 3
AR e9600
DI 10.1371/journal.pone.0009600
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 565XA
UT WOS:000275328300016
PM 20231899
ER
PT J
AU Shea, PR
Virtaneva, K
Kupko, JJ
Porcella, SF
Barry, WT
Wright, FA
Kobayashi, SD
Carmody, A
Ireland, RM
Sturdevant, DE
Ricklefs, SM
Babar, I
Johnson, CA
Graham, MR
Gardner, DJ
Bailey, JR
Parnell, MJ
DeLeo, FR
Musser, JM
AF Shea, Patrick R.
Virtaneva, Kimmo
Kupko, John J., III
Porcella, Stephen F.
Barry, William T.
Wright, Fred A.
Kobayashi, Scott D.
Carmody, Aaron
Ireland, Robin M.
Sturdevant, Daniel E.
Ricklefs, Stacy M.
Babar, Imran
Johnson, Claire A.
Graham, Morag R.
Gardner, Donald J.
Bailey, John R.
Parnell, Michael J.
DeLeo, Frank R.
Musser, James M.
TI Interactome analysis of longitudinal pharyngeal infection of cynomolgus
macaques by group A Streptococcus
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE epithelial growth factor receptor; host pathogen; microarray;
Streptococcus pyogenes; transcriptome
ID TRANSFER-RNA MODIFICATION; GROWTH-FACTOR RECEPTOR; T-CELL-ACTIVATION;
GENE-EXPRESSION; ISOPRENOID BIOSYNTHESIS; PATHOGEN INTERACTIONS;
ESCHERICHIA-COLI; HUMAN-SALIVA; PROTEIN; TRANSCRIPTOME
AB Relatively little is understood about the dynamics of global host pathogen transcriptome changes that occur during bacterial infection of mucosal surfaces. To test the hypothesis that group A Streptococcus (GAS) infection of the oropharynx provokes a distinct host transcriptome response, we performed genome-wide transcriptome analysis using a nonhuman primate model of experimental pharyngitis. We also identified host and pathogen biological processes and individual host and pathogen gene pairs with correlated patterns of expression, suggesting interaction. For this study, 509 host genes and seven biological pathways were differentially expressed throughout the entire 32-day infection cycle. GAS infection produced an initial widespread significant decrease in expression of many host genes, including those involved in cytokine production, vesicle formation, metabolism, and signal transduction. This repression lasted until day 4, at which time a large increase in expression of host genes was observed, including those involved in protein translation, antigen presentation, and GTP-mediated signaling. The interactome analysis identified 73 host and pathogen gene pairs with correlated expression levels. We discovered significant correlations between transcripts of GAS genes involved in hyaluronic capsule production and host endocytic vesicle formation, GAS GTPases and host fibrinolytic genes, and GAS response to interaction with neutrophils. We also identified a strong signal, suggesting interaction between host gamma delta T cells and genes in the GAS mevalonic acid synthesis pathway responsible for production of isopentenyl-pyrophosphate, a short-chain phospholipid that stimulates these T cells. Taken together, our results are unique in providing a comprehensive understanding of the host-pathogen interactome during mucosal infection by a bacterial pathogen.
C1 [Shea, Patrick R.; Musser, James M.] Methodist Hosp, Res Inst, Dept Pathol, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77030 USA.
[Virtaneva, Kimmo; Kupko, John J., III; Porcella, Stephen F.; Carmody, Aaron; Sturdevant, Daniel E.; Ricklefs, Stacy M.; Babar, Imran; Johnson, Claire A.] NIAID, Genom Unit, Res Technol Sect, NIH, Hamilton, MT 59840 USA.
[Kobayashi, Scott D.; Ireland, Robin M.; Graham, Morag R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA.
[Gardner, Donald J.; Bailey, John R.; Parnell, Michael J.] NIAID, Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Barry, William T.; Wright, Fred A.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
RP Musser, JM (reprint author), Methodist Hosp, Res Inst, Dept Pathol, Ctr Mol & Translat Human Infect Dis Res, 6535 Fannin, Houston, TX 77030 USA.
EM jmmusser@tmhs.org
OI DeLeo, Frank/0000-0003-3150-2516; Shea, Patrick/0000-0001-6804-5131
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX Quantitative PCR (TaqMan) validation and correlation analysis were
performed by Hannah Wilder and Craig Martens. We thank K. Stockbauer for
assistance with figures. This work was supported in part by the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 37
TC 15
Z9 15
U1 0
U2 3
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 MAR 9
PY 2010
VL 107
IS 10
BP 4693
EP 4698
DI 10.1073/pnas.0906384107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566KF
UT WOS:000275368400038
PM 20179180
ER
PT J
AU Biswal, BB
Mennes, M
Zuo, XN
Gohel, S
Kelly, C
Smith, SM
Beckmann, CF
Adelstein, JS
Buckner, RL
Colcombe, S
Dogonowski, AM
Ernst, M
Fair, D
Hampson, M
Hoptman, MJ
Hyde, JS
Kiviniemi, VJ
Kotter, R
Li, SJ
Lin, CP
Lowe, MJ
Mackay, C
Madden, DJ
Madsen, KH
Margulies, DS
Mayberg, HS
McMahon, K
Monk, CS
Mostofsky, SH
Nagel, BJ
Pekar, JJ
Peltier, SJ
Petersen, SE
Riedl, V
Rombouts, SARB
Rypma, B
Schlaggar, BL
Schmidt, S
Seidler, RD
Siegle, GJ
Sorg, C
Teng, GJ
Veijola, J
Villringer, A
Walter, M
Wang, LH
Weng, XC
Whitfield-Gabrieli, S
Williamson, P
Windischberger, C
Zang, YF
Zhang, HY
Castellanos, FX
Milham, MP
AF Biswal, Bharat B.
Mennes, Maarten
Zuo, Xi-Nian
Gohel, Suril
Kelly, Clare
Smith, Steve M.
Beckmann, Christian F.
Adelstein, Jonathan S.
Buckner, Randy L.
Colcombe, Stan
Dogonowski, Anne-Marie
Ernst, Monique
Fair, Damien
Hampson, Michelle
Hoptman, Matthew J.
Hyde, James S.
Kiviniemi, Vesa J.
Kotter, Rolf
Li, Shi-Jiang
Lin, Ching-Po
Lowe, Mark J.
Mackay, Clare
Madden, David J.
Madsen, Kristoffer H.
Margulies, Daniel S.
Mayberg, Helen S.
McMahon, Katie
Monk, Christopher S.
Mostofsky, Stewart H.
Nagel, Bonnie J.
Pekar, James J.
Peltier, Scott J.
Petersen, Steven E.
Riedl, Valentin
Rombouts, Serge A. R. B.
Rypma, Bart
Schlaggar, Bradley L.
Schmidt, Sein
Seidler, Rachael D.
Siegle, Greg J.
Sorg, Christian
Teng, Gao-Jun
Veijola, Juha
Villringer, Arno
Walter, Martin
Wang, Lihong
Weng, Xu-Chu
Whitfield-Gabrieli, Susan
Williamson, Peter
Windischberger, Christian
Zang, Yu-Feng
Zhang, Hong-Ying
Castellanos, F. Xavier
Milham, Michael P.
TI Toward discovery science of human brain function
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE database; neuroimaging; open access; reproducibility; resting state
ID RESTING-STATE NETWORKS; BASE-LINE; SEXUAL-DIMORPHISM; CONNECTIVITY; MRI;
ARCHITECTURE; CORTEX; FMRI; FLUCTUATIONS; ACTIVATION
AB Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (< 0.1 Hz)fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.
C1 [Mennes, Maarten; Zuo, Xi-Nian; Kelly, Clare; Adelstein, Jonathan S.; Castellanos, F. Xavier; Milham, Michael P.] NYU, Phyllis Green & Randolph Cowen Inst Pediat Neuros, Ctr Child Study, Langone Med Ctr, New York, NY 10016 USA.
[Biswal, Bharat B.; Gohel, Suril] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Radiol, Newark, NJ 07103 USA.
[Smith, Steve M.; Beckmann, Christian F.; Mackay, Clare] Univ Oxford, FMRIB Ctr, Oxford OX3 9DU, England.
[Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
[Colcombe, Stan] Univ Wales, Sch Psychol, Bangor, Gwynedd, Wales.
[Dogonowski, Anne-Marie; Madsen, Kristoffer H.] Univ Copenhagen, Hvidovre Hosp, Danish Res Ctr Magnet Resonance, DK-2650 Hvidovre, Denmark.
[Ernst, Monique] NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Fair, Damien] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA.
[Hampson, Michelle] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06511 USA.
[Hoptman, Matthew J.; Castellanos, F. Xavier] Nathan S Kline Inst Psychiat Res, Div Clin Res, Orangeburg, NY 10962 USA.
[Hyde, James S.; Li, Shi-Jiang] Med Coll Wisconsin, Biophys Res Inst, Milwaukee, WI 53226 USA.
[Kiviniemi, Vesa J.] Oulu Univ Hosp, Dept Diagnost Radiol, Oulu, Finland.
[Kotter, Rolf] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Ctr Neurosci, NL-6500 HB Nijmegen, Netherlands.
[Lowe, Mark J.] Cleveland Clin, Imaging Inst, Cleveland, OH 44195 USA.
[Madden, David J.; Wang, Lihong] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC 27710 USA.
[Margulies, Daniel S.] Max Planck Inst Human Cognit & Brain Sci, Dept Cognit Neurol, D-04103 Leipzig, Germany.
[Mayberg, Helen S.] Emory Univ, Sch Med, Dept Psychiat, Atlanta, GA 30322 USA.
[Mayberg, Helen S.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
[McMahon, Katie] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia.
[Monk, Christopher S.; Seidler, Rachael D.] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA.
[Mostofsky, Stewart H.] Kennedy Krieger Inst, Lab Neurocognit & Imaging Res, Baltimore, MD 21205 USA.
[Nagel, Bonnie J.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA.
[Pekar, James J.] Kennedy Krieger Inst, FM Kirby Res Ctr Funct Brain Imaging, Baltimore, MD 21205 USA.
[Peltier, Scott J.] Univ Michigan, Funct MRI Lab, Ann Arbor, MI 48109 USA.
[Petersen, Steven E.] Washington Univ, Sch Med, McDonnell Ctr Higher Brain Funct, St Louis, MO 63110 USA.
[Riedl, Valentin] Tech Univ Munich, Klinikum Rechts Isar, Dept Neurol, D-81675 Munich, Germany.
[Riedl, Valentin] Tech Univ Munich, Klinikum Rechts Isar, Dept Neuroradiol, D-81675 Munich, Germany.
[Rombouts, Serge A. R. B.] Leiden Univ, Inst Psychol, Med Ctr, Leiden, Netherlands.
[Rombouts, Serge A. R. B.] Leiden Univ, Dept Radiol, Med Ctr, Leiden, Netherlands.
[Rypma, Bart] Univ Texas Dallas, Ctr Brain Hlth, Richardson, TX 75080 USA.
[Rypma, Bart] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75080 USA.
[Schlaggar, Bradley L.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Schmidt, Sein; Villringer, Arno] Charite, Dept Neurol, D-10117 Berlin, Germany.
[Seidler, Rachael D.] Univ Michigan, Sch Kinesiol, Ann Arbor, MI 48109 USA.
[Siegle, Greg J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA.
[Sorg, Christian] Tech Univ Munich, Klinikum Rechts Isar, Dept Psychiat, D-81675 Munich, Germany.
[Teng, Gao-Jun; Zhang, Hong-Ying] Southeast Univ, Jiangsu Key Lab Mol & Funct Imaging, Dept Radiol, Zhong Da Hosp, Nanjing 210009, Peoples R China.
[Veijola, Juha] Univ Oulu, Dept Psychiat, Inst Clin Med, Oulu 90014, Finland.
[Veijola, Juha] Univ Oulu, Dept Publ Hlth Sci, Inst Hlth Sci, Oulu 90014, Finland.
[Villringer, Arno] Berlin NeuroImaging Ctr, D-10099 Berlin, Germany.
[Walter, Martin] Otto VonGuericke Univ Magdegurg, Dept Psychiat, D-39106 Magdeburg, Germany.
[Weng, Xu-Chu] Chinese Acad Sci, Lab Higher Brain Funct, Inst Psychol, Beijing 100864, Peoples R China.
[Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Williamson, Peter] Univ Western Ontario, Dept Psychiat, London, ON N6A 3H8, Canada.
[Windischberger, Christian] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria.
[Zang, Yu-Feng] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China.
RP Milham, MP (reprint author), NYU, Phyllis Green & Randolph Cowen Inst Pediat Neuros, Ctr Child Study, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA.
EM michael.milham@nyumc.org
RI Riedl, Valentin/G-5466-2013; Margulies, Daniel/L-4719-2016; Hampson,
Michelle/K-6732-2015; Li, Chong/F-4265-2015; Kelly, Clare/H-4629-2016;
Zuo, Xi-Nian/A-7273-2009; Williamson, Peter/F-7462-2010; Mennes,
Maarten/C-9924-2011; Beckmann, Christian/E-6374-2012; Wang,
Lihong/D-8960-2011; McMahon, Katie/C-6440-2009; ZANG,
Yu-Feng/J-1558-2012; Monk, Christopher/J-1805-2014; Milham,
Michael/K-9501-2014; Madsen, Kristoffer Hougaard/M-9547-2014
OI Castellanos, Francisco/0000-0001-9192-9437; Riedl,
Valentin/0000-0002-2861-8449; Margulies, Daniel/0000-0002-8880-9204;
Mackay, Clare/0000-0001-6111-8318; Zuo, Xi-Nian/0000-0001-9110-585X;
Hoptman, Matthew/0000-0003-4485-6102; Windischberger,
Christian/0000-0002-9944-0190; Smith, Stephen/0000-0001-8166-069X;
Hampson, Michelle/0000-0003-3173-4210; Kelly, Clare/0000-0001-8253-357X;
Mennes, Maarten/0000-0002-7279-3439; McMahon, Katie/0000-0002-6357-615X;
ZANG, Yu-Feng/0000-0003-1833-8010; Madsen, Kristoffer
Hougaard/0000-0001-8606-7641
FU National Institutes of Mental Health [R01MH083246, R01MH081218];
National Institute on Drug Abuse [R03DA024775, R01DA016979]; Autism
Speaks; National Institute of Neurological Disorders and Stroke
[R01NS049176]; Howard Hughes Medical Institute; National Institutes of
Health's Blueprint for Neurosciences Research [N02-EB-6-4281]
FX We thank David Kennedy and www.nitrc.org for supporting the 1000
Functional Connectomes Project data release, Avi Snyder for providing
helpful insights and advice concerning project goals, and Cameron
Craddock for helpful advice on this study. Financial support for the
1000 Functional Connectomes project was provided by grants from the
National Institutes of Mental Health (R01MH083246 and R01MH081218 to F.
X. C. and M. P. M.), National Institute on Drug Abuse (R03DA024775, to
C. K.; R01DA016979, to F. X. C.), Autism Speaks, National Institute of
Neurological Disorders and Stroke (R01NS049176, to B. B.), and the
Howard Hughes Medical Institute (to J.S.A. and R. L. B.), as well as
gifts to the NYU Child Study Center from the Stavros Niarchos
Foundation, Leon Levy Foundation, Joseph P. Healy, Linda and Richard
Schaps, and Jill and Bob Smith and an endowment provided by Phyllis
Green and Randolph Cowen. NITRC is funded by the National Institutes of
Health's Blueprint for Neurosciences Research
(neuro-scienceblueprint.nih.gov) (Contract N02-EB-6-4281, to TCG, Inc.).
NR 50
TC 1025
Z9 1045
U1 24
U2 218
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 MAR 9
PY 2010
VL 107
IS 10
BP 4734
EP 4739
DI 10.1073/pnas.0911855107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 566KF
UT WOS:000275368400045
PM 20176931
ER
PT J
AU Givens, JL
Tjia, J
Zhou, C
Emanuel, E
Ash, AS
AF Givens, Jane L.
Tjia, Jennifer
Zhou, Chao
Emanuel, Ezekiel
Ash, Arlene S.
TI Racial and Ethnic Differences in Hospice Use Among Patients With Heart
Failure
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID OF-LIFE CARE; BLACK-AND-WHITE; AFRICAN-AMERICANS; OLDER-ADULTS;
MEDICARE; ACCESS; CANCER; DIAGNOSES; BARRIERS; DEATH
AB Background: Heart failure is the leading noncancer diagnosis for patients in hospice care and the leading cause of hospitalization among Medicare beneficiaries. Racial and ethnic differences in hospice patients are well documented for patients with cancer but poorly described for those with heart failure.
Methods: On the basis of a national sample of 98 258 Medicare beneficiaries 66 years and older on January 1, 2001, with a diagnosis of heart failure who had at least 1 physician or hospital encounter and who were not enrolled in hospice care between January 1 and December 31, 2000, we determined the effect of race and ethnicity on hospice entry for patients with heart failure in 2001 after adjusting for sociodemographic, clinical, and geographic factors.
Results: In unadjusted analysis, blacks ( odds ratio [OR], 0.52) and Hispanics (0.43) used hospice care for heart failure less than whites. Racial and ethnic differences in patients who received hospice care for heart failure persisted after adjusting for markers of income, urbanicity, severity of illness, local density of hospice use, and medical comorbidity ( adjusted OR for blacks, 0.59; 95% confidence interval, 0.47-0.73; and adjusted OR for Hispanics, 0.49; 95% confidence interval, 0.37-0.66; compared with whites). Advanced age, greater comorbidity, emergency department visits, hospitalizations, and greater local density of hospice use were also associated with hospice use.
Conclusions: In a national sample of Medicare beneficiaries with heart failure, blacks and Hispanics used hospice care for heart failure less than whites after adjustment for individual and market factors. To understand the mechanisms underlying these findings, further examination of patient preferences and physician referral behavior is needed.
C1 [Givens, Jane L.] Beth Israel Deaconess Med Ctr, Hebrew SeniorLife Inst Aging Res, Boston, MA 02131 USA.
[Givens, Jane L.] Beth Israel Deaconess Med Ctr, Div Gerontol, Dept Med, Boston, MA 02131 USA.
[Zhou, Chao; Ash, Arlene S.] Boston Univ, Sch Med, Hlth Care Res Unit, Boston, MA 02118 USA.
[Tjia, Jennifer] Univ Massachusetts, Sch Med, Div Geriatr Med, Worcester, MA USA.
[Emanuel, Ezekiel] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Givens, JL (reprint author), Beth Israel Deaconess Med Ctr, Hebrew SeniorLife Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA.
EM janegivens@hrca.harvard.edu
RI Max, Mad/E-5238-2010
OI Max, Mad/0000-0001-6966-6829
FU Department of Bioethics of the Clinical Center of the National
Institutes of Health; National Institute on Aging Career Development
[K08AG021527]
FX This study was supported by contracts with the Department of Bioethics
of the Clinical Center of the National Institutes of Health. Dr Tjia is
supported by National Institute on Aging Career Development Award
K08AG021527.
NR 41
TC 34
Z9 34
U1 2
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD MAR 8
PY 2010
VL 170
IS 5
BP 427
EP 432
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 565PU
UT WOS:000275307300006
PM 20212178
ER
PT J
AU Beauvais, G
Jayanthi, S
McCoy, MT
Ladenheim, B
Cadet, JL
AF Beauvais, Genevieve
Jayanthi, Subramaniam
McCoy, Michael T.
Ladenheim, Bruce
Cadet, Jean Lud
TI Differential effects of methamphetamine and SCH23390 on the expression
of members of IEG families of transcription factors in the rat striatum
SO BRAIN RESEARCH
LA English
DT Article
DE IEG; RT-PCR; SCH23390; Signal transduction
ID INDUCED NEURONAL APOPTOSIS; IMMEDIATE-EARLY GENES; EARLY REPRESSOR ICER;
C-FOS; INDUCED NEUROTOXICITY; PROTEIN-KINASE; CELL-DEATH; REGULATED
TRANSCRIPTION; SYNAPTIC PLASTICITY; TERMINAL KINASE
AB Methamphetamine (METH) is a psychostimulant that can cause long-lasting neurodegenerative effects in humans and animals. These toxic effects appear to occur, in part, via activation of dopamine (DA) D1 receptors. This paper assessed the possibility that the DA D1 receptor antagonist, SCH23390, might inhibit METH-induced changes in the expression of several members of immediate early genes (IEGs) which are known to control more delayed expression of other genes. We found that injections of METH (4 x 10 mg/kg, given at 2 h intervals) caused significant increases in c-fos and fra-2 expression which lasted from 30 min to 4 h. Pre-treatment with SCH23390, given 30 min before each METH injection, completely blocked METH-induced expression of c-fos, but only partially inhibited fra-2 mRNA expression. These results were confirmed by Western blot analysis which showed METH-induced changes in c-Fos protein expression that were blocked by pretreatment with SCH23390. There were also delayed METH-induced DA D1 receptor- dependent effects on fosB mRNA expression. Even though fra-1 expression was not affected by pretreatment with METH alone, the repeated injections of SCH23390 caused substantial decreases in fra-1 mRNA expression in both the presence and absence of METH. The repeated injections of METH caused no changes in the mRNAs for c-jun, junB or junD. However, there were significant increases in the phosphorylation of c-Jun protein (ser63). Phosphorylation of c-Jun occurred in a delayed fashion (16 and 24 h after the last METH injections) and was attenuated by SCH23390 pretreatment. Interestingly, SCH23390 given alone caused significant decreases in phospho-c-Jun at all time-points. The METH injections also caused delayed induction in the expression of members of the Egr family of transcription factors in a DA D1 receptor- dependent fashion. Repeated injections of SCH23390 caused substantial suppression of basal striatal egr-1 and egr-2 mRNA expression but not of that of egr-3. Both crem and arc mRNA levels were induced by METH in a SCH23390-sensitive fashion. Moreover, multiple injections of SCH23390 given alone caused marked inhibition of basal arc expression. These results show that multiple injections of METH can differentially affect the expression of several IEGs, some of which occurred in a DA D1 receptor dependent fashion. The SCH23390-mediated suppression of basal fra-1, egr-1, and egr-2 mRNA levels suggests that their basal expression in the striatum might be dependent on tonic stimulation of the DA D1 receptor. Published by Elsevier B.V.
C1 [Beauvais, Genevieve; Jayanthi, Subramaniam; McCoy, Michael T.; Ladenheim, Bruce; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
[Beauvais, Genevieve] Univ Paris 05, F-75006 Paris, France.
RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Res Branch, NIH, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM jcadet@intra.nida.nih.gov
FU Intramural NIH HHS [ZIA DA000551-01]
NR 43
TC 18
Z9 20
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD MAR 8
PY 2010
VL 1318
BP 1
EP 10
DI 10.1016/j.brainres.2009.12.083
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 565RS
UT WOS:000275312600001
PM 20059987
ER
PT J
AU Mattson, MP
AF Mattson, Mark P.
TI The impact of dietary energy intake on cognitive aging
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Review
DE BDNF; diabetes; GLP-1; hippocampus; learning and memory; neurogenesis;
synaptic plasticity
AB Rodents that are insulin resistant and obese as the result of genetic factors, overeating and/or a sedentary lifestyle, exhibit cognitive deficits that worsen with advancing age compared to their more svelte counterparts. Data from epidemiological and clinical studies suggest similar adverse effects of excessive dietary energy intake and insulin resistance on cognition in humans. Our findings from studies of animal models suggest that dietary energy restriction can enhance neural plasticity and reduce the vulnerability of the brain to age-related dysfunction and disease. Dietary energy restriction may exert beneficial effects on the brain by engaging adaptive cellular stress response pathways resulting in the up-regulation of genes that encode proteins that promote neural plasticity and cell survival (e.g., neurotrophic factors, protein chaperones and redox enzymes). Two energy state-sensitive factors that are proving particularly important in regulating energy balance and improving/preserving cognitive function are brain-derived neurotrophic factor and glucagon-like peptide 1. Alternate day calorie restriction, novel insulin-sensitizing and neuroprotective agents, and drugs that activate adaptive stress response pathways, are examples of approaches for preserving cognitive function that show promise in preclinical studies.
C1 NIA, Biomed Res Ctr, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Mattson, MP (reprint author), NIA, Biomed Res Ctr, Neurosci Lab, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
FU Intramural Research Program of the National Institute on Aging
FX This work was supported by the Intramural Research Program of the
National Institute on Aging.
NR 124
TC 30
Z9 31
U1 2
U2 8
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1663-4365
J9 FRONT AGING NEUROSCI
JI Front. Aging Neurosci.
PD MAR 8
PY 2010
VL 2
AR 5
DI 10.3389/neuro.24.005.2010
PG 12
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA V26PH
UT WOS:000208557000001
PM 20552045
ER
PT J
AU Mukhopadhyay, D
Arnaoutov, A
Dasso, M
AF Mukhopadhyay, Debaditya
Arnaoutov, Alexei
Dasso, Mary
TI The SUMO protease SENP6 is essential for inner kinetochore assembly
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID MICROTUBULE INTERFACE; LIVING CELLS; CENP-A; COMPLEX; PATHWAY; MITOSIS;
IDENTIFICATION; CENTROMERES; PROGRESSION; CHECKPOINT
AB We have analyzed the mitotic function of SENP6, a small ubiquitin-like modifier (SUMO) protease that disassembles conjugated SUMO2/3 chains. Cells lacking SENP6 showed defects in spindle assembly and metaphase chromosome congression. Analysis of kinetochore composition in these cells revealed that a subset of proteins became undetectable on inner kinetochores after SENP6 depletion, particularly the CENP-H/I/K complex, whereas other changes in kinetochore composition mimicked defects previously reported to result from CENP-H/I/K depletion. We further found that CENP-I is degraded through the action of RNF4, a ubiquitin ligase which targets polysumoylated proteins for proteasomal degradation, and that SENP6 stabilizes CENP-I by antagonizing RNF4. Together, these findings reveal a novel mechanism whereby the finely balanced activities of SENP6 and RNF4 control vertebrate kinetochore assembly through SUMO-targeted destabilization of inner plate components.
C1 [Mukhopadhyay, Debaditya; Arnaoutov, Alexei; Dasso, Mary] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Dasso, M (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
EM mdasso@helix.nih.gov
OI Dasso, Mary/0000-0002-5410-1371
FU National Institute of Child Health and Human Development (NICHD) [Z01
HD001902-14, Z01 HD008740-07]
FX This work was supported by National Institute of Child Health and Human
Development intramural funds (NICHD project #Z01 HD001902-14 and # Z01
HD008740-07).
NR 39
TC 53
Z9 56
U1 0
U2 5
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 MAR 8
PY 2010
VL 188
IS 5
BP 681
EP 692
DI 10.1083/jcb.200909008
PG 12
WC Cell Biology
SC Cell Biology
GA 565XS
UT WOS:000275331800008
PM 20212317
ER
PT J
AU Kedar, VP
Darby, MK
Williams, JG
Blackshear, PJ
AF Kedar, Vishram P.
Darby, Martyn K.
Williams, Jason G.
Blackshear, Perry J.
TI Phosphorylation of Human Tristetraprolin in Response to Its Interaction
with the CbI Interacting Protein CIN85
SO PLOS ONE
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; MESSENGER-RNA DECAY; ZINC-FINGER PROTEINS;
GROWTH-FACTOR RECEPTORS; MAP KINASE PATHWAY; AU-RICH ELEMENTS;
DOWN-REGULATION; TRANSCRIPTION FACTOR; DEFICIENCY SYNDROME; SIGNALING
PATHWAY
AB Background: Tristetraprolin (TTP) is the prototype member of a family of CCCH tandem zinc finger proteins and is considered to be an anti-inflammatory protein in mammals. TTP plays a critical role in the decay of tumor necrosis factor alpha (TNF) mRNA, among others, by binding AU-rich RNA elements in the 3'-untranslated regions of this transcript and promoting its deadenylation and degradation.
Methodology/Principal Findings: We used yeast two-hybrid analysis to identify potential protein binding partners for human TTP (hTTP). Various regions of hTTP recovered 31 proteins that fell into 12 categories based on sequence similarities. Among these, the interactions between hTTP and CIN85, cytoplasmic poly (A) binding protein (PABP), nucleolin and heat shock protein 70 were confirmed by co-immunoprecipitation experiments. CIN85 and hTTP co-localized in the cytoplasm of cells as determined by confocal microscopy. CIN85 contains three SH3 domains that specifically bind a unique proline-arginine motif (PXXXPR) found in several CIN85 effectors. We found that the SH3 domains of CIN85 bound to a PXXXPR motif located near the C-terminus of hTTP. Co-expression of CIN85 with hTTP resulted in the increased phosphorylation of hTTP at serine residues in positions 66 and 93, possibly due in part to the demonstrated association of mitogen-activated protein kinase kinase kinase 4 (MEKK4) to both proteins. The presence of CIN85 did not appear to alter hTTP's binding to RNA probes or its stimulated breakdown of TNF mRNA.
Conclusions/Significance: These studies describe interactions between hTTP and nucleolin, cytoplasmic PABP, heat shock protein 70 and CIN85; these interactions were initially discovered by two-hybrid analysis, and confirmed by coimmunoprecipitation. We found that CIN85 binding to a C-terminal motif within hTTP led to the increased phosphorylation of hTTP, possibly through enhanced association with MEKK4. The functional consequences to each of the members of this putative complex remain to be determined.
C1 [Kedar, Vishram P.; Darby, Martyn K.; Blackshear, Perry J.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC USA.
[Williams, Jason G.] Natl Inst Environm Hlth Sci, Prot Microcharacterizat Core Facil, Res Triangle Pk, NC USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
RP Kedar, VP (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC USA.
EM black009@niehs.nih.gov
FU NIH; NIEHS
FX This project was entirely supported by the Intramural Research Program
of the NIH, NIEHS. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 78
TC 17
Z9 17
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 MAR 8
PY 2010
VL 5
IS 3
BP A213
EP A227
AR e9588
DI 10.1371/journal.pone.0009588
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 565WZ
UT WOS:000275328200020
PM 20221403
ER
PT J
AU Quaia, C
Ying, HS
Optican, LM
AF Quaia, Christian
Ying, Howard S.
Optican, Lance M.
TI The Viscoelastic Properties of Passive Eye Muscle in Primates. III:
Force Elicited by Natural Elongations
SO PLOS ONE
LA English
DT Article
ID MODEL; TISSUE
AB We have recently shown that in monkey passive extraocular muscles the force induced by a stretch does not depend on the entire length history, but to a great extent is only a function of the last elongation applied. This led us to conclude that Fung's quasi-linear viscoelastic (QLV) model, and more general nonlinear models based on a single convolution integral, cannot faithfully mimic passive eye muscles. Here we present additional data about the mechanical properties of passive eye muscles in deeply anesthetized monkeys. We show that, in addition to the aforementioned failures, previous models also grossly overestimate the force exerted by passive eye muscles during smooth elongations similar to those experienced during normal eye movements. Importantly, we also show that the force exerted by a muscle following an elongation is largely independent of the elongation itself, and it is mostly determined by the final muscle length. These additional findings conclusively rule out the use of classical viscoelastic models to mimic the mechanical properties of passive eye muscles. We describe here a new model that extends previous ones using principles derived from research on thixotropic materials. This model is able to account reasonably well for our data, and could thus be incorporated into models of the eye plant.
C1 [Quaia, Christian; Optican, Lance M.] NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA.
[Ying, Howard S.] Johns Hopkins Univ Hosp, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21287 USA.
RP Quaia, C (reprint author), NEI, Sensorimotor Res Lab, Bldg 10, Bethesda, MD 20892 USA.
EM quaiac@nei.nih.gov
FU National Eye Institute (CQ, LMO); National Institutes of Health (NIH)
[EY19347, EY15025]; Knights Templar Eye Foundation Young Investigator
Award; Research to Prevent Blindness Core Grant
FX This work was supported by the intramural research program of the
National Eye Institute (CQ, LMO), by National Institutes of Health (NIH)
grants NIH EY19347 and NIH EY15025 (HSY), the Knights Templar Eye
Foundation Young Investigator Award (HSY), and Research to Prevent
Blindness Core Grant (HSY). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 26
TC 10
Z9 10
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 8
PY 2010
VL 5
IS 3
BP A236
EP A254
AR e9595
DI 10.1371/journal.pone.0009595
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 565WZ
UT WOS:000275328200022
PM 20221406
ER
PT J
AU Thanos, PK
Habibi, R
Michaelides, M
Patel, UB
Suchland, K
Anderson, BJ
Robinson, JK
Wang, GJ
Grandy, DK
Volkow, ND
AF Thanos, Panayotis K.
Habibi, Rahila
Michaelides, Michael
Patel, Ujval B.
Suchland, Katherine
Anderson, Brenda J.
Robinson, John K.
Wang, Gene-Jack
Grandy, David K.
Volkow, Nora D.
TI Dopamine D4 receptor (D4R) deletion in mice does not affect operant
responding for food or cocaine
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Reward; Addiction; Reinforcement; Cognition
ID D-4 RECEPTOR; NOVELTY SEEKING; MUTANT MICE; GENE; POLYMORPHISM;
DISORDER; RATS; IMPULSIVITY; D2
AB In this study we examined the genetic contribution of the D4R in food and cocaine self-administration using D4R mice. Mice were examined for operant responding to food pellets or intravenous cocaine. Compared to wild-type mice (D4R(+/+)), both heterozygous (D4R(+/-)) and knockout (D4R(-/-)) mice showed no difference in responding for food or cocaine. Our findings suggest that the D4R is not directly involved in mediating operant response behaviors for food or cocaine. Published by Elsevier B.V.
C1 [Thanos, Panayotis K.; Habibi, Rahila; Michaelides, Michael; Patel, Ujval B.; Wang, Gene-Jack; Volkow, Nora D.] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
[Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Lab Neuroimaging, NIH, Bethesda, MD USA.
[Thanos, Panayotis K.; Habibi, Rahila; Michaelides, Michael; Anderson, Brenda J.; Robinson, John K.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
[Suchland, Katherine; Grandy, David K.] Oregon Hlth & Sci Univ, Portland, OR USA.
RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
EM thanos@bnl.gov
RI Michaelides, Michael/K-4736-2013
OI Michaelides, Michael/0000-0003-0398-4917
FU NIAAA (intramural Research Program, LNI); NIH IRTA program; Stony Brook
URECA program; BNL SULI program
FX Support contributed by: NIAAA (intramural Research Program, LNI), the
NIH IRTA program, the Stony Brook URECA program and the BNL SULI
program. We also thank N. Londono for her assistance with the D4 mouse
breeding colony.
NR 31
TC 9
Z9 9
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD MAR 5
PY 2010
VL 207
IS 2
BP 508
EP 511
DI 10.1016/j.bbr.2009.10.020
PG 4
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 558RC
UT WOS:000274761800033
PM 19853629
ER
PT J
AU Suzuki, K
Kimura, H
Wu, H
Kudo, N
Kim, WB
Suzuki, S
Yoshida, A
Caturegli, P
Kohn, LD
AF Suzuki, Koichi
Kimura, Hiroaki
Wu, Huhehasi
Kudo, Naoko
Kim, Won Bae
Suzuki, Sayuri
Yoshida, Akio
Caturegli, Patrizio
Kohn, Leonard D.
TI Excess iodide decreases transcription of NIS and VEGF genes in rat
FRTL-5 thyroid cells
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Iodide; Thyroid; NIS; VEGF; Thyroglobulin
ID SODIUM/IODIDE SYMPORTER GENE; BLOOD-FLOW; STIMULATING HORMONE; LUGOL
IODINE; EXPRESSION; HYPERTHYROIDISM; THYROGLOBULIN; SUPPRESSION;
THYROTROPIN; FOLLICLES
AB Although it is well known that an excess of iodide suppresses thyroid function and blood flow in vivo, the underlying molecular mechanisms are not fully known. The functional effect of iodide occurs at multiple steps, which include inhibition of sodium/iodide symporter (NIS) expression, transient block of organification, and inhibition of hormonal release. The vascular effect likely involves suppression of the vascular endothelial growth factor (VEGF) gene. In this report, we show that excess iodide coordinately suppresses the expression of the NIS and VEGF genes in FRTL-5 thyroid cells. We also demonstrate that the mechanism of iodide suppression of NIS gene expression is transcriptional, which is synergized by the addition of thyroglobulin. Based on the findings of reporter gene assays and electrophoretic gel mobility shift analysis, we also report two novel DNA binding proteins that responded specifically to iodide and modulated NIS promoter activity. The results suggest that excess iodide affects thyroid vascular function in addition to iodide uptake. This study provides additional insights into the mechanism of action of excess iodide on thyroid function. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Suzuki, Koichi; Wu, Huhehasi] Natl Inst Infect Dis, Leprosy Res Ctr, Lab Mol Diagnost, Higashimurayama, Tokyo 1890002, Japan.
[Suzuki, Koichi; Kudo, Naoko; Kim, Won Bae; Yoshida, Akio; Kohn, Leonard D.] NIDDK, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
[Suzuki, Koichi; Suzuki, Sayuri] Washington Hosp Ctr, Medstar Res Inst, Mol Endocrinol Lab, Washington, DC 20010 USA.
[Kimura, Hiroaki; Caturegli, Patrizio] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Kim, Won Bae] ASAN Med Ctr, Dept Internal Med, Div Endocrinol & Metab, Seoul 138736, South Korea.
[Suzuki, Sayuri] Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan.
[Yoshida, Akio] Tottori Univ, Grad Sch Med, Dept Genet & Regenerat Med, Div Regenerat Med & Therapeut, Tottori 6838504, Japan.
[Kohn, Leonard D.] Ohio Univ, Coll Osteopath Med, Edison Biotechnol Inst, Athens, OH 45701 USA.
[Kohn, Leonard D.] Ohio Univ, Coll Osteopath Med, Dept Biomed Sci, Athens, OH 45701 USA.
RP Suzuki, K (reprint author), Natl Inst Infect Dis, Leprosy Res Ctr, Lab Mol Diagnost, 4-2-1 Aoba Cho, Higashimurayama, Tokyo 1890002, Japan.
EM koichis@nih.go.jp
RI Suzuki, Sayuri/L-5291-2013;
OI Kim, Won Bae/0000-0003-4544-1750
FU Ministry of Education, Culture, Sport, Science, and Technology of Japan
[21591187]; NIH [DK55670]
FX This work was supported in part by a Grant-in-Aid for Scientific
Research by the Ministry of Education, Culture, Sport, Science, and
Technology of Japan (21591187 to K.S.), and in part by an NIH grant
(DK55670 to P.C.).
NR 32
TC 15
Z9 18
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 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD MAR 5
PY 2010
VL 393
IS 2
BP 286
EP 290
DI 10.1016/j.bbrc.2010.01.123
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 573WT
UT WOS:000275946700019
PM 20132794
ER
PT J
AU Koonin, EV
AF Koonin, Eugene V.
TI The Incredible Expanding Ancestor of Eukaryotes
SO CELL
LA English
DT Editorial Material
ID EVOLUTION; GENOMES; COMPLEX; GENES
C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU Intramural NIH HHS [ZIA LM000073-16]
NR 9
TC 41
Z9 41
U1 1
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 5
PY 2010
VL 140
IS 5
BP 606
EP 608
DI 10.1016/j.cell.2010.02.022
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 564EZ
UT WOS:000275197400007
PM 20211127
ER
PT J
AU Lakatta, EG
Maltsev, VA
Vinogradova, TM
AF Lakatta, Edward G.
Maltsev, Victor A.
Vinogradova, Tatiana M.
TI A Coupled SYSTEM of Intracellular Ca2+ Clocks and Surface Membrane
Voltage Clocks Controls the Timekeeping Mechanism of the Heart's
Pacemaker
SO CIRCULATION RESEARCH
LA English
DT Review
DE sinoatrial node cells; ion channels; local Ca2+ releases; sarcoplasmic
reticulum; ryanodine receptors
ID RABBIT SINOATRIAL NODE; CELL-DERIVED CARDIOMYOCYTES; RECTIFIER POTASSIUM
CURRENT; NA+-CA2+ EXCHANGE CURRENT; DEPENDENT PROTEIN-KINASE; PIG
VENTRICULAR MYOCYTES; SUSTAINED INWARD CURRENT; SPONTANEOUS BEATING
RATE; CAT RIGHT ATRIUM; SARCOPLASMIC-RETICULUM
AB Ion channels on the surface membrane of sinoatrial nodal pacemaker cells (SANCs) are the proximal cause of an action potential. Each individual channel type has been thoroughly characterized under voltage clamp, and the ensemble of the ion channel currents reconstructed in silico generates rhythmic action potentials. Thus, this ensemble can be envisioned as a surface "membrane clock" (M clock). Localized subsarcolemmal Ca2+ releases are generated by the sarcoplasmic reticulum via ryanodine receptors during late diastolic depolarization and are referred to as an intracellular "Ca2+ clock," because their spontaneous occurrence is periodic during voltage clamp or in detergent-permeabilized SANCs, and in silico as well. In spontaneously firing SANCs, the M and Ca2+ clocks do not operate in isolation but work together via numerous interactions modulated by membrane voltage, subsarcolemmal Ca2+, and protein kinase A and CaMKII-dependent protein phosphorylation. Through these interactions, the 2 subsystem clocks become mutually entrained to form a robust, stable, coupled-clock system that drives normal cardiac pacemaker cell automaticity. G protein-coupled receptors signaling creates pacemaker flexibility, ie, effects changes in the rhythmic action potential firing rate, by impacting on these very same factors that regulate robust basal coupled-clock system function. This review examines evidence that forms the basis of this coupled-clock system concept in cardiac SANCs. (Circ Res. 2010; 106: 659-673.)
C1 [Lakatta, Edward G.; Maltsev, Victor A.; Vinogradova, Tatiana M.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM LakattaE@grc.nia.nih.gov
FU National Institutes of Health, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Aging.
NR 105
TC 204
Z9 210
U1 4
U2 45
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD MAR 5
PY 2010
VL 106
IS 4
BP 659
EP 673
DI 10.1161/CIRCRESAHA.109.206078
PG 15
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 564CR
UT WOS:000275190500007
PM 20203315
ER
PT J
AU Rada, B
Leto, TL
AF Rada, Balazs
Leto, Thomas L.
TI Characterization of hydrogen peroxide production by Duox in bronchial
epithelial cells exposed to Pseudomonas aeruginosa
SO FEBS LETTERS
LA English
DT Article
DE NADPH oxidase; Hydrogen peroxide; Duox; Dual oxidase; Epithelial cell;
Pseudomonas
ID ATP-MEDIATED ACTIVATION; CYSTIC-FIBROSIS; HOST-DEFENSE; IMMUNE-RESPONSE;
III SYSTEM; INFECTION; OXIDASES; CHILDREN
AB Hydrogen peroxide production by the NADPH oxidase Duox1 occurs during activation of respiratory epithelial cells stimulated by purified bacterial ligands, such as lipopolysaccharide. Here, we characterize Duox activation using intact bacterial cells of several airway pathogens. We found that only Pseudomonas aeruginosa, not Burkholderia cepacia or Staphylococcus aureus, triggers H(2)O(2) production in bronchial epithelial cells in a calcium-dependent but predominantly ATP-independent manner. Moreover, by comparing mutant Pseudomonas strains, we identify several virulence factors that participate in Duox activation, including the type-three secretion system. These data provide insight on Duox activation by mechanisms unique to P. aeruginosa. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
C1 [Rada, Balazs; Leto, Thomas L.] NIAID, Lab Host Defenses, NIH, Rockville, MD 20852 USA.
RP Leto, TL (reprint author), NIAID, Lab Host Defenses, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA.
EM tleto@nih.gov
FU NIH, National Institute of Allergy and Infectious Diseases
FX We are grateful for research materials from the following sources:
Anti-Duox antibodies (Dr. Corinne Dupuy, Institut Gustave-Roussy,
FRE2939 CNRS), PAO1 strains (The Pseudomonas Mutant Library, UW,
Seattle); PA14 strains (Dr. Frederick Ausubel, Massachusetts General
Hospital, Boston); B. cepacia and S. aureus (Dr. Steven Holland, NIAID,
NIH). This work was supported by the Intramural Research Program of the
NIH, National Institute of Allergy and Infectious Diseases.
NR 20
TC 23
Z9 23
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD MAR 5
PY 2010
VL 584
IS 5
BP 917
EP 922
DI 10.1016/j.febslet.2010.01.025
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 559XK
UT WOS:000274862900012
PM 20085766
ER
PT J
AU Rohrl, J
Yang, D
Oppenheim, JJ
Hehlgans, T
AF Roehrl, Johann
Yang, De
Oppenheim, Joost J.
Hehlgans, Thomas
TI Specific Binding and Chemotactic Activity of mBD4 and Its Functional
Orthologue hBD2 to CCR6-expressing Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN BETA-DEFENSINS; HUMAN BETA-DEFENSIN-3; DENDRITIC CELLS;
EXPRESSION; IMMUNITY; KERATINOCYTES; INDUCTION; PEPTIDES; IMMATURE;
INNATE
AB beta-Defensins are small antimicrobial polypeptides that are mainly expressed by epithelial cells and play an important role in the antimicrobial innate immune response. In addition to the direct microbicidal effects of these polypeptides, members of the beta-defensin super family have the capacity to promote local innate inflammatory and systemic adaptive immune responses, which are in part mediated by the CC-chemokine receptor CCR6. Here we report the expression of recombinant mBD4 and its human orthologue hBD2 fused to the constant domain of human IgG(1) to obtain correct folding and to increase stability and solubility using the Drosophila S2 expression system. Purified recombinant mBD4:Ig and hBD2: Ig fusion proteins retained potent antimicrobial activity against Gram-negative and Gram-positive bacteria. Furthermore, these beta-defensin fusion proteins showed specific binding to CCR6-expressing cells as revealed by flow cytometry. Interestingly, although hBD2: Ig bound to both human and mouse CCR6-expressing cells, mBD4: Ig did only bind to mCCR6-expressing cells but not to hCCR6-expressing cells. Both beta-defensin fusion proteins demonstrated chemotactic activity for cells expressing the mouse CC-chemokine receptor CCR6. The chemokine ligand CCL20 competed with the beta-defensin fusion proteins for specific binding to CCR6 as analyzed by fluorescence-activated cell sorter analysis. Both beta-defensin fusion proteins demonstrated chemotactic activity for cells expressing the mouse CCR6 receptor, but mBD4: Ig did not induce chemotactic activity of cells expressing human CCR6. This result supports our finding that mBD4 does not interact with human CCR6-expressing cells. Further evidence for specific interaction of the beta-defensin fusion proteins with CCR6-expressing cells is demonstrated by the observation that CCL20 and beta-defensin fusion proteins desensitize each other in inducing chemotactic activity. In addition both mBD4: Ig and hBD2: Ig demonstrated CCR6-independent chemotaxis of freshly isolated mouse resident peritoneal cells and human peripheral blood mononuclear cells, indicating the interaction with another chemotaxis-inducing receptor. Thus, the beta-defensin fusion proteins used in this study retained their biological activity and are a feasible tool to identify and analyze specific beta-defensin receptor interactions.
C1 [Hehlgans, Thomas] Univ Regensburg, Inst Immunol, D-93042 Regensburg, Germany.
[Yang, De; Oppenheim, Joost J.] NCI Frederick, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res,Div Basic Sci,NIH, Frederick, MD 21702 USA.
RP Hehlgans, T (reprint author), Univ Regensburg, Inst Immunol, Franz Josef Strauss Allee 11, D-93042 Regensburg, Germany.
EM thomas.hehlgans@klinik.uni-regensburg.de
FU Bayerische Forschungsstifung [PDOK-62-08]
FX This work was authored, in whole or in part, by National Institutes of
Health staff. This work was supported by Bayerische Forschungsstifung
Grant PDOK-62-08 (to T.H.).
NR 25
TC 37
Z9 39
U1 0
U2 3
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 MAR 5
PY 2010
VL 285
IS 10
BP 7028
EP 7034
DI 10.1074/jbc.M109.091090
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 567AV
UT WOS:000275415600016
PM 20068036
ER
PT J
AU Fletcher, PL
Fletcher, MD
Weninger, K
Anderson, TE
Martin, BM
AF Fletcher, Paul L., Jr.
Fletcher, Maryann D.
Weninger, Keith
Anderson, Trevor E.
Martin, Brian M.
TI Vesicle-associated Membrane Protein (VAMP) Cleavage by a New
Metalloprotease from the Brazilian Scorpion Tityus serrulatus
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PANCREATIC ACINAR-CELLS; SNARE COMPLEX; REGULATED EXOCYTOSIS;
SINGLE-MOLECULE; BOTULINUM NEUROTOXINS; SECRETORY GRANULES; GUINEA-PIG;
FUSION; VENOM; BINDING
AB We present evidence that venom from the Brazilian scorpion Tityus serrulatus and a purified fraction selectively cleave essential SNARE proteins within exocrine pancreatic tissue. Western blotting for vesicle-associated membrane protein type v-SNARE proteins (or synaptobrevins) reveals characteristic alterations to venom-treated excised pancreatic lobules in vitro. Immunocytochemistry by electron microscopy confirms both the SNARE identity as VAMP2 and the proteolysis of VAMP2 as a marked decrease in secondary antibody-conjugated colloidal gold particles that are predominantly associated with mature zymogen granules. Studies with recombinant SNARE proteins were used to determine the specific cleavage site in VAMP2 and the susceptibility of VAMP8 (endobrevin). The VAMP2 cleavage site is between the transmembrane anchor and the SNARE motif that assembles into the ternary SNARE complex. Inclusion of divalent chelating agents ( EDTA) with fraction nu, an otherwise active purified component from venom, eliminates SNARE proteolysis, suggesting the active protein is a metalloprotease. The unique cleavages of VAMP2 and VAMP8 may be linked to pancreatitis that develops following scorpion envenomation as both of these v-SNARE proteins are associated with zymogen granule membranes in pancreatic acinar cells. We have isolated antarease, a metalloprotease from fraction nu that cleaves VAMP2, and report its amino acid sequence.
C1 [Fletcher, Paul L., Jr.; Fletcher, Maryann D.] E Carolina Univ, Dept Microbiol & Immunol, Brody Sch Med, Greenville, NC 27834 USA.
[Weninger, Keith; Anderson, Trevor E.] N Carolina State Univ, Dept Phys, Raleigh, NC 27695 USA.
[Martin, Brian M.] NIMH, Lab Neurotoxicol, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Fletcher, PL (reprint author), E Carolina Univ, Dept Microbiol & Immunol, Brody Sch Med, Greenville, NC 27834 USA.
EM fletcherpa@ecu.edu
FU East Carolina University Center for Coastal Informatics and Modeling
Funds; Burroughs Wellcome Fund; National Institutes of Health; NIMH;
Intramural Research Program
FX This work was supported in part by the East Carolina University Center
for Coastal Informatics and Modeling Funds ( to P. L. F.), a Career
Award at the Scientific Interface from the Burroughs Wellcome Fund ( to
K. W.), and by the National Institutes of Health, NIMH, Intramural
Research Program (to B. M. M.).
NR 55
TC 31
Z9 33
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 MAR 5
PY 2010
VL 285
IS 10
BP 7405
EP 7416
DI 10.1074/jbc.M109.028365
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 567AV
UT WOS:000275415600053
PM 20026600
ER
PT J
AU Umehara, T
Nakamura, Y
Jang, MK
Nakano, K
Tanaka, A
Ozato, K
Padmanabhan, B
Yokoyama, S
AF Umehara, Takashi
Nakamura, Yoshihiro
Jang, Moon Kyoo
Nakano, Kazumi
Tanaka, Akiko
Ozato, Keiko
Padmanabhan, Balasundaram
Yokoyama, Shigeyuki
TI Structural Basis for Acetylated Histone H4 Recognition by the Human BRD2
Bromodomain
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MITOTIC CHROMOSOMES; CRYSTAL-STRUCTURE; BINDING MODULES; LIVING CELLS;
CHROMATIN; PROTEINS; MITOSIS; ACETYLTRANSFERASES; TRANSCRIPTION;
ACTIVATION
AB Recognition of acetylated chromatin by the bromodomains and extra-terminal domain (BET) family proteins is a hallmark for transcriptional activation and anchoring viral genomes to mitotic chromosomes of the host. One of the BET family proteins BRD2 interacts with acetylated chromatin during mitosis and leads to transcriptional activation in culture cells. Here, we report the crystal structures of the N-terminal bromodomain of human BRD2 (BRD2-BD1; residues 74-194) in complex with each of three different Lys-12-acetylated H4 peptides. The BRD2-BD1 recognizes the H4 tail acetylated at Lys-12 (H4K12ac), whereas the side chain of hypoacetylated Lys-8 of H4 binds at the cavity of the dimer interface of BRD2-BD1. From binding studies, we identified the BRD2-BD1 residues that are responsible for recognition of the Lys-12-acetylated H4 tail. In addition, mutationto Lys-8 in the Lys-12-acetylated H4 tail decreased the binding to BRD2-BD1, implicating the critical role of Lys-8 in the Lys-12-acetylated H4 tail for the recognition by BRD2-BD1. Our findings provide a structural basis for deciphering the histone code by the BET bromodomain through the binding with a long segment of the histone H4 tail, which presumably prevents erasure of the histone code during the cell cycle.
C1 [Padmanabhan, Balasundaram; Yokoyama, Shigeyuki] RIKEN, Syst & Struct Biol Ctr, Yokohama, Kanagawa 2300045, Japan.
[Jang, Moon Kyoo; Ozato, Keiko] NICHHD, Dept Mol Growth Regulat, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Yokoyama, Shigeyuki] Univ Tokyo, Dept Biophys & Biochem, Grad Sch Sci, Bunkyo Ku, Tokyo 1130033, Japan.
RP Padmanabhan, B (reprint author), Aptuit Laurus Pvt, ICICI Knowledge Pk, Hyderabad 500078, Andhra Pradesh, India.
EM paddy.b@aptuitlaurus.com; yokoyama@biochem.s.u-tokyo.ac.jp
RI Umehara, Takashi/N-5683-2015;
OI Umehara, Takashi/0000-0003-3464-2960; Yokoyama,
Shigeyuki/0000-0003-3133-7338
FU National Institutes of Health; National Institute of Biomedical
Innovation; RIKEN Structural Genomics/Proteomics Initiative; Ministry of
Education, Culture, Sports, Science and Technology of Japan
FX This work was authored, in whole or in part, by National Institutes of
Health staff. This work was supported in part by the Program for
Promotion of Fundamental Studies in Health Sciences of the National
Institute of Biomedical Innovation, by the RIKEN Structural
Genomics/Proteomics Initiative, and the National Project on Protein
Structural and Functional Analyses, Ministry of Education, Culture,
Sports, Science and Technology of Japan.
NR 41
TC 44
Z9 46
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 MAR 5
PY 2010
VL 285
IS 10
BP 7610
EP 7618
DI 10.1074/jbc.M109.062422
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 567AV
UT WOS:000275415600072
PM 20048151
ER
PT J
AU Wang, T
Shah, YM
Matsubara, T
Zhen, YY
Tanabe, T
Nagano, T
Fotso, S
Krausz, KW
Zabriskie, TM
Idle, JR
Gonzalez, FJ
AF Wang, Ting
Shah, Yatrik M.
Matsubara, Tsutomu
Zhen, Yueying
Tanabe, Tomotaka
Nagano, Tomokazu
Fotso, Serge
Krausz, Kristopher W.
Zabriskie, T. Mark
Idle, Jeffrey R.
Gonzalez, Frank J.
TI Control of Steroid 21-oic Acid Synthesis by Peroxisome
Proliferator-activated Receptor alpha and Role of the
Hypothalamic-Pituitary-Adrenal Axis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; ALDO-KETO REDUCTASE; NEUROPEPTIDE-Y NPY; NAKED
PLASMID DNA; PPAR-ALPHA; ALDEHYDE DEHYDROGENASE; 20-ALPHA-HYDROXYSTEROID
DEHYDROGENASE; SUCCESSIVE REACTIONS; TISSUE DISTRIBUTION; OXIDATIVE
STRESS
AB A previous study identified the peroxisome proliferator-activated receptor alpha (PPAR alpha) activation biomarkers 21-steroid carboxylic acids 11 beta-hydroxy-3,20-dioxopregn-4-en-21-oic acid (HDOPA) and 11 beta,20-dihydroxy-3-oxo-pregn-4-en-21-oic acid (DHOPA). In the present study, the molecular mechanism and the metabolic pathway of their production were determined. The PPAR alpha-specific time-dependent increases in HDOPA and 20 alpha-DHOPA paralleled the development of adrenal cortex hyperplasia, hypercortisolism, and spleen atrophy, which was attenuated in adrenalectomized mice. Wy-14,643 activation of PPAR alpha induced hepatic FGF21, which caused increased neuropeptide Y and agouti-related protein mRNAs in the hypothalamus, stimulation of the agouti-related protein/neuropeptide Y neurons, and activation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in increased adrenal cortex hyperplasia and corticosterone production, revealing a link between PPAR alpha and the HPA axis in controlling energy homeostasis and immune regulation. Corticosterone was demonstrated as the precursor of 21-carboxylic acids both in vivo and in vitro. Under PPAR alpha activation, the classic reductive metabolic pathway of corticosterone was suppressed, whereas an alternative oxidative path-way was uncovered that leads to the sequential oxidation on carbon 21 resulting in HDOPA. The latter was then reduced to the end product 20 alpha-DHOPA. Hepatic cytochromes P450, aldehyde dehydrogenase (ALDH3A2), and 21-hydroxysteroid dehydrogenase (AKR1C18) were found to be involved in this pathway. Activation of PPAR alpha resulted in the induction of Aldh3a2 and Akr1c18, both of which were confirmed as target genes through introduction of promoter luciferase reporter constructs into mouse livers in vivo. This study underscores the power of mass spectrometry-based metabolomics combined with genomic and physiologic analyses in identifying downstream metabolic biomarkers and the corresponding upstream molecular mechanisms.
C1 [Wang, Ting; Shah, Yatrik M.; Matsubara, Tsutomu; Zhen, Yueying; Tanabe, Tomotaka; Nagano, Tomokazu; Krausz, Kristopher W.; Idle, Jeffrey R.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Fotso, Serge; Zabriskie, T. Mark] Oregon State Univ, Dept Pharmaceut Sci, Corvallis, OR 97331 USA.
[Idle, Jeffrey R.] Charles Univ Prague, Inst Pharmacol, Fac Med 1, Prague 12800, Czech Republic.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM fjgonz@helix.nih.gov
FU National Institutes of Health NCI Intramural Research; Center for
Gastrointestinal Biology and Disease [P30 DK34987]
FX This work was supported, in whole or in part, by National Institutes of
Health NCI Intramural Research Program. This work was also supported by
Center for Gastrointestinal Biology and Disease Grant P30 DK34987.
NR 43
TC 11
Z9 11
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 MAR 5
PY 2010
VL 285
IS 10
BP 7670
EP 7685
DI 10.1074/jbc.M109.090175
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 567AV
UT WOS:000275415600077
PM 20032461
ER
PT J
AU Kloer, DP
Rojas, R
Ivan, V
Moriyama, K
van Vlijmen, T
Murthy, N
Ghirlando, R
van der Sluijs, P
Hurley, JH
Bonifacino, JS
AF Kloer, Daniel P.
Rojas, Raul
Ivan, Viorica
Moriyama, Kengo
van Vlijmen, Thijs
Murthy, Namita
Ghirlando, Rodolfo
van der Sluijs, Peter
Hurley, James H.
Bonifacino, Juan S.
TI Assembly of the Biogenesis of Lysosome-related Organelles Complex-3
(BLOC-3) and Its Interaction with Rab9
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HERMANSKY-PUDLAK-SYNDROME; MYOSIN-VA; VESICLE TRAFFICKING; GUNMETAL
MOUSE; PROTEIN; GENE; FAMILY; HPS1; MELANOSOMES; TRANSPORT
AB The Hermansky-Pudlak syndrome (HPS) is a genetic hypopigmentation and bleeding disorder caused by defective biogenesis of lysosome-related organelles (LROs) such as melanosomes and platelet dense bodies. HPS arises from mutations in any of 8 genes in humans and 16 genes in mice. Two of these genes, HPS1 and HPS4, encode components of the biogenesis of lysosome-related organelles complex-3 (BLOC-3). Herein we show that recombinant HPS1-HPS4 produced in insect cells can be efficiently isolated as a 1:1 heterodimer. Analytical ultracentrifugation reveals that this complex has a molecular mass of 146 kDa, equivalent to that of the native complex and to the sum of the predicted molecular masses of HPS1 and HPS4. This indicates that HPS1 and HPS4 interact directly in the absence of any other protein as part of BLOC-3. Limited proteolysis and deletion analyses show that both subunits interact with one another throughout most of their lengths with the sole exception of a long, unstructured loop in the central part of HPS4. An interaction screen reveals a specific and strong interaction of BLOC-3 with the GTP-bound form of the endosomal GTPase, Rab9. This interaction is mediated by HPS4 and the switch I and II regions of Rab9. These characteristics indicate that BLOC-3 might function as a Rab9 effector in the biogenesis of LROs.
C1 [Ghirlando, Rodolfo; Hurley, James H.] NIDDK, NIH, Mol Biol Lab, Bethesda, MD 20892 USA.
[Rojas, Raul; Moriyama, Kengo; Murthy, Namita; Bonifacino, Juan S.] Eunice Kennedy Shriver NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Ivan, Viorica; van Vlijmen, Thijs; van der Sluijs, Peter] Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands.
RP Hurley, JH (reprint author), NIDDK, NIH, Mol Biol Lab, Bldg 50 Rm 4517, Bethesda, MD 20892 USA.
EM hurley@helix.nih.gov; juan@helix.nih.gov
RI van Vlijmen, Thijs/B-4069-2009; Ghirlando, Rodolfo/A-8880-2009; 何,
敏仪/E-6352-2015;
OI van Vlijmen, Thijs/0000-0002-5882-6660; Bonifacino, Juan
S./0000-0002-5673-6370
FU NICHD; NIDDK; Netherlands' Proteomics Center; DFG-NIH
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Programs of NICHD (to J. S. B.) and NIDDK (to J. H.
H.), the Netherlands' Proteomics Center (to P. v. d. S.), and the
DFG-NIH program (to D. P. K.).
NR 45
TC 37
Z9 38
U1 2
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 MAR 5
PY 2010
VL 285
IS 10
BP 7794
EP 7804
DI 10.1074/jbc.M109.069088
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 567AV
UT WOS:000275415600087
PM 20048159
ER
PT J
AU Pugeat, M
Nader, N
Hogeveen, K
Raverot, G
Dechaud, H
Grenot, C
AF Pugeat, Michel
Nader, Nancy
Hogeveen, Kevin
Raverot, Gerald
Dechaud, Henri
Grenot, Catherine
TI Sex hormone-binding globulin gene expression in the liver: Drugs and the
metabolic syndrome
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE SHBG; Sex steroid hormones; Risk factor; Diabetes; Metabolic syndrome;
Fructose
ID POLYCYSTIC-OVARY-SYNDROME; HUMAN HEPATOMA-CELLS; CARDIOVASCULAR
RISK-FACTORS; POSTMENOPAUSAL WOMEN; SHBG GENE; ANOREXIA-NERVOSA;
STEROID-HORMONES; THYROID-HORMONE; BREAST-CANCER; SERUM-LEVELS
AB Sex hormone-binding globulin (SHBG) is the main transport binding protein for sex steroid hormones in plasma and regulates their accessibility to target cells. Plasma SHBG is secreted by the liver under the control of hormones and nutritional factors. In the human hepatoma cell line (HepG2), thyroid and estrogenic hormones, and a variety of drugs including the antioestrogen tamoxifen, the phytoestrogen, genistein and mitotane (Op'DDD) increase SHBG production and SHBG gene promoter activity. In contrast, monosaccharides (glucose or fructose) effectively decrease SHBG expression by inducing lipogenesis, which reduces hepatic HNF-4 alpha levels, a transcription factor that play a critical role in controlling the SHBG promoter. Interestingly, diminishing hepatic lipogenesis and free fatty acid liver biosynthesis also appear to be associated with the positive effects of thyroid hormones and PPAR gamma antagonists on SHBG expression. This mechanism provides a biological explanation for why SHBG is a sensitive biomarker of insulin resistance and the metabolic syndrome, and why low plasma SHBG levels are a risk factor for developing hyperglycemia and type 2 diabetes, especially in women. These important advances in our knowledge of the regulation of SHBG expression in the liver open new approaches for identifying and preventing metabolic disorder-associated diseases early in life. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Pugeat, Michel; Dechaud, Henri; Grenot, Catherine] Groupement Hosp Est, Hosp Civils Lyon, F-69677 Bron, France.
[Pugeat, Michel; Hogeveen, Kevin; Raverot, Gerald] INSERM, U863, IFR 62, F-69003 Lyon, France.
[Pugeat, Michel; Hogeveen, Kevin; Raverot, Gerald; Dechaud, Henri; Grenot, Catherine] Univ Lyon 1, F-69003 Lyon, France.
[Nader, Nancy; Dechaud, Henri] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Pediat Endocrinol, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Pugeat, M (reprint author), Groupement Hosp Est, Hosp Civils Lyon, 59 Bd Pinel, F-69677 Bron, France.
EM michel.pugeat@chu-lyon.fr
RI Perez , Claudio Alejandro/F-8310-2010;
OI Perez , Claudio Alejandro/0000-0001-9688-184X; Raverot,
Gerald/0000-0002-9517-338X
NR 87
TC 40
Z9 44
U1 0
U2 16
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 MAR 5
PY 2010
VL 316
IS 1
SI SI
BP 53
EP 59
DI 10.1016/j.mce.2009.09.020
PG 7
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 553LR
UT WOS:000274368700007
PM 19786070
ER
PT J
AU Ahlers, JD
Belyakov, IM
AF Ahlers, Jeffrey D.
Belyakov, Igor M.
TI Memories that last forever: strategies for optimizing vaccine T-cell
memory
SO BLOOD
LA English
DT Review
ID MUCOSAL AIDS VACCINE; DENDRITIC CELLS; PROTECTIVE IMMUNITY;
VIRAL-INFECTION; CUTTING EDGE; IN-VIVO; SECONDARY EXPANSION; EFFECTOR
FUNCTIONS; RHESUS MACAQUES; THERAPEUTIC VACCINATION
AB For acute self-limiting infections a vaccine is successful if it elicits memory at least as good as the natural experience; however, for persistent and chronic infections such as HIV, hepatitis C virus (HCV), human papillomavirus (HPV), and human herpes viruses, this paradigm is not applicable. At best, during persistent virus infection the person must be able to maintain the integrity of the immune system in equilibrium with controlling replicating virus. New vaccine strategies are required that elicit both potent high-avidity CD8(+) T-cell effector/memory and central memory responses that can clear the nidus of initial virus-infected cells at mucosal surfaces to prevent mucosal transmission or significantly curtail development of disease. The objective of an HIV-1 T-cell vaccine is to generate functional CD8(+) effector memory cells at mucosal portals of virus entry to prevent viral transmission. In addition, long-lived CD8(+) and CD4(+) central memory cells circulating through secondary lymphoid organs and resident in bone marrow, respectively, are needed to provide a concerted second wave of defense that can contain virus at mucosal surfaces and prevent systemic dissemination. Further understanding of factors which can influence long-lived effector and central memory cell differentiation will significantly contribute to development of effective T-cell vaccines. In this review we will focus on discussing mechanisms involved in T-cell memory and provide promising new approaches toward expanding current vaccine strategies to enhance antiviral memory. (Blood. 2010;115:1678-1689)
C1 [Ahlers, Jeffrey D.] NIAID, NIH, Rockville, MD 20817 USA.
[Belyakov, Igor M.] Midwest Res Inst, Frederick, MD USA.
RP Ahlers, JD (reprint author), NIAID, NIH, 6700B Rockledge Dr,Rm 5138, Rockville, MD 20817 USA.
EM jahlers@niaid.nih.gov; igorbelyakov@yahoo.com
NR 133
TC 57
Z9 59
U1 1
U2 6
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 MAR 4
PY 2010
VL 115
IS 9
BP 1678
EP 1689
DI 10.1182/blood-2009-06-227546
PG 12
WC Hematology
SC Hematology
GA 571KR
UT WOS:000275751200007
PM 19903895
ER
PT J
AU Rutsch, S
Neppalli, VT
Shin, DM
DuBois, W
Morse, HC
Goldschmidt, H
Janz, S
AF Rutsch, Sebastian
Neppalli, Vishala T.
Shin, Dong-Mi
DuBois, Wendy
Morse, Herbert C., III
Goldschmidt, Hartmut
Janz, Siegfried
TI IL-6 and MYC collaborate in plasma cell tumor formation in mice
SO BLOOD
LA English
DT Article
ID HUMAN MULTIPLE-MYELOMA; C-MYC; BALB/C PLASMACYTOMAS; COMBINATION
THERAPY; INTERLEUKIN-6 IL-6; BONE-MARROW; MOUSE MODEL; B-CELLS; GROWTH;
NEOPLASMS
AB Interleukin-6 (IL-6) plays a critical role in the natural history of human plasma cell neoplasms (PCNs), such as plasma cell myeloma and plasmacytoma (PCT). IL-6 is also at the center of neoplastic plasma cell transformation in BALB/c (C) mice carrying a transgene, H2-L(d)-IL6, that encodes human IL-6 under control of the major histocompatibility complex H2-L(d) promoter: strain C. H2-L(d)-IL6. These mice are prone to PCT, but tumor development is incomplete with long latencies (similar to 40% PCT at 12 months of age). To generate a more robust mouse model of IL-6-dependent PCN, we intercrossed strain C.H2-L(d)-IL6 with strains C.iMyc(E mu) or C.iMyc(C alpha), 2 interrelated gene-insertion models of the chromosomal T(12; 15) translocation causing deregulated expression of Myc in mouse PCT. Deregulation of MYC is also a prominent feature of human PCN. We found that double-transgenic C.H2L(d)-IL6/iMyc(E mu) and C.H2-L(d)-IL6/iMyc(C alpha) mice develop PCT with full penetrance (100% tumor incidence) and short latencies (3-6 months). The mouse tumors mimic molecular hallmarks of their human tumor counterparts, including elevated IL-6/Stat3/Bcl-X(L) signaling. The newly developed mouse strains may provide a good preclinical research tool for the design and testing of new approaches to target IL-6 in treatment and prevention of human PCNs. (Blood. 2010;115:1746-1754)
C1 [Rutsch, Sebastian; Goldschmidt, Hartmut] Univ Heidelberg, Med Klin 5, Heidelberg, Germany.
[Neppalli, Vishala T.; Janz, Siegfried] Natl Ctr Tumor Dis, Heidelberg, Germany.
[Neppalli, Vishala T.; Janz, Siegfried] Univ Iowa, Dept Pathol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA.
[Shin, Dong-Mi; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD USA.
[DuBois, Wendy] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
RP Janz, S (reprint author), 500 Newton Rd,1046 ML, Iowa City, IA 52242 USA.
EM siegfried-janz@uiowa.edu
OI Morse, Herbert/0000-0002-9331-3705
FU NIH; National Institute of Allergy and Infectious Diseases; NCI
[P50CA097274]
FX This work was supported in part by the Intramural Research Program of
the NIH, the National Institute of Allergy and Infectious Diseases, and
Award No. P50CA097274 from the NCI.
NR 50
TC 27
Z9 27
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 MAR 4
PY 2010
VL 115
IS 9
BP 1746
EP 1754
DI 10.1182/blood-2009-08-237941
PG 9
WC Hematology
SC Hematology
GA 571KR
UT WOS:000275751200015
PM 20018915
ER
PT J
AU Glauser, TA
Cnaan, A
Shinnar, S
Hirtz, DG
Dlugos, D
Masur, D
Clark, PO
Capparelli, EV
Adamson, PC
AF Glauser, Tracy A.
Cnaan, Avital
Shinnar, Shlomo
Hirtz, Deborah G.
Dlugos, Dennis
Masur, David
Clark, Peggy O.
Capparelli, Edmund V.
Adamson, Peter C.
CA Childhood Absence Epilepsy Study
TI Ethosuximide, Valproic Acid, and Lamotrigine in Childhood Absence
Epilepsy.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID SEIZURES; MONOTHERAPY; CHILDREN; DIAGNOSIS
AB Background: Childhood absence epilepsy, the most common pediatric epilepsy syndrome, is usually treated with ethosuximide, valproic acid, or lamotrigine. The most efficacious and tolerable initial empirical treatment has not been defined.
Methods: In a double-blind, randomized, controlled clinical trial, we compared the efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug doses were incrementally increased until the child was free of seizures, the maximal allowable or highest tolerable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. Differential drug effects were determined by means of pairwise comparisons.
Results: The 453 children who were randomly assigned to treatment with ethosuximide (156), lamotrigine (149), or valproic acid (148) were similar with respect to their demographic characteristics. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar (53% and 58%, respectively; odds ratio with valproic acid vs. ethosuximide, 1.26; 95% confidence interval [CI], 0.80 to 1.98; P=0.35) and were higher than the rate for lamotrigine (29%; odds ratio with ethosuximide vs. lamotrigine, 2.66; 95% CI, 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P<0.001 for both comparisons). There were no significant differences among the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide (in 49% of the children vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P=0.03).
Conclusions: Ethosuximide and valproic acid are more effective than lamotrigine in the treatment of childhood absence epilepsy. Ethosuximide is associated with fewer adverse attentional effects. (ClinicalTrials.gov number, NCT00088452.)
N Engl J Med 2010;362:790-9.
C1 [Glauser, Tracy A.] Cincinnati Childrens Hosp, Div Neurol, Comprehens Epilepsy Ctr, Cincinnati, OH 45229 USA.
[Glauser, Tracy A.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Cnaan, Avital] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Shinnar, Shlomo; Masur, David] Albert Einstein Coll Med, Montefiore Med Ctr, New York, NY USA.
[Hirtz, Deborah G.] NINDS, Bethesda, MD 20892 USA.
[Dlugos, Dennis; Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Capparelli, Edmund V.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA.
[Capparelli, Edmund V.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA.
RP Glauser, TA (reprint author), Cincinnati Childrens Hosp, Div Neurol, Comprehens Epilepsy Ctr, 3333 Burnet Ave,MLC 2015, Cincinnati, OH 45229 USA.
EM tracy.glauser@cchmc.org
FU National Institutes of Health [NS045911, NS045803, 5 U10 HD031318, 5 U10
HD037249, 1 UL1 RR026314, P30 HD26979]
FX Supported by grants from the National Institutes of Health (NS045911,
NS045803, 5 U10 HD031318, 5 U10 HD037249, 1 UL1 RR026314, and P30
HD26979).
NR 37
TC 185
Z9 191
U1 1
U2 32
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 MAR 4
PY 2010
VL 362
IS 9
BP 790
EP 799
DI 10.1056/NEJMoa0902014
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 563DQ
UT WOS:000275108300006
PM 20200383
ER
PT J
AU Hesse, BW
Moser, RP
Rutten, LJ
AF Hesse, Bradford W.
Moser, Richard P.
Rutten, Lila J.
TI Surveys of Physicians and Electronic Health Information.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID NATIONAL TRENDS SURVEY; INTERNET
C1 [Hesse, Bradford W.; Moser, Richard P.] NCI, Bethesda, MD 20892 USA.
[Rutten, Lila J.] NCI, Frederick, MD 21701 USA.
RP Hesse, BW (reprint author), NCI, Bethesda, MD 20892 USA.
EM hesseb@mail.nih.gov
OI Hesse, Bradford/0000-0003-1142-1161
NR 5
TC 58
Z9 59
U1 2
U2 8
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 MAR 4
PY 2010
VL 362
IS 9
BP 859
EP 860
DI 10.1056/NEJMc0909595
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 563DQ
UT WOS:000275108300031
PM 20200398
ER
PT J
AU Jantz, D
Berg, JM
AF Jantz, Derek
Berg, Jeremy M.
TI Probing the DNA-Binding Affinity and Specificity of Designed Zinc Finger
Proteins
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID CONTROLLING GENE-EXPRESSION; FLUORESCENCE ANISOTROPY; TRANSCRIPTION
FACTORS; PHAGE DISPLAY; EQUILIBRIUM BINDING; CHIMERIC NUCLEASES;
ESTROGEN-RECEPTOR; CRYSTAL-STRUCTURE; SALT DEPENDENCE; LAC REPRESSOR
AB Engineered transcription factors and endonucleases based on designed Cys(2)His(2) zinc finger domains have proven to be effective tools for the directed regulation and modification of genes. The introduction of this technology into both research and clinical settings necessitates the development of rapid and accurate means of evaluating both the binding affinity and binding specificity of designed zinc finger domains. Using a fluorescence anisotropy-based DNA-binding assay, we examined the DNA-binding properties of two engineered zinc finger proteins that differ by a single amino acid. We demonstrate that the protein with the highest affinity for a particular DNA site need not be the protein that binds that site with the highest degree of specificity. Moreover, by comparing the binding characteristics of the two proteins at varying salt concentrations, we show that the ionic strength makes significant and variable contributions to both affinity and specificity. These results have significant implications for zinc finger design as they highlight the importance of considering affinity, specificity, and environmental requirements in designing a DNA-binding domain for a particular application.
C1 [Jantz, Derek; Berg, Jeremy M.] NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Berg, JM (reprint author), NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA.
EM bergj@mail.nih.gov
OI Berg, Jeremy/0000-0003-3022-0963
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of General Medical Sciences
FX This work was Supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases, and by
the National Institute of General Medical Sciences.
NR 52
TC 11
Z9 12
U1 0
U2 8
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 MAR 3
PY 2010
VL 98
IS 5
BP 852
EP 860
DI 10.1016/j.bpj.2009.11.021
PG 9
WC Biophysics
SC Biophysics
GA 564QV
UT WOS:000275232100013
PM 20197039
ER
PT J
AU Hondares, E
Rosell, M
Gonzalez, FJ
Giralt, M
Iglesias, R
Villarroya, F
AF Hondares, Elayne
Rosell, Meritxell
Gonzalez, Frank J.
Giralt, Marta
Iglesias, Roser
Villarroya, Francesc
TI Hepatic FGF21 Expression Is Induced at Birth via PPAR alpha in Response
to Milk Intake and Contributes to Thermogenic Activation of Neonatal
Brown Fat
SO CELL METABOLISM
LA English
DT Article
ID FIBROBLAST GROWTH FACTOR-21; INSULIN SENSITIVITY; METABOLIC REGULATOR;
LIPID-METABOLISM; GENE-EXPRESSION; MICE; LINK;
FIBROBLAST-GROWTH-FACTOR-21; INDUCTION; OBESITY
AB Plasma FGF21 levels and hepatic FGF21 gene expression increase dramatically after birth in mice. This induction is initiated by suckling, requires lipid intake, is impaired in PPAR alpha null neonates, and is mimicked by treatment with the PPAR alpha activator, Wy14,643. Neonates exhibit reduced FGF21 expression in response to fasting, in contrast to the upregulation occurring in adults. Changes in FGF21 expression due to suckling or nutritional manipulations were associated with circulating free fatty acid and ketone body levels. We mimicked the FGF21 postnatal rise by injecting FGF21 into fasting neonates, and found that this enhanced the expression of genes involved in thermogenesis within brown fat, and increased body temperature. Brown adipocytes treated with FGF21 exhibited increased expression of thermogenic genes, higher total and uncoupled respiration, and enhanced glucose oxidation. We propose that the induction of FGF21 production by the liver mediates direct activation of brown fat thermogenesis during the fetal-to-neonatal transition.
C1 [Hondares, Elayne; Rosell, Meritxell; Giralt, Marta; Iglesias, Roser; Villarroya, Francesc] Univ Barcelona, Inst Biomed, Dept Bioquim & Biol Mol, E-08028 Barcelona, Catalonia, Spain.
[Hondares, Elayne; Rosell, Meritxell; Giralt, Marta; Iglesias, Roser; Villarroya, Francesc] CIBER Fisiopatol Obesidad & Nutr CIBEROBN, Barcelona 08028, Catalonia, Spain.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Villarroya, F (reprint author), Univ Barcelona, Inst Biomed, Dept Bioquim & Biol Mol, E-08028 Barcelona, Catalonia, Spain.
EM fvillarroya@ub.edu
RI Giralt, Marta/A-4756-2013; Villarroya, Francesc/K-4357-2014;
OI Giralt, Marta/0000-0001-7968-4190; Villarroya,
Francesc/0000-0003-1266-9142
FU MCIN [SAF2008-01896]; Instituto de Salud Carlos III, Spain [PI081715]
FX This work was supported by grants from MCIN (SAF2008-01896) and
Instituto de Salud Carlos III (PI081715), Spain.
NR 18
TC 153
Z9 157
U1 3
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD MAR 3
PY 2010
VL 11
IS 3
BP 206
EP 212
DI 10.1016/j.cmet.2010.02.001
PG 7
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 565WE
UT WOS:000275325400007
PM 20197053
ER
PT J
AU Shi, Y
Oury, F
Yadav, VK
Wess, J
Liu, XS
Guo, XE
Murshed, M
Karsenty, G
AF Shi, Yu
Oury, Franck
Yadav, Vijay K.
Wess, Juergen
Liu, X. Sherry
Guo, X. Edward
Murshed, Monzur
Karsenty, Gerard
TI Signaling through the M-3 Muscarinic Receptor Favors Bone Mass Accrual
by Decreasing Sympathetic Activity
SO CELL METABOLISM
LA English
DT Article
ID ACETYLCHOLINE-RECEPTOR; NERVOUS-SYSTEM; LEPTIN REGULATION; KNOCKOUT
MICE; IN-VIVO; LACKING; GENE; STIMULATION; DISRUPTION; GROWTH
AB Bone remodeling is regulated by various neuronal inputs, including sympathetic tone, which is known to inhibit bone mass accrual. This aspect of sympathetic nervous system function raises the prospect that the other arm of the autonomic nervous system, the parasympathetic nervous system, may also affect bone remodeling. Here, we use various mutant mouse strains, each lacking one of the muscarinic receptors that mediate parasympathetic activity, to show that the parasympathetic nervous system acting through the M-3 muscarinic receptor is a positive regulator of bone mass accrual, increasing bone formation and decreasing bone resorption. Gene expression studies, cell-specific gene deletion experiments, and analysis of compound mutant mice showed that the parasympathetic nervous system favors bone mass accrual by acting centrally and by decreasing the sympathetic tone. By showing that both arms of the autonomic nervous system affect bone remodeling, this study further underscores the importance of neuronal regulation of bone.
C1 [Shi, Yu; Oury, Franck; Yadav, Vijay K.; Karsenty, Gerard] Columbia Univ, Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA.
[Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Liu, X. Sherry; Guo, X. Edward] Columbia Univ, Dept Biomed Engn, Bone Bioengn Lab, New York, NY 10027 USA.
[Murshed, Monzur] McGill Univ, Fac Dent, Div Biomed Sci, Montreal, PQ H3A 1A4, Canada.
[Murshed, Monzur] McGill Univ, Dept Med, Div Endocrinol & Metab, Montreal, PQ H3A 1A4, Canada.
RP Karsenty, G (reprint author), Columbia Univ, Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA.
EM gk2172@columbia.edu
RI yadav, VIJAY /Q-2540-2016;
OI yadav, VIJAY /0000-0003-2345-2846; Liu, Xiaowei/0000-0001-7247-2232
FU National Institutes of Health [DK58883]
FX We thank Dr. Patricia Ducy for critical reading of the manuscript and
constructive comments. This work was supported by grant DK58883 from
National Institutes of Health (G.K.).
NR 34
TC 33
Z9 36
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD MAR 3
PY 2010
VL 11
IS 3
BP 231
EP 238
DI 10.1016/j.cmet.2010.01.005
PG 8
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 565WE
UT WOS:000275325400010
PM 20197056
ER
PT J
AU Ng, L
Lyubarsky, A
Nikonov, SS
Ma, M
Srinivas, M
Kefas, B
St Germain, DL
Hernandez, A
Pugh, EN
Forrest, D
AF Ng, Lily
Lyubarsky, Arkady
Nikonov, Sergei S.
Ma, Michelle
Srinivas, Maya
Kefas, Benjamin
St Germain, Donald L.
Hernandez, Arturo
Pugh, Edward N., Jr.
Forrest, Douglas
TI Type 3 Deiodinase, a Thyroid-Hormone-Inactivating Enzyme, Controls
Survival and Maturation of Cone Photoreceptors
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID DEVELOPING MOUSE RETINA; IODOTHYRONINE DEIODINASE; DEVELOPMENTAL
EXPRESSION; ROD PHOTORESPONSE; RAINBOW-TROUT; COLOR-VISION; BRAIN;
OPSINS; MICE; ACHROMATOPSIA
AB Maturation of the mammalian nervous system requires adequate provision of thyroid hormone and mechanisms that enhance tissue responses to the hormone. Here, we report that the development of cones, the photoreceptors for daylight and color vision, requires protection from thyroid hormone by type 3 deiodinase, a thyroid hormone-inactivating enzyme. Type 3 deiodinase, encoded by Dio3, is expressed in the immature mouse retina. In Dio3(-/-) mice, similar to 80% of cones are lost through neonatal cell death. Cones that express opsin photopigments for response to both short (S) and medium-long (M) wavelength light are lost. Rod photoreceptors, which mediate dim light vision, remain essentially intact. Excessive thyroid hormone in wild-type pups also eliminates cones. Cone loss is mediated by cone-specific thyroid hormone receptor beta 2 (TR beta 2) as deletion of TR beta 2 rescues cones in Dio3(-/-) mice. However, rescued cones respond to short but not longer wavelength light because TR beta 2 under moderate hormonal stimulation normally induces M opsin and controls the patterning of M and S opsins over the retina. The results suggest that type 3 deiodinase limits hormonal exposure of the cone to levels that safeguard both cone survival and the patterning of opsins that is required for cone function.
C1 [Ng, Lily; Ma, Michelle; Kefas, Benjamin; Forrest, Douglas] NIDDKD, NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA.
[Lyubarsky, Arkady; Nikonov, Sergei S.; Pugh, Edward N., Jr.] Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Srinivas, Maya] Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA.
[St Germain, Donald L.; Hernandez, Arturo] Dartmouth Med Sch, Dept Physiol, Lebanon, NH 03766 USA.
RP Forrest, D (reprint author), NIDDKD, NIH, Clin Endocrinol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM forrestd@niddk.nih.gov
FU National Institutes of Health (NIH)/National Institute of Diabetes and
Digestive and Kidney Diseases [HD09020, DK42271, EY02660]
FX This work was supported in part by the intramural research program at
National Institutes of Health (NIH)/National Institute of Diabetes and
Digestive and Kidney Diseases, a Hirshl Award (D.F.), and NIH Grants
HD09020, DK42271 (D.L.S.), and EY02660 (E.N.P.). We thank V.A. Galton
for advice on this study.
NR 54
TC 68
Z9 69
U1 0
U2 3
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 MAR 3
PY 2010
VL 30
IS 9
BP 3347
EP 3357
DI 10.1523/JNEUROSCI.5267-09.2010
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 564CS
UT WOS:000275191000020
PM 20203194
ER
PT J
AU Threlfell, S
Clements, MA
Khodai, T
Pienaar, IS
Exley, R
Wess, J
Cragg, SJ
AF Threlfell, Sarah
Clements, Michael A.
Khodai, Tansi
Pienaar, Ilse S.
Exley, Richard
Wess, Juergen
Cragg, Stephanie J.
TI Striatal Muscarinic Receptors Promote Activity Dependence of Dopamine
Transmission via Distinct Receptor Subtypes on Cholinergic Interneurons
in Ventral versus Dorsal Striatum
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID NICOTINIC ACETYLCHOLINE-RECEPTORS; LONG-TERM POTENTIATION; CAT
CAUDATE-NUCLEUS; KNOCK-OUT MICE; MIDBRAIN DOPAMINE; PRIMATE STRIATUM;
AUTORECEPTOR FUNCTION; M2-MUSCARINIC DRUGS; MEDIATED MODULATION; MONKEY
STRIATUM
AB Striatal dopamine (DA) and acetylcholine (ACh) regulate motivated behaviors and striatal plasticity. Interactions between these neurotransmitters may be important, through synchronous changes in parent neuron activities and reciprocal presynaptic regulation of release. How DA signaling is regulated by striatal muscarinic receptors (mAChRs) is unresolved; contradictory reports indicate suppression or facilitation, implicating several mAChR subtypes on various neurons. We investigated whether mAChR regulation of DA signaling varies with presynaptic activity and identified the mAChRs responsible in sensorimotor-versus limbic-associated striatum. We detected DA in real time at carbon fiber microelectrodes in mouse striatal slices.
Broad-spectrum mAChR agonists [oxotremorine-M, APET (arecaidine propargyl ester tosylate)] decreased DA release evoked by low-frequency stimuli (1-10 Hz, four pulses) but increased the sensitivity of DA release to presynaptic activity, even enhancing release by high frequencies (e.g., >25 Hz for four pulses). These bidirectional effects depended on ACh input to striatal nicotinic receptors (nAChRs) on DA axons but not GABA or glutamate input. In caudate-putamen (CPu), knock-out of M(2)- or M(4)-mAChRs (not M(5)) prevented mAChR control of DA, indicating that M(2)- and M(4)-mAChRs are required. In nucleus accumbens (NAc) core or shell, mAChR function was prevented in M(4)-knock-outs, but not M(2)- or M(5)-knock-outs.
These data indicate that striatal mAChRs, by inhibiting ACh release from cholinergic interneurons and thus modifying nAChR activity, offer variable control of DA release probability that promotes how DA release reflects activation of dopaminergic axons. Furthermore, different coupling of striatal M(2)/M(4)-mAChRs to the control of DA release in CPu versus NAc suggests targets to influence DA/ACh function differentially between striatal domains.
C1 [Threlfell, Sarah; Clements, Michael A.; Khodai, Tansi; Pienaar, Ilse S.; Exley, Richard; Cragg, Stephanie J.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England.
[Khodai, Tansi] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England.
[Wess, Juergen] NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
RP Cragg, SJ (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Sherrington Bldg, Oxford OX1 3PT, England.
EM stephanie.cragg@dpag.ox.ac.uk
OI Threlfell, Sarah/0000-0002-3581-1327; Cragg,
Stephanie/0000-0001-9677-2256
FU Parkinson's Disease Society [G-0808, G-4067]; Biotechnology and
Biological Sciences Research Council-Eli Lilly Collaborative Award in
Science and Engineering; International Brain Research Organization
International
FX This work was supported by Parkinson's Disease Society Grants G-0808 and
G-4067, a Biotechnology and Biological Sciences Research Council-Eli
Lilly Collaborative Award in Science and Engineering, and an
International Brain Research Organization International Studentship
(I.S.P.). We thank Dr. K. Jennings for critical reading of this
manuscript.
NR 78
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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 MAR 3
PY 2010
VL 30
IS 9
BP 3398
EP 3408
DI 10.1523/JNEUROSCI.5620-09.2010
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 564CS
UT WOS:000275191000025
PM 20203199
ER
PT J
AU Rodriguez, AC
Schiffman, M
Herrero, R
Hildesheim, A
Bratti, C
Sherman, ME
Solomon, D
Guillen, D
Alfaro, M
Morales, J
Hutchinson, M
Katki, H
Cheung, L
Wacholder, S
Burk, RD
AF Cecilia Rodriguez, Ana
Schiffman, Mark
Herrero, Rolando
Hildesheim, Allan
Bratti, Concepcion
Sherman, Mark E.
Solomon, Diane
Guillen, Diego
Alfaro, Mario
Morales, Jorge
Hutchinson, Martha
Katki, Hormuzd
Cheung, Li
Wacholder, Sholom
Burk, Robert D.
TI Longitudinal Study of Human Papillomavirus Persistence and Cervical
Intraepithelial Neoplasia Grade 2/3: Critical Role of Duration of
Infection
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID CYTOLOGICALLY NORMAL WOMEN; COSTA-RICA; NATURAL-HISTORY; YOUNG-WOMEN;
COLOMBIAN WOMEN; FOLLOW-UP; CANCER; RISK; COHORT; POPULATION
AB Background The natural history of human papillomavirus (HPV) infections in older women is critical for preventive strategies, including vaccination and screening intervals, but is poorly understood. In a 7-year population-based cohort study in Guanacaste, Costa Rica, we examined whether women's age and the duration of carcinogenic HPV infections influenced subsequent persistence of infection and risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease.
Methods At enrollment, of the 9466 participants eligible for pelvic examination, 9175 were screened for cervical neoplasia using multiple methods; those with CIN 2 or worse disease were censored and treated. Participants at low risk of CIN 2 or worse (n = 6029) were rescreened at 5-7 years (passively followed), whereas higher-risk participants (n = 2115) and subsets of low-risk women (n = 540) and initially sexually inactive women (n = 410) were rescreened annually or semiannually (actively followed) for up to 7 years. HPV testing was done using a polymerase chain reaction-based method. We determined, by four age groups (18-25, 26-33, 34-41, and >= 42 years), the proportion of prevalent infections (found at baseline) and newly detected infections (first found during follow-up) that persisted at successive 1-year time points and calculated absolute risks of CIN 2 and CIN grade 3 (CIN 3) or worse during follow-up. P values are two-sided.
Results Regardless of the woman's age, newly detected infections were associated with very low absolute risks of persistence, CIN 2, or worse disease. For newly detected infections, the rate of progression to CIN 2+ (or CIN 3+), after 3 years of follow-up, was not higher for women aged 34 years and older than for younger women. Moreover, rates of newly detected infections declined sharply with age (in the actively followed group, at ages 18-25, 26-33, 34-41, and >= 42 years, rates were 35.9%, 30.6%, 18.1%, and 13.5%, respectively; P <.001). Among prevalent infections, persistent infections among older women (>= 42 years) was higher than that among younger age groups or new infections at any age (P <.01 for comparison of eight groups). Most (66 of 85) CIN 2 or worse detected during follow-up was associated with prevalent infections. Only a small subset (25 of 1128) of prevalent infections persisted throughout follow-up without apparent CIN 2 or worse.
Conclusions The rate of new infections declines with age, and new infections typically do not progress to CIN 2 or worse disease in older women; thus, overall potential benefit of prophylactic vaccination or frequent HPV screening to prevent or detect new carcinogenic HPV infections at older ages is low.
C1 [Cecilia Rodriguez, Ana; Herrero, Rolando; Bratti, Concepcion; Guillen, Diego; Alfaro, Mario; Morales, Jorge] Fdn INCIENSA, San Jose 10203, Costa Rica.
[Cecilia Rodriguez, Ana; Schiffman, Mark; Hildesheim, Allan; Sherman, Mark E.; Katki, Hormuzd; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA.
[Solomon, Diane] NCI, Canc Prevent Div, NIH, DHHS, Rockville, MD USA.
[Hutchinson, Martha] Brown Univ, Women & Infants Hosp, Dept Pathol, Providence, RI USA.
[Cheung, Li] Informat Management Serv Inc, Silver Spring, MD USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10467 USA.
RP Rodriguez, AC (reprint author), Fdn INCIENSA, 7Mo Piso, San Jose 10203, Costa Rica.
EM acrodriguez@racsa.co.cr
RI Katki, Hormuzd/B-4003-2015;
OI Cheung, Li/0000-0003-1625-4331
FU National Institutes of Health [N01-CP-21081, N01-CP-33061, N01-CP40542,
N01-CP-50535, N01-CP-81023, CA78527]
FX National Institutes of Health (N01-CP-21081, N01-CP-33061, N01-CP40542,
N01-CP-50535, N01-CP-81023, and intramural program CA78527 to R. D. B.).
The Guanacaste cohort (design and conduct of the study, sample
collection, management, analysis and interpretation of the data) for the
enrollment and follow-up phases were supported by the National Cancer
Institute, National Institutes of Health, Department of Health and Human
Services. A. C. R. was supported by an appointment to the Senior
Fellowship Program at the National Institutes of Health for analysis and
manuscript preparation. The program is administered by the Oak Ridge
Institute for Science and Education through an interagency agreement
between the US Department of Energy and the National Institutes of
Health.
NR 42
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U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAR 3
PY 2010
VL 102
IS 5
BP 315
EP 324
DI 10.1093/jnci/djq001
PG 10
WC Oncology
SC Oncology
GA 564YL
UT WOS:000275254600009
PM 20157096
ER
PT J
AU Guerreiro, RJ
Beck, J
Gibbs, JR
Santana, I
Rossor, MN
Schott, JM
Nalls, MA
Ribeiro, H
Santiago, B
Fox, NC
Oliveira, C
Collinge, J
Mead, S
Singleton, A
Hardy, J
AF Guerreiro, Rita J.
Beck, John
Gibbs, J. Raphael
Santana, Isabel
Rossor, Martin N.
Schott, Jonathan M.
Nalls, Michael A.
Ribeiro, Helena
Santiago, Beatriz
Fox, Nick C.
Oliveira, Catarina
Collinge, John
Mead, Simon
Singleton, Andrew
Hardy, John
TI Genetic Variability in CLU and Its Association with Alzheimer's Disease
SO PLOS ONE
LA English
DT Article
ID MULTILOCUS GENOTYPE DATA; GENOME-WIDE ASSOCIATION; APOLIPOPROTEIN-J;
AMYLOID-BETA; CEREBROSPINAL-FLUID; IDENTIFIES VARIANTS; SENILE PLAQUES;
CLUSTERIN GENE; BRAIN; EXPRESSION
AB Background: Recently, two large genome wide association studies in Alzheimer disease (AD) have identified variants in three different genes (CLU, PICALM and CR1) as being associated with the risk of developing AD. The strongest association was reported for an intronic single nucleotide polymorphism (SNP) in CLU.
Methodology/Principal Findings: To further characterize this association we have sequenced the coding region of this gene in a total of 495 AD cases and 330 healthy controls. A total of twenty-four variants were found in both cases and controls. For the changes found in more than one individual, the genotypic frequencies were compared between cases and controls. Coding variants were found in both groups (including a nonsense mutation in a healthy subject), indicating that the pathogenicity of variants found in this gene must be carefully evaluated. We found no common coding variant associated with disease. In order to determine if common variants at the CLU locus effect expression of nearby (cis) mRNA transcripts, an expression quantitative loci (eQTL) analysis was performed. No significant eQTL associations were observed for the SNPs previously associated with AD.
Conclusions/Significance: We conclude that common coding variability at this locus does not explain the association, and that there is no large effect of common genetic variability on expression in brain tissue. We surmise that the most likely mechanism underpinning the association is either small effects of genetic variability on resting gene expression, or effects on damage induced expression of the protein.
C1 [Guerreiro, Rita J.; Gibbs, J. Raphael; Nalls, Michael A.; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Guerreiro, Rita J.; Ribeiro, Helena; Oliveira, Catarina] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal.
[Beck, John; Collinge, John; Mead, Simon] UCL Inst Neurol, Dept Neurodegenerat Dis, MRC, Prion Unit, London, England.
[Gibbs, J. Raphael; Hardy, John] Reta Lila Weston Inst, London, England.
[Gibbs, J. Raphael; Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Gibbs, J. Raphael; Hardy, John] Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England.
[Santana, Isabel; Ribeiro, Helena; Santiago, Beatriz; Oliveira, Catarina] Coimbra Univ Hosp, Neurol Serv, Coimbra, Portugal.
[Rossor, Martin N.; Schott, Jonathan M.; Fox, Nick C.] UCL, Inst Neurol, Dementia Res Ctr, London, England.
RP Guerreiro, RJ (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM Singleta@mail.nih.gov
RI Oliveira, Catarina/F-3685-2010; Schott, Jonathan/A-9065-2011; Singleton,
Andrew/C-3010-2009; Mead, Simon/E-9414-2011; Hardy, John/C-2451-2009;
Guerreiro, Rita/A-1327-2011; Fox, Nick/B-1319-2009;
OI Schott, Jonathan/0000-0003-2059-024X; Mead, Simon/0000-0002-4326-1468;
Fox, Nick/0000-0002-6660-657X; Oliveira, Catarina/0000-0001-6942-4328;
Santana, Isabel/0000-0002-8114-9434
FU Intramural Research Program of the National Institute on Aging; National
Institutes of Health, Department of Health and Human Services [Z01
AG000950-06]; MRC Prion Unit and Fundacao para a Ciencia e Tecnologia,
Portugal [SFRH/BD/29647/2006, PIC/IC/83206/2007]; UK cohort; Department
of Health National Institute for Health Research Biomedical Research
Centres; MRC; HEFCE/NHS Senior lecturership
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health,
Department of Health and Human Services, project number Z01 AG000950-06;
MRC Prion Unit and Fundacao para a Ciencia e Tecnologia, Portugal [grant
SFRH/BD/29647/2006 and project PIC/IC/83206/2007]. The UK Medical
Research Council funded the analysis of the UK cohort. Some of this work
was done at University College London Hospitals/University College
London which received a proportion of funding from the Department of
Health National Institute for Health Research Biomedical Research
Centres funding scheme. The Dementia Research Centre in the Department
of Neurodegenerative Disease, UCL is an Alzheimer Research Trust
Coordinating Centre. NCF is funded by the MRC; JMS is in receipt of a
HEFCE/NHS Senior lecturership and JH of a MRC Returning Scientist Grant.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 36
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 3
PY 2010
VL 5
IS 3
AR e9510
DI 10.1371/journal.pone.0009510
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 562OZ
UT WOS:000275063400016
PM 20209083
ER
PT J
AU Mohanty, JG
Shukla, HD
Williamson, JD
Launer, LJ
Saxena, S
Rifkind, JM
AF Mohanty, Joy G.
Shukla, Hem D.
Williamson, Jefferey D.
Launer, Lenore J.
Saxena, Satya
Rifkind, Joseph M.
TI Alterations in the red blood cell membrane proteome in alzheimer's
subjects reflect disease-related changes and provide insight into
altered cell morphology
SO PROTEOME SCIENCE
LA English
DT Article
ID KNOCK-OUT MICE; ERYTHROCYTE-MEMBRANE; GEL-ELECTROPHORESIS;
MASS-SPECTROMETRY; OXIDATIVE STRESS; LIQUID-CHROMATOGRAPHY;
ALPHA-CHYMOTRYPSIN; ENDOTHELIAL-CELLS; PROTEINS; EXPRESSION
AB Background: Our earlier studies have shown that red blood cell (RBC) morphology in Alzheimer's disease (AD) subjects was altered (> 15% of the RBCs were elongated as compared to 5.9% in normal controls (p < 0.0001)). These results suggested alterations in the RBC membrane architecture in AD subjects, possibly due to RBC-beta-amyloid interactions and/or changes in the expression of membrane proteins. We hypothesized that the observed changes could be due to changes in the level of the protein components of the cytoskeleton and those linked to the RBC membrane. To examine this, we performed a proteomic analysis of RBC membrane proteins of AD subjects, and their age-matched controls using one pool of samples from each group, following their separation by SDS-PAGE, in-gel Tryptic digestion, LC-MS-MS of peptides generated, and a label-free approach of semi-quantitative analysis of their relative MS spectral intensities.
Results: The data suggest, (1) RBC shape/morphology changes in AD subjects are possibly attributed primarily to the changes (elevation or decrease) in the level of a series of membrane/cytoskeleton proteins involved in regulating the stability and elasticity of the RBC membrane, and (2) changes (elevation or decrease) in the level of a second series of proteins in the RBC membrane proteome reflect similar changes reported earlier by various investigators in AD or animal model of AD. Of particular interest, elevation of oxidative stress response proteins such as heat shock 90 kDa protein 1 alpha in AD subjects has been confirmed by western blot analysis in the RBC membrane proteome.
Conclusions: The results suggest that this study provides a potential link between the alterations in RBC membrane proteome in AD subjects and AD pathology.
C1 [Mohanty, Joy G.; Shukla, Hem D.; Saxena, Satya; Rifkind, Joseph M.] NIA, Baltimore, MD 21224 USA.
[Williamson, Jefferey D.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Launer, Lenore J.] NIA, Bethesda, MD 20892 USA.
RP Mohanty, JG (reprint author), NIA, Baltimore, MD 21224 USA.
EM MohantyJ@mail.nih.gov
FU Intramural Research Program of NIA
FX This research was supported entirely by the Intramural Research Program
of NIA, NIH although blood samples were obtained from Wake Forest
University. We are thankful to Agilent Technologies for their help in
analysis of RBC membrane proteome MS-MS data by SpectrumMill software.
There is no potential conflict with any institutions where work was
done. This is to state that all financial and material support for this
research has been born by the above mentioned two institutions, and
there are no potential conflicts. We are also thankful to Dr. Michel
Bernier of NIA for providing us a sample of cell extract expressing high
level of HSP-90 for our positive control, anti-HSP90 and anti-actin
antibodies for western blot analysis as a gift.
NR 53
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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 MAR 3
PY 2010
VL 8
AR 11
DI 10.1186/1477-5956-8-11
PG 9
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 577HZ
UT WOS:000276214900001
PM 20199679
ER
PT J
AU Motsinger-Reif, AA
Antas, PRZ
Oki, NO
Levy, S
Holland, SM
Sterling, TR
AF Motsinger-Reif, Alison A.
Antas, Paulo R. Z.
Oki, Noffisat O.
Levy, Shawn
Holland, Steven M.
Sterling, Timothy R.
TI Polymorphisms in IL-1 beta, vitamin D receptor Fok1, and Toll-like
receptor 2 are associated with extrapulmonary tuberculosis
SO BMC MEDICAL GENETICS
LA English
DT Article
ID MULTIFACTOR-DIMENSIONALITY REDUCTION; NRAMP1 GENE POLYMORPHISMS; INNATE
IMMUNE-RESPONSES; SLC11A1 FORMERLY NRAMP1; INTERFERON-GAMMA GENE;
PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; WEST-AFRICA; P2X(7)
GENE; SUSCEPTIBILITY
AB Background: Human genetic variants may affect tuberculosis susceptibility, but the immunologic correlates of the genetic variants identified are often unclear.
Methods: We conducted a pilot case-control study to identify genetic variants associated with extrapulmonary tuberculosis in patients with previously characterized immune defects: low CD4+ lymphocytes and low unstimulated cytokine production. Two genetic association approaches were used: 1) variants previously associated with tuberculosis risk; 2) single nucleotide polymorphisms (SNPs) in candidate genes involved in tuberculosis pathogenesis. Single locus association tests and multifactor dimensionality reduction (MDR) assessed main effects and multi-locus interactions.
Results: There were 24 extrapulmonary tuberculosis cases (18 black), 24 pulmonary tuberculosis controls (19 black) and 57 PPD+ controls (49 black). In approach 1, 22 SNPs and 3 microsatellites were assessed. In single locus association tests, interleukin (IL)-1 beta + 3953 C/T was associated with extrapulmonary tuberculosis compared to PPD+ controls (P = 0.049). Among the sub-set of patients who were black, genotype frequencies of the vitamin D receptor (VDR) Fok1 A/G SNP were significantly different in extrapulmonary vs. pulmonary TB patients (P = 0.018). In MDR analysis, the toll-like receptor (TLR) 2 microsatellite had 76% prediction accuracy for extrapulmonary tuberculosis in blacks (P = 0.002). In approach 2, 613 SNPs in 26 genes were assessed. None were associated with extrapulmonary tuberculosis.
Conclusions: In this pilot study among extrapulmonary tuberculosis patients with well-characterized immune defects, genetic variants in IL-1 beta, VDR Fok1, and TLR2 were associated with an increased risk of extrapulmonary disease. Additional studies of the underlying mechanism of these genetic variants are warranted.
C1 [Antas, Paulo R. Z.; Sterling, Timothy R.] Vanderbilt Univ, Sch Med, Div Infect Dis, Dept Med, Nashville, TN 37212 USA.
[Motsinger-Reif, Alison A.; Oki, Noffisat O.] N Carolina State Univ, Dept Stat, Bioinformat Res Ctr, Raleigh, NC 27695 USA.
[Levy, Shawn] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA.
[Holland, Steven M.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Sterling, Timothy R.] Vanderbilt Univ, Sch Med, Ctr Hlth Serv Res, Dept Med, Nashville, TN 37212 USA.
RP Sterling, TR (reprint author), Vanderbilt Univ, Sch Med, Div Infect Dis, Dept Med, Nashville, TN 37212 USA.
EM timothy.sterling@vanderbilt.edu
FU Vanderbilt Ingram Cancer Center [P30 CA68485]; Vanderbilt Digestive
Disease Center [P30 DK58404]; Vanderbilt Vision Center [P30 EY08126];
National Institutes of Allergy and Infectious Diseases [K23 AI01654, K24
AI065298]; CAPES Foundation (Brazil); Johns Hopkins Hospital General
Clinical Research Center [M01-RR00052]; Vanderbilt University Department
of Medicine
FX This work was presented in part at the 2007 Keystone Tuberculosis
Symposium, March 20-25, 2007, Vancouver, British Columbia. Abstract 341.
The authors thank the Vanderbilt DNA Sequencing and Genotyping Facility
of the Vanderbilt Institute for Integrative Genomics for assistance with
performing microsatellite genotyping (Robert Woodhall). They also thank
the Vanderbilt Center for Human Genetics Research for polymorphism
analysis (DNA Resources Core; Ping Mayo and Cara B. Sutcliffe) and
advice regarding study design (Marylyn D. Ritchie, Ph. D.). All
array-based genotyping was performed in the Vanderbilt Microarray Shared
Resource (John Mote). The Vanderbilt Microarray Shared Resource is
supported by the Vanderbilt Ingram Cancer Center (P30 CA68485), the
Vanderbilt Digestive Disease Center (P30 DK58404), and the Vanderbilt
Vision Center (P30 EY08126). This work was supported by the National
Institutes of Allergy and Infectious Diseases (K23 AI01654, K24
AI065298, and the intramural program), the CAPES Foundation (Brazil),
the Johns Hopkins Hospital General Clinical Research Center (M01-RR00052
from the National Center for Research Resources, National Institutes of
Health), and the Vanderbilt University Department of Medicine.
NR 52
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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 MAR 2
PY 2010
VL 11
AR 37
DI 10.1186/1471-2350-11-37
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 569ZU
UT WOS:000275642200001
PM 20196868
ER
PT J
AU Wacholder, S
Chen, BE
Wilcox, A
Macones, G
Gonzalez, P
Befano, B
Hildesheim, A
Rodriguez, AC
Solomon, D
Herrero, R
Schiffman, M
AF Wacholder, Sholom
Chen, Bingshu Eric
Wilcox, Allen
Macones, George
Gonzalez, Paula
Befano, Brian
Hildesheim, Allan
Cecilia Rodriguez, Ana
Solomon, Diane
Herrero, Rolando
Schiffman, Mark
CA CVT Grp
TI Risk of miscarriage with bivalent vaccine against human papillomavirus
(HPV) types 16 and 18: pooled analysis of two randomised controlled
trials
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID QUADRIVALENT VACCINE; DOUBLE-BLIND
AB Objective To assess whether vaccination against human papillomavirus (HPV) increases the risk of miscarriage.
Design Pooled analysis of two multicentre, phase three masked randomised controlled trials
Setting Multicentre trials in several continents and in Costa Rica.
Participants 26 130 women aged 15-25 at enrolment; 3599 pregnancies eligible for analysis.
Interventions Participants were randomly assigned to receive three doses of bivalent HPV 16/18 VLP vaccine with AS04 adjuvant (n=13 075) or hepatitis A vaccine as control (n=13 055) over six months.
Main outcome measures Miscarriage and other pregnancy outcomes.
Results The estimated rate of miscarriage was 11.5% in pregnancies in women in the HPV arm and 10.2% in the control arm. The one sided P value for the primary analysis was 0.16; thus, overall, there was no significant increase in miscarriage among women assigned to the HPV vaccine arm. In secondary descriptive analyses, miscarriage rates were 14.7% in the HPV vaccine arm and 9.1% in the control arm in pregnancies that began within three months after nearest vaccination.
Conclusion There is no evidence overall for an association between HPV vaccination and risk of miscarriage.
C1 [Wacholder, Sholom; Hildesheim, Allan; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Chen, Bingshu Eric] Queens Univ, NCIC Clin Trials Grp, Kingston, ON K7L 3N6, Canada.
[Wilcox, Allen] Natl Inst Environm Hlth Sci, Div Intramural Res, Res Triangle Pk, NC 27709 USA.
[Macones, George] Washington Univ, Dept Obstet & Gynecol, St Louis, MO 63130 USA.
[Gonzalez, Paula; Cecilia Rodriguez, Ana; Herrero, Rolando] Fdn INCIENSA, San Jose, Costa Rica.
[Befano, Brian] Informat Management Serv Inc, Silver Spring, MD 20904 USA.
[Solomon, Diane] NCI, Canc Prevent Div, Rockville, MD 20852 USA.
RP Wacholder, S (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM WacholdS@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015;
OI Hildesheim, Allan/0000-0003-0257-2363; Wilcox, Allen/0000-0002-3376-1311
FU National Cancer Institute, NIH Office for Research on Women's Health in
agreement with the Ministry of Health of Costa Rica [N01-CP-11005]; GSK
Biologicals; National Cancer Institute (NCI), National Institutes of
Health; National Institute of Environmental Health Sciences, National
Institutes of Health
FX The CVT trial is sponsored and funded by the National Cancer Institute
(N01-CP-11005) with support from the NIH Office for Research on Women's
Health and conducted in agreement with the Ministry of Health of Costa
Rica. PATRICIA is funded by GSK Biologicals. GSK Biologicals contributed
data from PATRICIA to the analysis, and commented on aspects of the
trial at the design stage and after the results were shared with
investigators of both trials, with the permission of the Data Safety
Monitoring Board of CVT. GSK Biologicals had no role in study design and
the collection, analysis, and interpretation of data from CVT in this
paper, or in the writing of the article. GSK Biologicals took no part in
the decision to submit an article for publication. The pooled analysis
reported here was supported by the Intramural Research Programs of the
National Cancer Institute (NCI) and the National Institute of
Environmental Health Sciences, both parts of the National Institutes of
Health.
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U1 1
U2 4
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD MAR 2
PY 2010
VL 340
AR c712
DI 10.1136/bmj.c712
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 565FI
UT WOS:000275274300023
PM 20197322
ER
PT J
AU Wu, YL
Brosh, RM
AF Wu, Yuliang
Brosh, Robert M., Jr.
TI Distinct roles of RECQ1 in the maintenance of genomic stability
SO DNA REPAIR
LA English
DT Review
DE RECQ1 (RECQL); RecQ; Helicase; Genomic stability; DNA repair
ID BLOOMS-SYNDROME HELICASE; REPLICATION PROTEIN-A; STRAND-ANNEALING
ACTIVITIES; HOLLIDAY JUNCTION DISSOLVASOME; ROTHMUND-THOMSON-SYNDROME;
TOPOISOMERASE-III-ALPHA; WERNER-SYNDROME PROTEIN; DNA HELICASE;
HOMOLOGOUS RECOMBINATION; NEUROSPORA-CRASSA
AB Five human RecQ helicases (WRN, BLM, RECQ4, RECQ5, RECQ1) exist in humans. Of these, three are genetically linked to diseases of premature aging and/or cancer. Neither RECQ1 nor RECQ5 has yet been implicated in a human disease. However, cellular studies and genetic analyses of model organisms indicate that RECQ1 (and RECQ5) play an important role in the maintenance of genomic stability. Biochemical studies of purified RECQ1 protein demonstrate that the enzyme catalyzes DNA unwinding and strand annealing, and these activities are likely to be important for its role in DNA repair. RECQ1 also physically and functionally interacts with proteins involved in genetic recombination. In this review, we will summarize our current knowledge of RECQ1 roles in cellular nucleic acid metabolism and propose avenues of investigation for future studies. Published by Elsevier B.V.
C1 [Wu, Yuliang; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
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 NIH; National Institute on Aging
FX This work was supported by the Intramural Research program of the NIH,
National Institute on Aging.
NR 115
TC 23
Z9 23
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD MAR 2
PY 2010
VL 9
IS 3
SI SI
BP 315
EP 324
DI 10.1016/j.dnarep.2009.12.010
PG 10
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 574TO
UT WOS:000276016800012
PM 20061189
ER
PT J
AU Rossi, ML
Ghosh, AK
Bohr, VA
AF Rossi, Marie L.
Ghosh, Avik K.
Bohr, Vilhelm A.
TI Roles of Werner syndrome protein in protection of genome integrity
SO DNA REPAIR
LA English
DT Review
DE Werner Syndrome; WRN; RecQ helicases
ID BASE-EXCISION-REPAIR; DOUBLE-STRAND BREAKS; ROTHMUND-THOMSON-SYNDROME;
SYNDROME GENE-PRODUCT; DNA-POLYMERASE-DELTA; SYNDROME RECQ HELICASE;
REPLICATION FORK PROGRESSION; WRN EXONUCLEASE ACTIVITY; BLOOM-SYNDROME
HELICASES; CORONARY-ARTERY-DISEASE
AB Werner syndrome protein (WRN) is one of a family of five human RecQ helicases implicated in the maintenance of genome stability. The conserved RecQ family also includes RecQ1, Bloom syndrome protein (BLM), RecQ4, and RecQ5 in humans, as well as Sgs1 in Saccharomyces cerevisiae, Rqh1 in Schizosaccharomyces pombe, and homologs in Caenorhabditis elegans, Xenopus laevis, and Drosophila melanogaster. Defects in three of the RecQ helicases, RecQ4, BLM, and WRN, cause human pathologies linked with cancer predisposition and premature aging. Mutations in the WRN gene are the causative factor of Werner syndrome (WS). WRN is one of the best characterized of the RecQ helicases and is known to have roles in DNA replication and repair, transcription, and telomere maintenance. Studies both in vitro and in vivo indicate that the roles of WRN in a variety of DNA processes are mediated by post-translational modifications, as well as several important protein-protein interactions. In this work, we will summarize some of the early studies on the cellular roles of WRN and highlight the recent findings that shed some light on the link between the protein with its cellular functions and the disease pathology. Published by Elsevier B.V.
C1 [Rossi, Marie L.; Ghosh, Avik K.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA.
RP Bohr, VA (reprint author), NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM BohrV@grc.nia.nih.gov
FU National Institutes of Health; National Institute on Aging
FX We thank Dr. Dharmendra K. Singh and Mr. Joshua A. Sommers for helpful
comments on the manuscript. This work was supported entirely by funds
from the Intramural Research Program of the National Institutes of
Health, National Institute on Aging. We regret that space limitations
and the breadth of this field prevented us from citing every relevant
reference.
NR 244
TC 96
Z9 98
U1 3
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD MAR 2
PY 2010
VL 9
IS 3
SI SI
BP 331
EP 344
DI 10.1016/j.dnarep.2009.12.011
PG 14
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 574TO
UT WOS:000276016800014
PM 20075015
ER
PT J
AU Simons-Morton, DG
Donato, K
Loria, CM
Pratt, CA
Ershow, AG
Morrissette, MA
Czajkowski, S
Arteaga, SS
Obarzanek, E
AF Simons-Morton, Denise G.
Donato, Karen
Loria, Catherine M.
Pratt, Charlotte A.
Ershow, Abby G.
Morrissette, Meredith A.
Czajkowski, Susan
Arteaga, S. Sonia
Obarzanek, Eva
TI Obesity Research and Programs at the National Heart, Lung, and Blood
Institute
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE obesity; body weight; mechanistic research; epidemiology; efficacy;
effectiveness; translation
ID RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE MODIFICATION; CORONARY
RISK-FACTORS; PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE; WEIGHT-LOSS;
DIETARY PATTERNS; HEALTH-PROGRAM; CLINICAL-TRIAL; PRIMARY-CARE
C1 [Simons-Morton, Denise G.; Donato, Karen; Loria, Catherine M.; Pratt, Charlotte A.; Ershow, Abby G.; Morrissette, Meredith A.; Czajkowski, Susan; Arteaga, S. Sonia; Obarzanek, Eva] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Simons-Morton, DG (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Suite 10018,MSC 7936, Bethesda, MD 20892 USA.
EM simonsd@nhlbi.nih.gov
NR 30
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 2
PY 2010
VL 55
IS 9
BP 917
EP 920
DI 10.1016/j.jacc.2009.09.058
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 559XS
UT WOS:000274865100012
PM 20185044
ER
PT J
AU Yugeta, A
Terao, Y
Fukuda, H
Hikosaka, O
Yokochi, F
Okiyama, R
Taniguchi, M
Takahashi, H
Hamada, I
Hanajima, R
Ugawa, Y
AF Yugeta, A.
Terao, Y.
Fukuda, H.
Hikosaka, O.
Yokochi, F.
Okiyama, R.
Taniguchi, M.
Takahashi, H.
Hamada, I.
Hanajima, R.
Ugawa, Y.
TI Effects of STN stimulation on the initiation and inhibition of saccade
in Parkinson disease
SO NEUROLOGY
LA English
DT Article
ID SUBTHALAMIC NUCLEUS STIMULATION; LOCAL DOPAMINE DEPLETION; MEMORY-GUIDED
SACCADES; NIGRA PARS RETICULATA; EYE-MOVEMENT CONTROL; SUPERIOR
COLLICULUS; BASAL GANGLIA; OCULOMOTOR FUNCTIONS; REMEMBERED SACCADES;
HUNTINGTONS-DISEASE
AB Objectives: The basal ganglia (BG) play an important role in controlling saccades. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely used as a treatment of Parkinson disease (PD) by altering the function of the BG. Nevertheless, the effects of STN DBS on saccade performance are not fully clarified in a systematic manner. In this study, we examined the effects of bilateral STN DBS on both the initiation and inhibition of saccades in PD.
Methods: Thirty-two patients with PD performed 4 oculomotor tasks. Two tasks (visually guided saccades and gap saccades) were reflexive and 2 (memory-guided saccades [MGS] and antisaccades) were volitional. While taking their regular doses of antiparkinsonian drugs, patients performed these tasks under 2 conditions: during DBS (DBS-on condition) and without DBS (DBS-off condition). Fifty-one age-matched subjects served as controls.
Results: In the DBS-on condition, parameters of saccade initiation were improved in all tasks, with shorter latencies and increased amplitudes, except for MGS latency. STN DBS improved the ability to suppress unwanted saccades to the cue stimulus in the MGS task. However, it did not suppress prosaccades during the antisaccade task.
Conclusions: These results suggest that deep brain stimulation (DBS) of the subthalamic nucleus (STN) affects the neural pathway common to both reflexive and volitional saccades, possibly by acting on the STN-substantia nigra pars reticulata-superior colliculi pathway. STN DBS may set the functional level of the superior colliculi appropriate for both saccade initiation and inhibition through this pathway. These findings provide novel insights into the pathophysiology of Parkinson disease and may yield better treatment strategies. Neurology (R) 2010; 74: 743-748
C1 [Yugeta, A.; Terao, Y.; Hanajima, R.] Univ Tokyo, Dept Neurol, Grad Sch Med, Bunkyo Ku, Tokyo 1138655, Japan.
[Fukuda, H.] Natl Inst Occupat Safety & Hlth, Kanagawa, Japan.
[Hikosaka, O.] NEI, Sensorimotor Res Lab, Natl Inst Hlth, Bethesda, MD USA.
[Yokochi, F.; Okiyama, R.; Taniguchi, M.; Takahashi, H.] Tokyo Metropolitan Neurol Hosp, Tokyo, Japan.
[Hamada, I.] Tokyo Metropolitan Inst Neurosci, Tokyo, Japan.
[Ugawa, Y.] Fukushima Med Univ, Sch Med, Dept Neurol, Fukushima, Japan.
RP Yugeta, A (reprint author), Univ Tokyo, Dept Neurol, Grad Sch Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM yugetaa-tky@umin.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology of Japan
[18590928, 16500194]; Ministry of Health, Labor and Welfare of Japan
[17231401]; Research Committee on Dystonia; Ministry of Health, Labor
and Welfare of Japan; Committee of the Study of Human Exposure; Ministry
of Internal Affairs and Communications; Fukushima Medical University;
National Eye Institute Intramural Research; Ministry of Internal Affairs
and Communications/Committee of the Study of Human Exposure
FX Supported by Research Project Grant-in-Aid for Scientific Research No.
18590928, a grant from the Support Center for Advanced
Telecommunications Technology Research, Research Project Grants-in-Aid
for Scientific Research No. 16500194 from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan, and grants for the
Research Committee on rTMS Treatment of Movement Disorders from the
Ministry of Health, Labor and Welfare of Japan (17231401), the Research
Committee on Dystonia, the Ministry of Health, Labor and Welfare of
Japan, grants from the Committee of the Study of Human Exposure to EMF,
Ministry of Internal Affairs and Communications, and a grant from
Fukushima Medical University Research Project.; Dr. Yugeta reports no
disclosures. Dr. Terao serves on the editorial board of Clinical
Neurophysiology and is funded by Research Project Grant-in-Aid for
Scientific Research No. 18590928. Dr. Fukuda reports no disclosures. Dr.
Hikosaka serves on the editorial boards of Neuroscience Research, Neural
Networks, and Current Opinion in Neurobiology; and is funded by the
National Eye Institute Intramural Research Program. Dr. Okiyama, Dr.
Yokochi, Dr. Taniguchi, Dr. Takahashi, and Dr. Hamada report no
disclosures. Dr. Hanajima serves on the editorial board of Clinical
Neurophysiology. Dr. Ugawa served on the editorial board and now serves
as an Associate Editor of Clinical Neurophysiology; serves on the
editorial boards of Movement Disorders, Brain Stimulation, and The
Cerebellum; and receives research support from the Ministry of
Education, Culture, Sports, Science, and Technology of Japan/Research
Project Grants-in-Aid for Scientific Research No. 16500194, the Ministry
of Health, Labor and Welfare of Japan/Research Committee on rTMS
Treatment of Movement Disorders, 17231401, and the Ministry of Internal
Affairs and Communications/Committee of the Study of Human Exposure to
EMF.
NR 38
TC 30
Z9 31
U1 2
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 MAR 2
PY 2010
VL 74
IS 9
BP 743
EP 748
DI 10.1212/WNL.0b013e3181d31e0b
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 562GG
UT WOS:000275037300008
PM 20194913
ER
PT J
AU Pardini, M
Krueger, F
Raymont, V
Grafman, J
AF Pardini, Matteo
Krueger, Frank
Raymont, Vanessa
Grafman, Jordan
TI Ventromedial prefrontal cortex modulates fatigue after penetrating
traumatic brain injury
SO NEUROLOGY
LA English
DT Article
ID MULTIPLE-SCLEROSIS; MACAQUE MONKEYS; HEAD-INJURY; DISORDERS; DEPRESSION;
REGIONS; SCALE; RAT; MRI
AB Background: Fatigue is a common and disabling symptom in neurologic disorders including traumatic penetrating brain injury (PBI). Despite fatigue's prevalence and impact on quality of life, its pathophysiology is not understood. Studies on effort perception in healthy subjects, animal behavioral paradigms, and recent evidence in different clinical populations suggest that ventromedial prefrontal cortex could play a significant role in fatigue pathophysiology in neurologic conditions.
Methods: We enrolled 97 PBI patients and 37 control subjects drawn from the Vietnam Head Injury Study registry. Fatigue was assessed with a self-report questionnaire and a clinician-rated instrument; lesion location and volume were evaluated on CT scans. PBI patients were divided in 3 groups according to lesion location: a nonfrontal lesion group, a ventromedial prefrontal cortex lesion (vmPFC) group, and a dorso/lateral prefrontal cortex (d/lPFC) group. Fatigue scores were compared among the 3 PBI groups and the healthy controls.
Results: Individuals with vmPFC lesions were significantly more fatigued than individuals with d/lPFC lesions, individuals with nonfrontal lesions, and healthy controls, while these 3 latter groups were equally fatigued. VmPFC volume was correlated with fatigue scores, showing that the larger the lesion volume, the higher the fatigue scores.
Conclusions: We demonstrated that ventromedial prefrontal cortex lesion (vmPFC) plays a critical role in penetrating brain injury-related fatigue, providing a rationale to link fatigue to different vmPFC functions such as effort and reward perception. The identification of the anatomic and cognitive basis of fatigue can contribute to developing pathophysiology-based treatments for this disabling symptom. Neurology (R) 2010; 74: 749-754
C1 [Pardini, Matteo; Krueger, Frank; Raymont, Vanessa; Grafman, Jordan] NINCDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Pardini, Matteo] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy.
[Krueger, Frank] George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA 22030 USA.
[Raymont, Vanessa] Natl Naval Med Ctr, Vietnam Head Injury Study, Henry M Jackson Fdn, Bethesda, MD USA.
RP Grafman, J (reprint author), NINCDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA.
EM GrafmanJ@ninds.nih.gov
RI Pardini, Matteo/F-8414-2010;
OI Pardini, Matteo/0000-0002-4740-1982; Grafman, Jordan
H./0000-0001-8645-4457
FU NIH/National Institute of Neurological Disorders and Stroke/CNS; Henry
M. Jackson Foundation [DAMD17-01-1-0675]; NIH/NINDS
FX Supported by the Intramural Research Program of the NIH/National
Institute of Neurological Disorders and Stroke/CNS and project grant
from the United States Army Medical Research and Material Command and
administered by the Henry M. Jackson Foundation (Vietnam Head Injury
Study Phase III: A 30 Year Post-Injury Follow-Up Study: Grant number:
DAMD17-01-1-0675).; Dr. Pardini, Dr. Krueger, and Dr. Raymont report no
disclosures. Dr. Grafman serves as Coeditor of Cortex and receives
research support from the Intramural Research Program NIH/NINDS and the
Henry M. Jackson Foundation.
NR 31
TC 22
Z9 22
U1 1
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 MAR 2
PY 2010
VL 74
IS 9
BP 749
EP 754
DI 10.1212/WNL.0b013e3181d25b6b
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 562GG
UT WOS:000275037300009
PM 20194914
ER
PT J
AU Marongiu, M
Deiana, M
Meloni, A
Marcia, L
Puddu, A
Cao, A
Schlessinger, D
Crisponi, L
AF Marongiu, Mara
Deiana, Manila
Meloni, Alessandra
Marcia, Loredana
Puddu, Alessandro
Cao, Antonio
Schlessinger, David
Crisponi, Laura
TI The Forkhead Transcription Factor Foxl2 Is Sumoylated in Both Human and
Mouse: Sumoylation Affects Its Stability, Localization, and Activity
SO PLOS ONE
LA English
DT Article
ID GRANULOSA-CELLS; SEX REVERSAL; EXPRESSION; RECEPTOR; PROTEIN; SUMO-1;
SOX9; SPERMATOGENESIS; INDUCTION; REPRESSES
AB The FOXL2 forkhead transcription factor is expressed in ovarian granulosa cells, and mutated FOXL2 causes the blepharophimosis, ptosis and epicanthus inversus syndrome (BPES) and predisposes to premature ovarian failure. Inactivation of Foxl2 in mice demonstrated its indispensability for female gonadal sex determination and ovary development and revealed its antagonism of Sox9, the effector of male testis development. To help to define the regulatory activities of FOXL2, we looked for interacting proteins. Based on yeast two-hybrid screening, we found that FOXL2 interacts with PIAS1 and UBC9, both parts of the sumoylation machinery. We showed that human FOXL2 is sumoylated in transfected cell lines, and that endogenous mouse Foxl2 is comparably sumoylated. This modification changes its cellular localization, stability and transcriptional activity. It is intriguing that similar sumoylation and regulatory consequences have also been reported for SOX9, the male counterpart of FOXL2 in somatic gonadal tissues.
C1 [Marongiu, Mara; Deiana, Manila; Meloni, Alessandra; Marcia, Loredana; Puddu, Alessandro; Cao, Antonio; Crisponi, Laura] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
[Puddu, Alessandro] Univ Cagliari, Cagliari, Italy.
[Schlessinger, David] NIA, NIH, Baltimore, MD 21224 USA.
RP Marongiu, M (reprint author), CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
EM laura.crisponi@inn.cnr.it
OI MARONGIU, MARA/0000-0002-7321-2384; Puddu,
Alessandro/0000-0002-9415-0477
FU Telethon Grant [GP0049Y01]; National Institute on Aging, National
Institutes of Health (NIH)
FX This work was supported by Telethon Grant GP0049Y01 to LC and in part by
the Intramural Research Program of the National Institute on Aging,
National Institutes of Health (NIH) to DS. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 23
TC 16
Z9 16
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 2
PY 2010
VL 5
IS 3
AR e9477
DI 10.1371/journal.pone.0009477
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 562OY
UT WOS:000275063300004
PM 20209145
ER
PT J
AU Buzza, MS
Netzel-Arnett, S
Shea-Donohue, T
Zhao, AP
Lin, CY
List, K
Szabo, R
Fasano, A
Bugge, TH
Antalis, TM
AF Buzza, Marguerite S.
Netzel-Arnett, Sarah
Shea-Donohue, Terez
Zhao, Aiping
Lin, Chen-Yong
List, Karin
Szabo, Roman
Fasano, Alessio
Bugge, Thomas H.
Antalis, Toni M.
TI Membrane-anchored serine protease matriptase regulates epithelial
barrier formation and permeability in the intestine
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE claudin-2; intestinal barrier; St14; type II transmembrane serine
protease; tight junction
ID SURFACE PROTEOLYTIC-ENZYMES; INFLAMMATORY-BOWEL-DISEASE; KINASE C-ZETA;
TIGHT JUNCTIONS; CELL-LINES; EXPRESSION; ACTIVATION; CLAUDIN-2;
DIFFERENTIATION; INHIBITION
AB The intestinal epithelium serves as a major protective barrier between the mammalian host and the external environment. Here we show that the transmembrane serine protease matriptase plays a pivotol role in the formation and integrity of the intestinal epithelial barrier. St14 hypomorphic mice, which have a 100-fold reduction in intestinal matriptase mRNA levels, display a 35% reduction in intestinal transepithelial electrical resistance (TEER). Matriptase is expressed during intestinal epithelial differentiation and colocalizes with E-cadherin to apical junctional complexes (AJC) in differentiated polarized Caco-2 monolayers. Inhibition of matriptase activity using a specific peptide inhibitor or by knockdown of matriptase by siRNA disrupts the development of TEER in barrier-forming Caco-2 monolayers and increases paracellular permeability to macromolecular FITC-dextran. Loss of matriptase was associated with enhanced expression and incorporation of the permeability associated, "leaky" tight junction protein claudin-2 at intercellular junctions. Knockdown of claudin-2 enhanced the development of TEER in matriptase-silenced Caco-2 monolayers, suggesting that the reduced barrier integrity was caused, at least in part, by an inability to regulate claudin-2 expression and incorporation into junctions. We find that matriptase enhances the rate of claudin-2 protein turnover, and that this is mediated indirectly through an atypical PKC zeta-dependent signaling pathway. These results support a key role for matriptase in regulating intestinal epithelial barrier competence, and suggest an intriguing link between pericellular serine protease activity and tight junction assembly in polarized epithelia.
C1 [Buzza, Marguerite S.; Netzel-Arnett, Sarah; Antalis, Toni M.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA.
[Buzza, Marguerite S.; Netzel-Arnett, Sarah; Antalis, Toni M.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA.
[Shea-Donohue, Terez; Zhao, Aiping; Fasano, Alessio] Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA.
[Lin, Chen-Yong] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
[List, Karin] Wayne State Univ, Dept Pharmacol, Detroit, MI 48201 USA.
[List, Karin] Karmanos Canc Inst, Detroit, MI 48201 USA.
[Szabo, Roman; Bugge, Thomas H.] Natl Inst Dent & Cranofacial Res, Proteases & Tissue Remodeling Sect, NIH, Bethesda, MD 20892 USA.
RP Antalis, TM (reprint author), Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA.
EM tantalis@som.umaryland.edu
FU National Institutes of Health ( NIH): [DK081376, CA098369, HL084387,
DK48373, AI/DK49316, HL07698, CA096851]; NIH Intramural Program;
Australian National Health and Medical Research Council [384359]
FX We thank E. Smith, J. Stiltz, and R. Sun for technical assistance.
CVS-3983 was provided by Dr. Ed Madison and Corvas International ( San
Diego, CA). This work was supported in part by grants from the National
Institutes of Health ( NIH): DK081376, CA098369, and HL084387 ( to T. M.
A.); DK48373 ( to A. F.); AI/DK49316 ( to T. S. D.); HL07698 ( to
S.N.A.); CA096851 ( to . Y.L.) and the NIH Intramural Program ( T. H.
B.). M. B. was supported by Australian National Health and Medical
Research Council CJ Martin Fellowship 384359.
NR 28
TC 79
Z9 79
U1 0
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 MAR 2
PY 2010
VL 107
IS 9
BP 4200
EP 4205
DI 10.1073/pnas.0903923107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563KP
UT WOS:000275131100047
PM 20142489
ER
PT J
AU Yim, YI
Sun, T
Wu, LG
Raimondi, A
De Camilli, P
Eisenberg, E
Greene, LE
AF Yim, Yang-In
Sun, Tao
Wu, Ling-Gang
Raimondi, Andrea
De Camilli, Pietro
Eisenberg, Evan
Greene, Lois E.
TI Endocytosis and clathrin-uncoating defects at synapses of auxilin
knockout mice
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Hsc70; gene targeting; synaptic transmission; vesicle recycling
ID G-ASSOCIATED KINASE; SYNAPTIC VESICLE ENDOCYTOSIS; KISS-AND-RUN;
MEDIATED ENDOCYTOSIS; PHOSPHOINOSITIDE METABOLISM; HIPPOCAMPAL SYNAPSES;
NERVE-TERMINALS; MULTIPLE ROLES; COATED PITS; ATPASE
AB Neuronally expressed auxilin and ubiquitously expressed cyclin-G-dependent kinase (GAK) are homologous proteins that act as cochaperones to support the Hsc70-dependent clathrin uncoating of clathrin-coated vesicles. GAK was previously shown to be essential in mouse during embryonic development and in the adult. We have now engineered an auxilin knockout mouse. Mutant mice had a high rate of early postnatal mortality and surviving pups generally had a lower body weight than wild-type pups, although they had a normal life span. GAK was up-regulated as much as 3-fold in the brains of both surviving neonates and adult mutant mice. An increased number of clathrin-coated vesicles and empty cages were present at knockout synapses both in situ and in primary neuronal cultures. Additionally, clathrin-mediated endocytosis of synaptic vesicles in knockout hippocampal neurons was impaired, most likely due to sequestration of coat components in assembled coats and cages. Collectively, our results demonstrate the specialized role of auxilin in the recycling of synaptic vesicles at synapses, but also show that its function can be partially compensated for by up-regulation of GAK.
C1 [Raimondi, Andrea; De Camilli, Pietro] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA.
[Raimondi, Andrea; De Camilli, Pietro] Yale Univ, Sch Med, Howard Hughes Med Inst, Program Cellular Neurosci Neurodegenerat & Repair, New Haven, CT 06510 USA.
[Yim, Yang-In; Eisenberg, Evan; Greene, Lois E.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Sun, Tao; Wu, Ling-Gang] NINDS, Synapt Transmiss Sect, NIH, Bethesda, MD 20892 USA.
RP De Camilli, P (reprint author), Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA.
EM pietro.decamilli@yale.edu; greenel@helix.nih.gov
FU National Institutes of Health [NS36251, DA018343]
FX We thank Dr. Chengyu Liu for assistance in making the knockout mice,
Valentina Cappello for help with electron microscopy, Dr. Mary Anne
Conti for helpful discussions, and Dr. JingPing Lin for help with the
statistical analysis. This work was supported in part by National
Institutes of Health Grants NS36251 and DA018343 to P.D.C.
NR 31
TC 31
Z9 32
U1 1
U2 9
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 MAR 2
PY 2010
VL 107
IS 9
BP 4412
EP 4417
DI 10.1073/pnas.1000738107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 563KP
UT WOS:000275131100083
PM 20160091
ER
PT J
AU Passwell, JH
Ashkenzi, S
Banet-Levi, Y
Ramon-Saraf, R
Farzam, N
Lerner-Geva, L
Even-Nir, H
Yerushalmi, B
Chu, CY
Shiloach, J
Robbins, JB
Schneerson, R
AF Passwell, Justen H.
Ashkenzi, Shai
Banet-Levi, Yonit
Ramon-Saraf, Reut
Farzam, Nahid
Lerner-Geva, Liat
Even-Nir, Hadas
Yerushalmi, Baruch
Chu, Chiayung
Shiloach, Joseph
Robbins, John B.
Schneerson, Rachel
CA Israeli Shigella Study Grp
TI Age-related efficacy of Shigella O-specific polysaccharide conjugates in
1-4-year-old Israeli children
SO VACCINE
LA English
DT Article
DE Shigellosis; Vaccines; Efficacy; Age-related
ID VACCINE DEVELOPMENT; DYSENTERIAE TYPE-1; ESCHERICHIA-COLI; FLEXNERI
TYPE-2A; IMMUNOGENICITY; SONNEI; ANTIBODIES; SAFETY; LIPOPOLYSACCHARIDE;
ANTIGENS
AB Background: Despite its high worldwide morbidity and mortality, there is yet no licensed vaccine for shigellosis. We reported the safety and immunogenicity of Shigella O-specific polysaccharide-protein conjugates in adults and young children and efficacy ofShigella sonnei conjugate in young adults.
Methods: A double-blinded, randomized and vaccine-controlled Phase3 evaluation of S. sonnei and Shigella flexneri 2a O-SP-rEPA conjugates, 25 mu Lg, injected IM twice, 6 weeks apart, into healthy 1 -4 years old, is reported. The children were followed for 2 years by telephone every other week and stool cultures were obtained for each episode of acute diarrhea (>= 3 loose stools/day or a bloody/mucous stool). Sera were taken randomly from 10% of the participants for IgG anti-LPS and anti-carrier levels.
Results: Of the 2799 enrollees, 1433 received S. sonnei and 1366 S. flexneri 2a conjugates; 2699 (96.4%) completed the 2-year follow-up. Local reactions occurred in similar to 5% and similar to 4% had temperatures >= 38.0 degrees C lasting 1-2 days. There were no serious adverse events attributable to the vaccines. Of the 3295 stool cultures obtained, 125 yielded S. sonnei and 21 S. flexneri 2a. Immunogenicity and efficacy were age-related. The overall efficacy of the S. sonnei conjugate was 27.5%; 71.1% (P= 0.043) in the 3-4 years old. The numbers for S.flexneri 2a were too few for meaningful analysis. Cross-protection by S.flexneri 2a for non-vaccine S. flextierl types was found, but the numbers were too few for statistical significance. There was an age-related rise of vaccine-specific IgG anti-LPS in both groups, peaking at about 10 weeks and declining thereafter, but remaining >= 4-fold higher than in the controls 2 years after the second dose.
Conclusions: Shigella conjugates are safe and immunogenic in 1-4 years old. The S. sonnei conjugate elicited 71.1% efficacy in the 3-4 years old and can be predicted to be efficacious in individuals older than 3 years of age. These results urge studies with our improved conjugates. Published by Elsevier Ltd.
C1 [Chu, Chiayung; Robbins, John B.; Schneerson, Rachel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Passwell, Justen H.; Banet-Levi, Yonit; Ramon-Saraf, Reut; Farzam, Nahid; Even-Nir, Hadas] Safra Childrens Hosp, Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel.
[Ashkenzi, Shai] Schneider Childrens Med Ctr, IL-49202 Petah Tiqwa, Israel.
[Lerner-Geva, Liat] Gertner Inst Epidemiol & Hlth Policy Res, IL-52621 Tel Hashomer, Israel.
[Yerushalmi, Baruch] Soroka Med Ctr, Saban Pediat Ctr, IL-84141 Beer Sheva, Israel.
[Shiloach, Joseph] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Schneerson, R (reprint author), NICHD, NIH, PDMI, 31 Ctr Dr,Room 2A29, Bethesda, MD 20892 USA.
EM schneerr@exchange.nih.gov
RI Berkun, Yackov/A-1694-2009
NR 33
TC 40
Z9 42
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD MAR 2
PY 2010
VL 28
IS 10
BP 2231
EP 2235
DI 10.1016/j.vaccine.2009.12.050
PG 5
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 573RZ
UT WOS:000275933600013
PM 20056180
ER
PT J
AU Pierce, MA
Ellis, RD
Martin, LB
Malkin, E
Tierney, E
Miura, K
Fay, MP
Marjason, J
Elliott, SL
Mullen, GED
Rausch, K
Zhu, DM
Long, CA
Miller, LH
AF Pierce, Mark A.
Ellis, Ruth D.
Martin, Laura B.
Malkin, Elissa
Tierney, Eveline
Miura, Kazutoyo
Fay, Michael P.
Marjason, Joanne
Elliott, Suzanne L.
Mullen, Gregory E. D.
Rausch, Kelly
Zhu, Daming
Long, Carole A.
Miller, Louis H.
TI Phase 1 safety and immunogenicity trial of the Plasmodium falciparum
blood-stage malaria vaccine AMA1-C1/ISA 720 in Australian adults
SO VACCINE
LA English
DT Article
DE AMA1; Malaria; ISA 720
ID APICAL MEMBRANE ANTIGEN-1; MONTANIDE ISA 720; RANDOMIZED
CONTROLLED-TRIAL; CLINICAL-TRIAL; IN-VITRO; CANDIDATE; ADJUVANT;
CHILDREN; ANTIBODIES; EFFICACY
AB A Phase I trial was conducted in malaria-naive adults to evaluate the recombinant protein vaccine apical membrane antigen I -Combination 1 (AMA1-C1) formulated in Montanide (R) ISA 720 (SEPPIC, France), a water-in-oil adjuvant. Vaccinations were halted early due to a formulation issue unrelated to stability or potency. Twenty-four subjects (12 in each group) were enrolled and received 5 or 20 mu g protein at 0 and 3 months and four subjects were enrolled and received one vaccination of 80 mu g protein. After first vaccination, nearly all subjects experienced mild to moderate local reactions and six experienced delayed local reactions occurring at Day 9 or later. After the second vaccination, three subjects experienced transient grade 3 (severe) local reactions; the remainder experienced grade I or 2 local reactions. All related systemic reactogenicity was grade 1 or 2, except one instance ofgrade 3 malaise. Anti-AMA1-C1 antibody responses were dose dependent and seen following each vaccination, with mean antibody levels 2-3 fold higher in the 20 mu g group compared to the 5 mu g group at most time points. In vitro growth-inhibitory activity was a function of the anti-AMA1 antibody titer. AMA1-C1 formulated in ISA 720 is immunogenic in malaria-naive Australian adults. It is reasonably tolerated, though some transient, severe, and late local reactions are seen. Published by Elsevier Ltd.
C1 [Pierce, Mark A.; Ellis, Ruth D.; Martin, Laura B.; Miura, Kazutoyo; Mullen, Gregory E. D.; Rausch, Kelly; Zhu, Daming; Miller, Louis H.] NIAID, MVDB, NIH, Rockville, MD 20852 USA.
[Malkin, Elissa; Tierney, Eveline] PATH Malaria Vaccine Initiat, Bethesda, MD USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Rockville, MD 20852 USA.
[Marjason, Joanne; Elliott, Suzanne L.] Q Pharm Pty Ltd, Brisbane, Qld, Australia.
[Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Ellis, RD (reprint author), NIAID, MVDB, NIH, Twinbrook 1,Room 1119,5640 Fishers Lane, Rockville, MD 20852 USA.
EM ellisru@niaid.nih.gov
RI Martin, Laura/N-1789-2013;
OI Martin, Laura/0000-0002-4431-4381; Fay, Michael P./0000-0002-8643-9625
FU Intramural NIH HHS [Z01 AI001005-01, Z99 AI999999, ZIA AI001005-03]
NR 31
TC 21
Z9 22
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD MAR 2
PY 2010
VL 28
IS 10
BP 2236
EP 2242
DI 10.1016/j.vaccine.2009.12.049
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 573RZ
UT WOS:000275933600014
PM 20051276
ER
PT J
AU Guo, DL
Myrdal, PB
Karlage, KL
O'Connell, SP
Wissinger, TJ
Tabibi, SE
Yalkowsky, SH
AF Guo, Duoli
Myrdal, Paul B.
Karlage, Kelly L.
O'Connell, Sean P.
Wissinger, Travis J.
Tabibi, S. Esmail
Yalkowsky, Samuel H.
TI Stability of 5-Fluoro-2 '-deoxycytidine and Tetrahydrouridine in
Combination
SO AAPS PHARMSCITECH
LA English
DT Article
DE degradation mechanism; FdCyd; NSC-112907; NSC-48006; THU
ID METHYLTRANSFERASE INHIBITOR 5-FLUORO-2'-DEOXYCYTIDINE; CYTIDINE
DEAMINASE; METABOLISM; MICE
AB In vivo, the DNA methyltransferase inhibitor, 5-fluoro-2'-deoxycytidine (FdCyd, NSC-48006), is rapidly converted to its unwanted metabolites. Tetrahydrouridine (THU, NSC-112907), a cytidine deaminase inhibitor can block the first metabolic step in FdCyd catabolism. Clinical studies have shown that co-administration with THU can inhibit the metabolism of FdCyd. The National Cancer Institute is particularly interested in a 1:5 FdCyd/THU formulation. The purpose of this study was to investigate the in vitro pH stability of FdCyd and THU individually and in combination. A stability-indicating high-performance liquid chromatography method for the quanti. cation of both compounds and their degradants was developed using a ZIC (R)-HILIC column. The effect of THU and FdCyd on the in vitro degradation of each other was studied as a function of pH from 1.0 to 7.4 in aqueous solutions at 37 degrees C. The degradation of FdCyd appears to be first-order and acid-catalyzed. THU equilibrates with at least one of its degradants. The combination of FdCyd and THU in solution does not affect the stability of either compound. The stability and compatibility of FdCyd and THU in the solid state at increased relative humidity and at various temperatures are also evaluated.
C1 [Guo, Duoli; Myrdal, Paul B.; Karlage, Kelly L.; O'Connell, Sean P.; Wissinger, Travis J.; Yalkowsky, Samuel H.] Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA.
[Tabibi, S. Esmail] NCI, Pharmaceut Resources Branch, Bethesda, MD 20892 USA.
RP Guo, DL (reprint author), Univ Arizona, Coll Pharm, 1703 E Mabel, Tucson, AZ 85721 USA.
EM guod@pharmacy.arizona.edu
FU National Cancer Institute [N01-CM-27142]
FX This work was supported by National Cancer Institute under the contract
N01-CM-27142.
NR 5
TC 6
Z9 7
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1530-9932
J9 AAPS PHARMSCITECH
JI AAPS PharmSciTech
PD MAR
PY 2010
VL 11
IS 1
BP 247
EP 252
DI 10.1208/s12249-010-9383-2
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 612SC
UT WOS:000278921800031
PM 20151336
ER
PT J
AU Lehner, T
Insel, T
AF Lehner, Thomas
Insel, Thomas
TI Psychiatric Education in the Genomic Era
SO ACADEMIC PSYCHIATRY
LA English
DT Editorial Material
ID GENETICS
C1 [Lehner, Thomas] NIMH, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA.
RP Lehner, T (reprint author), NIMH, Div Neurosci & Basic Behav Sci, NIH, 6001 Execut Blvd,Rm 7189,MSC 9643, Bethesda, MD 20892 USA.
EM tlehner@mail.nih.gov
NR 15
TC 4
Z9 4
U1 1
U2 2
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1042-9670
J9 ACAD PSYCHIATR
JI Acad. Psych.
PD MAR-APR
PY 2010
VL 34
IS 2
BP 87
EP 89
PG 3
WC Education & Educational Research; Psychiatry
SC Education & Educational Research; Psychiatry
GA 567GX
UT WOS:000275434500002
PM 20224010
ER
PT J
AU Bluemke, DA
AF Bluemke, David A.
TI Magnetic Fields and the Brain at High Field Strengths What Do We Know?
SO ACADEMIC RADIOLOGY
LA English
DT Editorial Material
C1 Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA.
RP Bluemke, DA (reprint author), Natl Inst Biomed Imaging & Bioengn, 10 Ctr Dr,Room 10-1C355, Bethesda, MD 20892 USA.
EM bluemked@nih.gov
OI Bluemke, David/0000-0002-8323-8086
FU Intramural NIH HHS [ZIA CL090019-01, ZIA EB000072-01]
NR 4
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 1076-6332
J9 ACAD RADIOL
JI Acad. Radiol.
PD MAR
PY 2010
VL 17
IS 3
BP 269
EP 270
DI 10.1016/j.acra.2009.12.008
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 564RX
UT WOS:000275235500001
PM 20152723
ER
PT J
AU Ouimet, MC
Simons-Morton, BG
Zador, PL
Lerner, ND
Freedman, M
Duncan, GD
Wang, J
AF Ouimet, Marie Claude
Simons-Morton, Bruce G.
Zador, Paul L.
Lerner, Neil D.
Freedman, Mark
Duncan, Glen D.
Wang, Jing
TI Using the US National Household Travel Survey to estimate the impact of
passenger characteristics on young drivers' relative risk of fatal crash
involvement
SO ACCIDENT ANALYSIS AND PREVENTION
LA English
DT Article
DE Fatality; Crash risk; Adolescents; Young drivers; Passengers; Gender
ID QUASI-INDUCED EXPOSURE; TEENAGE PASSENGERS; VEHICLE; DEATHS; INJURY;
GENDER
AB Motor vehicle crashes are the main cause of morbidity and mortality in teenagers and young adults in the United States. Driving exposure and passenger presence, which can both vary by driver and passenger characteristics, are known to influence crash risk. Some studies have accounted for driving exposure in calculating young driver fatal crash risk in the presence of passengers, but none have estimated crash risk by driver sex and passenger age and sex. One possible reason for this gap is that data collection on driving exposure often precludes appropriate analyses. The purpose of this study was to examine, per 10 million vehicle trips (VT) and vehicle-miles traveled (VMT), the relative risk of fatal crash involvement in 15-20-year-old male and female drivers as a function of their passenger's age and sex, using solo driving as the referent. The Fatality Analysis Reporting System provided fatal motor vehicle crash data from 1999 to 2003 and the 2001 National Household Travel Survey (NHTS) provided VT and VMT. The NHTS collects driving exposure for both household and non-household members (e.g., friends. colleagues), but demographic characteristics only on household members. Missing age and sex of non-household passengers were imputed with hot deck using information from household passengers' trips with non-household drivers, thereby enabling the calculation of crash rate and relative risk estimates based upon driver and passenger characteristics. Using this approach, the highest risk was found for young male drivers with 16-20-year-old passengers (relative risk [RR] per 10 million VT = 7.99: 95% confidence interval [CI], 7.34-8.69: RR per 10 million VMT = 9.94; 95% CI, 9.13-10.81). Relative risk was also high for 21-34-year-old passengers, again particularly when both drivers and passengers were male. These effects warrant further investigation and underscore the importance of considering driving exposure by passenger characteristics in understanding crash risk. Additionally, as all imputation techniques are imperfect, a more accurate estimation of U.S. fatal crash risk per distance driven would require national surveys to collect data on non-household passenger characteristics. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Ouimet, Marie Claude] Univ Sherbrooke, Fac Med & Hlth Sci, Longueuil, PQ J4K 0A8, Canada.
[Ouimet, Marie Claude; Simons-Morton, Bruce G.; Wang, Jing] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[Zador, Paul L.; Lerner, Neil D.; Freedman, Mark] WESTAT Corp, Rockville, MD 20850 USA.
RP Ouimet, MC (reprint author), Univ Sherbrooke, Fac Med & Hlth Sci, 150 Charles Le Moyne PL,Room 200, Longueuil, PQ J4K 0A8, Canada.
EM Marie.Claude.Ouimet@USherbrooke.ca
OI Simons-Morton, Bruce/0000-0003-1099-6617
FU Intramural NIH HHS [ZIA HD001707-11]; NICHD NIH HHS [263-HD-510791]
NR 30
TC 40
Z9 41
U1 1
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0001-4575
J9 ACCIDENT ANAL PREV
JI Accid. Anal. Prev.
PD MAR
PY 2010
VL 42
IS 2
BP 689
EP 694
DI 10.1016/j.aap.2009.10.017
PG 6
WC Ergonomics; Public, Environmental & Occupational Health; Social
Sciences, Interdisciplinary; Transportation
SC Engineering; Public, Environmental & Occupational Health; Social
Sciences - Other Topics; Transportation
GA 568GO
UT WOS:000275510600043
PM 20159095
ER
PT J
AU Ma, BY
Tsai, CJ
Pan, YP
Nussinov, R
AF Ma, Buyong
Tsai, Chung-Jung
Pan, Yongping
Nussinov, Ruth
TI Why Does Binding of Proteins to DNA or Proteins to Proteins Not
Necessarily Spell Function?
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID LATENT EVOLUTIONARY POTENTIALS; ESTROGEN-RECEPTOR;
CONFORMATIONAL-CHANGES; MOLECULAR-DYNAMICS; FOLDING FUNNELS; NETWORK
MOTIFS; ALLOSTERY; ENZYME; SPECIFICITY; COMPLEX
AB Studies of binding are often question: first, is the observed binding functional, and second, if it is, which function? Is it activation or repression? The first question relates to binding at different sites; the second relates to binding at similar sites. These questions apply to transcription factors binding to genomic DNA and to protein interaction domains binding to their partners. Here, we explain that both can be understood in terms of allostery and the cellular (or in vitro) environment. The idea is simple yet powerful; it emphasizes the role of allostery in defining whether binding between transcription factors and (cognate or noncognate) DNA sequences will lead to function and to the type of function. Allosteric effects are the outcome of dynamically shifting populations; thus binding to even slightly different DNA sequences will lead to different transcription factor conformations that can be reflected in the binding sites to their co-regulators. Currently, allostery is not considered when trying to understand how binding phenomena determine the functional outcome. Allosteric effects can enhance the binding specificity in a function-oriented manner. Here we provide a biological rationale that considers cellular crowding effects.
C1 [Ma, Buyong; Tsai, Chung-Jung; Pan, Yongping; Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
EM ruthnu@helix.nih.gov
RI Ma, Buyong/F-9491-2011
OI Ma, Buyong/0000-0002-7383-719X
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with Federal funds from
the National Cancer Institute, National Institutes of Health, under
contract number 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
NR 58
TC 22
Z9 22
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD MAR
PY 2010
VL 5
IS 3
BP 265
EP 272
DI 10.1021/cb900293a
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 569VA
UT WOS:000275629200002
PM 20151694
ER
PT J
AU Robbins, AH
Coman, RM
Bracho-Sanchez, E
Fernandez, MA
Gilliland, CT
Li, M
Agbandje-McKenna, M
Wlodawer, A
Dunn, BM
McKenna, R
AF Robbins, Arthur H.
Coman, Roxana M.
Bracho-Sanchez, Edith
Fernandez, Marty A.
Gilliland, C. Taylor
Li, Mi
Agbandje-McKenna, Mavis
Wlodawer, Alexander
Dunn, Ben M.
McKenna, Robert
TI Structure of the unbound form of HIV-1 subtype A protease: comparison
with unbound forms of proteases from other HIV subtypes
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID NON-B-SUBTYPES; DRUG-RESISTANCE; X-RAY; C PROTEASE;
REVERSE-TRANSCRIPTASE; CRYSTAL-STRUCTURE; GENETIC SUBTYPES; MOLECULAR
EPIDEMIOLOGY; ANTIRETROVIRAL THERAPY; INHIBITOR RESISTANCE
AB The crystal structure of the unbound form of HIV-1 subtype A protease (PR) has been determined to 1.7 angstrom resolution and refined as a homodimer in the hexagonal space group P6(1) to an R(cryst) of 20.5%. The structure is similar in overall shape and fold to the previously determined subtype B, C and F PRs. The major differences lie in the conformation of the flap region. The flaps in the crystal structures of the unbound subtype B and C PRs, which were crystallized in tetragonal space groups, are either semi-open or wide open. In the present structure of subtype A PR the flaps are found in the closed position, a conformation that would be more anticipated in the structure of HIV protease complexed with an inhibitor. The amino-acid differences between the subtypes and their respective crystal space groups are discussed in terms of the differences in the flap conformations.
C1 [Robbins, Arthur H.; Coman, Roxana M.; Bracho-Sanchez, Edith; Fernandez, Marty A.; Gilliland, C. Taylor; Agbandje-McKenna, Mavis; Dunn, Ben M.; McKenna, Robert] Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
[Li, Mi] SAIC Frederick, Basic Res Program, Frederick, MD USA.
[Li, Mi; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA.
RP Dunn, BM (reprint author), Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
EM bdunn@ufl.edu; rmckenna@ufl.edu
FU US Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; NIH [AI-28571, HHSN2612008000001E]; National
Cancer Institute; Center for Cancer Research
FX We acknowledge the use of beamline 22-ID of the Southeast Regional
Collaborative Access Team (SER-CAT) located at the Advanced Photon
Source, Argonne National Laboratory. Use of the APS was supported by the
US Department of Energy, Office of Science, Office of Basic Energy
Sciences under Contract No. W-31-109-Eng-38. This project was supported
in part by NIH grant AI-28571 to BMD, in part by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research (AW) and in part by Federal funds from the National Cancer
Institute, NIH under Contract No. HHSN2612008000001E (ML). The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does the mention of
trade names, commercial products
NR 65
TC 14
Z9 14
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0907-4449
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD MAR
PY 2010
VL 66
BP 233
EP 242
DI 10.1107/S0907444909054298
PN 3
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 555SX
UT WOS:000274536400002
PM 20179334
ER
PT J
AU Munasinghe, JP
Banerjee, M
Acosta, MT
Banks, M
Heffer, A
Silva, AC
Koretsky, A
Theodore, WH
AF Munasinghe, J. P.
Banerjee, M.
Acosta, M. T.
Banks, M.
Heffer, A.
Silva, A. C.
Koretsky, A.
Theodore, W. H.
TI Arterial spin labeling demonstrates that focal amygdalar glutamatergic
agonist infusion leads to rapid diffuse cerebral activation
SO ACTA NEUROLOGICA SCANDINAVICA
LA English
DT Article
DE glutamate receptors; KA; ATPA; AMPA; MRI; CBF; seizures
ID TEMPORAL-LOBE EPILEPSY; GENERALIZED STATUS EPILEPTICUS; REGIONAL
NEURONAL DAMAGE; GLUR5 KAINATE RECEPTORS; BLOOD-FLOW; KAINIC ACID;
STRUCTURAL ALTERATIONS; IMAGING ABNORMALITIES; ANESTHETIZED RATS;
SEIZURES
AB Objectives - To investigate acute effects of intra-amygdalar excitatory amino acid administration on blood flow, relaxation time and apparent diffusion coefficient in rat brain. Materials and methods - Several days after MR-compatible cannula placement in right basolateral amygdala, anesthetized rats were imaged at 7 T. Relative cerebral blood flow (CBF) was measured before and 60 min after infusion of 10 nmol KA, cAMPA, ATPA, or normal saline using arterial spin labeling. Quantitative T(2) and diffusion-weighted images were acquired. rCBF, T(2) and ADC values were evaluated in bilateral basolateral amygdala, hippocampus, basal ganglia, frontal and parietal regions. Results KA led to the highest, and ATPA lowest bilateral rCBF increases. Time courses varied among drugs. T(2) for KA and AMPA was higher while ADC was lower for KA. Conclusions - Intra-amygdalar injection of GluR agonists evoked bilateral seizure activity and increased rCBF, greater for KA and AMPA than selective ATPA GluR5 activation.
C1 [Acosta, M. T.; Theodore, W. H.] Natl Inst Neurol Disorders & Stroke, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
[Munasinghe, J. P.; Heffer, A.; Silva, A. C.; Koretsky, A.] Natl Inst Neurol Disorders & Stroke, MRI Res Facil, Bethesda, MD 20892 USA.
[Banerjee, M.; Acosta, M. T.; Banks, M.] Natl Inst Neurol Disorders & Stroke, Epilepsy Res Sect, Bethesda, MD 20892 USA.
[Heffer, A.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Theodore, WH (reprint author), Natl Inst Neurol Disorders & Stroke, Clin Epilepsy Sect, NIH, Bldg 10,Room 5N-250, Bethesda, MD 20892 USA.
EM theodorw@ninds.nih.gov
RI Silva, Afonso/A-7129-2009; Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU Intramural NIH HHS [Z01 NS002236-32]
NR 36
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-6314
J9 ACTA NEUROL SCAND
JI Acta Neurol. Scand.
PD MAR
PY 2010
VL 121
IS 3
BP 209
EP 216
DI 10.1111/j.1600-0404.2009.01188.x
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 548TV
UT WOS:000273991300011
PM 19951270
ER
PT J
AU Racz, GZ
Bori, E
Foldes, A
Demeter, I
Toth, M
Qi, S
Varga, G
AF Racz, G. Z.
Bori, E.
Foldes, A.
Demeter, I
Toth, M.
Qi, S.
Varga, G.
TI Toward an artificial salivary gland to treat xerostomia
SO ACTA PHYSIOLOGICA HUNGARICA
LA English
DT Meeting Abstract
C1 [Racz, G. Z.; Bori, E.; Foldes, A.; Demeter, I; Varga, G.] Semmelweis Univ, Dept Oral Biol, H-1085 Budapest, Hungary.
[Toth, M.] Semmelweis Univ, Dept Hlth Sci & Sports Med, H-1085 Budapest, Hungary.
[Qi, S.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AKADEMIAI KIADO RT
PI BUDAPEST
PA PRIELLE K U 19, PO BOX 245,, H-1117 BUDAPEST, HUNGARY
SN 0231-424X
J9 ACTA PHYSIOL HUNG
JI Acta Physiol. Hung.
PD MAR
PY 2010
VL 97
IS 1
BP 130
EP 130
PG 1
WC Physiology
SC Physiology
GA 570AU
UT WOS:000275644800100
ER
PT J
AU Wu, LT
Pan, JJ
Yang, CM
Reeve, BB
Blazer, DG
AF Wu, Li-Tzy
Pan, Jeng-Jong
Yang, Chongming
Reeve, Bryce B.
Blazer, Dan G.
TI An item response theory analysis of DSM-IV criteria for hallucinogen
abuse and dependence in adolescents
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Differential item functioning; Ecstasy; Hallucinogen use disorder; Item
response theory; MDMA
ID NATIONAL EPIDEMIOLOGIC SURVEY; USE DISORDERS; MDMA
3,4-METHYLENEDIOXYMETHAMPHETAMINE; CANNABIS ABUSE; DRUG-ABUSE; ALCOHOL;
METHAMPHETAMINE; ECSTASY; USERS
AB Aim: This study applied both item response theory (IRT) and multiple indicators-multiple causes (MIMIC) methods to evaluate item-level psychometric properties of diagnostic questions for hallucinogen use disorders (HUDs), differential item functioning (DIF), and predictors of latent HUD.
Methods: Data were drawn from 2004-2006 National Surveys on Drug Use and Health. Analyses were based on 1548 past-year hallucinogen users aged 12-17 years. Substance use and symptoms were assessed by audio computer-assisted self-interviewing methods.
Results: Abuse and dependence criteria empirically were arrayed along a single continuum of severity. All abuse criteria indicated middle-to-high severity on the IRT-defined HUD continuum, while dependence criteria captured a wider range from the lowest (tolerance and time spent) to the highest (taking larger amounts and inability to cut down) severity levels. There was indication of DIF by hallucinogen users' age, gender, race/ethnicity, and ecstasy use status. Adjusting for DIF, ecstasy users (vs. non-ecstasy hallucinogen users), females (vs. males), and whites (vs. Hispanics) exhibited increased odds of HUD.
Conclusions: Symptoms of hallucinogen abuse and dependence empirically do not reflect two discrete conditions in adolescents. Trends and problems related to hallucinogen use among girls and whites should be examined further to inform the designs of effective gender-appropriate and culturally sensitive prevention programs. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Wu, Li-Tzy; Blazer, Dan G.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Sch Med,Duke Clin Res Inst, Durham, NC 27710 USA.
[Pan, Jeng-Jong] Vet Hlth Adm, Washington, DC 20420 USA.
[Yang, Chongming] Duke Univ, Social Sci Res Inst, Durham, NC 27705 USA.
[Reeve, Bryce B.] NCI, Bethesda, MD 20814 USA.
RP Wu, LT (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Sch Med,Duke Clin Res Inst, Box 3419, Durham, NC 27710 USA.
EM litzy.wu@duke.edu
FU National Institute on Drug Abuse of the National Institutes of Health
[R01DA019623, R01DA019901]
FX This work was supported by research grants from the National Institute
on Drug Abuse of the National Institutes of Health (R01DA019623 and
R01DA019901; Principal investigator Li-Tzy Wu). The sponsoring agency
had no further role in study design and analysis. in the writing of the
report, and in the decision to submit the paper for publication, The
opinions expressed in this paper are solely those of the authors.
NR 30
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U1 2
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD MAR
PY 2010
VL 35
IS 3
BP 273
EP 277
DI 10.1016/j.addbeh.2009.10.009
PG 5
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 552BV
UT WOS:000274262500017
PM 19896773
ER
PT J
AU Ernst, M
Luckenbaugh, DA
Moolchan, ET
Temple, VA
Jennessa, J
Korelitz, KE
London, ED
Kimes, AS
AF Ernst, Monique
Luckenbaugh, David A.
Moolchan, Eric T.
Temple, Veronica A.
Jennessa, Jessica
Korelitz, Katherine E.
London, Edythe D.
Kimes, Alane S.
TI Decision-making and facial emotion recognition as predictors of
substance-use initiation among adolescents
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Smoking; Alcohol; Marijuana; Adolescent development; Drug
experimentation
ID PREFRONTAL CORTEX; ALCOHOL-USE; ADULTS
AB This 4-year longitudinal study examined whether performance on a decision-making task and an emotion-processing task predicted the initiation of tobacco, marijuana, or alcohol use among 77 adolescents. Of the participants, 64% met criteria for an externalizing behavioral disorder; 33% did not initiate substance use; 13% used one of the three substances under investigation, 18% used two, and 36% used all three. Initiation of substance use was associated with enhanced recognition of angry emotion. but not with risky decision-making. In conclusion, adolescents who initiate drug use present vulnerability in the form of bias towards negative emotion but not toward decisions that involve risk. (C) 2009 Published by Elsevier Ltd.
C1 [Ernst, Monique; Luckenbaugh, David A.; Temple, Veronica A.; Jennessa, Jessica; Korelitz, Katherine E.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Moolchan, Eric T.; Kimes, Alane S.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[London, Edythe D.] Univ Calif Los Angeles, Semel Inst, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[London, Edythe D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA.
RP Ernst, M (reprint author), Bldg 15K,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ernstm@mail.nih.gov
RI Reis, Aline/G-9573-2012
FU National Institute of Mental Health; National Institute on Drug Abuse;
Philip Morris
FX Funding comes from the Intramural Research Program of the National
Institute of Mental Health and the National Institute on Drug Abuse.
Work by Dr. London was supported in part by a grant to UCLA from Philip
Morris which has no involvement with the design, collection, analyses,
or interpretation of data, writing the manuscript or the decision to
submit the manuscript for publication.
NR 12
TC 9
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U1 5
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD MAR
PY 2010
VL 35
IS 3
BP 286
EP 289
DI 10.1016/j.addbeh.2009.10.014
PG 4
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 552BV
UT WOS:000274262500020
PM 19914005
ER
PT J
AU Pringle, B
Chambers, D
Wang, PS
AF Pringle, Beverly
Chambers, David
Wang, Philip S.
TI Toward Enough of the Best for All: Research to Transform the Efficacy,
Quality, and Reach of Mental Health Care for Youth
SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES
RESEARCH
LA English
DT Editorial Material
ID DISORDERS
C1 [Pringle, Beverly; Chambers, David] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
[Wang, Philip S.] NIMH, Off Director, Bethesda, MD 20892 USA.
RP Pringle, B (reprint author), NIMH, Div Serv & Intervent Res, Room 7165,Mail Stop 9631,6001 Execut Blvd, Bethesda, MD 20892 USA.
EM bpringle@mail.nih.gov; dchamber@mail.nih.gov; wangphi@mail.nih.gov
NR 17
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U1 1
U2 3
PU MAIK NAUKA/INTERPERIODICA/SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA
SN 0894-587X
J9 ADM POLICY MENT HLTH
JI Adm. Policy. Ment. Health
PD MAR
PY 2010
VL 37
IS 1-2
SI SI
BP 191
EP 196
DI 10.1007/s10488-010-0266-3
PG 6
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 602AJ
UT WOS:000278110200029
PM 20112059
ER
PT J
AU Gallagher, AR
Germino, GG
Somlo, S
AF Gallagher, Anna Rachel
Germino, Gregory G.
Somlo, Stefan
TI Molecular Advances in Autosomal Dominant Polycystic Kidney Disease
SO ADVANCES IN CHRONIC KIDNEY DISEASE
LA English
DT Article
DE Polycystic kidney; Cilia; Polycystin; TRP channel; GPS cleavage
AB Autosomal dominant polycystic disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. The understanding of the pathogenesis of ADPKD has advanced significantly since the discovery of the 2 causative genes, PKD1 and PKD2. Dominantly inherited gene mutations followed by somatic second-hit mutations inactivating the normal copy of the respective gene result in renal tubular cyst formation that deforms the kidney and eventually impairs its function. The respective gene products, polycystin-1 and polycystin-2, work together in a common cellular pathway. Polycystin-1, a large receptor molecule, forms a receptor-channel complex with polycystin-2, which is a cation channel belonging to the TRP family. Both polycystin proteins have been localized to the primary cilium, a nonmotile microtubule-based structure that extends from the apical membrane of tubular cells into the lumen. Here we discuss recent insights in the pathogenesis of ADPKD including the genetics of ADPKD, the properties of the respective polycystin proteins, the role of cilia, and some cell-signaling pathways that have been implicated in the pathways related to PKD1 and PKD2. (C) 2010 by the National Kidney Foundation, Inc. All rights reserved.
C1 [Germino, Gregory G.] NIDDK, NIH, Bethesda, MD 20892 USA.
Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA.
Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
RP Germino, GG (reprint author), NIDDK, NIH, MSC 2560,31 Ctr Dr,Bldg 31,Rm 9A52, Bethesda, MD 20892 USA.
EM germinogg@niddk.nih.gov; stefan.somlo@yale.edu
OI Germino, Gregory/0000-0002-3609-5588
FU NIH/NIDDK [DK51041, DK54053, DK57328]
FX Supported by grants from NIH/NIDDK including DK51041, DK54053 and
DK57328 (SS) and the Intramural Research Program of the NIH, NIDDK
(GGG).
NR 104
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U1 1
U2 10
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1548-5595
J9 ADV CHRONIC KIDNEY D
JI Adv. Chronic Kidney Dis.
PD MAR
PY 2010
VL 17
IS 2
BP 118
EP 130
DI 10.1053/j.ackd.2010.01.002
PG 13
WC Urology & Nephrology
SC Urology & Nephrology
GA V24KE
UT WOS:000208408500003
PM 20219615
ER
PT J
AU Jayachandran, M
Preston, CC
Hunter, LW
Jahangir, A
Owen, WG
Korach, KS
Miller, VM
AF Jayachandran, Muthuvel
Preston, Claudia C.
Hunter, Larry W.
Jahangir, Arshad
Owen, Whyte G.
Korach, Kenneth S.
Miller, Virginia M.
TI Loss of estrogen receptor beta decreases mitochondrial energetic
potential and increases thrombogenicity of platelets in aged female mice
SO AGE
LA English
DT Article
DE Aging; Estrogen receptors; Microparticles; Mitochondria; Platelet energy
metabolism; Procoagulant activity
ID ER-BETA; CARDIOVASCULAR-DISEASE; ELECTRON-TRANSPORT; GENE ESR2;
IN-VITRO; MICROPARTICLES; ALPHA; EXPRESSION; BLOOD; CELL
AB Platelets derived from aged (reproductively senescent) female mice with genetic deletion of estrogen receptor beta (beta ER) are more thrombogenic than those from age-matched wild-type (WT) mice. Intracellular processes contributing to this increased thrombogenicity are not known. Experiments were designed to identify subcellular localization of estrogen receptors and evaluate both glycolytic and mitochondrial energetic processes which might affect platelet activation. Platelets and blood from aged (22-24 months) WT and estrogen receptor beta knockout (beta ERKO) female mice were used in this study. Body, spleen weight, and serum concentrations of follicle-stimulating hormone and 17 beta-estradiol were comparable between WT and beta ERKO mice. Number of spontaneous deaths was greater in the beta ERKO colony (50% compared to 30% in WT) over the course of 24 months. In resting (nonactivated) platelets, estrogen receptors did not appear to colocalize with mitochondria by immunostaining. Lactate production and mitochondrial membrane potential of intact platelets were similar in both groups of mice. However, activities of NADH dehydrogenase, cytochrome bc (1) complex, and cytochrome c oxidase of the electron transport chain were reduced in mitochondria isolated from platelets from beta ERKO compared to WT mice. There were a significantly higher number of phosphatidylserine-expressing platelet-derived microvesicles in the plasma and a greater thrombin-generating capacity in beta ERKO compared to WT mice. These results suggest that deficiencies in beta ER affect energy metabolism of platelets resulting in greater production of circulating thrombogenic microvesicles and could potentially explain increased predisposition to thromboembolism in some elderly females.
C1 [Jayachandran, Muthuvel; Miller, Virginia M.] Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, Rochester, MN 55905 USA.
[Jayachandran, Muthuvel; Hunter, Larry W.; Miller, Virginia M.] Mayo Clin, Coll Med, Dept Surg, Rochester, MN 55905 USA.
[Preston, Claudia C.; Jahangir, Arshad] Mayo Clin, Coll Med, Div Cardiovasc Dis, Rochester, MN 55905 USA.
[Owen, Whyte G.] Mayo Clin, Coll Med, Div Hematol, Rochester, MN 55905 USA.
[Owen, Whyte G.] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
[Korach, Kenneth S.] Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA.
RP Jayachandran, M (reprint author), Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, 200 1st St SW, Rochester, MN 55905 USA.
EM jaya.m@mayo.edu
OI Korach, Kenneth/0000-0002-7765-418X
FU National Institutes of Health [NHLBI HL78638, NHLBI HL089542]; National
Institute of Aging [AG 21201]; American Heart Association [AHA
08-30503Z]; Mayo Foundation; Division of Intramural Research of the
NIEHS
FX This work is supported by the National Institutes of Health (NHLBI
HL78638 and NHLBI HL089542), the National Institute of Aging (AG 21201),
the American Heart Association (AHA 08-30503Z), the Mayo Foundation, and
Division of Intramural Research of the NIEHS.
NR 64
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U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
J9 AGE
JI Age
PD MAR
PY 2010
VL 32
IS 1
BP 109
EP 121
DI 10.1007/s11357-009-9119-y
PG 13
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 561GD
UT WOS:000274963000011
PM 19908165
ER
PT J
AU Blagosklonny, MV
Campisi, J
Sinclair, DA
Bartke, A
Blasco, MA
Bonner, WM
Bohr, VA
Brosh, RM
Brunet, A
DePinho, RA
Donehower, LA
Finch, CE
Finkel, T
Gorospe, M
Gudkov, AV
Hall, MN
Hekimi, S
Helfand, SL
Karlseder, J
Kenyon, C
Kroemer, G
Longo, V
Nussenzweig, A
Osiewacz, HD
Peeper, DS
Rando, TA
Rudolph, KL
Sassone-Corsi, P
Serrano, M
Sharpless, NE
Skulachev, VP
Tilly, JL
Tower, J
Verdin, E
Vijg, J
AF Blagosklonny, Mikhail V.
Campisi, Judy
Sinclair, David A.
Bartke, Andrzej
Blasco, Maria A.
Bonner, William M.
Bohr, Vilhelm A.
Brosh, Robert M., Jr.
Brunet, Anne
DePinho, Ronald A.
Donehower, Lawrence A.
Finch, Caleb E.
Finkel, Toren
Gorospe, Myriam
Gudkov, Andrei V.
Hall, Michael N.
Hekimi, Siegfried
Helfand, Stephen L.
Karlseder, Jan
Kenyon, Cynthia
Kroemer, Guido
Longo, Valter
Nussenzweig, Andre
Osiewacz, Heinz D.
Peeper, Daniel S.
Rando, Thomas A.
Rudolph, K. Lenhard
Sassone-Corsi, Paolo
Serrano, Manuel
Sharpless, Norman E.
Skulachev, Vladimir P.
Tilly, Jonathan L.
Tower, John
Verdin, Eric
Vijg, Jan
TI Impact papers on aging in 2009
SO AGING-US
LA English
DT Review
DE aging; senescence; signal transduction; genes for longevity
ID LIFE-SPAN EXTENSION; SINGLE-NUCLEOTIDE POLYMORPHISMS;
TELOMERE-DYSFUNCTIONAL MICE; STEM-CELL HOMEOSTASIS; DNA-DAMAGE RESPONSE;
DROSOPHILA-MELANOGASTER; DIETARY RESTRICTION; PROTEIN-KINASE;
GENETICALLY INTERACTS; CALORIE RESTRICTION
AB The editorial board of Aging reviews research papers published in 2009, which they believe have or will have a significant impact on aging research. Among many others, the topics include genes that accelerate aging or in contrast promote longevity in model organisms, DNA damage responses and telomeres, molecular mechanisms of life span extension by calorie restriction and pharmacologic interventions into aging. The emerging message in 2009 is that aging is not random but determined by a genetically-regulated longevity network and can be decelerated both genetically and pharmacologically.
C1 [Blagosklonny, Mikhail V.] Roswell Pk Canc Inst, Dept Cell Stress Biol, BLSC, Buffalo, NY 14263 USA.
[Campisi, Judy] Buck Inst Age Res, Novato, CA USA.
[Sinclair, David A.] Harvard Univ, Sch Med, Boston, MA USA.
[Bartke, Andrzej] So Illinois Univ, Springfield, IL USA.
[Blasco, Maria A.; Serrano, Manuel] Spanish Natl Canc Ctr, Madrid, Spain.
[Bonner, William M.; Nussenzweig, Andre] NCI, NIH, Bethesda, MD 20892 USA.
[Bohr, Vilhelm A.; Brosh, Robert M., Jr.; Gorospe, Myriam] NIA, NIH, Baltimore, MD 21224 USA.
[Brunet, Anne; Rando, Thomas A.] Stanford Univ, Stanford, CA 94305 USA.
[DePinho, Ronald A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Donehower, Lawrence A.] Baylor Coll Med, Houston, TX 77030 USA.
[Finch, Caleb E.; Longo, Valter; Tower, John] Univ So Calif, Los Angeles, CA USA.
[Finkel, Toren] NHLBI, NIH, Bethesda, MD 20892 USA.
[Hall, Michael N.] Univ Basel, Basel, Switzerland.
[Hekimi, Siegfried] McGill Univ, Montreal, PQ, Canada.
[Helfand, Stephen L.] Brown Univ, Providence, RI 02912 USA.
[Karlseder, Jan] Salk Inst Biol Studies, La Jolla, CA USA.
[Kenyon, Cynthia; Verdin, Eric] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Kroemer, Guido] INSERM, U848, Villejuif, France.
[Osiewacz, Heinz D.] Goethe Univ Frankfurt, Frankfurt, Germany.
[Peeper, Daniel S.] Netherlands Canc Inst, Amsterdam, Netherlands.
[Rudolph, K. Lenhard] Hannover Med Sch, D-3000 Hannover, Germany.
[Sassone-Corsi, Paolo] Univ Calif Irvine, Irvine, CA USA.
[Sharpless, Norman E.] Univ N Carolina, Chapel Hill, NC USA.
[Skulachev, Vladimir P.] Moscow MV Lomonosov State Univ, Moscow, Russia.
[Tilly, Jonathan L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Vijg, Jan] Albert Einstein Coll Med, Bronx, NY 10467 USA.
RP Blagosklonny, MV (reprint author), Roswell Pk Canc Inst, Dept Cell Stress Biol, BLSC, L3-312,Elm & Carlton St, Buffalo, NY 14263 USA.
EM Blagosklonny@oncotarget.com
RI Osiewacz, Heinz/D-3454-2011; Sassone-Corsi, Paolo/H-6182-2011;
Skulachev, Vladimir/J-4164-2012; Kroemer, Guido/B-4263-2013; Serrano,
Manuel/H-2634-2015; Blasco , Maria A./M-1694-2014; Bartke,
Andzej/D-6640-2017;
OI Skulachev, Vladimir/0000-0003-4886-2243; Serrano,
Manuel/0000-0001-7177-9312; Blasco , Maria A./0000-0002-4211-233X;
Bartke, Andzej/0000-0002-2569-557X; Verdin, Eric/0000-0003-3703-3183;
Sinclair, David/0000-0002-9936-436X
FU NCI NIH HHS [R01 CA084628]; NIA NIH HHS [R01 AG011833, R01 AG024353, R01
AG028730]
NR 115
TC 19
Z9 20
U1 0
U2 7
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD MAR
PY 2010
VL 2
IS 3
BP 111
EP 121
PG 11
WC Cell Biology
SC Cell Biology
GA 589AE
UT WOS:000277115300001
PM 20351400
ER
PT J
AU Schug, TT
Li, XL
AF Schug, Thaddeus T.
Li, Xiaoling
TI Surprising sirtuin crosstalk in the heart
SO AGING-US
LA English
DT Article
DE Sirtuins; insulin-like growth factor; cardiac hypertrophy
ID CALORIE RESTRICTION; OXIDATIVE STRESS; LIFE-SPAN; RESISTANCE; DISEASE;
CARDIOMYOCYTES; TRANSCRIPTION; DEACETYLASE; PROTECTS; MICE
C1 [Schug, Thaddeus T.; Li, Xiaoling] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP Schug, TT (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM schugt@niehs.nih.gov
NR 22
TC 9
Z9 10
U1 0
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD MAR
PY 2010
VL 2
IS 3
BP 129
EP 132
PG 4
WC Cell Biology
SC Cell Biology
GA 589AE
UT WOS:000277115300003
PM 20375467
ER
PT J
AU Milner, JA
Trujillo, EB
AF Milner, John A.
Trujillo, Elaine B.
TI Public Health Genomics: translating nutrigenomics research into
population health benefits
SO AGRO FOOD INDUSTRY HI-TECH
LA English
DT Article
DE Nutritional genomics; nutrigenomics; nutrigenetics; epigenomics; public
health; genetic testing; personalized nutrition; bioactive food
components; DNA; single nucleotide polymorphism
ID DIET; POLYMORPHISMS; NUTRITION; OBESITY; RISK; FAT
AB The "omics of nutrition", which includes nutrigenetics, epigenomics, transcriptomics, proteomics, and metabolomics are fundamental to the understanding of genetic-diet interactions that influence key cellular processes and ultimately affect phenotype. A multitude of food components have been reported to alter the expression of a gene or its products. However, the response is highly dependent on the quantity and duration of exposures and variation in the target being influenced by the food component(s). Personalized nutrition, which builds on knowledge of the "omics", will assist in identifying those who benefit most, or put themselves at risk, as a result of dietary intervention strategies.
C1 [Milner, John A.; Trujillo, Elaine B.] NCI, NIH, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD 20892 USA.
RP Milner, JA (reprint author), NCI, NIH, Nutr Sci Res Grp, Canc Prevent Div, 6130 Execut Blvd,Suite 3164, Rockville, MD 20892 USA.
NR 24
TC 0
Z9 0
U1 1
U2 7
PU TEKNOSCIENZE PUBL
PI MILANO
PA VIALE BRIANZA 22, 20127 MILANO, ITALY
SN 1722-6996
J9 AGRO FOOD IND HI TEC
JI Agro Food Ind. Hi-Tech
PD MAR-APR
PY 2010
VL 21
IS 2
BP 32
EP 34
PG 3
WC Biotechnology & Applied Microbiology; Food Science & Technology
SC Biotechnology & Applied Microbiology; Food Science & Technology
GA 601YM
UT WOS:000278104200008
ER
PT J
AU Phillips, KA
Cofrancesco, J
Sisson, S
Wu, AW
Bass, EB
Berkenblit, G
AF Phillips, Karran A.
Cofrancesco, Joseph, Jr.
Sisson, Stephen
Wu, Albert W.
Bass, Eric B.
Berkenblit, Gail
TI A Multicenter Study of Internal Medicine Residents' Perceptions of
Training, Competence, and Performance in Outpatient HIV Care
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID UNITED-STATES; PHYSICIANS; INFECTION; AIDS; VIRUS
AB Routine HIV screening is recommended by the Centers for Disease Control and Prevention (CDC), but it is unknown how well internal medicine residents are trained in HIV risk assessment, testing, counseling, and initial management of HIV patients. We sought to determine internal medicine residents' attitudes about HIV training and the factors that influence their HIV care performance utilizing a cross-sectional survey of 321 second-and third-year internal medicine residents from four programs in Baltimore, Boston, Detroit, and New York City between March and June 2006. Measurements included HIV care experience; attitudes, competency, and adequacy of HIV training; and basic HIV care performance and factors impacting performance. Two hundred twenty-three residents (69%) completed the survey. While 50% of residents reported over 30 HIV inpatient encounters in the past year, the majority of residents had limited outpatient exposure providing care for only 1-5 HIV outpatients. Managing HIV patients was rated an excellent educational opportunity by 89% of residents and 77% planned to care for HIV patients in the future. However, 39% stated that they did not feel competent to provide HIV outpatient care. Higher rates of residents reported deficiency in oupatient HIV training compared to outpatient non-HIV training (p<0.05) or inpatient HIV training (p<0.05). Residents reported substandard HIV risk assessment, testing, counseling, and initial management performance. Self-reported proficiency correlated with the number of HIV outpatients cared for and perceived training adequacy. Current residency training in HIV care remains largely inpatient-based and residents frequently rate HIV outpatient training as inadequate.
C1 [Phillips, Karran A.] Natl Inst Drug Abuse, Natl Inst Hlth, Baltimore, MD USA.
[Cofrancesco, Joseph, Jr.; Sisson, Stephen; Wu, Albert W.; Bass, Eric B.; Berkenblit, Gail] Johns Hopkins Sch Med, Baltimore, MD USA.
RP Berkenblit, G (reprint author), 601 N Caroline St, Baltimore, MD 21287 USA.
EM gberken@jhmi.edu
FU Osler Center for Clinical Excellence
FX We would like to acknowledge the assistance of Ms. Jeanne Macrae, Mr.
Bruce Martin, Ms. Elizabeth Thompson, and Dr. Baker-Genaw in technical
support of the survey administration. We acknowledge methodological
consultation provided by Hsin-Chieh Yeh, Ph. D., Core Faculty of the
Johns Hopkins General Internal Medicine Methods Core. This project was
supported by the Osler Center for Clinical Excellence at Johns Hopkins.
NR 20
TC 4
Z9 4
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD MAR
PY 2010
VL 24
IS 3
BP 159
EP 164
DI 10.1089/apc.2009.0302
PG 6
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 566EI
UT WOS:000275352500004
PM 20214483
ER
PT J
AU Magnusson, A
Goransson, M
Heilig, M
AF Magnusson, Asa
Goransson, Mona
Heilig, Markus
TI Early onset alcohol dependence with high density of family history is
not "male limited"
SO ALCOHOL
LA English
DT Article
DE Alcoholism; Women; Subtypes; Personality; Heritability; Illicit drugs
ID SUBSTANCE USE DISORDERS; IDENTIFICATION TEST AUDIT; CROSS-FOSTERING
ANALYSIS; PERSONALITY-TRAITS; UNITED-STATES; PSYCHIATRIC-DISORDERS;
EPIDEMIOLOGIC SURVEY; GENDER-DIFFERENCES; MENTAL-DISORDERS;
DRUG-DEPENDENCE
AB Objective: Based on classical adoption studies, early onset type II alcoholism was originally described as "male limited." We examined the possible expression of this subtype in present day alcohol-dependent women. Detailed systematic assessment was obtained from 200 treatment-seeking alcohol-dependent women and 189 healthy population controls. Women fulfilling type II alcoholism criteria had higher alcoholism severity as measured by The Alcohol Use Disorders Identification Test and markedly higher use of illicit drugs. Both alcoholism subtypes scored higher than normal on anxiety and impulsivity traits, but type II women scored markedly higher on aggression subscales than either of the other groups. Importantly, density of family history was markedly higher in type II women, suggesting a higher heritability. Despite its original description as male limited, early onset alcoholism with high density of family history is likely to be a valid construct in women. Its recognition has important implications for diagnosis, treatment, and research. Published by Elsevier Inc.
C1 [Heilig, Markus] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA.
[Magnusson, Asa; Goransson, Mona; Heilig, Markus] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, 10 Ctr Dr,10-1E-5334, Bethesda, MD 20892 USA.
EM markus.heilig@mail.nih.gov
OI Heilig, Markus/0000-0003-2706-2482
FU County of Stockholm; National Institute on Alcohol Abuse and Alcoholism
FX The authors gratefully acknowledge the help by staffs at the
participating treatment centers and input on the manuscript by Prof
Nancy Pedersen. This work was supported by funding from the County of
Stockholm and National Institute on Alcohol Abuse and Alcoholism
intramural research funds. The authors have no competing interests.
NR 60
TC 9
Z9 9
U1 2
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD MAR
PY 2010
VL 44
IS 2
BP 131
EP 139
DI 10.1016/j.alcohol.2010.01.001
PG 9
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 626LW
UT WOS:000279968500001
PM 20193873
ER
PT J
AU Kohlstadt, I
Vitiello, B
AF Kohlstadt, Ingrid
Vitiello, Benedetto
TI Use of Atypical Antipsychotics in Children: Balancing Safety and
Effectiveness
SO AMERICAN FAMILY PHYSICIAN
LA English
DT Editorial Material
C1 [Kohlstadt, Ingrid] US FDA, Off Pediat Therapeut, Rockville, MD 20857 USA.
[Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA.
RP Kohlstadt, I (reprint author), US FDA, Off Pediat Therapeut, Rockville, MD 20857 USA.
EM kohlstadt@fda.hhs.gov
NR 9
TC 5
Z9 5
U1 2
U2 2
PU AMER ACAD FAMILY PHYSICIANS
PI KANSAS CITY
PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA
SN 0002-838X
J9 AM FAM PHYSICIAN
JI Am. Fam. Physician
PD MAR 1
PY 2010
VL 81
IS 5
BP 585
EP +
PG 2
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 565MK
UT WOS:000275297200002
PM 20187594
ER
PT J
AU Leosdottir, M
Willenheimer, R
Plehn, J
Borgquist, R
Gudmundsson, P
Harris, TB
Launer, LJ
Bjornsdottir, H
Nilsson, PM
Gudnason, V
AF Leosdottir, Margret
Willenheimer, Ronnie
Plehn, Jonathan
Borgquist, Rasmus
Gudmundsson, Petri
Harris, Tamara B.
Launer, Lenore J.
Bjornsdottir, Halldora
Nilsson, Peter M.
Gudnason, Vilmundur
TI Myocardial structure and function by echocardiography in relation to
glucometabolic status in elderly subjects from 2 population-based
cohorts: A cross-sectional study
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID IMPAIRED GLUCOSE-TOLERANCE; VENTRICULAR DIASTOLIC FUNCTION;
CONGESTIVE-HEART-FAILURE; DIABETIC CARDIOMYOPATHY; STANDARDS COMMITTEE;
OF-ECHOCARDIOGRAPHY; INSULIN-RESISTANCE; QUANTIFICATION; FRAMINGHAM;
RECOMMENDATIONS
AB Background Left ventricular (LV) diastolic dysfunction has been associated with impaired glucometabolic status. However, studies of older subjects are lacking. We examined associations between echocardiographic indices of LV diastolic function and LV mass index (LVMI) and glucometabolic status among middle-aged and elderly subjects free from heart disease, hypothesizing that the associations would be comparative to younger cohorts.
Methods We examined the Age Gene/Environment Susceptibility Reykjavik Study (Iceland; n = 607, 76 +/- 6 years) and the Malmo Preventive Project Re-Examination Study (MPP-RES) cohorts (Sweden; n = 1,519, 67 +/- 6 years), evaluating associations with multivariable regression analysis.
Results In the Age Gene/Environment Susceptibility Reykjavik Study, LVMI was positively correlated with glycosylated hemoglobin (HbA1c) (P = .001). Otherwise, echocardiographic variables were not associated with glucometabolic status. In the MPP-RES, LVMI increased with increasing glucometabolic disturbance among both older (7-80 years) and middle-aged (57-69 years) subjects. Among older subjects, HbA1c was positively correlated with 2 variables reflecting LV diastolic function: late transmitral peak flow velocity (A) (P = .001) and early transmitral peak flow velocity (E)/early diastolic peak tissue velocity (Em) (P = .046). In middle-aged MPP-RES subjects, increasing glucometabolic disturbance was correlated with increasing late diastolic peak tissue velocity (Am) (P = .002) and, after age adjustment, with increasing A (P = .001) and decreasing Em/Am (P = .009). With age adjustment, Am and A were positively correlated with fasting glucose and HbA1c.
Conclusions Contrary to our hypothesis, in 2 independent cohorts of older individuals, associations between glucometabolic status and LV diastolic function were generally weak. These contrast with previous reports, as well as with observations among middle-aged subjects in the present study. Changes in LV diastolic function may be more age-related than associated with glucose metabolism in older subjects. (Am Heart J 2010; 159: 414-420.e4.)
C1 [Leosdottir, Margret] Malmo Univ Hosp, Dept Cardiol, S-20502 Malmo, Sweden.
[Willenheimer, Ronnie; Nilsson, Peter M.] Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Malmo, Sweden.
[Willenheimer, Ronnie] Heart Hlth Grp, Malmo, Sweden.
[Plehn, Jonathan] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Borgquist, Rasmus] Univ Lund Hosp, Dept Cardiol, S-22185 Lund, Sweden.
[Gudmundsson, Petri] Malmo Univ, Dept Biomed Lab Sci, Malmo, Sweden.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Bjornsdottir, Halldora; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
RP Leosdottir, M (reprint author), Malmo Univ Hosp, Dept Cardiol, S-20502 Malmo, Sweden.
EM margret.leosdottir@med.lu.se
RI Gudnason, Vilmundur/K-6885-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Leosdottir,
Margret/0000-0003-1677-1566
FU NIH [N01-AG-12100]; NIA Intramural Research Program, Bethesda; Swedish
Heart-Lung Foundation; Merck, Sharp Dohme; Hulda and E Conrad Mossfelts
Foundation; Ernhold Lundstroms Foundation (Sweden); Helga Jonsdottir and
Sigurlidi Kristjansson Memorial Foundation (Iceland)
FX The AGES-RS study was funded by an NIH contract N01-AG-12100, the NIA
Intramural Research Program, Bethesda (MD), Hjartavernd (the Icelandic
Heart Association, Iceland), and the Althingi (the Icelandic
Parliament). Additionally, this study was supported by The Swedish
Heart-Lung Foundation; Merck, Sharp & Dohme; Hulda and E Conrad
Mossfelts Foundation; Ernhold Lundstroms Foundation (Sweden); and Helga
Jonsdottir and Sigurlidi Kristjansson Memorial Foundation (Iceland).
NR 26
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U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD MAR
PY 2010
VL 159
IS 3
BP 414
EP U113
DI 10.1016/j.ahj.2009.12.028
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 571XH
UT WOS:000275788900012
PM 20211303
ER
PT J
AU Flegal, KM
Graubard, BI
Williamson, DF
Gail, MH
AF Flegal, Katherine M.
Graubard, Barry I.
Williamson, David F.
Gail, Mitchell H.
TI Sources of differences in estimates of obesity-associated deaths from
first National Health and Nutrition Examination Survey (NHANES I) hazard
ratios
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID UNITED-STATES; BODY-MASS; OVERWEIGHT; MORTALITY; SMOKING; RISK;
UNDERWEIGHT; POPULATION; FRACTIONS; MORBIDITY
AB Background: Estimates of obesity-associated deaths in the United States for 1991 were published by Allison et al (JAMA 1999; 282: 1530-8) and subsequently for 2000 by Mokdad et al (JAMA 2004; 291: 1238-45). Flegal et al (JAMA 2005; 293: 1861-7) then published lower estimates of obesity-associated deaths for 2000. All 3 studies incorporated data from the first National Health and Nutrition Examination Survey (NHANES I).
Objective: The objective was to clarify the effects of methodologic differences between the 3 studies in estimates of obesity-associated deaths in the US population by using NHANES I hazard ratios.
Design: The earlier reports used imputed smoking data for much of the NHANES I sample rather than the available reported data and applied a method of calculating attributable fractions that did not adjust for the effects of age, sex, and smoking on mortality in the target US population and did not account for effect modification by age. The effects of these and other methodologic factors were examined.
Results: The NHANES I hazard ratios in the earlier reports were too low, probably because of the imputed smoking data. The low hazard ratios obscured the magnitude and direction of the bias arising from the incompletely adjusted attributable fraction method. When corrected hazard ratios were used, the incompletely adjusted attributable fraction method overestimated obesity-associated mortality in the target population by > 100,000 deaths.
Conclusion: Methodologic sources of bias in the reports by Allison et al and Mokdad et al include the assessment of smoking status in NHANES I and the method of calculating attributable fractions. Am J Clin Nutr 2010;91:519-27.
C1 [Flegal, Katherine M.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Graubard, Barry I.; Gail, Mitchell H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Williamson, David F.] Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA 30322 USA.
RP Flegal, KM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 3311 Toledo Rd,Room 4201, Hyattsville, MD 20782 USA.
EM kmf2@cdc.gov
RI Flegal, Katherine/A-4608-2013;
OI Flegal, Katherine/0000-0002-0838-469X
NR 33
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U1 0
U2 5
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAR
PY 2010
VL 91
IS 3
BP 519
EP 527
DI 10.3945/ajcn.2009.28222
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 557YM
UT WOS:000274706500005
PM 20107197
ER
PT J
AU Yang, G
Gao, YT
Shu, XO
Cai, QY
Li, GL
Li, HL
Ji, BT
Rothman, N
Dyba, M
Xiang, YB
Chung, FL
Chow, WH
Zheng, W
AF Yang, Gong
Gao, Yu-Tang
Shu, Xiao-Ou
Cai, Qiuyin
Li, Guo-Liang
Li, Hong-Lan
Ji, Bu-Tian
Rothman, Nathaniel
Dyba, Marcin
Xiang, Yong-Bing
Chung, Fung-Lung
Chow, Wong-Ho
Zheng, Wei
TI Isothiocyanate exposure, glutathione S-transferase polymorphisms, and
colorectal cancer risk
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID CRUCIFEROUS VEGETABLE CONSUMPTION; ABERRANT CRYPT FOCI; COLON-CANCER;
DIETARY ISOTHIOCYANATES; MULTIETHNIC COHORT; BROCCOLI SPROUTS; COOKING
DURATION; WOMENS HEALTH; SHANGHAI; HUMANS
AB Background: Isothiocyanates, compounds found primarily in cruciferous vegetables, have been shown in laboratory studies to possess anticarcinogenic activity. Glutathione S-transferases (GSTs) are involved in the metabolism and elimination of isothiocyanates; thus, genetic variations in these enzymes may affect in vivo bioavailability and the activity of isothiocyanates.
Objective: The objective was to prospectively evaluate the association between urinary isothiocyanate concentrations and colorectal cancer risk as well as the potential modifying effect of GST genotypes on the association.
Design: A nested case-control study of 322 cases and 1251 controls identified from the Shanghai Women's Health Study was conducted.
Results: Urinary isothiocyanate concentrations were inversely associated with colorectal cancer risk; the inverse association was statistically significant or nearly significant in the GSTM1-null (P for trend = 0.04) and the GSTT1-null (P for trend = 0.07) genotype groups. The strongest inverse association was found among individuals with both the GSTM1-null and the GSTT1-null genotypes, with an adjusted odds ratio of 0.51 (95% CI: 0.27, 0.95), in a comparison of the highest with the lowest tertile of urinary isothiocyanates. No apparent associations between isothiocyanate concentration and colorectal cancer risk were found among individuals who carried either the GSTM1 or GSTT1 gene (P for interaction, 0.05).
Conclusion: This study suggests that isothiocyanate exposure may reduce the risk of colorectal cancer, and this protective effect may be modified by the GSTM1 and GSTT1 genes. Am J Clin Nutr 2010; 91: 704-11.
C1 [Yang, Gong; Shu, Xiao-Ou; Cai, Qiuyin; Li, Guo-Liang; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Div Epidemiol,Dept Med, Nashville, TN 37203 USA.
[Gao, Yu-Tang; Li, Hong-Lan; Xiang, Yong-Bing] Shanghai Canc Inst, Shanghai, Peoples R China.
[Ji, Bu-Tian; Rothman, Nathaniel; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Dyba, Marcin; Chung, Fung-Lung] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
RP Yang, G (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Div Epidemiol,Dept Med, 6th Floor,Suite 600,2525West End Ave, Nashville, TN 37203 USA.
EM gong.yang@vanderbilt.edu
RI LI, GUOLIANG/E-7359-2015;
OI LI, GUOLIANG/0000-0001-8493-4684; Dyba, Marcin/0000-0001-6311-6877
FU USPHS [R01CA70867, R01CA 122364]; NIH [N02 CP1101066]; [P30CA68485]
FX Supported by USPHS grant R01CA70867. The Shanghai Women's Health Study
was supported in part by the NIH Intramural Research Program (N02
CP1101066). GY was supported in part by USPHS grant R01CA 122364. The
biospecimens were prepared at the Survey and Biospecimen Shared
Resource, which is supported in part by P30CA68485.
NR 48
TC 31
Z9 33
U1 0
U2 2
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAR
PY 2010
VL 91
IS 3
BP 704
EP 711
DI 10.3945/ajcn.2009.28683
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 557YM
UT WOS:000274706500027
PM 20042523
ER
PT J
AU Hall, KD
Chow, CC
AF Hall, Kevin D.
Chow, Carson C.
TI Estimating the quantitative relation between food energy intake and
changes in body weight
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Letter
C1 [Hall, Kevin D.; Chow, Carson C.] NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA.
RP Hall, KD (reprint author), NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA.
EM kevinh@niddk.nih.gov
RI Hall, Kevin/F-2383-2010; Chow, Carson/A-7970-2009
NR 4
TC 7
Z9 7
U1 0
U2 2
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAR
PY 2010
VL 91
IS 3
BP 816
EP 816
DI 10.3945/ajcn.2009.28922
PG 1
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 557YM
UT WOS:000274706500042
PM 20071643
ER
PT J
AU Jenkins, RA
AF Jenkins, Richard A.
TI Applied Roles and the Future of Community Psychology
SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY
LA English
DT Article
DE Practice; Participation; Future directions
ID DECISION-MAKING; HIV; THAILAND; TRIAL
AB The roles for community psychologists have changed over the past several decades. These changes have implications for training, traditional academic roles, and the capacity of the field to maintain its integrity and further development. Changes in the scope of community psychology as a field as well as the roles of community psychologists are described with consideration of how they may affect participation in the field, retention of membership in SCRA, and potential directions for training.
C1 NIDA, Prevent Res Branch, NIH, Bethesda, MD 20892 USA.
RP Jenkins, RA (reprint author), NIDA, Prevent Res Branch, NIH, 6001 Executive Blvd,Rm 5185 MSC 9589, Bethesda, MD 20892 USA.
EM jenkinsri@mail.nih.gov
NR 15
TC 1
Z9 3
U1 1
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0091-0562
J9 AM J COMMUN PSYCHOL
JI Am. J. Community Psychol.
PD MAR
PY 2010
VL 45
IS 1-2
BP 68
EP 72
DI 10.1007/s10464-009-9285-1
PG 5
WC Public, Environmental & Occupational Health; Psychology,
Multidisciplinary; Social Work
SC Public, Environmental & Occupational Health; Psychology; Social Work
GA 562YU
UT WOS:000275092800005
PM 20094769
ER
PT J
AU Jensen, RA
Shea, S
Ranjit, N
Diez-Roux, A
Wong, TY
Klein, R
Klein, BEK
Cotch, MF
Siscovick, DS
AF Jensen, Richard A.
Shea, Steven
Ranjit, Nalini
Diez-Roux, Ana
Wong, Tien Y.
Klein, Ronald
Klein, Barbara E. K.
Cotch, Mary Frances
Siscovick, David S.
TI Psychosocial Risk Factors and Retinal Microvascular Signs
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE anger; anxiety; depression; microvessels; psychology; social; retina;
social support
ID CORONARY-HEART-DISEASE; BLUE MOUNTAINS EYE; ATHEROSCLEROSIS RISK; VESSEL
DIAMETERS; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; YOUNG-ADULTS;
DIABETIC-RETINOPATHY; ARTERIOLAR DIAMETER; DEPRESSION SYMPTOMS
AB The association between psychosocial risk factors and retinal microvascular signs was examined in the Multi-Ethnic Study of Atherosclerosis. Subjects were recruited from Baltimore, Maryland; Chicago, Illinois; Forsyth County, North Carolina; Los Angeles County, California; New York, New York; and St. Paul, Minnesota. Levels of depressive symptoms, trait anger, trait anxiety, chronic burdens, emotional support, and cynical distrust were assessed by questionnaire (from July 2000 to July 2002). Digital retinal images (from August 2002 to January 2004) from 6,147 participants were used to evaluate retinopathy and retinal vascular caliber. After controlling for potential confounding factors, the authors found that subjects without access to emotional support (Enriched Social Support Instrument score of < 19 vs. >= 19) had 60% greater odds of retinopathy (odds ratio = 1.6, 95% confidence interval (CI): 1.3, 2.0). Subjects with high Spielberger trait-anxiety scale scores (>= 22 vs. < 14) and subjects with high depressive symptoms (Center for Epidemiology Studies Depression Scale score, >= 16 vs. < 16) were also more likely to have retinopathy (odds ratio = 1.4, 95% CI: 1.1, 1.9 and odds ratio = 1.5, 95% CI: 1.2, 1.9), respectively. In this cross-sectional study, lack of emotional support, increased trait anxiety, and more depressive symptoms were associated with retinopathy signs, independently of other known risk factors.
C1 [Jensen, Richard A.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Shea, Steven] Columbia Univ, Dept Med & Epidemiol, New York, NY USA.
[Ranjit, Nalini; Diez-Roux, Ana] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ctr Social Epidemiol & Populat Hlth, Ann Arbor, MI 48109 USA.
[Wong, Tien Y.] Univ Melbourne, Ctr Eye Res, Melbourne, Vic, Australia.
[Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117595, Singapore.
[Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
RP Jensen, RA (reprint author), 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA.
EM richaj@uw.edu
OI Cotch, Mary Frances/0000-0002-2046-4350
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165,
N01-HC-95169, T32HL007902]; National Institutes of Health [Z01Ey000403]
FX This work was supported by the National Heart, Lung, and Blood Institute
(contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 to MESA);
a National Institutes of Health Intramural Research Award (National Eye
Institute award Z01Ey000403 to M. F. C.); and a National Heart, Lung,
and Blood Institute Training Grant (T32HL007902 to R.A.J.).
NR 57
TC 8
Z9 8
U1 1
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAR 1
PY 2010
VL 171
IS 5
BP 522
EP 531
DI 10.1093/aje/kwp414
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 558YY
UT WOS:000274786500002
PM 20035010
ER
PT J
AU Rodondi, N
Marques-Vidal, P
Butler, J
Sutton-Tyrrell, K
Cornuz, J
Satterfield, S
Harris, T
Bauer, DC
Ferrucci, L
Vittinghoff, E
Newman, AB
AF Rodondi, Nicolas
Marques-Vidal, Pedro
Butler, Javed
Sutton-Tyrrell, Kim
Cornuz, Jacques
Satterfield, Suzanne
Harris, Tamara
Bauer, Douglas C.
Ferrucci, Luigi
Vittinghoff, Eric
Newman, Anne B.
CA Hlth Aging Body Compisition Study
TI Markers of Atherosclerosis and Inflammation for Prediction of Coronary
Heart Disease in Older Adults
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE atherosclerosis; cohort studies; coronary disease; inflammation
ID C-REACTIVE PROTEIN; ANKLE BRACHIAL INDEX; CARDIOVASCULAR EVENTS; RISK
PREDICTION; MYOCARDIAL-INFARCTION; MULTIPLE BIOMARKERS; ROC CURVE;
ALL-CAUSE; HEALTH; MORTALITY
AB Although both inflammatory and atherosclerosis markers have been associated with coronary heart disease (CHD) risk, data directly comparing their predictive value are limited. The authors compared the value of 2 atherosclerosis markers (ankle-arm index (AAI) and aortic pulse wave velocity (aPWV)) and 3 inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)) in predicting CHD events. Among 2,191 adults aged 70-79 years at baseline (1997-1998) from the Health, Aging, and Body Composition Study cohort, the authors examined adjudicated incident myocardial infarction or CHD death ("hard" events) and "hard" events plus hospitalization for angina or coronary revascularization (total CHD events). During 8 years of follow-up between 1997-1998 and June 2007, 351 participants developed total CHD events (197 "hard" events). IL-6 (highest quartile vs. lowest: hazard ratio = 1.82, 95% confidence interval: 1.33, 2.49; P-trend < 0.001) and AAI (AAI < 0.9 vs. AAI 1.01-1.30: hazard ratio = 1.57, 95% confidence interval: 1.14, 2.18) predicted CHD events above traditional risk factors and modestly improved global measures of predictive accuracy. CRP, TNF-alpha, and aPWV had weaker associations. IL-6 and AAI accurately reclassified 6.6% and 3.3% of participants, respectively (P's < 0.05). Results were similar for "hard" CHD, with higher reclassification rates for AAI. IL-6 and AAI are associated with future CHD events beyond traditional risk factors and modestly improve risk prediction in older adults.
C1 [Rodondi, Nicolas; Cornuz, Jacques] Univ Lausanne, Fac Biol & Med, Dept Ambulatory Care & Community Med, CH-1011 Lausanne, Switzerland.
[Marques-Vidal, Pedro] Univ Lausanne, Univ Inst Social & Prevent Med, CH-1011 Lausanne, Switzerland.
[Marques-Vidal, Pedro] Univ Lausanne, Ctr Cardiovasc & Metab Res CardioMet, CH-1011 Lausanne, Switzerland.
[Butler, Javed] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA.
[Sutton-Tyrrell, Kim; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Satterfield, Suzanne] Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA.
[Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Ferrucci, Luigi] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Bauer, Douglas C.; Vittinghoff, Eric] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Sch Med, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA.
RP Rodondi, N (reprint author), Univ Lausanne, Fac Biol & Med, Dept Ambulatory Care & Community Med, Bugnon 44, CH-1011 Lausanne, Switzerland.
EM nicolas.rodondi@hospvd.ch
RI Newman, Anne/C-6408-2013; Marques-Vidal, Pedro/C-9449-2009
OI Newman, Anne/0000-0002-0106-1150; Marques-Vidal,
Pedro/0000-0002-4548-8500
FU National Institute on Aging, US National Institutes of Health
[N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute on
Aging; Swiss National Science Foundation [3200B0-116097]
FX This research was supported by grants N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 from the
National Institute on Aging, US National Institutes of Health, and in
part by the Intramural Research Program of the National Institute on
Aging. The National Institute on Aging funded the Health, Aging, and
Body Composition study, reviewed the manuscript, and approved its
publication. This research was partially supported by grant
3200B0-116097 to Dr. Nicolas Rodondi from the Swiss National Science
Foundation.
NR 35
TC 40
Z9 48
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAR 1
PY 2010
VL 171
IS 5
BP 540
EP 549
DI 10.1093/aje/kwp428
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 558YY
UT WOS:000274786500004
PM 20110287
ER
PT J
AU Koster, A
van Gool, CH
Kempen, GIJM
Penninx, BWJH
Lee, JS
Rubin, SM
Tylavsky, FA
Yaffe, K
Newman, AB
Harris, TB
Pahor, M
Ayonayon, HN
van Eijk, JTM
Kritchevsky, SB
AF Koster, Annemarie
van Gool, Coen H.
Kempen, Gertrudis I. J. M.
Penninx, Brenda W. J. H.
Lee, Jung Sun
Rubin, Susan M.
Tylavsky, Frances A.
Yaffe, Kristine
Newman, Anne B.
Harris, Tamara B.
Pahor, Marco
Ayonayon, Hilsa N.
van Eijk, Jacques Th. M.
Kritchevsky, Stephen B.
CA Hlth ABC Study
TI Late-Life Depressed Mood and Weight Change Contribute to the Risk of
Each Other
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE Depression; weight change; aging
ID OLDER PERSONS; BODY-COMPOSITION; AMSTERDAM; SYMPTOMS; STRESS; HEALTH;
WOMEN; DISABILITY; COMMUNITY; FRAILTY
AB Objective: Weight change may be considered an effect of depression. In turn, depression may follow weight change. Deteriorations in health may mediate these associations. The objective was to examine reciprocal associations between depressed mood and weight change, and the potentially mediating role of deteriorations in health (interim hospitalizations and incident mobility imitation) in these associations. Methods: Data were from 2406 black and white men and women, aged 70-79 from Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health, Aging and Body composition (Health ABC) study. Depressed mood at baseline (T1) and 3-year follow-up (T4) was measured with the CES-D scale. Three weight change groups (T1-T4) were created: loss (>= 5% loss), stable (within +/- 5% loss or gain), and weight gain (>= 5% gain). Results: At T1 and T4, respectively 4.4% and 9.5% of the analysis sample had depressed mood. T1 depressed mood was associated with weight gain over the 3-year period (OR: 1.91; 95% CI: 1.13-3.22). Weight loss over the 3-year period was associated with T4 depressed mood (OR: 1.51; 95% CI: 1.05-2.16). Accounting for deteriorations in health in the reciprocal associations between weight change and depressed mood reduced effect sizes between 16-27%. Conclusions: In this study, depressed mood predicted weight gain over three years, while weight loss over three years predicted depressed mood. These associations were partly mediated through deteriorations in health. Implications for clinical practice and prevention include increased awareness that depressed mood can cause weight change, but can also be preceded by deteriorations in health and weight change. (Am J Geriatr Psychiatry 2010; 18: 236-244)
C1 [Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Koster, Annemarie; van Gool, Coen H.; Kempen, Gertrudis I. J. M.; van Eijk, Jacques Th. M.] Univ Maastricht, Fac Hlth Med & Life Sci, Care & Publ Hlth Res Inst, Maastricht, Netherlands.
[Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Lee, Jung Sun] Univ Georgia, Dept Food, Athens, GA USA.
[Lee, Jung Sun] Univ Georgia, Dept Nutr, Athens, GA USA.
[Rubin, Susan M.; Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Rubin, Susan M.; Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Tylavsky, Frances A.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat Neurol & Epidemiol, San Francisco, CA 94143 USA.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Pahor, Marco] Univ Florida, Coll Med, Inst Aging, Dept Aging & Geriatr Res, Gainesville, FL USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sticht Ctr Aging & Rehabil, Winston Salem, NC 27103 USA.
RP Koster, A (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Suite 3C309, Bethesda, MD 20892 USA.
EM kostera@mail.nih.gov
RI Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013; Kempen,
Gertrudis/H-5978-2016;
OI Newman, Anne/0000-0002-0106-1150; Kempen, Gertrudis/0000-0002-7053-2198;
Kritchevsky, Stephen/0000-0003-3336-6781
FU National Institute on Aging [N01-AG-6 -2101, N01-AG-6 -2103,
N01-AG-6-2106]; Intramural Research Program of NIH; National Institute
on Aging
FX This study was supported by National Institute on Aging contracts
N01-AG-6 -2101, N01-AG-6 -2103, and N01-AG-6-2106. This research was
supported (in part) by the Intramural Research Program of NIH, National
Institute on Aging.
NR 39
TC 16
Z9 17
U1 4
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2010
VL 18
IS 3
BP 236
EP 244
DI 10.1097/JGP.0b013e3181c65837
PG 9
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 567PD
UT WOS:000275458200007
PM 20224519
ER
PT J
AU Taylor, WD
Neigh, GN
Aizenstein, HJ
Evans, JD
AF Taylor, Warren D.
Neigh, Gretchen N.
Aizenstein, Howard J.
Evans, Jovier D.
TI NEUROSCIENCE ADVANCES IN THE STUDY OF LATE LIFE DEPRESSION
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry
CY MAR 05-08, 2010
CL Savannah, GA
SP Amer Assoc Geriat Psychiat
C1 [Taylor, Warren D.] Duke Univ, Med Ctr, Durham, NC USA.
[Aizenstein, Howard J.] Univ Pittsburgh, Pittsburgh, PA USA.
[Neigh, Gretchen N.] Emory Univ, Atlanta, GA 30322 USA.
[Evans, Jovier D.] NIMH, Bethesda, MD 20892 USA.
RI Neigh, Gretchen/G-3662-2011
OI Neigh, Gretchen/0000-0003-0955-9161
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2010
VL 18
IS 3
SU 1
BP S22
EP S23
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 753PB
UT WOS:000289790800023
ER
PT J
AU Li, YH
Zheng, TZ
Kilfoy, BA
Lan, Q
Holford, T
Han, XS
Zhao, P
Dai, M
Leaderer, B
Rothman, N
Zhang, YW
AF Li, Yonghong
Zheng, Tongzhang
Kilfoy, Briseis A.
Lan, Qing
Holford, Theodore
Han, Xuesong
Zhao, Ping
Dai, Min
Leaderer, Brian
Rothman, Nat
Zhang, Yawei
TI Genetic polymorphisms in cytochrome P450s, GSTs, NATs, alcohol
consumption and risk of non-Hodgkin lymphoma
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Letter
ID TOBACCO SMOKING; EXPOSURE OCCURS; DRINKING; WOMEN; ASSOCIATION;
METABOLISM; INDUCTION; IMPACT; CANCER; RATS
AB The aim of this study was to investigate whether genetic polymorphisms in cytochrome P450s (CYPs), glutathione S-transferases (GSTs), and N-acetyltransterases (NATs) genes modify the relationship between alcohol consumption and risk of non-Hodgkin's lymphoma (NHL) in a population-based, case-control study including 1,115 Connecticut women. Although we did not find strong evidence that the genetic polymorphisms modify the relationship between alcohol consumption and risk of NHL, we identified significant interactions for multiple GSTs and NATs and alcohol intake among persons with DLBCL. Our results confer support investigation of the gene-environment interaction in a larger study population of DLBCL.
C1 [Li, Yonghong; Zheng, Tongzhang; Holford, Theodore; Han, Xuesong; Leaderer, Brian; Zhang, Yawei] Yale Univ, Sch Publ Hlth, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
[Li, Yonghong] China CDC, Natl Inst Environm Hlth & Related Prod Safety, Dept Epidemiol, Beijing, Peoples R China.
[Kilfoy, Briseis A.; Lan, Qing; Rothman, Nat] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Zhao, Ping; Dai, Min] Chinese Acad Med Sci, Canc Inst Hosp, Beijing 100037, Peoples R China.
RP Zhang, YW (reprint author), Yale Univ, Sch Publ Hlth, Dept Epidemiol & Publ Hlth, 60 Coll St,LEPH 440, New Haven, CT 06520 USA.
EM yawei.zhang@yale.edu
RI Aschebrook-Kilfoy, Briseis/A-2537-2012
FU FIC NIH HHS [D43 TW008323, D43 TW007864]; Intramural NIH HHS [Z01
CP010123-12]; NCI NIH HHS [R01 CA062006]; NCRR NIH HHS [UL1 RR024139]
NR 30
TC 2
Z9 2
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD MAR
PY 2010
VL 85
IS 3
BP 213
EP 215
DI 10.1002/ajh.21608
PG 3
WC Hematology
SC Hematology
GA 568GK
UT WOS:000275510100011
PM 20131310
ER
PT J
AU Nelson, RG
Tuttle, KR
AF Nelson, Robert G.
Tuttle, Katherine R.
TI Prevention of Diabetic Kidney Disease: Negative Clinical Trials With
Renin-Angiotensin System Inhibitors
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Editorial Material
ID BLOOD-GLUCOSE CONTROL; TYPE-2; COMPLICATIONS; MICROALBUMINURIA;
PROGRESSION; MELLITUS; NEPHROPATHY; METFORMIN; OUTCOMES; THERAPY
C1 [Nelson, Robert G.] NIH, Phoenix, AZ 85014 USA.
[Tuttle, Katherine R.] Univ Washington, Spokane, WA USA.
[Tuttle, Katherine R.] Univ Washington, Sch Med, Seattle, WA USA.
RP Nelson, RG (reprint author), NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
EM rgnelson@mail.nih.gov
RI Nelson, Robert/B-1470-2012
FU Intramural NIH HHS [Z99 DK999999]
NR 23
TC 6
Z9 6
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD MAR
PY 2010
VL 55
IS 3
BP 426
EP 430
DI 10.1053/j.ajkd.2009.10.001
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 563DW
UT WOS:000275109000007
PM 20005029
ER
PT J
AU Muntner, P
Anderson, A
Charleston, J
Chen, Z
Ford, V
Makos, G
O'Connor, A
Perumal, K
Rahman, M
Steigerwalt, S
Teal, V
Townsend, R
Weir, M
Wright, JT
AF Muntner, Paul
Anderson, Amanda
Charleston, Jeanne
Chen, Zhen
Ford, Virginia
Makos, Gail
O'Connor, Andrew
Perumal, Kalyani
Rahman, Mahboob
Steigerwalt, Susan
Teal, Valerie
Townsend, Raymond
Weir, Matthew
Wright, Jackson T., Jr.
CA CRIC Study Investigators
TI Hypertension Awareness, Treatment, and Control in Adults With CKD:
Results From the Chronic Renal Insufficiency Cohort (CRIC) Study
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Hypertension; awareness; treatment; control; chronic kidney disease
ID CHRONIC KIDNEY-DISEASE; UNITED-STATES; BLOOD-PRESSURE; CONTROLLED
TRIALS; RISK-FACTORS; PREVALENCE; METAANALYSIS; POPULATION; REDUCTION
AB Background: A low rate of blood pressure control has been reported in patients with chronic kidney disease (CKD). These data were derived from population-based samples with a low rate of CKD awareness.
Study Design: Cross-sectional.
Setting & Participants: Data from the baseline visit of the Chronic Renal Insufficiency Cohort (CRIC) Study (n = 3,612) were analyzed. Participants with an estimated glomerular filtration rate of 20-70 mL/min/1.73 m(2) were identified from physician offices and review of laboratory databases.
Outcomes: Prevalence and awareness of hypertension, treatment patterns, control rates, and factors associated with hypertension control.
Measurements: Following a standardized protocol, blood pressure was measured 3 times by trained staff, and hypertension was defined as systolic blood pressure >= 140 mm Hg and/or diastolic blood pressure >= 90 mm Hg and/or self-reported antihypertensive medication use. Patients' awareness and treatment of hypertension were defined using self-report, and 2 levels of hypertension control were evaluated: systolic/diastolic blood pressure <140/90 and <130/80 mm Hg.
Results: The prevalence of hypertension was 85.7%, and 98.9% of CRIC participants were aware of this diagnosis and 98.3% were treated with medications, whereas 67.1% and 46.1% had hypertension controlled to <140/90 and <130/80 mm Hg, respectively. Of CRIC participants with hypertension, 15%, 25%, 26%, and 32% were using 1, 2, 3, and >= 4 antihypertensive medications, respectively. After multivariable adjustment, older patients, blacks, and those with higher urinary albumin excretion were less likely, whereas participants using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were more likely to have controlled their hypertension to <140/90 and <130/80 mm Hg.
Limitations: Data were derived from a single study visit.
Conclusions: Despite almost universal hypertension awareness and treatment in this cohort of patients with CKD, rates of hypertension control were suboptimal. Am J Kidney Dis 00:00-00 (C) 2009 by the National Kidney Foundation, Inc Am J Kidney Dis 55: 441-451. (C) 2010 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Muntner, Paul] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA.
[Anderson, Amanda; Ford, Virginia; Teal, Valerie; Townsend, Raymond] Univ Penn, Philadelphia, PA 19104 USA.
[Charleston, Jeanne] Johns Hopkins Univ, Baltimore, MD USA.
[Chen, Zhen] NIH, Rockville, MD USA.
[Makos, Gail; Steigerwalt, Susan] St Johns Hosp, Detroit, MI USA.
[Rahman, Mahboob] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Louis Stokes Cleveland VA Med Ctr, Cleveland, OH 44106 USA.
[Perumal, Kalyani] Univ Illinois, Chicago, IL USA.
[Weir, Matthew] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA.
RP Muntner, P (reprint author), Univ Alabama, Dept Epidemiol, 1665 Univ Blvd,Ste 230J, Birmingham, AL 35294 USA.
EM pmuntner@uab.edu
OI Teal, Valerie/0000-0001-7116-5353
FU National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK),
National Institutes of Health (NIH), Bethesda, MD [K01 DK064860,
5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028,
5U01DK60980, 5U01DK060963, 5U01DK060902]
FX Dr Muntner received support through a career development grant (K01
DK064860) from the National Institute of Diabetes, Digestive and Kidney
Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD. The
CRIC Study is supported by cooperative agreement project grants
5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028,
5U01DK60980, 5U01DK060963, and 5U01DK060902 from the NIDDK, NIH.
NR 15
TC 75
Z9 91
U1 1
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD MAR
PY 2010
VL 55
IS 3
BP 441
EP 451
DI 10.1053/j.ajkd.2009.09.014
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 563DW
UT WOS:000275109000009
PM 19962808
ER
PT J
AU Hoerger, TJ
Wittenborn, JS
Segel, JE
Burrows, NR
Imai, K
Eggers, P
Pavkov, ME
Jordan, R
Hailpern, SM
Schoolwerth, AC
Williams, DE
AF Hoerger, Thomas J.
Wittenborn, John S.
Segel, Joel E.
Burrows, Nilka R.
Imai, Kumiko
Eggers, Paul
Pavkov, Meda E.
Jordan, Regina
Hailpern, Susan M.
Schoolwerth, Anton C.
Williams, Desmond E.
CA Ctr Dis Control & Prevent CKD Init
TI A Health Policy Model of CKD: 1. Model Construction, Assumptions, and
Validation of Health Consequences
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Chronic kidney disease; cost-effectiveness; model; validation
ID CHRONIC KIDNEY-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; CORONARY
HEART-DISEASE; ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE;
RENAL-DISEASE; US ADULTS; NATIONAL-HEALTH; UNITED-STATES; PREVALENCE
AB Background: A cost-effectiveness model that accurately represents disease progression, outcomes, and associated costs is necessary to evaluate the cost-effectiveness of interventions for chronic kidney disease (CKD).
Study Design: We developed a microsimulation model of the incidence, progression, and treatment of CKD. The model was validated by comparing its predictions with survey and epidemiologic data sources.
Setting & Population: US patients.
Model, Perspective, & Timeframe: The model follows up disease progression in a cohort of simulated patients aged 30 until age 90 years or death. The model consists of 7 mutually exclusive states representing no CKD, 5 stages of CKD, and death. Progression through the stages is governed by a person's glomerular filtration rate and albuminuria status. Diabetes, hypertension, and other risk factors influence CKD and the development of CKD complications in the model. Costs are evaluated from the health care system perspective.
Intervention: Usual care, including incidental screening for persons with diabetes or hypertension.
Outcomes: Progression to CKD stages, complications, and mortality.
Results: The model provides reasonably accurate estimates of CKD prevalence by stage. The model predicts that 47.1% of 30-year-olds will develop CKD during their lifetime, with 1.7%, 6.9%, 27.3%, 6.9%, and 4.4% ending at stages 1-5, respectively. Approximately 11% of persons who reach stage 3 will eventually progress to stage 5. The model also predicts that 3.7% of persons will develop end-stage renal disease compared with an estimate of 3.0% based on current end-stage renal disease lifetime incidence.
Limitations: The model synthesizes data from multiple sources rather than a single source and relies on explicit assumptions about progression. The model does not include acute kidney failure.
Conclusion: The model is well validated and can be used to evaluate the cost-effectiveness of CKD interventions. The model also can be updated as better data for CKD progression become available. Am J Kidney Dis 55: 452-462. (C) 2010 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Hoerger, Thomas J.; Wittenborn, John S.; Segel, Joel E.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Burrows, Nilka R.; Pavkov, Meda E.; Jordan, Regina; Hailpern, Susan M.; Williams, Desmond E.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Imai, Kumiko] UNICEF Swaziland, Mbabane, Swaziland.
[Eggers, Paul] NIDDKD, Bethesda, MD 20892 USA.
[Schoolwerth, Anton C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
RP Hoerger, TJ (reprint author), RTI Int, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA.
EM tjh@rti.org
FU CDC [200-2002-00776]
FX This research was supported by funding (contract 200-2002-00776) from
the CDC.
NR 39
TC 30
Z9 30
U1 0
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD MAR
PY 2010
VL 55
IS 3
BP 452
EP 462
DI 10.1053/j.ajkd.2009.11.016
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 563DW
UT WOS:000275109000010
PM 20116911
ER
PT J
AU Hoerger, TJ
Wittenborn, JS
Segel, JE
Burrows, NR
Imai, K
Eggers, P
Pavkov, ME
Jordan, R
Hailpern, SM
Schoolwerth, AC
Williams, DE
AF Hoerger, Thomas J.
Wittenborn, John S.
Segel, Joel E.
Burrows, Nilka R.
Imai, Kumiko
Eggers, Paul
Pavkov, Meda E.
Jordan, Regina
Hailpern, Susan M.
Schoolwerth, Anton C.
Williams, Desmond E.
CA Ctr Dis Control & Prevent CKD Init
TI A Health Policy Model of CKD: 2. The Cost-Effectiveness of
Microalbuminuria Screening
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Chronic kidney disease; cost-effectiveness; model; microalbuminuria;
screening; renal; end-stage renal disease (ESRD)
ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; CONVERTING
ENZYME-INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; NONDIABETIC
RENAL-DISEASE; SERUM CREATININE; UNITED-STATES; NEPHROPATHY; OUTCOMES;
PROTEINURIA
AB Background: Microalbuminuria screening may detect chronic kidney disease in its early stages, allowing for treatment that delays or prevents disease progression. The cost-effectiveness of microalbuminuria screening has not been determined.
Study Design: A cost-effectiveness model simulating disease progression and costs.
Setting & Population: US patients.
Model, Perspective, and Timeframe: The microsimulation model follows up disease progression and costs in a cohort of simulated patients from age 50 to 90 years or death. Costs are evaluated from the health care system perspective.
Intervention: Microalbuminuria screening at 1-, 2-, 5-, or 10-year intervals followed by treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. We considered universal screening, as well as screening targeted at persons with diabetes, persons with hypertension but no diabetes, and persons with neither diabetes nor hypertension.
Outcomes: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.
Results: For the full model population, universal screening increases costs and increases QALYs. Universal annual screening starting at age 50 years has a cost-effectiveness ratio of $73,000/QALY relative to no screening and $145,000/QALY relative to usual care. Cost-effectiveness ratios improved with longer screening intervals. Relative to no screening, targeted annual screening has cost-effectiveness ratios of $21,000/QALY, $55,000/QALY, and $155,000/QALY for persons with diabetes, those with hypertension, and those with neither current diabetes nor current hypertension, respectively.
Limitations: Results necessarily are based on a microsimulation model because of the long time horizon appropriate for chronic kidney disease. The model includes only health care costs.
Conclusions: Microalbuminuria screening is cost-effective for patients with diabetes or hypertension, but is not cost-effective for patients with neither diabetes nor hypertension unless screening is conducted at longer intervals or as part of existing physician visits. Am J Kidney Dis 55: 463-473. (C) 2010 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Hoerger, Thomas J.; Wittenborn, John S.; Segel, Joel E.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Burrows, Nilka R.; Pavkov, Meda E.; Jordan, Regina; Hailpern, Susan M.; Williams, Desmond E.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Imai, Kumiko] UNICEF Swaziland, Mbabane, Swaziland.
[Eggers, Paul] NIDDKD, Bethesda, MD 20892 USA.
[Schoolwerth, Anton C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
RP Hoerger, TJ (reprint author), RTI Int, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA.
EM tjh@rti.org
FU CDC [200-2002-00776]
FX This research was supported by funding (contract 200-2002-00776) from
the CDC.
NR 39
TC 54
Z9 54
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD MAR
PY 2010
VL 55
IS 3
BP 463
EP 473
DI 10.1053/j.ajkd.2009.11.017
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 563DW
UT WOS:000275109000011
PM 20116910
ER
PT J
AU Jolly, SE
Burrows, NR
Chen, SC
Li, SY
Jurkovitz, CT
Narva, AS
Norris, KC
Shlipak, MG
AF Jolly, Stacey E.
Burrows, Nilka Rios
Chen, Shu-Cheng
Li, Suying
Jurkovitz, Claudine T.
Narva, Andrew S.
Norris, Keith C.
Shlipak, Michael G.
TI Racial and Ethnic Differences in Albuminuria in Individuals With
Estimated GFR Greater Than 60 mL/min/1.73 m(2): Results From the Kidney
Early Evaluation Program (KEEP)
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Albuminuria; health disparities; Kidney Early Evaluation Program (KEEP);
screening
ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE VALUES; RENAL-DISEASE;
NONDIABETIC INDIVIDUALS; CARDIOVASCULAR EVENTS; GENERAL-POPULATION;
AMERICAN-INDIANS; NATIONAL-HEALTH; HEART-FAILURE; UNITED-STATES
AB Background: Albuminuria is an important marker for chronic kidney disease and progression to end-stage renal disease in the general population; understanding racial and ethnic differences can help inform efforts to reduce health disparities. We sought to estimate independent associations of race/ethnicity with albuminuria to determine whether observed differences were attributable to known kidney disease risk factors.
Methods: This cross-sectional study included 64,161 Kidney Early Evaluation Program (KEEP) participants, 2000-2008, with estimated glomerular filtration rate >= 60 mL/min/1.73 m(2), not on regular dialysis therapy, and without a previous kidney transplant. Albuminuria (urine albumin-creatinine ratio >= 30 mg/g) was examined by self-reported race and ethnicity. Covariates were age, sex, educational level, body mass index, diabetes status or glucose level, hypertension status or blood pressure measurement, smoking status, health insurance status, and geographic region.
Results: Albuminuria prevalences were 8% (n = 2,303) in whites, 11% (n = 2,310) in African Americans, 9% (n = 730) in Hispanics, 10% (n = 381) in Asians, and 15% (n = 344) in American Indians/ Alaska Natives. Compared with whites, odds of albuminuria were higher for all groups after multivariate adjustment. Odds were highest for American Indians/Alaska Natives (adjusted OR, 1.93; 95% CI, 1.70-2.20), then Asians (adjusted OR, 1.42; 95% CI, 1.26-1.61), African Americans (adjusted OR, 1.38; 95% CI, 1.29-1.47), and Hispanics (adjusted OR, 1.19; 95% CI, 1.08-1.31).
Conclusions: In the KEEP study population, albuminuria prevalence was higher in African Americans, Hispanics, Asians, and American Indians/Alaska Natives than in non-Hispanic whites, suggesting a need for screening for early detection of kidney damage, especially in people at increased risk, in the community primary care setting. Am J Kidney Dis 55(S2):S15-S22. (c) 2010 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Jolly, Stacey E.] Cleveland Clin, Inst Med, Cleveland, OH 44195 USA.
[Burrows, Nilka Rios] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA.
[Chen, Shu-Cheng; Li, Suying] Minneapolis Med Res Fdn Inc, Chron Dis Res Grp, Minneapolis, MN USA.
[Jurkovitz, Claudine T.] Christiana Care Hlth Syst, Ctr Outcomes Res, Newark, DE USA.
[Narva, Andrew S.] NIDDK, Bethesda, MD USA.
[Norris, Keith C.] Charles R Drew Univ Med & Sci, Dept Internal Med, Los Angeles, CA 90059 USA.
[Shlipak, Michael G.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA.
RP Jolly, SE (reprint author), Cleveland Clin, Inst Med, 9500 Euclid Ave,G10, Cleveland, OH 44195 USA.
EM jollys@ccf.org
FU National Kidney Foundation Inc; Amgen; Abbott; Novartis; Siemens;
Genentech; Genzyme; Nephroceuticals; Pfizer; LifeScan; Suplena; National
Institute of Diabetes and Digestive and Kidney Diseases [R01 DK 066488]
FX The KEEP is a program of the National Kidney Foundation Inc and is
supported by Amgen, Abbott, Novartis, Siemens, Genentech, Genzyme,
Nephroceuticals, Pfizer, LifeScan, and Suplena. Dr Shlipak's work was
supported by the American Heart Association Established Investigator
Award and R01 DK 066488 from the National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 41
TC 18
Z9 19
U1 0
U2 2
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 MAR
PY 2010
VL 55
IS 3
SU 2
BP S15
EP S22
DI 10.1053/j.ajkd.2009.09.034
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 559WU
UT WOS:000274859800003
PM 20172444
ER
PT J
AU Kaplan, L
Foster, R
Shen, YP
Parry, DM
McMaster, ML
O'Leary, MC
Gusella, JF
AF Kaplan, Lee
Foster, Rosemary
Shen, Yiping
Parry, Dilys M.
McMaster, Mary L.
O'Leary, Melanie Collins
Gusella, James F.
TI Monozygotic Twins Discordant for Neurofibromatosis 1
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE neurofibromatosis type 1; monozygotic twins; discordance; post-zygotic
mutation
ID SEGMENTAL NEUROFIBROMATOSIS; NF1 GENE; TYPE-1 NF1; VONRECKLINGHAUSEN
NEUROFIBROMATOSIS; NONSENSE MUTATION; MOSAICISM; POLYMORPHISMS;
METHYLATION; FREQUENCY; SEQUENCE
AB We present monozygotic twins discordant for the autosomal dominant disorder neurofibromatosis type 1 (NF1). The affected twin was diagnosed with NF1 at age 12, based upon accepted clinical criteria for the disorder. Both twins were re-examined at ages 35 and 57, at which times the unaffected twin continued to show no clinical manifestations of NF1. Short tandem repeat marker (STR) genotyping at 10 loci on chromosome 17 and 10 additional loci dispersed across the genome revealed identical genotypes for the twins, confirming their monozygosity. The affected twin has three children, two of whom also have NF1, while the unaffected twin has two children, both unaffected. Using lymphoblastoid, fibroblast, and buccal cell samples collected from both twins and from other family members in three generations, we discovered a pathogenic nonsense mutation in exon 40 of the NF1 gene. This mutation was found in all cell samples from the affected twin and her affected daughter, and in lymphoblastoid and buccal cells but not fibroblasts from the unaffected twin. We also found a novel non-synonymous change in exon 16 of the NF1 gene that was transmitted from the unaffected mother to both twins and co-segregated with the pathogenic mutation in the ensuing generation. All cells from the twins were heterozygous for this apparent exon 16 polymorphism and for single nucleotide polymorphisms (SNPs) within 2.5 kb flanking the site of the exon 40 nonsense mutation. This suggests that the NF1 gene of the unaffected twin differed in the respective lymphoblastoid cells and fibroblasts only at the mutation site itself, making post-zygotic mutation leading to mosaicism the most likely mechanism of phenotypic discordance. Although the unaffected twin is a mosaic, the distribution of the mutant allele among different cells and tissues appears to be insufficient to cause overt clinical manifestations of NF1. (C) 2010 Wiley-Liss, Inc.
C1 [Kaplan, Lee; Shen, Yiping; O'Leary, Melanie Collins; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kaplan, Lee; Shen, Yiping; O'Leary, Melanie Collins; Gusella, James F.] Harvard Univ, Sch Med, Ctr Neurofibromatosis & Allied Disorders, Boston, MA USA.
[Foster, Rosemary] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Foster, Rosemary] Ctr Regenerat Med, Boston, MA USA.
[Foster, Rosemary] Harvard Stem Cell Inst, Boston, MA USA.
[Shen, Yiping] Childrens Hosp, DNA Diagnost Lab, Dept Lab Med, Boston, MA 02115 USA.
[Parry, Dilys M.; McMaster, Mary L.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, CPZN-5830,185 Cambridge St, Boston, MA 02114 USA.
EM gusella@helix.mgh.harvard.edu
FU NINDS [NS22224, NS24279]; Neurofibromatosis, Inc., Northeast; S. Sydney
De Young Foundation
FX The authors would like to thank the family members who have contributed
samples and time in the clinic so that we could perform this research
project. Also we thank Mary Anne Anderson and the CHGR Cell Culture
Resource for making the stable cell lines, James Mull for technical
assistance, and Tammy Gillis and the CHGR Genomics Resource for DNA
sequence analysis. Funded by grants from the NINDS (NS22224, NS24279),
Neurofibromatosis, Inc., Northeast, and the S. Sydney De Young
Foundation.
NR 43
TC 20
Z9 20
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD MAR
PY 2010
VL 152A
IS 3
BP 601
EP 606
DI 10.1002/ajmg.a.33271
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 576OV
UT WOS:000276155200010
PM 20186797
ER
PT J
AU van den Berg, L
Delemarre-van de Waa, H
Han, JC
Ylstra, B
Eijk, P
Nesterova, M
Heutink, P
Stratakis, CA
AF van den Berg, Linda
Delemarre-van de Waa, Henriette
Han, Joan C.
Ylstra, Bauke
Eijk, Paul
Nesterova, Maria
Heutink, Peter
Stratakis, Constantine A.
TI Investigation of a Patient With a Partial Trisomy 16q Including the Fat
Mass and Obesity Associated Gene (FTO): Fine Mapping and FTO Gene
Expression Study
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE 16q duplication; obesity; FTO; CGH; qPCR; imprinting; SLC6A2; ADHD; BBS2
ID IN-SITU HYBRIDIZATION; INTERSTITIAL DUPLICATION; PRENATAL-DIAGNOSIS;
ADULT OBESITY; VARIANTS; MICROARRAY; RESOLUTION; CHILDHOOD; ANOMALIES;
INFANT
AB A female patient with a partial trisomy 16q was described previously. Her clinical characteristics included obesity, severe anisomastia, moderate to severe mental retardation, attention deficit hyperactivity disorder, dysmorphic facies, and contractions of the small joints. In this article, we describe a more detailed analysis of the genetic anomaly in this patient. We were particularly interested in the involvement of the fat mass and obesity associated gene (PTO) in her duplication. Single nucleotide polymorphisms in FTO have been associated with obesity. The breakpoints of the duplication were precisely mapped using high-resolution oligonucleotide array comparative genomic hybridization (CGH). We found that the duplication spans 11.45 Mb on 16q11.2 to 16q13 and it includes FTO. The increased copy number of FTO was confirmed with a qPCR on genomic DNA of the patient. We investigated the influence of the increased FTO copy number on FTO gene expression in immortalized lymphocytes from the patient using qPCR. No evidence of increased FTO expression was detected in the patient's lymphocytes. We discuss these findings and we review clinical findings in patients with overlapping 16q duplications to determine the relationship between increased FTO copy number and obesity. Our review suggests that duplication of the FTO gene does not necessarily result in obesity. (C) 2010 Wiley-Liss, Inc.
C1 [van den Berg, Linda; Heutink, Peter] Vrije Univ Amsterdam, Dept Clin Genet, Sect Med Genom, Med Ctr, NL-1081 BT Amsterdam, Netherlands.
[van den Berg, Linda; Delemarre-van de Waa, Henriette] Leiden Univ, Dept Pediat, Med Ctr, Leiden, Netherlands.
[van den Berg, Linda] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Han, Joan C.; Nesterova, Maria; Stratakis, Constantine A.] NICHHD, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Ylstra, Bauke; Eijk, Paul] Vrije Univ Amsterdam, Micro Array Core Facil, Dept Pathol, Med Ctr, NL-1081 BT Amsterdam, Netherlands.
RP Heutink, P (reprint author), Vrije Univ Amsterdam, Dept Clin Genet, Sect Med Genom, Med Ctr, van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands.
EM p.heutink@vumc.nl
RI Ylstra, Bauke/D-2906-2012
OI Ylstra, Bauke/0000-0001-9479-3010
FU U.S. Public Health Service
FX We thank Burcu Anar, Carola van Berkel, Koen de Groot, Katarina Rak,
Patrizia Rizzu, and Claudia Ruivenkamp for technical assistance. Zoltan
Bochdanovits, Martijn Breuning, Mikael Kubista, Jan Ruijter, Erik
Sistermans, Sabine Spijker, Jo Vandesompele, and Mark van de Wiel are
thanked for their advice on data analysis. We thank Goran Anneren, John
Barber, Angela Barnicoat, Christine de Die, John Engelen, Jean-Pierre
Fryns, and Peter Gustavsson for providing information about the obesity
phenotype of their patients. JCH is a commissioned officer in the U.S.
Public Health Service.
NR 35
TC 14
Z9 14
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD MAR
PY 2010
VL 152A
IS 3
BP 630
EP 637
DI 10.1002/ajmg.a.33229
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 576OV
UT WOS:000276155200014
PM 20186806
ER
PT J
AU Goes, FS
Willour, VL
Zandi, PP
Belmonte, PL
MacKinnon, DF
Mondimore, FM
Schweizer, B
DePaulo, JR
Gershon, ES
McMahon, FJ
Potash, JB
AF Goes, F. S.
Willour, V. L.
Zandi, P. P.
Belmonte, P. L.
MacKinnon, D. F.
Mondimore, F. M.
Schweizer, B.
DePaulo, J. R., Jr.
Gershon, E. S.
McMahon, F. J.
Potash, J. B.
CA Natl Inst Mental Hlth Genetics Ini
TI Sex-Specific Association of the Reelin Gene With Bipolar Disorder
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE genetics; bipolar disorder; schizophrenia; overlap; neurodevelopment
ID MAJOR DEPRESSION; SCHIZOPHRENIA; LINKAGE; BRAIN; NEURONS; DEMETHYLATION;
METAANALYSIS; POPULATION; RECEPTORS; PEDIGREES
AB The Reelin gene (RELN) encodes a secretory glycoprotein critical for brain development and synaptic plasticity. Post-mortem studies have shown lower Reelin protein levels in the brains of patients with schizophrenia and bipolar disorder (BP) compared with controls. In a recent genome-wide association study of schizophrenia, the strongest association was found in a marker within RELN, although this association was seen only in women. In this study, we investigated whether genetic variation in RELN is associated with BP in a large family sample. We genotyped 75 tagSNPs and 6 coding SNPs in 1,188 individuals from 318 nuclear families, including 554 affected offspring. Quality control measures, transmission-disequilibrium tests (TDTs), and empirical simulations were performed in PLINK. We found a significant overtransmission of the C allele of rs362719 to BP offspring (OR=1.47, P=5.9 x 10(-4)); this withstood empirical correction for testing of multiple markers (empirical P=0.048). In a hypothesis-driven secondary analysis, we found that the association with rs362719 was almost entirely accounted for by overtransmission of the putative risk allele to affected females (OR(Female)=1.79, P=8.9x10(-5) vs. OR(Male)=1.12, P=0.63). These results provide preliminary evidence that genetic variation in RELN is associated with susceptibility to BP and, in particular, to BP in females. However, our findings should be interpreted with caution until further replication and functional assays provide convergent support. (C) 2009 Wiley-Liss, Inc.
C1 [Goes, F. S.; Willour, V. L.; Zandi, P. P.; Belmonte, P. L.; MacKinnon, D. F.; Mondimore, F. M.; Schweizer, B.; DePaulo, J. R., Jr.; Potash, J. B.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA.
[Willour, V. L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
[Gershon, E. S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA.
[McMahon, F. J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Mood & Anxiety Program, NIH,US Dept HHS, Bethesda, MD 20892 USA.
RP Potash, JB (reprint author), Meyer 4-119,600 N Wolfe St, Baltimore, MD 21287 USA.
EM jpotash@jhmi.edu
OI McMahon, Francis/0000-0002-9469-305X
FU NIMH NIH HHS [K01 MH072866, K01 MH072866-01, K99 MH086049-02, K99
MH086049]
NR 36
TC 29
Z9 29
U1 2
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD MAR
PY 2010
VL 153B
IS 2
BP 549
EP 553
DI 10.1002/ajmg.b.31018
PG 5
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 566NI
UT WOS:000275377900022
PM 19691043
ER
PT J
AU Wang, Y
Adamczyk, A
Shugart, YY
Samuels, JF
Grados, MA
Greenberg, BD
Knowles, JA
McCracken, JT
Rauch, SL
Murphy, DL
Rasmussen, SA
Cullen, B
Pinto, A
Fyer, AJ
Piacentini, J
Pauls, DL
Bienvenu, OJ
Riddle, M
Liang, KY
Valle, D
Wang, T
Nestadt, G
AF Wang, Y.
Adamczyk, A.
Shugart, Y. Y.
Samuels, J. F.
Grados, M. A.
Greenberg, B. D.
Knowles, J. A.
McCracken, J. T.
Rauch, S. L.
Murphy, D. L.
Rasmussen, S. A.
Cullen, B.
Pinto, A.
Fyer, A. J.
Piacentini, J.
Pauls, D. L.
Bienvenu, O. J.
Riddle, M.
Liang, K. Y.
Valle, D.
Wang, T.
Nestadt, G.
TI A Screen of SLC1A1 for OCD-Related Alleles
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE OCD; SLC1A1; polymorphism
ID OBSESSIVE-COMPULSIVE DISORDER; CONFORMATION POLYMORPHISM; TRANSPORTER
GENE; ASSOCIATION; AUGMENTATION; LINKAGE
AB SLC1A1, which encodes the neuronal and epithelial glutamate transporter, is a promising candidate gene for obsessive-compulsive disorder (OCD). In this study, we conducted capillary electrophoresis single-strand conformation polymorphism (CE-SSCP) screen for all 12 identified exons, including all coding regions and similar to 50 bp of flanking introns of the human SLC1A1 in 378 OCD-affected individuals. Full sequencing was completed on samples that showed an aberrant SSCP tracing for identification of the underlying sequence variants. Our aim was to determine if there are differences in the frequencies of relatively common alleles, or rare functional alleles, in 378 OCD cases and 281 ethnically matched controls. We identified one non-synonymous coding SNP (c.490A > G, T164A) and three synonymous coding SNP (c.81G>C, A27A; c.414A>G, T138T; c.1110T > C, T370T) in case samples. We found no statistical differences in genotype and allele frequencies of common cSNPs in SLC1A1 between the OCD cases and controls. The rare variant T164A was found only in one family. Further investigation of this variant is necessary to determine whether and how it is related to OCD. There was no other evidence of significant accumulation of deleterious coding mutations in SLC1A1 in the OCD cases. (C) 2009 Wiley-Liss, Inc.
C1 [Wang, Y.; Samuels, J. F.; Grados, M. A.; Cullen, B.; Bienvenu, O. J.; Riddle, M.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Adamczyk, A.; Valle, D.; Wang, T.] Johns Hopkins Univ, Sch Med, Dept Pediat, Mckusick Nathan Inst Genet Med, Baltimore, MD 21205 USA.
[Shugart, Y. Y.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Greenberg, B. D.; Rasmussen, S. A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA.
[Knowles, J. A.] Univ So Calif, Dept Psychiat, Los Angeles, CA USA.
[McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA.
[Rauch, S. L.; Pauls, D. L.] Harvard Univ, Sch Med, Boston, MA USA.
[Rauch, S. L.; Pauls, D. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Rauch, S. L.; Pauls, D. L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA.
[Pinto, A.; Fyer, A. J.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Liang, K. Y.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
RP Wang, Y (reprint author), 1629 Thames St,Suite 401, Baltimore, MD 21231 USA.
EM ywang37@jhmi.edu
RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Adamczyk,
Abby/E-4457-2014; Pinto, Anthony/D-2718-2017;
OI Adamczyk, Abby/0000-0001-7653-295X; Pinto, Anthony/0000-0002-6078-7242;
Samuels, Jack/0000-0002-6715-7905
NR 16
TC 18
Z9 19
U1 1
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD MAR
PY 2010
VL 153B
IS 2
BP 675
EP 679
DI 10.1002/ajmg.b.31001
PG 5
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 566NI
UT WOS:000275377900036
PM 19569082
ER
PT J
AU Romero, R
Conde-Agudelo, A
AF Romero, Roberto
Conde-Agudelo, Agustin
TI What gestation cut-off should be used for magnesium sulfate treatment of
women threatening to deliver preterm? REPLY
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Letter
ID CONTROLLED-TRIAL; CEREBRAL-PALSY; PREVENTION; BIRTH
C1 [Romero, Roberto; Conde-Agudelo, Agustin] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA.
RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, 3990 John R,4 Brush, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
NR 6
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAR
PY 2010
VL 202
IS 3
BP E9
EP E10
DI 10.1016/j.ajog.2009.09.011
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 568IV
UT WOS:000275516900047
ER
PT J
AU Bailit, JL
Gregory, KD
Reddy, UM
Gonzalez-Quintero, VH
Hibbard, JU
Ramirez, MM
Branch, DW
Burkman, R
Haberman, S
Hatjis, CG
Hoffman, MK
Kominiarek, M
Landy, HJ
Learman, LA
Troendle, J
Van Veldhuisen, P
Wilkins, I
Sun, LP
Zhang, J
AF Bailit, Jennifer L.
Gregory, Kimberly D.
Reddy, Uma M.
Gonzalez-Quintero, Victor H.
Hibbard, Judith U.
Ramirez, Mildred M.
Branch, D. Ware
Burkman, Ronald
Haberman, Shoshana
Hatjis, Christos G.
Hoffman, Matthew K.
Kominiarek, Michelle
Landy, Helain J.
Learman, Lee A.
Troendle, James
Van Veldhuisen, Paul
Wilkins, Isabelle
Sun, Liping
Zhang, Jun
TI Maternal and neonatal outcomes by labor onset type and gestational age
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine
CY FEB 01-06, 2010
CL Chicago, IL
SP Soc Maternal Fetal Med
DE elective delivery; hysterectomy; maternal outcomes; neonatal outcomes
ID PRETERM BIRTH; TERM; RATES
AB OBJECTIVE: We sought to determine maternal and neonatal outcomes by labor onset type and gestational age.
STUDY DESIGN: We used electronic medical records data from 10 US institutions in the Consortium on Safe Labor on 115,528 deliveries from 2002 through 2008. Deliveries were divided by labor onset type (spontaneous, elective induction, indicated induction, unlabored cesarean). Neonatal and maternal outcomes were calculated by labor onset type and gestational age.
RESULTS: Neonatal intensive care unit admissions and sepsis improved with each week of gestational age until 39 weeks (P < .001). After adjusting for complications, elective induction of labor was associated with a lower risk of ventilator use (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.28-0.53), sepsis (OR, 0.36; 95% CI, 0.26-0.49), and neonatal intensive care unit admissions (OR, 0.52; 95% CI, 0.48-0.57) compared to spontaneous labor. The relative risk of hysterectomy at term was 3.21 (95% CI, 1.08-9.54) with elective induction, 1.16 (95% CI, 0.24-5.58) with indicated induction, and 6.57 (95% CI, 1.78-24.30) with cesarean without labor compared to spontaneous labor.
CONCLUSION: Some neonatal outcomes improved until 39 weeks. Babies born with elective induction are associated with better neonatal outcomes compared to spontaneous labor. Elective induction may be associated with an increased hysterectomy risk.
C1 [Bailit, Jennifer L.] Case Western Reserve Univ, Div Maternal Fetal Med, Dept Obstet & Gynecol, Cleveland, OH 44106 USA.
[Bailit, Jennifer L.] Case Western Reserve Univ, Ctr Hlth Care Res & Policy, MetroHealth Med Ctr, Cleveland, OH 44106 USA.
[Gregory, Kimberly D.] Cedars Sinai Med Ctr, Burns & Allen Res Inst, Los Angeles, CA 90048 USA.
[Reddy, Uma M.; Troendle, James; Sun, Liping; Zhang, Jun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Gonzalez-Quintero, Victor H.] Univ Miami, Sch Med, Miami, FL USA.
[Hibbard, Judith U.; Wilkins, Isabelle] Univ Illinois, Dept Obstet & Gynecol, Sch Med, Chicago, IL 60612 USA.
[Ramirez, Mildred M.] Univ Texas Med Sch Houston, Dept Obstet & Gynecol, Houston, TX USA.
[Branch, D. Ware] Intermt HealthCare, Salt Lake City, UT USA.
[Burkman, Ronald] Baystate Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA.
[Haberman, Shoshana] Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA.
[Hatjis, Christos G.] Summa Hlth Syst, Akron, OH USA.
[Hoffman, Matthew K.] Christiana Care Hlth Syst, Wilmington, DE USA.
[Kominiarek, Michelle; Learman, Lee A.] Indiana Univ Clarian Hlth, Indianapolis, IN USA.
[Landy, Helain J.] MedStar Hlth, Washington, DC USA.
[Van Veldhuisen, Paul] Emmes Corp, Rockville, MD USA.
RP Bailit, JL (reprint author), Case Western Reserve Univ, Div Maternal Fetal Med, Dept Obstet & Gynecol, Cleveland, OH 44106 USA.
FU Intramural NIH HHS; NICHD NIH HHS [HHSN267200603425C]; None [8421358]
NR 7
TC 21
Z9 23
U1 0
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAR
PY 2010
VL 202
IS 3
AR 245.e1
DI 10.1016/j.ajog.2010.01.051
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 568IV
UT WOS:000275516900013
PM 20207242
ER
PT J
AU Hashima, JN
Lai, YL
Wapner, RJ
Sorokin, Y
Dudley, DJ
Peaceman, A
Spong, CY
Iams, JD
Leveno, KJ
Harper, M
Caritis, SN
Varner, M
Miodovnik, M
Mercer, BM
Thorp, JM
O'Sullivan, MJ
Ramin, SM
Carpenter, M
Rouse, DJ
Sibai, B
AF Hashima, Jason N.
Lai, Yinglei
Wapner, Ronald J.
Sorokin, Yoram
Dudley, Donald J.
Peaceman, Alan
Spong, Catherine Y.
Iams, Jay D.
Leveno, Kenneth J.
Harper, Margaret
Caritis, Steve N.
Varner, Michael
Miodovnik, Menachem
Mercer, Brian M.
Thorp, John M.
O'Sullivan, Mary J.
Ramin, Susan M.
Carpenter, Marshall
Rouse, Dwight J.
Sibai, Baha
CA Eunice Kennedy Shriver Natl Inst C
TI The effect of maternal body mass index on neonatal outcome in women
receiving a single course of antenatal corticosteroids
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine
CY JAN 26-31, 2009
CL San Diego, CA
SP Soc Maternal Fetal Med
DE antenatal corticosteroids; BMI; neonatal morbidity; obesity; prematurity
ID PREGNANCY; OBESITY; RISK
AB OBJECTIVE: The aim of this study was to determine the effect of maternal body mass index on the incidence of neonatal prematurity morbidities in those who receive corticosteroids.
STUDY DESIGN: This was a secondary analysis of a trial of corticosteroids in women at risk for preterm birth. Women receiving a single course of corticosteroids were classified by their prepregnancy body mass index (<25 and >= 25) and compared on a composite outcome comprised of several neonatal morbidities and on each individual outcome.
RESULTS: Of 183 eligible women, 96 (52.5%) had a body mass index of <25 and 87 (47.5%) had a body mass index of >= 25. The composite outcome occurred more frequently in the body mass index of >= 25 group (28.7%), compared with those with a body mass index of <25 (18.8%), although this was not statistically significant (odds ratio, 1.75; 95% confidence interval, 0.83-3.72). Body mass index was not associated with outcomes after adjusting for confounding.
CONCLUSION: Maternal body mass index did not affect neonatal prematurity morbidities in those receiving corticosteroids.
C1 [Hashima, Jason N.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA.
[Lai, Yinglei] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Wapner, Ronald J.] Drexel Univ, Philadelphia, PA 19104 USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Dudley, Donald J.; Varner, Michael] Univ Utah, Salt Lake City, UT USA.
[Peaceman, Alan] Northwestern Univ, Chicago, IL 60611 USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA.
[Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
[Miodovnik, Menachem] Columbia Univ, New York, NY USA.
[Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH USA.
[Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA.
[O'Sullivan, Mary J.] Univ Miami, Miami, FL USA.
[Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA.
[Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA.
[Sibai, Baha] Univ Tennessee, Memphis, TN USA.
RP Hashima, JN (reprint author), 181 SW Sam Jackson Pk Rd,L458, Portland, OR 97239 USA.
EM hashimaj@ohsu.edu
RI Varner, Michael/K-9890-2013;
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973;
Peaceman, Alan/0000-0002-4515-4850
FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [M01 RR000080,
M01-RR-000080]; NICHD NIH HHS [U10 HD027917-12, HD21410, HD21414,
HD27860, HD27861, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208,
HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, R24
HD050924, U01 HD036801, U01 HD036801-02, U01 HD036801-03, U01
HD036801-04, U01 HD036801-05, U01 HD036801-06, U01 HD036801-07, U01
HD036801-08, U01 HD036801-09, U01 HD036801-10, U01 HD036801-10S1, U01
HD036801-10S2, U10 HD021410, U10 HD021410-14, U10 HD021410-15, U10
HD021410-15S1, U10 HD021410-16, U10 HD021410-16S1, U10 HD021410-17, U10
HD021410-17S1, U10 HD021410-18, U10 HD021410-19, U10 HD021410-20, U10
HD021410-21, U10 HD021410-22, U10 HD021414-09S1, U10 HD021414-14, U10
HD021414-14S1, U10 HD021414-15, U10 HD021414-15S1, U10 HD021414-15S2,
U10 HD027860, U10 HD027860-09, U10 HD027860-10, U10 HD027860-11, U10
HD027860-11S1, U10 HD027860-12, U10 HD027860-12S1, U10 HD027860-13, U10
HD027860-14, U10 HD027860-15, U10 HD027860-15S1, U10 HD027861-09, U10
HD027861-10, U10 HD027861-10S1, U10 HD027861-10S2, U10 HD027869, U10
HD027869-09, U10 HD027869-10, U10 HD027869-10S1, U10 HD027869-11, U10
HD027869-12, U10 HD027869-13, U10 HD027869-14, U10 HD027869-15, U10
HD027869-16, U10 HD027869-16S1, U10 HD027869-17, U10 HD027869-18, U10
HD027905, U10 HD027905-09, U10 HD027905-10, U10 HD027915, U10
HD027915-08, U10 HD027915-09, U10 HD027915-10, U10 HD027915-11, U10
HD027915-12, U10 HD027915-13, U10 HD027915-14, U10 HD027915-15, U10
HD027915-16, U10 HD027915-17, U10 HD027915-18, U10 HD027917, U10
HD027917-09, U10 HD027917-09S1, U10 HD027917-10, U10 HD027917-10S1, U10
HD027917-11, U10 HD027917-13, U10 HD027917-14, U10 HD027917-15, U10
HD027917-16, U10 HD027917-17, U10 HD027917-18, U10 HD034116, U10
HD034116-04, U10 HD034116-05, U10 HD034116-05S1, U10 HD034116-06, U10
HD034116-07, U10 HD034116-08, U10 HD034116-09, U10 HD034116-10, U10
HD034116-11, U10 HD034116-11S1, U10 HD034116-12, U10 HD034116-13, U10
HD034122, U10 HD034122-04, U10 HD034122-04S1, U10 HD034122-05, U10
HD034136, U10 HD034136-04, U10 HD034136-05, U10 HD034136-06, U10
HD034136-07, U10 HD034136-08, U10 HD034136-09, U10 HD034136-10, U10
HD034136-10S1, U10 HD034136-10S2, U10 HD034208, U10 HD034208-04, U10
HD034208-05, U10 HD034208-05S1, U10 HD034208-06, U10 HD034208-06S1, U10
HD034208-07, U10 HD034208-08, U10 HD034208-08S1, U10 HD034208-09, U10
HD034208-10, U10 HD034208-11, U10 HD034208-12, U10 HD036801, U10
HD036801-11, U10 HD040485, U10 HD040485-01, U10 HD040485-02, U10
HD040485-03, U10 HD040485-04, U10 HD040485-05, U10 HD040485-06, U10
HD040485-07, U10 HD040485-07S1, U10 HD040485-08, U10 HD040485-09, U10
HD040500, U10 HD040500-01, U10 HD040500-01S1, U10 HD040500-02, U10
HD040500-03, U10 HD040500-04, U10 HD040500-05, U10 HD040500-06, U10
HD040500-07, U10 HD040500-08, U10 HD040500-09, U10 HD040512, U10
HD040512-01, U10 HD040512-02, U10 HD040512-02S1, U10 HD040512-03, U10
HD040512-04, U10 HD040512-05, U10 HD040512-06, U10 HD040512-07, U10
HD040512-08, U10 HD040512-09, U10 HD040544, U10 HD040544-01, U10
HD040544-02, U10 HD040544-03, U10 HD040544-04, U10 HD040544-05, U10
HD040544-06, U10 HD040544-07, U10 HD040544-08, U10 HD040544-09, U10
HD040545, U10 HD040545-01, U10 HD040545-02, U10 HD040545-02S1, U10
HD040545-03, U10 HD040545-04, U10 HD040545-05, U10 HD040545-06, U10
HD040545-07, U10 HD040545-08, U10 HD040545-09, U10 HD040560, U10
HD040560-01, U10 HD040560-02, U10 HD040560-03, U10 HD040560-04, U10
HD040560-05, U10 HD040560-06, U10 HD040560-07, U10 HD040560-08, U10
HD040560-09, UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208, UG1
HD040485, UG1 HD040500, UG1 HD040512, UG1 HD040544, UG1 HD040545, UG1
HD040560]
NR 10
TC 2
Z9 2
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAR
PY 2010
VL 202
IS 3
AR 263.e1
DI 10.1016/j.ajog.2009.10.859
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 568IV
UT WOS:000275516900019
PM 20022589
ER
PT J
AU Daniel, E
Thorne, JE
Newcomb, CW
Pujari, SS
Kacmaz, RO
Levy-Clarke, GA
Nussenblatt, RB
Rosenbaum, JT
Suhler, EB
Foster, CS
Jabs, DA
Kempen, JH
AF Daniel, Ebenezer
Thorne, Jennifer E.
Newcomb, Craig W.
Pujari, Siddharth S.
Kacmaz, R. Oktay
Levy-Clarke, Grace A.
Nussenblatt, Robert B.
Rosenbaum, James T.
Suhler, Eric B.
Foster, C. Stephen
Jabs, Douglas A.
Kempen, John H.
TI Mycophenolate Mofetil for Ocular Inflammation
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID EYE DISEASE; IMMUNOSUPPRESSIVE THERAPY; UVEITIS; AGENT; DRUGS
AB PURPOSE: To evaluate mycophenolate mofetil as a single noncorticosteroid immunosuppressive treatment for noninfectious ocular inflammatory diseases.
DESIGN: Retrospective cohort study.
METHODS: Characteristics of patients with noninfectious ocular inflammation treated with mycophenolate mofetil at 4 subspecialty clinics from 1995 to 2007 were abstracted by expert reviewers in a standardized chart review of every eye at every visit. Main outcomes measured were control of inflammation, corticosteroid-sparing effects, and discontinuation of mycophenolate mofetil (including the reasons for discontinuation). Survival analysis was used to estimate the incidence of outcomes, and to identify risk factors for each.
RESULTS: Among 236 patients (397 eyes) treated with mycophenolate mofetil monotherapy, 20.3%, 11.9%, and 39.8% had anterior uveitis, intermediate uveitis, and posterior uveitis or panuveitis respectively; 14% had scleritis; 7.6% had mucous membrane pemphigoid; and 6.4% had other ocular inflammatory diseases. By Kaplan-Meier estimation, complete control of inflammation-sustained over consecutive visits spanning at least 28 days-was achieved in 53% and 73% of patients within 6 months and 1 year respectively. Systemic corticosteroid dosage was reduced to 10 mg of prednisone or less, while maintaining sustained control of inflammation, in 41% and 55% of patients in 6 months and 1 year respectively. Twelve percent of patients discontinued mycophenolate mofetil within the first year because of side effects of therapy.
CONCLUSIONS: Given sufficient time, mycophenolate mofetil was effective in managing ocular inflammation in approximately half of the treated patients. Treatment, limiting side effects were observed in 12% of patients and typically were reversible. (Am J Ophthalmol 2010;149: 423-432. (C) 2010 by Elsevier Inc. All rights reserved.)
C1 [Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Sch Med, Philadelphia, PA 19104 USA.
[Daniel, Ebenezer] Univ Penn, Sch Med, Fundus Photograph Reading Ctr, Philadelphia, PA 19104 USA.
[Newcomb, Craig W.; Jabs, Douglas A.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Newcomb, Craig W.; Kempen, John H.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA.
[Thorne, Jennifer E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Pujari, Siddharth S.; Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Dept Ophthalmol, Tarpon Springs, FL USA.
[Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
[Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA.
[Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Kacmaz, R. Oktay; Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Sch Med, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM john.kempen@uphs.upenn.edu
OI Daniel, Ebenezer/0000-0002-2027-2316
FU NEI NIH HHS [R01 EY014943-05, EY014943, R56 EY014943, R01 EY014943]
NR 27
TC 77
Z9 81
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD MAR
PY 2010
VL 149
IS 3
BP 423
EP 432
DI 10.1016/j.ajo.2009.09.026
PG 10
WC Ophthalmology
SC Ophthalmology
GA 565MD
UT WOS:000275296400011
PM 20042178
ER
PT J
AU Olsen, RJ
Kobayashi, SD
Ayeras, AA
Ashraf, M
Graves, SF
Ragasa, W
Humbird, T
Greaver, JL
Cantu, C
Swain, JL
Jenkins, L
Blasdel, T
Cagle, PT
Gardner, DJ
DeLeo, FR
Musser, JM
AF Olsen, Randall J.
Kobayashi, Scott D.
Ayeras, Ara A.
Ashraf, Madiha
Graves, Shawna F.
Ragasa, Willie
Humbird, Tammy
Greaver, Jamieson L.
Cantu, Constance
Swain, Jody L.
Jenkins, Leslie
Blasdel, Terry
Cagle, Philip T.
Gardner, Donald J.
DeLeo, Frank R.
Musser, James M.
TI Lack of a Major Role of Staphylococcus aureus Panton-Valentine
Leukocidin in Lower Respiratory Tract Infection in Nonhuman Primates
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID LYMPHOID-TISSUE IBALT; VIRULENCE DETERMINANTS; NECROTIZING PNEUMONIA;
SKIN INFECTIONS; HEALTHY-ADULTS; INFLUENZA; DISEASE; EPIDEMIOLOGY;
USA300; VIRUS
AB Panton-Valentine leukocidin (PVL) is a two-component cytolytic toxin epidemiologically linked to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, including serious invasive infections caused by the epidemic clone referred to as strain USA300. Although PVL has long been known to be a S. aureus virulence molecule in vitro, the relative contribution of this leukotoxin to invasive CA-MRSA infections such as pneumonia remains controversial. We developed a nonhuman primate model of CA-MRSA pneumonia and used it to test the hypothesis that PVL contributes to lower respiratory tract infections caused by S. aureus strain USA300. The lower respiratory tract disease observed in this monkey model mimicked the clinical and pathological features of early mild to moderate S. aureus pneumonia in humans, including fine-structure histopathology. In this experiment using a large sample of monkeys and multiple time points of examination, no involvement of PVL in virulence could be de-tected. Compared with the wild-type parental USA300 strain, the isogenic PVL deletion-mutant strain caused equivalent lower respiratory tract pathology. We conclude that PVL does not contribute to lower respiratory tract infection in this nonhuman primate model of human CA-MRSA pneumonia. (Am J Pathol 2010, 176:1346-1354; DOI: 10.2353/ajpath.2010.090960)
C1 [Olsen, Randall J.; Ayeras, Ara A.; Ashraf, Madiha; Ragasa, Willie; Cantu, Constance; Cagle, Philip T.; Musser, James M.] Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77030 USA.
[Gardner, Donald J.] Methodist Hosp, Res Inst, Comparat Med Program, Houston, TX 77030 USA.
[Olsen, Randall J.; Musser, James M.] Methodist Hosp, Dept Pathol, Houston, TX 77030 USA.
[Ashraf, Madiha] Methodist Hosp, Dept Med, Houston, TX 77030 USA.
[Kobayashi, Scott D.; Graves, Shawna F.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Swain, Jody L.] NIAID, Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Humbird, Tammy; Greaver, Jamieson L.; Blasdel, Terry] Univ Houston, Div Res, Houston, TX 77004 USA.
[Jenkins, Leslie] Baylor Coll Med, Ctr Comparat Med, Houston, TX 77030 USA.
RP Musser, JM (reprint author), Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, B490,6565 Fannin St, Houston, TX 77030 USA.
EM jmmusser@tmhs.org
OI DeLeo, Frank/0000-0003-3150-2516
FU American Heart Association Fellow-to-Faculty Transition Award; National
Institutes of Health, National Institute of Allergy and Infectious
Diseases
FX Supported by American Heart Association Fellow-to-Faculty Transition
Award (to R.J.O.) and Intramural Research Program of the National
Institutes of Health, National Institute of Allergy and Infectious
Diseases.
NR 50
TC 29
Z9 30
U1 0
U2 3
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD MAR
PY 2010
VL 176
IS 3
BP 1346
EP 1354
DI 10.2353/ajpath.2010.090960
PG 9
WC Pathology
SC Pathology
GA 565MI
UT WOS:000275297000031
PM 20093487
ER
PT J
AU Ghosh, S
Hoenerhoff, MJ
Clayton, N
Myers, P
Stumpo, DJ
Maronpot, RR
Blackshear, PJ
AF Ghosh, Sanjukta
Hoenerhoff, Mark J.
Clayton, Natasha
Myers, Page
Stumpo, Deborah J.
Maronpot, Robert R.
Blackshear, Perry J.
TI Left-Sided Cardiac Valvulitis in Tristetraprolin-Deficient Mice The Role
of Tumor Necrosis Factor alpha
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MESSENGER-RNA STABILITY; AORTIC-VALVE SCLEROSIS; AU-RICH ELEMENTS;
TNF-ALPHA; TRANSGENIC MICE; RHEUMATOID-ARTHRITIS; MONOCLONAL-ANTIBODY;
HEART-DISEASE; RECEPTOR; OVEREXPRESSION
AB Inflammation may play a role in the etiology of both degenerative and rheumatic cardiac valve diseases. We report here that mice deficient in tristetraprolin (TTP), a protein with known anti-inflammatory functions, develop severe left-sided cardiac valvulitis. TTP is an mRNA binding protein that inhibits inflammation by destabilizing the mRNA encoding tumor necrosis factor alpha (TNF). This leads in turn to a TNF-excess syndrome characterized by systemic inflammation. Evaluation of hearts from TrP(-/-) mice demonstrated gross thickening of the mitral and aortic but not the tricuspid or pulmonary valves, accompanied by inflammatory cell infiltrates. To determine whether TNF played a role in the development of this valvulitis, we examined mice deficient in both TNF receptors and in TTP; four of five of these mice exhibited no histological evidence of valvulitis, but one mouse had aortic valve leaflet thickening with a cellular infiltrate. Four additional mice had no external evidence of valvular thickening. Cardiac valves of transgenic mice expressing human TNF developed mild aortic valve leaflet edema without evidence of hypercellularity. Thus, TTP deficiency in mice leads to left-sided cardiac valvulitis with prominent inflammatory cell involvement, due, at least in part, to excess TNF. These findings support the potential involvement of TNF and inflammation in the development of cardiac valve disease in man. (Am J Pathol 2010, 176:1484-1493; DOI: 10.2353/ajpath.2010.090498)
C1 [Ghosh, Sanjukta; Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Labs Signal Transduct, Res Triangle Pk, NC 27709 USA.
[Myers, Page] NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
RP Blackshear, PJ (reprint author), NIEHS, Labs Signal Transduct, Box F1-13,111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM black009@niehs.nih.gov
FU NIH, NIEHS
FX Supported by the Intramural Research Program of the NIH, NIEHS.
NR 55
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U1 0
U2 0
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD MAR
PY 2010
VL 176
IS 3
BP 1484
EP 1493
DI 10.2353/ajpath.2010.090498
PG 10
WC Pathology
SC Pathology
GA 565MI
UT WOS:000275297000044
PM 20093488
ER
PT J
AU Hall, KD
AF Hall, Kevin D.
TI Predicting metabolic adaptation, body weight change, and energy intake
in humans
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE mathematical model; energy metabolism; macronutrient metabolism; body
composition
ID NONEXERCISE ACTIVITY THERMOGENESIS; RANDOMIZED CONTROLLED-TRIAL;
DIETARY-PROTEIN INTAKE; AMINO-ACID OXIDATION; HIGH-FAT DIET; ADAPTIVE
THERMOGENESIS; INDIRECT CALORIMETRY; LOSS MAINTENANCE; ADIPOSE-TISSUE;
IN-VIVO
AB Hall KD. Predicting metabolic adaptation, body weight change, and energy intake in humans. Am J Physiol Endocrinol Metab 298: E449-E466, 2010. First published November 24, 2009; doi:10.1152/ajpendo.00559.2009.-Complex interactions between carbohydrate, fat, and protein metabolism underlie the body's remarkable ability to adapt to a variety of diets. But any imbalances between the intake and utilization rates of these macronutrients will result in changes in body weight and composition. Here, I present the first computational model that simulates how diet perturbations result in adaptations of fuel selection and energy expenditure that predict body weight and composition changes in both obese and nonobese men and women. No model parameters were adjusted to fit these data other than the initial conditions for each subject group (e.g., initial body weight and body fat mass). The model provides the first realistic simulations of how diet perturbations result in adaptations of whole body energy expenditure, fuel selection, and various metabolic fluxes that ultimately give rise to body weight change. The validated model was used to estimate free-living energy intake during a long-term weight loss intervention, a variable that has never previously been measured accurately.
C1 NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Hall, KD (reprint author), NIDDK, Lab Biol Modeling, NIH, 12 S Dr,Rm 4007, Bethesda, MD 20892 USA.
EM kevinh@niddk.nih.gov
RI Hall, Kevin/F-2383-2010
FU National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 119
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U2 20
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD MAR
PY 2010
VL 298
IS 3
BP E449
EP E466
DI 10.1152/ajpendo.00559.2009
PG 18
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 557YA
UT WOS:000274705200010
PM 19934407
ER
PT J
AU Zemkova, H
Kucka, M
Li, S
Gonzalez-Iglesias, AE
Tomic, M
Stojilkovic, SS
AF Zemkova, Hana
Kucka, Marek
Li, Shuo
Gonzalez-Iglesias, Arturo E.
Tomic, Melanija
Stojilkovic, Stanko S.
TI Characterization of purinergic P2X(4) receptor channels expressed in
anterior pituitary cells
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE adenosine 5 '-triphosphatase; adenosine 5 '-triphosphatase-gated
receptor channels; calcium; lactotrophs; prolactin; ivermectin
ID EXTRACELLULAR NUCLEOTIDES; PROLACTIN-RELEASE; ATP RECEPTORS;
INTRACELLULAR CALCIUM; HORMONE-RELEASE; P2 RECEPTORS; RAT; TRIPHOSPHATE;
DESENSITIZATION; NEURONS
AB Zemkova H, Kucka M, Li S, Gonzalez-Iglesias AE, Tomic M, Stojilkovic SS. Characterization of purinergic P2X(4) receptor channels expressed in anterior pituitary cells. Am J Physiol Endocrinol Metab 298: E644-E651, 2010. First published December 15, 2009; doi:10.1152/ajpendo.00558.2009.-Anterior pituitary cells express cation-conducting P2X receptor channels (P2XRs), but their molecular identity, electrophysiological properties, cell-specific expression pattern, and physiological roles have been only partially characterized. In this study, we show by quantitative RT-PCR that mRNA transcripts for the P2X4 subunit are the most abundant in rat anterior pituitary tissue and confirm the P2X(4)R protein expression by Western blot analysis. Single-cell patch-clamp recordings show that extracellular ATP induced an inward depolarizing current in a majority of thyrotropin-releasing hormone-responsive pituitary cells, which resembled the current profile generated by recombinant P2X4R. The channels were activated and desensitized in a dose-dependent manner and deactivated rapidly. Activation of these channels led to stimulation of electrical activity and promotion of voltage-gated and voltage-insensitive Ca2+ influx. In the presence of ivermectin, a specific allosteric modulator of P2X(4)Rs, there was an approximately fourfold increase in the maximum amplitude of the ATP-induced inward current, accompanied by an increase in the sensitivity of receptors for ATP, slowed deactivation of receptors, and enhanced ATP-induced prolactin release. These results indicate that thyrotropin-releasing hormone-responsive cells, including lactotrophs, express homomeric and/or heteromeric P2X(4)Rs, which facilitate Ca2+ influx and hormone secretion.
C1 [Zemkova, Hana; Kucka, Marek; Li, Shuo; Gonzalez-Iglesias, Arturo E.; Tomic, Melanija; Stojilkovic, Stanko S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Zemkova, Hana] Acad Sci Czech Republic, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, Prague, Czech Republic.
RP Stojilkovic, SS (reprint author), NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bldg 49,Rm 6A-36,49 Convent Dr, Bethesda, MD 20892 USA.
EM stankos@helix.nih.gov
RI Zemkova, Hana/C-1844-2012; Tomic, Melanija/C-3371-2016
FU National Institute of Child Health and Human Development; National
Institutes of Health; Grant Agency of the Czech Republic [305/07/0681];
Centrum for Neuroscience [LC554]
FX This work was supported by the Intramural Research Program of the
National Institute of Child Health and Human Development, National
Institutes of Health, the Grant Agency of the Czech Republic
(305/07/0681), and Centrum for Neuroscience Grant LC554.
NR 52
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U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
EI 1522-1555
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD MAR
PY 2010
VL 298
IS 3
BP E644
EP E651
DI 10.1152/ajpendo.00558.2009
PG 8
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 557YA
UT WOS:000274705200028
PM 20009029
ER
PT J
AU Ohse, T
Vaughan, MR
Kopp, JB
Krofft, RD
Marshall, CB
Chang, AM
Hudkins, KL
Alpers, CE
Pippin, JW
Shankland, SJ
AF Ohse, Takamoto
Vaughan, Michael R.
Kopp, Jeffrey B.
Krofft, Ronald D.
Marshall, Caroline B.
Chang, Alice M.
Hudkins, Kelly L.
Alpers, Charles E.
Pippin, Jeffrey W.
Shankland, Stuart J.
TI De novo expression of podocyte proteins in parietal epithelial cells
during experimental glomerular disease
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE glomerulonephritis; differentiation; phenotype; FSGS; membranous
nephropathy
ID EXPERIMENTAL MEMBRANOUS NEPHROPATHY; FOCAL SEGMENTAL GLOMERULOSCLEROSIS;
TO-MESENCHYMAL TRANSITION; CRESCENTIC GLOMERULONEPHRITIS; DIFFERENTIAL
EXPRESSION; PROGENITOR CELLS; NEPHRIN; ACTIN; PROLIFERATION; MOUSE
AB Ohse T, Vaughan MR, Kopp JB, Krofft RD, Marshall CB, Chang AM, Hudkins KL, Alpers CE, Pippin JW, Shankland SJ. De novo expression of podocyte proteins in parietal epithelial cells during experimental glomerular disease. Am J Physiol Renal Physiol 298: F702-F711, 2010. First published December 9, 2009; doi:10.1152/ajprenal.00428.2009.-Studies have shown that certain cells of the glomerular tuft begin to express proteins considered unique to other cell types upon injury. Little is known about the response of parietal epithelial cells (PEC) to injury. To determine whether PECs change their phenotype upon injury to also express proteins traditionally considered podocyte specific, the following four models of glomerular disease were studied: the transforming growth factor (TGF)-beta 1 transgenic mouse model of global glomerulosclerosis, the adriamycin model of focal segmental glomerulosclerosis (FSGS), the anti-glomerular basement membrane (GBM) model of crescentic glomerulonephritis, and the passive Heymann nephritis model of membranous nephropathy. Double immunostaining was performed with antibodies to podocyte-specific proteins (synaptopodin and Wilms' tumor 1) and antibodies to PEC specific proteins (paired box gene 8 and claudin-1). No double staining was detected in normal mice. In contrast, the results showed a statistical increase in the number of cells attached to Bowman basement membrane that were double-positive for both podocyte/PEC proteins in TGF-beta;1 transgenic, anti-GBM, and membranous animals. Double-positive cells for both podocyte and PEC proteins were also statistically increased in the glomerular tuft in TGF-beta 1 transgenic, anti-GBM, and FSGS mice. These results are consistent with glomerular cells coexpressing podocyte and PEC proteins in experimental glomerular disease, but not under normal circumstances.
C1 [Ohse, Takamoto; Vaughan, Michael R.; Krofft, Ronald D.; Marshall, Caroline B.; Chang, Alice M.; Pippin, Jeffrey W.; Shankland, Stuart J.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA.
[Kopp, Jeffrey B.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Hudkins, Kelly L.; Alpers, Charles E.] Natl Inst Diabet Digest & Kidney Dis, Kidney Dis Sect, NIH, Bethesda, MD USA.
RP Shankland, SJ (reprint author), Univ Washington, Div Nephrol, Box 356521,BB-1265 HSB,1959 NE Pacific St, Seattle, WA 98195 USA.
EM stuartjs@u.washington.edu
OI Kopp, Jeffrey/0000-0001-9052-186X
FU National Institutes of Health; National Institute of Diabetes and
Digestive and Kidney Diseases Intramural Research Program [ZO1 DK043308]
FX This work was supported by a National Institutes of Health to S. J.
Shankland. J. B. Kopp is supported by the National Institute of Diabetes
and Digestive and Kidney Diseases Intramural Research Program (ZO1
DK043308).
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PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD MAR
PY 2010
VL 298
IS 3
BP F702
EP F711
DI 10.1152/ajprenal.00428.2009
PG 10
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 572TM
UT WOS:000275856000024
PM 20007346
ER
PT J
AU Sakairi, T
Abe, Y
Kajiyama, H
Bartlett, LD
Howard, LV
Jat, PS
Kopp, JB
AF Sakairi, Toru
Abe, Yoshifusa
Kajiyama, Hiroshi
Bartlett, Linda D.
Howard, Lilian V.
Jat, Parmijit S.
Kopp, Jeffrey B.
TI Conditionally immortalized human podocyte cell lines established from
urine
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE focal segmental glomerulosclerosis; SV40 large T antigen; human
telomerase
ID MESSENGER-RNA EXPRESSION; GENE-EXPRESSION; SEGMENTAL GLOMERULOSCLEROSIS;
EPITHELIAL-CELLS; GLOMERULAR PODOCYTES; DIABETIC-NEPHROPATHY;
RENAL-DISEASE; EXCRETION; NEPHRIN; INJURY
AB Sakairi T, Abe Y, Kajiyama H, Bartlett LD, Howard LV, Jat PS, Kopp JB. Conditionally immortalized human podocyte cell lines established from urine. Am J Physiol Renal Physiol 298: F557-F567, 2010. First published December 9, 2009; doi:10.1152/ajprenal.00509.2009.-Evidence suggests that loss of podocytes into urine contributes to development of glomerular diseases; shed podocytes are frequently viable and proliferate in culture conditions. To determine the phenotypic characteristics of viable urinary cells derived from human subjects, we established long-term urinary cell culture from two patients with focal segmental glomerulosclerosis and two healthy volunteers, via transformation with the thermosensitive SV40 large T antigen (U19tsA58) together with human telomerase (hTERT). Characterization of arbitrarily selected two clonal cell lines from each human subject was carried out. mRNA expression for the podocyte markers synaptopodin, nestin, and CD2AP were detected in all eight clones. Podocin mRNA was absent from all eight clones. The expression of nephrin, Wilms' tumor 1 (WT1), and podocalyxin mRNA varied among the clones, which may be due to transformation and/or cloning. These results suggest that podocyte cell lines can be established consistently from human urine. The generation of podocyte cell lines from urine of patients and healthy volunteers is novel and will help to advance studies of podocyte cell biology. Further improvements in the approaches to cell transformation and/or cell culture techniques are needed to allow cultured podocytes to fully reproduce in vivo characteristics.
C1 [Sakairi, Toru; Abe, Yoshifusa; Bartlett, Linda D.; Howard, Lilian V.; Kopp, Jeffrey B.] Natl Inst Diabet Digest & Kidney Dis, Kidney Dis Sect, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA.
[Kajiyama, Hiroshi] Saitama Med Univ, Dept Rheumatol & Appl Immunol, Saitama, Japan.
[Jat, Parmijit S.] UCL, Inst Neurol, Dept Neurodegenerat Dis, London, England.
RP Kopp, JB (reprint author), Natl Inst Diabet Digest & Kidney Dis, Kidney Dis Sect, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA.
EM jbkopp@nih.gov
OI Kopp, Jeffrey/0000-0001-9052-186X
FU National Institute of Diabetes and Digestive and Kidney Diseases [ZO1
DK043308]
FX This study was supported by the Intramural Research Program, National
Institute of Diabetes and Digestive and Kidney Diseases (project ZO1
DK043308).
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PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD MAR
PY 2010
VL 298
IS 3
BP F557
EP F567
DI 10.1152/ajprenal.00509.2009
PG 11
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 572TM
UT WOS:000275856000009
PM 19955187
ER
PT J
AU Farhat, T
Iannotti, RJ
Simons-Morton, BG
AF Farhat, Tilda
Iannotti, Ronald J.
Simons-Morton, Bruce G.
TI Overweight, Obesity, Youth, and Health-Risk Behaviors
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID BODY-MASS INDEX; CORONARY-HEART-DISEASE; CHILDHOOD OBESITY;
PHYSICAL-ACTIVITY; BULLYING BEHAVIORS; MENTAL-HEALTH; WEIGHT;
ADOLESCENCE; CHILDREN; ASSOCIATIONS
AB Background: The prevalence and severity of obesity have increased among children and adolescents. Although the medical and psychosocial consequences of youth obesity have been well documented, comparatively less information exists on the association of overweight/obesity with healthrisk behaviors, which are considered to be a primary threat to adolescent health.
Purpose: This study aims to examine the association of overweight and obesity with health-risk behaviors among U.S. youth.
Methods: Self-reported height and weight, substance use, violence, and bullying were assessed in a nationally representative sample of students aged 11-17 years (N=7825) who participated in the 2005-2006 Health Behaviors in School-Aged Children survey. Data were analyzed in 2009.
Results: Significant gender and age differences in the relationship of overweight/ obesity with risk behaviors were observed. Overweight and obesity were significantly associated with substance use among girls only: Frequent smoking and drinking were associated with overweight and obesity among younger girls, whereas these behaviors were associated with obesity arriong older girls. Frequent smoking and cannabis use were associated with over-weight among younger girls only. Relationships between violent behavior and overweight/obesity were mainly observed among boys: Younger obese boys were more likely to be victims of bullying, whereas older obese boys were more likely to carry weapons compared to boys of normal weight.
Conclusions: Overweight and obese young people are at risk of developing health-compromising behaviors that may compound medical and social problems associated with excess weight. (Am J Prev Med 2010;38(3):258-267) Published by Elsevier Inc. on behalf of Arrierican journal of Preventive Medicine
C1 [Farhat, Tilda; Iannotti, Ronald J.; Simons-Morton, Bruce G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
RP Farhat, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B13C, Bethesda, MD 20892 USA.
EM farhatti@mail.nih.gov
OI Simons-Morton, Bruce/0000-0003-1099-6617
FU NIH; Eunice Kennedy Shriver National Institute of Child Health and Human
Development [N01-HD-5-3401]
FX This research was supported in part by the intramural research program
of the NIH, Eunice Kennedy Shriver National Institute of Child Health
and Human Development (Contract N01-HD-5-3401).; No financial
disclosures were reported by the authors of this paper.
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAR
PY 2010
VL 38
IS 3
BP 258
EP 267
DI 10.1016/j.amepre.2009.10.038
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 566OW
UT WOS:000275383100003
PM 20171527
ER
PT J
AU Abrams, DB
Graham, AL
Levy, DT
Mabry, PL
Orleans, CT
AF Abrams, David B.
Graham, Amanda L.
Levy, David T.
Mabry, Patricia L.
Orleans, C. Tracy
TI Boosting Population Quits Through Evidence-Based Cessation Treatment and
Policy
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID CLINICAL PREVENTIVE SERVICES; RANDOMIZED CONTROLLED-TRIAL; NICOTINE
PATCH THERAPY; TREATING TOBACCO USE; SMOKING-CESSATION; UNITED-STATES;
HEALTH-CARE; SIMULATION-MODEL; CIGARETTE-SMOKING; MEDICAID COVERAGE
AB Only large increases in adult cessation will rapidly reduce population smoking prevalence. Evidence-based smoking-cessation treatments and treatment policies exist but are underutilized. More needs to be done to coordinate the widespread, efficient dissemination and implementation of effective treatments and policies. This paper is the first in a series of three to demonstrate the impact of an integrated, comprehensive systems approach to cessation treatment and policy. This paper provides an analytic framework and selected literature review that guide the two subsequent computer simulation modeling papers to show how critical leverage points may have an impact on reductions in smoking prevalence. Evidence is reviewed from the U.S. Public Health Service 2008 clinical practice guideline and other sources regarding the impact of five cessation treatment policies on quit attempts, use of evidence-based treatment, and quit rates. Cessation treatment policies would: (1) expand cessation treatment coverage and provider reimbursement; (2) mandate adequate funding for the use and promotion of evidence-based state-sponsored telephone quitlines; (3) support healthcare systems changes to prompt, guide, and incentivize tobacco treatment; (4) support and promote evidence-based treatment via the Internet; and (5) improve individually tailored, stepped-care approaches and the long-term effectiveness of evidence-based treatments. This series of papers provides an analytic framework to inform heuristic simulation models in order to take a new look at ways to markedly increase population smoking cessation by implementing a defined set of treatments and treatment-related policies with the potential to improve motivation to quit, evidence-based treatment use, and long-term effectiveness. (Am J Prev Med 2010;38(3S):S351-S363) (C) 2010 American journal of Preventive Medicine
C1 [Abrams, David B.; Graham, Amanda L.] Amer Legacy Fdn, Steven Schroeder Inst Tobacco Res & Policy Studie, Washington, DC 20036 USA.
[Levy, David T.] Univ Baltimore, Pacific Inst Res & Evaluat, Calverton, MD USA.
[Mabry, Patricia L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Orleans, C. Tracy] Robert Wood Johnson Fdn, Princeton, NJ 08540 USA.
RP Abrams, DB (reprint author), Amer Legacy Fdn, Steven Schroeder Inst Tobacco Res & Policy Studie, 1724 Massachusetts Ave NW, Washington, DC 20036 USA.
EM dabrams@americanlegacy.org
OI Graham, Amanda/0000-0003-3036-9653
FU Office of Behavioral and Social Sciences Research (OBSSR) at the NIH;
Robert Wood Johnson Foundation (RWJF)
FX This paper was conducted under the auspices of the national Consumer
Demand Roundtable and was supported by funds provided by the Office of
Behavioral and Social Sciences Research (OBSSR) at the NIH and the
Robert Wood Johnson Foundation (RWJF). The findings and conclusions in
this report are those of the authors and do not necessarily represent
the views of the American Legacy Foundation, the University of
Baltimore, OBSSR, or RWJF.
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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 MAR
PY 2010
VL 38
IS 3
SU 3
BP S351
EP S363
DI 10.1016/j.amepre.2009.12.011
PG 13
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 566OX
UT WOS:000275383200009
PM 20176308
ER
PT J
AU Backinger, CL
Malarcher, AM
AF Backinger, Cathy L.
Malarcher, Ann M.
TI The Things That Get Measured Are the Things That Get Done
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
C1 [Backinger, Cathy L.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
[Malarcher, Ann M.] CDC, Epidemiol Branch, Off Smoking & Hlth, Atlanta, GA 30333 USA.
RP Backinger, CL (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4050, Rockville, MD 20852 USA.
EM backingc@mail.nih.gov
FU National Cancer Institute; CDC
FX The authors thank Allison Rose and Rene Arrazola for their assistance in
reviewing the state and national survey questions, Ami Hurd for her
assistance in gathering and organizing background materials for the
commentary, and Dr. C. Tracy Orleans and Dr. Gary Giovino for their
input into the conceptualization of the major themes for the
commentary.; The findings and conclusions in this report are those of
the authors and do not necessarily represent any official position of
the National Cancer Institute, the NIH, or the CDC.; This work was
supported by the National Cancer Institute and the CDC.
NR 18
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U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAR
PY 2010
VL 38
IS 3
SU 3
BP S433
EP S436
DI 10.1016/j.amepre.2009.12.005
PG 4
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 566OX
UT WOS:000275383200020
PM 20176319
ER
PT J
AU Backinger, CL
Thornton-Bullock, A
Miner, C
Orleans, CT
Siener, K
DiClemente, CC
Phillips, TM
Rowden, JN
Arkin, E
AF Backinger, Cathy L.
Thornton-Bullock, Amber
Miner, Cindy
Orleans, C. Tracy
Siener, Karen
DiClemente, Carlo C.
Phillips, Todd M.
Rowden, Jessica N.
Arkin, Elaine
TI Building Consumer Demand for Tobacco-Cessation Products and Services The
National Tobacco Cessation Collaborative's Consumer Demand Roundtable
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID SMOKING-CESSATION; CIGARETTE-SMOKING; SMOKERS; PROGRAMS; IMPACT; SALES
C1 [Phillips, Todd M.; Rowden, Jessica N.; Arkin, Elaine] Acad Educ Dev, Washington, DC 20009 USA.
[Backinger, Cathy L.] NCI, Bethesda, MD 20892 USA.
[Miner, Cindy] Natl Inst Drug Abuse, Bethesda, MD USA.
[DiClemente, Carlo C.] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA.
[Thornton-Bullock, Amber] Amer Legacy Fdn, Washington, DC USA.
[Orleans, C. Tracy] Robert Wood Johnson Fdn, Princeton, NJ 08540 USA.
[Siener, Karen] CDC, Atlanta, GA 30333 USA.
RP Phillips, TM (reprint author), Acad Educ Dev, 1825 Connecticut Ave NW, Washington, DC 20009 USA.
EM tphillip@aed.org
NR 32
TC 18
Z9 19
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAR
PY 2010
VL 38
IS 3
SU 3
BP S307
EP S311
DI 10.1016/j.amepre.2009.12.002
PG 5
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 566OX
UT WOS:000275383200002
PM 20176301
ER
PT J
AU Levy, DT
Mabry, PL
Graham, AL
Orleans, CT
Abrams, DB
AF Levy, David T.
Mabry, Patricia L.
Graham, Amanda L.
Orleans, C. Tracy
Abrams, David B.
TI Reaching Healthy People 2010 by 2013 A SimSmoke Simulation
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID NICOTINE REPLACEMENT THERAPIES; REDUCING SMOKING PREVALENCE; TOBACCO
CONTROL OBJECTIVES; PUBLIC-POLICIES; NATIONAL QUITLINE;
CIGARETTE-SMOKING; UNITED-STATES; MODEL; CESSATION; DEMAND
AB Background: Healthy People (HP2010) set as a goal to reduce adult smoking prevalence to 12% by 2010.
Purpose: This paper uses simulation modeling to examine the effects of three tobacco control policies and cessation treatment policies-alone and in conjunction-on population smoking prevalence.
Methods: Building on previous versions of the SimSmoke model, the effects of a defined set of policies on quit attempts, treatment use, and treatment effectiveness are estimated as potential levers to reduce smoking prevalence. The analysis considers the effects of (1) price increases through cigarette tax increases, (2) smokefree indoor air laws, (3) mass media/educational policies, and (4) evidence-based and promising cessation treatment policies.
Results: Evidence-based cessation treatment policies have the strongest effect, boosting the population quit rate by 78.8% in relative terms. Treatment policies are followed by cigarette tax increases (65.9%); smokefree air laws (31.8%); and mass media/educational policies (18.2%). Relative to the status quo in 2020, the model projects that smoking prevalence is reduced by 14.3% through a nationwide tax increase of $2.00, by 7.2% through smokefree laws, by 4.7% through mass media/educational policies, and by 16.5% through cessation treatment policies alone. Implementing all of the above policies at the same time would increase the quit rate by 296%, such that the HP2010 smoking prevalence goal of 12% is reached by 2013.
Conclusions: The impact of a combination of policies led to some surprisingly positive possible futures in lowering smoking prevalence to 12% within just several years. Simulation models can be a useful tool for evaluating complex scenarios in which policies are implemented simultaneously, and for which there are limited data. (Am J Prev Med 2010;38(3S):S373-S381) (C) 2010 American Journal of Preventive Medicine
C1 [Levy, David T.] Univ Baltimore, Pacific Inst Res & Evaluat, Calverton, MD 20705 USA.
[Mabry, Patricia L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Graham, Amanda L.; Abrams, David B.] Amer Legacy Fdn, Steven A Schroeder Inst Tobacco Res & Policy Stud, Washington, DC USA.
[Orleans, C. Tracy] Robert Wood Johnson Fdn, Princeton, NJ 08540 USA.
RP Levy, DT (reprint author), Univ Baltimore, Pacific Inst Res & Evaluat, 11720 Beltsville Dr,Suite 900, Calverton, MD 20705 USA.
EM Levy@pire.org
OI Graham, Amanda/0000-0003-3036-9653
FU Office of Behavioral and Social Sciences Research (OBSSR) at the NIH;
Robert Wood Johnson Foundation (RWJF); Cancer Intervention and
Surveillance Modeling Network (CISNET) of the Division of Cancer Control
and Population Sciences (DCCPS), National Cancer Institute (NCI)
[UO1-CA97450-02]
FX This paper was conducted under the auspices of the national Consumer
Demand Roundtable and was supported by funds provided by the Office of
Behavioral and Social Sciences Research (OBSSR) at the NIH and the
Robert Wood Johnson Foundation (RWJF). David Levy also received funding
from the Cancer Intervention and Surveillance Modeling Network (CISNET)
of the Division of Cancer Control and Population Sciences (DCCPS),
National Cancer Institute (NCI) under grant UO1-CA97450-02. The findings
and conclusions in this report are those of the authors and do not
necessarily represent the views of the American Legacy Foundation, the
University of Baltimore, NCI, OBSSR, or RWJF.
NR 61
TC 22
Z9 23
U1 0
U2 7
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 MAR
PY 2010
VL 38
IS 3
SU 3
BP S373
EP S381
DI 10.1016/j.amepre.2009.11.018
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 566OX
UT WOS:000275383200011
PM 20176310
ER
PT J
AU Levy, DT
Graham, AL
Mabry, PL
Abrams, DB
Orleans, CT
AF Levy, David T.
Graham, Amanda L.
Mabry, Patricia L.
Abrams, David B.
Orleans, C. Tracy
TI Modeling the Impact of Smoking-Cessation Treatment Policies on Quit
Rates
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID OVER-THE-COUNTER; NICOTINE REPLACEMENT; SIMULATION-MODEL; METAANALYSIS;
BENEFITS
AB Background: Smoking-cessation treatment policies could yield substantial increases in adult quit rates in the U.S.
Purpose: The goals of this paper are to model the effects of individual cessation treatment policies on population quit rates, and to illustrate the potential benefits of combining policies to leverage their synergistic effects.
Methods: A mathematical model is updated to examine the impact of five cessation treatment policies on quit attempts, treatment use, and treatment effectiveness. Policies include: (1) expand cessation treatment coverage and provider reimbursement; (2) mandate adequate funding for the use and promotion of evidence-based, state-sponsored telephone quitlines; (3) support healthcare system changes to prompt, guide, and incentivize tobacco treatment; (4) support and promote evidence-based treatment via the Internet; and (5) improve individually tailored, stepped-care approaches and the long-term effectiveness of evidence-based treatments.
Results: The annual baseline population quit rate is 4.3% of all current smokers. implementing any policy in isolation is projected to increase the quit rate to between 4.5% and 6%. By implementing all five policies in combination, the quit rate is projected to increase to 10.9%, or 2.5 times the baseline rate.
Conclusions: if fully implemented in a coordinated fashion, cessation treatment policies could reduce smoking prevalence from its current rate of 20.5% to 17.2% within 1 year. By modeling the policy impacts on the components of the population quit rate (quit attempts, treatment use, treatment effectiveness), key indicators are identified that need to be analyzed in attempts to improve the effect of cessation treatment policies. (Am J Prev Med 2010;38(3S):S364-S372) (C) 2010 American journal of Preventive Medicine
C1 [Levy, David T.] Univ Baltimore, Pacific Inst Res & Evaluat, Calverton, MD 20705 USA.
[Mabry, Patricia L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Graham, Amanda L.; Abrams, David B.] Amer Legacy Fdn, Steven A Schroeder Inst Tobacco Res & Policy Stud, Washington, DC USA.
[Orleans, C. Tracy] Robert Wood Johnson Fdn, Princeton, NJ 08540 USA.
RP Levy, DT (reprint author), Univ Baltimore, Pacific Inst Res & Evaluat, 11720 Beltsville Dr,Suite 900, Calverton, MD 20705 USA.
EM Levy@pire.org
OI Graham, Amanda/0000-0003-3036-9653
FU Office of Behavioral and Social Sciences Research (OBSSR) at the NIH;
Robert Wood Johnson Foundation (RWJF); Cancer Intervention and
Surveillance Modeling Network (CISNET) of the Division of Cancer Control
and Population Sciences (DCCPS), National Cancer Institute (NCI)
[UO1-CA97450-02]
FX This paper was conducted under the auspices of the national Consumer
Demand Roundtable and was supported by funds provided by the Office of
Behavioral and Social Sciences Research (OBSSR) at the NIH and the
Robert Wood Johnson Foundation (RWJF). David Levy also received funding
from the Cancer Intervention and Surveillance Modeling Network (CISNET)
of the Division of Cancer Control and Population Sciences (DCCPS),
National Cancer Institute (NCI) under grant UO1-CA97450-02. The findings
and conclusions in this report are those of the authors and do not
necessarily represent the views of the American Legacy Foundation, the
University of Baltimore, NCI, OBSSR, or RWJF.
NR 30
TC 38
Z9 39
U1 0
U2 4
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 MAR
PY 2010
VL 38
IS 3
SU 3
BP S364
EP S372
DI 10.1016/j.amepre.2009.11.016
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 566OX
UT WOS:000275383200010
PM 20176309
ER
PT J
AU Orleans, CT
Mabry, PL
Abrams, DB
AF Orleans, C. Tracy
Mabry, Patricia L.
Abrams, David B.
TI Increasing Tobacco Cessation in America A Consumer Demand Perspective
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID PRESCRIPTION DRUGS; SCIENCE; HEALTH
C1 [Orleans, C. Tracy] Robert Wood Johnson Fdn, Princeton, NJ 08543 USA.
[Mabry, Patricia L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Abrams, David B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Washington, DC USA.
Amer Legacy Fdn, Schroeder Inst Tobacco Res & Policy Studies, Washington, DC USA.
RP Orleans, CT (reprint author), Robert Wood Johnson Fdn, Coll Rd E, Princeton, NJ 08543 USA.
EM torlean@rwjf.org
NR 30
TC 9
Z9 10
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAR
PY 2010
VL 38
IS 3
SU 3
BP S303
EP S306
DI 10.1016/j.amepre.2010.01.013
PG 4
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 566OX
UT WOS:000275383200001
PM 20176300
ER
PT J
AU Vick, SJ
Paukner, A
AF Vick, Sarah-Jane
Paukner, Annika
TI Variation and Context of Yawns in Captive Chimpanzees (Pan troglodytes)
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Article
DE chimpanzee; yawn; chimpFACS; facial expression
ID MACACA-FASCICULARIS; PRIMATES; BEHAVIOR; ARCTOIDES; ANXIETY; HUMANS;
SPHINX
AB Primate yawns are usually categorized according to context (e.g. as a threat, anxious, or rest yawn), but there has been little consideration of whether these yawns are best regarded as a unitary behavior that only differs with respect to the context in which it is observed. This study examined the context and precise morphology of yawns in a group of 11 captive chimpanzees. Focal video sampling was used to describe the morphology and intensity of 124 yawns using ChimpFACS, a system for coding facial movements. Two distinct forms of yawn were identified, a full yawn and a yawn which is modified by additional actions that reduce the mouth aperture. These modified yawns may indicate some degree of voluntary control over facial movement in chimpanzees and, consequently, multiple functions of yawning according to context. To assess context effects, mean activity levels (resting, locomotion, and grooming) and scratching rates were compared one minute before and after each yawn. Locomotion was significantly increased following both types of yawn, whereas scratching rates significantly increased following modified yawns but decreased following full yawns. In terms of individual differences, males did not yawn more than females, although male yawns were of higher intensity, both in the degree of mouth opening and in the amount of associated head movement. These data indicate that yawning is associated with a change in activity levels in chimpanzees, but only modified yawns may be related to increased arousal. Different types of yawn can therefore be differentiated at the morphological level as well as context level. Am. J. Primatol. 72:262-269, 2010. (C) 2009 Wiley-Liss, Inc.
C1 [Vick, Sarah-Jane; Paukner, Annika] Univ Stirling, Dept Psychol, Stirling FK9 4LA, Scotland.
[Paukner, Annika] NIH, Comparat Ethol Lab, Anim Ctr, Poolesville, MD USA.
RP Vick, SJ (reprint author), Univ Stirling, Dept Psychol, Stirling FK9 4LA, Scotland.
EM sarah-jane.vick@stir.ac.uk
RI Vick, Sarah-Jane/B-5426-2009
OI Vick, Sarah-Jane/0000-0001-8741-9653
FU Royal Zoological Society of Scotland (RZSS); Amercian Society of
Primatology
FX Contract grant sponsors: Royal Zoological Society of Scotland (RZSS);
Amercian Society of Primatology's Principles.
NR 49
TC 13
Z9 13
U1 1
U2 7
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD MAR
PY 2010
VL 72
IS 3
BP 262
EP 269
DI 10.1002/ajp.20781
PG 8
WC Zoology
SC Zoology
GA 555KF
UT WOS:000274508900007
PM 20014109
ER
PT J
AU Fee, E
Bu, LP
AF Fee, Elizabeth
Bu, Liping
TI Isaac Williams Brewer (1867-1928): An Unsung Hero
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA.
[Bu, Liping] Alma Coll, Dept Hist, Alma, MI USA.
RP Fee, E (reprint author), NIH, Hist Med Div, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
NR 5
TC 1
Z9 1
U1 0
U2 0
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD MAR
PY 2010
VL 100
IS 3
BP 423
EP 423
DI 10.2105/AJPH.2009.184424
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 564YD
UT WOS:000275253800014
PM 20075307
ER
PT J
AU Bu, LP
Fee, E
AF Bu, Liping
Fee, Elizabeth
TI Communicating With Pictures: The Vision of Chinese Anti-Malaria Posters
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Bu, Liping] Alma Coll, Dept Hist, Alma, MI 48801 USA.
[Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
RP Bu, LP (reprint author), Alma Coll, Dept Hist, 614 W Super St, Alma, MI 48801 USA.
EM bulipi@alma.edu
NR 3
TC 1
Z9 1
U1 0
U2 0
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD MAR
PY 2010
VL 100
IS 3
BP 424
EP 425
DI 10.2105/AJPH.2009.177667
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 564YD
UT WOS:000275253800015
PM 20075311
ER
PT J
AU Mazaki-Tovi, S
Vaisbuch, E
Romero, R
Kusanovic, JP
Chaiworapongsa, T
Kim, SK
Nhan-Chang, CL
Gomez, R
Yoon, BH
Yeo, L
Mittal, P
Ogge, G
Gonzalez, JM
Hassan, SS
AF Mazaki-Tovi, Shali
Vaisbuch, Edi
Romero, Roberto
Kusanovic, Juan Pedro
Chaiworapongsa, Tinnakorn
Kim, Sun Kwon
Nhan-Chang, Chia-Ling
Gomez, Ricardo
Yoon, Bo H.
Yeo, Lami
Mittal, Pooja
Ogge, Giovanna
Gonzalez, Juan M.
Hassan, Sonia S.
TI Maternal Plasma Concentration of the Pro-Inflammatory Adipokine
Pre-B-Cell-Enhancing Factor (PBEF)/Visfatin Is Elevated In Pregnant
Patients with Acute Pyelonephritis
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Article
DE Acute bacterial infection; adipokines; BMI; cytokine; infection;
inflammation; maternal obesity; overweight; pregnancy; urinary tract
infection
ID GESTATIONAL DIABETES-MELLITUS; SERUM ADIPONECTIN MULTIMERS;
RESPIRATORY-DISTRESS-SYNDROME; FACTOR GENE POLYMORPHISMS; VISFATIN
CONCENTRATIONS; AMNIOTIC-FLUID; ADIPOSE-TISSUE; PRETERM LABOR;
BIRTH-WEIGHT; INSULIN-RESISTANCE
AB Problem
Visfatin/pre-B-cell-enhancing factor (PBEF) has been implicated in the regulation of the innate immune system, as well as in glucose metabolism. Specifically, visfatin plays a requisite role in delayed neutrophil apoptosis in patients with sepsis. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma visfatin concentration in normal weight and overweight/obese patients.
Method of study
This cross-sectional study included the following groups: (1) normal pregnant women (n = 200) and (2) pregnant women with pyelonephritis (n = 40). Maternal plasma visfatin concentrations were determined by ELISA. Non-parametric statistics was used for analyses.
Results
(1) The median maternal plasma visfatin concentration was significantly higher in patients with pyelonephritis than in those with a normal pregnancy; (2) among overweight/obese pregnant women, those with pyelonephritis had a significantly higher median plasma visfatin concentration than women with a normal pregnancy; and (3) pyelonephritis was independently associated with higher maternal plasma visfatin concentrations after adjustment for maternal age, pre-gestational body mass index, smoking status, gestational age at sampling, and birthweight.
Conclusion
Acute pyelonephritis during pregnancy is associated with a high circulating maternal visfatin concentration. These findings suggest that visfatin/PBEF may play a role in the regulation of the complex and dynamic crosstalk between inflammation and metabolism during pregnancy.
C1 [Mazaki-Tovi, Shali; Vaisbuch, Edi; Romero, Roberto; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Nhan-Chang, Chia-Ling; Yeo, Lami; Mittal, Pooja; Ogge, Giovanna; Gonzalez, Juan M.; Hassan, Sonia S.] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Detroit, MI 48201 USA.
[Mazaki-Tovi, Shali; Vaisbuch, Edi; Romero, Roberto; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Nhan-Chang, Chia-Ling; Yeo, Lami; Mittal, Pooja; Ogge, Giovanna; Gonzalez, Juan M.; Hassan, Sonia S.] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Bethesda, MD USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Gomez, Ricardo] Pontificia Univ Catolica Chile, CEDIP Ctr Perinatal Diag & Res, Dept Obstet & Gynecol, Sotero del Rio Hosp, Santiago, Chile.
[Yoon, Bo H.] Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea.
RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Box 4,3990 John R, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
RI Yoon, Bo Hyun/H-6344-2011;
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Intramural NIH HHS [Z01 HD002400-17, ZIA HD002400-18]
NR 99
TC 11
Z9 11
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1046-7408
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD MAR
PY 2010
VL 63
IS 3
BP 252
EP 262
DI 10.1111/j.1600-0897.2009.00804.x
PG 11
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 553SV
UT WOS:000274388000011
PM 20085562
ER
PT J
AU Cho, KJ
Seo, JM
Shin, Y
Yoo, MH
Park, CS
Lee, SH
Chang, YS
Cho, SH
Kim, JH
AF Cho, Kyung-Jin
Seo, Ji-Min
Shin, YoungHyun
Yoo, Min-Hyuk
Park, Choon-Sik
Lee, Shin-Hwa
Chang, Yoon-Seok
Cho, Sang-Heon
Kim, Jae-Hong
TI Blockade of Airway Inflammation and Hyperresponsiveness by Inhibition of
BLT2, a Low-Affinity Leukotriene B-4 Receptor
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE asthma; lipid mediator; inflammation; reactive oxygen species; BLT2
ID NF-KAPPA-B; T-CELL RECRUITMENT; EOSINOPHIL ACCUMULATION; TRANSCRIPTION
FACTOR; MEDIATES CHEMOTAXIS; OXIDATIVE STRESS; NADPH OXIDASE; MURINE
MODEL; MOUSE MODEL; ASTHMA
AB BLT2 is a low-affinity receptor for leukotriene B-4 (LTB4), a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase pathway. Unlike BLT1, a high-affinity receptor for LTB4, no clear physiological function has yet been identified for BLT2, especially with regard to the pathogenesis of asthma. The aim of this study was to investigate whether BLT2 plays a role in the pathogenesis of asthma. A murine model of allergic asthma was used to evaluate the role of BLT2 in ovalbumin-induced airway inflammation and airway hyperresponsiveness. The levels of BLT2 mRNA and its ligand, LTB4, in the lung airway were highly elevated after ovalbumin challenge, and down-regulation of BLT2 with antisense BLT2 oligonucleotides markedly attenuated airway inflammation and airway hyperresponsiveness. Further analysis, aimed at identifying mediators downstream of BLT2, revealed that BLT2 activation led to elevation of reactive oxygen species and subsequent activation of NF-kappa B, thus inducing the expression of vascular cell adhesion molecule-1, which is known to be involved in eosinophil infiltration into the lung airway. Together, our results suggest that BLT2 plays a pivotal, mediatory role in the pathogenesis of asthma, acting through a "reactive oxygen species-NF-kappa B"-linked inflammatory signaling pathway.
C1 [Cho, Kyung-Jin; Seo, Ji-Min; Shin, YoungHyun; Kim, Jae-Hong] Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea.
[Yoo, Min-Hyuk] NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
[Park, Choon-Sik; Lee, Shin-Hwa] Soonchunhyang Univ, Div Allergy & Resp Dis, Puchon, South Korea.
[Chang, Yoon-Seok; Cho, Sang-Heon] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea.
RP Kim, JH (reprint author), Korea Univ, Sch Life Sci & Biotechnol, 5-1 Anam Dong, Seoul 136701, South Korea.
EM jhongkim@korea.ac.kr
RI Cho, Sang Heon/J-2793-2012; Chang, Yoon-Seok/J-5628-2012; Kim,
Jae-Hong/B-2530-2009;
OI Park, Choon-Sik/0000-0003-2977-0255; Chang,
Yoon-Seok/0000-0003-3157-0447
FU New Drug Target Discovery; Korean Ministry of Education, Science, and
Technology
FX This work was supported by the New Drug Target Discovery grant and the
Diseases Network Research Program grant from the Korean Ministry of
Education, Science, and Technology.
NR 49
TC 29
Z9 30
U1 0
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD MAR
PY 2010
VL 42
IS 3
BP 294
EP 303
DI 10.1165/rcmb.2008-0445OC
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 562UQ
UT WOS:000275080900006
PM 19448154
ER
PT J
AU Klimstra, DS
Modlin, IR
Adsay, NV
Chetty, R
Deshpande, V
Gonen, M
Jensen, RT
Kidd, M
Kulke, MH
Lloyd, RV
Moran, C
Moss, SF
Oberg, K
O'Toole, D
Rindi, G
Robert, ME
Suster, S
Tang, LH
Tzen, CY
Washington, MK
Wiedenmann, B
Yao, J
AF Klimstra, David S.
Modlin, Irvin R.
Adsay, N. Volkan
Chetty, Runjan
Deshpande, Vikram
Goenen, Mithat
Jensen, Robert T.
Kidd, Mark
Kulke, Matthew H.
Lloyd, Ricardo V.
Moran, Cesar
Moss, Steven F.
Oberg, Kjell
O'Toole, Dermot
Rindi, Guido
Robert, Marie E.
Suster, Saul
Tang, Laura H.
Tzen, Chin-Yuan
Washington, Mary Kay
Wiedenmann, Betram
Yao, James
TI Pathology Reporting of Neuroendocrine Tumors: Application of the Delphic
Consensus Process to the Development of a Minimum Pathology Data Set
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE neuroendocrine tumor; consensus; carcinoid tumor; Delphic;
classification
ID PANCREATIC ENDOCRINE TUMORS; SMALL-CELL CARCINOMA; SOMATOSTATIN RECEPTOR
SCINTIGRAPHY; MOLECULAR TARGETED THERAPY; PROGNOSTIC-FACTORS;
GASTROINTESTINAL-TRACT; LOW-GRADE; GASTROENTEROPANCREATIC TUMORS;
CLASSIFICATION-SYSTEM; PRECURSOR LESIONS
AB Epithelial neuroendocrine tumors (NETs) have been the subject of much debate regarding their optimal classification. Although multiple systems of nomenclature, grading, and staging have been proposed, none has achieved universal acceptance. To help define the underlying common features of these classification systems and to identify the minimal pathology data that should be reported to ensure consistent clinical management and reproducibility of data from therapeutic trials, a multidisciplinary team of physicians interested in NETs was assembled. At a group meeting, the participants discussed a series of "yes'' or "no'' questions related to the pathology of NETs and the minimal data to be included in the reports. After discussion, anonymous votes were taken, using the Delphic principle that 80% agreement on a vote of either yes or no would define a consensus. Questions that failed to achieve a consensus were rephrased once or twice and discussed, and additional votes were taken. Of 108 questions, 91 were answerable either yes or no by more than 80% of the participants. There was agreement about the importance of proliferation rate for tumor grading, the landmarks to use for staging, the prognostic factors assessable by routine histology that should be reported, the potential for tumors to progress biologically with metastasis, and the current status of advanced immunohistochemical and molecular testing for treatment-related biomarkers. The lack of utility of a variety of immunohistochemical stains and pathologic findings was also agreed upon. A consensus could not be reached for the remaining 17 questions, which included both minor points related to extent of disease assessment and some major areas such as terminology, routine immunohistochemical staining for general neuroendocrine markers, use of Ki67 staining to assess proliferation, and the relationship of tumor grade to degree of differentiation. On the basis of the results of the Delphic voting, a minimum pathology data set was developed. Although there remains disagreement among experts about the specific classification system that should be used, there is agreement about the fundamental pathology data that should be reported. Examination of the areas of disagreement reveals significant opportunities for collaborative study to resolve unanswered questions.
C1 [Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, Surg Pathol Serv, New York, NY 10065 USA.
[Goenen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
[Modlin, Irvin R.; Kidd, Mark] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA.
[Robert, Marie E.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
[Adsay, N. Volkan] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA.
[Chetty, Runjan] Toronto Gen Hosp, Dept Pathol, Toronto, ON, Canada.
[Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Jensen, Robert T.] Natl Inst Diabet Digest & Kidney Dis, Bethesda, MD USA.
[Lloyd, Ricardo V.] Mayo Clin, Dept Pathol, Rochester, MN USA.
[Moran, Cesar] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Yao, James] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA.
[Moss, Steven F.] Brown Univ, Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA.
[Oberg, Kjell] Univ Upsalla, Dept Med Sci, Upsalla, Sweden.
[O'Toole, Dermot] St James Hosp, Dept Med, Dublin, Ireland.
[O'Toole, Dermot] Trinity Coll Dublin, Dublin, Ireland.
[Rindi, Guido] Univ Parma, Dept Pathol & Lab Med, I-43100 Parma, Italy.
[Suster, Saul] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA.
[Tzen, Chin-Yuan] Cathay Gen Hosp, Dept Pathol, Taipei, Taiwan.
[Washington, Mary Kay] Vanderbilt Univ Sch Med, Dept Pathol, Nashville, TN USA.
[Wiedenmann, Betram] Univ Berlin, Charite Hosp, Dept Internal Med, Berlin, Germany.
RP Klimstra, DS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, Surg Pathol Serv, 1275 York Ave, New York, NY 10065 USA.
EM klimstrd@mskcc.org
RI Gonen, Mithat/E-4826-2012;
OI RINDI, Guido/0000-0003-2996-4404
FU Novartis Corporation
FX Supported by Novartis Corporation.
NR 100
TC 151
Z9 173
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD MAR
PY 2010
VL 34
IS 3
BP 300
EP 313
DI 10.1097/PAS.0b013e3181ce1447
PG 14
WC Pathology; Surgery
SC Pathology; Surgery
GA 570RZ
UT WOS:000275697000002
PM 20118772
ER
PT J
AU Dojcinov, SD
Venkataraman, G
Raffeld, M
Pittaluga, S
Jaffe, ES
AF Dojcinov, Stefan D.
Venkataraman, Girish
Raffeld, Mark
Pittaluga, Stefania
Jaffe, Elaine S.
TI EBV Positive Mucocutaneous Ulcer-A Study of 26 Cases Associated With
Various Sources of Immunosuppression
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE Epstein Barr virus; immunosuppression; mucocutaneous;
lymphoproliferative
ID EPSTEIN-BARR-VIRUS; CELL LYMPHOPROLIFERATIVE DISORDERS; CD8(+) T-CELLS;
OPTIMAL PRIMER SELECTION; CHAIN-REACTION ANALYSIS;
NON-HODGKINS-LYMPHOMAS; PERIPHERAL-BLOOD; ELDERLY-PATIENTS;
CYTOMEGALOVIRUS SEROPOSITIVITY; LYMPHOCYTE SUBPOPULATIONS
AB We describe a series of Epstein Barr virus (EBV)-positive circumscribed, ulcerative lesions associated with various types of immunosuppression (IS). The study group (26 patients) comprised 10 males and 16 females, median age 77 years (range 42 to 101). IS in 9 cases included azathioprine (AZA), methotrexate (MTX) or cyclosporin-A (CyA). Seventeen patients had age-related immunosenescence. Patients presented with isolated sharply circumscribed ulcers involving oropharyngeal mucosa (16), skin (6), and gastrointestinal tract (4). Lesions were histologically characterized by a polymorphous infiltrate and atypical large B-cell blasts often with Hodgkin/Reed-Sternberg (HRS) cell-like morphology. The B cells showed strong CD30 and EBER positivity, some with reduced CD20 expression, in a background of abundant T cells. CD15 was positive in 43% of cases (10/23). The pathologic features were identical regardless of the anatomic site or cause of IS. Polymerase chain reaction revealed 39% (7/18) clonal Ig gene rearrangements with 38% (6/16) and 31% (5/16) clonal and restricted T-cell patterns, respectively. Twenty-five percent of patients (5/20) received standard chemotherapy and/or radiotherapy. Forty-five percent (9/20) regressed spontaneously with no treatment and 15% (3/20) were characterized by a relapsing and remitting course. All of the iatrogenic lesions (6/6) with available follow-up responded to reduction of IS. All patients achieved complete remission with no disease-associated deaths over a median follow-up period of 22 months (range 3 to 72). We propose EBV-positive mucocutaneous ulcer as a newly recognized clinicopathologic entity with Hodgkin-like features and a self-limited, indolent course, generally responding well to conservative management. Association with various forms of IS implies a common pathogenetic mechanism. The localized nature of the disease may be owing to a minimal and localized lapse in immunosurveillance over EBV.
C1 [Dojcinov, Stefan D.] Univ Wales Hosp, Dept Pathol, All Wales Lymphoma Panel, Cardiff CF14 4XN, S Glam, Wales.
[Venkataraman, Girish; Raffeld, Mark; Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Dojcinov, SD (reprint author), Univ Wales Hosp, Dept Pathol, All Wales Lymphoma Panel, Heath Pk, Cardiff CF14 4XN, S Glam, Wales.
EM dojcinov@cf.ac.uk
OI Venkataraman, Girish/0000-0002-8674-2608; Jaffe,
Elaine/0000-0003-4632-0301
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health; British Division of the International Academy of
Pathology; British Society for Haematology
FX Supported by funding from: The Center for Cancer Research, National
Cancer Institute, National Institutes of Health, and the British
Division of the International Academy of Pathology and the British
Society for Haematology.
NR 71
TC 132
Z9 135
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD MAR
PY 2010
VL 34
IS 3
BP 405
EP 417
DI 10.1097/PAS.0b013e3181cf8622
PG 13
WC Pathology; Surgery
SC Pathology; Surgery
GA 570RZ
UT WOS:000275697000013
PM 20154586
ER
PT J
AU Henkin, RI
Potolicchio, SJ
Levy, LM
Moharram, R
Velicu, I
Martin, BM
AF Henkin, Robert I.
Potolicchio, Samuel J.
Levy, Lucien M.
Moharram, Ramy
Velicu, Irina
Martin, Brian M.
TI Carbonic Anhydrase I, II, and VI, Blood Plasma, Erythrocyte and Saliva
Zinc and Copper Increase After Repetitive Transcranial Magnetic
Stimulation
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article
DE Carbonic anhydrase; Zinc; Copper; Sensory changes after transcranial
magnetic stimulation; Mass spectrometry
ID MOTOR CORTEX EXCITABILITY; IDIOPATHIC PARKINSONS-DISEASE; OLFACTORY-BULB
NEURONS; HUMAN PAROTID-SALIVA; CEREBROSPINAL-FLUID LEVELS; HUMAN NASAL
MUCUS; ALZHEIMERS-DISEASE; MULTIPLE-SCLEROSIS; DOPAMINE RELEASE;
ELECTROMAGNETIC-FIELDS
AB Introduction: Repetitive transcranial magnetic stimulation (rTMS) has been used to treat symptoms from many disorders; biochemical changes occurred with this treatment. Preliminary studies with rTMS in patients with taste and smell dysfunction improved sensory function and increased salivary carbonic anhydrase (CA) VI and erythrocyte CA I, II. To obtain more information about these changes after rTMS, we measured changes in several CA enzymes, proteins, and trace metals in their blood plasma, erythrocytes, and saliva. Methods: Ninety-three patients with taste and smell dysfunction were studied before and after rTMS in an open clinical trial. Before and after rTMS, we measured erythrocyte CA I, II and salivary CA VI, zinc and copper in parotid saliva, blood plasma, and erythrocytes, and appearance of novel salivary proteins by using mass spectrometry. Results: After rTMS, CA I, II and CA VI activity and zinc and copper in saliva, plasma, and erythrocytes increased with significant sensory benefit. Novel salivary proteins were induced at an m/z value of 21.5K with a repetitive pattern at intervals of 5K m/z. Conclusions: rTMS induced biochemical changes in specific enzymatic activities, trace metal concentrations, and induction of novel salivary proteins, with sensory improvement in patients with taste and smell dysfunction. Because patients with several neurologic disorders exhibit taste and smell dysfunction, including Parkinson disease, Alzheimer disease, and multiple sclerosis, and because rTMS improved their clinical symptoms, the biochemical changes we observed may be relevant not only in our patients with taste and smell dysfunction but also in patients with neurologic disorders with these sensory abnormalities.
C1 [Henkin, Robert I.; Moharram, Ramy; Velicu, Irina] Taste & Smell Clin, Washington, DC 20016 USA.
[Potolicchio, Samuel J.; Levy, Lucien M.] George Washington Univ, Med Ctr, Washington, DC 20037 USA.
[Moharram, Ramy; Martin, Brian M.] NIMH, NIH, DHHS, Bethesda, MD 20892 USA.
RP Henkin, RI (reprint author), Taste & Smell Clin, 5125 MacArthur Blvd NW, Washington, DC 20016 USA.
EM doc@tasteandsmell.com
FU Intramural NIH HHS [ZIA MH002344-24]
NR 202
TC 4
Z9 4
U1 3
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-9629
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD MAR
PY 2010
VL 339
IS 3
BP 249
EP 257
DI 10.1097/MAJ.0b013e3181cda0e3
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 567CD
UT WOS:000275419000011
PM 20090508
ER
PT J
AU Zhu, WH
Zhu, DS
Madan, RA
Gulley, JL
Figg, WD
Dahut, WL
AF Zhu, Wenhui
Zhu, David S.
Madan, Ravi A.
Gulley, James L.
Figg, William D.
Dahut, William L.
TI Treatment of Castration-Resistant Prostate Cancer: Updates on
Therapeutics Targeting the Androgen Receptor Signaling Pathway
SO AMERICAN JOURNAL OF THERAPEUTICS
LA English
DT Review
DE androgen receptor; castration-resistant prostate cancer; MDV3100;
abiraterone
ID SECONDARY HORMONAL-THERAPY; PHASE-II TRIAL; DEPRIVATION THERAPY; PTEN
EXPRESSION; IN-VITRO; INHIBITORS; PROGRESSION; ACTIVATION; MECHANISM;
CARCINOMA
AB Androgens play a critical role in the progression of castration-resistant prostate cancer through androgen receptor (AR)-regulated signaling pathways. Progress has been made in the development of potent agents designed to suppress androgen function by blocking the AR, inhibiting the synthesis of androgens, or targeting downstream AR signaling pathways. This review summarizes the development of novel therapies based on current insights into AR signaling pathways in castration-resistant prostate cancer.
C1 [Zhu, Wenhui; Zhu, David S.; Madan, Ravi A.; Gulley, James L.; Figg, William D.; Dahut, William L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Dahut, WL (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Room 12N226, Bethesda, MD 20892 USA.
EM dahutw@mail.nih.gov
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
NR 53
TC 5
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1075-2765
EI 1536-3686
J9 AM J THER
JI Am. J. Ther.
PD MAR-APR
PY 2010
VL 17
IS 2
BP 176
EP 181
DI 10.1097/MJT.0b013e3181c6c0b2
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 574SX
UT WOS:000276014900008
PM 20019584
ER
PT J
AU Calsyn, DA
Cousins, SJ
Hatch-Maillette, MA
Forcehimes, A
Mandler, R
Doyle, SR
Woody, G
AF Calsyn, Donald A.
Cousins, Sarah J.
Hatch-Maillette, Mary A.
Forcehimes, Alyssa
Mandler, Raul
Doyle, Suzanne R.
Woody, George
TI Sex under the Influence of Drugs or Alcohol: Common for Men in Substance
Abuse Treatment and Associated with High-Risk Sexual Behavior
SO AMERICAN JOURNAL ON ADDICTIONS
LA English
DT Article
ID CONDOM USE; SELF-REPORTS; HIV; USERS; METAANALYSIS; DRINKING; PARTNERS
AB Sex under the influence of drugs or alcohol is associated with high-risk sexual behavior. Heterosexual men (n = 505) in substance abuse treatment completed a computer-administered interview assessing sexual risk behaviors. Most men (73.3%) endorsed sex under the influence in the prior 90 days, and 39.1% endorsed sex under the influence during their most recent sexual event. Sex under the influence at the most recent event was more likely to involve anal intercourse, sex with a casual partner, and less condom use. Patients might benefit from interventions targeting sexual behavior and substance use as mutual triggers.
C1 [Calsyn, Donald A.; Hatch-Maillette, Mary A.; Doyle, Suzanne R.] Univ Washington, Alcohol & Drug Abuse Inst, Seattle, WA 98105 USA.
[Calsyn, Donald A.; Hatch-Maillette, Mary A.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA.
[Cousins, Sarah J.] Univ Calif Los Angeles, Intergrated Subst Abuse Programs, Los Angeles, CA USA.
[Forcehimes, Alyssa] Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87131 USA.
[Mandler, Raul] NIDA, Ctr Clin Trials Network, Rockville, MD USA.
[Woody, George] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Woody, George] Treatment Res Inst, Philadelphia, PA USA.
RP Calsyn, DA (reprint author), Univ Washington, Alcohol & Drug Abuse Inst, 1107 NE 45th St,Ste 120, Seattle, WA 98105 USA.
EM calsyn@u.washington.edu
FU NIDA NIH HHS [U10 DA13711, U10 DA13045, U10 DA13043, U10 DA13038, U10
DA013711, U10 DA013045, U10 DA013043, U10 DA013038, U10 DA013727, U10
DA013035, U10 DA013714, U10 DA013714-05, U10 DA013732, U10 DA015815, U10
DA015833, U10 DA13035, U10 DA13714, U10 DA13727, U10 DA13732, U10
DA15815, U10 DA15833]
NR 32
TC 13
Z9 13
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1055-0496
J9 AM J ADDICTION
JI Am. J. Addict.
PD MAR-APR
PY 2010
VL 19
IS 2
BP 119
EP 127
DI 10.1111/j.1521-0391.2009.00022.x
PG 9
WC Substance Abuse
SC Substance Abuse
GA 556VJ
UT WOS:000274621100003
PM 20163383
ER
PT J
AU Weiss, RD
Potter, JS
Copersino, ML
Prather, K
Jacobs, P
Provost, S
Chim, D
Selzer, J
Ling, W
AF Weiss, Roger D.
Potter, Jennifer S.
Copersino, Marc L.
Prather, Kristi
Jacobs, Petra
Provost, Scott
Chim, David
Selzer, Jeffrey
Ling, Walter
TI Conducting Clinical Research with Prescription Opioid Dependence:
Defining the Population
SO AMERICAN JOURNAL ON ADDICTIONS
LA English
DT Article
ID METHADONE-MAINTENANCE TREATMENT; PRIMARY-CARE; HEROIN DEPENDENCE;
DRUG-USE; BUPRENORPHINE; USERS; ABUSE
AB Most treatment studies of opioid-dependent populations have focused predominantly on heroin users, despite a recent increase in those dependent upon prescription opioids. A key methodological challenge involved in studying the latter group involves defining the population. Specifically, researchers must decide whether to include (1) concurrent heroin users and (2) individuals with pain. The multi-site Prescription Opioid Addiction Treatment Study is examining treatments for this population. This paper describes various inclusion criteria considered by the study team related to heroin use and pain. The goal was to recruit a distinct but generalizable population of individuals dependent upon prescription opioids.
C1 [Weiss, Roger D.; Potter, Jennifer S.; Copersino, Marc L.; Provost, Scott] McLean Hosp, Belmont, MA 02478 USA.
[Weiss, Roger D.; Potter, Jennifer S.; Copersino, Marc L.; Provost, Scott] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA.
[Potter, Jennifer S.] Univ Texas San Antonio, Dept Psychiat, San Antonio, TX USA.
[Prather, Kristi] Duke Univ, Clin Res Inst, Durham, NC USA.
[Jacobs, Petra] NIDA, Ctr Clin Trials Network, Rockville, MD USA.
[Chim, David; Ling, Walter] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA USA.
[Selzer, Jeffrey] Long Isl Jewish Med Ctr, Addict Recovery Serv, Long Isl City, NY USA.
RP Weiss, RD (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA.
EM rweiss@mclean.harvard.edu
RI Chim, David/E-9855-2010; Potter, Jennifer/C-6720-2008
OI Potter, Jennifer/0000-0002-7250-4422
FU NIDA NIH HHS [K23 DA022297, K24 DA022288, K24 DA022288-03, T32 DA007272,
T32 DA07272, U10 DA013035, U10 DA013045, U10 DA015831, U10 DA015831-08,
U10 DA13035, U10 DA15831]
NR 19
TC 9
Z9 9
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1055-0496
J9 AM J ADDICTION
JI Am. J. Addict.
PD MAR-APR
PY 2010
VL 19
IS 2
BP 141
EP 146
DI 10.1111/j.1521-0391.2009.00017.x
PG 6
WC Substance Abuse
SC Substance Abuse
GA 556VJ
UT WOS:000274621100006
PM 20163386
ER
PT J
AU Yeum, KJ
Orioli, M
Regazzoni, L
Carini, M
Rasmussen, H
Russell, RM
Aldini, G
AF Yeum, Kyung-Jin
Orioli, Marica
Regazzoni, Luca
Carini, Marina
Rasmussen, Helen
Russell, Robert M.
Aldini, Giancarlo
TI Profiling histidine dipeptides in plasma and urine after ingesting beef,
chicken or chicken broth in humans
SO AMINO ACIDS
LA English
DT Article
DE Carnosine; Anserine; Histidine-dipeptides; Absorption kinetic; Chicken
ID TANDEM MASS-SPECTROMETRY; CONTAINING PEPTIDES; SERUM CARNOSINASE;
MICHAEL ADDUCTS; MUSCLE; ANSERINE; TISSUES; HOMOCARNOSINE; CONSTITUENTS;
ABSORPTION
AB The in vitro metabolic stability of histidine-dipeptides (HD), carnosine (CAR) and anserine (ANS), in human serum, and their absorption kinetics after ingesting pure carnosine or HD rich foods in humans have been investigated. Healthy women (n = 4) went through four phases of taking one dose of either 450 mg of pure carnosine, 150 g beef (B), 150 g chicken (C), or chicken broth (CB) from 150 g chicken with a > 2-week washout period between each phase. Blood samples were collected at 0, 30, 60, 100, 180, 240, and 300 min, and urine samples before and after (up to 7 h) ingesting pure carnosine or food. Both plasma and urine samples were analyzed for HD concentrations using a sensitive and selective LC-ESI-MS/MS method. CAR was undetectable in plasma after ingesting pure carnosine, B, C or CB. By contrast, plasma ANS concentration was significantly increased (P < 0.05) after ingesting C or CB, respectively. Urinary concentrations of both CAR and ANS were 13- to 14-fold increased after ingesting B, and 14.8- and 243-fold after CB ingestion, respectively. Thus, dietary HD, which are rapidly hydrolyzed by carnosinase in plasma, and excreted in urine, may act as reactive carbonyl species sequestering agents.
C1 [Yeum, Kyung-Jin; Rasmussen, Helen] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Orioli, Marica; Regazzoni, Luca; Carini, Marina; Aldini, Giancarlo] Univ Milan, Fac Pharm, Dept Pharmaceut Sci, I-20133 Milan, Italy.
[Russell, Robert M.] NIH, Off Director, Washington, DC USA.
RP Yeum, KJ (reprint author), Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM kyungjin.yeum@tufts.edu
RI orioli, marica/F-7606-2015; Regazzoni, Luca/D-4212-2014; CARINI,
MARINA/D-3084-2015
OI aldini, giancarlo/0000-0002-2355-6744; orioli,
marica/0000-0003-1558-9551; Regazzoni, Luca/0000-0001-7199-7141; CARINI,
MARINA/0000-0003-3407-5425
FU U. S. Department of Agriculture [581950-9-001]
FX This research has been supported by the U. S. Department of Agriculture,
under agreement number 581950-9-001. Any opinions, findings, conclusion,
or recommendations expressed in this publication are those of the
authors and do not necessarily reflect the view of the U. S. Department
of Agriculture.
NR 35
TC 18
Z9 21
U1 1
U2 19
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD MAR
PY 2010
VL 38
IS 3
BP 847
EP 858
DI 10.1007/s00726-009-0291-2
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 569WT
UT WOS:000275634200019
PM 19381778
ER
PT J
AU Johann, DJ
Wei, BR
Prieto, DA
Chan, KC
Ye, XY
Valera, VA
Simpson, RM
Rudnick, PA
Xiao, Z
Issaq, HJ
Linehan, WM
Stein, SE
Veenstra, TD
Blonder, J
AF Johann, Donald J., Jr.
Wei, Bih-Rong
Prieto, DaRue A.
Chan, King C.
Ye, Xiaying
Valera, Vladimir A.
Simpson, R. Mark
Rudnick, Paul A.
Xiao, Zhen
Issaq, Haleem J.
Linehan, W. Marston
Stein, Stephen E.
Veenstra, Timothy D.
Blonder, Josip
TI Combined Blood/Tissue Analysis for Cancer Biomarker Discovery:
Application to Renal Cell Carcinoma
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID GENE-EXPRESSION; BREAST-CANCER; PROTEOMICS; TUMOR; CADHERIN; COMPLEX
AB A method that relies on subtractive tissue-directed shotgun proteomics to identify tumor proteins in the blood of a patient newly diagnosed with cancer is described. To avoid analytical and statistical biases caused by physiologic variability of protein expression in the human population, this method was applied on clinical specimens obtained from a single patient diagnosed with nonmetastatic renal cell carcinoma (RCC). The proteomes extracted from tumor, normal adjacent tissue and preoperative plasma were analyzed using 2D-liquid chromatography-mass spectrometry (LC-MS). The lists of identified proteins were filtered to discover proteins that (i) were found in the tumor but not normal tissue, (ii) were identified in matching plasma, and (iii) whose spectral count was higher in tumor tissue than plasma. These filtering criteria resulted in identification of eight tumor proteins in the blood. Subsequent Western-blot analysis confirmed the presence of cadherin-5, cadherin-11, DEAD-box protein-23, and pyruvate kinase in the blood of the patient in the study as well as in the blood of four other patients diagnosed with RCC. These results demonstrate the utility of a combined blood/tissue analysis strategy that permits the detection of tumor proteins in the blood of a patient diagnosed with RCC.
C1 [Prieto, DaRue A.; Chan, King C.; Ye, Xiaying; Xiao, Zhen; Issaq, Haleem J.; Veenstra, Timothy D.; Blonder, Josip] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Johann, Donald J., Jr.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Wei, Bih-Rong; Simpson, R. Mark] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Valera, Vladimir A.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Rudnick, Paul A.; Stein, Stephen E.] Natl Inst Stand & Technol, NIST Mass Spectrometry Data Ctr, Gaithersburg, MD 20899 USA.
RP Blonder, J (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA.
EM blonderj@mail.nih.gov
FU National Cancer Institute; National Institutes of Health [N01-CO-12400]
FX The authors declare that they have no competing financial interests,
This project has been funded in whole or in part with federal funds
front the National Cancer Institute, National Institutes of Health,
under Contract N01-CO-12400. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services nor does mention of trade names, commercial products,
or organizations imply endorsement by the United States Government.
NR 25
TC 21
Z9 22
U1 2
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD MAR 1
PY 2010
VL 82
IS 5
BP 1584
EP 1588
DI 10.1021/ac902204k
PG 5
WC Chemistry, Analytical
SC Chemistry
GA 559QN
UT WOS:000274841300005
PM 20121140
ER
PT J
AU Tuleuova, N
Jones, CN
Yan, J
Ramanculov, E
Yokobayashi, Y
Revzin, A
AF Tuleuova, Nazgul
Jones, Caroline N.
Yan, Jun
Ramanculov, Erlan
Yokobayashi, Yohei
Revzin, Alexander
TI Development of an Aptamer Beacon for Detection of Interferon-Gamma
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID ELECTROCHEMICAL DETECTION; PROTEIN; FLUORESCENCE; BINDING;
IMMOBILIZATION; QUANTITATION; MICROARRAYS; MOLECULES; SWITCH; CELLS
AB Traditional antibody-based affinity sensing strategies employ multiple reagents and washing steps and are unsuitable for real-time detection of analyte binding. Aptamers, on the other hand, may be designed to monitor binding events directly, in real-time, without the need for secondary labels. The goal of the present study was to design ail aptamer beacon for fluorescence resonance energy transfer (FRET)based detection of interferon-gamma (IFN-gamma)-an important inflammatory cytokine. Variants of DNA aptamer modified with biotin moieties and spacers were immobilized oil avidin-coated surfaces and characterized by surface plasmon resonance (SPR). The SPR studies showed that immobilization of aptamer via the 3' end resulted in the best binding IFN-gamma (K(d) = 3.44 nM). This optimal aptamer variant was then used to construct a beacon by hybridizing fluorophore-labeled aptamer with an antisense oligonucleotide strand carrying a quencher. SPR studies revealed that IFN-gamma binding with an aptamer beacon occurred within 15 min of analyte introduction-suggesting dynamic replacement of the quencher-complementary strand by IFN-gamma molecules. To further highlight biosensing applications, aptamer beacon molecules were immobilized inside microfluidic channels and challenged with varying concentration of analyte. Fluorescence microscopy revealed low fluorescence in the absence of analyte and high fluorescence after introduction of IFN-gamma. Importantly, unlike traditional antibody-based immunoassays, tire signal was observed directly upon binding of analyte without the need for multiple washing steps. The surface immobilized aptamer beacon had a linear range from 5 to 100 nM and a lower limit of detection of 5 nM IFN-gamma. In conclusion, we designed a FRET-based aptamer beacon for monitoring of an inflammatory cytokine-IFN-gamma. In the future, this biosensing strategy will be employed to monitor dynamics of cytokine production by the immune cells.
C1 [Tuleuova, Nazgul; Jones, Caroline N.; Yan, Jun; Yokobayashi, Yohei; Revzin, Alexander] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA.
[Tuleuova, Nazgul; Ramanculov, Erlan] Natl Biotechnol Ctr, Astana, Kazakhstan.
RP Revzin, A (reprint author), Univ Calif Davis, Dept Biomed Engn, 451 E Hlth Sci Dr 2519, Davis, CA 95616 USA.
EM arevzin@ucdavis.edu
RI Yokobayashi, Yohei/B-5898-2009; Yan, Jun/E-8783-2012; Ramanculov,
Erlan/E-2823-2013
OI Yokobayashi, Yohei/0000-0002-2417-1934;
FU National Center for Biotechnology, Republic of Kazakhstan; NSF EFRI
FX We thank Prof. Laura Marcu and Dr. Yinghua Sun in the Department of
Biomedical Engineering at UC Davis for use of fluorescence microscope.
NT was supported by a fellowship from the National Center for
Biotechnology, Republic of Kazakhstan. These studies were supported by
an NSF EFRI grant awarded to AR.
NR 35
TC 73
Z9 75
U1 4
U2 78
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD MAR 1
PY 2010
VL 82
IS 5
BP 1851
EP 1857
DI 10.1021/ac9025237
PG 7
WC Chemistry, Analytical
SC Chemistry
GA 559QN
UT WOS:000274841300043
PM 20121141
ER
PT J
AU Mehrotra, N
Freire, AX
Bauer, DC
Harris, TB
Newman, AB
Kritchevsky, SB
Meibohm, B
AF Mehrotra, Nitin
Freire, Amado X.
Bauer, Douglas C.
Harris, Tamara B.
Newman, Anne B.
Kritchevsky, Stephen B.
Meibohm, Bernd
TI Predictors of Mortality in Elderly Subjects with Obstructive Airway
Disease: The PILE Score
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Obstructive Airway Disease; Mortality; Elderly; Interleukin-6; Cox
Proportional Hazards Modeling
ID C-REACTIVE PROTEIN; PERIPHERAL MUSCLE WEAKNESS; PULMONARY-DISEASE;
LUNG-FUNCTION; HEALTH ABC; SYSTEMIC INFLAMMATION; RESPIRATORY SYMPTOMS;
EXERCISE CAPACITY; SKELETAL-MUSCLE; COPD PATIENTS
AB PURPOSE: To identify significant covariates in addition to spirometry that predict mortality in elderly subjects with obstructive airway disease (OAD).
METHODS: Two hundred sixty-eight (268) participants with OAD from the Health, Aging and Body Composition study, a community-based observational cohort of well-functioning elderly aged 70-79 years, were followed on average for 6.1 years. Covariates related to pulmonary and physical function, comorbidity, demographics, and three inflammatory markers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein) were evaluated for their association with all-cause mortality (31%) by means of Kaplan Meier analysis and Cox proportional hazards modeling.
RESULTS: Percent predicted forced expiratory volume in one second (PPFEV1; hazard ratio [HR] = 2.03, p < 0.0001). knee extensor strength (HR = 1.36, p = 0.0002), interleukin-6 (HR = 1.37, p = 0.0002) and 400 m corridor walk time (HR = 1.24, p = 0.008) significantly predicted mortality. A multidimensional index, the PILE score, was constructed from PPFEV(1), interleukin-6, and knee extensor strength. Each one-point increase in PILE score (range: 1-10) was associated with a 30% increase in mortality (95% confidence interval: 0.16-0.47) after adjusting for age, race, gender, smoking, and comorbidity, resulting in a 10.4-fold higher risk of death between the highest and lowest risk category.
CONCLUSIONS: Subjects with OAD have a wide gradient of risk for mortality that can potentially he incorporated in clinical decision making. Ann Epidemiol 2010;20:223-232. (C) 2010 Elsevier Inc. All rights reserved,
C1 [Meibohm, Bernd] Univ Tennessee, Hlth Sci Ctr, Dept Pharmaceut Sci, Coll Pharm, Memphis, TN 38163 USA.
[Freire, Amado X.] Univ Tennessee, Hlth Sci Ctr, Dept Med, Memphis, TN 38163 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol & Med, Pittsburgh, PA USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27109 USA.
RP Meibohm, B (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Pharmaceut Sci, Coll Pharm, 874 Union Ave,Suite 5P, Memphis, TN 38163 USA.
EM bmeibohm@utmem.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Freire, Amado/0000-0001-7500-8291;
Kritchevsky, Stephen/0000-0003-3336-6781
FU National Institutes of Health [R01-HL-074104, N01-AG-6-2101,
N01-AG-6-2103, N01-AG-6-2106]; National Institute on Aging
FX This work was supported by research grants and contracts R01-HL-074104,
N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 by the National
Institutes of Health. This research, was also supported in part by the
Intramural Research Program of the NIH, National Institute On Aging.
NR 52
TC 17
Z9 17
U1 2
U2 4
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 MAR
PY 2010
VL 20
IS 3
BP 223
EP 232
DI 10.1016/j.annepidem.2009.11.005
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 584MZ
UT WOS:000276757700007
PM 20159492
ER
PT J
AU Hopping, SB
Joshi, AS
Tanna, N
Janjanin, S
AF Hopping, Steven B.
Joshi, Arjun S.
Tanna, Neil
Janjanin, Sasa
TI Volumetric Facelift: Evaluation of Rhytidectomy With Alloplastic
Augmentation
SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY
LA English
DT Article
DE aging; alloplast; face; facelift; implant; rhytidectomy
ID SURGERY; COMPLICATIONS
AB Objectives: Facial aging occurs as a result of soft tissue atrophy and resorption of the bony skeleton which results in a loss of soft tissue volume and laxity of the overlying skin Volumetric augmentation is a key component of facial rejuvenation surgery, and should be considered of equal importance to soft tissue lining Augmentation can be accomplished with synthetic fillers. autologous grafts, soft tissue repositioning techniques, and/or alloplastic implants Only alloplastic implants. however, provide truly long-term volumetric correction To date. there have been no large series dealing with the complications and results of implantation performed concurrently with rhytidectomy. which we have termed-volumetric rhytidectomy We present our experience with 100 patients treated with a combination of malar and chin implants and rhytidectomy. compared to 200 patients who underwent rhytidectomy alone
Methods: The authors performed a retrospective review of patients treated with a combination of silicone malar and chin augmentation with rhytidectomy versus patients treated with rhytidectomy alone Both groups of patients underwent close postoperative evaluation at 3 days. 1 week, 2 weeks, and 1 month All patients were surveyed at 6 months to assess aesthetic satisfaction Complication rates were noted and tabulated Statistical analysis was performed to evaluate for any differences in the two groups
Results: Between 2002 and 2006, 100 patients underwent malar and chin implantation along with rhytidectomy, 200 patients underwent rhytidectomy alone In the first group, there were a total of 6 cases in which implant removal was necessary, and 2 cases m which revision was required There were no statistically significant differences (p<0 05) observed between the two groups with respect to major or minor hematoma, seroma, infection, sensory nerve injury, facial nerve injury. hypertrophic scarring. dehiscence. skin sloughing. or revision.
Conclusions: Volumetric rhytidectomy reliably augments the malar and mental areas, allows for subtle skeletal contouring. and results in successful rejuvenation Rhytidectomy is relatively safe to perform concurrently with silicone augmentation. and does not result in an increased complication rate as compared to rhytidectomy alone
C1 [Hopping, Steven B.] George Washington Univ, Ctr Cosmet Surg, Washington, DC 20037 USA.
[Hopping, Steven B.; Joshi, Arjun S.; Tanna, Neil] George Washington Univ, Div Otolaryngol Head & Neck Surg, Washington, DC 20037 USA.
[Tanna, Neil] Univ Calif Los Angeles, Div Plast Surg, Los Angeles, CA USA.
[Janjanin, Sasa] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Hopping, SB (reprint author), George Washington Univ, Ctr Cosmet Surg, 2440 M St NW,Suite 205, Washington, DC 20037 USA.
NR 18
TC 10
Z9 10
U1 0
U2 0
PU ANNALS PUBL CO
PI ST LOUIS
PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA
SN 0003-4894
J9 ANN OTO RHINOL LARYN
JI Ann. Otol. Rhinol. Laryngol.
PD MAR
PY 2010
VL 119
IS 3
BP 174
EP 180
PG 7
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 580BH
UT WOS:000276421300005
PM 20392030
ER
PT J
AU Merion, RM
Shearon, TH
Berg, CL
Everhart, JE
Abecassis, MM
Shaked, A
Fisher, RA
Trotter, JF
Brown, RS
Terrault, NA
Hayashi, PH
Hong, JC
AF Merion, Robert M.
Shearon, Tempie H.
Berg, Carl L.
Everhart, James E.
Abecassis, Michael M.
Shaked, Abraham
Fisher, Robert A.
Trotter, James F.
Brown, Robert S., Jr.
Terrault, Norah A.
Hayashi, Paul H.
Hong, Johnny C.
CA A2ALL Study Grp
TI Hospitalization Rates Before and After Adult-to-Adult Living Donor or
Deceased Donor Liver Transplantation
SO ANNALS OF SURGERY
LA English
DT Article
ID BILIARY COMPLICATIONS; RESOURCE UTILIZATION; BILE-DUCT; RECONSTRUCTION;
RECIPIENTS; CIRRHOSIS; OUTCOMES; A2ALL; STRICTURES; COHORT
AB Objective: To compare rates of hospitalization before and after adult-to-adult living donor liver transplant (LDLT) and deceased donor liver transplant (DDLT).
Summary Background Data: LDLT recipients have been reported to have lower mortality but a higher complication rate than DDLT recipients. The higher complication rate may be associated with greater consumption of inpatient hospital resources and a higher burden of disease for LDLT recipients.
Methods: Data from the 9-center Adult-to-Adult Living Donor Liver Transplantation retrospective cohort study were analyzed to determine pretransplant, transplant, and posttransplant hospitalizations among LDLT candidates (potential living donor was evaluated) who received LDLT or DDLT. Hospital days and admission rates for LDLT and DDLT patients were calculated per patient-year at risk, starting from the date of initial potential donor history and physical examination. Rates were compared using over-dispersed Poisson regression models.
Results: Among 806 candidates, 384 received LDLT and 215 received DDLT. In addition to the 599 transplants, there were 1913 recipient hospitalizations (485 pretransplant; 1428 posttransplant). Mean DDLT recipient pretransplant, transplant, and posttransplant lengths of stay were 5.8 +/- 6.3, 27.0 +/- 32.6, and 9.0 +/- 14.1 days, respectively, and for LDLT were 4.1 +/- 3.7, 21.4 +/- 24.3, and 7.8 +/- 11.4 days, respectively. Compared with DDLT, LDLT recipients had significantly lower adjusted pretransplant hospital day and admission rates, but significantly higher posttransplant rates. Significantly higher LDLT admission rates were observed for biliary tract morbidity throughout the second posttransplant year. Overall hospitalization rates starting from the point of potential donor evaluation were significantly higher for eventual recipients of LDLT.
Conclusions: LDLT recipients, despite lower acuity of disease, have higher hospitalization requirements when compared with DDLT recipients. Continuing efforts are warranted to reduce the incidence of complications requiring post-LDLT inpatient admission, with particular emphasis on biliary tract issues.
C1 [Merion, Robert M.] Univ Michigan, Dept Surg, Ann Arbor, MI 48103 USA.
[Shearon, Tempie H.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48103 USA.
[Berg, Carl L.] Univ Virginia, Dept Med, Charlottesville, VA USA.
[Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA.
[Abecassis, Michael M.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA.
[Shaked, Abraham] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA.
[Fisher, Robert A.] Virginia Commonwealth Univ, Med Coll Virginia, Dept Surg, Richmond, VA 23298 USA.
[Trotter, James F.] Univ Colorado, Dept Surg, Aurora, CO USA.
[Brown, Robert S., Jr.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA.
[Terrault, Norah A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Hayashi, Paul H.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Hong, Johnny C.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA.
RP Merion, RM (reprint author), Univ Michigan, Dept Surg, 315 W Huron,Suite 240, Ann Arbor, MI 48103 USA.
EM merionb@umich.edu
RI Abecassis, Michael/F-7977-2011
FU National Institutes of Health (NIDDK) [U01-DK62536, U01-DK62444,
U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496,
U01-DK62498, U01-DK62505, U01-DK62531]; American Society of Transplant
Surgeons; US Department of Health and Human Services, Health Resources
and Services Administration
FX Supported in part by the National Institutes of Health (NIDDK grant
numbers U01-DK62536, U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484,
U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531), the
American Society of Transplant Surgeons, and the US Department of Health
and Human Services, Health Resources and Services Administration.
NR 20
TC 16
Z9 16
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
J9 ANN SURG
JI Ann. Surg.
PD MAR
PY 2010
VL 251
IS 3
BP 542
EP 549
DI 10.1097/SLA.0b013e3181ccb370
PG 8
WC Surgery
SC Surgery
GA 562OD
UT WOS:000275060800025
PM 20130466
ER
PT J
AU Sharma, S
Gao, P
Steele, VE
AF Sharma, Sheela
Gao, Pu
Steele, Vernon E.
TI Quantitative Morphometry of Respiratory Tract Epithelial Cells as a Tool
for Testing Chemopreventive Agent Efficacy
SO ANTICANCER RESEARCH
LA English
DT Article
DE Nuclear density; morphometry; chemopreventive agents; rat tracheal
epithelial cells
ID MALE F344 RATS; FUMARIC-ACID; COLON CARCINOGENESIS; IN-VITRO; OLTIPRAZ;
HEPATOCARCINOGENESIS; TRANSFORMATION; AZOXYMETHANE; INHIBITION; MICE
AB Previously, we developed a 30-day transformation assay (focus inhibition, FIA) of rat tracheal epithelial (RTE) cells to identify cancer preventive agents. This study reports nuclear density (ND) as a morphometric biomarker for efficacy evaluation of at an early stage before transformed foci appear. Positive (oltipraz, D-carvone, fumaric acid, and 2-amino-4-methylpyridine or 2-A-MPR) and negative agents (myristoleic acid, anethole trithione, hydrocortisone, and 3'-hydro-xyflavanone), identified from FIA, were tested for their effect on ND. RTE cells plated for 24 h were treated with a carcinogen, benzo[a] pyrene (B[c]P) or plus a test agent. The data based on the number of nuclei in agent-treated and control cells at day 14 showed that all FIA-positive agents inhibited ND from 23-66% at 0.3-1000.0 mu M and except for myristoleic acid, all of the FIA-negative compounds were also negative in the morphometty assay. As there is strong correlation between the FIA and morphometry data, morphometry analysis is useful for rapid screening of potential chemopreventive agents.
C1 [Sharma, Sheela; Gao, Pu] Alion Sci & Technol Inc, Cellular & Mol Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Steele, Vernon E.] NCI, Chemoprevent Agent Dev Res Grp, NIH, Bethesda, MD 20892 USA.
RP Sharma, S (reprint author), Hamner Inst Hlth Sci, Div Toxicol & Preclin Studies, POB 12137, Res Triangle Pk, NC 27709 USA.
EM ssharma@thehamner.org
FU National Cancer Institute [N01-CN-43301]
FX This study was supported by funds from the National Cancer Institute
(N01-CN-43301), U.S.A.
NR 30
TC 0
Z9 1
U1 0
U2 0
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD MAR
PY 2010
VL 30
IS 3
BP 737
EP 742
PG 6
WC Oncology
SC Oncology
GA 581YH
UT WOS:000276561300005
PM 20392991
ER
PT J
AU Fabrega, A
Martin, RG
Rosner, JL
Tavio, MM
Vila, J
AF Fabrega, Anna
Martin, Robert G.
Rosner, Judah L.
Tavio, M. Mar
Vila, Jordi
TI Constitutive SoxS Expression in a Fluoroquinolone-Resistant Strain with
a Truncated SoxR Protein and Identification of a New Member of the
marA-soxS-rob Regulon, mdtG
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID MULTIPLE-ANTIBIOTIC-RESISTANCE; ESCHERICHIA-COLI STRAINS; MEDIATED
QUINOLONE RESISTANCE; URINARY-TRACT-INFECTIONS; ACRAB EFFLUX PUMP;
TRANSCRIPTIONAL ACTIVATOR; CIPROFLOXACIN RESISTANCE; REGULATORY PROTEIN;
MUTATIONS; GENES
AB Elevated levels of fluoroquinolone resistance are frequently found among Escherichia coli clinical isolates. This study investigated the antibiotic resistance mechanisms of strain NorE5, derived in vitro by exposing an E. coli clinical isolate, PS5, to two selection steps with increasing concentrations of norfloxacin. In addition to the amino acid substitution in GyrA (S83L) present in PS5, NorE5 has an amino acid change in ParC (S80R). Furthermore, we now find by Western blotting that NorE5 has a multidrug resistance phenotype resulting from the overexpression of the antibiotic resistance efflux pump AcrAB-TolC. Microarray and gene fusion analyses revealed significantly increased expression in NorE5 of soxS, a transcriptional activator of acrAB and tolC. The high soxS activity is attributable to a frameshift mutation that truncates SoxR, rendering it a constitutive transcriptional activator of soxS. Furthermore, microarray and reverse transcription-PCR analyses showed that mdtG (yceE), encoding a putative efflux pump, is overexpressed in the resistant strain. SoxS, MarA, and Rob activated an mdtG::lacZ fusion, and SoxS was shown to bind to the mdtG promoter, showing that mdtG is a member of the marA-soxS-rob regulon. The mdtG marbox sequence is in the backward or class I orientation within the promoter, and its disruption resulted in a loss of inducibility by MarA, SoxS, and Rob. Thus, chromosomal mutations in parC and soxR are responsible for the increased antibiotic resistance of NorE5.
C1 [Vila, Jordi] Univ Barcelona, Microbiol Serv, Ctr Diagnost Biomed, Hosp Clin,Fac Med,Dept Microbiol,Sch Med, E-08036 Barcelona, Spain.
[Tavio, M. Mar] Univ Las Palmas Gran Canaria, Sch Hlth Sci, Las Palmas Gran Canaria 35016, Spain.
[Martin, Robert G.; Rosner, Judah L.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Vila, J (reprint author), Univ Barcelona, Microbiol Serv, Ctr Diagnost Biomed, Hosp Clin,Fac Med,Dept Microbiol,Sch Med, Villarroel 170, E-08036 Barcelona, Spain.
EM jvila@ub.edu
RI Vila, Jordi/P-3613-2016;
OI Vila, Jordi/0000-0002-8025-3926; Fabrega-Santamaria,
Anna/0000-0002-3866-2291
FU Spanish Ministry of Health [FIS 05/0068]; Departament d'Universitats,
Recerca i Societat de la Informacio de la Generalitat de Catalunya;
Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Spanish
Network for Research in Infectious Diseases [REIPI RE06/0008]; European
Community [HEALTH-F3-2008-223031]
FX This study has been supported by the Spanish Ministry of Health (FIS
05/0068), by 2009 SGR 1256 from the Departament d'Universitats, Recerca
i Societat de la Informacio de la Generalitat de Catalunya, and by the
Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Spanish
Network for Research in Infectious Diseases (REIPI RE06/0008). This work
has also been supported by funding from the European Community (TROCAR
contract HEALTH-F3-2008-223031).
NR 49
TC 13
Z9 16
U1 1
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD MAR
PY 2010
VL 54
IS 3
BP 1218
EP 1225
DI 10.1128/AAC.00944-09
PG 8
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 558HY
UT WOS:000274733300035
PM 20008776
ER
PT J
AU Pyrgos, V
Mickiene, D
Sein, T
Cotton, M
Fransesconi, A
Mizrahi, I
Donoghue, M
Bundrant, N
Kim, SY
Hardwick, M
Shoham, S
Walsh, TJ
AF Pyrgos, Vasilios
Mickiene, Diane
Sein, Tin
Cotton, Margaret
Fransesconi, Andrea
Mizrahi, Isaac
Donoghue, Martha
Bundrant, Nikkida
Kim, Su-Young
Hardwick, Matthew
Shoham, Shmuel
Walsh, Thomas J.
TI Effects of Immunomodulatory and Organism-Associated Molecules on the
Permeability of an In Vitro Blood-Brain Barrier Model to Amphotericin B
and Fluconazole
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; FUNGAL-INFECTIONS;
STEADY-STATE; PHARMACOKINETICS; PENETRATION; SERUM; EFFICACY; DISEASE;
HUMANS
AB Amphotericin B (AMB) is used to treat fungal infections of the central nervous system (CNS). However, AMB shows poor penetration into the CNS and little is known about the factors affecting its permeation through the blood-brain barrier (BBB). Therefore, we studied immunomodulatory and organism-associated molecules affecting the permeability of an in vitro BBB model to AMB. We examined the effects of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), lipopolysaccharide (LPS), lipoteichoic acid (LTA), zymosan (ZYM), dexamethasone (DEX), cyclosporine, and tacrolimus on transendothelial electrical resistance (TEER); endothelial tight junctions; filamentous actin; and permeability to deoxycholate AMB (DAMB), liposomal AMB (LAMB), and fluconazole. Proinflammatory cytokines and organism-associated molecules significantly decreased the mean TEER by 40.7 to 100% (P <= 0.004). DEX increased the mean TEER by 18.2 to 26.4% (P <= 0.04). TNF-alpha and LPS increased the permeability to AMB by 8.2 to 14.5% compared to that for the controls (1.1 to 2.4%) (P <= 0.04). None of the other molecules affected the model's permeability to AMB. By comparison, the BBB model's permeability to fluconazole was > 78% under all conditions studied, without significant differences between the controls and the experimental groups. LPS and TNF-alpha decreased tight-junction protein zona occludens 1 (ZO-1) between endothelial cells. In conclusion, IL-1 beta, ZYM, and LTA increased the permeability of the BBB to small ions but not to AMB, whereas TNF-alpha and LPS, which disrupted the endothelial layer integrity, increased the permeability to AMB.
C1 [Pyrgos, Vasilios; Mickiene, Diane; Sein, Tin; Cotton, Margaret; Fransesconi, Andrea; Donoghue, Martha; Bundrant, Nikkida; Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Mizrahi, Isaac; Hardwick, Matthew; Shoham, Shmuel] Washington Hosp Ctr, Infect Dis Sect, Washington, DC 20010 USA.
[Donoghue, Martha] Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA.
[Hardwick, Matthew; Shoham, Shmuel] MedStar Hlth, MedStar Res Inst, Hyattsville, MD USA.
RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bldg 10,Room 13N-240, Bethesda, MD 20892 USA.
EM thomaswalshmd@gmail.com
FU National Cancer Institute
FX The research was funded by the intramural program of the National Cancer
Institute.
NR 20
TC 7
Z9 7
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD MAR
PY 2010
VL 54
IS 3
BP 1305
EP 1310
DI 10.1128/AAC.01263-09
PG 6
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 558HY
UT WOS:000274733300047
PM 19995929
ER
PT J
AU Wang, GS
Watson, KM
Peterkofsky, A
Buckheit, RW
AF Wang, Guangshun
Watson, Karen M.
Peterkofsky, Alan
Buckheit, Robert W., Jr.
TI Identification of Novel Human Immunodeficiency Virus Type 1-Inhibitory
Peptides Based on the Antimicrobial Peptide Database
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID HIV; MICROBICIDES; REPLICATION; INHIBIT; AGENTS; ASSAY
AB To identify novel anti-HIV-1 peptides based on the antimicrobial peptide database (APD; http://aps.unmc.edu/AP/main.php), we have screened 30 candidates and found 11 peptides with 50% effective concentrations (EC(50)) of < 10 mu M and therapeutic indices (TI) of up to 17. Furthermore, among the eight peptides ( with identical amino acid compositions but different sequences) generated by shuffling the sequence of an aurein 1.2 analog, two had a TI twice that of the original sequence. Because antiviral peptides in the database have an arginine/lysine (R/K) ratio of >1, increases in the Arg contents of amphibian maximin H5 and dermaseptin S9 peptides and the database-derived GLK-19 peptide improved the TIs. These examples demonstrate that the APD is a rich resource and a useful tool for developing novel HIV-1-inhibitory peptides.
C1 [Wang, Guangshun] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
[Watson, Karen M.; Buckheit, Robert W., Jr.] ImQuest BioSci Inc, Frederick, MD 21704 USA.
[Peterkofsky, Alan] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Wang, GS (reprint author), Univ Nebraska Med Ctr, Eppley Canc Inst, Room ECI 3018,986805 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM gwang@unmc.edu
FU UNEMED; Nebraska Medical Center; NHLBI
FX This study was financially supported by funds from UNEMED and the Eppley
Institute of the University of Nebraska Medical Center (to G.W.) and, in
part, by intramural funds from the NHLBI (to A.P.).
NR 23
TC 43
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U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD MAR
PY 2010
VL 54
IS 3
BP 1343
EP 1346
DI 10.1128/AAC.01448-09
PG 4
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 558HY
UT WOS:000274733300056
PM 20086159
ER
PT J
AU Ishizuya-Oka, A
Hasebe, T
Shi, YB
AF Ishizuya-Oka, Atsuko
Hasebe, Takashi
Shi, Yun-Bo
TI Apoptosis in amphibian organs during metamorphosis
SO APOPTOSIS
LA English
DT Article
DE Amphibian metamorphosis; Apoptosis; Thyroid hormone; Organ remodeling;
Cell-ECM interactions
ID THYROID-HORMONE-RECEPTOR; PROGRAMMED CELL-DEATH; XENOPUS-LAEVIS
TADPOLES; MATRIX-METALLOPROTEINASE STROMELYSIN-3; GENE-EXPRESSION
PROGRAM; ANURAN LARVAL SKIN; DUPLICATED MATRIX-METALLOPROTEINASE-9
GENES; INTESTINAL EPITHELIAL-CELLS; DEPENDENT TAIL REGRESSION;
MESENCEPHALIC 5TH NUCLEUS
AB During amphibian metamorphosis, the larval tissues/organs rapidly degenerate to adapt from the aquatic to the terrestrial life. At the cellular level, a large quantity of apoptosis occurs in a spatiotemporally-regulated fashion in different organs to ensure timely removal of larval organs/tissues and the development of adult ones for the survival of the individuals. Thus, amphibian metamorphosis provides us a good opportunity to understand the mechanisms regulating apoptosis. To investigate this process at the molecular level, a number of thyroid hormone (TH) response genes have been isolated from several organs of Xenopus laevis tadpoles and their expression and functional analyses are now in progress using modern molecular and genetic technologies. In this review, we will first summarize when and where apoptosis occurs in typical larva-specific and larval-to-adult remodeling amphibian organs to highlight that the timing of apoptosis is different in different tissues/organs, even though all are induced by the same circulating TH. Next, to discuss how TH spatiotemporally regulates the apoptosis, we will focus on apoptosis of the X. laevis small intestine, one of the best characterized remodeling organs. Functional studies of TH response genes using transgenic frogs and culture techniques have shown that apoptosis of larval epithelial cells can be induced by TH either cell-autonomously or indirectly through interactions with extracellular matrix (ECM) components of the underlying basal lamina. Here, we propose that multiple intra- and extracellular apoptotic pathways are coordinately controlled by TH to ensure massive but well-organized apoptosis, which is essential for the proper progression of amphibian metamorphosis.
C1 [Ishizuya-Oka, Atsuko; Hasebe, Takashi] Nippon Med Sch, Dept Biol, Kawasaki Ku, Kanagawa 2110063, Japan.
[Shi, Yun-Bo] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Ishizuya-Oka, A (reprint author), Nippon Med Sch, Dept Biol, Kawasaki Ku, Kanagawa 2110063, Japan.
EM a-oka@nms.ac.jp; shi@helix.nih.gov
FU JSPS [20570060]; Intramural Research Program of NICHD; NIH
FX This work was supported in part by the JSPS Grants-in-Aid for Scientific
Research (C) (Grant number 20570060 to A.I.-O.) and in part by the
Intramural Research Program of NICHD, NIH.
NR 153
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U1 0
U2 12
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1360-8185
J9 APOPTOSIS
JI Apoptosis
PD MAR
PY 2010
VL 15
IS 3
SI SI
BP 350
EP 364
DI 10.1007/s10495-009-0422-y
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 567EG
UT WOS:000275425400010
PM 20238476
ER
PT J
AU Gualco, G
Weiss, LM
Harrington, WJ
Bacchi, CE
AF Gualco, Gabriela
Weiss, Lawrence M.
Harrington, William J., Jr.
Bacchi, Carlos E.
TI BCL6, MUM1, and CD10 Expression in Mantle Cell Lymphoma
SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
LA English
DT Article
DE malignant lymphoma; mantle cell lymphoma; BCL-6; CD10; MUM1;
immunohistochemistry; t(11;14); FISH
ID V-H GENES; MUM1/IRF4 EXPRESSION; ABERRANT EXPRESSION; TISSUE MICROARRAY;
MULTIPLE-MYELOMA; CD5; HETEROGENEITY; REARRANGEMENT; HISTOGENESIS;
MUTATIONS
AB Mantle cell lymphoma (MCL) characteristically express CD20, CD5, and cyclin-D1, carries the translocation t(11; 14) (q13; q32) and typically has no expression of germinal center cell markers. So-called aberrant phenotypes such as CD5 negative and cyclin-D1-negative MCL have been described. Also few cases with CD10 and/or BCL-6 protein expression have been reported. We analyzed 127 MCL looking for the frequency of aberrant immunophenotype, CD10, BCL-6, and MUM1 expression. All cases were CD20 and cyclin-D1 positive, 96% expressed CD5, and 98% showed the t(11; 14). BCL-6 expression was observed in 12% of the cases and MUM1 in 35%. No one case showed CD10 positivity in 30% or more neoplastic cells. Only 3 cases showed 10% to 20% of tumoral cells positive for CD10. MUM1 expression was observed in 67% of the BCL-6 positive cases. Thirty-two percent of the cases showed a MUM1+/BCL-6-/CD10- phenotype and 56% had a triple-negative-pattern. Aberrant phenotype is infrequent but not rare, and does not rule out a diagnosis of MCL in an otherwise typical case.
C1 [Gualco, Gabriela; Bacchi, Carlos E.] Consultoria Patol, BR-18602010 Botucatu, SP, Brazil.
[Harrington, William J., Jr.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Harrington, William J., Jr.] Fogarty Int Ctr, Sylvester Canc Ctr, AIDS & TB Program, Miami, FL USA.
[Weiss, Lawrence M.] City Hope Natl Med Ctr, Div Pathol, Duarte, CA 91010 USA.
RP Bacchi, CE (reprint author), Consultoria Patol, Rua Major Leonidas Cardoso 739, BR-18602010 Botucatu, SP, Brazil.
EM bacchi@conspat.com.br
FU NIH [R01CA1219-09]
FX This study was partially supported by NIH R01CA1219-09 (W. H.). No
conflict of interest to declare.
NR 35
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U1 0
U2 1
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 MAR
PY 2010
VL 18
IS 2
BP 103
EP 108
DI 10.1097/PAI.0b013e3181bb9edf
PG 6
WC Anatomy & Morphology; Medical Laboratory Technology; Pathology
SC Anatomy & Morphology; Medical Laboratory Technology; Pathology
GA 563UI
UT WOS:000275160000001
PM 19826251
ER
PT J
AU Diskin, B
Thomas, JL
AF Diskin, Boris
Thomas, James L.
TI Notes on accuracy of finite-volume discretization schemes on irregular
grids
SO APPLIED NUMERICAL MATHEMATICS
LA English
DT Article
DE Irregular grids; Accuracy analysis; Truncation error; Discretization
error
ID DIFFERENCE SCHEMES; SUPRACONVERGENCE; CONVERGENCE; MESHES
AB These notes rebut some overreaching conclusions of Svard et al., 2008 [19] concerning relations between truncation and discretization errors on irregular grids. Convergence of truncation errors severely degrades on general irregular grids. Such degradation does not necessarily imply a less than design-order convergence of discretization errors. (C) 2009 IMACS. Published by Elsevier B.V. All rights reserved.
C1 [Diskin, Boris] NIA, Hampton, VA 23681 USA.
[Diskin, Boris] Univ Virginia, Dept Mech & Aerosp Engn, Charlottesville, VA 22902 USA.
[Thomas, James L.] NASA, Computat Aerosci Branch, Langley Res Ctr, Hampton, VA 23681 USA.
RP Diskin, B (reprint author), NIA, 100 Explorat Way, Hampton, VA 23681 USA.
EM bdiskin@nianet.org; James.L.Thomas@nasa.gov
NR 22
TC 7
Z9 7
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-9274
EI 1873-5460
J9 APPL NUMER MATH
JI Appl. Numer. Math.
PD MAR
PY 2010
VL 60
IS 3
BP 224
EP 226
DI 10.1016/j.apnum.2009.12.001
PG 3
WC Mathematics, Applied
SC Mathematics
GA 585PP
UT WOS:000276839200005
ER
PT J
AU Iwamoto, FM
Fine, HA
AF Iwamoto, Fabio M.
Fine, Howard A.
TI Bevacizumab for Malignant Gliomas
SO ARCHIVES OF NEUROLOGY
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; ANTI-ANGIOGENIC THERAPY; RECURRENT
GLIOBLASTOMA; PLUS IRINOTECAN; END-POINT; SURVIVAL; TUMORS; PROGRESSION;
PHASE-2; ADULTS
AB Malignant gliomas are the most common and aggressive primary brain tumors in adults. Despite optimal treatment with surgery, radiotherapy, and temozolomide, tumor recurrences are frequent and patients with malignant gliomas continue to have poor prognoses. Malignant gliomas are often highly vascularized, and significant advances have been made in the last few decades in our understanding of the mechanisms of tumor angiogenesis. Recently, bevacizumab, an antibody against vascular endothelial growth factor, has demonstrated significant activity in recurrent glioblastomas, resulting in US Food and Drug Administration approval and raising the prospect for other antiangiogenic drugs now entering clinical trials. Arch Neurol. 2010; 67(3): 285-288
C1 [Fine, Howard A.] NCI, Neurooncol Branch, Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
RP Fine, HA (reprint author), NCI, Neurooncol Branch, Natl Inst Neurol Disorders & Stroke, NIH, 9030 Old Georgetown Rd,Bloch Bldg 82,Room 225, Bethesda, MD 20892 USA.
EM hfine@mail.nih.gov
FU National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (Center for Cancer Research of the
National Cancer Institute and National Institute of Neurological
Disorders and Stroke).
NR 32
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U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0003-9942
EI 1538-3687
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD MAR
PY 2010
VL 67
IS 3
BP 285
EP 288
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 565QG
UT WOS:000275308600004
PM 20212225
ER
PT J
AU Ambrosius, WT
Danis, RP
Goff, DC
Greven, CM
Gerstein, HC
Cohen, RM
Riddle, MC
Miller, ME
Buse, JB
Bonds, DE
Peterson, KA
Rosenberg, YD
Perdue, LH
Esser, BA
Seaquist, LA
Felicetta, JV
Chew, EY
AF Ambrosius, Walter T.
Danis, Ronald P.
Goff, David C., Jr.
Greven, Craig M.
Gerstein, Hertzel C.
Cohen, Robert M.
Riddle, Matthew C.
Miller, Michael E.
Buse, John B.
Bonds, Denise E.
Peterson, Kevin A.
Rosenberg, Yves D.
Perdue, Letitia H.
Esser, Barbara A.
Seaquist, Lea A.
Felicetta, James V.
Chew, Emily Y.
CA ACCORD Study Grp
TI Lack of Association Between Thiazolidinediones and Macular Edema in Type
2 Diabetes The ACCORD Eye Substudy
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID MYOCARDIAL-INFARCTION; HARD EXUDATE; RETINOPATHY; ROSIGLITAZONE; RISK;
PIOGLITAZONE; MELLITUS; EVENTS
AB Objective: To assess the cross-sectional association of thiazolidinediones with diabetic macular edema (DME).
Methods: The cross-sectional association of DME and visual acuity with thiazolidinediones was examined by means of baseline fundus photographs and visual acuity measurements from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Visual acuity was assessed in 9690 participants in the ACCORD trial, and 3473 of these participants had fundus photographs that were centrally read in a standardized fashion by masked graders to assess DME and retinopathy from October 23, 2003, to March 10, 2006.
Results: Among the subsample, 695 (20.0%) people had used thiazolidinediones, whereas 217 (6.2%) people had DME. Thiazolidinedione use was not associated with DME in unadjusted (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.71-1.44; P=.95) and adjusted (OR, 0.97; 95% CI, 0.67-1.40; P=.86) analyses. Significant associations with DME were found for retinopathy severity (P<.001) and age (OR, 0.97; 95% CI, 0.952-0.997; P=.03) but not for hemoglobin A(1c) (P=.06), duration of diabetes (P=.65), sex (P=.72), and ethnicity (P=.20). Thiazolidinedione usewas associated with slightly greater visual acuity (0.79 letter; 95% CI, 0.20-1.38; P=.009) of uncertain clinical significance.
Conclusions: In a cross-sectional analysis of data from the largest study to date, no association was observed between thiazolidinedione exposure and DME in patients with type 2 diabetes; however, we cannot exclude a modest protective or harmful association.
Trial Registration: clinicaltrials.gov Identifier: NCT00542178
C1 [Ambrosius, Walter T.; Miller, Michael E.; Perdue, Letitia H.] Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27109 USA.
[Goff, David C., Jr.] Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA.
[Greven, Craig M.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Greven, Craig M.] Wake Forest Univ, Sch Med, Dept Ophthalmol, Winston Salem, NC 27109 USA.
[Danis, Ronald P.; Esser, Barbara A.] Univ Wisconsin, Dept Ophthalmol, Fundus Photograph Reading Ctr, Madison, WI USA.
[Gerstein, Hertzel C.] McMaster Univ, Hamilton, ON, Canada.
[Gerstein, Hertzel C.] Hamilton Hlth Sci, Hamilton, ON, Canada.
[Cohen, Robert M.] Univ Cincinnati, Med Ctr, Dept Internal Med, Div Endocrinol Diabet & Metab, Cincinnati, OH 45267 USA.
[Riddle, Matthew C.] Oregon Hlth & Sci Univ, Dept Med, Div Endocrinol Diabet Clin Nutr, Portland, OR 97201 USA.
[Buse, John B.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
[Bonds, Denise E.] NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Rosenberg, Yves D.] NHLBI, Div Cardiovasc Dis, NIH, Bethesda, MD 20892 USA.
[Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Peterson, Kevin A.; Seaquist, Lea A.] Univ Minnesota, Sch Med, Dept Family Med & Community Hlth, Minneapolis, MN 55455 USA.
[Felicetta, James V.] Phoenix VA Hlth Care Syst, Phoenix, AZ USA.
RP Ambrosius, WT (reprint author), Wake Forest Univ Hlth Sci, Dept Biostat Sci, Div Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM wambrosi@wfubmc.edu
OI Peterson, Kevin/0000-0002-6914-8586
FU National Eye Institute and the National Heart, Lung, and Blood Institute
of the National Institutes of Health
FX This study was funded by the National Eye Institute and the National
Heart, Lung, and Blood Institute of the National Institutes of Health.
NR 41
TC 26
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U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD MAR
PY 2010
VL 128
IS 3
BP 312
EP 318
PG 7
WC Ophthalmology
SC Ophthalmology
GA 565QC
UT WOS:000275308100006
PM 20212201
ER
PT J
AU Bradley, KT
Arber, DA
Brown, MS
Chang, CC
Coupland, SE
de Baca, ME
Ellis, DW
Foucar, K
Hsi, ED
Jaffe, ES
Lill, MC
McClure, SP
Medeiros, LJ
Perkins, SL
Hussong, JW
AF Bradley, Kyle T.
Arber, Daniel A.
Brown, Michael S.
Chang, Chung-Che
Coupland, Sarah E.
de Baca, Monica E.
Ellis, David W.
Foucar, Kathryn
Hsi, Eric D.
Jaffe, Elaine S.
Lill, Michael C.
McClure, Stephen P.
Medeiros, L. Jeffrey
Perkins, Sherrie L.
Hussong, Jerry W.
CA Members Canc Comm
Coll Amer Pathologists
TI Protocol for the Examination of Specimens From Patients With
Hematopoietic Neoplasms of the Ocular Adnexa
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID LYMPHOID-TISSUE-TYPE; CELL LYMPHOMA; REAL CLASSIFICATION; FEATURES;
ORBIT; CONJUNCTIVA; TUMORS
C1 [Hussong, Jerry W.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA.
[Lill, Michael C.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA.
[Bradley, Kyle T.] Emory Univ Hosp, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Arber, Daniel A.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Brown, Michael S.] Yellowstone Pathol Inst Inc, Billings, MT USA.
[Chang, Chung-Che] Methodist Hosp, Dept Pathol, Houston, TX 77030 USA.
[Coupland, Sarah E.] Royal Liverpool Univ Hosp, Dept Pathol, Liverpool, Merseyside, England.
[de Baca, Monica E.] Phys Lab Ltd, Dept Pathol & Lab Med, Sioux Falls, SD USA.
[Ellis, David W.] Flinders Med Ctr, Dept Anat Pathol, Bedford Pk, SA, Australia.
[Foucar, Kathryn] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA.
[Hsi, Eric D.] Cleveland Clin, Dept Clin Pathol, Cleveland, OH 44106 USA.
[Jaffe, Elaine S.] NCI, Dept Pathol, Bethesda, MD 20892 USA.
[McClure, Stephen P.] Presbyterian Pathol Grp, Dept Pathol & Lab Med, Charlotte, NC USA.
[Medeiros, L. Jeffrey] Univ Texas Houston, MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA.
[Perkins, Sherrie L.] Univ Utah, Hlth Sci Ctr, Dept Pathol, Salt Lake City, UT 84132 USA.
RP Hussong, JW (reprint author), Cedars Sinai Med Ctr, Dept Pathol & Lab Med, 8700 Beverly Blvd,Room 4708, Los Angeles, CA 90048 USA.
EM hussongj@cshs.org
NR 27
TC 1
Z9 1
U1 0
U2 2
PU COLLEGE AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD MAR
PY 2010
VL 134
IS 3
BP 336
EP 340
PG 5
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA 568NL
UT WOS:000275529200003
PM 20196660
ER
PT J
AU Barnes, W
D'Angelo, L
Yamazaki, M
Belzer, M
Schroeder, S
Palmer-Castor, J
Futterman, D
Kapogiannis, B
Muenz, L
Harris, DR
Ellen, JM
AF Barnes, William
D'Angelo, Lawrence
Yamazaki, Michiyo
Belzer, Marvin
Schroeder, Sybil
Palmer-Castor, Judith
Futterman, Donna
Kapogiannis, Bill
Muenz, Larry
Harris, D. Robert
Ellen, Jonathan M.
CA Adolescent Trials Network HIV AIDS
TI Identification of HIV-Infected 12-to 24-Year-Old Men and Women in 15 US
Cities Through Venue-Based Testing
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Article
ID UNITED-STATES; PREVALENCE
AB Objective: To test whether "venue-based testing" could identify human immunodeficiency virus (HIV) infection in US youth, 12 to 24 years of age, who were otherwise not aware of their infection. Racial and ethnic minority women and men who have sex with men (WSM and MSM) compose the majority of new HIV cases among adolescents and young adults.
Design: Cross-sectional study.
Setting: Selected venues in communities surrounding the 15 Adolescent Trials Network for HIV/AIDS Interventions (ATN) clinical sites over a 3-month period.
Participants: At each venue, ATN sites recruited 20 to 30 English-or Spanish-speaking at-risk youth (12 to 24 years of age), resulting in a total of 1217 study participants, including 611 MSM and 606 WSM.
Intervention: Venue-based HIV testing with 2 components: an anonymous audio computer-assisted self-administered interview and an anonymous HIV antibody assay.
Main Outcome Measure: The prevalence of HIV infection in MSM and WSM.
Results: The prevalence of HIV infection in MSM and WSM was 15.3% and 0.3%, respectively. Sixty percent of the MSM and 100% of the WSM claimed to not know of their infection.
Conclusion: Venue-based testing may be an important strategy to identify HIV-infected younger MSM; however, other strategies are needed for WSM. Arch Pediatr Adolesc Med. 2010; 164(3): 273-276
C1 [Barnes, William; D'Angelo, Lawrence] Childrens Natl Med Ctr, Div Adolescent & Young Adult Med, Washington, DC 20010 USA.
[Muenz, Larry; Harris, D. Robert] Westat Corp, Washington, DC USA.
[Yamazaki, Michiyo; Ellen, Jonathan M.] Johns Hopkins Sch Med, Div Gen Pediat & Adolescent Med, Dept Pediat, Baltimore, MD USA.
[Kapogiannis, Bill] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA.
[Belzer, Marvin] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA.
[Schroeder, Sybil] Tulane Sch Med, Sect Adolescent Med, Dept Pediat, New Orleans, LA USA.
[Palmer-Castor, Judith] Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA 02115 USA.
[Futterman, Donna] Albert Einstein Coll Med, Dept Pediat, Bronx, NY USA.
RP Yamazaki, M (reprint author), Ctr Tower,5200 Eastern Ave,Ste 4200, Baltimore, MD 21224 USA.
FU ATN and Connect through the National Institute of Child Health and Human
Development; National Institutes on Drug Abuse, Mental Health, and
Alcohol Abuse and Alcoholism
FX Funding/Support: The ATN and Connect to Protect were funded, at the time
of this study, through the National Institute of Child Health and Human
Development (Dr Kapogiannis, Audrey Rogers, PhD, MPH, Robert Nugent,
PhD, Leslie Serchuck, MD, and Sonia Lee, PhD), with supplemental funding
from the National Institutes on Drug Abuse (Nicolette Borek, PhD),
Mental Health (Andrew Forsyth, PhD, Pim Brouwers, PhD), and Alcohol
Abuse and Alcoholism (Kendall Bryant, PhD).
NR 8
TC 15
Z9 15
U1 0
U2 8
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 1072-4710
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD MAR
PY 2010
VL 164
IS 3
BP 273
EP 276
PG 4
WC Pediatrics
SC Pediatrics
GA 562IA
UT WOS:000275042300011
PM 20194262
ER
PT J
AU Rivara, FP
Alexander, D
AF Rivara, Frederick P.
Alexander, Duane
TI Randomized Controlled Trials and Pediatric Research
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Editorial Material
C1 [Rivara, Frederick P.] Univ Washington, Inst Child Hlth, Seattle, WA 98115 USA.
[Alexander, Duane] NIH, Bethesda, MD 20892 USA.
RP Rivara, FP (reprint author), Univ Washington, Inst Child Hlth, 6200 NE 74th St,Ste 110, Seattle, WA 98115 USA.
EM fpr@uw.edu
NR 5
TC 4
Z9 4
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 1072-4710
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD MAR
PY 2010
VL 164
IS 3
BP 296
EP 297
PG 3
WC Pediatrics
SC Pediatrics
GA 562IA
UT WOS:000275042300017
PM 20194268
ER
PT J
AU Safaeian, M
van Doorslaer, K
Schiffman, M
Chen, ZG
Rodriguez, AC
Herrero, R
Hildesheim, A
Burk, RD
AF Safaeian, Mahboobeh
van Doorslaer, Koenraad
Schiffman, Mark
Chen, Zigui
Rodriguez, Ana Cecilia
Herrero, Rolando
Hildesheim, Allan
Burk, Robert D.
TI Lack of heterogeneity of HPV16 E7 sequence compared with HPV31 and HPV73
may be related to its unique carcinogenic properties
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS TYPE-16; POPULATION; VARIANTS
AB To assess the role of human papillomavirus virus (HPV) genetics in cervical lesions, we sequenced the E7 gene of HPV16, 31, or 73 from singly infected women who (1) cleared the infection quickly, (2) had type-specific persistent infection, or (3) progressed to CIN2 or worse lesions. Four of the 296 HPV16 E7 nucleotides were variable, compared with 7 of 296 for HPV31 E7 and 4 of 296 for HPV73 E7. While most of the polymorphisms in HPV31 and -73 resulted in non-synonymous amino acid changes, the polymorphisms in the HPV16 E7 resulted in synonymous changes. The lack of heterogeneity of HPV16 E7 suggests high evolutionary purifying selection that might be related to the unique carcinogenicity of HPV16.
C1 [Safaeian, Mahboobeh; Schiffman, Mark; Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[van Doorslaer, Koenraad; Chen, Zigui; Burk, Robert D.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Rodriguez, Ana Cecilia; Herrero, Rolando] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica.
RP Safaeian, M (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM safaeianm@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015; Chen, Zigui/E-8490-2017;
OI Hildesheim, Allan/0000-0003-0257-2363; Van Doorslaer,
Koenraad/0000-0002-2985-0733
FU NCI NIH HHS [R01 CA078527, U01 CA078527, U01 CA078527-12]
NR 10
TC 3
Z9 3
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 MAR
PY 2010
VL 155
IS 3
BP 367
EP 370
DI 10.1007/s00705-009-0579-2
PG 4
WC Virology
SC Virology
GA 560XW
UT WOS:000274939600009
PM 20049619
ER
PT J
AU Ward, MM
AF Ward, Michael M.
TI Medicare Reimbursement and the Use of Biologic Agents: Incentives,
Access, the Public Good, and Optimal Care
SO ARTHRITIS CARE & RESEARCH
LA English
DT Editorial Material
ID RHEUMATOID-ARTHRITIS; MODERNIZATION ACT; CHEMOTHERAPY; ETANERCEPT;
INFLIXIMAB; IMPACT
C1 NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), NIAMSD, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU Intramural NIH HHS [Z01 AR041153-03, Z01 AR041153-04, ZIA AR041170-02,
Z01 AR041170-01, ZIA AR041153-05]
NR 16
TC 3
Z9 3
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 2151-464X
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD MAR
PY 2010
VL 62
IS 3
BP 293
EP 295
DI 10.1002/acr.20088
PG 3
WC Rheumatology
SC Rheumatology
GA 639MP
UT WOS:000280979200001
PM 20391473
ER
PT J
AU Feingold, KR
Kazemi, MR
Magra, AL
McDonald, CM
Chui, LG
Shigenaga, JK
Patzek, SM
Chan, ZW
Londos, C
Grunfeld, C
AF Feingold, Kenneth R.
Kazemi, Mahmood R.
Magra, Amy L.
McDonald, Carol M.
Chui, Lisa G.
Shigenaga, Judy K.
Patzek, Sophie M.
Chan, Zoe W.
Londos, Constantine
Grunfeld, Carl
TI ADRP/ADFP and Mal1 expression are increased in macrophages treated with
TLR agonists
SO ATHEROSCLEROSIS
LA English
DT Article
DE Acute phase response; Atherosclerosis; Endotoxin; Zymosan; Foam cell
ID DIFFERENTIATION-RELATED PROTEIN; TOLL-LIKE RECEPTOR-4;
LOW-DENSITY-LIPOPROTEIN; PAT FAMILY PROTEINS; FOAM CELL-FORMATION;
BINDING PROTEIN; LIPID-ACCUMULATION; CHLAMYDIA-PNEUMONIAE; MURINE
MACROPHAGES; APOLIPOPROTEIN-E
AB Activation of macrophages by TLR agonists enhances foam cell formation, but the underlying mechanisms are not understood. We examined the effects of TLR agonists on ADRP/ADFP, a protein associated with forming lipid droplets, and Mal1 a fatty acid-binding protein, in two mouse macrophage cell lines and human monocytes. Low doses of LPS, a TLR4 agonist increased both mRNA and protein levels of ADRP/ADFP and Mal1 in RAW 264.7 macrophages. Following pretreatment with Intralipid, fatty acids, or acetyl-LDL to increase triglyceride or cholesterol ester storage, LPS treatment still increased ADRP/ADFP and Mal1 mRNA levels. LPS also induced ADRP/ADFP and Mal1 in J774 macrophages and ADRP/ADFP in human monocytes. Zymosan, a fungal product that activates TLR2, poly-I:C, a viral mimetic that activates TLR3, and imiquimod, a TLR7 agonist, also increased ADRP/ADFP. Zymosan, but not poly-I: C or imiquimod, induced Mal1. In contrast, neither gene was induced by TNF alpha, IL-1 beta, IL-6, or interferon-gamma. Thus TLR agonists induce ADRP/ADFP and Mal1, which likely contributes to macrophage triglyceride and cholesterol ester storage leading to foam cell formation. Published by Elsevier Ireland Ltd.
C1 [Feingold, Kenneth R.; Kazemi, Mahmood R.; McDonald, Carol M.; Chui, Lisa G.; Shigenaga, Judy K.; Patzek, Sophie M.; Chan, Zoe W.; Grunfeld, Carl] Dept Vet Affairs Med Ctr, Metab Sect, San Francisco, CA USA.
[Feingold, Kenneth R.; Kazemi, Mahmood R.; McDonald, Carol M.; Chui, Lisa G.; Shigenaga, Judy K.; Patzek, Sophie M.; Chan, Zoe W.; Grunfeld, Carl] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Magra, Amy L.; Londos, Constantine] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Feingold, KR (reprint author), SFVAMC Metab Sect, 4150 Clement St,111F, San Francisco, CA 94121 USA.
EM kenneth.feingold@ucsf.edu
FU Research Service of the Department of Veterans Affairs, National
Institutes of Health [5R01HD029706]; Albert L. and Janet A. Shultz
Supporting Foundation
FX This work was supported by grants from the Research Service of the
Department of Veterans Affairs, National Institutes of Health Grant
5R01HD029706, and the Albert L. and Janet A. Shultz Supporting
Foundation.
NR 45
TC 24
Z9 32
U1 0
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD MAR
PY 2010
VL 209
IS 1
BP 81
EP 88
DI 10.1016/j.atherosclerosis.2009.08.042
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 563BV
UT WOS:000275101500013
PM 19748622
ER
PT J
AU Lleo, A
Invernizzi, P
Gao, B
Podda, M
Gershwin, ME
AF Lleo, Ana
Invernizzi, Pietro
Gao, Bin
Podda, Mauro
Gershwin, M. Eric
TI Definition of human autoimmunity - autoantibodies versus autoimmune
disease
SO AUTOIMMUNITY REVIEWS
LA English
DT Article
DE Autoantibody; Autoantigen; Tolerance; B cell; Autoimmune disease
ID PRIMARY BILIARY-CIRRHOSIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CONGENITAL
HEART-BLOCK; B-CELLS; ANTIMITOCHONDRIAL ANTIBODIES; ANTIPHOSPHOLIPID
ANTIBODIES; APOPTOTIC NEUTROPHILS; NATURAL ANTIBODIES; PATHOGENIC ROLE;
MARGINAL ZONE
AB The critical function of the immune system is to discriminate self from non-self. Tolerance against self-antigens is a highly regulated process and, in order to maintain it, the immune system must be able to distinguish self-reactive lymphocytes as they develop. The presence of autoantibodies is the consequence of breakdown of tolerance and, although they are an important serological feature of autoimmune diseases, their presence is not exclusive of these conditions. Antibodies against self-antigens are also found in cancer, during massive tissue damage and even in healthy subjects. Natural autoantibodies provide immediate protection against infection and also prevent inflammation by facilitating the clearance of oxidized lipids, oxidized proteins, and apoptotic cells: their role in development of autoimmunity is still unclear. Detection of serum autoantibodies in clinical practice has become more available to clinicians worldwide while providing a powerful diagnostic tool. This review discusses the clinical significance of autoantibodies, their pathogenic mechanisms in autoimmune diseases and, finally, illustrates the technology available for appropriate autoantibody detection. (C) 2009 Elsevier By. All rights reserved.
C1 [Gershwin, M. Eric] Univ Calif Davis, Sch Med, Genome & Biomed Sci Facil, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA.
[Lleo, Ana; Invernizzi, Pietro; Podda, Mauro] IRCCS Ist Clin Humanitas, Div Internal Med, Rozzano, Italy.
[Lleo, Ana; Invernizzi, Pietro; Podda, Mauro] IRCCS Ist Clin Humanitas, Hepatobiliary Immunopathol Unit, Rozzano, Italy.
[Podda, Mauro] Univ Milan, Dept Translat Med, I-20122 Milan, Italy.
[Gao, Bin] NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD USA.
RP Gershwin, ME (reprint author), Univ Calif Davis, Sch Med, Genome & Biomed Sci Facil, Div Rheumatol Allergy & Clin Immunol, 451 E Hlth Sci Dr,Suite 6510, Davis, CA 95616 USA.
EM megershwin@ucdavis.edu
OI LLEO DE NALDA, Ana/0000-0002-0561-7902; Invernizzi,
Pietro/0000-0003-3262-1998
NR 60
TC 99
Z9 101
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-9972
EI 1873-0183
J9 AUTOIMMUN REV
JI Autoimmun. Rev.
PD MAR
PY 2010
VL 9
IS 5
SI SI
BP A259
EP A266
DI 10.1016/j.autrev.2009.12.002
PG 8
WC Immunology
SC Immunology
GA 580SN
UT WOS:000276470100003
PM 19963079
ER
PT J
AU Fouchier, RAM
Smith, DI
AF Fouchier, Ron A. M.
Smith, Derek I.
TI Use of Antigenic Cartography in Vaccine Seed Strain Selection
SO AVIAN DISEASES
LA English
DT Article; Proceedings Paper
CT 7th International Symposium on Avian Influenza
CY APR 05-08, 2009
CL Univ Georgia, Athens, GA
HO Univ Georgia
DE influenza A virus; vaccine; HI antibodies; antigenic drift
ID AVIAN INFLUENZA-VIRUS; A H3N2 VIRUSES; SEASONAL INFLUENZA; GENETIC
EVOLUTION; DISEASE; BURDEN
AB Human influenza A viruses are classic examples of antigenically variable pathogens that have a seemingly endless capacity to evade the host's immune response. The viral hemagglutinin (HA) and neuraminidase (NA) proteins are the main targets of our antibody response to combat infections. HA and NA continuously change ro escape from Immoral immunity, a process known as antigenic drift. As a result of antigenic drift, the human influenza vaccine is updated frequently. The World Health Organization (WHO) coordinates a global influenza surveillance network that, by the hemagglutination inhibition (HI) assay, routinely characterizes the antigenic properties of circulating strains in order to select new seed viruses for such vaccine updates. To facilitate a quantitative interpretation and easy visualization of HI data, a new computational technique called "antigenic cartography" was developed. Since its development, antigenic cartography has been applied routinely to assist the WHO with influenza surveillance activities. Until recently, antigenic variation was not considered a serious issue with influenza vaccines for poultry. However, because of the diversification of the Asian H5N1 lineage since 1996 into multiple genetic clades and subclades, and because of the long-term use of poultry vaccines against H5 in some parts of the world, this issue needs to be re-addressed. The antigenic properties of panels of avian H5N1 viruses were characterized by HI assay, using mammalian or avian antisera, and analyzed using antigenic cartography methods. These analyses revealed antigenic differences between circulating H5N1 viruses and the H5 viruses used in poultry vaccines. Considerable antigenic variation was also observed within and between H5N1 clades. These observations have important implications for the efficacy and long-term use of poultry vaccines.
C1 [Fouchier, Ron A. M.; Smith, Derek I.] Erasmus MC, Dept Virol, NL-3015 GE Rotterdam, Netherlands.
[Smith, Derek I.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
[Smith, Derek I.] Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA.
RP Fouchier, RAM (reprint author), Erasmus MC, Dept Virol, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands.
EM r.fouchier@erasmusmc.nl
RI Fouchier, Ron/A-1911-2014
OI Fouchier, Ron/0000-0001-8095-2869
FU NIH HHS [DP1-OD000490-01]; NINDS NIH HHS [HHNSN266200700010C]
NR 14
TC 22
Z9 22
U1 1
U2 6
PU AMER ASSOC AVIAN PATHOLOGISTS
PI ATHENS
PA 953 COLLEGE STATION RD, ATHENS, GA 30602-4875 USA
SN 0005-2086
J9 AVIAN DIS
JI Avian Dis.
PD MAR
PY 2010
VL 54
IS 1
SU S
BP 220
EP 223
DI 10.1637/8740-032509-ResNote.1
PG 4
WC Veterinary Sciences
SC Veterinary Sciences
GA 580NF
UT WOS:000276455300009
PM 20521635
ER
PT J
AU Schmitt, JE
Wallace, GL
Lenroot, RK
Ordaz, SE
Greenstein, D
Clasen, L
Kendler, KS
Neale, MC
Giedd, JN
AF Schmitt, J. Eric
Wallace, Gregory L.
Lenroot, Rhoshel K.
Ordaz, Sarah E.
Greenstein, Dede
Clasen, Liv
Kendler, Kenneth S.
Neale, Michael C.
Giedd, Jay N.
TI A Twin Study of Intracerebral Volumetric Relationships
SO BEHAVIOR GENETICS
LA English
DT Article
DE Twin; Cerebrum; MRI; Genetics; Pediatrics
ID HUMAN BRAIN EVOLUTION; CORTICAL DEVELOPMENT; FACTOR MODELS;
HOMO-SAPIENS; MRI DATA; MULTIVARIATE; MULTIMETHOD; MULTITRAIT; SIZE;
HERITABILITY
AB Using high resolution magnetic resonance imaging data, we examined the interrelationships between eight cerebral lobar volumetric measures via both exploratory and confirmatory factor analyses in a large sample (N = 484) of pediatric twins and singletons. These analyses suggest the presence of strong genetic correlations between cerebral structures, particularly between regions of like tissue type or in spatial proximity. Structural modeling estimated that most of the variance in all structures is associated with highly correlated lobar latent factors, with differences in genetic covariance and heritability driven by a common genetic factor that influenced gray and white matter differently. Reanalysis including total brain volume as a covariate dramatically reduced the total residual variance and disproportionately influenced the additive genetic variance in all regions of interest.
C1 [Schmitt, J. Eric; Kendler, Kenneth S.; Neale, Michael C.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA.
[Wallace, Gregory L.; Lenroot, Rhoshel K.; Greenstein, Dede; Clasen, Liv; Giedd, Jay N.] NIMH, Pediat Imaging Unit, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Ordaz, Sarah E.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.
RP Schmitt, JE (reprint author), Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, 800 E Leigh St,Suite 100,POB 980003, Richmond, VA 23298 USA.
EM eric.schmitt@stanfordalumni.org
RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015;
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Wallace,
Gregory/0000-0003-0329-5054
FU NIH [MH-65322, MH-20030, DA-18673]
FX This research was supported by the intramural research program of the
NIH as well as NIH grants MH-65322, MH-20030, and DA-18673.
NR 42
TC 17
Z9 17
U1 8
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-8244
J9 BEHAV GENET
JI Behav. Genet.
PD MAR
PY 2010
VL 40
IS 2
SI SI
BP 114
EP 124
DI 10.1007/s10519-010-9332-6
PG 11
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA 561GM
UT WOS:000274964000002
PM 20112130
ER
PT J
AU Wallace, GL
Lee, NR
Prom-Wormley, EC
Medland, SE
Lenroot, RK
Clasen, LS
Schmitt, JE
Neale, MC
Giedd, JN
AF Wallace, Gregory L.
Lee, Nancy Raitano
Prom-Wormley, Elizabeth C.
Medland, Sarah E.
Lenroot, Rhoshel K.
Clasen, Liv S.
Schmitt, James E.
Neale, Michael C.
Giedd, Jay N.
TI A Bivariate Twin Study of Regional Brain Volumes and Verbal and
Nonverbal Intellectual Skills During Childhood and Adolescence
SO BEHAVIOR GENETICS
LA English
DT Article
DE Twin; Magnetic resonance imaging; Brain; Intelligence; Verbal; Nonverbal
ID GENETIC INFLUENCES; MRI DATA; INTELLIGENCE; CHILDREN
AB Twin studies indicate that both intelligence and brain structure are moderately to highly heritable. Recent bivariate studies of adult twins also suggest that intelligence and brain morphometry are influenced by shared genetic factors. The current study examines shared genetic and environmental factors between brain morphometry and intelligence in a sample of children and adolescents (twins, twin siblings, and singletons; n = 649, ages 4-19). To extend previous studies, brain morphometric data were parsed into subregions (lobar gray/white matter volumes, caudate nucleus, lateral ventricles) and intelligence into verbal and nonverbal skills (Wechsler Vocabulary and Block Design subtests). Phenotypic relationships between brain volumes and intelligence were small. Verbal skills shared unique environmental effects with gray matter volumes while nonverbal skills shared genetic effects with both global and regional gray and white matter. These results suggest that distinct mechanisms contribute to the small phenotypic relationships between brain volumes and verbal versus nonverbal intelligence.
C1 [Wallace, Gregory L.; Lee, Nancy Raitano; Lenroot, Rhoshel K.; Clasen, Liv S.; Giedd, Jay N.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Prom-Wormley, Elizabeth C.; Medland, Sarah E.; Schmitt, James E.; Neale, Michael C.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA.
[Medland, Sarah E.] Queensland Inst Med Res, Genet Epidemiol Unit, Brisbane, Qld 4006, Australia.
RP Wallace, GL (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,4C110,MSC-1367,10 Ctr Dr, Bethesda, MD 20892 USA.
EM gregwallace@mail.nih.gov
RI Lee, Nancy Raitano/F-2565-2011; Giedd, Jay/A-3080-2008; Giedd,
Jay/B-7302-2012; Medland, Sarah/C-7630-2013; Giedd, Jay/J-9644-2015;
Lee, Nancy/M-7492-2016;
OI Giedd, Jay/0000-0003-0827-3460; Medland, Sarah/0000-0003-1382-380X;
Giedd, Jay/0000-0003-2002-8978; Lee, Nancy/0000-0002-6663-0713;
Prom-Wormley, Elizabeth/0000-0001-9230-9723; Wallace,
Gregory/0000-0003-0329-5054
FU NIH [MH-20030]; National Institute of Mental Health; NHMRC Australia,
Sidney [443036; SEM]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Mental Health (GW, NRL, LSC, RL, JG),
extramural grant funding from the NIH (MH-20030; EP-W, SEM, JES, MCN),
and an NHMRC Australia, Sidney Sax Public Fellowship (443036; SEM). We
would like to express our gratitude to the individuals who volunteered
their time to contribute to this research.
NR 47
TC 14
Z9 14
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-8244
J9 BEHAV GENET
JI Behav. Genet.
PD MAR
PY 2010
VL 40
IS 2
SI SI
BP 125
EP 134
DI 10.1007/s10519-009-9329-1
PG 10
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA 561GM
UT WOS:000274964000003
PM 20112131
ER
PT J
AU Arellano-Plancarte, A
Hernandez-Aranda, J
Catt, KJ
Olivares-Reyes, JA
AF Arellano-Plancarte, Araceli
Hernandez-Aranda, Judith
Catt, Kevin J.
Olivares-Reyes, J. Alberto
TI Angiotensin-induced EGF receptor transactivation inhibits insulin
signaling in C9 hepatic cells
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Angiotensin II; Insulin; EGF receptor transactivation; Insulin
resistance; Akt
ID EPIDERMAL-GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; PROTEIN-KINASE-C; SERINE
PHOSPHORYLATION; SKELETAL-MUSCLE; MAP KINASE; CROSS-TALK;
SERINE/THREONINE PHOSPHORYLATION; TYROSINE PHOSPHORYLATION;
GLUCOSE-TRANSPORT
AB To investigate the potential interactions between the angiotensin II (Ang II) and insulin signaling systems, regulation of IRS-1 phosphorylation and insulin-induced Akt activation by Ang II were examined in clone 9 (C9) hepatocytes. In these cells, Ang II specifically inhibited activation of insulininduced Akt Thr(308) and its immediate downstream substrate GSK-3 alpha/beta in a time-dependent fashion, with similar to 70% reduction at 15 min. These inhibitory actions were associated with increased IRS-1 phosphorylation of Ser(636)/Ser(639) that was prevented by selective blockade of EGFR tyrosine kinase activity with AG1478. Previous studies have shown that insulin-induced phosphorylation of IRS-1 on Ser(636)/Ser(639) is mediated mainly by the PI3K/mTOR/S6K-1 sequence. Studies with specific inhibitors of PI3K (wortmannin) and mTOR (rapamycin) revealed that Ang II stimulates IRS-1 phosphorylation of Ser(636)/Ser(639) via the PI3K/mTOR/S6K-1 pathway. Both inhibitors blocked the effect of Ang II on insulin-induced activation of Akt. Studies using the specific MEK inhibitor, PD98059, revealed that ERK1/2 activation also mediates Ang II-induced S6K-1 and IRS-1 phosphorylation, and the impairment of Akt Thr308 and GSK-3 alpha/beta phosphorylation. Further studies with selective inhibitors showed that PI3K activation was upstream of ERK, suggesting a new mechanism for Ang II-induced impairment of insulin signaling. These findings indicate that Ang 11 has a significant role in the development of insulin resistance by a mechanism that involves EGFR transactivation and the PI3K/ERK1/2/mTOR-S6K-1 pathway. (c) 2009 Elsevier Inc. All rights reserved.
C1 [Arellano-Plancarte, Araceli; Hernandez-Aranda, Judith; Olivares-Reyes, J. Alberto] Cinvestav IPN, Lab Signal Transduct, Dept Biochem, Ctr Res & Adv Studies,Natl Polytech Inst, Mexico City 07360, DF, Mexico.
[Catt, Kevin J.] NICHHD, Sect Hormonal Regulat, PDEGEN, NIH, Bethesda, MD 20892 USA.
RP Olivares-Reyes, JA (reprint author), Cinvestav IPN, Lab Signal Transduct, Dept Biochem, Ctr Res & Adv Studies,Natl Polytech Inst, AP 14-740, Mexico City 07360, DF, Mexico.
EM jolivare@cinvestav.mx
FU Cinvestav-IPN; CONACYT/SEP Research Grants [39485-Q/48777, 169944]
FX This research was supported by Cinvestav-IPN and CONACYT/SEP Research
Grants 39485-Q/48777 (to J.A. O.-R.); by CONACYT fellowship grant, No.
169944 and Apoyo Integral para la Formacion de Doctores en Ciencia,
Modalidad A, Tesista de Doctorado, CONACYT (to A. A.-P.). The authors
thank Norma Cirnes for her help in the preparation of the figures.
NR 70
TC 11
Z9 12
U1 0
U2 2
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 MAR 1
PY 2010
VL 79
IS 5
BP 733
EP 745
DI 10.1016/j.bcp.2009.10.014
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 546SN
UT WOS:000273831800009
PM 19879250
ER
PT J
AU Kristie, TM
Liang, Y
Vogel, JL
AF Kristie, Thomas M.
Liang, Yu
Vogel, Jodi L.
TI Control of alpha-herpesvirus IE gene expression by HCF-1 coupled
chromatin modification activities
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE HCF-1; Herpesvirus; Coactivator; Set1; LSD1
ID SIMPLEX-VIRUS TYPE-1; HOST-CELL FACTOR; LATENCY-ASSOCIATED TRANSCRIPT;
HISTONE ACETYLTRANSFERASE COMPLEX; DNA-BINDING STRUCTURE;
IMMEDIATE-EARLY GENES; COACTIVATOR HCF-1; LYTIC INFECTION; HOMEO DOMAIN;
METHYLTRANSFERASE COMPLEX
AB The immediate early genes of the alpha-herpesviruses HSV and VZV are transcriptionally regulated by viral and cellular factors in a complex combinatorial manner. Despite this complexity and the apparent redundancy of activators, the expression of the viral IE genes is critically dependent upon the cellular transcriptional coactivator HCF-1. Although the role of HCF-1 had remained elusive, recent studies have demonstrated that the protein is a component of multiple chromatin modification complexes including the Set1/MLL1 histone H3K4 methyltransferases. Studies using model viral promoter-reporter systems as well as analyses of components recruited to the viral genome during the initiation of infection have elucidated the significance of HCF-1 chromatin modification complexes in contributing to the final state of modified histones assembled on the viral IE promoters. Strikingly, the absence of HCF-1 results in the accumulation of nucleosomes bearing repressive marks on the viral IE promoters and silencing of viral gene expression. Published by Elsevier B.V.
C1 [Kristie, Thomas M.; Liang, Yu; Vogel, Jodi L.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Kristie, TM (reprint author), NIAID, Viral Dis Lab, NIH, 4-129,4 Ctr Dr, Bethesda, MD 20892 USA.
EM Thomas_kristie@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX We thank T. Pierson for the critical reading of this manuscript. Studies
done in the Kristie Laboratory were supported by the Intramural Research
Program, National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 108
TC 40
Z9 40
U1 0
U2 4
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 MAR-APR
PY 2010
VL 1799
IS 3-4
SI SI
BP 257
EP 265
DI 10.1016/j.bbagrm.2009.08.003
PG 9
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 578UF
UT WOS:000276320800011
PM 19682612
ER
PT J
AU de Souza, RF
Iyer, LM
Aravind, L
AF de Souza, Robson F.
Iyer, Lakshminarayan M.
Aravind, L.
TI Diversity and evolution of chromatin proteins encoded by DNA viruses
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE Chromatin; SWI2/SNF2; E6; E7; E1A; PHD; Treble clef; LXCXE; RecA; A18R;
Topoisomerase; ATPase; Rad52; HEH; Histone; Methylase; Demethylase;
Jumonji
ID HERPES-SIMPLEX-VIRUS; SARCOMA-ASSOCIATED HERPESVIRUS; STRAND ANNEALING
PROTEINS; LARGE TUMOR-ANTIGEN; CELL-CYCLE CONTROL; RNA-POLYMERASE-II;
BINDING-PROTEIN; VACCINIA VIRUS; CRYSTAL-STRUCTURE; COMPARATIVE GENOMICS
AB Double-stranded DNA viruses display a great variety of proteins that interact with host chromatin. Using the wealth of available genomic and functional information, we have systematically surveyed chromatin-related proteins encoded by dsDNA viruses. The distribution of viral chromatin-related proteins is primarily influenced by viral genome size and the superkingdom to which the host of the virus belongs. Smaller viruses usually encode multifunctional proteins that mediate several distinct interactions with host chromatin proteins and viral or host DNA. Larger viruses additionally encode several enzymes, which catalyze manipulations of chromosome structure, chromatin remodeling and covalent modifications of proteins and DNA. Among these viruses, it is also common to encounter transcription factors and DNA-packaging proteins such as histones and IHF/HU derived from cellular genomes, which might play a role in constituting virus-specific chromatin states. Through all size ranges a subset of domains in viral chromatin proteins appears to have been derived from those found in host proteins. Examples include the Zn-finger domains of the E6 and E7 proteins of papillomaviruses, SET domain methyltransferases and Jumonji-related demethylases in certain nucleocytoplasmic large DNA viruses and BEN domains in poxviruses and polydnaviruses. In other cases, chromatin-interacting modules, such as the LXCXE motif, appear to have been widely disseminated across distinct viral lineages, resulting in similar retinoblastoma targeting strategies. Viruses, especially those with large linear genomes, have evolved a number of mechanisms to manipulate viral chromosomes in the process of replication-associated recombination. These include topoisomerases, Rad50/SbcC-like ABC ATPases and a novel recombinase system in bacteriophages utilizing RecA and Rad52 homologs. Larger DNA viruses also encode SWI2/SNF2 and A18-like ATPases which appear to play specialized roles in transcription and recombination. Finally, it also appears that certain domains of viral provenance have given rise to key functions in eukaryotic chromatin such as a HEH domain of chromosome tethering proteins and the TET/JBP-like cytosine and thymine hydroxylases. Published by Elsevier B.V.
C1 [de Souza, Robson F.; Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM aravind@mail.nih.gov
FU National Library of Medicine, NIH
FX Work by the authors is supported by the intramural funds of the National
Library of Medicine, NIH. Due to space considerations we have been
regrettably unable to cite a large number of original works in this
field.
NR 169
TC 26
Z9 26
U1 1
U2 10
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 MAR-APR
PY 2010
VL 1799
IS 3-4
SI SI
BP 302
EP 318
DI 10.1016/j.bbagrm.2009.10.006
PG 17
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 578UF
UT WOS:000276320800016
PM 19878744
ER
PT J
AU Taymans, JM
Cookson, MR
AF Taymans, Jean-Marc
Cookson, Mark R.
TI Mechanisms in dominant parkinsonism: The toxic triangle of LRRK2,
alpha-synuclein, and tau
SO BIOESSAYS
LA English
DT Article
DE genetics; kinases; microtubule; neurodegeneration; Parkinson's disease;
synapse
ID DISEASE-ASSOCIATED MUTATIONS; COUPLED RECEPTOR KINASES; LEWY BODY
DISEASE; MICE LACKING; MOUSE-BRAIN; GENE LRRK2;
LEUCINE-RICH-REPEAT-KINASE-2 LRRK2; NEUROFIBRILLARY TANGLES;
DOPAMINERGIC-NEURONS; ALZHEIMERS-DISEASE
AB Parkinson's disease (PD) is generally sporadic but a number of genetic diseases have parkinsonism as a clinical feature. Two dominant genes, a-synuclein (SNCA) and leucine-rich repeat kinase 2 (LRRK2), are important for understanding inherited and sporadic PD. SNCA is a major component of pathologic inclusions termed Lewy bodies found in PD. LRRK2 is found in a significant proportion of PD cases. These two proteins may be linked as most LRRK2 PD cases have SNCA-positive Lewy bodies. Mutations in both proteins are associated with toxic effects in model systems although mechanisms are unclear. LRRK2 is an intracellular signaling protein possessing both GTPase and kinase activities that may contribute to pathogenicity. A third protein, tau, is implicated as a risk factor for PD. We discuss the potential relationship between these genes and suggest a model for PD pathogenesis where LRRK2 is upstream of pathogenic effects through SNCA, tau, or both proteins.
C1 [Taymans, Jean-Marc; Cookson, Mark R.] NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Taymans, Jean-Marc] Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Div Mol Med, Dept Mol & Cellular Med, Leuven, Belgium.
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
OI Taymans, Jean-Marc/0000-0001-5503-5524
FU NIH; NIH, National Institute on Aging; Flemish fund for scientific
research (FWO, Flanders, Belgium)
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging. J-MT is a postdoctoral
researcher of the Flemish fund for scientific research (FWO, Flanders,
Belgium) and a Fulbright research scholar.
NR 116
TC 48
Z9 48
U1 0
U2 2
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0265-9247
J9 BIOESSAYS
JI Bioessays
PD MAR
PY 2010
VL 32
IS 3
BP 227
EP 235
DI 10.1002/bies.200900163
PG 9
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 568FY
UT WOS:000275508900006
PM 20127702
ER
PT J
AU Drevets, WC
Furey, ML
AF Drevets, Wayne C.
Furey, Maura L.
TI Replication of Scopolamine's Antidepressant Efficacy in Major Depressive
Disorder: A Randomized, Placebo-Controlled Clinical Trial
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Anticholinergic; antimuscarinic; mood disorders; treatment
ID INDUCTION TEST; RATING-SCALE; CHRM2 GENE; SLEEP; SENSITIVITY; GLUTAMATE;
SUPERSENSITIVITY; PHARMACOTHERAPY; ASSOCIATION; HIPPOCAMPUS
AB Background: We previously reported that intravenous (IV) scopolamine administration produced rapid and robust antidepressant effects in a sample consisting of both unipolar and bipolar depressives. The present study aimed to replicate this finding in an independent sample limited to unipolar depressives.
Methods: Outpatients with major depressive disorder (MDD; n = 23; 22 were included in analyses) participated in a double-blind, placebo-controlled, crossover trial. Subjects were randomized into either a P/S or S/P sequence (P = block of three placebo sessions; S = block of three scopolamine sessions; [4.0 mu g/kg IV]). Sessions occurred 3 to 5 days apart, such that time spent in each block lasted 1.5 to 2 weeks and the interval between blocks was 3 to 5 days. The Montgomery-Asberg Depression Rating Scale (MADRS) served as the primary outcome measure.
Results: Following the initial block, the group receiving scopolamine first (S/P) showed a 32% reduction in MADRS scores (p < .001), which exceeded the corresponding change of 6.5% under placebo (P/S;p = .009), confirming the a-priori hypothesis. Improvement was significant at the first evaluation that followed scopolamine administration (p = .011). In Block 2, the P/S group showed a 53% reduction in MADRS scores (p = .001) following scopolamine versus placebo, whereas the reduction seen in S/P subjects who received scopolamine during Block 1 persisted as they received placebo during Block 2. Scopolamine induced drowsiness, blurred vision, dry mouth, light-headedness, and reduced blood pressure, which were sufficiently well tolerated that no subject dropped out because of side effects.
Conclusions: These results replicate previous finding that scopolamine produces a rapid and robust antidepressant response.
C1 [Drevets, Wayne C.; Furey, Maura L.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
RP Furey, ML (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, Bldg 15K,Room 201, Bethesda, MD 20892 USA.
EM mfurey@mail.nih.gov
RI Furey, Maura/H-5273-2013
FU National Institutes of Health, National Institute of Mental Health
FX We thank Ashish Khanna, Mark Opal, Summer Peck, and Elana Hoffman for
technical support; Michele Drevets and Joan Williams for patient
recruitment and evaluation; David Luckenbaugh for statistical advice;
and Paul Carlson, Alan Mallinger, Carlos Zarate, Meena Vythilingam, and
the 5SW Day Hospital nursing staff for medical support. This research
was supported by the National Institutes of Health, National Institute
of Mental Health Intramural Research Program.
NR 41
TC 103
Z9 107
U1 3
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAR 1
PY 2010
VL 67
IS 5
BP 432
EP 438
DI 10.1016/j.biopsych.2009.11.021
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 563BL
UT WOS:000275100300006
PM 20074703
ER
PT J
AU Perez-Edgar, K
Bar-Haim, Y
McDermott, JM
Gorodetsky, E
Hodgkinson, CA
Goldman, D
Ernst, M
Pine, DS
Fox, NA
AF Perez-Edgar, Koraly
Bar-Haim, Yair
McDermott, Jennifer Martin
Gorodetsky, Elena
Hodgkinson, Colin A.
Goldman, David
Ernst, Monique
Pine, Daniel S.
Fox, Nathan A.
TI Variations in the serotonin-transporter gene are associated with
attention bias patterns to positive and negative emotion faces
SO BIOLOGICAL PSYCHOLOGY
LA English
DT Article
DE Anxiety; Attention bias; Serotonin-transporter gene polymorphism;
5-HTTLPR; Dot-probe task; Intermediate phenotypes
ID 5-HTTLPR GENOTYPE; ANXIETY-DISORDER; STRESS-RESPONSE; AMYGDALA;
CHILDREN; THREAT; RISK; ADOLESCENTS; ACTIVATION; DEPRESSION
AB Both attention biases to threat and a serotonin-transporter gene polymorphism (5-HTTLPR) have been linked to heightened neural activation to threat and the emergence of anxiety. The short allele of 5-HTTLPR may act via its effect on neurotransmitter availability, while attention biases shape broad patterns of cognitive processing. We examined individual differences in attention bias to emotion faces as a function of 5-HTTLPR genotype. Adolescents (N = 117) were classified for presumed SLC6A4 expression based on 5-HTTLPR low (SS, SL(G), or L(G)L(G)), intermediate (SL(A) or L(A)L(G)), or high (L(A)L(A)). Participants completed the dot-probe task, measuring attention biases toward or away from angry and happy faces. Biases for angry faces increased with the genotype-predicted neurotransmission levels (low > intermediate > high). The reverse pattern was evident for happy faces. The data indicate a linear relation between 5-HTTLPR allelic status and attention biases to emotion, demonstrating a genetic mechanism for biased attention using ecologically valid stimuli that target socioemotional adaptation. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Perez-Edgar, Koraly] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[Bar-Haim, Yair] Tel Aviv Univ, Tel Aviv, Israel.
[McDermott, Jennifer Martin] Univ Wisconsin, Madison, WI USA.
[Gorodetsky, Elena; Ernst, Monique; Pine, Daniel S.] NIMH, Bethesda, MD USA.
[Hodgkinson, Colin A.; Goldman, David] NIAAA, Bethesda, MD USA.
[Fox, Nathan A.] Univ Maryland, College Pk, MD 20742 USA.
RP Perez-Edgar, K (reprint author), George Mason Univ, Dept Psychol, 4400 Univ Dr,MS3F5, Fairfax, VA 22030 USA.
EM kperezed@gmu.edu
RI Goldman, David/F-9772-2010;
OI Goldman, David/0000-0002-1724-5405; Perez-Edgar,
Koraly/0000-0003-4051-9563
FU John D. and Catherine T. MacArthur Foundation; NIH [MH074454, HD17899];
NIMH [MH073569]; NARSAD (Blowitz-Ridgeway Young Investigator Award)
FX We would like to thank Stacey Barton, Melissa Ghera, Dalit H. Marshall,
and Kirsten VanMeenen for their assistance in data collection. Funding
for the study was provided by grants to Nathan A. Fox from the John D.
and Catherine T. MacArthur Foundation and NIH (MH074454 and HD17899) and
to Koraly Perez-Edgar from the NIMH (MH073569) and NARSAD
(Blowitz-Ridgeway Young Investigator Award).
NR 24
TC 35
Z9 35
U1 6
U2 27
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-0511
J9 BIOL PSYCHOL
JI Biol. Psychol.
PD MAR
PY 2010
VL 83
IS 3
BP 269
EP 271
DI 10.1016/j.biopsycho.2009.08.009
PG 3
WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology,
Experimental
SC Psychology; Behavioral Sciences
GA 576EI
UT WOS:000276126700013
ER
PT J
AU Nakamura, N
Mori, C
Eddy, EM
AF Nakamura, Noriko
Mori, Chisato
Eddy, Edward M.
TI Molecular Complex of Three Testis-Specific Isozymes Associated with the
Mouse Sperm Fibrous Sheath: Hexokinase 1, Phosphofructokinase M, and
Glutathione S-Transferase mu class 5
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE flagellum; gamete biology; gametogenesis; glycolysis; multienzyme
complex; sperm; spermatogenesis; testis
ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE-S; PORIN-BINDING DOMAIN;
SPERMATOGENIC CELLS; GLYCOLYTIC ENZYME; MAMMALIAN SPERMATOZOA;
MALE-FERTILITY; RAT TESTIS; GENE; EXPRESSION; LACTATE
AB Mammalian sperm require ATP for motility, and most of it is generated by glycolysis. The glycolytic enzymes segregate to the principal piece region of the flagellum, where some are bound tightly to a novel cytoskeletal structure defining this region, the fibrous sheath (FS), and others are easily extracted with detergents. One of the latter is the spermatogenic cell-specific variant isozyme of hexokinase type 1 (HK1S), characterized by an N-terminal 24-amino acid spermatogenic cell-specific region (SSR). Yeast two-hybrid screens carried out using the SSR as bait determined that HK1S is tethered to muscle-type phosphofructokinase (PFKM) in the principal piece region. This led to the identification of four testis-specific Pfkm splice variants, one that overlapped a variant reported previously (Pfkm_v1) and three that were novel (Pfkm_v2, Pfkm_v3, and Pfkm_v4). They differ from Pfkm transcripts found in somatic cells by encoding a novel 67-amino acid N-terminal extension, the testis-specific region (TSR), producing a spermatogenic cell-specific PFKM variant isozyme (PFKMS). An antiserum generated to the TSR demonstrated that PFKMS is present in the principal piece and is insoluble in 1% Triton X-100 detergent. In subsequent yeast two-hybrid screens, the TSR was found to interact with glutathione S-transferase mu class 5 (GSTM5), identified previously as a spermatogenic cell-specific component of the FS. These results demonstrated that HK1S is tethered in the principal piece region by PFKMS, which in turn is bound tightly to GSTM5 in the FS.
C1 [Nakamura, Noriko; Eddy, Edward M.] NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Mori, Chisato] Chiba Univ, Grad Sch Med, Dept Bioenvironm Med, Chuo Ku, Chiba, Japan.
RP Eddy, EM (reprint author), NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM eddy@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences
FX Supported by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences.
NR 43
TC 20
Z9 25
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1603 MONROE ST, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD MAR
PY 2010
VL 82
IS 3
BP 504
EP 515
DI 10.1095/biolreprod.109.080580
PG 12
WC Reproductive Biology
SC Reproductive Biology
GA 557YY
UT WOS:000274707900005
PM 19889946
ER
PT J
AU Hosnijeh, FS
Krop, EJM
Portengen, L
Rabkin, CS
Linseisen, J
Vineis, P
Vermeulen, R
AF Hosnijeh, Fatemeh Saberi
Krop, Esmeralda J. M.
Portengen, Luetzen
Rabkin, Charles S.
Linseisen, Jakob
Vineis, Paolo
Vermeulen, Roel
TI Stability and reproducibility of simultaneously detected plasma and
serum cytokine levels in asymptomatic subjects
SO BIOMARKERS
LA English
DT Article
DE Cytokine; freeze-thaw cycle; reproducibility
ID SOLUBLE ACTIVATION MARKERS; BEAD-BASED IMMUNOASSAYS;
NON-HODGKIN-LYMPHOMA; MULTIPLEX IMMUNOASSAY; SAMPLE; COLLECTION; ASSAYS;
CELLS
AB Blood levels of cyto- and chemokines might reflect immune deregulations which might be related to lymphomagenesis. Potential utility of stored blood samples of a prospective cohort was evaluated by the effect of different blood sample types and freeze-thaw cycles on analyte levels. Bead-based immunoassays were performed on two fresh samples (serum, citrate and heparin plasma) of 10 asymptomatic adults collected 14 days apart and on aliquots of the first samples which were put through one to three freeze-thaw cycles to measure 11 cytokines, four chemokines and two adhesion molecules. Median coefficients of variation (CVs) of the measured analytes were 20%, 24% and 32% in serum, citrate and heparin plasma, respectively. Strong correlations (rank correlation coefficient 0.74-0.98) were observed between sample types, although small differences in analyte levels were observed for most analytes. Freeze-thaw cycles did not markedly change analyte levels. Our study supports the use of this assay among asymptomatic subjects in epidemiological studies.
C1 [Hosnijeh, Fatemeh Saberi; Krop, Esmeralda J. M.; Portengen, Luetzen; Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, NL-3584 CK Utrecht, Netherlands.
[Hosnijeh, Fatemeh Saberi] Zanjan Univ Med Sci, Zanjan, Iran.
[Rabkin, Charles S.] NCI, Rockville, MD USA.
[Linseisen, Jakob] Helmholtz Zentrum Munchen, Inst Epidemiol, Munich, Germany.
[Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England.
[Vermeulen, Roel] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
RP Vermeulen, R (reprint author), Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Jenalaan 18D, NL-3584 CK Utrecht, Netherlands.
EM R.C.H.Vermeulen@uu.nl
RI Linseisen, Jakob/B-5353-2014; Vermeulen, Roel/F-8037-2011; Saberi
Hosnijeh, Fatemeh/N-6684-2013
OI Linseisen, Jakob/0000-0002-9386-382X; Vermeulen,
Roel/0000-0003-4082-8163;
FU ECNIS Network of Excellence, European Union [FOOD-CT-2005-513943];
Iranian Ministry of Health and Medical Education at Utrecht University
FX We thank all the anonymous blood donors who participated in this study.
This work was supported by the ECNIS Network of Excellence
(Environmental Cancer Risk, Nutrition and Individual Susceptibility),
operating within the European Union 6th Framework Program, Priority 5:
'Food Quality and Safety (FOOD-CT-2005-513943). The first author also
acknowledges the Iranian Ministry of Health and Medical Education for
support of a PhD programme at Utrecht University.
NR 21
TC 20
Z9 20
U1 0
U2 2
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1354-750X
J9 BIOMARKERS
JI Biomarkers
PD MAR
PY 2010
VL 15
IS 2
BP 140
EP 148
DI 10.3109/13547500903340570
PG 9
WC Biotechnology & Applied Microbiology; Toxicology
SC Biotechnology & Applied Microbiology; Toxicology
GA 612OA
UT WOS:000278907900006
PM 19848603
ER
PT J
AU Yang, S
Prentice, R
AF Yang, Song
Prentice, Ross
TI Improved Logrank-Type Tests for Survival Data Using Adaptive Weights
SO BIOMETRICS
LA English
DT Article
DE Clinical trials; Proportional and nonproportional hazards; Survival
analysis; Time-varying treatment effect; Weighted logrank tests
ID RIGHT-CENSORED DATA; LOG-RANK TEST; STATISTICS; EFFICIENCY; TRIALS;
MODEL
AB P>For testing for treatment effects with time-to-event data, the logrank test is the most popular choice and has some optimality properties under proportional hazards alternatives. It may also be combined with other tests when a range of nonproportional alternatives are entertained. We introduce some versatile tests that use adaptively weighted logrank statistics. The adaptive weights utilize the hazard ratio obtained by fitting the model of Yang and Prentice (2005, Biometrika 92, 1-17). Extensive numerical studies have been performed under proportional and nonproportional alternatives, with a wide range of hazard ratios patterns. These studies show that these new tests typically improve the tests they are designed to modify. In particular, the adaptively weighted logrank test maintains optimality at the proportional alternatives, while improving the power over a wide range of nonproportional alternatives. The new tests are illustrated in several real data examples.
C1 [Yang, Song] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Prentice, Ross] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
RP Yang, S (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr MSC 7913, Bethesda, MD 20892 USA.
EM yangso@nhlbi.nih.gov; rprentic@whi.org
FU NIH [CA 53996]
FX The authors are grateful to editor Dr David M. Zucker, the associate
editor, and the referee for their helpful comments that led to
improvement of the article. The research of RP is supported by NIH grant
CA 53996.
NR 29
TC 11
Z9 11
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
EI 1541-0420
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2010
VL 66
IS 1
BP 30
EP 38
DI 10.1111/j.1541-0420.2009.01243.x
PG 9
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 571CH
UT WOS:000275727200005
PM 19397582
ER
PT J
AU Huang, CY
Qin, J
Wang, MC
AF Huang, C. -Y.
Qin, J.
Wang, M. -C.
TI Semiparametric Analysis for Recurrent Event Data with Time-Dependent
Covariates and Informative Censoring
SO BIOMETRICS
LA English
DT Article
DE Comparable recurrence times; Frailty; Pairwise pseudolikelihood;
Proportional rate model
ID PANEL COUNT DATA; REGRESSION-ANALYSIS; ASYMPTOTIC PROPERTIES; FRAILTY
MODELS; SURVIVAL
AB P>Recurrent event data analyses are usually conducted under the assumption that the censoring time is independent of the recurrent event process. In many applications the censoring time can be informative about the underlying recurrent event process, especially in situations where a correlated failure event could potentially terminate the observation of recurrent events. In this article, we consider a semiparametric model of recurrent event data that allows correlations between censoring times and recurrent event process via frailty. This flexible framework incorporates both time-dependent and time-independent covariates in the formulation, while leaving the distributions of frailty and censoring times unspecified. We propose a novel semiparametric inference procedure that depends on neither the frailty nor the censoring time distribution. Large sample properties of the regression parameter estimates and the estimated baseline cumulative intensity functions are studied. Numerical studies demonstrate that the proposed methodology performs well for realistic sample sizes. An analysis of hospitalization data for patients in an AIDS cohort study is presented to illustrate the proposed method.
C1 [Huang, C. -Y.; Qin, J.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Wang, M. -C.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
RP Huang, CY (reprint author), NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM huangchi@niaid.nih.gov
FU National Institutes of Health [R01 AI078835]; NIDA [DA 04334, DA 08009]
FX MCW's work was supported by National Institutes of Health grant R01
AI078835. The authors thank Drs David Vlahov and Steffanie Strathdee for
providing the data from the ALIVE study, which was supported by NIDA
grants DA 04334 and DA 08009. Comments from Drs Mike Proschan and Dean
Follmann have improved the presentation of this article.
NR 31
TC 19
Z9 19
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
EI 1541-0420
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2010
VL 66
IS 1
BP 39
EP 49
DI 10.1111/j.1541-0420.2009.01266.x
PG 11
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 571CH
UT WOS:000275727200006
PM 19459839
ER
PT J
AU Yu, K
Wheeler, W
Li, QZ
Bergen, AW
Caporaso, N
Chatterjee, N
Chen, JB
AF Yu, Kai
Wheeler, William
Li, Qizhai
Bergen, Andrew W.
Caporaso, Neil
Chatterjee, Nilanjan
Chen, Jinbo
TI A Partially Linear Tree-based Regression Model for Multivariate Outcomes
SO BIOMETRICS
LA English
DT Article
DE Generalized estimating equation; Genetic association study; Model
selection; Multiple-comparison adjustment; Tree-based model
ID CLASSIFICATION TREES; LONGITUDINAL DATA; ASSOCIATION
AB P>In the genetic study of complex traits, especially behavior related ones, such as smoking and alcoholism, usually several phenotypic measurements are obtained for the description of the complex trait, but no single measurement can quantify fully the complicated characteristics of the symptom because of our lack of understanding of the underlying etiology. If those phenotypes share a common genetic mechanism, rather than studying each individual phenotype separately, it is more advantageous to analyze them jointly as a multivariate trait to enhance the power to identify associated genes. We propose a multilocus association test for the study of multivariate traits. The test is derived from a partially linear tree-based regression model for multiple outcomes. This novel tree-based model provides a formal statistical testing framework for the evaluation of the association between a multivariate outcome and a set of candidate predictors, such as markers within a gene or pathway, while accommodating adjustment for other covariates. Through simulation studies we show that the proposed method has an acceptable type I error rate and improved power over the univariate outcome analysis, which studies each component of the complex trait separately with multiple-comparison adjustment. A candidate gene association study of multiple smoking-related phenotypes is used to demonstrate the application and advantages of this new method. The proposed method is general enough to be used for the assessment of the joint effect of a set of multiple risk factors on a multivariate outcome in other biomedical research settings.
C1 [Yu, Kai; Li, Qizhai; Caporaso, Neil; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
[Wheeler, William] Informat Management Serv Inc, Rockville, MD 20892 USA.
[Li, Qizhai] CAS, Acad Math & Syst Sci, Beijing 100190, Peoples R China.
[Bergen, Andrew W.] SRI Int, Ctr Hlth Sci, Mol Genet Program, Menlo Pk, CA 94025 USA.
[Chen, Jinbo] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
RP Yu, K (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
EM yuka@mail.nih.gov
OI Bergen, Andrew/0000-0002-1237-7644
FU NIH; National Cancer Institute; National Science Foundation of China
[10371126]; [U01 DA020830]
FX This research utilized the high-performance computational capabilities
of the Biowulf PC/Linux cluster at the National Institutes of Health,
Bethesda, Maryland, USA (http://biowulf.nih.gov). The work of KY, QL,
NC, and NC was supported in part by the Intramural Program of the NIH
and the National Cancer Institute. The work of QL was also partially
supported by the National Science Foundation of China, No. 10371126. AWB
was supported by U01 DA020830.
NR 21
TC 8
Z9 8
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2010
VL 66
IS 1
BP 89
EP 96
DI 10.1111/j.1541-0420.2009.01235.x
PG 8
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 571CH
UT WOS:000275727200011
PM 19432770
ER
PT J
AU Zheng, G
Li, ZH
Gail, MH
Gastwirth, JL
AF Zheng, Gang
Li, Zhaohai
Gail, Mitchell H.
Gastwirth, Joseph L.
TI Impact of Population Substructure on Trend Tests for Genetic
Case-Control Association Studies
SO BIOMETRICS
LA English
DT Article
DE Allele frequency matching; Bias; Cryptic relatedness; Disease rate
heterogeneity; Population stratification; Variance distortion
ID GENOMIC CONTROL; SAMPLE-SIZE; STRATIFICATION; VARIANTS; MARKERS; POWER
AB P>Hidden population substructure in case-control data has the potential to distort the performance of Cochran-Armitage trend tests (CATTs) for genetic associations. Three possible scenarios that may arise are investigated here: (i) heterogeneity of genotype frequencies across unidentified subpopulations (PSI), (ii) heterogeneity of genotype frequencies and disease risk across unidentified subpopulations (PSII), and (iii) cryptic correlations within unidentified subpopulations. A unified approach is presented for deriving the bias and variance distortion under the three scenarios for any CATT in a general family. Using these analytical formulas, we evaluate the excess type I errors of the CATTs numerically in the presence of population substructure. Our results provide insight into the properties of some proposed corrections for bias and variance distortion and show why they may not fully correct for the effects of population substructure.
C1 [Zheng, Gang] NHLBI, Off Biostat Res, DPPS, Bethesda, MD 20892 USA.
[Li, Zhaohai; Gastwirth, Joseph L.] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
[Li, Zhaohai; Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, EPS, Bethesda, MD 20892 USA.
RP Zheng, G (reprint author), NHLBI, Off Biostat Res, DPPS, 6701 Rockledge Dr,MSC 7913, Bethesda, MD 20892 USA.
EM zhengg@nhlbi.nih.gov
FU NIH [EY014478]; NSF
FX We thank Dr Hong Zhang for several helpful discussions and suggestions.
We also thank the editor, an associate editor, and a reviewer for their
very thoughtful and useful suggestions and comments, which greatly
improved our presentation. The work of ZL was partially supported by an
NIH grant EY014478. The work of JLG was partially supported by an NSF
grant.
NR 30
TC 4
Z9 4
U1 0
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2010
VL 66
IS 1
BP 196
EP 204
DI 10.1111/j.1541-0420.2009.01264.x
PG 9
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 571CH
UT WOS:000275727200023
PM 19432788
ER
PT J
AU Joo, J
Kwak, MJ
Zheng, G
AF Joo, Jungnam
Kwak, Minjung
Zheng, Gang
TI Improving Power for Testing Genetic Association in Case-Control Studies
by Reducing the Alternative Space
SO BIOMETRICS
LA English
DT Article
DE Genetic models; Hardy-Weinberg disequilibrium; MAX; Robust tests; Trend
tests
ID GENOME-WIDE ASSOCIATION; EFFICIENCY ROBUST-TESTS; SAMPLE-SIZE;
DISEQUILIBRIUM; STATISTICS; SURVIVAL; DISEASES; MARKERS; MODELS
AB To detect association between a genetic marker and a disease in case-control studies, the Cochran-Armitage trend test is typically used. The trend test is locally optimal when the genetic model is correctly specified. However, in practice, the underlying genetic model, and hence the optimal trend test, are usually unknown. In this case, Pearson's chi-squared test, the maximum of three trend test statistics (optimal for the recessive, additive, and dominant models), and the test based on genetic model selection (GMS) are useful. In this article, we first modify the existing GMS method so that it can be used when the risk allele is unknown. Then we propose a new approach by excluding a genetic model that is not supported by the data. Using either the model selection or exclusion, the alternative space is reduced conditional on the observed data, and hence the power to detect a true association can be increased. Simulation results are reported and the proposed methods are applied to the genetic markers identified from the genome-wide association studies conducted by the Wellcome Trust Case-Control Consortium. The results demonstrate that the genetic model exclusion approach usually performs better than existing methods under its worst situation across scientifically plausible genetic models we considered.
C1 [Joo, Jungnam; Kwak, Minjung; Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
RP Joo, J (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM jooj@nhlbi.nih.gov
NR 25
TC 11
Z9 12
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2010
VL 66
IS 1
BP 266
EP 276
DI 10.1111/j.1541-0420.2009.01241.x
PG 11
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 851OO
UT WOS:000297280600008
PM 19397584
ER
PT J
AU Yu, BB
Ghosh, P
AF Yu, Binbing
Ghosh, Pulak
TI Joint Modeling for Cognitive Trajectory and Risk of Dementia in the
Presence of Death
SO BIOMETRICS
LA English
DT Article
DE Change point; Competing risks; Dementia; Markov chain Monte Carlo
ID CHANGE-POINT; DECLINE; CHANGEPOINT; EDUCATION
AB Dementia is characterized by accelerated cognitive decline before and after diagnosis as compared to normal aging. It has been known that cognitive impairment occurs long before the diagnosis of dementia. For individuals who develop dementia, it is important to determine the time when the rate of cognitive decline begins to accelerate and the subsequent gap time to dementia diagnosis. For normal aging individuals, it is also useful to understand the trajectory of cognitive function until their death. A Bayesian change-point model is proposed to fit the trajectory of cognitive function for individuals who develop dementia. In real life, people in older ages are subject to two competing risks, e. g., dementia and dementia-free death. Because the majority of people do not develop dementia, a mixture model is used for survival data with competing risks, which consists of dementia onset time after the change point of cognitive function decline for demented individuals and death time for nondemented individuals. The cognitive trajectories and the survival process are modeled jointly and the parameters are estimated using the Markov chain Monte Carlo method. Using data from the Honolulu Asia Aging Study, we show the trajectories of cognitive function and the effect of education, apolipoprotein E 4 genotype, and hypertension on cognitive decline and the risk of dementia.
C1 [Yu, Binbing] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Ghosh, Pulak] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
[Ghosh, Pulak] Emory Univ, Dept Biostat, Atlanta, GA 30322 USA.
RP Yu, BB (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
EM yubi@mail.nih.gov; pulakghosh@gmail.com
FU National Institute on Aging
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging. We thank two anonymous reviewers and
the associate editor for their helpful suggestions.
NR 25
TC 11
Z9 11
U1 8
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2010
VL 66
IS 1
BP 294
EP 300
DI 10.1111/j.1541-0420.2009.01261.x
PG 7
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 851OO
UT WOS:000297280600011
PM 19432791
ER
PT J
AU Jha, A
Mukherjee, C
Prasad, AK
Parmar, VS
Vadaparti, M
Das, U
De Clercq, E
Balzarini, J
Stables, JP
Shrivastav, A
Sharma, RK
Dimmock, JR
AF Jha, Amitabh
Mukherjee, Chandrani
Prasad, Ashok K.
Parmar, Virinder S.
Vadaparti, Manjula
Das, Umashankar
De Clercq, Erik
Balzarini, Jan
Stables, James P.
Shrivastav, Anuraag
Sharma, Rajendra K.
Dimmock, Jonathan R.
TI Derivatives of aryl amines containing the cytotoxic 1,4-dioxo-2-butenyl
pharmacophore
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE 1,4-Dioxo-2-butenyl; Cytotoxicity; N-Arylmaleamates; N-Arylfumaramates;
N-Arylmaleimides; N-Arylisomaleimides; Structure-activity relationships;
Molecular modeling
ID AGENTS; INHIBITION; CYSTEINE
AB Several series of compounds containing the 1,4-dioxo-2-butenyl moiety have been prepared as candidate cytotoxins, including the methyl N-arylmaleamates, methyl N-arylfumaramates, and N-arylmaleimides. In addition, the N-arylisomaleimides were synthesized which are the structural isomers of N-arylmaleimides. These compounds were evaluated against human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 cells. Methyl N-arylfumaramates showed the highest cytotoxic potencies and, in particular, methyl N-(3,4-dichlorophenyl)fumaramate is six times more potent than melphalan towards L1210 cells and is equipotent with this drug in the Molt 4/C8 assay. Electrophilicity of compounds under investigation was demonstrated by carrying out thiolation using model benzyl mercaptan on representative compounds. Methyl N-(3,4-dichlorophenyl)fumaramate and methyl N-(4-chlorophenyl)maleamate inhibited human N- myristoyltransferase, a possible molecular target, in high micromolar range. QSAR and molecular modeling revealed some correlations between different structural features of a number of the molecules and cytotoxic potencies. Methyl N-arylfumaramates were well tolerated in mice in comparison to the analogs in other series of compounds tested. The data obtained in this investigation affords guidelines for preparing new series of molecules with greater potencies. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Jha, Amitabh; Mukherjee, Chandrani; Vadaparti, Manjula] Acadia Univ, Dept Chem, Wolfville, NS B4P 2R6, Canada.
[Mukherjee, Chandrani; Prasad, Ashok K.; Parmar, Virinder S.] Univ Delhi, Dept Chem, Delhi 110007, India.
[Das, Umashankar; Dimmock, Jonathan R.] Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada.
[De Clercq, Erik; Balzarini, Jan] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium.
[Stables, James P.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20852 USA.
[Shrivastav, Anuraag; Sharma, Rajendra K.] Univ Saskatchewan, Coll Med, Dept Pathol, Saskatoon, SK S7N 4H4, Canada.
[Shrivastav, Anuraag; Sharma, Rajendra K.] Canc Res Unit, Saskatoon, SK S7N 4H4, Canada.
RP Jha, A (reprint author), Acadia Univ, Dept Chem, Wolfville, NS B4P 2R6, Canada.
EM ajha@acadiau.ca
RI Jha, Amitabh/B-5452-2010
OI Jha, Amitabh/0000-0002-6305-0721
FU Nova Scotia Health Research Foundation; Canadian Institutes of Health
Research; Fonds voor Wetenschappelijk Onderzoek-Vlaanderen; Department
of Biotechnology, DBT, New Delhi
FX The authors thank the following agencies for financial support, namely
the Nova Scotia Health Research Foundation (A.J.), Canadian Institutes
of Health Research (A.J., J.R.D., R.K. S), Fonds voor Wetenschappelijk
Onderzoek-Vlaanderen (J.B., E.D.C.), and the Department of
Biotechnology, DBT, New Delhi (A.K.P.). Appreciation is extended to Mrs.
Lizette van Berckelaer for conducting the Molt 4/C8, CEM and L1210
assays, and the National Institute of Neurological Disorders and Stroke,
MD, U. S. A. for undertaking the short-term toxicity studies in mice. Dr
Mike Lumsden of Atlantic Region Magnetic Resonance Centre, Dalhousie
University is thanked for his help in recording 1D NOESY experiments on
certain samples.
NR 22
TC 9
Z9 10
U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD MAR 1
PY 2010
VL 20
IS 5
BP 1510
EP 1515
DI 10.1016/j.bmcl.2010.01.098
PG 6
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 558BG
UT WOS:000274714600008
PM 20149656
ER
PT J
AU Ballet, S
Marczak, ED
Feytens, D
Salvadori, S
Sasaki, Y
Abell, AD
Lazarus, LH
Balboni, G
Tourwe, D
AF Ballet, Steven
Marczak, Ewa D.
Feytens, Debby
Salvadori, Severo
Sasaki, Yusuke
Abell, Andrew D.
Lazarus, Lawrence H.
Balboni, Gianfranco
Tourwe, Dirk
TI Novel multiple opioid ligands based on 4-aminobenzazepinone (Aba),
azepinoindole (Aia) and tetrahydroisoquinoline (Tic) scaffolds
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Designed multiple ligands; Constrained amino acids; Dual mu/delta opioid
antagonists
ID RECEPTOR ANTAGONISTS; BIVALENT LIGANDS; DOUBLE-ENKEPHALINS; SIDE-CHAIN;
ANALOGS; AGONISTS; PHARMACOPHORE; PEPTIDE; POTENT; BINALTORPHIMINE
AB The dimerization and trimerization of the Dmt-Tic, Dmt-Aia and Dmt-Aba pharmacophores provided multiple ligands which were evaluated in vitro for opioid receptor binding and functional activity. Whereas the Tic-and Aba multimers proved to be dual and balanced delta/mu antagonists, as determined by the functional [S(35)] GTP gamma S binding assay, the dimerization of potent Aia-based 'parent' ligands unexpectedly resulted in substantial less efficient receptor binding and non-active dimeric compounds. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Ballet, Steven; Feytens, Debby; Tourwe, Dirk] Vrije Univ Brussels, Dept Organ Chem, B-1050 Brussels, Belgium.
[Ballet, Steven; Abell, Andrew D.] Univ Adelaide, Sch Chem & Phys, Adelaide, SA 5005, Australia.
[Marczak, Ewa D.; Lazarus, Lawrence H.] Natl Inst Environm Hlth Sci, Med Chem Grp, LP, Res Triangle Pk, NC 27709 USA.
[Salvadori, Severo] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy.
[Salvadori, Severo] Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy.
[Sasaki, Yusuke] Tohoku Pharmaceut Univ, Dept Pharmacol, Aoba Ku, Sendai, Miyagi 9818558, Japan.
[Balboni, Gianfranco] Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy.
RP Ballet, S (reprint author), Vrije Univ Brussels, Dept Organ Chem, B-1050 Brussels, Belgium.
EM sballet@vub.ac.be
OI SALVADORI, Severo/0000-0002-8224-2358
FU Scientific Research-Flanders (Belgium); Australian Research Council
[20103228]; NIH; NIEHS
FX S. Ballet and D. Feytens are Research Assistants of the Fund of
Scientific Research-Flanders (Belgium). This research was supported by
the Australian Research Council (Grant 20103228) and in part supported
by the Intramural Research Program of the NIH and NIEHS. We also thank
Professor Peter Schiller (IRCM, Montreal) for the valuable comments
during the preparation of this manuscript.
NR 38
TC 5
Z9 5
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD MAR 1
PY 2010
VL 20
IS 5
BP 1610
EP 1613
DI 10.1016/j.bmcl.2010.01.055
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 558BG
UT WOS:000274714600032
PM 20137938
ER
PT J
AU Otani, T
Hashizume, T
Nagaoka, T
Fukuda, T
Tang, CK
Salomon, DS
Seno, M
AF Otani, Takayuki
Hashizume, Toshihiro
Nagaoka, Tadahiro
Fukuda, Tomoko
Tang, Careen K.
Salomon, David S.
Seno, Masaharu
TI Production of biologically active IgG hinge-tag soluble epidermal growth
factor receptors (ErbB)
SO BIOTECHNOLOGY LETTERS
LA English
DT Article
DE Epidermal growth factor receptors; ErbB; Extracellular domain; Hinge
region; Homodimer; Soluble receptor
ID EXTRACELLULAR DOMAINS; BINDING; AFFINITY; LIGAND; CELLS
AB The extracellular domains (ECD) of epidermal growth factor receptors, ErbB1, 2, 3 and 4, were designed as soluble dimeric forms. Each ECD was fused to a short hinge region derived from IgG, such that the stable dimer could be formed with disulfide bridges. This hinge-tagged design minimized the molecular weight to approximately 50% of the conventional Fc-fusion design without an Fc domain of IgG. The refolded dimers could be easily analyzed and characterized by SDS-PAGE. Hinge-tagged soluble ErbBs demonstrated significant affinity for betacellulin and heregulin. The IgG hinge-tag should be a simple method to design soluble dimers that would be useful for high throughput screening of ligands, antagonists or derivatives.
C1 [Otani, Takayuki; Hashizume, Toshihiro; Fukuda, Tomoko; Seno, Masaharu] Okayama Univ, Dept Med & Bioengn Sci, Grad Sch Nat Sci & Technol, Kita Ku, Okayama 7008530, Japan.
[Nagaoka, Tadahiro; Salomon, David S.] NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Tang, Careen K.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
RP Seno, M (reprint author), Okayama Univ, Dept Med & Bioengn Sci, Grad Sch Nat Sci & Technol, Kita Ku, 3-1-1 Tsushima Naka, Okayama 7008530, Japan.
EM mseno@cc.okayama-u.ac.jp
RI SENO, Masaharu /B-2092-2011;
OI SENO, Masaharu /0000-0001-8547-6259; Nagaoka,
Tadahiro/0000-0002-9391-0243
FU Ministry of Education, Culture, Sports, Science and Technology
[18300164, 21300179]
FX We thank Ms. N. Hironaka for the construction of sErbB2 and sErbB3
expression plasmid. This research was partly supported by the Ministry
of Education, Culture, Sports, Science and Technology Grant-in-Aid for
Scientific Research (B) Nos. 18300164 and 21300179.
NR 15
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-5492
J9 BIOTECHNOL LETT
JI Biotechnol. Lett.
PD MAR
PY 2010
VL 32
IS 3
BP 361
EP 366
DI 10.1007/s10529-009-0160-9
PG 6
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 555UW
UT WOS:000274542600004
PM 19898750
ER
PT J
AU Suppes, T
Hellemann, G
Frye, MA
McElroy, S
Nolen, W
Kupka, R
Leverich, G
Grunze, H
AF Suppes, T.
Hellemann, G.
Frye, M. A.
McElroy, S.
Nolen, W.
Kupka, R.
Leverich, G.
Grunze, H.
TI Mixed depression in bipolar disorder: prevalence rate and clinical
correlates during naturalistic follow up
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 4th Biennial Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 17-20, 2010
CL Sao Paulo, BRAZIL
SP Int Soc Bipolar Disorders
C1 [Suppes, T.] Stanford Univ, Stanford, CA 94305 USA.
[Hellemann, G.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Frye, M. A.] Mayo Clin, Dept Psychiat, Rochester, MN USA.
[McElroy, S.] Lindner Ctr HOPE, Mason, OH USA.
[Nolen, W.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Kupka, R.] Univ Med Ctr, Utrecht, Netherlands.
[Kupka, R.] Altrecht Inst Mental Hlth Care, Utrecht, Netherlands.
[Leverich, G.] NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Grunze, H.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
RI Nolen, Willem/E-9006-2014
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 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2010
VL 12
SU 1
BP 52
EP 52
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 566BL
UT WOS:000275344600188
ER
PT J
AU Post, RM
Nolen, WA
Kupka, RW
Altshuler, LL
Frye, MA
Suppes, T
McElroy, SL
Keck, PE
Grunze, H
Rowe, M
Leverich, GS
AF Post, R. M.
Nolen, W. A.
Kupka, R. W.
Altshuler, L. L.
Frye, M. A.
Suppes, T.
McElroy, S. L.
Keck, P. E.
Grunze, H.
Rowe, M.
Leverich, G. S.
TI Increased risk factors and poor long-term outcome in the US compared to
Holland and Germany
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 4th Biennial Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 17-20, 2010
CL Sao Paulo, BRAZIL
SP Int Soc Bipolar Disorders
C1 [Post, R. M.] Bipolar Collaborat Network, Bethesda, MD USA.
[Nolen, W. A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Kupka, R. W.] Altrecht Inst Mental Hlth Care, Utrecht, Netherlands.
[Kupka, R. W.] Univ Med Ctr, Utrecht, Netherlands.
[Altshuler, L. L.] Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Mood Disorders Res Program, Los Angeles, CA 90024 USA.
[Frye, M. A.] Mayo Clin, Dept Psychiat, Rochester, MN USA.
[Suppes, T.] Stanford Univ, Stanford, CA 94305 USA.
[McElroy, S. L.; Keck, P. E.] Lindner Ctr HOPE, Mason, OH USA.
[Grunze, H.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England.
[Rowe, M.; Leverich, G. S.] NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA.
RI Nolen, Willem/E-9006-2014
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 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2010
VL 12
SU 1
BP 62
EP 63
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 566BL
UT WOS:000275344600226
ER
PT J
AU Schulze, T
AF Schulze, T.
TI Genome-wide association studies in bipolar disorder and beyond
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 4th Biennial Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 17-20, 2010
CL Sao Paulo, BRAZIL
SP Int Soc Bipolar Disorders
C1 [Schulze, T.] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA.
[Schulze, T.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2010
VL 12
SU 1
BP 64
EP 64
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 566BL
UT WOS:000275344600232
ER
PT J
AU Gracious, BL
Chirieac, MC
Costescu, S
Finucane, TL
Youngstrom, EA
Hibbeln, JR
AF Gracious, Barbara L.
Chirieac, Madalina C.
Costescu, Stefan
Finucane, Teresa L.
Youngstrom, Eric A.
Hibbeln, Joseph R.
TI Randomized, placebo-controlled trial of flax oil in pediatric bipolar
disorder
SO BIPOLAR DISORDERS
LA English
DT Article
DE adolescents; bipolar disorder; children; flax oil; omega-3 fatty acid
ID POLYUNSATURATED FATTY-ACIDS; POSTMORTEM ORBITOFRONTAL CORTEX; BLOOD-CELL
MEMBRANES; DOUBLE-BLIND; EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID;
CHOLESTERYL ESTERS; DEPRESSED-PATIENTS; ARACHIDONIC-ACID; MOOD DISORDERS
AB Objectives:
This clinical trial evaluated whether supplementation with flax oil, containing the omega-3 fatty acid alpha-linolenic acid (alpha-LNA), safely reduced symptom severity in youth with bipolar disorder.
Methods:
Children and adolescents aged 6-17 years with symptomatic bipolar I or bipolar II disorder (n = 51), manic, hypomanic, mixed, or depressed, were randomized to either flax oil capsules containing 550 mg alpha-LNA per 1 gram or an olive oil placebo adjunctively or as monotherapy. Doses were titrated to 12 capsules per day as tolerated over 16 weeks. Primary outcomes included changes in the Young Mania Rating Scale, Child Depression Rating Scale-Revised, and Clinical Global Impressions-Bipolar ratings using Kaplan-Meier survival analyses.
Results:
There were no significant differences in primary outcome measures when compared by treatment assignment. However, clinician-rated Global Symptom Severity was negatively correlated with final serum omega-3 fatty acid compositions: %alpha-LNA (r = -0.45, p < 0.007), % eicosapentaenoic acid (EPA) (r = -0.47, p < 0.005); and positively correlated with final arachidonic acid (AA) (r = 0.36, p < 0.05) and docosapentaenoic acid (DPA) n-6 (r = 0.48, p < 0.004). The mean duration of treatment for alpha-LNA was 11.8 weeks versus 8 weeks for placebo; however, the longer treatment duration for alpha-LNA was not significant after controlling for baseline variables. Subjects discontinued the study for continued depressive symptoms.
Conclusions:
Studies of essential fatty acid supplementation are feasible and well tolerated in the pediatric population. Although flax oil may decrease severity of illness in children and adolescents with bipolar disorder who have meaningful increases in serum EPA percent levels and/or decreased AA and DPA n-6 levels, individual variations in conversion of alpha-LNA to EPA and docosahexaenoic acid as well as dosing burden favor the use of fish oil both for clinical trials and clinical practice. Additionally, future research should focus on adherence and analysis of outcome based on changes in essential fatty acid tissue compositions, as opposed to group randomization alone.
C1 [Gracious, Barbara L.; Chirieac, Madalina C.; Costescu, Stefan; Finucane, Teresa L.] Univ Rochester, Lab Mood Disorders Children & Adolescents, Strong Mem Hosp, Dept Psychiat,Med Ctr, Rochester, NY 14642 USA.
[Youngstrom, Eric A.] Univ N Carolina, Dept Psychiat & Psychol, Chapel Hill, NC USA.
[Hibbeln, Joseph R.] NIAAA, Sect Nutr Neurochem, NIH, Bethesda, MD USA.
RP Gracious, BL (reprint author), Univ Rochester, Med Ctr, Dept Psychiat, 300 Crittenden Blvd, Rochester, NY 14642 USA.
EM barbara_gracious@urmc.rochester.edu
FU Stanley Medical Research Foundation; National Research Service Award
Institutional Training [T32-MH-018911]; National Center for Research
Resources (NCRR) [1-KL2-RR024136-1]; National Institutes of Health (NIH)
FX This research was funded by the Stanley Medical Research Foundation, and
National Research Service Award Institutional Training Grant
T32-MH-018911. This publication was made possible by Grant
#1-KL2-RR024136-1 from the National Center for Research Resources
(NCRR), a component of the National Institutes of Health (NIH), and the
NIH Roadmap for Medical Research. Its contents are solely the
responsibility of the authors and do not necessarily represent the
official view of the NCRR or the NIH. Information on the NCRR is
available at http://www.ncrr.nih.gov/. Information on re-engineering the
Clinical Research Enterprise can be obtained from
http://nihroadmap.nih.gov/clinicalresearch/overview-translational. asp.
We thank the families who participated in the study and also thank Dr.
Ann Moser, Jeffrey Swan, Resa Whipkey, Lauren Rios, Stephen Bean,
Michael Banchy, and Carolyn Myers for their assistance.
NR 59
TC 36
Z9 36
U1 2
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2010
VL 12
IS 2
BP 142
EP 154
PG 13
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 574SR
UT WOS:000276014200003
PM 20402707
ER
PT J
AU Mathew, S
Fu, LZ
Hasebe, T
Ishizuya-Oka, A
Shi, YB
AF Mathew, Smita
Fu, Liezhen
Hasebe, Takashi
Ishizuya-Oka, Atsuko
Shi, Yun-Bo
TI Tissue-Dependent Induction of Apoptosis by Matrix Metalloproteinase
Stromelysin-3 During Amphibian Metamorphosis
SO BIRTH DEFECTS RESEARCH PART C-EMBRYO TODAY-REVIEWS
LA English
DT Review
DE matrix metalloproteinase; stromelysin-3; metamorphosis; Xenopus laevis;
tumor invasion; apoptosis
ID THYROID-HORMONE RECEPTOR; XENOPUS-LAEVIS METAMORPHOSIS; 67-KDA LAMININ
RECEPTOR; DUPLICATED MATRIX-METALLOPROTEINASE-9 GENES; IMPLICATES
DISTINCT FUNCTIONS; INDUCED TAIL RESORPTION; EXTRACELLULAR-MATRIX;
BREAST-CANCER; FROG METAMORPHOSIS; TADPOLE TAIL
AB Matrix metalloproteinases (MMPs) are a superfamily of Zn(2+)-dependent proteases that are capable of cleaving the proteinaceous component of the extracellular matrix (ECM). The ECM is a critical medium for cell-cell interactions and can also directly signal cells through cell surface ECM receptors, such as integrins. In addition, many growth factors and signaling molecules are stored in the ECM. Thus, ECM remodeling and/or degradation by MMPs are expected to affect cell fate and behavior during many developmental and pathological processes. Numerous studies have shown that the expression of MMP mRNAs and proteins associates tightly with diverse developmental and pathological processes, such as tumor metastasis and mammary gland involution. In vivo evidence to support the roles of MMPs in these processes has been much harder to get. Here, we will review some of our studies on MMP11, or stromelysin-3, during the thyroid hormone-dependent amphibian metamorphosis, a process that resembles the so-called postembryonic development in mammals (from a few months before to several months after birth in humans when organ growth and maturation take place). Our investigations demonstrate that stromelysin-3 controls apoptosis in different tissues via at least two distinct mechanisms. Birth Defects Research (Part C) 90:55-66,2010. (C) 2010 Wiley-Liss, Inc.
C1 [Hasebe, Takashi; Ishizuya-Oka, Atsuko] Nippon Med Sch, Dept Biol, Kawasaki 2110063, Japan.
[Mathew, Smita; Fu, Liezhen; Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, Program Cellular Regulat & Metab,NIH, Bethesda, MD 20892 USA.
RP Ishizuya-Oka, A (reprint author), Nippon Med Sch, Dept Biol, Kawasaki 2110063, Japan.
EM a-oka@nms.ac.jp; shi@helix.nih.gov
FU NIH; JSPS [20570060]
FX Supported by the Intramural Research Program of NICHD, NIH, and a grant
from JSPS Grants-in-Aid for Scientific Research (C) (20570060)
NR 130
TC 8
Z9 8
U1 2
U2 6
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1542-975X
J9 BIRTH DEFECTS RES C
JI Birth Defects Res. Part C-Embryo Today-Rev.
PD MAR
PY 2010
VL 90
IS 1
BP 55
EP 66
DI 10.1002/bdrc.20170
PG 12
WC Developmental Biology; Reproductive Biology
SC Developmental Biology; Reproductive Biology
GA 578IJ
UT WOS:000276286600005
PM 20301218
ER
PT J
AU Aronin, CEP
Tuan, RS
AF Aronin, Caren E. Petrie
Tuan, Rocky S.
TI Therapeutic Potential of the Immunomodulatory Activities of Adult
Mesenchymal Stem Cells
SO BIRTH DEFECTS RESEARCH PART C-EMBRYO TODAY-REVIEWS
LA English
DT Review
DE mesenchymal stem cells; immunomodulation; regenerative medicine
ID MARROW STROMAL CELLS; TOLL-LIKE RECEPTOR-4; VERSUS-HOST-DISEASE;
PROLIFERATION IN-VITRO; HUMAN ADIPOSE-TISSUE; BONE-MARROW;
EXTRACELLULAR-MATRIX; T-CELLS; LYMPHOCYTE-PROLIFERATION; PROGENITOR
CELLS
AB Adult mesenchymal stem cells (MSCs) include a select population of resident cells within adult tissues, which retain the ability to differentiate along several tissue-specific lineages under defined media conditions and have finite expansion potential in vitro. These adult progenitor populations have been identified in various tissues, but it remains unclear exactly what role both transplanted and native MSCs play in processes of disease and regeneration. Interestingly, increasing evidence reveals a unique antiinflammatory immunomodulatory phenotype shared among this population, lending support to the idea that MSCs play a central role in early tissue remodeling responses where a controlled inflammatory response is required. However, additional evidence suggests that MSCs may not retain infinite immune privilege and that the context with which these cells are introduced in vivo may influence their immune phenotype. Therefore, understanding this dynamic micro-environment in which MSCs participate in complex feedback loops acting upon and being influenced by a plethora of secreted cytokines, extracellular matrix molecules, and fragments will be critical to elucidating the role of MSCs in the intertwined processes of immunomodulation and tissue repair. Birth Defects Research (Part C) 90:67-74, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Tuan, Rocky S.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Ctr Cellular & Mol Engn, Pittsburgh, PA 15219 USA.
[Aronin, Caren E. Petrie; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Tuan, RS (reprint author), Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Ctr Cellular & Mol Engn, 450 Technol Dr,Room 221, Pittsburgh, PA 15219 USA.
EM rst13@pitt.edu
FU NIH [201 AR41131]; Pennsylvania Department of Health
FX Grant sponsor: Intramural Research Program, NIH; Grant number: 201
AR41131; and Pennsylvania Department of Health.
NR 95
TC 33
Z9 34
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-975X
EI 1542-9768
J9 BIRTH DEFECTS RES C
JI Birth Defects Res. Part C-Embryo Today-Rev.
PD MAR
PY 2010
VL 90
IS 1
BP 67
EP 74
DI 10.1002/bdrc.20174
PG 8
WC Developmental Biology; Reproductive Biology
SC Developmental Biology; Reproductive Biology
GA 578IJ
UT WOS:000276286600006
ER
PT J
AU Lynch, AM
Murphy, JR
Gibbs, RS
Levine, RJ
Giclas, PC
Salmon, JE
Holers, VM
AF Lynch, A. M.
Murphy, J. R.
Gibbs, R. S.
Levine, R. J.
Giclas, P. C.
Salmon, J. E.
Holers, V. M.
TI The interrelationship of complement-activation fragments and
angiogenesis-related factors in early pregnancy and their association
with pre-eclampsia
SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
LA English
DT Article
DE Angiogenesis-related factors; complement-activating factors; obesity;
pre-eclampsia
ID PLACENTAL GROWTH-FACTOR; INTRAUTERINE GROWTH; ANTIANGIOGENIC FACTORS;
ALTERNATIVE PATHWAY; SOLUBLE ENDOGLIN; ADIPOSE-TISSUE; 2 PARTS; RISK;
RESTRICTION; IMMUNOLOGY
AB Objective To determine the interrelationships during early pregnancy of complement-activation fragments Bb, C3a and sC5b-9, and angiogenesis-related factors placental growth factor (PiGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), and their associations with pre-eclampsia.
Design Prospective cohort study.
Setting Denver complement study (June 2005-June 2008).
Population A total of 668 pregnant women with singleton gestations, recruited between 10 and 15 weeks of gestation.
Methods Using univariable and multivariable logistic regression analysis, concentrations of complement-activation fragments and angiogenesis-related factors were compared between 10 and 15 weeks of gestation in women who subsequently did or did not develop pre-eclampsia. Interrelationships between these variables were tested using the non-parametric Spearman rank correlation coefficient.
Main outcome measure Pre-eclampsia. The association of complement-activation fragments and angiogenesis-related factors with obesity was also examined.
Results The mean (+/-SD) levels of complement Bb in early pregnancy among women who did and did not develop pre-eclampsia were 0.84 (+/-0.26) mu g/ml and 0.69 (+/-0.2) mu g/ml, respectively (P = 0.001). Concentrations of PiGF were significantly (P = 0.01) lower (31 +/- 12 pg/ml) in early pregnancy in the pre-eclamptic group of women, as compared with the normotensive group (39 +/- 32 pg/ml). The adjusted odds ratio (AOR) of Bb and PiGF were 2.1 (CI = 1.4-3.1, P < 0.0003) and 0.2 (CI = 0.07-0.7, P = 0.01), respectively. There was no significant difference in the levels of C3a, sC5b-9, sFlt-1 and sEng in early pregnancy among women who developed pre-eclampsia, compared with women who remained normotensive during pregnancy. Higher levels of Bb (P = 0.0001) and C3a (P = 0.03), and lower levels of sFlt-1 (P = 0.0002) and sEng (P = 0.0001) were found among women with obesity, compared with non-obese controls. No meaningful relationships were found between the complement-activation fragments and the angiogenesis-related factors.
Conclusions In this cohort during early pregnancy, increased concentrations of complement-activation factor Bb and lower concentrations of PiGF were associated with the development of pre-eclampsia later in pregnancy.
C1 [Lynch, A. M.; Gibbs, R. S.] Univ Colorado, Denver Sch Med, Dept Obstet & Gynecol, Aurora, CO 80045 USA.
[Murphy, J. R.] Natl Jewish Hlth, Denver, CO USA.
[Levine, R. J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Giclas, P. C.] Natl Jewish Hlth, Div Allergy & Immunol, Dept Pediat, Denver, CO USA.
[Salmon, J. E.] Hosp Special Surg, Weill Cornell Med Ctr, New York, NY 10021 USA.
[Holers, V. M.] Univ Colorado, Denver Sch Med, Div Rheumatol, Dept Med, Aurora, CO 80045 USA.
[Holers, V. M.] Univ Colorado, Denver Sch Med, Div Rheumatol, Dept Immunol, Aurora, CO 80045 USA.
RP Lynch, AM (reprint author), Univ Colorado, Denver Sch Med, Dept Obstet & Gynecol, Mail Stop B198,12631 E 17th Ave, Aurora, CO 80045 USA.
EM anne.lynch@ucdenver.edu
FU American Heart Association [0865481G]; Center for Women's Health
Research; List Family Foundation; University of Colorado Denver; NICHD
[K23 HD049684]; NIH [R01 AI 55007, R01 AR49772]; Eunice Kennedy Shriver
National Institute of Child Health and Human Development
FX This research was supported by grants to AML from the American Heart
Association (0865481G), the Center for Women's Health Research and the
List Family Foundation, University of Colorado Denver, and the NICHD
(K23 HD049684). VMH is supported by NIH R01 AI 55007 and JES is
supported by NIH R01 AR49772. RJL is supported by the intramural
research programme of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development.
NR 37
TC 35
Z9 40
U1 0
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1470-0328
J9 BJOG-INT J OBSTET GY
JI BJOG
PD MAR
PY 2010
VL 117
IS 4
BP 456
EP 462
DI 10.1111/j.1471-0528.2009.02473.x
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 553SX
UT WOS:000274388200011
PM 20074261
ER
PT J
AU Pierorazio, PM
Ferrucci, L
Kettermann, A
Longo, DL
Metter, EJ
Carter, HB
AF Pierorazio, Phillip M.
Ferrucci, Luigi
Kettermann, Anna
Longo, Dan L.
Metter, E. Jeffrey
Carter, H. Ballentine
TI Serum testosterone is associated with aggressive prostate cancer in
older men: results from the Baltimore Longitudinal Study of Aging
SO BJU INTERNATIONAL
LA English
DT Article
DE prostate cancer; testosterone; high-risk
ID RANDOMIZED CONTROLLED-TRIAL; RADICAL PROSTATECTOMY; PATHOLOGICAL STAGE;
REPLACEMENT THERAPY; HORMONE-LEVELS; LEVEL; HYPOGONADISM; PREDICTOR;
RISK
AB OBJECTIVE
To evaluate the relationship between testosterone levels and the development of high-risk prostate cancer, by prospectively examining serum androgen concentrations in a well-studied cohort, as the role of testosterone in prostate cancer progression is debated.
PATIENTS AND METHODS
The study comprised 781 men in the Baltimore Longitudinal Study of Aging who had sex steroid measurements before a diagnosis of prostate cancer, or at their last visit for those without cancer (no cancer, 636; cancer, not high risk, 109; cancer, high risk, 36). High-risk cancer was defined as death from prostate cancer, a prostate specific antigen (PSA) level of >= 20 ng/mL at diagnosis, or a Gleason score of >= 8. The hazard ratio (HR) of high-risk disease was determined using a Cox proportional hazards regression model with simple updating, and risk rates were stratified by age and tercile for androgens of interest based on the proportional hazards analyses.
RESULTS
The likelihood of high-risk prostate cancer doubled per unit (0.1) increase in the free testosterone index (FTI) for patients aged > 65 years (HR 2.07, 95% confidence interval, CI, 1.01-4.23; P = 0.047); the likelihood for men aged < 65 years was inversely related to the FTI (HR 0.96, 95% CI 0.35-2.6; P = 0.9). The risk rate per person-years increased from lowest to highest tercile of FTI for the oldest men (age > 70 years) but this trend was not apparent among younger men.
CONCLUSION
Higher levels of serum free testosterone are associated with an increased risk of aggressive prostate cancer among older men. These data highlight the importance of prospective trials to insure the safety of testosterone-replacement therapy.
C1 [Pierorazio, Phillip M.; Kettermann, Anna; Carter, H. Ballentine] Johns Hopkins Univ, Sch Med, Dept Urol, James Buchanan Brady Urol Inst,Johns Hopkins Hosp, Baltimore, MD 21287 USA.
[Ferrucci, Luigi; Longo, Dan L.; Metter, E. Jeffrey] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
RP Pierorazio, PM (reprint author), Johns Hopkins Univ, Sch Med, Dept Urol, James Buchanan Brady Urol Inst,Johns Hopkins Hosp, Marburg 100,600 N Wolfe St, Baltimore, MD 21287 USA.
EM philpierorazio@jhmi.edu
FU NIH; National Institute on Ageing
FX Supported by the Intramural Research Program of the NIH, National
Institute on Ageing.
NR 28
TC 28
Z9 29
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD MAR
PY 2010
VL 105
IS 6
BP 824
EP 829
DI 10.1111/j.1464-410X.2009.08853.x
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 560VY
UT WOS:000274933400013
PM 19751256
ER
PT J
AU Tay, K
Dunleavy, K
Wilson, WH
AF Tay, Kevin
Dunleavy, Kieron
Wilson, Wyndham H.
TI Novel agents for B-cell non-Hodgkin lymphoma: Science and the promise
SO BLOOD REVIEWS
LA English
DT Review
DE Drug targets; Lymphoma; Novel agents; Small molecules; Immunotherapy
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ANTI-CD20 MONOCLONAL-ANTIBODY; NF-KAPPA-B;
PROTEASOME INHIBITOR BORTEZOMIB; REFRACTORY FOLLICULAR LYMPHOMA; HISTONE
DEACETYLASE INHIBITORS; CHIMERIC ANTIGEN RECEPTOR; BCL-2 FAMILY-MEMBERS;
MULTICENTER PHASE-II; C-BETA INHIBITOR
AB There has been tremendous insight gained in the last two decades from basic science research. New molecular targets in neoplastic cells are emerging and provide the rationale for clinical development of novel agents in non-Hodgkin lymphoma. These novel agents can be broadly categorized into two groups. The first is by immunotherapy which includes novel monoclonal antibodies and immunomodulating drugs, which takes advantage of or optimizes immune system function. The other group of drugs target small molecules that may play an important role in tumorigenesis. The mechanisms of anti-tumor activity include targeting apoptotic pathways, inhibition of proteasomes, mammalian target of rapamycin (mTOR), cyclin-dependent kinases and histone deacetylases. The purpose of this review is to focus on these novel agents and the various treatment approaches that are currently being evaluated in non-Hodgkin lymphoma. Published by Elsevier Ltd.
C1 [Tay, Kevin; Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Wilson, WH (reprint author), NCI, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM wilsonw@mail.nih.gov
NR 143
TC 6
Z9 8
U1 0
U2 2
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0268-960X
EI 1532-1681
J9 BLOOD REV
JI Blood Rev.
PD MAR
PY 2010
VL 24
IS 2
BP 69
EP 82
DI 10.1016/j.blre.2010.01.001
PG 14
WC Hematology
SC Hematology
GA 576CM
UT WOS:000276121500003
PM 20153097
ER
PT J
AU Senchenko, VN
Anedchenko, EA
Kondratieva, TT
Krasnov, GS
Dmitriev, AA
Zabarovska, VI
Pavlova, TV
Kashuba, VI
Lerman, MI
Zabarovsky, ER
AF Senchenko, Vera N.
Anedchenko, Ekaterina A.
Kondratieva, Tatiana T.
Krasnov, George S.
Dmitriev, Alexei A.
Zabarovska, Veronika I.
Pavlova, Tatiana V.
Kashuba, Vladimir I.
Lerman, Michael I.
Zabarovsky, Eugene R.
TI Simultaneous down-regulation of tumor suppressor genes RBSP3/CTDSPL,
NPRL2/G21 and RASSF1A in primary non-small cell lung cancer
SO BMC CANCER
LA English
DT Article
ID HUMAN-CHROMOSOME 3P21.3; HUMAN EPITHELIAL MALIGNANCIES; HOMOZYGOUS
DELETION REGION; REAL-TIME PCR; IN-VIVO; EPIGENETIC INACTIVATION;
PROGNOSTIC-SIGNIFICANCE; CARCINOMA; EXPRESSION; PROMOTER
AB Background: The short arm of human chromosome 3 is involved in the development of many cancers including lung cancer. Three bona fide lung cancer tumor suppressor genes namely RBSP3 (AP20 region), NPRL2 and RASSF1A (LUCA region) were identified in the 3p21.3 region. We have shown previously that homozygous deletions in AP20 and LUCA sub-regions often occurred in the same tumor (P < 10(-6)).
Methods: We estimated the quantity of RBSP3, NPRL2, RASSF1A, GAPDH, RPN1 mRNA and RBSP3 DNA copy number in 59 primary non-small cell lung cancers, including 41 squamous cell and 18 adenocarcinomas by real-time reverse transcription-polymerase chain reaction based on TaqMan technology and relative quantification.
Results: We evaluated the relationship between mRNA level and clinicopathologic characteristics in non-small cell lung cancer. A significant expression decrease (>= 2) was found for all three genes early in tumor development: in 85% of cases for RBSP3; 73% for NPRL2 and 67% for RASSF1A (P < 0.001), more strongly pronounced in squamous cell than in adenocarcinomas. Strong suppression of both, NPRL2 and RBSP3 was seen in 100% of cases already at Stage I of squamous cell carcinomas. Deregulation of RASSF1A correlated with tumor progression of squamous cell (P = 0.196) and adenocarcinomas (P < 0.05). Most likely, genetic and epigenetic mechanisms might be responsible for transcriptional inactivation of RBSP3 in non-small cell lung cancers as promoter methylation of RBSP3 according to NotI microarrays data was detected in 80% of squamous cell and in 38% of adenocarcinomas. With NotI microarrays we tested how often LUCA (NPRL2, RASSF1A) and AP20 (RBSP3) regions were deleted or methylated in the same tumor sample and found that this occured in 39% of all studied samples (P < 0.05).
Conclusion: Our data support the hypothesis that these TSG are involved in tumorigenesis of NSCLC. Both genetic and epigenetic mechanisms contribute to down-regulation of these three genes representing two tumor suppressor clusters in 3p21.3. Most importantly expression of RBSP3, NPRL2 and RASSF1A was simultaneously decreased in the same sample of primary NSCLC: in 39% of cases all these three genes showed reduced expression (P < 0.05).
C1 [Senchenko, Vera N.; Anedchenko, Ekaterina A.; Krasnov, George S.; Dmitriev, Alexei A.; Zabarovsky, Eugene R.] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Struct & Funct Genom, Moscow, Russia.
[Senchenko, Vera N.; Zabarovska, Veronika I.; Pavlova, Tatiana V.; Kashuba, Vladimir I.; Zabarovsky, Eugene R.] Karolinska Inst, Ctr Microbiol & Tumor Biol, Dept Clin Sci & Educ, Stockholm, Sweden.
[Kondratieva, Tatiana T.] Russian Acad Sci, Blokhin Canc Res Ctr, Moscow, Russia.
[Kashuba, Vladimir I.] Ukrainian Acad Sci, Inst Mol Biol & Genet, UA-252627 Kiev, Ukraine.
[Lerman, Michael I.] NCI, Canc Causing Genes Sect, Immunobiol Lab, Ctr Canc Res, Frederick, MD 21701 USA.
RP Senchenko, VN (reprint author), Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Struct & Funct Genom, Moscow, Russia.
EM versen@eimb.ru; Eugene.Zabarovsky@ki.se
RI Dmitriev, Alexey/D-6109-2011; Senchenko, Vera/C-8992-2014; Krasnov,
George/E-6529-2014;
OI Dmitriev, Alexey/0000-0002-6827-9584; Senchenko,
Vera/0000-0002-3119-515X; Krasnov, George/0000-0002-6493-8378
FU Russian Foundation for Basic Research [05-04-49408]; Agency of Science
and Innovations [02.512.11.2241, 1-2008/07/07]; Swedish Cancer Society;
Swedish Research Council; Swedish Foundation for International
Cooperation in Research and Higher Education (STINT); Swedish Institute;
Karolinska Institute
FX The authors are grateful to Ms. Leah V. Lerman, esq. for the help in
preparation of the manuscript. This study was financially supported by
the Russian Foundation for Basic Research (project no 05-04-49408), The
Agency of Science and Innovations (State Contracts no 02.512.11.2241,
Agreement 1-2008/07/07) and by research grants from the Swedish Cancer
Society, the Swedish Research Council, the Swedish Foundation for
International Cooperation in Research and Higher Education (STINT), the
Swedish Institute, and Karolinska Institute.
NR 51
TC 30
Z9 36
U1 0
U2 5
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 MAR 1
PY 2010
VL 10
AR 75
DI 10.1186/1471-2407-10-75
PG 13
WC Oncology
SC Oncology
GA 571ZW
UT WOS:000275796400001
PM 20193080
ER
PT J
AU Anderlini, P
Pedersen, T
Confer, D
Pulsipher, M
Rizzo, D
Stroncek, D
Leitman, S
O'Donnell, P
AF Anderlini, P.
Pedersen, T.
Confer, D.
Pulsipher, M.
Rizzo, D.
Stroncek, D.
Leitman, S.
O'Donnell, P.
TI Evaluation, consent and care of related donors and recipients at
haematopoietic stem cell transplant centres in the United States:
practice patterns and potential for conflict of interest
SO BONE MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the
European-Group-for-Blood-and-Marrow-Transplantat/9th Meeting of the EBMT
Data-Management-Group/26th Meeting of the EBMT Nurses Group/2nd EBMT
Qual Management Meeting
CY MAR 21-24, 2010
CL Vienna, AUSTRIA
SP European Grp Blood & Marrow Transplantat, EBMT Data Management Grp, EBMT Nurses Grp
C1 [Anderlini, P.] UTMDACC, Houston, TX USA.
[Pedersen, T.; Confer, D.] NMDP, Minneapolis, MN USA.
[Pulsipher, M.] Univ Utah, Med Ctr, Salt Lake City, UT USA.
[Rizzo, D.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Stroncek, D.; Leitman, S.] NIH, Bethesda, MD 20892 USA.
[O'Donnell, P.] FHCRC, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD MAR
PY 2010
VL 45
SU 2
BP S70
EP S71
PG 2
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 595LF
UT WOS:000277611300171
ER
PT J
AU Rezvani, K
Yong, A
Mielke, S
Jafarpour, B
Savani, B
Le, Q
Eniafe, R
Boss, C
Kurlander, R
Barrett, J
AF Rezvani, K.
Yong, A.
Mielke, S.
Jafarpour, B.
Savani, B.
Le, Q.
Eniafe, R.
Boss, C.
Kurlander, R.
Barrett, J.
TI Repeated vaccination with PR1 and WT1 peptides admixed in Montanide
adjuvant fails to induce sustained anti-leukaemia responses in patients
with myeloid malignancies
SO BONE MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the
European-Group-for-Blood-and-Marrow-Transplantat/9th Meeting of the EBMT
Data-Management-Group/26th Meeting of the EBMT Nurses Group/2nd EBMT
Qual Management Meeting
CY MAR 21-24, 2010
CL Vienna, AUSTRIA
SP European Grp Blood & Marrow Transplantat, EBMT Data Management Grp, EBMT Nurses Grp
C1 [Rezvani, K.] Hammersmith Hosp, London, England.
[Yong, A.; Jafarpour, B.; Le, Q.; Eniafe, R.; Boss, C.; Kurlander, R.; Barrett, J.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD MAR
PY 2010
VL 45
SU 2
BP S83
EP S83
PG 1
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 595LF
UT WOS:000277611300201
ER
PT J
AU Sirohi, B
Chandrasekar, P
Seibel, N
Ruhnke, M
Powles, R
Taylor, T
AF Sirohi, B.
Chandrasekar, P.
Seibel, N.
Ruhnke, M.
Powles, R.
Taylor, T.
TI Efficacy of micafungin neutropenic patients with invasive candidiasis
and candidaemia
SO BONE MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the
European-Group-for-Blood-and-Marrow-Transplantat/9th Meeting of the EBMT
Data-Management-Group/26th Meeting of the EBMT Nurses Group/2nd EBMT
Qual Management Meeting
CY MAR 21-24, 2010
CL Vienna, AUSTRIA
SP European Grp Blood & Marrow Transplantat, EBMT Data Management Grp, EBMT Nurses Grp
C1 [Sirohi, B.] Max Can Ctr, New Delhi, India.
[Chandrasekar, P.] Wayne State Univ, Sch Med, Detroit, MI USA.
[Seibel, N.] Natl Inst Hlth, Bethesda, MD USA.
[Ruhnke, M.] Humboldt Univ, Campus Charite Mitte, Berlin, Germany.
[Powles, R.] Parkside Oncol Clin, Wimbledon, England.
[Taylor, T.] Astellas Pharma Europe, Staines, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD MAR
PY 2010
VL 45
SU 2
BP S220
EP S221
PG 2
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 595LF
UT WOS:000277611301020
ER
PT J
AU Williams, K
Pavletic, S
Hnatiuk, O
Hakim, F
Mitchell, S
Gea-Banacloche, J
Comis, L
Cowen, E
Baird, K
Louie, A
Shelhamer, J
Blacklock-Schuver, B
Avila, D
Carpenter, A
Gress, R
AF Williams, K.
Pavletic, S.
Hnatiuk, O.
Hakim, F.
Mitchell, S.
Gea-Banacloche, J.
Comis, L.
Cowen, E.
Baird, K.
Louie, A.
Shelhamer, J.
Blacklock-Schuver, B.
Avila, D.
Carpenter, A.
Gress, R.
TI Preliminary results of a phase II trial of montelukast for the treatment
of bronchiolitis obliterans syndrome after HSCT
SO BONE MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the
European-Group-for-Blood-and-Marrow-Transplantat/9th Meeting of the EBMT
Data-Management-Group/26th Meeting of the EBMT Nurses Group/2nd EBMT
Qual Management Meeting
CY MAR 21-24, 2010
CL Vienna, AUSTRIA
SP European Grp Blood & Marrow Transplantat, EBMT Data Management Grp, EBMT Nurses Grp
C1 [Williams, K.; Pavletic, S.; Hakim, F.; Gea-Banacloche, J.; Baird, K.; Blacklock-Schuver, B.; Avila, D.; Carpenter, A.; Gress, R.] NCI, Bethesda, MD 20892 USA.
[Hnatiuk, O.; Mitchell, S.; Comis, L.; Cowen, E.; Louie, A.; Shelhamer, J.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD MAR
PY 2010
VL 45
SU 2
BP S48
EP S48
PG 1
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 595LF
UT WOS:000277611300117
ER
PT J
AU Levesque, S
Wilson, B
Gregoria, V
Thorpe, LB
Dallas, S
Polikov, VS
Hong, JS
Block, ML
AF Levesque, Shannon
Wilson, Belinda
Gregoria, Vincent
Thorpe, Laura B.
Dallas, Shannon
Polikov, Vadim S.
Hong, Jau-Shyong
Block, Michelle L.
TI Reactive microgliosis: extracellular mu-calpain and microglia-mediated
dopaminergic neurotoxicity
SO BRAIN
LA English
DT Article
DE microglia; inflammation-mediated neurodegeneration; oxidative stress;
chronic neurotoxicity; extracellular mu-calpain; reactive microgliosis;
Parkinson's disease
ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; ACUTE BRAIN-DAMAGE;
PARKINSONS-DISEASE; NADPH OXIDASE; SUBSTANTIA-NIGRA; OXIDATIVE STRESS;
ACTIVATED MICROGLIA; SURROGATE MARKERS; CELL-MIGRATION; LIVER-INJURY
AB Microglia, the innate immune cells in the brain, can become chronically activated in response to dopaminergic neuron death, fuelling a self-renewing cycle of microglial activation followed by further neuron damage (reactive microgliosis), which is implicated in the progressive nature of Parkinson's disease. Here, we use an in vitro approach to separate neuron injury factors from the cellular actors of reactive microgliosis and discover molecular signals responsible for chronic and toxic microglial activation. Upon injury with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium, N27 cells (dopaminergic neuron cell line) released soluble neuron injury factors that activated microglia and were selectively toxic to dopaminergic neurons in mixed mesencephalic neuron-glia cultures through nicotinamide adenine dinucleotide phosphate oxidase. mu-Calpain was identified as a key signal released from damaged neurons, causing selective dopaminergic neuron death through activation of microglial nicotinamide adenine dinucleotide phosphate oxidase and superoxide production. These findings suggest that dopaminergic neurons may be inherently susceptible to the pro-inflammatory effects of neuron damage, i.e. reactive microgliosis, providing much needed insight into the chronic nature of Parkinson's disease.
C1 [Levesque, Shannon; Gregoria, Vincent; Thorpe, Laura B.; Block, Michelle L.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA.
[Wilson, Belinda; Hong, Jau-Shyong] Natl Inst Environm Hlth Sci, Dept Neuropharmacol, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA.
[Dallas, Shannon] Natl Inst Environm Hlth Sci, Intracellular Regulat Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA.
[Polikov, Vadim S.] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA.
RP Block, ML (reprint author), Virginia Commonwealth Univ, Dept Anat & Neurobiol, Sanger Hall,Room 9-048,1101 E Marshall St,Med Cam, Richmond, VA 23298 USA.
EM mblock@vcu.edu
FU National Institute of Environmental Health Sciences/National Institute
of Health Pathway [R00ES01549]; NIH; National Institute of Environmental
Health Sciences [K99ES015409-01]
FX National Institute of Environmental Health Sciences/National Institute
of Health Pathway to Independence Award (R00ES01549) and in part by the
Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences, in fulfilment of the Pathway to
Independence Award (K99ES015409-01).
NR 52
TC 51
Z9 56
U1 0
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD MAR
PY 2010
VL 133
BP 808
EP 821
DI 10.1093/brain/awp333
PN 3
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 575DI
UT WOS:000276046000016
PM 20123724
ER
PT J
AU Shaikh, AG
Hong, S
Liao, K
Tian, J
Solomon, D
Zee, DS
Leigh, RJ
Optican, LM
AF Shaikh, Aasef G.
Hong, Simon
Liao, Ke
Tian, Jing
Solomon, David
Zee, David S.
Leigh, R. John
Optican, Lance M.
TI Oculopalatal tremor explained by a model of inferior olivary hypertrophy
and cerebellar plasticity
SO BRAIN
LA English
DT Article
DE vestibular; gap junction; connexin; motor disorders; eye movement
ID HARMALINE-INDUCED TREMOR; ESSENTIAL PALATAL TREMOR; OLIVOCEREBELLAR
SYSTEM; VESTIBULAR NUCLEUS; PENDULAR NYSTAGMUS; NEURONS; MYOCLONUS;
MONKEY; CAT; IMMUNOCYTOCHEMISTRY
AB The inferior olivary nuclei clearly play a role in creating oculopalatal tremor, but the exact mechanism is unknown. Oculopalatal tremor develops some time after a lesion in the brain that interrupts inhibition of the inferior olive by the deep cerebellar nuclei. Over time the inferior olive gradually becomes hypertrophic and its neurons enlarge developing abnormal soma-somatic gap junctions. However, results from several experimental studies have confounded the issue because they seem inconsistent with a role for the inferior olive in oculopalatal tremor, or because they ascribe the tremor to other brain areas. Here we look at 3D binocular eye movements in 15 oculopalatal tremor patients and compare their behaviour to the output of our recent mathematical model of oculopalatal tremor. This model has two mechanisms that interact to create oculopalatal tremor: an oscillator in the inferior olive and a modulator in the cerebellum. Here we show that this dual mechanism model can reproduce the basic features of oculopalatal tremor and plausibly refute the confounding experimental results. Oscillations in all patients and simulations were aperiodic, with a complicated frequency spectrum showing dominant components from 1 to 3 Hz. The model's synchronized inferior olive output was too small to induce noticeable ocular oscillations, requiring amplification by the cerebellar cortex. Simulations show that reducing the influence of the cerebellar cortex on the oculomotor pathway reduces the amplitude of ocular tremor, makes it more periodic and pulse-like, but leaves its frequency unchanged. Reducing the coupling among cells in the inferior olive decreases the oscillation's amplitude until they stop (at similar to 20% of full coupling strength), but does not change their frequency. The dual-mechanism model accounts for many of the properties of oculopalatal tremor. Simulations suggest that drug therapies designed to reduce electrotonic coupling within the inferior olive or reduce the disinhibition of the cerebellar cortex on the deep cerebellar nuclei could treat oculopalatal tremor. We conclude that oculopalatal tremor oscillations originate in the hypertrophic inferior olive and are amplified by learning in the cerebellum.
C1 [Shaikh, Aasef G.; Tian, Jing; Solomon, David; Zee, David S.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA.
[Hong, Simon; Optican, Lance M.] NEI, Sensorimotor Res Lab, NIH, DHHS, Bethesda, MD 20892 USA.
[Liao, Ke; Leigh, R. John] Vet Affairs Med Ctr, Dept Neurol, Cleveland, OH 44106 USA.
[Liao, Ke; Leigh, R. John] Case Western Reserve Univ, Cleveland, OH 44106 USA.
RP Optican, LM (reprint author), 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA.
EM lanceoptican@nih.gov
RI liao, ke/B-1453-2010
FU Office of Research and Development, Medical Research Service, Department
of Veterans Affairs; National Eye Institute [EY01849, EY06717, EY08060];
Evenor Armington Fund; National Eye Institute, NIH, DHHS
FX Office of Research and Development, Medical Research Service, Department
of Veterans Affairs; National Eye Institute (grants EY01849, EY06717 and
EY08060); Evenor Armington Fund; Intramural Research Program, National
Eye Institute, NIH, DHHS; Philanthropic funds to the JHH vestibular
laboratory and JHH movement disorders division (Fellowship support to A.
S.).
NR 67
TC 40
Z9 40
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD MAR
PY 2010
VL 133
BP 923
EP 940
DI 10.1093/brain/awp323
PN 3
PG 18
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 575DI
UT WOS:000276046000026
PM 20080879
ER
PT J
AU Correia, S
Hubbard, E
Hassenstab, J
Yip, A
Vymazal, J
Herynek, V
Giedd, J
Murphy, DL
Greenberg, BD
AF Correia, Stephen
Hubbard, Emily
Hassenstab, Jason
Yip, Agustin
Vymazal, Josef
Herynek, Vit
Giedd, Jay
Murphy, Dennis L.
Greenberg, Benjamin D.
TI Basal Ganglia MR Relaxometry in Obsessive-Compulsive Disorder: T2
Depends Upon Age of Symptom Onset
SO BRAIN IMAGING AND BEHAVIOR
LA English
DT Article
DE Obsessive-compulsive disorder; Basal ganglia; Age of onset; Iron;
Magnetic Resonance Imaging
ID VOXEL-BASED MORPHOMETRY; BRAIN FERRITIN IRON; GRAY-MATTER;
CAUDATE-NUCLEUS; NEURODEGENERATIVE DISEASES; STRUCTURAL ABNORMALITIES;
PARKINSONS-DISEASE; TOURETTES-SYNDROME; RELAXATION-TIMES; LESIONS
AB Dysfunction in circuits linking frontal cortex and basal ganglia (BG) is strongly implicated in obsessive-compulsive disorder (OCD). On MRI studies, neuropsychiatric disorders with known BG pathology have abnormally short T2 relaxation values (a putative biomarker of elevated iron) in this region. We asked if BG T2 values are abnormal in OCD. We measured volume and T2 and T1 relaxation rates in BG of 32 adults with OCD and 33 matched controls. There were no group differences in volume or T1 values in caudate, putamen, or globus pallidus (GP). The OCD group had lower T2 values (suggesting higher iron content) in the right GP, with a trend in the same direction for the left GP. This effect was driven by patients whose OCD symptoms began from around adolescence to early adulthood. The results suggest a possible relationship between age of OCD onset and iron deposition in the basal ganglia.
C1 [Correia, Stephen] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Vet Affairs Med Ctr, Providence, RI 02908 USA.
[Hubbard, Emily] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA.
[Yip, Agustin; Greenberg, Benjamin D.] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Butler Hosp, Providence, RI 02908 USA.
[Vymazal, Josef] Hosp Homolca, MR Unit, Dept Radiodiagnost, Prague, Czech Republic.
[Herynek, Vit] Inst Clin & Expt Med, Dept Radiodiagnost & Intervent Radiol, MRI Unit, Prague, Czech Republic.
[Giedd, Jay] NIMH, Unit Brain Imaging, Clin Psychiat Branch, Intramural Res Ctr,NIH,Clin Ctr, Bethesda, MD 20892 USA.
[Murphy, Dennis L.] NIMH, Clin Sci Lab, Intramural Res Program, Bethesda, MD 20892 USA.
RP Correia, S (reprint author), Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Vet Affairs Med Ctr, 830 Chalkstone Ave, Providence, RI 02908 USA.
EM stephen_correia@brown.edu
RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015;
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Yip,
Agustin/0000-0003-2641-3439
FU National Institute of Mental Health; Department of Veterans Affairs
FX We wish to thank David Strong, Ph.D. for his contribution to the
statistical analyses. This work was supported by the Intramural Research
Program at the National Institute of Mental Health and the Department of
Veterans Affairs. The contents of this manuscript do not represent the
views of the Department of Veterans Affairs or the United States.
NR 84
TC 7
Z9 7
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1931-7557
J9 BRAIN IMAGING BEHAV
JI Brain Imaging Behav.
PD MAR
PY 2010
VL 4
IS 1
BP 35
EP 45
DI 10.1007/s11682-009-9083-2
PG 11
WC Neuroimaging
SC Neurosciences & Neurology
GA 583DK
UT WOS:000276652900003
PM 20503112
ER
PT J
AU Kato, GJ
Taylor, JG
AF Kato, Gregory J.
Taylor, James G.
TI Pleiotropic effects of intravascular haemolysis on vascular homeostasis
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Review
DE sickle cell disease; thalassaemia; vasculopathy; haemolysis; nitric
oxide
ID SICKLE-CELL-DISEASE; NITRIC-OXIDE BIOAVAILABILITY; BETA-THALASSEMIA
MAJOR; PRIAPISM FOLLOWING SPLENECTOMY; PYRUVATE-KINASE DEFICIENCY;
REGURGITANT JET VELOCITY; VON-WILLEBRAND-FACTOR; PULMONARY-HYPERTENSION;
PLATELET ACTIVATION; ENDOTHELIAL-CELLS
AB The breakdown of senescent or defective red blood cells releases red cell contents, especially haemoglobin, which scavenges nitric oxide (NO) and decomposes to haem and free iron. These are potent oxidants, all of which have promoted the evolution of inducible and vasculoprotective compensatory pathways to rapidly clear and detoxify haemoglobin, haem and iron. Chronic haemolytic red cell disorders as diverse as sickle cell disease, thalassaemia, unstable haemoglobinopathy, cytoskeletal defects and enzymopathies have been linked to a clinical constellation of pulmonary hypertension, priapism, leg ulceration and possibly cerebrovascular disease and thrombosis. Besides free haemoglobin, haemolysis has been associated with extracellular arginase that limits substrate availability to NO synthase, endogenous inhibitors of NO synthase activity, and inappropriate activation of haemostatic pathways. This article reviews the haemolytic disorders that have been reported to manifest vascular complications, and explores the speculative possibility that haemolysis mediates some of the vascular complications of inflammation and diabetes.
C1 [Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Taylor, James G.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Kato, GJ (reprint author), NHLBI, Sickle Cell Vasc Dis Sect, Pulm & Vasc Med Branch, NIH, 10 Ctr Dr,MSC 1476,Bldg 10 CRC,Room 5-5140, Bethesda, MD 20892 USA.
EM gkato@mail.nih.gov
RI Kato, Gregory/I-7615-2014;
OI Kato, Gregory/0000-0003-4465-3217; Taylor, James/0000-0002-4421-1809
FU Intramural NIH HHS [ZIA HL006014-01, ZIA HL006014-02]
NR 130
TC 31
Z9 31
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD MAR
PY 2010
VL 148
IS 5
BP 690
EP 701
DI 10.1111/j.1365-2141.2009.08004.x
PG 12
WC Hematology
SC Hematology
GA 554AF
UT WOS:000274407200002
PM 19958359
ER
PT J
AU Andersson, TML
Lambert, PC
Derolf, AR
Kristinsson, SY
Eloranta, S
Landgren, O
Bjorkholm, M
Dickman, PW
AF Andersson, Therese M. -L.
Lambert, Paul C.
Derolf, Asa Rangert
Kristinsson, Sigurdur Yngvi
Eloranta, Sandra
Landgren, Ola
Bjorkholm, Magnus
Dickman, Paul W.
TI Temporal trends in the proportion cured among adults diagnosed with
acute myeloid leukaemia in Sweden 1973-2001, a population-based study
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE acute myeloid leukaemia; cure models; survival; relative survival;
population-based study
ID STEM-CELL TRANSPLANTATION; ACUTE NONLYMPHOCYTIC LEUKEMIA; CANCER
SURVIVAL ANALYSIS; CONSOLIDATION THERAPY; REGRESSION-MODELS; PATIENT
SURVIVAL; ELDERLY-PATIENTS; REMISSION; CYTARABINE; 1ST
AB P>Large age-dependant differences in temporal trends in 1- and 5-year relative survival have been observed in patients with acute myeloid leukaemia (AML) in Sweden. This investigation used an alternative approach to studying patient survival that simultaneously estimated the proportion of patients cured from their cancer and the survival of the 'uncured'. We conducted a population-based study including 6439 AML patients aged 19-80 years in Sweden between 1973 and 2001. Mixture cure models were estimated, with age at diagnosis categorised (19-40, 41-60, 61-70 and 71-80) and year of diagnosis modelled using splines. In 1975 the cure proportion was < 6% in all age groups and the median survival time for 'uncured' patients was < 0 center dot 5 years. In 2000 the cure proportion was 68% (95% confidence interval 56-77%) in the youngest group, and 32% (25-39%), 8% (3-21%), and 4% (2-8%) in the other groups, respectively. The median survival times for 'uncured' were 0 center dot 74 (0 center dot 43-1 center dot 26), 0 center dot 71 (0 center dot 53-0 center dot 97), 0 center dot 69 (0 center dot 51-0 center dot 95) and 0 center dot 37 (0 center dot 31-0 center dot 44) years, respectively. A dramatic improvement in the cure proportion was seen in younger patients, whereas improvement in older ages was mainly within the survival of the 'uncured'. This novel approach of analysing survival data could be a valuable tool for physicians, patients, health care planners and health economists.
C1 [Andersson, Therese M. -L.; Lambert, Paul C.; Eloranta, Sandra; Dickman, Paul W.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
[Lambert, Paul C.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[Derolf, Asa Rangert; Kristinsson, Sigurdur Yngvi; Landgren, Ola; Bjorkholm, Magnus] Karolinska Inst, Karolinska Univ Hosp Solna, Dept Med, Div Haematol, SE-17177 Stockholm, Sweden.
[Landgren, Ola] NCI, NIH, Bethesda, MD 20892 USA.
RP Andersson, TML (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, SE-17177 Stockholm, Sweden.
EM therese.m-l.andersson@ki.se
RI Dickman, Paul/B-4572-2013; Kristinsson, Sigurdur /M-2910-2015;
Andersson, Therese/E-7107-2016
OI Dickman, Paul/0000-0002-5788-3380; Kristinsson, Sigurdur
/0000-0002-4964-7476; Andersson, Therese/0000-0001-8644-9041
FU Swedish Cancer Society; Swedish Research Council; Stockholm County
Council; Karolinska Institutet Foundations
FX This work was supported by grants from the Swedish Cancer Society,
Swedish Research Council, Stockholm County Council, and the Karolinska
Institutet Foundations.
NR 42
TC 8
Z9 8
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD MAR
PY 2010
VL 148
IS 6
BP 918
EP 924
DI 10.1111/j.1365-2141.2009.08026.x
PG 7
WC Hematology
SC Hematology
GA 562ZM
UT WOS:000275094900011
PM 19995394
ER
PT J
AU Lee, S
Tsang, A
Kessler, RC
Jin, R
Sampson, N
Andrade, L
Karam, EG
Mora, MEM
Merikangas, K
Nakane, Y
Popovici, DG
Posada-Villa, J
Sagar, R
Wells, JE
Zarkov, Z
Petukhova, M
AF Lee, Sing
Tsang, Adley
Kessler, Ronald C.
Jin, Robert
Sampson, Nancy
Andrade, Laura
Karam, Elie G.
Medina Mora, Maria Elena
Merikangas, Kathleen
Nakane, Yoshibumi
Popovici, Daniela Georgeta
Posada-Villa, Jose
Sagar, Rajesh
Wells, J. Elisabeth
Zarkov, Zahari
Petukhova, Maria
TI Rapid-cycling bipolar disorder: cross-national community study
SO BRITISH JOURNAL OF PSYCHIATRY
LA English
DT Article
ID WORLD-HEALTH-ORGANIZATION; TREATMENT ENHANCEMENT PROGRAM; WEEKLY
SYMPTOMATIC STATUS; NATURAL-HISTORY; I-DISORDER; UNMET NEED; STEP-BD;
DSM-IV; VALIDITY; VERSION
AB Background
The epidemiology of rapid-cycling bipolar disorder in the community is largely unknown.
Aims
To investigate the epidemiological characteristics of rapid cycling and non-rapid-cycling bipolar disorder in a large cross-national community sample.
Method
The Composite International Diagnostic interview (CIDI version 3.0) was used to examine the prevalence, severity, comorbidity, impairment, suicidality, sociodemographics, childhood adversity and treatment of rapid-cycling and non-rapid-cycling bipolar disorder in ten countries (n=54257).
Results
The 12-month prevalence of rapid-cycling bipolar disorder was 0.3%. Roughly a third and two-fifths of participants with lifetime and 12-month bipolar disorder respectively met criteria for rapid cycling. Compared with the non-rapid-cycling, rapid-cycling bipolar disorder was associated with younger age at onset, higher persistence, more severe depressive symptoms, greater impairment from depressive symptoms, more out-of-role days from mania/hypomania, more anxiety disorders and an increased likelihood of using health services. Associations regarding childhood, family and other sociodemographic correlates were less clear cut.
Conclusions
The community epidemiological profile of rapid-cycling bipolar disorder confirms most but not all current clinically based knowledge about the illness.
Declaration of interest
R.C.K. has been a consultant for GlaxoSmithKline Inc, Kaiser Permanente, Pfizer Inc, Sanofi-Aventis, Shire Pharmaceuticals and Wyeth-Ayerst; has served on advisory boards for Eli Lilly & Company and Wyeth-Ayerst, and has had research support for his epidemiological studies from Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Johnson & Johnson Pharmaceuticals, Ortho-McNeil Pharmaceuticals Inc, Pfizer Inc and Sanofi-Avertis.
C1 [Lee, Sing] Chinese Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China.
[Tsang, Adley] Chinese Univ Hong Kong, Hong Kong Mood Disorders Ctr, Hong Kong, Hong Kong, Peoples R China.
[Kessler, Ronald C.; Jin, Robert; Sampson, Nancy] Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA.
[Andrade, Laura] Univ Sao Paulo, LIM Dept 23, Sect Psychiat Epidemiol, BR-05508 Sao Paulo, Brazil.
[Andrade, Laura] Univ Sao Paulo, Sch Med, Inst Psychiat, BR-05508 Sao Paulo, Brazil.
[Karam, Elie G.] Balamand Univ, IDRAAC, MIND, St George Hosp Univ Med Ctr,Fac Med, Beirut, Lebanon.
[Medina Mora, Maria Elena] Natl Inst Psychiat, Mexico City, DF, Mexico.
[Merikangas, Kathleen] NIMH, Mood & Anxiety Disorders Programs, Div Intramural Res Programs, Bethesda, MD 20892 USA.
[Nakane, Yoshibumi] Nagasaki Int Univ, Grad Sch Nagasaki, Div Human Sociol, Nagasaki, Japan.
[Posada-Villa, Jose] Colegio Mayor de Cundinamarca Univ, Bogota, Colombia.
[Sagar, Rajesh] All India Inst Med Sci, Dept Psychiat, Delhi, India.
[Wells, J. Elisabeth] Christchurch Sch Med & Hlth Sci, Dept Publ Hlth & Gen Practice, Christchurch, New Zealand.
[Zarkov, Zahari] Natl Ctr Publ Hlth Protect, Sofia, Bulgaria.
[Petukhova, Maria] Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA.
RP Lee, S (reprint author), Prince Wales Hosp, Hong Kong Mood Disorders Ctr, 7A,Block E,Staff Quarters, Shatin, Hong Kong, Peoples R China.
EM singlee@cuhk.edu.hk
RI Andrade, Laura Helena/F-3023-2010; Lee, Sing/O-2136-2015
OI Andrade, Laura Helena/0000-0002-2362-3521;
FU Bristol-Myers Squibb; Eli Lilly Company; GlaxoSmithKline; Johnson &
Johnson Pharmaceuticals; Ortho-McNeil Pharmaceuticals Inc; Pfizer Inc;
Sanofi-Avertis
FX R.C.K. has been a consultant for GlaxoSmithKline Inc, Kaiser Permanente,
Pfizer Inc, Sanofi-Aventis, Shire Pharmaceuticals and Wyeth-Ayerst; has
served on advisory boards for Eli Lilly & Company and Wyeth-Ayerst, and
has had research support for his epidemiological studies from
Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Johnson &
Johnson Pharmaceuticals, Ortho-McNeil Pharmaceuticals Inc, Pfizer Inc
and Sanofi-Avertis.
NR 45
TC 14
Z9 15
U1 2
U2 3
PU ROYAL COLLEGE OF PSYCHIATRISTS
PI LONDON
PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG,
ENGLAND
SN 0007-1250
J9 BRIT J PSYCHIAT
JI Br. J. Psychiatry
PD MAR
PY 2010
VL 196
IS 3
BP 217
EP 225
DI 10.1192/bjp.bp.109.067843
PG 9
WC Psychiatry
SC Psychiatry
GA 568IL
UT WOS:000275515800011
PM 20194545
ER
PT J
AU Binet, R
Ythier, D
Robles, A
Collado, M
Larrieu, D
Brambilla, E
Brambilla, C
Serrano, M
Harris, C
Pedeux, R
AF Binet, Romuald
Ythier, Damien
Robles, Ana
Collado, Manuel
Larrieu, Delphine
Brambilla, Elisabeth
Brambilla, Christian
Serrano, Manuel
Harris, Curtis
Pedeux, Remy
TI WNT16B, a new biomarker of senescent cells in vitro and in vivo, is
necessary for the p53-dependent activation of p21WAF1 in cellular
senescence
SO BULLETIN DU CANCER
LA English
DT Meeting Abstract
C1 INSERM, U823, F-75654 Paris 13, France.
UJF, Inst Albert Bonniot, Grenoble, France.
NCI, LHC, NIH, Bethesda, MD USA.
CNIO, Madrid, Spain.
INSERM, U917, Rennes, France.
EM romuald.binet@e.ujf-grenoble.fr
RI Binet, Romuald/I-7938-2012; Brambilla, Elisabeth/L-8796-2013; BRAMBILLA,
CHRISTIAN/K-2285-2013; Collado, Manuel/K-8140-2014
OI Binet, Romuald/0000-0003-0636-2195; Collado, Manuel/0000-0002-0330-0880
NR 1
TC 0
Z9 0
U1 0
U2 2
PU JOHN LIBBEY EUROTEXT LTD
PI MONTROUGE
PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE
SN 0007-4551
J9 B CANCER
JI Bull. Cancer
PD MAR
PY 2010
VL 97
SI SI
BP S67
EP S67
PG 1
WC Oncology
SC Oncology
GA 584CD
UT WOS:000276726700081
ER
PT J
AU Baum, CE
Price, DK
Figg, WD
AF Baum, Caitlin E.
Price, Douglas K.
Figg, William D.
TI Sarcosine as a potential prostate cancer biomarker and therapeutic
target
SO CANCER BIOLOGY & THERAPY
LA English
DT Editorial Material
DE sarcosine; prostate cancer; biomarker; PSA; metastasis
C1 [Baum, Caitlin E.; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU Intramural NIH HHS [NIH0012636439]; PHS HHS [NIH0012636439]
NR 7
TC 10
Z9 10
U1 1
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD MAR 1
PY 2010
VL 9
IS 5
BP 341
EP 342
PG 2
WC Oncology
SC Oncology
GA 584SQ
UT WOS:000276773500002
PM 20150759
ER
PT J
AU Baum, CE
Ockers, SB
English, BC
Price, DK
Sartor, O
Figg, WD
AF Baum, Caitlin E.
Ockers, Sandra B.
English, Bevin C.
Price, Douglas K.
Sartor, Oliver
Figg, William D.
TI Androgen receptor sequence and variations in several common prostate
cancer cell lines
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE androgen receptor; prostate cancer; LnCAP; SNP; CAG; repeat; genotype;
DU145
ID GENE; INDEPENDENCE; PROGRESSION; MUTATIONS; DOMAIN
AB The androgen receptor gene (AR) plays an important role in molecular signaling and regulation and the subsequent cellular growth of prostate cancer. In addition, it is a highly variable region of the genome. We used direct nucleotide sequencing to genotype the entire exogenous coding region of the androgen receptor in ten commonly used prostate cancer cell lines. Our analysis confirmed the presence or absence of several known SNPs in the cell lines studied. We also assayed the number of CAG-repeat and GGC-repeat sequences for each for the ten cell lines.
Our analysis identified three new mutations, one each in the DU145, LnCAP and RWPE-2 cell lines. In DU145, the DNA isolated in our lab was heterozygous at G527G (T>C transition), a polymorphism not previously reported. The LnCAP cells cultured in our lab were found to have a T>C transition (heterozygous), resulting in a S641P change that was not present in the ATCC cell line DNA. Lastly, a homozygous G>T transversion was found in RWPE-2 cells, resulting in the S187I change. This is potentially significant for use in cell culture and future cell model development.
C1 [Baum, Caitlin E.; Ockers, Sandra B.; English, Bevin C.; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Sartor, Oliver] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
[Sartor, Oliver] Tulane Univ, Sch Med, Dept Urol, New Orleans, LA 70112 USA.
RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU National Institutes of Health, National Cancer Institute, Bethesda, MD;
Southwest Oncology Group (SWOG); National Cancer Institute, NIH,
Department of Health and Human Services [P01CA106451]
FX This study was supported in part by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Bethesda,
MD.; The authors thank Southwest Oncology Group (SWOG) for the support
during this study. This work is supported by National Cancer Institute,
NIH, Department of Health and Human Services grant P01CA106451.
NR 13
TC 0
Z9 0
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD MAR 1
PY 2010
VL 9
IS 5
BP 383
EP 388
PG 6
WC Oncology
SC Oncology
GA 584SQ
UT WOS:000276773500009
PM 20061791
ER
PT J
AU Koshiol, J
Rotunno, M
Consonni, D
Pesatori, AC
De Matteis, S
Goldstein, AM
Chaturvedi, AK
Wacholder, S
Landi, MT
Lubin, JH
Caporaso, NE
AF Koshiol, Jill
Rotunno, Melissa
Consonni, Dario
Pesatori, Angela Cecilia
De Matteis, Sara
Goldstein, Alisa M.
Chaturvedi, Anil K.
Wacholder, Sholom
Landi, Maria Teresa
Lubin, Jay H.
Caporaso, Neil E.
TI Lower Risk of Lung Cancer after Multiple Pneumonia Diagnoses
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID CIGARETTE-SMOKING; FAMILY-HISTORY; EPIDEMIOLOGIC EVIDENCE;
RESPIRATORY-DISEASE; PULMONARY-DISEASE; NONSMOKING WOMEN; UNITED-STATES;
CHINA; INTENSITY; TUBERCULOSIS
AB Background: Although pneumonia has been suggested as a risk factor for lung cancer, previous studies have not evaluated the influence of number of pneumonia diagnoses in relation to lung cancer risk.
Methods: The Environment And Genetics in Lung cancer Etiology (EAGLE) population-based study of 2,100 cases and 2,120 controls collected information on pneumonia more than 1 year before enrollment from 1,890 cases and 2,078 controls.
Results: After adjusting for study design variables, smoking, and chronic bronchitis, pneumonia was associated with decreased risk of lung cancer [odds ratio (OR), 0.79; 95% confidence interval (CI), 0.64-0.97], especially among individuals with three or more diagnoses versus none (OR, 0.35; 95% CI, 0.16-0.75). Adjustment for chronic bronchitis contributed to this inverse association. In comparison, pulmonary tuberculosis was not associated with lung cancer (OR, 0.96; 95% CI, 0.62-1.48).
Conclusions: The apparent protective effect of pneumonia among individuals with multiple pneumonia diagnoses may reflect an underlying difference in immune response and requires further investigation and confirmation. Therefore, careful evaluation of the number of pneumonia episodes may shed light on lung cancer etiology. Cancer Epidemiol Biomarkers Prev; 19(3); 716-21. (C) 2010 AACR.
C1 [Koshiol, Jill; Rotunno, Melissa; Goldstein, Alisa M.; Chaturvedi, Anil K.; Wacholder, Sholom; Landi, Maria Teresa; Lubin, Jay H.; Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Consonni, Dario; Pesatori, Angela Cecilia; De Matteis, Sara] Univ Milan, Dept Occupat & Environm Hlth, EPOCA Res Ctr, Milan, Italy.
[Consonni, Dario; Pesatori, Angela Cecilia; De Matteis, Sara] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Epidemiol Unit, Milan, Italy.
RP Koshiol, J (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,MSC 7248, Bethesda, MD 20892 USA.
EM koshiolj@mail.nih.gov
RI Chaturvedi, Anil/J-2024-2015;
OI Chaturvedi, Anil/0000-0003-2696-8899; pesatori,
angela/0000-0002-0261-3252
FU NIH; National Cancer Institute; Office of Preventive Oncology, National
Cancer Institute, Bethesda, MD
FX Intramural Research Program of the NIH and the National Cancer Institute
and the Cancer Prevention Fellowship Program, Office of Preventive
Oncology, National Cancer Institute, Bethesda, MD.
NR 26
TC 5
Z9 5
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAR
PY 2010
VL 19
IS 3
BP 716
EP 721
DI 10.1158/1055-9965.EPI-09-0873
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 607CF
UT WOS:000278475300011
PM 20200440
ER
PT J
AU Orom, H
Kiviniemi, MT
Underwood, W
Ross, L
Shavers, VL
AF Orom, Heather
Kiviniemi, Marc T.
Underwood, Willie, III
Ross, Levi
Shavers, Vickie L.
TI Perceived Cancer Risk: Why Is It Lower Among Nonwhites than Whites?
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID BREAST-CANCER; FAMILY-HISTORY; AFRICAN-AMERICAN; COLON-CANCER;
ETHNIC-DIFFERENCES; SOCIAL NETWORKS; UNITED-STATES; POPULATION;
PREDICTORS; WOMEN
AB Background: We explored racial/ethnic differences in perceived cancer risk and determinants of these differences in a nationally representative sample of whites, blacks, Hispanics, and Asians.
Methods: Multiple regression techniques, including mediational analyses, were used to identify determinants and quantify racial/ethnic differences in the perception of the risk of developing cancer among 5,581 adult respondents to the 2007 Health Information Trends Survey (HINTS).
Results: Blacks, Hispanics, and Asians reported lower perceived cancer risk than whites [Bs = -0.40, -0.34, and -0.69, respectively; (Ps < 0.001)]. Contributing factors included relatively lower likelihood of reporting a family history of cancer, lower likelihood of having smoked, and a less strong belief that everything causes cancer among nonwhites than among whites. Racial/ethnic differences in perceived risk were attenuated in older respondents because perceived cancer risk was negatively associated with age for whites but not for nonwhites.
Conclusions: Nonwhites had lower perceptions of cancer risk than whites. Some of the racial/ethnic variability in perceived risk may be due to racial and ethnic differences in awareness of one's family history of cancer and its relevance for cancer risk, experiences with behavioral risk factors, and salience of cancer risk information. Cancer Epidemiol Biomarkers Prev; 19(3); 746-54. (C) 2010 AACR.
C1 [Orom, Heather] SUNY Buffalo, Dept Hlth Behav, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14214 USA.
[Underwood, Willie, III] Roswell Pk Canc Inst, Dept Urol Oncol, Buffalo, NY 14263 USA.
[Underwood, Willie, III; Ross, Levi] Roswell Pk Canc Inst, Dept Hlth Dispar, Buffalo, NY 14263 USA.
[Shavers, Vickie L.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Orom, H (reprint author), SUNY Buffalo, Dept Hlth Behav, Sch Publ Hlth & Hlth Profess, 304 Kimball Tower,3435 Main St, Buffalo, NY 14214 USA.
EM horom@buffalo.edu
RI Kiviniemi, Marc/B-8513-2013;
OI Kiviniemi, Marc/0000-0002-1299-8416; Ross, Levi/0000-0002-3833-0836
FU NIH [K07CA106225]; Astella/AUA Foundation
FX During the preparation of this manuscript, supported was granted by NIH
grant K07CA106225 (M. T. Kiviniemi) and by an Astella/AUA Foundation
Rising Star in Urology Award (W. Underwood).
NR 40
TC 45
Z9 45
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAR
PY 2010
VL 19
IS 3
BP 746
EP 754
DI 10.1158/1055-9965.EPI-09-1085
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 607CF
UT WOS:000278475300015
PM 20160278
ER
PT J
AU Meyer, TE
O'Brien, TG
Andreotti, G
Yu, K
Li, QZ
Gao, YT
Rashid, A
Shen, MC
Wang, BS
Han, TQ
Zhang, BH
Niwa, S
Fraumeni, JF
Hsing, AW
AF Meyer, Tamra E.
O'Brien, Thomas G.
Andreotti, Gabriella
Yu, Kai
Li, Qizhai
Gao, Yu-Tang
Rashid, Asif
Shen, Ming-Chang
Wang, Bing-Sheng
Han, Tian-Quan
Zhang, Bai-He
Niwa, Shelley
Fraumeni, Joseph F., Jr.
Hsing, Ann W.
TI Androgen Receptor CAG Repeat Length and Risk of Biliary Tract Cancer and
Stones
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID X-CHROMOSOME INACTIVATION; TESTOSTERONE LEVELS; PROSTATE-CANCER;
BREAST-CANCER; HEALTHY-MEN; POLYMORPHISM; GENE; WOMEN; FLUTAMIDE;
HIRSUTISM
AB Biliary tract cancers, encompassing cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, are rare but highly fatal. Gallstones represent the major risk factor for biliary tract cancer, and share with gallbladder cancer a female predominance and an association with reproductive factors and obesity. Although estrogens have been implicated in earlier studies of gallbladder cancer, there are no data on the role of androgens. Because intracellular androgen activity is mediated through the androgen receptor (AR), we examined associations between AR CAG repeat length [(CAG)(n)] and the risk of biliary tract cancers and stones in a population-based study of 331 incident cancer cases, 837 gallstone cases, and 750 controls from Shanghai, China, where the incidence rates for biliary tract cancer are rising sharply. Men with (CAG)(n) >24 had a significant 2-fold risk of gallbladder cancer [odds ratio (OR), 2.00; 95% confidence interval (CI), 1.07-3.73], relative to those with (CAG)(n) <= 22. In contrast, women with (CAG)(n) >24 had reduced gallbladder cancer isk (OR, 0.69; 95% CI, 0.43-1.09) relative to those with (CAG)(n) <= 22; P interaction sex = 0.01, which was most pronounced for women ages 68 to 74 (OR, 0.48; 95% CI, 0.25-0.93; P interaction age = 0.02). No associations were found for bile duct cancer or gallstones. Reasons for the heterogeneity of genetic effects by gender and age are unclear but may reflect an interplay between AR and the levels of androgen as well as estrogen in men and older women. Further studies are needed to confirm these findings and clarify the mechanisms involved. Cancer Epidemiol Biomarkers Prev; 19(3); 787-93. (C) 2010 AACR.
C1 [Meyer, Tamra E.; Andreotti, Gabriella; Yu, Kai; Li, Qizhai; Fraumeni, Joseph F., Jr.; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[O'Brien, Thomas G.] Lankenau Inst Med Res, Wynnewood, PA USA.
[Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing, Peoples R China.
[Rashid, Asif] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Gao, Yu-Tang] Shanghai Canc Inst, Shanghai 200433, Peoples R China.
[Shen, Ming-Chang] Shanghai Tumor Hosp, Shanghai, Peoples R China.
[Wang, Bing-Sheng] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China.
[Han, Tian-Quan] Shanghai Med Univ 2, Ruijin Hosp, Dept Surg, Shanghai, Peoples R China.
[Zhang, Bai-He] Second Mil Med Univ, Inst Oriental Hepatobiliary Surg, Shanghai, Peoples R China.
[Niwa, Shelley] WESTAT Corp, Rockville, MD 20850 USA.
RP Meyer, TE (reprint author), NCI, Div Canc Epidemiol & Genet, EPS Room 5032,6120 Execut Blvd, Rockville, MD 20852 USA.
EM meyerte@mail.nih.gov
FU NIH; National Cancer Institute, NIH [N01-CO-12400]
FX Grant Support; Intramural Research Program of the NIH and National
Cancer Institute, NIH under contract N01-CO-12400. The contents of this
publication 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
U.S. Government.
NR 39
TC 3
Z9 3
U1 0
U2 3
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 MAR
PY 2010
VL 19
IS 3
BP 787
EP 793
DI 10.1158/1055-9965.EPI-09-0973
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 607CF
UT WOS:000278475300019
PM 20200439
ER
PT J
AU Wideroff, L
Garceau, AO
Greene, MH
Dunn, M
McNeel, T
Mai, P
Willis, G
Gonsalves, L
Martin, M
Graubard, BI
AF Wideroff, Louise
Garceau, Anne O.
Greene, Mark H.
Dunn, Marsha
McNeel, Timothy
Mai, Phuong
Willis, Gordon
Gonsalves, Lou
Martin, Michael
Graubard, Barry I.
TI Coherence and Completeness of Population-based Family Cancer Reports
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID PRIMARY-CARE; COLORECTAL-CANCER; RISK-ASSESSMENT; HISTORY; IMPACT;
DISPARITIES; PREVALENCE; PREVENTION; PROSTATE; DISEASES
AB Background: Although family history of cancer is widely ascertained in research and clinical care, little is known about assessment methods, accuracy, or other quality measures. Given its widespread use in cancer screening and surveillance, better information is needed about the clarity and accuracy of family history information reported in the general population.
Methods: This telephone survey in Connecticut examined coherence and completeness of reports from 1,019 respondents about 20,504 biological relatives.
Results: Of 2,657 cancer reports, 97.7% were judged consistent with malignancy (versus benign or indeterminate conditions); 79% were site specific, 10.1% had unspecified cancer sites, and 8.6% had "ill-defined" sites. Only 6.1% of relatives had unknown histories. Unknown histories and ambiguous sites were significantly higher for second-degree relatives. The adjusted percentage of first-degree relative reports with ambiguous sites increased with decreasing education and African-American race of survey respondents, and with deceased vital status of relatives. Ambiguous second-degree relative reports were also associated with deceased vital status and with male gender of respondents.
Conclusions: These findings suggest that family history of cancer reports from the general population are generally complete and coherent.
Impact: Strategies are needed to improve site specificity and thus maximize the utility of such information in primary care settings. Cancer Epidemiol Biomarkers Prev; 19(3); 799-810. (C) 2010 AACR.
C1 [Wideroff, Louise; Garceau, Anne O.; Greene, Mark H.; Mai, Phuong; Willis, Gordon; Graubard, Barry I.] NCI, Bethesda, MD 20892 USA.
[Dunn, Marsha] Westat Corp, Rockville, MD USA.
[McNeel, Timothy] Informat Management Serv Inc, Silver Spring, MD USA.
[Gonsalves, Lou] Connecticut Tumor Registry, Hartford, CT USA.
[Martin, Michael] Sligo Gen Hosp, Dept Med Oncol, Sligo, Ireland.
RP Wideroff, L (reprint author), NIDA, Epidemiol Res Branch, Div Epidemiol Serv & Prevent Res, 6001 Execut Blvd,Suite 5153 MSC 9589, Bethesda, MD 20892 USA.
EM wideroff@nih.gov
RI Hernandez, Jessica/G-6527-2011
FU Division of Cancer Control and Population Sciences, National Cancer
Institute [N01-PC-95039, N02-PC-25001]; Department of Health and Human
Services, NIH, National Cancer Institute, Division of Cancer
Epidemiology and Genetics
FX Grant Support; Division of Cancer Control and Population Sciences,
National Cancer Institute contracts N01-PC-95039 and N02-PC-25001 and
Intramural Research Program of the Department of Health and Human
Services, NIH, National Cancer Institute, Division of Cancer
Epidemiology and Genetics (M. H. Greene, P. Mai, M. Martin, and B. I.
Graubard).
NR 50
TC 8
Z9 8
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 MAR
PY 2010
VL 19
IS 3
BP 799
EP 810
DI 10.1158/1055-9965.EPI-09-1138
PG 12
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 607CF
UT WOS:000278475300021
PM 20160272
ER
PT J
AU Lindstrom, S
Hunter, DJ
Gronberg, H
Stattin, P
Wiklund, F
Xu, JF
Chanock, SJ
Hayes, R
Kraft, P
AF Lindstroem, Sara
Hunter, David J.
Gronberg, Henrik
Stattin, Par
Wiklund, Fredrik
Xu, Jianfeng
Chanock, Stephen J.
Hayes, Richard
Kraft, Peter
TI Sequence Variants in the TLR4 and TLR6-1-10 Genes and Prostate Cancer
Risk. Results Based on Pooled Analysis from Three Independent Studies
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ASSOCIATION; TOLL-LIKE-RECEPTOR-4
AB Background: Genetic variation in two members of the Toll-like receptor family, TLR4 and the gene cluster TLR6-1-10, has been implicated in prostate cancer in several studies but the associated alleles have not been consistent across reports.
Methods: We did a pooled analysis combining genotype data from three case-control studies, Cancer of the Prostate in Sweden, the Health Professionals Follow-up Study, and the Prostate, Lung, Colon and Ovarian Cancer Screening Trial, with data from 3,101 prostate cancer cases and 2,523 controls. We did imputation to obtain dense coverage of the genes and comparable genotype data for all cohorts. In total, 58 single nucleotide polymorphisms in TLR4 and 96 single nucleotide polymorphisms in TLR6-1-10 were genotyped or imputed and analyzed in the entire data set. We did a cohort-specific analysis as well as meta-analysis and pooled analysis. We also evaluated whether the analyses differed by age or disease severity.
Results: We observed no overall association between genetic variation at the TLR4 and TLR6-1-10 loci and risk of prostate cancer.
Conclusions: Common germ line genetic variation in TLR4 and TLR6-1-10 did not seem to have a strong association with risk of prostate cancer.
Impact: This study suggests that earlier associations between prostate cancer risk and TLR4 and TLR6-1-10 sequence variants were chance findings. To definitely assess the causal relationship between TLR sequence variants and prostate cancer risk, very large sample sizes are needed. Cancer Epidemiol Biomarkers Prev; 19(3); 873-6. (C) 2010 AACR.
C1 [Lindstroem, Sara; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Lindstroem, Sara; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Hunter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Gronberg, Henrik; Wiklund, Fredrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Stattin, Par] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
[Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Hayes, Richard] NYU, Div Epidemiol, Langone Med Ctr, New York, NY USA.
RP Lindstrom, S (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Bldg 2,Room 249B,655 Huntington Ave, Boston, MA 02115 USA.
EM slindstr@hsph.harvard.edu
OI Hayes, Richard/0000-0002-0918-661X
FU NCI NIH HHS [U01 CA098233-04, CA098233, U01 CA098233]
NR 11
TC 22
Z9 23
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 MAR
PY 2010
VL 19
IS 3
BP 873
EP 876
DI 10.1158/1055-9965.EPI-09-0618
PG 4
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 607CF
UT WOS:000278475300030
PM 20200442
ER
PT J
AU Lee, KH
Shu, XO
Gao, YT
Ji, BT
Yang, G
Blair, A
Rothman, N
Zheng, W
Chow, WH
Kang, D
AF Lee, Kyoung-Ho
Shu, Xiao-Ou
Gao, Yu-Tang
Ji, Bu-Tian
Yang, Gong
Blair, Aaron
Rothman, Nathaniel
Zheng, Wei
Chow, Wong-Ho
Kang, Daehee
TI Breast Cancer and Urinary Biomarkers of Polycyclic Aromatic Hydrocarbon
and Oxidative Stress in the Shanghai Women's Health Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID LIPID-PEROXIDATION; ANTIOXIDANT STATUS; CHINESE WOMEN; DNA ADDUCTS;
RISK; MALONDIALDEHYDE; 1-HYDROXYPYRENE; CARCINOGENESIS; SMOKING; DAMAGE
AB Polycyclic aromatic hydrocarbon (PAH) exposure and oxidative stress from such and other exposures have been associated with breast cancer in some studies. To further evaluate the role of PAH metabolites and oxidative stress on the development of breast cancer, we conducted a nested case-control study in the Shanghai Women's Health Study.
We measured urinary 1-hydroxypyrene and 2-naphthol as PAH metabolites and urinary levels of 8-hydroxy-2'-deoxyguanosine and malondialdehyde as oxidative stress biomarkers in 327 breast cancer cases and 654 controls in the Shanghai Women's Health Study. Information on demographic characteristics, past medical history, lifestyles, history of menstruation, pregnancy history, eating and drinking habit, history of residence, employment history, family history, husband's information, and physical activity were collected by a self-administered questionnaire.
The mean age was 52.3 in breast cancer cases (n = 354) and 52.5 in controls (n = 708). Age at menarche (P = 0.04), months of breast-feeding the first baby (P = 0.05), and grade of education (P(trend) < 0.01) were significantly different between cases and controls. No association was observed for PAH metabolites and the oxidative stress biomarkers of urinary malondialdehyde and 8-hydroxy-2'-deoxyguanosine and risk of breast cancer.
This nested case-control study provides no evidence of association between PAH exposure and oxidative stress and risk of breast cancer in Shanghai women. Cancer Epidemiol Biomarkers Prev; 19(3); 877-83. (C) 2010 AACR.
C1 [Lee, Kyoung-Ho; Kang, Daehee] Seoul Natl Univ, Dept Prevent Med, Coll Med, Inst Environm Med,SNUMRC, Seoul 110799, South Korea.
[Shu, Xiao-Ou; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Div Epidemiol, Dept Med, Vanderbilt Epidemiol Ctr, Nashville, TN USA.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Ji, Bu-Tian; Blair, Aaron; Rothman, Nathaniel; Chow, Wong-Ho] NCI, Occupat & Environm Epidemiol Branch, Rockville, MD USA.
[Blair, Aaron] Canc Care Ontario, Occupat Canc Res Ctr, Toronto, ON, Canada.
[Kang, Daehee] Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul 110799, South Korea.
[Kang, Daehee] Seoul Natl Univ, Coll Med, Seoul 110799, South Korea.
RP Kang, D (reprint author), Seoul Natl Univ, Dept Prevent Med, Coll Med, Inst Environm Med,SNUMRC, 28 Yongon Dong, Seoul 110799, South Korea.
EM dhkang@snu.ac.kr
RI Kang, Dae Hee/E-8631-2012
FU NCI NIH HHS [N02 CP1101066, P30CA68485, R01 CA064277, R01 CA064277-11,
R37 CA70867]
NR 32
TC 12
Z9 12
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAR
PY 2010
VL 19
IS 3
BP 877
EP 883
DI 10.1158/1055-9965.EPI-09-1098
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 607CF
UT WOS:000278475300031
PM 20160264
ER
PT J
AU Garg, H
Salcedo, R
Trinchieri, G
Blumenthal, R
AF Garg, H.
Salcedo, R.
Trinchieri, G.
Blumenthal, R.
TI Improved nonviral cancer suicide gene therapy using survivin
promoter-driven mutant Bax
SO CANCER GENE THERAPY
LA English
DT Article
DE gene therapy; cancer; apoptosis; Bax; survivin promoter
ID CONDITIONALLY REPLICATIVE ADENOVIRUSES; IN-VIVO; PROAPOPTOTIC FUNCTION;
ANTITUMOR-ACTIVITY; INDUCED APOPTOSIS; OVARIAN-CANCER; BREAST-CANCER;
LUNG-CANCER; CELL-DEATH; EXPRESSION
AB Suicide gene vectors are being developed in many laboratories as an attractive approach to cancer therapy. However, the development of these therapies is hampered by safety concerns and limitations of efficacy. The use of tumor-specific promoters, such as survivin promoter, can provide much needed specificity to target tumor cells. However, the expression levels from these promoters is often suboptimal and hence it is imperative to enhance the activity of the cytotoxic gene of interest. We tested apoptotic activity of several mutants of proapoptotic gene bax that constitutively translocate to the mitochondria and induce apoptosis. One of these mutants with deletion of serine at position S184 (S184del) was found to be most active and showed significant antitumor activity when expressed by the survivin promoter. In vitro testing shows that this vector (Sur-BaxS184del) induces cell killing in a variety of tumor cell lines of different origin with significantly higher efficacy than wild-type bax (Sur-BaxWT). The increase in cytotoxicity was a result of enhanced induction of apoptosis in tumor cells. In contrast to cytomegalovirus (CMV) promoter-driven bax (CMV-Bax), Sur-BaxS184del caused minimum toxicity in normal human dermal fibroblasts validating its specificity and safety. In a mouse tumor model (DA-3, murine breast cancer cells), we show that intratumoral injection of Sur-BaxS184del resulted in tumor growth retardation to the same level as CMV-Bax. This study highlights the effectiveness of using bax mutants in combination with survivin promoter for tumor-targeted suicide gene therapy in a nonviral vector. Cancer Gene Therapy (2010) 17, 155-163; doi:10.1038/cgt.2009.63; published online 9 October 2009
C1 [Garg, H.; Blumenthal, R.] NCI, Nanobiol Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Salcedo, R.; Trinchieri, G.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Garg, H.] Texas Tech Univ, Hlth Sci Ctr, Ctr Excellence Infect Dis, El Paso, TX USA.
[Salcedo, R.] NCI, SAIC Frederick Inc, Ctr Canc Res, Frederick, MD 21702 USA.
RP Blumenthal, R (reprint author), NCI, Nanobiol Program, Ctr Canc Res, POB B,Bldg 469,Room 152,Miller Dr, Frederick, MD 21702 USA.
EM blumenthalr@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank Rei Ming Dai, Loretta Scheetz and Donna Butcher for technical
help. This research was supported (in part) by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 35
TC 11
Z9 11
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0929-1903
J9 CANCER GENE THER
JI Cancer Gene Ther.
PD MAR
PY 2010
VL 17
IS 3
BP 155
EP 163
DI 10.1038/cgt.2009.63
PG 9
WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Research & Experimental Medicine
GA 555KC
UT WOS:000274508500002
PM 19816523
ER
PT J
AU Boehm, AL
Higgins, J
Franzusoff, A
Schlom, J
Hodge, JW
AF Boehm, Amanda L.
Higgins, Jack
Franzusoff, Alex
Schlom, Jeffrey
Hodge, James W.
TI Concurrent vaccination with two distinct vaccine platforms targeting the
same antigen generates phenotypically and functionally distinct T-cell
populations
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE Vaccinia; Saccharomyces cerevisiae; Carcinoembryonic antigen (CEA);
T-cell populations; Antitumor immunity
ID THERAPEUTIC ANTITUMOR RESPONSES; BOOST IMMUNIZATION STRATEGIES;
SEMLIKI-FOREST-VIRUS; IMMUNE-RESPONSES; DIVERSIFIED PRIME; REPERTOIRE
DIVERSITY; DNA PRIME; ADENOVIRUS; CARCINOMA; AVIDITY
AB Studies comparing two or more vaccine platforms have historically evaluated each platform based on its ability to induce an immune response and may conclude that one vaccine is more efficacious than the other(s), leading to a recommendation for development of the more effective vaccine for clinical studies. Alternatively, these studies have documented the advantages of a diversified prime and boost regimen due to amplification of the antigen-specific T-cell population. We hypothesize here that two vaccine platforms targeting the same antigen might induce shared and distinct antigen-specific T-cell populations, and examined the possibility that two distinct vaccines could be used concomitantly.
Using recombinant poxvirus and yeast vaccines, we compared the T-cell populations induced by these two platforms in terms of serum cytokine response, T-cell gene expression, T-cell receptor phenotype, antigen-specific cytokine expression, T-cell avidity, and T-cell antigen-specific tumor cell lysis.
These studies demonstrate for the first time that vaccination with a recombinant poxvirus platform (rV/F-CEA/TRICOM) or a heat-killed yeast vaccine platform (yeast-CEA) elicits T-cell populations with both shared and unique phenotypic and functional characteristics. Furthermore, both the antigen and the vector play a role in the induction of distinct T-cell populations.
In this study, we demonstrate that concurrent administration of two vaccines targeting the same antigen induces a more diverse T-cell population that leads to enhanced antitumor efficacy. These studies provide the rationale for future clinical studies investigating concurrent administration of vaccine platforms targeting a single antigen to enhance the antigen-specific immune response.
C1 [Boehm, Amanda L.; Higgins, Jack; Schlom, Jeffrey; Hodge, James W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Franzusoff, Alex] GlobeImmune Inc, Louisville, CO 80027 USA.
RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA.
EM js141c@nih.gov; jh241d@nih.gov
RI Hodge, James/D-5518-2015
OI Hodge, James/0000-0001-5282-3154
FU Intramural NIH HHS [Z01 BC010661-03]
NR 41
TC 28
Z9 28
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD MAR
PY 2010
VL 59
IS 3
BP 397
EP 408
DI 10.1007/s00262-009-0759-7
PG 12
WC Oncology; Immunology
SC Oncology; Immunology
GA 537GM
UT WOS:000273101200006
PM 19756595
ER
PT J
AU Cook, JA
Choudhuri, R
DeGraff, W
Gamson, J
Mitchell, JB
AF Cook, John A.
Choudhuri, Rajani
DeGraff, William
Gamson, Janet
Mitchell, James B.
TI Halofuginone enhances the radiation sensitivity of human tumor cell
lines
SO CANCER LETTERS
LA English
DT Article
DE Radiation sensitizer; TGF-beta; Halofuginone; Fibrosis
ID TGF-BETA; HEPATOCELLULAR-CARCINOMA; H2AX PHOSPHORYLATION; HISTONE H2AX;
CANCER CELLS; DNA-DAMAGE; GROWTH; INHIBITION; THERAPY; INJURY
AB Transforming growth factor beta (TGF-beta) is implicated in radiation-induced fibrosis of normal tissues in patients receiving radiotherapy. Inhibiting the TGF-beta signaling pathway by various means has been shown to reduce radiation-induced fibrosis in pre-clinical studies. The present study evaluated the effects of interfering with the TGE-beta signaling pathway on the radiosensitivity of selected human tumor cell lines using the plant-derived alkaloid, halofuginone. Halofuginone treatment inhibited cell growth, halted cell cycle progression, decreased radiation-induced DNA damage repair, and decreased TGF-beta receptor II protein levels, leading to increased cellular radiosensitization. These data further support the goal of manipulating the TGE-beta pathway to achieve a positive increase in the therapeutic gain in clinical radiotherapy. Published by Elsevier Ireland Ltd.
C1 [Cook, John A.; Choudhuri, Rajani; DeGraff, William; Gamson, Janet; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA.
EM jbm@helix.nih.gov
FU Intramural Research Program, Center for Cancer Research, National Cancer
Institute, NIH
FX This research was supported by the Intramural Research Program, Center
for Cancer Research, National Cancer Institute, NIH.
NR 35
TC 7
Z9 13
U1 2
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD MAR 1
PY 2010
VL 289
IS 1
BP 119
EP 126
DI 10.1016/j.canlet.2009.08.009
PG 8
WC Oncology
SC Oncology
GA 578EI
UT WOS:000276275900014
PM 19713035
ER
PT J
AU Satia, JA
Barlow, J
Armstrong-Brown, J
Watters, JL
AF Satia, Jessie A.
Barlow, Jameta
Armstrong-Brown, Janelle
Watters, Joanne L.
TI Qualitative Study to Explore Prospect Theory and Message Framing and
Diet and Cancer Prevention-Related Issues Among African American
Adolescents
SO CANCER NURSING
LA English
DT Article
DE Adolescents; African Americans; Cancer prevention; Diet; Interventions;
Message framing; Nutrition; Prospect Theory
ID CORONARY-HEART-DISEASE; GAIN-FRAMED MESSAGES; PHYSICAL-ACTIVITY;
VEGETABLE CONSUMPTION; SEDENTARY BEHAVIOR; LIFE-STYLE; RISK; FRUIT;
PERCEPTIONS; NUTRITION
AB Background: There is a dearth of knowledge regarding factors that may motivate African American adolescents to consume healthier diets. Objective: To develop and test cancer prevention messages based on Prospect Theory on motivation to improve dietary intake in African American adolescents and to explore other salient factors that may inform dietary intervention design and implementation in this population. Methods: Semistructured in-person qualitative interviews were conducted with 13 African American male and female adolescents, aged 12 to 16 years, in North Carolina. Prospect Theory and message framing were used to guide the design of the 4 sets of diet-related messages related to cancer prevention: short-term, gain-framed; long-term, gain-framed; short-term, loss-framed; and long-term, loss-framed messages. Data were also collected on demographic, behavioral, and psychological factors; usual health behaviors; and preferences for intervention delivery. Results: Most respondents found the gain-framed, short-term messages most salient for both fruits/vegetables (8 [61.5%]) and fat consumption (7 [53.8%]). For fat consumption only, 2 (15.4%) found the loss-framed, short-term messages pertinent; none found the loss-framed, long-term messages relevant for either dietary variable. All indicated interest in participating in a dietary intervention/education program; most preferred the Internet as a channel for intervention delivery. Participants expressed diverse views regarding knowledge, attitudes, and beliefs regarding healthy eating. Conclusion: The gain-framed, short-term messages were most salient for motivating the majority of respondents to consume a healthy diet and most expressed a strong interest in participating in programs about diet and nutrition, with the Internet as the preferred communication channel. Implications for Practice: Researchers conducting dietary interventions and education initiatives and medical professionals who counsel African American adolescents should consider using Prospect Theory as a theoretical framework, should focus on gain-framed, short-term messages regarding cancer prevention, and should use the Internet for data collection and intervention and information delivery.
C1 [Satia, Jessie A.] Univ N Carolina, Dept Nutr, Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Satia, Jessie A.] Univ N Carolina, Dept Epidemiol, Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Satia, Jessie A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Barlow, Jameta] Duke Univ, Duke Ctr Clin Hlth Policy Res, Durham, NC USA.
[Armstrong-Brown, Janelle] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27599 USA.
[Watters, Joanne L.] NCI, Nutr Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
RP Satia, JA (reprint author), Univ N Carolina, Dept Nutr, Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
EM jsatia@unc.edu
FU National Institutes of Health, Department of Health and Human Services
[U01CA114629]; [K22CA096556]; [DK056350]
FX This study was funded by grants K22CA096556, DK056350, and Carolina
Community Network grant no. U01CA114629 from the National Institutes of
Health, Department of Health and Human Services.
NR 48
TC 5
Z9 5
U1 3
U2 17
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 MAR-APR
PY 2010
VL 33
IS 2
BP 102
EP 109
DI 10.1097/NCC.0b013e3181be5e8a
PG 8
WC Oncology; Nursing
SC Oncology; Nursing
GA 568XY
UT WOS:000275560700004
PM 20142738
ER
PT J
AU Bevans, M
Castro, K
Prince, P
Shelburne, N
Prachenko, O
Loscalzo, M
Soeken, K
Zabora, J
AF Bevans, Margaret
Castro, Kathleen
Prince, Patricia
Shelburne, Nonniekaye
Prachenko, Olena
Loscalzo, Matthew
Soeken, Karen
Zabora, James
TI An Individualized Dyadic Problem-Solving Education Intervention for
Patients and Family Caregivers During Allogeneic Hematopoietic Stem Cell
Transplantation A Feasibility Study
SO CANCER NURSING
LA English
DT Article
DE Caregivers; Coping skills; Education; Hematopoietic stem cell
transplant; Oncology; Problem-solving
ID BONE-MARROW-TRANSPLANTATION; CANCER-PATIENTS; PROSTATE-CANCER;
PSYCHOSOCIAL INTERVENTIONS; UNIPOLAR DEPRESSION; THERAPY; CARE;
ADAPTATION; DISTRESS; EFFICACY
AB Background: Allogeneic hematopoietic stem cell transplantation (HSCT) generates multiple problems that vary in complexity and create significant distress for both patients and their caregivers. Interventions that address patient and family caregiver distress during allogeneic hematopoietic stem cell transplantation ( HSCT) have not been tested. Objective: To evaluate the feasibility of conducting an individualized dyadic problem-solving education (PSE) intervention during HSCT and estimate a preliminary effect size on problem-solving skills and distress. Methods: The PSE intervention consisted of 4 sessions of the Prepared Family Caregiver PSE model. Data were collected with an interventionist log, subject interviews and standardized questionnaires. Results: Of the 34 adult dyads screened, 24 were ineligible primarily because of being non-English-speaking (n = 11) and inconsistent caregivers (n = 10). Ten dyads (n = 20) were enrolled, and 8 dyads (n = 16) completed the intervention. Of the 31 sessions, 29 were completed (94%). Worsening patient condition was the primary reason for sessions to be incomplete. Patients attended 90% of the sessions; caregivers attended 74%. Reasons for missed sessions included patient symptom distress and limited caregiver availability. Dyads reported being very satisfied (mean, 4.8 [SD, 1.8]; range, 1-5), stating "an opportunity to talk'' and "creative thinking'' were most beneficial. Conclusion: Results suggest that dyads can participate in PSE during HSCT and view it as beneficial. Participants identified the active process of solving problems as helpful. Implications for Practice: Targeted interventions that promote effective, meaningful behaviors are needed to guide patients and caregivers through HSCT. Future research recommendations include testing a version of PSE with fewer sessions, including spousal and nonspousal caregivers and those who are non-English speaking.
C1 [Bevans, Margaret; Castro, Kathleen; Prince, Patricia; Shelburne, Nonniekaye; Prachenko, Olena] NIH, Bethesda, MD 20892 USA.
[Loscalzo, Matthew] City Hope Natl Med Ctr, Duarte, CA USA.
[Zabora, James] Natl Catholic Sch Social Serv, Washington, DC USA.
[Soeken, Karen] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA.
RP Bevans, M (reprint author), 5061 Durham Rd W, Columbia, MD 21044 USA.
EM mbevans@cc.nih.gov
FU National Institutes of Health, Clinical Center
FX This study was funded by the Intramural Research Program of the National
Institutes of Health, Clinical Center.
NR 53
TC 10
Z9 10
U1 3
U2 10
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 MAR-APR
PY 2010
VL 33
IS 2
BP E24
EP E32
DI 10.1097/NCC.0b013e3181be5e6d
PG 9
WC Oncology; Nursing
SC Oncology; Nursing
GA 568XY
UT WOS:000275560700015
PM 20142739
ER
PT J
AU Neuhouser, ML
Till, C
Kristal, A
Goodman, P
Hoque, A
Platz, EA
Hsing, AW
Albanes, D
Parnes, HL
Pollak, M
AF Neuhouser, Marian L.
Till, Cathee
Kristal, Alan
Goodman, Phyllis
Hoque, Ashraful
Platz, Elizabeth A.
Hsing, Ann W.
Albanes, Demetrius
Parnes, Howard L.
Pollak, Michael
TI Finasteride Modifies the Relation between Serum C-Peptide and Prostate
Cancer Risk: Results from the Prostate Cancer Prevention Trial
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID BODY-MASS INDEX; GROWTH-FACTOR-I; MIDDLE-AGED MEN; INSULIN-RESISTANCE;
BREAST-CANCER; METABOLIC SYNDROME; GENETIC ASSOCIATION;
CELL-PROLIFERATION; GLUCOSE-TOLERANCE; SUPPLEMENT USE
AB Hyperinsulinemia and obesity-related metabolic disturbances are common and have been associated with increased cancer risk and poor prognosis. To investigate this issue in relation to prostate cancer, we conducted a nested case-control study within the Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled trial testing finasteride versus placebo for primary prevention of prostate cancer. Cases (n = 1,803) and controls (n = 1,797) were matched on age, PCPT treatment arm, and family history of prostate cancer; controls included all eligible non-whites. Baseline bloods were assayed for serum C-peptide (marker of insulin secretion) and leptin (an adipokine) using ELISA. All outcomes were biopsy determined. Logistic regression calculated odds ratios (OR) for total prostate cancer and polytomous logistic regression calculated ORs for low-grade (Gleason <7) and high-grade (Gleason >7) disease. Results were stratified by PCPT treatment arm for C-peptide. For men on placebo, higher versus lower serum C-peptide was associated with a nearly 2-fold increased risk of high-grade prostate cancer (Gleason >7; multivariate-adjusted OR, 1.88; 95% confidence interval, 1.19-2.97; P(trend) = 0.004). When C-peptide was modeled as a continuous variable, every unit increase in log(C-peptide) resulted in a 39% increased risk of high-grade disease (P = 0.01). In contrast, there was no significant relationship between C-peptide and high-grade prostate cancer among men receiving finasteride. Leptin was not independently associated with high-grade prostate cancer. In conclusion, these results support findings from other observational studies that high serum C-peptide and insulin resistance, but not leptin, are associated with increased risk of high-grade prostate cancer. Our novel finding is that the C-peptide-associated risk was attenuated by use of finasteride. Cancer Prev Res; 3(3); 279-89. (C) 2010 AACR.
C1 [Neuhouser, Marian L.; Till, Cathee; Kristal, Alan; Goodman, Phyllis] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Kristal, Alan] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Hoque, Ashraful] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA.
[Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Hsing, Ann W.; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Parnes, Howard L.] NCI, Prostate & Urol Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Pollak, Michael] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Pollak, Michael] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
RP Neuhouser, ML (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA.
EM mneuhous@fhcrc.org
RI Albanes, Demetrius/B-9749-2015;
OI Kristal, Alan/0000-0002-7329-1617
FU National Cancer Institute at the NIH; U.S. Department of Health and
Human Services [P01 CA108964]
FX National Cancer Institute at the NIH, U.S. Department of Health and
Human Services (P01 CA108964).
NR 75
TC 14
Z9 15
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2010
VL 3
IS 3
BP 279
EP 289
DI 10.1158/1940-6207.CAPR-09-0188
PG 11
WC Oncology
SC Oncology
GA 563UG
UT WOS:000275159800005
PM 20179296
ER
PT J
AU Camalier, CE
Young, MR
Bobe, G
Perella, CM
Colburn, NH
Beck, GR
AF Camalier, Corinne E.
Young, Matthew R.
Bobe, Gerd
Perella, Christine M.
Colburn, Nancy H.
Beck, George R., Jr.
TI Elevated Phosphate Activates N-ras and Promotes Cell Transformation and
Skin Tumorigenesis
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID INHIBITED 3T3 CELLS; INORGANIC-PHOSPHATE; PARATHYROID-HORMONE;
OSTEOBLAST CELLS; HIGH PHOSPHORUS; SERUM CONCENTRATION; TUMOR
PROGRESSION; GENE-EXPRESSION; JB6 CELLS; OSTEOPONTIN
AB Recent results suggest a paradigm shift from viewing inorganic phosphate as a passive requirement for basic cell functions to an active regulator of cell behavior. We have previously shown that elevated concentrations of phosphate increased cell proliferation and expression of protumorigenic genes such as Fra1 and osteopontin in a preosteoblast cell line. Therefore, we hypothesized that elevated phosphate concentrations would promote cell transformation in vitro and tumorigenesis in vivo. Supplementation of medium with phosphate increased anchorage-independent transformation and proliferation of BALB/c mouse JB6 epidermal cells, activation of N-ras, ERK1/2, and activator protein-1, and increased gene expression of Fra-1, COX-2, and osteopontin in a dose-dependent manner. These in vitro results led to the hypothesis that varying the levels of dietary inorganic phosphate would alter tumorigenesis in the mouse model of skin carcinogenesis. Female FVB/N mice were treated with 7,12-dimethylbenz (a) anthracene/12-O-tetradecanoylphorbol-13-acetate and fed high-or low-phosphate diets (1.2% versus 0.2% of the diet) for 19 weeks. The high-phosphate diet increased skin papilloma number by similar to 50% without changing feed intake and body weights. High dietary phosphate increased serum concentrations of phosphate, parathyroid hormone, and osteopontin and decreased serum concentrations of calcium. Thus, we conclude that elevated phosphate promotes cell transformation and skin tumorigenesis partly by increasing the availability of phosphate for activation of N-ras and its downstream targets, which defines reducing dietary phosphate as a novel target for chemoprevention. Cancer Prev Res; 3(3); 359-70. (C) 2010 AACR.
C1 [Camalier, Corinne E.; Beck, George R., Jr.] Emory Univ, Sch Med, Dept Med, Div Endocrinol Metab & Lipids, Atlanta, GA 30322 USA.
[Young, Matthew R.; Bobe, Gerd; Colburn, Nancy H.] NCI, Gene Regulat Sect, Frederick, MD 21701 USA.
[Camalier, Corinne E.; Beck, George R., Jr.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA.
[Perella, Christine M.] NCI, Lab Anim Sci Program, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA.
[Bobe, Gerd] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA.
RP Beck, GR (reprint author), Emory Univ, Sch Med, Dept Med, Div Endocrinol Metab & Lipids, 101 Woodruff Circle,WMRB 1026, Atlanta, GA 30322 USA.
EM george.beck@emory.edu
FU NIH/National Cancer Institute [CA136059]; NIH/NIAMS [AR056090]; Emory
University Research Committee; National Cancer Institute, NIH
FX G. R. Beck, Jr. and C. E. Camalier are supported in part by grants from
the NIH/National Cancer Institute (CA136059), NIH/NIAMS (AR056090),
Emory University Research Committee grant, and M. R. Young, G. Bobe, C.
M. Perella, and N.H. Colburn supported by federal funds from the
National Cancer Institute, NIH.
NR 63
TC 25
Z9 26
U1 2
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2010
VL 3
IS 3
BP 359
EP 370
DI 10.1158/1940-6207.CAPR-09-0068
PG 12
WC Oncology
SC Oncology
GA 563UG
UT WOS:000275159800013
PM 20145188
ER
PT J
AU McCormick, DL
Rao, KVN
Johnson, WD
Bosland, MC
Lubet, RA
Steele, VE
AF McCormick, David L.
Rao, K. V. N.
Johnson, William D.
Bosland, Maarten C.
Lubet, Ronald A.
Steele, Vernon E.
TI Null Activity of Selenium and Vitamin E as Cancer Chemopreventive Agents
in the Rat Prostate
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; SYRIAN GOLDEN-HAMSTERS;
METHYL-N-NITROSOUREA; PREVENTION TRIAL; SERUM SELENIUM; INTRAEPITHELIAL
NEOPLASIA; GLUTATHIONE PEROXIDASE; BIOLOGICAL-MATERIALS; DIETARY
SELENIUM; RISK
AB To evaluate the potential efficacy of selenium and vitamin E as inhibitors of prostate carcinogenesis, four chemoprevention studies using a common protocol were done in a rat model of androgen-dependent prostate cancer. After stimulation of prostate epithelial cell proliferation by a sequential regimen of cyproterone acetate followed by testosterone propionate, male Wistar-Unilever rats received a single i.v. injection of N-methyl-N-nitrosourea (MNU) followed by chronic androgen stimulation via subcutaneous implantation of testosterone pellets. At 1 week post-MNU, groups of carcinogen-treated rats (39-44/group) were fed either a basal diet or a basal diet supplemented with L-selenomethionine (3 or 1.5 mg/kg diet; study 1), DL-alpha-tocopherol (vitamin E, 4,000 or 2,000 mg/kg diet; study 2), L-selenomethionine + vitamin E (3 + 2,000 mg/kg diet or 3 + 500 mg/kg diet; study 3), or selenized yeast (target selenium levels of 9 or 3 mg/kg diet; study 4). Each chemoprevention study was terminated at 13 months post-MNU, and prostate cancer incidence was determined by histopathologic evaluation. No statistically significant reductions in prostate cancer incidence were identified in any group receiving dietary supplementation with selenium and/or vitamin E. These data do not support the hypotheses that selenium and vitamin E are potent cancer chemopreventive agents in the prostate, and when considered with the recent clinical data reported in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), show the predictive nature of this animal model for human prostate cancer chemoprevention. Cancer Prev Res; 3(3); 381-92. (C) 2010 AACR.
C1 [McCormick, David L.; Rao, K. V. N.; Johnson, William D.] IIT, Res Inst, Life Sci Grp, Chicago, IL 60616 USA.
[Bosland, Maarten C.] NYU, Sch Med, Nelson Inst Environm Med, New York, NY USA.
[Lubet, Ronald A.; Steele, Vernon E.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP McCormick, DL (reprint author), IIT, Res Inst, Life Sci Grp, 10 W 35th St, Chicago, IL 60616 USA.
EM dmccormick@iitri.org
FU Division of Cancer Prevention, National Cancer Institute, Department of
Health and Human Services [N01-CN-35566-02, N01-CN-95113, N01-CN-65120];
NIH [P30-ES-00260, P30-CA-16087]
FX Research supported by contracts N01-CN-35566-02, N01-CN-95113, and
N01-CN-65120 from the Division of Cancer Prevention, National Cancer
Institute, Department of Health and Human Services, and by NIH center
grants P30-ES-00260 and P30-CA-16087.
NR 51
TC 21
Z9 24
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2010
VL 3
IS 3
BP 381
EP 392
DI 10.1158/1940-6207.CAPR-09-0176
PG 12
WC Oncology
SC Oncology
GA 563UG
UT WOS:000275159800015
PM 20145190
ER
PT J
AU Safaeian, M
Schiffman, M
Gage, J
Castle, PE
Solomon, D
Wheeler, CM
AF Safaeian, Mahboobeh
Schiffman, Mark
Gage, Julia
Castle, Philip E.
Solomon, Diane
Wheeler, Cosette M.
TI Comment re: Detection of Cervical Precancer by HPV Genotype Response
SO CANCER RESEARCH
LA English
DT Letter
C1 [Safaeian, Mahboobeh; Schiffman, Mark; Gage, Julia; Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Solomon, Diane] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Wheeler, Cosette M.] Univ New Mexico, Sch Med, Dept Mol Genet & Microbiol, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Wheeler, Cosette M.] Univ New Mexico, Sch Med, Dept Obstet & Gynecol, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
RP Safaeian, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 1
PY 2010
VL 70
IS 5
BP 2137
EP 2137
DI 10.1158/0008-5472.CAN-09-3750
PG 1
WC Oncology
SC Oncology
GA 607FZ
UT WOS:000278485800042
ER
PT J
AU Kosaka, N
Ogawa, M
Paik, DS
Paik, CH
Choyke, PL
Kobayashi, H
AF Kosaka, Nobuyuki
Ogawa, Mikako
Paik, David S.
Paik, Chang H.
Choyke, Peter L.
Kobayashi, Hisataka
TI Semiquantitative assessment of the microdistribution of
fluorescence-labeled monoclonal antibody in small peritoneal
disseminations of ovarian cancer
SO CANCER SCIENCE
LA English
DT Article
ID BINDING-SITE BARRIER; SOLID TUMORS; MODELING ANALYSIS;
RADIOIMMUNOTHERAPY; THERAPY; PENETRATION; RESISTANCE; LYMPHOMA; DELIVERY
AB Uniform antibody microdistribution throughout tumor nodules is crucial for antibody-targeted therapy, because non-uniform microdistribution leads to suboptimal therapeutic effect, a commonly observed limitation of therapeutic antibodies. Herein, we evaluated the microdistribution of different doses of intraperitoneally injected fluorescence-labeled full-antibody trastuzumab (15, 50, and 150 mu g) and its Fab fragment (trastuzumab-Fab: 15 and 50 mu g) in a mouse model of ovarian cancer with peritoneal disseminated tumor. A semiquantitative approach (central/peripheral accumulation ratio; C/P ratio) was developed using in situ fluorescence microscopy. Furthermore, we compared the microdistribution of intact trastuzumab with a mixed injection of trastuzumab and trastuzumab-Fab or serial injections of trastuzumab using in situ multicolor fluorescence microscopy. Fluorescence images after the administration of 15 or 50 mu g trastuzumab and 15 mu g trastuzumab-Fab demonstrated antibody accumulation in the tumor periphery, whereas administration of 150 mu g trastuzumab and 50 mu g trastuzumab-Fab showed relatively uniform accumulation throughout the tumor nodule. Using serial injections (19-h interval) of trastuzumab-rhodamine green and carboxytetramethylrhodamine (TAMRA), it was observed that the latterly injected trastuzumab-TAMRA was distributed more centrally than trastuzumab-rhodamine green injected first, whereas no difference was observed in the control mixed-injection group. Moreover, the mixed injection of trastuzumab and trastuzumab-Fab showed that trastuzumab-Fab distributed more centrally than the same amount of co-injected trastuzumab. Our results suggest that the strategies of increasing dose and using Fab fragments can be used to achieve a uniform antibody distribution within peritoneal disseminated nodules after intraperitoneal injection. Furthermore, serial-injection and mixed-injection strategies can modify antibody microdistribution within tumors and have the potential for preferential delivery of anticancer drugs to either the tumor periphery or its center. (Cancer Sci 2010; 101: 820-825)
C1 [Kosaka, Nobuyuki; Ogawa, Mikako; Paik, David S.; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
[Paik, Chang H.] NIH, Dept Nucl Med, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 25
TC 13
Z9 13
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1347-9032
J9 CANCER SCI
JI Cancer Sci.
PD MAR
PY 2010
VL 101
IS 3
BP 820
EP 825
DI 10.1111/j.1349-7006.2009.01423.x
PG 6
WC Oncology
SC Oncology
GA 556VQ
UT WOS:000274621800036
PM 19961490
ER
PT J
AU Zabirnyk, O
Liu, W
Khalil, S
Sharma, A
Phang, JM
AF Zabirnyk, Olga
Liu, Wei
Khalil, Shadi
Sharma, Anit
Phang, James M.
TI Oxidized low-density lipoproteins upregulate proline oxidase to initiate
ROS-dependent autophagy
SO CARCINOGENESIS
LA English
DT Article
ID ACTIVATED-RECEPTOR-GAMMA; SMOOTH-MUSCLE-CELLS; OXIDATIVE STRESS;
COLORECTAL-CANCER; LIGAND ACTIVATION; TUMOR-SUPPRESSOR; CYCLE PROTEINS;
APOPTOSIS; ATHEROSCLEROSIS; EXPRESSION
AB Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy.
C1 [Zabirnyk, Olga] NCI, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Zabirnyk, O (reprint author), NCI, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res,NIH, Bldg 538,Room 144, Frederick, MD 21702 USA.
EM olga_zabirnyk@yahoo.com; phangj@mail.nih.gov
RI liu, wei /E-7340-2012
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research
FX Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Center for Cancer Research.
NR 52
TC 31
Z9 36
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD MAR
PY 2010
VL 31
IS 3
BP 446
EP 454
DI 10.1093/carcin/bgp299
PG 9
WC Oncology
SC Oncology
GA 564VE
UT WOS:000275245200017
PM 19942609
ER
PT J
AU Dossus, L
Kaaks, R
Canzian, F
Albanes, D
Berndt, SI
Boeing, H
Buring, J
Chanock, SJ
Clavel-Chapelon, F
Feigelson, HS
Gaziano, JM
Giovannucci, E
Gonzalez, C
Haiman, CA
Hallmans, G
Hankinson, SE
Hayes, RB
Henderson, BE
Hoover, RN
Hunter, DJ
Khaw, KT
Kolonel, LN
Kraft, P
Ma, J
Le Marchand, L
Lund, E
Peeters, PHM
Stampfer, M
Stram, DO
Thomas, G
Thun, MJ
Tjonneland, A
Trichopoulos, D
Tumino, R
Riboli, E
Virtamo, J
Weinstein, SJ
Yeager, M
Ziegler, RG
Cox, DG
AF Dossus, Laure
Kaaks, Rudolf
Canzian, Federico
Albanes, Demetrius
Berndt, Sonja I.
Boeing, Heiner
Buring, Julie
Chanock, Stephen J.
Clavel-Chapelon, Francoise
Feigelson, Heather Spencer
Gaziano, John M.
Giovannucci, Edward
Gonzalez, Carlos
Haiman, Christopher A.
Hallmans, Goran
Hankinson, Susan E.
Hayes, Richard B.
Henderson, Brian E.
Hoover, Robert N.
Hunter, David J.
Khaw, Kay-Tee
Kolonel, Laurence N.
Kraft, Peter
Ma, Jing
Le Marchand, Loic
Lund, Eiliv
Peeters, Petra H. M.
Stampfer, Meir
Stram, Dan O.
Thomas, Gilles
Thun, Michael J.
Tjonneland, Anne
Trichopoulos, Dimitrios
Tumino, Rosario
Riboli, Elio
Virtamo, Jarmo
Weinstein, Stephanie J.
Yeager, Meredith
Ziegler, Regina G.
Cox, David G.
TI PTGS2 and IL6 genetic variation and risk of breast and prostate cancer:
results from the Breast and Prostate Cancer Cohort Consortium (BPC3)
SO CARCINOGENESIS
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BASE-LINE CHARACTERISTICS;
SINGLE-NUCLEOTIDE POLYMORPHISMS; GROWTH-FACTOR-I; COX-2 GENE; CHRONIC
INFLAMMATION; INTERLEUKIN-6 GENE; DNA-DAMAGE; ASSOCIATION;
CYCLOOXYGENASE-2
AB Genes involved in the inflammation pathway have been associated with cancer risk. Genetic variants in the interleukin-6 (IL6) and prostaglandin-endoperoxide synthase-2 (PTGS2, encoding for the COX-2 enzyme) genes, in particular, have been related to several cancer types, including breast and prostate cancers. We conducted a study within the Breast and Prostate Cancer Cohort Consortium to examine the association between IL6 and PTGS2 polymorphisms and breast and prostate cancer risk. Twenty-seven polymorphisms, selected by pairwise tagging, were genotyped on 6292 breast cancer cases and 8135 matched controls and 8008 prostate cancer cases and 8604 matched controls. The large sample sizes and comprehensive single nucleotide polymorphism tagging in this study gave us excellent power to detect modest effects for common variants. After adjustment for multiple testing, none of the associations examined remained statistically significant at P = 0.01. In analyses not adjusted for multiple testing, one IL6 polymorphism (rs6949149) was marginally associated with breast cancer risk (TT versus GG, odds ratios (OR): 1.32; 99% confidence intervals (CI): 1.00-1.74, P(trend) = 0.003) and two were marginally associated with prostate cancer risk (rs6969502-AA versus rs6969502-GG, OR: 0.87, 99% CI: 0.75-1.02; P(trend) = 0.002 and rs7805828-AA versus rs7805828-GG, OR: 1.11, 99% CI: 0.99-1.26; P(trend) = 0.007). An increase in breast cancer risk was observed for the PTGS2 polymorphism rs7550380 (TT versus GG, OR: 1.38, 99% CI: 1.04-1.83). No association was observed between PTGS2 polymorphisms and prostate cancer risk. In conclusion, common genetic variation in these two genes might play at best a limited role in breast and prostate cancers.
C1 [Dossus, Laure; Kaaks, Rudolf; Canzian, Federico] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Albanes, Demetrius; Berndt, Sonja I.; Chanock, Stephen J.; Hoover, Robert N.; Weinstein, Stephanie J.; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Boeing, Heiner; Hayes, Richard B.; Thomas, Gilles; Yeager, Meredith] German Inst Human Nutr, Dept Epidemiol, D-14558 Postdam Rehbruecke, Nuthetal, Germany.
[Buring, Julie] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA 02215 USA.
[Clavel-Chapelon, Francoise] Inst Gustave Roussy, F-94805 Villejuif, France.
[Clavel-Chapelon, Francoise] INSERM, ERI 20, EA 4045, F-94805 Villejuif, France.
[Feigelson, Heather Spencer; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30303 USA.
[Feigelson, Heather Spencer] Kaiser Permanente, Denver, CO 80237 USA.
[Gaziano, John M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging,Dept Med, Boston, MA 02215 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA.
[Giovannucci, Edward; Hankinson, Susan E.; Ma, Jing; Stampfer, Meir] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA.
[Giovannucci, Edward; Stampfer, Meir; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Gonzalez, Carlos] Catalan Inst Oncol ICO Idibell ISCIII RETICC, Unit Nutr Environm & Canc, Barcelona 08907, Spain.
[Haiman, Christopher A.; Henderson, Brian E.; Stram, Dan O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden.
[Hayes, Richard B.] NYU, Sch Med, Dept Environm Med, Div Epidemiol, New York, NY 10012 USA.
[Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Dept Epidemiol, Boston, MA 02215 USA.
[Khaw, Kay-Tee; Le Marchand, Loic] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
[Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96822 USA.
[Lund, Eiliv] Univ Tromso, Inst Community Med, N-9037 Tromso, Norway.
[Peeters, Petra H. M.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands.
[Thomas, Gilles] Ctr Leon Berard, INSERM, U590, F-69373 Lyon, France.
[Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark.
[Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens 11527, Greece.
[Tumino, Rosario] Canc Registry Azienda Osped Civile MP Arezzo, I-97100 Ragusa, Italy.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FI-00271 Helsinki, Finland.
[Yeager, Meredith] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Dossus, L (reprint author), German Canc Res Ctr, Div Canc Epidemiol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
EM l.dossus@dkfz.de
RI Dossus, Laure/B-2875-2013; Clavel-Chapelon, Francoise/G-6733-2014;
Albanes, Demetrius/B-9749-2015; Cox, David/A-2023-2009
OI Dossus, Laure/0000-0003-2716-5748; Hayes, Richard/0000-0002-0918-661X;
Cox, David/0000-0002-2152-9259
FU National Cancer Institute [CA98233, CA98710, CA98216, CA98758]
FX National Cancer Institute under U01 grants (CA98233, CA98710, CA98216,
CA98758).
NR 55
TC 39
Z9 42
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD MAR
PY 2010
VL 31
IS 3
BP 455
EP 461
DI 10.1093/carcin/bgp307
PG 7
WC Oncology
SC Oncology
GA 564VE
UT WOS:000275245200018
PM 19965896
ER
PT J
AU Mukhopadhyay, P
Rajesh, M
Batkai, S
Patel, V
Kashiwaya, Y
Liaudet, L
Evgenov, OV
Mackie, K
Hasko, G
Pacher, P
AF Mukhopadhyay, Partha
Rajesh, Mohanraj
Batkai, Sandor
Patel, Vivek
Kashiwaya, Yoshihiro
Liaudet, Lucas
Evgenov, Oleg V.
Mackie, Ken
Hasko, Gyoergy
Pacher, Pal
TI CB1 cannabinoid receptors promote oxidative stress and cell death in
murine models of doxorubicin-induced cardiomyopathy and in human
cardiomyocytes
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Heart failure; CB1 receptor; Endocannabinoids; Rimonabant; SR141716;
AM281
ID ISCHEMIA-REPERFUSION INJURY; ENDOCANNABINOID SYSTEM;
ISCHEMIA/REPERFUSION INJURY; INDUCED CARDIOTOXICITY; NITRIC-OXIDE;
IN-VITRO; PEROXYNITRITE; DYSFUNCTION; MICE; SUPEROXIDE
AB Here we investigated the mechanisms by which cardiovascular CB1 cannabinoid receptors may modulate the cardiac dysfunction, oxidative stress, and interrelated cell death pathways associated with acute/chronic cardiomyopathy induced by the widely used anti-tumour compound doxorubicin (DOX).
Both load-dependent and -independent indices of left-ventricular function were measured by the Millar pressure-volume conductance system. Mitogen-activated protein kinase (MAPK) activation, cell-death markers, and oxidative/nitrosative stress were measured by molecular biology/biochemical methods and flow cytometry. DOX induced left-ventricular dysfunction, oxidative/nitrosative stress coupled with impaired antioxidant defense, activation of MAPK (p38 and JNK), and cell death and/or fibrosis in hearts of wide-type mice (CB1+/+), and these effects were markedly attenuated in CB1 knockouts (CB1-/-). In human primary cardiomyocytes expressing CB1 receptors (demonstrated by RT-PCR, western immunoblot, and flow cytometry) DOX, likewise the CB1 receptor agonist HU210 and the endocannabinoid anandamide (AEA), induced MAPK activation and cell death. The DOX-induced MAPK activation and cell death were significantly enhanced when DOX was co-administered with CB1 agonists AEA or HU210. Remarkably, cell death and MAPK activation induced by AEA, HU210, and DOX +/- AEA/HU210 were largely attenuated by either CB1 antagonists (rimonabant and AM281) or by inhibitors of p38 and JNK MAPKs. Furthermore, AEA or HU210 in primary human cardiomyocytes triggered increased reactive oxygen species generation.
CB1 activation in cardiomyocytes may amplify the reactive oxygen/nitrogen species-MAPK activation-cell death pathway in pathological conditions when the endocannabinoid synthetic or metabolic pathways are dysregulated by excessive inflammation and/or oxidative/nitrosative stress, which may contribute to the pathophysiology of various cardiovascular diseases.
C1 [Mukhopadhyay, Partha; Rajesh, Mohanraj; Batkai, Sandor; Patel, Vivek; Pacher, Pal] NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
[Kashiwaya, Yoshihiro] NIAAA, Lab Metab Control, NIH, Bethesda, MD 20892 USA.
[Liaudet, Lucas] Univ Hosp, Dept Intens Care Med, Lausanne, Switzerland.
[Evgenov, Oleg V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
[Mackie, Ken] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA.
[Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA.
RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA.
EM pacher@mail.nih.gov
RI MUKHOPADHYAY, PARTHA/G-3890-2010; Mackie, Kenneth/B-7358-2011; Batkai,
Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Mackie, Ken/E-3715-2013;
Batkai, Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017
OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher,
Pal/0000-0001-7036-8108; Mackie, Ken/0000-0001-8501-6199; Liaudet,
Lucas/0000-0003-2670-4930
FU National Institutes of Health/NIAAA [DA11322]; Swiss National Fund for
Scientific Research [PP00B-68882/1]
FX This study was supported by the Intramural research program of the
National Institutes of Health/NIAAA (to P. P.) and DA11322 (to K. M.),
Swiss National Fund for Scientific Research Grant PP00B-68882/1 (to L.
L.).
NR 48
TC 71
Z9 76
U1 2
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAR 1
PY 2010
VL 85
IS 4
BP 773
EP 784
DI 10.1093/cvr/cvp369
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 555DO
UT WOS:000274487900017
PM 19942623
ER
PT J
AU Torres, SM
March, TH
Carter, MM
McCash, CL
Seilkop, SK
Poirier, MC
Walker, DM
Walker, VE
AF Torres, Salina M.
March, Thomas H.
Carter, Meghan M.
McCash, Consuelo L.
Seilkop, Steven K.
Poirier, Miriam C.
Walker, Dale M.
Walker, Vernon E.
TI In Utero Exposure of Female CD-1 Mice to AZT and/or 3TC: I. Persistence
of Microscopic Lesions in Cardiac Tissue
SO CARDIOVASCULAR TOXICOLOGY
LA English
DT Article
DE AZT; 3TC; Cardiotoxicity; Electron microscopy; Histopathology;
Mitochondrial pathology; PTAH stain; Transplacental exposure; Trichrome
stain; Ultrastructural pathology
ID REVERSE-TRANSCRIPTASE INHIBITORS; TO-CHILD TRANSMISSION; MITOCHONDRIAL
TOXICITY; PERINATAL EXPOSURE; PATAS MONKEYS; ANTIRETROVIRAL THERAPY;
NUCLEOSIDE ANALOGS; DYSFUNCTION; HIV; ZIDOVUDINE
AB The current study was designed to delineate temporal changes in cardiomyocytes and mitochondria at the light and electron microscopic levels in hearts of mice exposed transplacentally to commonly used nucleoside analogs (NRTIs). Pregnant CD-1 mice were given 80 mg AZT/kg, 40 mg 3TC/kg, 80 mg AZT/kg plus 40 mg 3TC/kg, or vehicle alone during the last 7 days of gestation, and hearts from female mouse pups were examined at 13 and 26 weeks postpartum for histopathological or ultrastructural changes in cross-sections of both the ventricles and the interventricular septum. Using light microscopy and special staining techniques, transplacental exposure to AZT, 3TC, or AZT/3TC was shown to induce significant histopathological changes in myofibrils; these changes were more widespread at 13 weeks than at 26 weeks postpartum. While most light microscopic lesions resolved, some became more severe between 13 and 26 weeks postpartum. Transplacental NRTI exposure also resulted in progressive drug-specific changes in the number and ultrastructural integrity of cardiac mitochondria. These light and electron microscopic findings show that a subset of changes in cardiac mitochondria and myofibrils persisted and progressed months after transplacental exposure of an animal model to NRTIs, with combined AZT/3TC exposure yielding additive effects compared with either drug alone.
C1 [Torres, Salina M.; Walker, Vernon E.] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA.
[Torres, Salina M.; March, Thomas H.; Carter, Meghan M.; McCash, Consuelo L.; Walker, Vernon E.] Lovelace Resp Res Inst, Albuquerque, NM 87108 USA.
[Seilkop, Steven K.] SKS Consulting Serv, Siler City, NC 27344 USA.
[Poirier, Miriam C.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Walker, Dale M.; Walker, Vernon E.] BioMosaics Inc, Burlington, VT 05405 USA.
[Walker, Vernon E.] Univ Vermont, Dept Pathol, Genet Toxicol Lab, Burlington, VT 05405 USA.
RP Walker, VE (reprint author), Univ Vermont, Dept Pathol, Genet Toxicol Lab, 665 Spear St, Burlington, VT 05405 USA.
EM vwalker@uvm.edu
FU NIH [R01 HL 72727]; National Heart, Lung, and Blood Institute
FX We wish to thank Mr. Steve Randock, Ms. Cynthia Herrera, and Ms. Wendy
Piper (LRRI) for technical assistance in preparing figures and the
manuscript. This work was supported, in part, by NIH grants R01 HL 72727
to VEW and 1 F31 HL081928 to SMT from the National Heart, Lung, and
Blood Institute. The contents of this paper are solely the
responsibility of the authors and do not necessarily represent the
official views of the National Institutes of Health.
NR 39
TC 8
Z9 8
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1530-7905
J9 CARDIOVASC TOXICOL
JI Cardiovasc. Toxicol.
PD MAR
PY 2010
VL 10
IS 1
BP 37
EP 50
DI 10.1007/s12012-010-9061-3
PG 14
WC Cardiac & Cardiovascular Systems; Toxicology
SC Cardiovascular System & Cardiology; Toxicology
GA 553XA
UT WOS:000274398900005
PM 20101476
ER
PT J
AU Anderson, HV
Rosenfield, KA
White, CJ
Ho, KKL
Spertus, JA
Jones, PG
Tang, FM
Cates, CU
Jaff, MR
Koroshetz, WJ
Katzan, IL
Hopkins, LN
Rumsfeld, JS
Brindis, RG
AF Anderson, H. Vernon
Rosenfield, Kenneth A.
White, Christopher J.
Ho, Kalon K. L.
Spertus, John A.
Jones, Philip G.
Tang, Fengming
Cates, Christopher U.
Jaff, Michael R.
Koroshetz, Walter J.
Katzan, Irene L.
Hopkins, L. Nelson
Rumsfeld, John S.
Brindis, Ralph G.
TI Clinical Features and Outcomes of Carotid Artery Stenting by Clinical
Expert Consensus Criteria: A Report From the CARE Registry
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE peripheral vascular disease; quantitative vascular angiography; total
occlusions
ID RISK PATIENTS; ENDARTERECTOMY; PROTECTION; PREDICTORS
AB Background: In 2007, a multispecialty society task force published a clinical expert consensus document (CECD) on carotid stenting (CAS), containing recommendations for appropriate patient selection and quality of care. The CECD also inspired creation of a large, national registry of carotid revascularization, the Carotid Artery Revascularization and Endarterectomy (CARE) registry. Our goal here was to investigate whether initial CAS procedures submitted to CARE conformed to CECD recommendations, and examine their clinical outcomes. Methods: We analyzed CAS procedures for the period January 1, 2005 through December 31, 2008. These were grouped into those that conformed to CECD recommendations [CECD(+), n = 4,636, 79.8%] and those that did not [CECD(), n = 1,168, 20.2%]. Results: The CECD(+) patients were older than CECD() patients (71.5 +/- 10.3 vs. 67.6 +/- 10.3 years, P = 0.001, respectively), and more frequently had chronic kidney disease (46.9% vs. 17.8%, P = 0.001), chronic lung disease (33.0% vs. 12.4%, P = 0.001), ejection fraction <= 0.30 (13.5% vs. 5.5%, P = 0.001) and contralateral carotid artery occlusion (12.7% vs. 4.6%, P = 0.001). Clinical outcomes at 30 days were similar, including death (1.24% vs. 0.76%, P = 0.184), stroke (5.32% vs. 5.34%, P = 0.954), and death, stroke, or MI (7.04% vs. 6.95%, P = 0.944). Conclusions: Most CAS procedures submitted to CARE conformed to CECD recommendations for patient selection. For reported data, clinical outcomes at 30 days were similar for procedures meeting and those not meeting recommendations, and were similar to outcomes reported by other large registries. These findings suggest that acceptable patient selection criteria for CAS are employed as it expands beyond investigators into more widespread clinical practice. (C) 2010 Wiley-Liss, Inc.
C1 [Anderson, H. Vernon] Univ Texas Hlth Sci Ctr, Div Cardiol, Houston, TX 77030 USA.
[Rosenfield, Kenneth A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[White, Christopher J.] Ochsner Clin Fdn, Dept Cardiol, New Orleans, LA USA.
[Ho, Kalon K. L.] Beth Israel Deaconess Med Ctr, Dept Cardiol, Boston, MA 02215 USA.
[Spertus, John A.; Jones, Philip G.; Tang, Fengming] St Lukes Hosp, Mid Amer Heart Inst, Dept Cardiol, Kansas City, MO 64111 USA.
[Cates, Christopher U.] Emory Univ Hosp, Dept Cardiol, Atlanta, GA 30322 USA.
[Jaff, Michael R.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA.
[Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Katzan, Irene L.] Cleveland Clin, Cerebrovasc Ctr, Cleveland, OH 44106 USA.
[Katzan, Irene L.] Cleveland Clin, Dept Neurol, Cleveland, OH 44106 USA.
[Hopkins, L. Nelson] SUNY Buffalo, Millard Fillmore Hosp, Dept Neurosurg, Buffalo, NY 14260 USA.
[Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA.
[Rumsfeld, John S.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Brindis, Ralph G.] Amer Coll Cardiol, Washington, DC USA.
RP Anderson, HV (reprint author), Univ Texas Hlth Sci Ctr, Div Cardiol, 6431 Fannin,1246, Houston, TX 77030 USA.
EM h.v.anderson@uth.tmc.edu
RI White, Christopher/J-6686-2012
OI White, Christopher/0000-0001-8618-7539
NR 10
TC 7
Z9 7
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1522-1946
J9 CATHETER CARDIO INTE
JI Catheter. Cardiovasc. Interv.
PD MAR 1
PY 2010
VL 75
IS 4
BP 519
EP 525
DI 10.1002/ccd.22333
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 582HW
UT WOS:000276588600009
PM 20088016
ER
PT J
AU McNeely, S
Conti, C
Sheikh, T
Patel, H
Zabludoff, S
Pommier, Y
Schwartz, G
Tse, A
AF McNeely, Samuel
Conti, Chiara
Sheikh, Tahir
Patel, Himali
Zabludoff, Sonya
Pommier, Yves
Schwartz, Gary
Tse, Archie
TI Chk1 inhibition after replicative stress activates a double strand break
response mediated by ATM and DNA-dependent protein kinase
SO CELL CYCLE
LA English
DT Article
DE Chk1; ATM; DNA-PK; AZD7762; gemcitabine
ID TOPOISOMERASE-I POISON; CHECKPOINT ABROGATION; SIGNALING PATHWAYS;
DAMAGE RESPONSE; MRE11-RAD50-NBS1 COMPLEX; CANCER CELLS; GEMCITABINE;
PHOSPHORYLATION; REPAIR; 2,2-DIFLUORODEOXYCYTIDINE
AB Checkpoint kinase 1 (Chk1) regulates cell cycle checkpoints and DNA damage repair in response to genotoxic stress. Inhibition of Chk1 is an emerging strategy for potentiating the cytotoxicity of chemotherapeutic drugs. Here, we demonstrate that AZD7762, an ATP-competitive Chk1/2 inhibitor induces gamma H2AX in gemcitabine-treated cells by altering both dynamics and stability of replication forks, allowing the firing of suppressed replication origins as measured by DNA fiber combing and causing a dramatic increase in DNA breaks as measured by comet assay. Furthermore, we identify ATM and DNA-PK, rather than ATR, as the kinases mediating gamma H2AX induction, suggesting AZD7762 converts stalled forks into double strand breaks (DSBs). Consistent with DSB formation upon fork collapse, cells deficient in DSB repair by lack of BRCA2, XRCC3 or DNA-PK were selectively more sensitive to combined AZD7762 and gemcitabine. Checkpoint abrogation by AZD7762 also caused premature mitosis in gemcitabine-treated cells arrested in G(1)/early S-phase. Prevention of premature mitotic entry via Cdk1 siRNA knockdown suppressed apoptosis. These results demonstrate that chemosensitization of gemcitabine by Chk1 inhibition results from at least three cellular events, namely, activation of origin firing, destabilization of stalled replication forks and entry of cells with damaged DNA into lethal mitosis. Additionally, the current study indicates that the combination of Chk1 inhibitor and gemcitabine may be particularly effective in targeting tumors with specific DNA repair defects.
C1 [McNeely, Samuel; Sheikh, Tahir; Schwartz, Gary; Tse, Archie] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Patel, Himali] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Conti, Chiara; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Zabludoff, Sonya] AstraZeneca R&D Boston, Waltham, MA USA.
RP Tse, A (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
EM atse@dsi.com
FU AstraZeneca; NCI [5K08CA116612]
FX This work was supported in part by AstraZeneca and NCI grant
5K08CA116612. We thank Dr. Irene Orlow (Memorial Sloan-Kettering Cancer
Center) for assistance with the comet assay.
NR 53
TC 56
Z9 58
U1 0
U2 5
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD MAR 1
PY 2010
VL 9
IS 5
BP 995
EP 1004
DI 10.4161/cc.9.5.10935
PG 10
WC Cell Biology
SC Cell Biology
GA 578QB
UT WOS:000276307700034
PM 20160494
ER
PT J
AU Jia, YF
Wu, SL
Isenberg, JS
Dai, SJ
Sipes, JM
Field, L
Zeng, BX
Bandle, RW
Ridnour, LA
Wink, DA
Ramchandran, R
Karger, BL
Roberts, DD
AF Jia, Yifeng
Wu, Shiaw-Lin
Isenberg, Jeff S.
Dai, Shujia
Sipes, John M.
Field, Lyndsay
Zeng, Bixi
Bandle, Russell W.
Ridnour, Lisa A.
Wink, David A.
Ramchandran, Ramani
Karger, Barry L.
Roberts, David D.
TI Thiolutin inhibits endothelial cell adhesion by perturbing Hsp27
interactions with components of the actin and intermediate filament
cytoskeleton
SO CELL STRESS & CHAPERONES
LA English
DT Article
DE Hsp27; Arp2/3; Intermediate filaments; Angiogenesis; Mass spectrometry
ID SMOOTH-MUSCLE-CELLS; ALPHA-B-CRYSTALLIN; HEAT-SHOCK; FOCAL ADHESIONS;
PHOSPHORYLATED HSP27; PROTEIN-KINASE; HEAT-SHOCK-PROTEIN-27; EXPRESSION;
NESTIN; ANGIOGENESIS
AB Thiolutin is a dithiole synthesized by Streptomyces sp. that inhibits endothelial cell adhesion and tumor growth. We show here that thiolutin potently inhibits developmental angiogenesis in zebrafish and vascular outgrowth from tissue explants in 3D cultures. Thiolutin is a potent and selective inhibitor of endothelial cell adhesion accompanied by rapid induction of HSPB1 (Hsp27) phosphorylation. The inhibitory effects of thiolutin on endothelial cell adhesion are transient, potentially due to a compensatory increase in Hsp27 protein levels. Accordingly, heat shock induction of Hsp27 limits the anti-adhesive activity of thiolutin. Thiolutin treatment results in loss of actin stress fibers, increased cortical actin as cells retract, and decreased cellular F-actin. Mass spectrometric analysis of Hsp27 binding partners following immunoaffinity purification identified several regulatory components of the actin cytoskeleton that associate with Hsp27 in a thiolutin-sensitive manner including several components of the Arp2/3 complex. Among these, ArpC1a is a direct binding partner of Hsp27. Thiolutin treatment induces peripheral localization of phosphorylated Hsp27 and Arp2/3. Hsp27 also associates with the intermediate filament components vimentin and nestin. Thiolutin treatment specifically ablates Hsp27 interaction with nestin and collapses nestin filaments. These results provide new mechanistic insights into regulation of cell adhesion and cytoskeletal dynamics by Hsp27.
C1 [Jia, Yifeng; Isenberg, Jeff S.; Sipes, John M.; Field, Lyndsay; Zeng, Bixi; Bandle, Russell W.; Ramchandran, Ramani; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ramchandran, Ramani] Med Coll Wisconsin, Dept Pediat, Childrens Res Inst, Milwaukee, WI 53226 USA.
[Wu, Shiaw-Lin; Dai, Shujia; Karger, Barry L.] Northeastern Univ, Barnett Inst, Boston, MA 02115 USA.
[Ridnour, Lisa A.; Wink, David A.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Room 2A33,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU NIH [GM 1584, CA 128616]; NCI; Center for Cancer Research (DDR); Barnett
Institute [934]
FX We thank Susan Garfield for guidance with confocal imaging. The authors
acknowledge support from the Intramural Research Program of the NIH,
NCI, Center for Cancer Research (DDR) and NIH grants GM 1584 (BLK) and
CA 128616 (JSI). Contribution Number 934 from the Barnett Institute.
NR 66
TC 22
Z9 25
U1 0
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1355-8145
J9 CELL STRESS CHAPERON
JI Cell Stress Chaperones
PD MAR
PY 2010
VL 15
IS 2
BP 165
EP 181
DI 10.1007/s12192-009-0130-0
PG 17
WC Cell Biology
SC Cell Biology
GA 552KH
UT WOS:000274288200004
PM 19579057
ER
PT J
AU Im, K
Jo, HJ
Mangin, JF
Evans, AC
Kim, SI
Lee, JM
AF Im, Kiho
Jo, Hang Joon
Mangin, Jean-Francois
Evans, Alan C.
Kim, Sun I.
Lee, Jong-Min
TI Spatial Distribution of Deep Sulcal Landmarks and Hemispherical
Asymmetry on the Cortical Surface
SO CEREBRAL CORTEX
LA English
DT Article
DE brain development; cortical folding; functional lateralization; magnetic
resonance imaging; sulcal pits
ID AUTOMATED 3-D EXTRACTION; HUMAN BRAIN; CEREBRAL-CORTEX; STRUCTURAL
ASYMMETRIES; PLANUM TEMPORALE; FOLDING PATTERNS; GENETIC-CONTROL;
GENERIC MODEL; LANGUAGE; VOLUME
AB The locally deepest regions of major sulci, the sulcal pits, are thought to be the first cortical folds to develop and are closely related to functional areas. We examined the spatial distribution of sulcal pits across the entire cortical region, and assessed the hemispheric asymmetry in their frequency and distribution in a large group of normal adult brains. We automatically extracted sulcal pits from magnetic resonance imaging data using surface-based methods and constructed a group map from 148 subjects. The spatial distribution of the sulcal pits was relatively invariant between individuals, showing high frequency and density in specific focal areas. The left and right sulcal pits were spatially covariant in the regions of the earliest developed sulci. The sulcal pits with great spatial invariance appear to be useful as stable anatomical landmarks. We showed the most significant asymmetry in the frequency and spatial variance of sulcal pits in the superior temporal sulcus, which might be related to the lateralization of language function to the left hemisphere, developing more consistently and strongly than for the right. Our analyses support previous empirical and theoretical studies, and provide additional insights concerning the anatomical and functional development of the brain.
C1 [Im, Kiho; Kim, Sun I.; Lee, Jong-Min] Hanyang Univ, Dept Biomed Engn, Seoul 133791, South Korea.
[Jo, Hang Joon] NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Mangin, Jean-Francois] CEA, I2BM, LNAO, F-91190 Gif Sur Yvette, France.
[Evans, Alan C.] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada.
RP Lee, JM (reprint author), Hanyang Univ, Dept Biomed Engn, POB 55, Seoul 133605, South Korea.
EM ljm@hanyang.ac.kr
RI JO, HANG JOON/D-1775-2011
OI JO, HANG JOON/0000-0002-9180-3831
FU Korea government (MEST) [R0A-2007-000-20068-0]
FX Korea Science and Engineering Foundation (KOSEF) NRL program grant
funded by the Korea government (MEST) (grant number
R0A-2007-000-20068-0).
NR 67
TC 43
Z9 43
U1 1
U2 8
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 MAR
PY 2010
VL 20
IS 3
BP 602
EP 611
DI 10.1093/cercor/bhp127
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 555DU
UT WOS:000274488600010
PM 19561060
ER
PT J
AU Gronich, N
Kumar, A
Zhang, YW
Efimov, IR
Soldatov, NM
AF Gronich, Naomi
Kumar, Azad
Zhang, Yuwei
Efimov, Igor R.
Soldatov, Nikolai M.
TI Molecular remodeling of ion channels, exchangers and pumps in atrial and
ventricular myocytes in ischemic cardiomyopathy
SO CHANNELS
LA English
DT Article
DE ischemic cardiomyopathy; molecular profiling; atrial myocytes;
ventricular myocytes; ion channels; phospholemman; Na(+),K(+)-ATPase;
CLIC
ID CARDIAC SODIUM-CHANNEL; HEART-FAILURE; K+ CHANNEL; POTASSIUM CHANNEL;
CALCIUM-CHANNEL; GENE-EXPRESSION; MESSENGER-RNA; TISSUE DISTRIBUTION;
MOUSE HEART; RAT-HEART
AB existing molecular knowledge base of cardiovascular diseases is rudimentary because of lack of specific attribution to cell type and function. The aim of this study was to investigate cell-specific molecular remodeling in human atrial and ventricular myocytes associated with ischemic cardiomyopathy. Our strategy combines two technological innovations, laser-capture microdissection of identified cardiac cells in selected anatomical regions of the heart and splice microarray of a narrow catalog of the functionally most important genes regulating ion homeostasis. We focused on expression of a principal family of genes coding for ion channels, exchangers and pumps (Ce&P genes) that are involved in electrical, mechanical and signaling functions of the heart and constitute the most utilized drug targets. We found that (1) Ce&P genes remodel in a cell-specific manner: ischemic cardiomyopathy affected 63 Ce&P genes in ventricular myocytes and 12 essentially different genes in atrial myocytes. (2) Only few of the identified Ce&P genes were previously linked to human cardiac disfunctions. (3) The ischemia-affected Ce&P genes include nuclear chloride channels, adrenoceptors, cyclic nucleotide-gated channels, auxiliary subunits of Na(+), K(+) and Ca(2+) channels, and cell-surface Ce&Ps. (4) In both atrial and ventricular myocytes ischemic cardiomyopathy reduced expression of CACNG7 and induced overexpression of FXYD1, the gene crucial for Na(+) and K(+) homeostasis. Thus, our cell-specific molecular profiling defined new landmarks for correct molecular modeling of ischemic cardiomyopathy and development of underlying targeted therapies.
C1 [Gronich, Naomi; Kumar, Azad; Zhang, Yuwei; Soldatov, Nikolai M.] NIA, NIH, Baltimore, MD 21224 USA.
[Efimov, Igor R.] Washington Univ, St Louis, MO USA.
RP Soldatov, NM (reprint author), NIA, NIH, Baltimore, MD 21224 USA.
EM soldatovN@grc.nia.nih.gov
RI Efimov, Igor/B-8040-2010
OI Efimov, Igor/0000-0002-1483-5039
FU National Institutes of Health, National Institute on Aging [Z01
AG000294-08]; National Heart, Lung and Blood Institute [RO1 HL085369]
FX The authors thank Kevin Becker and William H. Wood (Gene Expression and
Genomics Unit, NIA) for development of splice microarray slides, Heather
Jordan and Weiyin Zhou (ExonHit Therapeutics) for help with splice
microarray analysis, and Cardiac Transplantation Unit of the Washington
University in St. Louis, MO for help with cardiac tissues. This work was
supported in part by the Intramural Research Program of the National
Institutes of Health, National Institute on Aging (Z01 AG000294-08 to
Nikolai M. Soldatov) and by the National Heart, Lung and Blood Institute
grant (RO1 HL085369 to Igor R. Efimov).
NR 101
TC 9
Z9 10
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1933-6950
J9 CHANNELS
JI Channels
PD MAR-APR
PY 2010
VL 4
IS 2
BP 101
EP 107
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 587IE
UT WOS:000276983200007
PM 20090424
ER
PT J
AU Thai, KM
Windisch, A
Stork, D
Weinzinger, A
Schiesaro, A
Guy, RH
Timin, EN
Hering, S
Ecker, GF
AF Thai, Khac-Minh
Windisch, Andreas
Stork, Daniela
Weinzinger, Anna
Schiesaro, Andrea
Guy, Robert H.
Timin, Eugen N.
Hering, Steffen
Ecker, Gerhard F.
TI The hERG Potassium Channel and Drug Trapping: Insight from Docking
Studies with Propafenone Derivatives
SO CHEMMEDCHEM
LA English
DT Article
DE docking; drug trapping; hERG; ion channels; propafenone
ID QT INTERVAL PROLONGATION; K+ CHANNEL; MOLECULAR DETERMINANTS; STRUCTURAL
BASIS; HOMOLOGY MODEL; INHIBITION; BLOCKERS; BINDING; BLOCKADE;
CLASSIFICATION
AB The inner cavity of the hERG potassium ion channel can accommodate large, structurally diverse compounds that can be trapped in the channel by closure of the activation gate. A small set of propafenone derivatives was synthesized, and both use-dependency and recovery from block were tested in order to gain insight into the behavior of these compounds with respect to trapping and non-trapping. Ligand-protein docking into homology models of the closed and open state of the hERG channel provides the first evidence for the molecular basis of drug trapping.
C1 [Thai, Khac-Minh; Schiesaro, Andrea; Ecker, Gerhard F.] Univ Vienna, Dept Med Chem, Emerging Field Pharmacoinformat, A-1090 Vienna, Austria.
[Windisch, Andreas; Stork, Daniela; Weinzinger, Anna; Timin, Eugen N.; Hering, Steffen] Univ Vienna, Dept Pharmacol & Toxicol, A-1090 Vienna, Austria.
[Thai, Khac-Minh] Univ Med & Pharm Ho Chi Minh City, Fac Pharm, Dept Pharmaceut Chem, Ho Chi Minh City, Vietnam.
[Guy, Robert H.] NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA.
RP Ecker, GF (reprint author), Univ Vienna, Dept Med Chem, Emerging Field Pharmacoinformat, Althanstr 14, A-1090 Vienna, Austria.
EM gerhard.f.ecker@univie.ac.at
RI Stary-Weinzinger, Anna/A-3629-2014;
OI Stary-Weinzinger, Anna/0000-0002-9202-0484; Thai,
Khac-Minh/0000-0002-5279-9614; Ecker, Gerhard/0000-0003-4209-6883
FU PhD program 'Molecular Drug Targets' of the University of Vienna
FX Khac-Minh Thai thanks the ASEA-Uninet, the Austrian Ministry for Science
and Research, and the Austrian Exchange Service 6AD for providing a PhD
scholarship. This work was supported by the PhD program 'Molecular Drug
Targets' of the University of Vienna.
NR 46
TC 15
Z9 15
U1 0
U2 2
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1860-7179
EI 1860-7187
J9 CHEMMEDCHEM
JI ChemMedChem
PD MAR
PY 2010
VL 5
IS 3
BP 436
EP 442
DI 10.1002/cmdc.200900374
PG 7
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 568KM
UT WOS:000275521200013
PM 20146282
ER
PT J
AU Schecter, A
Colacino, J
Sjodin, A
Needham, L
Birnbaum, L
AF Schecter, Arnold
Colacino, Justin
Sjodin, Andreas
Needham, Larry
Birnbaum, Linda
TI Partitioning of polybrominated diphenyl ethers (PBDEs) in serum and milk
from the same mothers
SO CHEMOSPHERE
LA English
DT Article
DE PBDE; Partitioning; Milk; Blood; Serum
ID BROMINATED FLAME RETARDANTS; HIGH-THROUGHPUT EXTRACTION; IN-HOUSE DUST;
POLYCHLORINATED-BIPHENYLS; BREAST-MILK; 2,2',4,4',5-PENTABROMODIPHENYL
ETHER; DEVELOPMENTAL EXPOSURE; ADIPOSE-TISSUE; CLEANUP METHOD; BLOOD
AB We and others have previously described partitioning of chemicals, including polychlorinated-p-dioxins, dibenzofurans, and biphenyls in different types of human tissues and fluids, including blood and milk. Additionally, we previously reported the blood to milk partitioning of polybrominated diphenyl ethers (PBDEs) in a group of 11 women. Partitioning is of importance in understanding the toxicokinetics of these compounds and also in clinical medicine in improving estimates of levels in different matrices including blood and milk. In this study we extend these findings, describing the levels of PBDEs detected in the serum and milk of 29 women from Texas. The median sum of the levels of the four most detected congeners (BDE 47, 99, 100, and 153) in serum was 27.8 ng g(-1) lipid (range 6.7-501.6 ng g(-1) lipid). In milk, the median sum of the levels of the same congeners was 39.7 ng g(-1) lipid (range 12.9-580.3 ng g(-1) lipid). The levels detected in breast milk in this study are similar to those we reported in 2003, where a median total PBDE level of 34 ng g-1 lipid was reported. When congener specific blood to milk partitioning ratios were calculated for BDEs 47, 99, 100, and 153, the relatively small tetrabrominated congener, BDE 47, was found in higher concentrations in milk compared to blood, while the higher molecular weight hexabrominated congener, BIDE 153, was found in approximately equal quantities in blood and milk, on a lipid normalized basis. The reason for the differential partitioning of PBDE congeners in milk and blood could be due to variation in toxicokinetics, specifically distribution based on molecular size or molecular weight. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Schecter, Arnold] Univ Texas Dallas, Sch Publ Hlth, Dallas, TX 75390 USA.
[Colacino, Justin] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Sjodin, Andreas; Needham, Larry] Ctr Dis Control & Prevent, Atlanta, CA USA.
[Birnbaum, Linda] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Schecter, A (reprint author), Univ Texas Dallas, Sch Publ Hlth, 5323 Harry Hines,V8-112, Dallas, TX 75390 USA.
EM arnold.schecter@utsouthwestern.edu
RI Sjodin, Andreas/F-2464-2010; Needham, Larry/E-4930-2011
NR 35
TC 48
Z9 54
U1 3
U2 21
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0045-6535
J9 CHEMOSPHERE
JI Chemosphere
PD MAR
PY 2010
VL 78
IS 10
BP 1279
EP 1284
DI 10.1016/j.chemosphere.2009.12.016
PG 6
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA 571RN
UT WOS:000275772600014
PM 20079522
ER
PT J
AU Colombo, RE
Hill, SC
Claypool, RJ
Holland, SM
Olivier, KN
AF Colombo, Rhonda E.
Hill, Suvimol C.
Claypool, Reginald J.
Holland, Steven M.
Olivier, Kenneth N.
TI Familial Clustering of Pulmonary Nontuberculous Mycobacterial Disease
SO CHEST
LA English
DT Article
ID AVIUM COMPLEX; INFECTION; DISORDERS
AB Background: Nontuberculous mycobacteria (NTM) are environmental organisms associated with pulmonary disease without person-to-person transmission. Although genetic causes of disseminated NTM infection are well characterized, genetic causes for most human susceptibility to pulmonary NTM infection have not been determined.
Methods: Family histories for relevant disease characteristics were obtained as part of an ongoing natural history study. Six families were identified in which at least two blood relatives had pulmonary NTM. A systematic review of medical records extracted data relevant to pulmonary infection and baseline demographics. Data were reconfirmed by telephone interviews.
Results: Familial clustering of pulmonary NTM was proven in six families. Four of the families were white, and the majority of affected individuals were women. The average age at diagnosis was 56.4 +/- 10.7 years, the average height was 167.5 +/- 8.7 cm, and the mean BMI was 22.0 +/- 2.98 kg/m(2). Scoliosis was present in 31%. Five of 12 patients bad cystic fibrosis transmembrane conductance regulator gene variations, but none had classic cystic fibrosis. Infections were caused by both slow and rapid growing mycobacteria, including Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium kansasii, Mycobacterium abscessus, and Mycobacterium massiliense. Family members were typically infected with different species of NTM.
Conclusion: We identified six familial clusters of pulmonary NTM infection, suggesting that there are genetic factors contributing to host susceptibility to pulmonary infection with NTM among some individuals with nodular bronchiectatic disease. CHEST 2010; 137(3):629-634
C1 [Colombo, Rhonda E.; Claypool, Reginald J.; Holland, Steven M.; Olivier, Kenneth N.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Hill, Suvimol C.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
RP Olivier, KN (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike,Bldg 10,Room 11N234, Bethesda, MD 20892 USA.
EM olivierk@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 11
TC 26
Z9 26
U1 0
U2 0
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD MAR
PY 2010
VL 137
IS 3
BP 629
EP 634
DI 10.1378/chest.09-1173
PG 6
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 567WC
UT WOS:000275477100020
PM 19858235
ER
PT J
AU Ryall, JG
Church, JE
Lynch, GS
AF Ryall, James G.
Church, Jarrod E.
Lynch, Gordon S.
TI Novel role for beta-adrenergic signalling in skeletal muscle growth,
development and regeneration
SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
LA English
DT Article
DE beta-adrenergic signalling; beta-adrenoceptor agonists; cancer cachexia;
differentiation; muscle damage; muscle injury and repair; muscle
regeneration; muscular dystrophy; myogenesis; sarcopenia
ID FOXO TRANSCRIPTION FACTORS; MAMMALIAN TARGET; GENE-EXPRESSION;
MESSENGER-RNA; BETA-2-ADRENERGIC RECEPTOR; FUNCTIONAL REPAIR; C2C12
MYOGENESIS; ATROPHY INVOLVE; CLENBUTEROL; RAPAMYCIN
AB P>1. In adult mammals, skeletal muscle mass is maintained through a precise balance of protein synthesis and protein degradation, whereas during development cellular (not protein) turnover predominates. When protein balance is shifted towards synthesis, skeletal muscle hypertrophy ensues. In contrast, increased protein degradation leads to skeletal muscle atrophy. Insulin-like growth factor (IGF)-I is among the best documented of the growth factors and regulates skeletal muscle mass by increasing protein synthesis and decreasing protein degradation. However, an IGF-I-independent growth pathway has been identified that involves the activation of beta-adrenoceptors and subsequent skeletal muscle growth, development and hypertrophy.
2. Although the importance of beta-adrenergic signalling in the heart has been well documented and continues to receive significant attention, it is only more recently that we have started to appreciate the importance of this signalling pathway in skeletal muscle structure and function. Studies have identified an important role for beta-adrenoceptors in myogenesis and work from our laboratory has identified a novel role for beta-adrenoceptors in regulating skeletal muscle regeneration after myotoxic injury. In addition, new data suggest that beta-adrenoceptors are markedly upregulated during differentiation of C2C12 cells.
3. It is now clear that beta-adrenoceptors play an important role in regulating skeletal muscle structure and function. Importantly, a clearer understanding of the pathways regulating skeletal muscle mass may lead to the identification of novel therapeutic targets for the treatment of muscle wasting disorders, including sarcopenia, cancer cachexia and the muscular dystrophies.
C1 [Ryall, James G.; Church, Jarrod E.; Lynch, Gordon S.] Univ Melbourne, Dept Physiol, Basic & Clin Myol Lab, Parkville, Vic 3052, Australia.
[Ryall, James G.] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
RP Lynch, GS (reprint author), Univ Melbourne, Dept Physiol, Melbourne, Vic 3010, Australia.
EM gsl@unimelb.edu.au
RI Lynch, Gordon/G-9553-2015
OI Lynch, Gordon/0000-0001-9220-9810
FU Australian Research Council [DP0665071, DP0772781]; National Health and
Medical Research Council of Australia (NHMRC) [454561, 509313, 520034];
Muscular Dystrophy Association (Tucson, AZ, USA) [4167]; Pfizer Inc.
FX The authors are grateful for research grant funding from the Australian
Research Council Discovery-Project funding scheme (DP0665071,
DP0772781), the National Health and Medical Research Council of
Australia (NHMRC; 454561, 509313), the Muscular Dystrophy Association
(Tucson, AZ, USA; 4167) and Pfizer Inc. (New York, NY, USA). JGR is
supported by a Biomedical Overseas Research Fellowship from the NHMRC
(520034).
NR 48
TC 13
Z9 13
U1 0
U2 11
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0305-1870
J9 CLIN EXP PHARMACOL P
JI Clin. Exp. Pharmacol. Physiol.
PD MAR
PY 2010
VL 37
IS 3
BP 397
EP 401
DI 10.1111/j.1440-1681.2009.05312.x
PG 5
WC Pharmacology & Pharmacy; Physiology
SC Pharmacology & Pharmacy; Physiology
GA 560MY
UT WOS:000274908000024
PM 19793099
ER
PT J
AU Wells, DK
Ward, MM
AF Wells, D. K.
Ward, M. M.
TI Nephritis and the risk of acute myocardial infarction in patients with
systemic lupus erythematosus
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Article
DE Systemic lupus erythematosus; myocardial infarction; cardiovascular
disease; lupus nephritis
ID PRIMARY ANTIPHOSPHOLIPID SYNDROME; CORONARY-ARTERY CALCIFICATION;
CARDIOVASCULAR-DISEASE; VASCULAR EVENTS; ACCELERATED ATHEROSCLEROSIS;
VENOUS THROMBOEMBOLISM; RHEUMATOID-ARTHRITIS; HEART-DISEASE; COHORT;
WOMEN
AB Background
Patients with systemic lupus erythematosus (SLE) have an increased risk of acute myocardial infarction (AMI). We examined if nephritis or other clinical manifestations of SLE identified patients at increased risk.
Methods
In this population-based case-control study, we identified patients with SLE hospitalized with an AMI in California in 1996-2000. We compared the frequency of six manifestations of SLE (nephritis, pleuritis, hemolytic anemia, thrombocytopenia, psychosis/major depression, seizures) and of venous thrombosis/pulmonary embolism, in this group (n=535) to the frequency of these manifestations in two control groups: patients with SLE hospitalised for pulmonary disease (n=529), and patients with SLE hospitalized for gastrointestinal bleeding (n=349).
Results
Nephritis was present in 23.7% of patients with AMI, 11.0% of patients with pulmonary disease and 25.2% of patients with gastrointestinal bleeding. In adjusted analyses, nephritis was more common in the AMI group (odds ratio (OR) 2.85, 95% confidence interval (CI) 1.97-4.14; p<.0001) than in the pulmonary disease control group. Among women, nephritis was more common in the AMI group (OR 2.83; 95% CI 1.33-6.01; p=0.007) than in the gastrointestinal bleeding control group. Psychosis/major depression was less common among patients with AMI.
Conclusions
Among patients with SLE, nephritis was associated with 2.8-fold increased risk of AMI.
C1 [Wells, D. K.; Ward, M. M.] NIAMSD, Intramural Res Program, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), NIAMS, NIH, IRP, Bldg 10 CRC,Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health.
NR 49
TC 8
Z9 12
U1 0
U2 0
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD MAR-APR
PY 2010
VL 28
IS 2
BP 223
EP 229
PG 7
WC Rheumatology
SC Rheumatology
GA 604UL
UT WOS:000278303900010
PM 20483044
ER
PT J
AU Huang, H
Menefee, M
Edgerly, M
Zhuang, S
Kotz, H
Poruchynsky, M
Huff, LM
Bates, S
Fojo, T
AF Huang, Hui
Menefee, Michael
Edgerly, Maureen
Zhuang, Sen
Kotz, Herb
Poruchynsky, Marianne
Huff, Lyn Mickley
Bates, Susan
Fojo, Tito
TI A Phase II Clinical Trial of Ixabepilone (Ixempra; BMS-247550; NSC
710428), an Epothilone B Analog, in Patients with Metastatic Renal Cell
Carcinoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MICROTUBULE-STABILIZING AGENTS; PREVIOUSLY TREATED PATIENTS; HIGH-DOSE
INTERLEUKIN-2; HUMAN TUMOR XENOGRAFTS; BREAST-CANCER; INTERFERON
ALPHA-2A; DESOXYEPOTHILONE-B; 96-HOUR PACLITAXEL; UNITED-STATES; THERAPY
AB Purpose: Ixabepilone (Ixempra; BMS-247550) is an epothilone B analog and nontaxane microtubule-stabilizing compound with clinical activity in a range of solid tumors. This phase II study was conducted to assess the efficacy and safety of ixabepilone in patients with metastatic renal cell carcinoma.
Experimental Design: Patients with metastatic renal cell carcinoma who had measurable disease and had not received previous cytotoxic or targeted therapy were treated with 6 mg/m(2) ixabepilone i.v. daily for 5 days every 3 weeks. Levels of Glu-terminated and acetylated tubulin, markers of microtubule stabilization, were assessed by Western blot. VHL gene mutation status was determined by sequencing.
Results: Eighty-seven patients received a total of 590 cycles, with a median of 5 cycles (range, 1-29). The overall response rate was 13% (Response Evaluation Criteria in Solid Tumor). One patient had a complete response, 10 patients had partial responses, and 59 patients had stable disease. The median duration of response was 5.5 months. The median overall survival of renal cell carcinoma Motzer grade 0 and 1 patients with clear cell histology was 19.25 months. Treatment-related adverse events were primarily alopecia, gastrointestinal toxicity, neuropathy, and fatigue. Biopsies were done at baseline and after five doses of ixabepilone. Microtubule target engagement was achieved in 84.6% to 92.3% of patients evaluated. No correlation was identified between the target engagement, VHL gene mutation status, and clinical response.
Conclusion: Ixabepilone can cause tumor regression in some patients with metastatic renal cell carcinoma and could be considered in combination regimens with other therapies. Clin Cancer Res; 16(5); 1634-41. (C) 2010 AACR.
C1 [Huang, Hui; Menefee, Michael; Edgerly, Maureen; Zhuang, Sen; Kotz, Herb; Poruchynsky, Marianne; Huff, Lyn Mickley; Bates, Susan; Fojo, Tito] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Huang, Hui] N Calif Kaiser Permanente, Dept Hematol & Oncol, Vallejo, CA USA.
RP Fojo, T (reprint author), NCI, Med Oncol Branch, NIH, Bldg 10,Room 12N226,900 Rockville Pike, Bethesda, MD 20892 USA.
EM tfojo@helix.nih.gov
NR 43
TC 25
Z9 25
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 1
PY 2010
VL 16
IS 5
BP 1634
EP 1641
DI 10.1158/1078-0432.CCR-09-0379
PG 8
WC Oncology
SC Oncology
GA 607ZJ
UT WOS:000278545500031
PM 20179242
ER
PT J
AU Robinson, ES
Matulonis, UA
Ivy, P
Berlin, ST
Tyburski, K
Penson, RT
Humphreys, BD
AF Robinson, Emily S.
Matulonis, Ursula A.
Ivy, Percy
Berlin, Suzanne T.
Tyburski, Karin
Penson, Richard T.
Humphreys, Benjamin D.
TI Rapid Development of Hypertension and Proteinuria with Cediranib, an
Oral Vascular Endothelial Growth Factor Receptor Inhibitor
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; BLOOD-PRESSURE; ANGIOGENESIS INHIBITOR;
BREAST-CANCER; BEVACIZUMAB; TRIAL; EXPRESSION; PACLITAXEL; REGRESSION;
SORAFENIB
AB Background and objectives: Hypertension and proteinuria are common but poorly understood renal toxicities of vascular endothelial growth factor (VEGF) receptor signaling pathway inhibitors. In this phase II study of cediranib (AZD2171) for recurrent epithelial ovarian cancer, the time course and severity of BP changes and proteinuria were characterized.
Design, setting, participants, & measurements: 46 women ages 41 to 77 years were treated with cediranib. 26% had baseline hypertension. Twice-daily BP was recorded. Urinalyses were performed every 2 weeks, and in some patients proteinuria was further quantified.
Results: 31 women (67%) developed hypertension by day 3; 87% by the end of the study. 43%, developed grade >= 3 hypertension. Mean systolic BP increase over 3 days was 18 mmHg. Women above the mean age (>= 57 years) had a larger rise in systolic BP by day 3 (15.9 versus 7.0 mmHg). 14 women developed proteinuria. There was a dose response (45 versus 30 mg daily). Proteinuria also developed rapidly, with 7 of 14 women developing proteinuria within 2 weeks. Only 7 of 20 women who developed grade 3 hypertension developed proteinuria.
Conclusions: Cediranib induced a rapid but variable rise in BP within 3 days of initiation in most patients. Proteinuria was common and also developed rapidly. The rapid development of hypertension suggests that acute inhibition of VEGF-dependent vasodilation might explain the BP rise with VEGF inhibitors. Clinicians must be vigilant in early detection and management of toxicities of this expanding drug class, especially in older patients. Clin J Am Soc Nephrol 5: 477-483, 2010. doi: 10.2215/CJN.08111109
C1 [Robinson, Emily S.; Humphreys, Benjamin D.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA.
[Matulonis, Ursula A.; Berlin, Suzanne T.; Tyburski, Karin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Humphreys, Benjamin D.] Dana Farber Canc Inst, Adult Survivorship Program, Boston, MA 02115 USA.
[Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Penson, Richard T.] Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA.
RP Robinson, ES (reprint author), Channing Labs, 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA.
EM Erobinson11@partners.org; bhumphreys@partners.org
FU National Kidney Foundation; Madeline Franchi Ovarian Cancer Fund;
Ovations for the Cure; National Institutes of Health [DK073628, UL1 RR
025758-02]
FX Support for this research was provided by a National Kidney Foundation
Fellowship Grant (to E.S.R.), The Madeline Franchi Ovarian Cancer Fund,
Ovations for the Cure, National Institutes of Health grant DK073628 (to
B.D.H.), and a pilot grant from Harvard Catalyst: National Institutes of
Health grant UL1 RR 025758-02 with financial contributions from
participating institutions (to B.D.H.).
NR 34
TC 36
Z9 38
U1 0
U2 1
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD MAR
PY 2010
VL 5
IS 3
BP 477
EP 483
DI 10.2215/CJN.08111109
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 565WB
UT WOS:000275325000014
PM 20056761
ER
PT J
AU Voermans, NC
Guillard, M
Doedee, R
Lammens, M
Huizing, M
Padberg, GW
Wevers, RA
van Engelen, BG
Lefeber, DJ
AF Voermans, N. C.
Guillard, M.
Doedee, R.
Lammens, M.
Huizing, M.
Padberg, G. W.
Wevers, R. A.
van Engelen, B. G.
Lefeber, D. J.
TI Clinical features, lectin staining, and a novel GNE frameshift mutation
in hereditary inclusion body myopathy
SO CLINICAL NEUROPATHOLOGY
LA English
DT Article
DE Hereditary Inclusion Body Myopathy; HIBM; distal myopathy; muscular
dystrophy; sialic acid; UDP-GlcNAc 2-epimerase/ManNAc kinase;
hyposialylation; PNA lectin; glycosylation
ID ACETYLGLUCOSAMINE 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; O-GLYCAN
BIOSYNTHESIS; DISTAL MYOPATHY; RIMMED VACUOLES; N-ACETYLMANNOSAMINE;
ACID BIOSYNTHESIS; RAT-LIVER; HYPOSIALYLATION; GLYCOPROTEINS;
PURIFICATION
AB We present a comprehensive report of two siblings with hereditary inclusion body myopathy (HIBM). The clinical features and histological characteristics of the muscle biopsies showed the typical pattern of predominantly distal vacuolar myopathy with quadriceps sparing. This was confirmed by muscle MRI. PNA lectin staining showed an increased signal at the sarcolemma in patient muscle sections compared to control muscle, indicating reduced sialylation of glycoconjugates. Mutation analysis revealed compound heterozygous mutations in the GNE gene, encoding the key enzyme in sialic acid synthesis UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase: a missense mutation (c.2086G > A; p.V696M) previously described in HIBM patients of Indian origin, and a novel frame shift mutation (c.1295delA; p.K432RfsX17) leading to a premature stopcodon. These findings confirmed the diagnosis of HIBM on the histological, molecular and biochemical level.
C1 [Voermans, N. C.; Lammens, M.; Padberg, G. W.; Wevers, R. A.; van Engelen, B. G.; Lefeber, D. J.] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands.
[Guillard, M.; Doedee, R.; Wevers, R. A.; Lefeber, D. J.] Radboud Univ Nijmegen, Med Ctr, Lab Pediat & Neurol, NL-6500 HB Nijmegen, Netherlands.
[Lammens, M.] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6500 HB Nijmegen, Netherlands.
[Huizing, M.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Voermans, NC (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Neurol, Donders Inst Brain Cognit & Behav, POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM n.voermans@neuro.umcn.nl
RI van Engelen, Baziel/D-3475-2009; lefeber, dirk/G-5063-2012; Engelen,
B.G.M./H-8027-2014; Padberg, G.W.A.M./H-8079-2014; Lefeber,
Dirk/A-2146-2014; Wevers, Ron/H-8116-2014; Voermans, N.C./L-4724-2015
OI Wevers, Ron/0000-0003-2278-9746;
FU National Human Genome Research Institute, National Institutes of Health,
Bethesda, MD, USA; NWO, The Netherlands Organization for Scientific
Research, The Netherlands
FX We are grateful to Mrs. K. Verrijp for her assistance in the staining
procedures of muscle biopsies. This work was partially supported by the
Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health, Bethesda, MD, USA (M. Huizing)
and by the NWO, The Netherlands Organization for Scientific Research,
The Netherlands (N.C. Voermans).
NR 21
TC 7
Z9 7
U1 0
U2 2
PU DUSTRI-VERLAG DR KARL FEISTLE
PI DEISENHOFEN-MUENCHEN
PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY
SN 0722-5091
J9 CLIN NEUROPATHOL
JI Clin. Neuropathol.
PD MAR-APR
PY 2010
VL 29
IS 2
BP 71
EP 77
PG 7
WC Clinical Neurology; Pathology
SC Neurosciences & Neurology; Pathology
GA 572QX
UT WOS:000275849000003
PM 20175955
ER
PT J
AU Jin, SH
Lin, P
Hallett, M
AF Jin, Seung-Hyun
Lin, Peter
Hallett, Mark
TI Linear and nonlinear information flow based on time-delayed mutual
information method and its application to corticomuscular interaction
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Linear and nonlinear information flow; Time-delayed mutual information;
Surrogate tests; Corticomuscular interaction; Model-free connectivity
measure
ID SCIENTIFIC HYPOTHESIS GENERATION; MOTOR CORTEX; STATISTICAL ASSESSMENT;
FINGER MOVEMENTS; CEREBRAL-CORTEX; SURROGATE DATA; HUMAN BRAIN; EEG;
TASK; COHERENCE
AB Objective: To propose a model-free method to show linear and nonlinear information flow based on time-delayed mutual information (TDMI) by employing uni- and bi-variate surrogate tests and to investigate whether there are contributions of the nonlinear information flow in corticomuscular (CM) interaction.
Methods: Using simulated data, we tested whether our method would successfully detect the direction of information flow and identify a relationship between two simulated time series. As an experimental data application, we applied this method to investigate CM interaction during a right wrist extension task.
Results: Results of simulation tests show that we can correctly detect the direction of information flow and the relationship between two time series without a prior knowledge of the dynamics of their generating systems. As experimental results, we found both linear and nonlinear information flow from contralateral sensorimotor cortex to muscle.
Conclusions: Our method is a viable model-free measure of temporally varying causal interactions that is capable of distinguishing linear and nonlinear information flow. With respect to experimental application, there are both linear and nonlinear information flows in CM interaction from contralateral sensorimotor cortex to muscle, which may reflect the motor command from brain to muscle.
Significance: This is the first study to show separate linear and nonlinear information flow in CM interaction. (C) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Jin, Seung-Hyun; Lin, Peter; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Jin, SH (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 7D37,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA.
EM jinse@mail.nih.gov
FU NINDS, NIH; Korean Government (MOEHRD) [KRF-2006-352-H00006]
FX This research was supported in part by the Intramural Research program
of the NINDS, NIH. S. H. Jin was supported by a Korea Research
Foundation Grant funded by the Korean Government (MOEHRD)
(KRF-2006-352-H00006). The authors thank Dr. Ou Bai for use of his
MATLAB scripts (http://www.engineering.vcu.edu/eegbci/bci2vr_index.html)
for preprocessing of our EEG and sEMG data.
NR 76
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Z9 26
U1 1
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
EI 1872-8952
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD MAR
PY 2010
VL 121
IS 3
BP 392
EP 401
DI 10.1016/j.clinph.2009.09.033
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 556AE
UT WOS:000274557800020
PM 20044309
ER
PT J
AU Leung, E
Tasker, SL
Atkinson, L
Vaillancourt, T
Schulkin, J
Schmidt, LA
AF Leung, Eman
Tasker, Susan L.
Atkinson, Leslie
Vaillancourt, Tracy
Schulkin, Jay
Schmidt, Louis A.
TI Perceived Maternal Stress During Pregnancy and Its Relation to Infant
Stress Reactivity at 2 Days and 10 Months of Postnatal Life
SO CLINICAL PEDIATRICS
LA English
DT Article
DE stress reactivity; newborns; maternal stress; pregnancy; cortisol; HPA
functioning
ID PITUITARY-ADRENAL AXIS; PRENATAL STRESS; CORTISOL; BEHAVIOR; CHILDREN;
ANXIETY; HEALTH; BRAIN; BIRTH; RATS
AB Background. Although the negative impact of maternal stress during pregnancy on stress reactivity in offspring is well documented in nonhuman animals, we know little about these relations in humans and their lasting effects. Aim. The authors examined the relation between perceived maternal stress during pregnancy and stability of infant stress reactivity across the first year of postnatal life in humans. Study design. Perceived maternal stress during pregnancy was measured in the immediate postpartum period and again at 10 months after delivery in 84 mothers and examined in relation to behavioral and neuroendocrine stress reactivity measures in their healthy, full-term infants. Outcome measures. Salivary cortisol was collected between 24 to 48 hours of postnatal life in response to a heel stick and again at 10 months of age in response to a toy removal task in the same sample of infants. Behavioral reactivity was coded from direct observation during the toy removal task. Results . Perceived maternal stress during pregnancy and neonatal cortisol reactivity each remained stable across the first 10 months of postnatal life. Maternal stress during pregnancy predicted infant cortisol reactivity at 2 days and 10 months after birth as well as behavioral reactivity at 10 months. Neonatal cortisol reactivity predicted 10-month behavioral reactivity. Conclusion . These preliminary findings suggest that maternal stress during pregnancy may negatively affect neonatal stress reactivity within 24 to 48 hours after birth, and these influences may persist through the first year of postnatal life.
C1 [Schmidt, Louis A.] McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON L8S 4K1, Canada.
[Leung, Eman; Atkinson, Leslie] Univ Toronto, Toronto, ON, Canada.
[Leung, Eman; Atkinson, Leslie] Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Tasker, Susan L.] Univ Victoria, Victoria, BC, Canada.
[Atkinson, Leslie] Ryerson Univ, Toronto, ON, Canada.
[Vaillancourt, Tracy] Univ Ottawa, Ottawa, ON, Canada.
[Schulkin, Jay] Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA.
[Schulkin, Jay] NIMH, NIH, Bethesda, MD 20892 USA.
[Schulkin, Jay] Georgetown Univ, Sch Med, Washington, DC USA.
RP Schmidt, LA (reprint author), McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON L8S 4K1, Canada.
EM schmidtl@mcmaster.ca
RI Vaillancourt, Tracy/F-8949-2015;
OI LEUNG, Eman/0000-0002-8267-1785; Atkinson, Leslie/0000-0003-1265-3298
FU Natural Sciences and Engineering Research Council (NSERC) of Canada
FX This research was funded by a grant from the Natural Sciences and
Engineering Research Council (NSERC) of Canada awarded to Louis A.
Schmidt.
NR 36
TC 10
Z9 10
U1 3
U2 12
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0009-9228
J9 CLIN PEDIATR
JI Clin. Pediatr.
PD MAR
PY 2010
VL 49
IS 2
BP 158
EP 165
DI 10.1177/0009922809346570
PG 8
WC Pediatrics
SC Pediatrics
GA 544SD
UT WOS:000273678700009
PM 20080522
ER
PT J
AU LaSala, PR
Holbrook, M
AF LaSala, P. Rocco
Holbrook, Michael
TI Tick-Borne Flaviviruses
SO CLINICS IN LABORATORY MEDICINE
LA English
DT Article
DE Flavivirus; Vector; Host; Tick-borne; Encephalitis
ID HEMORRHAGIC-FEVER VIRUS; NEUTRALIZATION TESTS; SAUDI-ARABIA; LOUPING
ILL; ENCEPHALITIS; INFECTION; DISEASE; MRI; TRANSMISSION; VACCINATION
AB There has been a remarkable increase in tick-borne flaviviral disease incidence throughout the past 2 decades. Transmission of tick-borne viruses, like other vector-borne agents, is impacted by a very broad set of factors, both natural (eg, climate and ecology) and man-made (eg, human mobility and agricultural patterns). As our encroachment into areas of virus endemicity intensifies, and as changes in global economic and environmental conditions continue to promote the expansion of tick populations, we will undoubtedly continue to observe attendant increases in rates of disease attributable to these vector-borne pathogens. This article focuses on a some of the major tick-borne flaviviral diseases, caused in particular by tick-borne encephalitis virus, louping ill virus, Powassan virus, Kyasanur Forest disease virus, and Omsk hemorrhagic fever virus, as well as their subtypes.
C1 [LaSala, P. Rocco] W Virginia Univ, Dept Pathol, Clin Microbiol Lab, Morgantown, WV 26506 USA.
[Holbrook, Michael] Univ Texas Med Branch, Dept Pathol, Robert Shope Lab BSL 4, Galveston, TX 77555 USA.
[Holbrook, Michael] NIAID, Integrated Res Facil, Frederick, MD 21702 USA.
RP LaSala, PR (reprint author), W Virginia Univ, Dept Pathol, Clin Microbiol Lab, 2190 Hlth Sci N,POB 9203, Morgantown, WV 26506 USA.
EM plasala@hsc.wvu.edu
NR 36
TC 13
Z9 13
U1 3
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 0272-2712
J9 CLIN LAB MED
JI Clin. Lab. Med.
PD MAR
PY 2010
VL 30
IS 1
BP 221
EP +
DI 10.1016/j.cll.2010.01.002
PG 16
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 618MA
UT WOS:000279358200011
PM 20513549
ER
PT J
AU Maheu, FS
Dozier, M
Guyer, AE
Mandell, D
Peloso, E
Poeth, K
Jenness, J
Lau, JYF
Ackerman, JP
Pine, DS
Ernst, M
AF Maheu, Francoise S.
Dozier, Mary
Guyer, Amanda E.
Mandell, Darcy
Peloso, Elizabeth
Poeth, Kaitlin
Jenness, Jessica
Lau, Jennifer Y. F.
Ackerman, John P.
Pine, Daniel S.
Ernst, Monique
TI A preliminary study of medial temporal lobe function in youths with a
history of caregiver deprivation and emotional neglect
SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; GENERALIZED
ANXIETY DISORDER; EARLY INSTITUTIONAL DEPRIVATION; PREFRONTAL CORTEX
ACTIVATION; MAJOR DEPRESSIVE DISORDER; MALTREATED CHILDREN; FACIAL
EXPRESSIONS; FOSTER-CARE; DEVELOPMENTAL EXAMINATION
AB Previous research findings have linked caregiver deprivation and emotional neglect with sensitivity to threatening cues. The present preliminary study investigated whether dysfunctions of the medial temporal lobe could underlie these associations. Using fMRI, we measured medial temporal lobe responses to emotional faces (angry, fearful, happy, neutral) among 30 youths. Eleven of the youths had a history of caregiver deprivation and emotional neglect. Attention states (i.e., attention to anger, fear, or physical attributes, or passive viewing) were systematically manipulated. Relative to comparison youths, youths with a history of caregiver deprivation and emotional neglect showed significantly greater left amygdala and left anterior hippocampus activation during the processing of threatening information. To our knowledge, these findings are the first to demonstrate altered medial temporal lobe function during the processing of threat cues in youths with a history of caregiver deprivation and emotional neglect.
C1 [Maheu, Francoise S.] CHU Ste Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada.
[Maheu, Francoise S.] Univ Montreal, Dept Psychiat, Fac Med, Montreal, PQ H3T 1C5, Canada.
[Dozier, Mary; Peloso, Elizabeth] Univ Delaware, Newark, DE USA.
[Guyer, Amanda E.; Mandell, Darcy; Poeth, Kaitlin; Jenness, Jessica; Pine, Daniel S.; Ernst, Monique] NIMH, Bethesda, MD 20892 USA.
[Lau, Jennifer Y. F.] Univ Oxford, Oxford, England.
[Ackerman, John P.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
RP Maheu, FS (reprint author), CHU Ste Justine, Res Ctr, 3175 Cote Ste Catherine, Montreal, PQ H3T 1C5, Canada.
EM francoise.maheu@umontreal.ca
FU National Alliance for Research on Schizophrenia and Depression Young
Investigator; Fonds de la Recherche en Sante du Quebec; Edna Bennett
Pierce; NIMH [52135, 74374]
FX The present study was supported by a National Alliance for Research on
Schizophrenia and Depression Young Investigator Award and a postdoctoral
fellowship from the Fonds de la Recherche en Sante du Quebec to F.S.M.,
by funding from Edna Bennett Pierce, by NIMH Grants 52135 and 74374 to
M.D., and by the NIMH Intramural Research Program. The authors thank the
anonymous reviewers for their helpful comments in revising the
manuscript. Address correspondence to F.S. Maheu, Research Centre, CHU
Ste-Justine and Psychiatry Department, Faculty of Medicine, University
of Montreal, 3175 Cote-Ste-Catherine, Montreal, QC, H3T 1C5 Canada
(e-mail: francoise.maheu@umontreal.ca).
NR 101
TC 70
Z9 70
U1 13
U2 25
PU PSYCHONOMIC SOC INC
PI AUSTIN
PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA
SN 1530-7026
J9 COGN AFFECT BEHAV NE
JI Cogn. Affect. Behav. Neurosci.
PD MAR
PY 2010
VL 10
IS 1
SI SI
BP 34
EP 49
DI 10.3758/CABN.10.1.34
PG 16
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 653DF
UT WOS:000282066600004
PM 20233954
ER
PT J
AU Robles, AI
Harris, CC
AF Robles, Ana I.
Harris, Curtis C.
TI Clinical Outcomes and Correlates of TP53 Mutations and Cancer
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID P53 TUMOR-SUPPRESSOR; CELL LUNG-CANCER; HEPATOCELLULAR-CARCINOMA
PATIENTS; CHRONIC LYMPHOCYTIC-LEUKEMIA; COMMON GENETIC-VARIATION; CODON
72 POLYMORPHISM; LI-FRAUMENI-SYNDROME; BREAST-CANCER; COLORECTAL-CANCER;
PLASMA DNA
AB The initial observation that p53 accumulation might serve as a surrogate biomarker for TP53 mutation has been the cornerstone for vast translational efforts aimed at validating its clinical use for the diagnosis, prognosis, and treatment of cancer. Early on, it was realized that accurate evaluation of p53 status and function could not be achieved through protein-expression analysis only. As our understanding of the p53 pathway has evolved and more sophisticated methods for assessment of p53 functional integrity have become available, the clinical and molecular epidemiological implications of p53 abnormalities in cancers are being revealed. They include diagnostic testing for germline p53 mutations, and the assessment of selected p53 mutations as biomarkers of carcinogen exposure and cancer risk and prognosis. Here, we describe the strengths and limitations of the most frequently used techniques for determination of p53 status in tumors, as well as the most remarkable latest findings relating to its clinical and epidemiological value.
C1 [Robles, Ana I.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM harrisc@mail.nih.gov
RI Xie, Huangming/B-2260-2012
NR 103
TC 76
Z9 78
U1 0
U2 10
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD MAR
PY 2010
VL 2
IS 3
AR a001016
DI 10.1101/cshperspect.a001016
PG 15
WC Cell Biology
SC Cell Biology
GA 625GA
UT WOS:000279881700005
PM 20300207
ER
PT J
AU Erickson, HS
Gannot, G
Tangrea, MA
Chuaqui, RF
Gillespie, JW
Emmert-Buck, MR
AF Erickson, Heidi S.
Gannot, Gallya
Tangrea, Michael A.
Chuaqui, Rodrigo F.
Gillespie, John W.
Emmert-Buck, Michael R.
TI High Throughput Screening of Normal and Neoplastic Tissue Samples
SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
LA English
DT Article
DE Tissue; microdissection; high throughput screening; biomarker discovery;
biomarker validation; technologies; review
ID HUMAN PROSTATE-CANCER; LASER-CAPTURE MICRODISSECTION; POLYMERASE
CHAIN-REACTION; COMPARATIVE GENOMIC HYBRIDIZATION; NUCLEOTIDE
POLYMORPHISM ARRAYS; PHASE PROTEIN MICROARRAYS; PARAFFIN-EMBEDDED
TISSUES; GENE-EXPRESSION ANALYSIS; HIGH-RESOLUTION ANALYSIS;
MASS-SPECTROMETRY
AB The capacity to rapidly and efficiently elucidate a reliable set of disease specific biomarkers is paramount to enable a future of personalized medicine. High throughput screening methods applied to human clinical samples for the discovery of diagnostic, prognostic, and therapeutic targets address this need. Although the ability to analyze either thousands of markers from one sample or one marker from thousands of samples is the current state of high throughput screening, it would be ideal to have the ability to analyze thousands of markers from thousands of samples to expedite the early discovery phase of biomarkers and their validation. This review summarizes the current state of high throughput screening of tissue specimens and discusses its applications. In addition, the rationale, difficulties, strategies, and development of new technologies to address the need for improved high throughput capabilities are discussed.
C1 [Gillespie, John W.] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Erickson, Heidi S.; Gannot, Gallya; Tangrea, Michael A.; Chuaqui, Rodrigo F.; Emmert-Buck, Michael R.] NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Erickson, Heidi S.; Gannot, Gallya; Tangrea, Michael A.; Chuaqui, Rodrigo F.; Emmert-Buck, Michael R.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Erickson, Heidi S.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Thorac Mol Pathol Lab, Houston, TX 77030 USA.
[Tangrea, Michael A.] NCI, Tumor Angiogenesis Sect, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Gillespie, JW (reprint author), NCI, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM jgill1230@gmail.com
FU NIH; National Cancer Institute; Center for Cancer Research
FX This review was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 144
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U1 0
U2 0
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1386-2073
J9 COMB CHEM HIGH T SCR
JI Comb. Chem. High Throughput Screen
PD MAR
PY 2010
VL 13
IS 3
BP 253
EP 267
PG 15
WC Biochemical Research Methods; Chemistry, Applied; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy
GA 568EO
UT WOS:000275505200004
PM 20015016
ER
PT J
AU Williams, RV
Ravishankar, C
Zak, V
Evans, F
Atz, AM
Border, WL
Levine, J
Li, JS
Mahony, L
Mital, S
Pearson, GD
Prakash, A
Hsu, DT
AF Williams, Richard V.
Ravishankar, Chitra
Zak, Victor
Evans, Frank
Atz, Andrew M.
Border, William L.
Levine, Jami
Li, Jennifer S.
Mahony, Lynn
Mital, Seema
Pearson, Gail D.
Prakash, Ashwin
Hsu, Daphne T.
CA Pediat Heart Network Investigators
TI Birth Weight and Prematurity in Infants with Single Ventricle
Physiology: Pediatric Heart Network Infant Single Ventricle Trial
Screened Population
SO CONGENITAL HEART DISEASE
LA English
DT Article
DE Single Ventricle Physiology; Preterm Birth; Low Birth Weight; Small for
Gestational Age
ID FOR-GESTATIONAL-AGE; CARDIOVASCULAR MALFORMATIONS; UNITED-STATES;
RISK-FACTORS; NORWOOD PROCEDURE; GROWTH; CHILDREN; PALLIATION;
MORTALITY; PATTERNS
AB Objectives. Although congenital heart disease is associated with low birth weight and prematurity, there is little information about these birth outcomes in infants with single ventricle physiology. We describe the birth outcomes (i.e., gestational age and birth weight) in neonates with single ventricle physiology screened for enrollment in the Pediatric Heart Network's Infant Single Ventricle Trial, compare these outcomes with US norms, and examine the association of birth outcomes with anatomic diagnosis and race.
Patients and Methods. All neonates with single ventricle physiology presenting to Infant Single Ventricle Trial centers were screened for enrollment. Demographic data and anatomic diagnoses were obtained from medical records.
Results. A total of 1245 neonates with single ventricle physiology were screened at 10 centers (63 to 266 per center). Diagnoses included hypoplastic left heart syndrome in 49%, unbalanced atrioventricular septal defect in 12%, and tricuspid atresia in 9%. Preterm birth occurred in 16% of neonates with single ventricle physiology vs. 12% in normal neonates (P < .001), low birth weight (< 2.5 kg) in 18% vs. 8% in normals (P < .001), and small for gestational age (< 10th percentile by definition) in 22% vs. 10% in normals (P < .001). A genetic syndrome was reported in 8%. The percentage of preterm birth, low birth weight, and small for gestational age was similar between screened neonates with and without hypoplastic left heart syndrome.
Conclusions. In this large, contemporary cohort of neonates with single ventricle physiology, rates of preterm birth, low birth weight, and small for gestational age were higher than in the general population, but similar between screened neonates with and without hypoplastic left heart syndrome.
C1 [Williams, Richard V.] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Ravishankar, Chitra] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Zak, Victor] New England Res Inst, Watertown, MA 02172 USA.
[Evans, Frank; Pearson, Gail D.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Atz, Andrew M.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA.
[Border, William L.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH USA.
[Levine, Jami] Childrens Hosp Boston, Dept Cardiol, Boston, MA USA.
[Li, Jennifer S.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Mahony, Lynn] Univ Texas SW, Dept Pediat, Dallas, TX USA.
[Mital, Seema] Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada.
[Prakash, Ashwin; Hsu, Daphne T.] Columbia Univ, Dept Pediat, New York, NY 10027 USA.
RP Williams, RV (reprint author), Primary Childrens Med Ctr, 100 Mario Capecchi Dr, Salt Lake City, UT 84113 USA.
EM richard.williams@imail.org
OI Hsu, Daphne/0000-0002-2654-0430
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068292, HL068290, HL068288, HL085057]; Food Drug
and Administration Office of Orphan Products Development
FX Supported by U01 grants from the National Heart, Lung, and Blood
Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292,
HL068290, HL068288, and HL085057) and from the Food Drug and
Administration Office of Orphan Products Development.
NR 26
TC 11
Z9 11
U1 0
U2 1
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1747-079X
J9 CONGENIT HEART DIS
JI Congenit. Heart Dis.
PD MAR-APR
PY 2010
VL 5
IS 2
BP 96
EP 103
DI 10.1111/j.1747-0803.2009.00369.x
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 748UG
UT WOS:000289417500003
PM 20412481
ER
PT J
AU Weiss, RD
Potter, JS
Provost, SE
Huang, Z
Jacobs, P
Hasson, A
Lindblad, R
Connery, HS
Prather, K
Ling, W
AF Weiss, Roger D.
Potter, Jennifer Sharpe
Provost, Scott E.
Huang, Zhen
Jacobs, Petra
Hasson, Albert
Lindblad, Robert
Connery, Hilary Smith
Prather, Kristi
Ling, Walter
TI A multi-site, two-phase, Prescription Opioid Addiction Treatment Study
(POATS): Rationale, design, and methodology
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Adaptive treatment research design; Buprenorphine; Opioid; Pain; Drug
abuse; Counseling
ID METHADONE-MAINTENANCE TREATMENT; PRIMARY-CARE; BUPRENORPHINE TREATMENT;
HEROIN DEPENDENCE; SUBSTANCE USE; PAIN; DETOXIFICATION; DEPRESSION;
USERS
AB The National Institute on Drug Abuse Clinical Trials Network launched the Prescription Opioid Addiction Treatment Study (POATS) in response to rising rates of prescription opioid dependence and gaps in understanding the optimal course of treatment for this population. POATS employed a multi-site, two-phase adaptive, sequential treatment design to approximate clinical practice. The study took place at 10 community treatment programs around the United States. Participants included men and women age >= 18 who met Diagnostic and Statistical Manual, 4th Edition criteria for dependence upon prescription opioids, with physiologic features; those with a prominent history of heroin use (according to pre-specified criteria) were excluded. All participants received buprenorphine/naloxone (bup/nx). Phase 1 consisted of 4 weeks of bup/nx treatment, including a 14-day dose taper, with 8 weeks of follow-up. Phase 1 participants were monitored for treatment response during these 12 weeks. Those who relapsed to opioid use, as defined by pre-specified criteria, were invited to enter Phase 2; Phase 2 consisted of 12 weeks of bup/nx stabilization treatment, followed by a 4-week taper and 8 weeks of post-treatment follow-up. Participants were randomized at the beginning of Phase 1 to receive bup/nx, paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual drug counseling). Eligible participants entering Phase 2 were re-randomized to either EMM or SMM. POATS was developed to determine what benefit, if any, EMM offers over SMM in short-term and longer-term treatment paradigm. This paper describes the rationale and design of the study. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Weiss, Roger D.; Potter, Jennifer Sharpe; Provost, Scott E.; Connery, Hilary Smith; Prather, Kristi] McLean Hosp, Div Alcohol & Drug Abuse, Belmont, MA 02478 USA.
[Weiss, Roger D.; Potter, Jennifer Sharpe; Connery, Hilary Smith] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA.
[Weiss, Roger D.; Potter, Jennifer Sharpe; Provost, Scott E.; Hasson, Albert; Connery, Hilary Smith; Prather, Kristi; Ling, Walter] NIDA, Clin Trials Network, Bethesda, MD USA.
[Potter, Jennifer Sharpe] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Huang, Zhen] Duke Clin Res Inst, Durham, NC 27705 USA.
[Jacobs, Petra] NIDA, Ctr Clin Trials Network, Rockville, MD 20892 USA.
[Hasson, Albert; Ling, Walter] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90025 USA.
[Lindblad, Robert] EMMES Corp, Rockville, MD 20847 USA.
RP Weiss, RD (reprint author), McLean Hosp, Div Alcohol & Drug Abuse, 115 Mill St, Belmont, MA 02478 USA.
EM rweiss@mclean.harvard.edu
RI Potter, Jennifer/C-6720-2008
OI Potter, Jennifer/0000-0002-7250-4422
FU NIDA Clinical Trials Network [U10 DA015831, U10 DA013045,
HHSN2712005220HC, K24 DA022288, K23 DA022297]
FX We thank the staff and participants at the community treatment programs
and regional research and training centers of the National Institute on
Drug Abuse Clinical Trials Network for their involvement in this
project, including Chestnut Ridge Hospital (Appalachian Tri-State Node),
San Francisco General Hospital (California/Arizona Node), St. Luke's
Roosevelt Hospital and Long Island Jewish Medical Center-Addiction
Recovery Services (Long Island Node), Bellevue Hospital Center (New York
Node), McLean Hospital (Northern New England Node), East Indiana
Treatment Center (Ohio Valley Node), Adapt, Inc. (Oregon/Hawaii Node),
Integrated Substance Abuse Programs (Pacific Node), Behavioral Health
Service of Pickens County (Southern Consortium Node), and Providence
Behavioral Health Services (Washington Node). We also thank the staff of
the Clinical Coordinating Center (The EMMES Corporation, Rockville, MD)
and the Data and Statistics Center (The Duke Clinical Research
Institute, Durham, NC), and the staff of the Center for the Clinical
Trials Network at the National Institute on Drug Abuse (Rockville, MD)
for their work on this project; This work was supported by NIDA Clinical
Trials Network Grants U10 DA015831 (RDW, Northern New England Node); and
U10 DA013045 (WL, Pacific Node); NIDA Contract HHSN2712005220HC (Duke
Clinical Research Institute); and NIDA Grants K24 DA022288 (RDW) and K23
DA022297 (JSP). Some NIDA personnel were involved in the study and in
the authorship of this paper.
NR 37
TC 33
Z9 33
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAR
PY 2010
VL 31
IS 2
BP 189
EP 199
DI 10.1016/j.cct.2010.01.003
PG 11
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 576FJ
UT WOS:000276129400011
PM 20116457
ER
PT J
AU Suarez, RO
Golby, A
Whalen, S
Sato, S
Theodore, WH
Kufta, CV
Devinsky, O
Balish, M
Bromfield, EB
AF Suarez, Ralph O.
Golby, Alexandra
Whalen, Stephen
Sato, Susumu
Theodore, William H.
Kufta, Conrad V.
Devinsky, Orrin
Balish, Marshall
Bromfield, Edward B.
TI Contributions to singing ability by the posterior portion of the
superior temporal gyrus of the non-language-dominant hemisphere: First
evidence from subdural cortical stimulation, Wada testing, and fMRI
SO CORTEX
LA English
DT Article
DE Singing laterality; Cortical stimulation; fMRI; Wada test; Music ability
ID FUNCTIONAL MRI; BROCAS AREA; MUSIC; PERCEPTION; LATERALIZATION; BRAIN;
SPEAKING; CORTEX; SYNTAX; AMUSIA
AB Introduction: Although the substrates that mediate singing abilities in the human brain are not well understood, invasive brain mapping techniques used for clinical decision making such as intracranial electro-cortical testing and Wada testing offer a rare opportunity to examine music-related function in a select group of subjects, affording exceptional spatial and temporal specificity.
Methods: We studied eight patients with medically refractory epilepsy undergoing indwelling subdural electrode seizure focus localization. All patients underwent Wada testing for language lateralization. Functional assessment of language and music tasks was done by electrode grid cortical stimulation. One patient was also tested non-invasively with functional magnetic resonance imaging (fMRI). Functional organization of singing ability compared to language ability was determined based on four regions-of-interest (ROIs): left and right inferior frontal gyrus (IFG), and left and right posterior superior temporal gyrus (pSTG).
Results: In some subjects, electrical stimulation of dominant pSTG can interfere with speech and not singing, whereas stimulation of non-dominant pSTG area can interfere with singing and not speech. Stimulation of the dominant IFG tends to interfere with both musical and language expression, while non-dominant IFG stimulation was often observed to cause no interference with either task; and finally, that stimulation of areas adjacent to but not within non-dominant pSTG typically does not affect either ability. Functional fMRI mappings of one subject revealed similar music/language dissociation with respect to activation asymmetry within the ROIs.
Conclusion: Despite inherent limitations with respect to strictly research objectives, invasive clinical techniques offer a rare opportunity to probe musical and language cognitive processes of the brain in a select group of patients. (c) 2009 Elsevier Srl. All rights reserved.
C1 [Suarez, Ralph O.; Golby, Alexandra; Whalen, Stephen] Harvard Univ, Dept Neurosurg, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Suarez, Ralph O.; Golby, Alexandra] Harvard Univ, Dept Radiol, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Bromfield, Edward B.] Harvard Univ, Dept Neurol, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Sato, Susumu; Theodore, William H.; Kufta, Conrad V.; Devinsky, Orrin; Balish, Marshall; Bromfield, Edward B.] NINDS, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Kufta, Conrad V.] Hanger Orthoped Grp, Bethesda, MD USA.
[Devinsky, Orrin] NYU, Dept Neurol, New York, NY 10016 USA.
[Balish, Marshall] Washington VA Med Ctr, Dept Neurol, Washington, DC USA.
RP Suarez, RO (reprint author), Harvard Univ, Dept Neurosurg, Sch Med, Brigham & Womens Hosp, Room CA-138,75 Francis St, Boston, MA 02115 USA.
EM rosuarez@bwh.harvard.edu
OI Devinsky, Orrin/0000-0003-0044-4632
FU National Institutes of Health (NIH) [NINDS, K08-NS048063-02, NIBIB,
T32-EB002177, NCRR, U41-RR019703, 3U41RR019703-03S1]
FX The subjects' motivation and cooperation made this study possible. Drs.
Paul Fedio, Christine Cox, and Aaron Nelson performed neuropsychological
testing and assisted with intracarotid amytal testing. Ms. Kathleen
Kelley, Ms. Patricia Reeves, Mr. Robert Long, and Mr. Hugh Malek
provided invaluable assistance with EEG and video recording. Mr. Joseph
Bucolo ably assisted with technical aspects of stimulation. We also
gratefully acknowledge Drs. Tracey Milligan and Joseph Madsen for their
excellent medical and surgical care of patient 8. Partial support for
this research was provided by National Institutes of Health (NIH)
grants: NINDS, K08-NS048063-02 (AJG); NIBIB, T32-EB002177 (ROS); NCRR,
U41-RR019703 (AJG) and 3U41RR019703-03S1 (ROS). The authors would like
to dedicate this article in loving memory of our respected colleague and
dear friend, Dr. Edward Bromfield.
NR 46
TC 13
Z9 14
U1 2
U2 11
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 0010-9452
J9 CORTEX
JI Cortex
PD MAR
PY 2010
VL 46
IS 3
BP 343
EP 353
DI 10.1016/j.cortex.2009.04.010
PG 11
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 563PZ
UT WOS:000275146500008
PM 19570530
ER
PT J
AU Berra, L
Cressoni, M
Bassi, GL
Kolobow, T
Panigada, M
Zanella, A
AF Berra, Lorenzo
Cressoni, Massimo
Li Bassi, Gianluigi
Kolobow, Theodor
Panigada, Mauro
Zanella, Alberto
CA Gravity VAP Network
TI Continuous lateral rotation therapy to prevent ventilator-associated
pneumonia: The neglected effects of gravity on pathogenesis of
ventilator-associated pneumonia
SO CRITICAL CARE MEDICINE
LA English
DT Letter
C1 [Berra, Lorenzo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Cressoni, Massimo; Panigada, Mauro] Fdn IRCCS Policlin, Milan, Italy.
[Li Bassi, Gianluigi] Hosp Clin Barcelona, Barcelona, Spain.
[Kolobow, Theodor] NIH, Bethesda, MD 20892 USA.
[Zanella, Alberto] Osped San Gerardo, Monza, Italy.
RP Berra, L (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Cressoni, Massimo/B-7315-2017; Panigada, Mauro/K-4650-2014;
OI Cressoni, Massimo/0000-0002-0089-2905; Panigada,
Mauro/0000-0003-4841-9794; zanella, Alberto/0000-0002-2967-2527
NR 3
TC 0
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAR
PY 2010
VL 38
IS 3
BP 1018
EP 1019
DI 10.1097/CCM.0b013e3181cc40fc
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA 565CI
UT WOS:000275266200070
PM 20168183
ER
PT J
AU Lamuraglia, M
Bridal, SL
Santin, M
Izzi, G
Rixe, O
Paradiso, A
Lucidarme, O
AF Lamuraglia, Michele
Bridal, S. Lori
Santin, Mathieu
Izzi, Gianni
Rixe, Olivier
Paradiso, Angelo
Lucidarme, Olivier
TI Clinical relevance of contrast-enhanced ultrasound in monitoring
anti-angiogenic therapy of cancer: Current status and perspectives
SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
LA English
DT Review
DE Angiogenesis; Monitoring anti-angiogenesis treatment; Contrast-enhanced
ultrasound (CEUS); Contrast agent
ID GASTROINTESTINAL STROMAL TUMORS; ENDOTHELIAL GROWTH-FACTOR; ISOLATED
LIMB PERFUSION; BLOOD-FLOW; ANTIANGIOGENIC THERAPY; COMPUTED-TOMOGRAPHY;
DOPPLER ULTRASOUND; TISSUE PERFUSION; SOLID TUMORS; AGENTS
AB Angiogenesis regulation is one of the newest fronts in the fight against cancer. Anti-angiogenic therapy is based on inhibiting factors required to solicit vessel formation thus cutting-off the tumor's supply of nutriments and oxygen. Initial vascular response is followed by formation of necrosis. Volumetric regression occurs more tardively. Effective monitoring of this new therapeutic approach thus requires imaging techniques that can detect early microvascular changes. A number of clinical studies provide evidence that contrast-enhanced ultrasound (CEUS) can provide early indication of tumor response to anti-angiogenic therapy. More sophisticated imaging and analysis techniques for CEUS and contrast agents targeted for adhesion to anti-angiogenic markers have also demonstrated promise in animal model studies. This review underlines the relevance of CEUS for anti-angiogenic therapy monitoring by summarizing the current clinical results, emerging CEUS techniques and preclinical data. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Lamuraglia, Michele] Univ Paris 06, Lab Imagerie Parametr, CNRS, UMR 7623, F-75006 Paris, France.
[Lamuraglia, Michele; Izzi, Gianni; Paradiso, Angelo] Natl Canc Inst Bari Giovanni Paolo II, I-70126 Bari, Italy.
[Lamuraglia, Michele; Lucidarme, Olivier] Hop La Pitie Salpetriere, Serv Radiol Polyvalente Diagnost & Intervent, F-75651 Paris, France.
[Rixe, Olivier] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Lamuraglia, M (reprint author), Univ Paris 06, Lab Imagerie Parametr, CNRS, UMR 7623, 15 Rue Ecole Med, F-75006 Paris, France.
EM michele.lamuraglia@gmail.com
OI Bridal, S. Lori/0000-0001-5053-5423
FU Martine Midy Foundation
FX Authors acknowledge financial support from the Martine Midy Foundation,
in particular for the fellowship of M. Lamuraglia.
NR 49
TC 41
Z9 43
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1040-8428
J9 CRIT REV ONCOL HEMAT
JI Crit. Rev. Oncol./Hematol.
PD MAR
PY 2010
VL 73
IS 3
BP 202
EP 212
DI 10.1016/j.critrevonc.2009.06.001
PG 11
WC Oncology; Hematology
SC Oncology; Hematology
GA 561QH
UT WOS:000274993000003
PM 19546008
ER
PT J
AU Favoni, RE
Pattarozzi, A
Lo Casto, M
Barbieri, F
Gatti, M
Paleari, L
Bajetto, A
Porcile, C
Gaudino, G
Mutti, L
Corte, G
Florio, T
AF Favoni, R. E.
Pattarozzi, A.
Lo Casto, M.
Barbieri, F.
Gatti, M.
Paleari, L.
Bajetto, A.
Porcile, C.
Gaudino, G.
Mutti, L.
Corte, G.
Florio, T.
TI Gefitinib Targets EGFR Dimerization and ERK1/2 Phosphorylation to
Inhibit Pleural Mesothelioma Cell Proliferation
SO CURRENT CANCER DRUG TARGETS
LA English
DT Review
DE Human malignant pleural mesothelioma cells; EGFR targeting; Gefitinib;
preclinical chemotherapy
ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; HUMAN-MALIGNANT
MESOTHELIOMA; ZD1839 IRESSA; IMATINIB MESYLATE; ZD-1839 IRESSA;
OVARIAN-CANCER; LINES; THERAPY; TRANSACTIVATION
AB Altered EGFR activity is a causal factor for human tumor development, including malignant pleural mesotheliomas. The aim of the present study was the evaluation of the effects of Gefitinib on EGF-induced mesothelioma cell proliferation and the intracellular mechanisms involved. Cell proliferation, DNA synthesis and apoptosis were measured by MTT, thymidine incorporation and FACS analysis; EGFR, ERK1/2 and Akt expression and phosphorylation by Western blot, whereas receptor sites were analyzed by binding studies. Gefitinib inhibited EGF-induced proliferation in two mesothelioma cell lines, derived from pleural effusion (IST-Mes2) or tumor biopsy (ZL55). The treatment with Gefitinib induced cell cycle arrest in both cell lines, while apoptosis was observed only for high concentrations and prolonged drug exposure. EGF-dependent mesothelioma cell proliferation was mediated by EGFR and ERK1/2 phosphorylation, while Akt was not affected. Gefitinib inhibited both EGFR and ERK1/2 activation, being maximal at drug concentrations that induce cytostatic effects, suggesting that the proapoptotic activity of Gefitinib is independent from EGFR inhibition. Gefitinib treatment increased EGFR Bmax, possibly through membrane stabilization of inactive receptor dimers that we show to be induced by the drug also in the absence of EGF. EGFR activation of ERK1/2 represents a key pathway for pleural mesothelioma cell proliferation. Low concentrations of Gefitinib cause mesothelioma cell cycle arrest through the blockade of EGFR activity while high concentrations induce apoptosis. Finally, we propose that the formation of inactive EGFR dimers may contribute to the antitumoral activity of Gefitinib.
C1 [Favoni, R. E.; Corte, G.] Ist Nazl Ric Canc, Natl Canc Inst, Dept Translat Oncol, Gene Transfer Lab, I-16132 Genoa, Italy.
[Lo Casto, M.] Ist Nazl Ric Canc, Natl Canc Inst, Dept Translat Oncol, Mol Oncol & Angiogenesis Lab, I-16132 Genoa, Italy.
[Paleari, L.] Ist Nazl Ric Canc, Natl Canc Inst, Lung Canc Unit, Dept Adv Diagnost Technol, I-16132 Genoa, Italy.
[Pattarozzi, A.; Barbieri, F.; Gatti, M.; Bajetto, A.; Porcile, C.; Corte, G.; Florio, T.] Univ Genoa, Pharmacol Sect, Dept Oncol Biol & Genet, I-16132 Genoa, Italy.
[Gaudino, G.] Univ Piemonte Orientale, DISCAFF Dept, I-28100 Novara, Italy.
[Gaudino, G.] Univ Piemonte Orientale, DFBC Ctr, I-28100 Novara, Italy.
[Mutti, L.] Vercelli Hosp, Dept Gen Med, I-13100 Vercelli, Italy.
[Mutti, L.] Vercelli Hosp, Lab Clin Oncol, I-13100 Vercelli, Italy.
RP Favoni, RE (reprint author), Ist Nazl Ric Canc, Lab Trasferimento Genico, Dept Oncol Traslaz, IST Nord, B3,Rm18,Largo Rosanna Benzi 10, I-16132 Genoa, Italy.
EM roberto.favoni@istge.it
RI Florio, Tullio/A-2211-2012; Barbieri, Federica/L-8753-2015;
OI Florio, Tullio/0000-0002-2394-996X; Barbieri,
Federica/0000-0001-8988-6896; Monica, Gatti/0000-0002-2016-0285
NR 45
TC 11
Z9 11
U1 1
U2 4
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1568-0096
J9 CURR CANCER DRUG TAR
JI Curr. Cancer Drug Targets
PD MAR
PY 2010
VL 10
IS 2
BP 176
EP 191
PG 16
WC Oncology
SC Oncology
GA 579YB
UT WOS:000276412300006
PM 20088784
ER
PT J
AU Guha, R
Gilbert, K
Fox, G
Pierce, M
Wild, D
Yuan, HP
AF Guha, Rajarshi
Gilbert, Kevin
Fox, Geoffrey
Pierce, Marlon
Wild, David
Yuan, Huapeng
TI Advances in Cheminformatics Methodologies and Infrastructure to Support
the Data Mining of Large, Heterogeneous Chemical Datasets
SO CURRENT COMPUTER-AIDED DRUG DESIGN
LA English
DT Article
DE Cheminformatics; web-service; WSDL; distributed; QSAR; diversity;
cancer; malaria
ID STRUCTURE-ACTIVITY LANDSCAPE; WEB SERVICE INFRASTRUCTURE;
PLASMODIUM-FALCIPARUM; MOLECULAR DIVERSITY; ACTIVITY CLIFFS; SEMANTIC
WEB; E-SCIENCE; MODELS; IDENTIFICATION; DATABASES
AB In recent years, there has been an explosion in the availability of publicly accessible chemical information, including chemical structures of small molecules, structure-derived properties and associated biological activities in a variety of assays. These data sources present us with a significant opportunity to develop and apply computational tools to extract and understand the underlying structure-activity relationships. Furthermore, by integrating chemical data sources with biological information (protein structure, gene expression and so on), we can attempt to build up a holistic view of the effects of small molecules in biological systems. Equally important is the ability for non-experts to access and utilize state of the art cheminformatics method and models. In this review we present recent developments in cheminformatics methodologies and infrastructure that provide a robust, distributed approach to mining large and complex chemical datasets. In the area of methodology development, we highlight recent work on characterizing structure-activity landscapes, Quantitative Structure Activity Relationship (QSAR) model domain applicability and the use of chemical similarity in text mining. In the area of infrastructure, we discuss a distributed web services framework that allows easy deployment and uniform access to computational (statistics, cheminformatics and computational chemistry) methods, data and models. We also discuss the development of PubChem derived databases and highlight techniques that allow us to scale the infrastructure to extremely large compound collections, by use of distributed processing on Grids. Given that the above work is applicable to arbitrary types of cheminformatics problems, we also present some case studies related to virtual screening for anti-malarials and predictions of anti-cancer activity.
C1 [Guha, Rajarshi] NIH, Chem Genom Ctr, Rockville, MD 20850 USA.
[Guha, Rajarshi; Gilbert, Kevin; Fox, Geoffrey; Wild, David] Indiana Univ, Sch Informat, Bloomington, IN 47408 USA.
[Fox, Geoffrey; Pierce, Marlon; Yuan, Huapeng] Indiana Univ, Community Grids Labs, Bloomington, IN 47408 USA.
RP Guha, R (reprint author), NIH, Chem Genom Ctr, Rockville, MD 20850 USA.
EM guhar@mail.nih.gov
RI Wild, David/B-1741-2009;
OI Pierce, Marlon/0000-0002-9582-5712
NR 79
TC 16
Z9 16
U1 3
U2 15
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1573-4099
EI 1875-6697
J9 CURR COMPUT-AID DRUG
JI Curr. Comput.-Aided Drug Des.
PD MAR
PY 2010
VL 6
IS 1
BP 50
EP 67
PG 18
WC Chemistry, Medicinal; Computer Science, Interdisciplinary Applications
SC Pharmacology & Pharmacy; Computer Science
GA 563QZ
UT WOS:000275149800004
PM 20370695
ER
PT J
AU Yoon, V
Fridkis-Hareli, M
Munisamy, S
Lee, J
Anastasiades, D
Stevceva, L
AF Yoon, V.
Fridkis-Hareli, M.
Munisamy, S.
Lee, J.
Anastasiades, D.
Stevceva, L.
TI The GP120 Molecule of HIV-1 and its Interaction with T Cells
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE Gp120; HIV; CD4+; CD8+; CTLs; viral escape; anergy; apoptosis
ID IMMUNODEFICIENCY-VIRUS TYPE-1; NECROSIS-FACTOR-ALPHA; BLOOD
MONONUCLEAR-CELLS; CD4 CROSS-LINKING; ENVELOPE GLYCOPROTEIN; DISEASE
PROGRESSION; IMMUNE-RESPONSES; FAS ANTIGEN; INFECTED INDIVIDUALS;
LYMPHOCYTE RESPONSES
AB The gp120 molecule of HIV-1 is a glycoprotein that is part of the outer layer of the virus. It presents itself as viral membrane spikes consisting of 3 molecules of gp120 linked together and anchored to the membrane by gp41 protein. Gp120 is essential for viral infection as it facilitates HIV entry into the host cell and this is its best-known and most researched role in HIV infection. However, it is becoming increasingly evident that gp120 might also be facilitating viral persistence and continuing HIV infection by influencing the T cell immune response to the virus. Several mechanisms might be involved in this process of which gp120 binding to the CD4 receptor of T cells is the best known and most important interaction as it facilitates viral entry into the CD4+ cells and their depletion, a hallmark of the HIV infection. Gp120 is shed from the viral membrane and accumulates in lymphoid tissues in significant amounts. Here, it can induce apoptosis and severely alter the immune response to the virus by dampening the antiviral CTL response thus impeding the clearance of HIV. The effects of gp120 and how it interacts and influences T cell immune response to the virus is an important topic and this review aims to summarize what has been published so far in hopes of providing guidance for future work in this area.
C1 [Stevceva, L.] NIAID, Virol Branch, Dept Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
[Anastasiades, D.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA.
[Munisamy, S.; Lee, J.] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Cambridge CB2 0SP, England.
[Fridkis-Hareli, M.] ME Biotechnol Consulting, Sudbury, MA USA.
[Yoon, V.] Massachusetts Gen Hosp E, Partners AIDS Res Ctr & Infect Dis Med, Charlestown, MA 02129 USA.
RP Stevceva, L (reprint author), NIAID, Virol Branch, Dept Microbiol & Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lstevceva@yahoo.com
NR 86
TC 10
Z9 10
U1 2
U2 14
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 0929-8673
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD MAR
PY 2010
VL 17
IS 8
BP 741
EP 749
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 549DR
UT WOS:000274024900003
PM 20088758
ER
PT J
AU Klatt, NR
Brenchley, JM
AF Klatt, Nichole R.
Brenchley, Jason M.
TI Th17 cell dynamics in HIV infection
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Article
DE HIV; immune activation; microbial translocation; T cell; Th17
ID CD4(+) T-CELLS; IMMUNODEFICIENCY VIRUS-INFECTION;
SYSTEMIC-LUPUS-ERYTHEMATOSUS; INFLAMMATORY-BOWEL-DISEASE; SOOTY
MANGABEYS; SIV INFECTION; HOST-DEFENSE; MYCOBACTERIUM-TUBERCULOSIS;
MICROBIAL TRANSLOCATION; CROHNS-DISEASE
AB Purpose of review
Th17 cells are a newly identified subtype of CD4(+) T cells that respond to bacterial and fungal antigens and are important in mucosal immunology. Because HIV infection results in loss of CD4(+) T cells as well as disruption to the gastrointestinal tract that causes microbial translocation and immune activation, Th17 cells potentially play an important role in HIV pathogenesis. Here we examine the relationship between Th17 cells and HIV disease pathogenesis.
Recent findings
Th17 cells are preferentially lost from the gastrointestinal tract of HIV-infected individuals, which is not entirely due to direct infection, as Th17 cells can be infected in vivo, but are not preferentially infected. Long-term highly active antiretroviral therapy (HAART) can result in restoration of Th17 cells in the gastrointestinal, which may be associated with better disease prognosis. Furthermore, other cells, such as V delta 1 T cells, can make IL-17 in vivo during HIV infection and may contribute to antibacterial immunity after loss of Th17 cells.
Summary
Recent studies have improved our understanding of the role for Th17 cells during HIV infection; however, more studies are needed to discern better the detrimental consequences of loss of Th17 cells during HIV infection.
C1 [Brenchley, Jason M.] NIAID, Immunopathogenesis Unit, Mol Microbiol Lab, NIH,VSV, Bethesda, MD 20892 USA.
RP Brenchley, JM (reprint author), NIAID, Immunopathogenesis Unit, Mol Microbiol Lab, NIH,VSV, 9000 Rockville Pike,Bldg 4,Room 307, Bethesda, MD 20892 USA.
EM jbrenchl@niaid.nih.gov
FU NIAID, NIH
FX J.M.B. and N.R.K. are funded by the intramural research program, NIAID,
NIH. The authors disclose no competing interests.
NR 76
TC 56
Z9 56
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD MAR
PY 2010
VL 5
IS 2
BP 135
EP 140
DI 10.1097/COH.0b013e3283364846
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 828NB
UT WOS:000295507100005
PM 20543590
ER
PT J
AU Cecchinato, V
Franchini, G
AF Cecchinato, Valentina
Franchini, Genoveffa
TI Th17 cells in pathogenic simian immunodeficiency virus infection of
macaques
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Article
DE gut; simian immunodeficiency virus; Th17
ID SIV INFECTION; T-CELLS; DEPLETION; IL-23; GUT
AB Purpose of review
We discuss studies on a subset of CD4(+)T cells, designated Th17, and their role in the pathogenesis of human and simian acquired immune deficiency, caused by infection with HIV and simian immunodeficiency virus (SIV), respectively. Most of the Th17 cells are lost within 2 weeks from infection at mucosal sites of SIV-infected macaques and are not replenished over time. Comparison of simian pathogenic and nonpathogenic models of SIV infection suggests that Th17 cells contribute to the pathogenesis of AIDS.
Recent findings
Th17 cells, a recently identified subset of T helper cells, play a major role in both inducing autoimmune disorders and fencing off extracellular pathogens. Several groups have reported that the number of Th17 cells is decreased in the gut of HIV-infected and SIV-infected hosts. The loss of Th17 cells from the mucosal compartment has been associated with the dissemination of Salmonella typhimurium that is normally contained locally by the host immune system. It is believed that microbial translocation sustains immune activation in HIV infection and contributes to AIDS.
Summary
Understanding the mechanisms that lead to disruption of mucosal integrity, viral spread, and chronic immune activation is of crucial importance for the design of efficient vaccines and therapeutic intervention for HIV.
C1 [Cecchinato, Valentina] Inst Biomed Res, Bellinzona, Switzerland.
[Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA.
RP Franchini, G (reprint author), 9000 Rockville Pike,Bldg 41,Room D-804, Bethesda, MD 20892 USA.
EM franchig@mail.nih.gov
FU Intramural NIH HHS [Z01 BC005688-17]
NR 17
TC 19
Z9 19
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD MAR
PY 2010
VL 5
IS 2
BP 141
EP 145
DI 10.1097/COH.0b013e32833653ec
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 828NB
UT WOS:000295507100006
PM 20543591
ER
PT J
AU Milner, JD
Sandler, NG
Douek, DC
AF Milner, Joshua D.
Sandler, Netanya G.
Douek, Daniel C.
TI Th17 cells, Job's syndrome and HIV: opportunities for bacterial and
fungal infections
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Article
DE HIV; hyper IgE syndrome; Job's syndrome; STAT3; Th17
ID HYPER-IGE SYNDROME; HYPERIMMUNOGLOBULIN-E SYNDROME; CHRONIC
VIRAL-INFECTION; STAPHYLOCOCCUS-AUREUS INFECTIONS;
FOLLICULAR-HELPER-CELLS; T-CELLS; DISEASES SOCIETY; EPITHELIAL-CELLS;
STAT3 MUTATIONS; RISK-FACTORS
AB Purpose of review
Patients with hyper IgE syndrome (HIES) share with HIV patients a predisposition to infections, including candidiasis in autosomal dominant HIES (AD-HIES) and molluscum contagiosum and other viral infections in other disorders of elevated IgE with infectious predilections. This review highlights the underlying pathogenesis of these diseases and their relevance to HIV infection.
Recent findings
Patients with mutations in STAT3, who lack Th17 cells, develop AD-HIES, whereas other disorders of elevated IgE may be caused by mutations in Tyk2 or DOCK8, the latter of which is associated with decreased expansion of CD8 more so than CD4 T cells. Recent studies on patients with recurrent mucocutaneous candidiasis have led to the discovery of mutations in CARD9 and DECTIN-1, genes key to the production of the Th17-driving cytokines IL-1 beta, IL-6, and IL-23. Studies of the peripheral blood of HIV-positive patients have shown a decreased Th17:Th1 ratio, and Th17 cells were preferentially depleted from the gastrointestinal tract within weeks of simian immunodeficiency virus infection in rhesus macaques.
Summary
The consequences of inadequate Th17 production in primary immunodeficiency syndromes illustrate the role of Th17 cells in controlling pathogens to which HIV-positive individuals are susceptible. Further understanding of the pathogenesis of opportunistic disease in HIV infection will probably require exploring the role of Th17 cells.
C1 [Sandler, Netanya G.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Milner, Joshua D.] NIAID, Allerg Inflammat Unit, Lab Allerg Dis, Vaccine Res Ctr,NIH, Bethesda, MD 20892 USA.
RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA.
EM ddouek@mail.nih.gov
OI Utay, Netanya/0000-0002-6407-8670
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX The present work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 67
TC 23
Z9 23
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD MAR
PY 2010
VL 5
IS 2
BP 179
EP 183
DI 10.1097/COH.0b013e328335ed3e
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 828NB
UT WOS:000295507100012
PM 20543597
ER
PT J
AU Wang, MY
Monticone, RE
Lakatta, EG
AF Wang, Mingyi
Monticone, Robert E.
Lakatta, Edward G.
TI Arterial aging: a journey into subclinical arterial disease
SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
LA English
DT Review
DE angiotensin II; arterial aging; arterial disease
ID SMOOTH-MUSCLE-CELLS; VASCULAR ENDOTHELIAL DYSFUNCTION; CROSS-LINK
BREAKER; FACTOR-KAPPA-B; ANGIOTENSIN-II; OXIDATIVE STRESS;
HYPERTENSIVE-RATS; MATRIX METALLOPROTEINASE-2; PROGENITOR CELLS; MMP-2
ACTIVITY
AB Purpose of review
Age-associated arterial alterations in cells, matrix, and biomolecules are the foundation for the initiation and progression of cardiovascular diseases in older persons. This review focuses on the latest advances on the intertwining of aging and disease within the arterial wall at the cell and molecular levels.
Recent findings
Endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation/invasion/secretion, matrix fragmentation, collagenization and glycation are characteristics of an age-associated arterial phenotype that creates a microenvironment enriched with reactive oxygen species (ROS) for the pathogenesis of arterial disease. This niche creates an age-associated arterial secretory phenotype (AAASP), which is orchestrated by the concerted effects of numerous age-modified angiotensin II signaling molecules. Most of these biomolecular, cell, and matrix modifications that constitute the AAASP can be elicited by experimental hypertension or atherosclerosis at a younger age. The arterial AAASP also shares features of a senescence-associated secretory phenotype (SASP) identified in other mesenchymocytes, that is, fibroblasts.
Summary
A subclinical AAASP evolves during aging. Targeting this subclinical AAASP may reduce the incidence and progression of the quintessential age-associated arterial diseases, that is, hypertension and atherosclerosis.
C1 [Wang, Mingyi; Monticone, Robert E.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM lakattae@grc.nia.nih.gov
FU National Institute on Aging, National Institutes of Health
FX Funding: This research was supported by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health.
NR 62
TC 75
Z9 79
U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1062-4821
J9 CURR OPIN NEPHROL HY
JI Curr. Opin. Nephrol. Hypertens.
PD MAR
PY 2010
VL 19
IS 2
BP 201
EP 207
DI 10.1097/MNH.0b013e3283361c0b
PG 7
WC Urology & Nephrology; Peripheral Vascular Disease
SC Urology & Nephrology; Cardiovascular System & Cardiology
GA 562OU
UT WOS:000275062900013
PM 20040868
ER
PT J
AU Bechlioulis, A
Naka, KK
Calis, KA
Makrigiannakis, A
Michalis, L
Kalantaridou, SN
AF Bechlioulis, Aris
Naka, Katerina K.
Calis, Karim A.
Makrigiannakis, Antonis
Michalis, Lampros
Kalantaridou, Sophia N.
TI Cardiovascular Effects of Endogenous Estrogen and Hormone Therapy
SO CURRENT VASCULAR PHARMACOLOGY
LA English
DT Article
DE Atherosclerosis; hormone therapy; menopause; vascular endothelium;
estrogen; estrogen receptor polymorphisms
ID CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; HEALTHY POSTMENOPAUSAL
WOMEN; RANDOMIZED CONTROLLED-TRIAL; ENDOTHELIAL PROGENITOR CELLS;
CONJUGATED EQUINE ESTROGENS; ALPHA GENE POLYMORPHISMS; NITRIC-OXIDE
SYNTHASE; ESTROGEN/PROGESTIN INTERVENTIONS PEPI; DENSITY-LIPOPROTEIN
CHOLESTEROL
AB The incidence of cardiovascular disease is low in healthy premenopausal women and increases with age especially after the menopause; this difference has been attributed to the loss of endogenous estrogen. Atherosclerosis is a chronic inflammatory condition of the vascular wall that may result in an acute clinical event by inducing plaque rupture/erosion leading to thrombosis. A growing body of evidence suggests that the spectrum of the effects of estrogen on vascular pathophysiology is complex and may depend largely on the state of vascular pathology. In relatively healthy vessels, estrogen prevents the development and progression of atherosclerotic lesions, while in the presence of established atherosclerotic plaques, estrogen fails to inhibit the progression of atherosclerosis or may even trigger cardiovascular events. The mechanisms responsible for this are not yet fully elucidated. It is possible that postmenopausal estrogen/progestogen therapy may be beneficial in perimenopausal and early menopausal women prior to atherosclerotic plaque formation, but it may not prevent progression of atherosclerotic plaques and acute cardiovascular events in older women with cardiovascular risk factors or women with established atherosclerosis. Various formulations, doses and routes of hormone therapy administration as well as the genetic background of women should also be taken into account when considering the benefit-to-risk ratio of hormone therapy use.
C1 [Naka, Katerina K.; Michalis, Lampros] Univ Ioannina, Sch Med, Dept Cardiol, GR-45110 Ioannina, Greece.
[Bechlioulis, Aris; Naka, Katerina K.; Michalis, Lampros; Kalantaridou, Sophia N.] Univ Ioannina, Michaelid Cardiac Ctr, GR-45110 Ioannina, Greece.
[Calis, Karim A.] NIH, Clin Res Ctr, Bethesda, MD 20892 USA.
[Makrigiannakis, Antonis] Univ Crete, Sch Med, Dept Obstet & Gynaecol, Iraklion, Greece.
[Kalantaridou, Sophia N.] Univ Ioannina, Sch Med, Dept Obstet & Gynaecol, GR-45110 Ioannina, Greece.
RP Michalis, L (reprint author), Univ Ioannina, Sch Med, Dept Cardiol, Univ Campus, GR-45110 Ioannina, Greece.
EM lmihalis@cc.uoi.gr
RI Bechlioulis, Aris/D-4814-2011
NR 142
TC 9
Z9 9
U1 0
U2 1
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-1611
J9 CURR VASC PHARMACOL
JI Current Vascular Pharmacology
PD MAR
PY 2010
VL 8
IS 2
BP 249
EP 258
PG 10
WC Pharmacology & Pharmacy; Peripheral Vascular Disease
SC Pharmacology & Pharmacy; Cardiovascular System & Cardiology
GA 563WS
UT WOS:000275167500008
PM 19485910
ER
PT J
AU Dagur, PK
Tatlici, G
Gourley, M
Samsel, L
Raghavachari, N
Liu, PC
Liu, DL
Mccoy, JP
AF Dagur, Pradeep Kumar
Tatlici, Gulnaz
Gourley, Mark
Samsel, Leigh
Raghavachari, Nalini
Liu, Poching
Liu, Delong
McCoy, J. Philip, Jr.
TI CD146+T Lymphocytes Are Increased in Both the Peripheral Circulation and
in the Synovial Effusions of Patients with Various Musculoskeletal
Diseases and Display Pro-inflammatory Gene Profiles
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Article
DE T cells; CD146; synovial effusion; arthritis
ID JUVENILE IDIOPATHIC ARTHRITIS; RHEUMATOID-ARTHRITIS; T-CELLS; ADHESION
MOLECULES; ENDOTHELIAL-CELLS; ANTIGEN; EXPRESSION; RECEPTOR; SUBSET;
BLOOD
AB Twenty-eight synovial effusions (SE) were obtained from 24 patients, paired samples of peripheral blood (PB) from 10 of these patients, and PB from 36 healthy individuals for analysis of CD146 on T-lymphocytes by flow cytometry. CD146+ or CD146 T-lymphocytes were sorted from three SE to study gene expression profiles and selected genes revalidated using QPCR assays. We found more CD3+CD146+ and CD4+CD146+ T-lymphocytes in PB from patients compared with PB of healthy individuals (4.71% +/- 2.48% vs. 2.53% +/- 1.08%, P = 0.028) and (6.29% +/- 2.74% vs. 2.41% +/- 0.96%, P = 0.0017), respectively, whereas CD8+CD146+ T-Iymphocytes were not significantly different (2.55% +/- 1.65% vs. 3.18% +/- 2.59%, P = 0.5008). SE displayed CD146 staining on 16.32% +/- 6.06% of CD3+ cells. This expression was skewed toward CD4+ T-lymphocytes, with CD146 present on 24.06% +/- 8.20% of the CD4+ T-lymphocytes compared with 6.19% +/- 5.22% of the CD8+ T-lymphocytes. CD146 on CD3+, CD4+ and CD8+ T-lymphocytes in SE was significantly higher compared with PB in patients (P<0.0001, P<0.0001 and P = 0.0036, respectively). Gene expression profiles of sorted CD146+CD4+CD3+ vs. CD146-CD4+CD3+ T-lymphocytes (n = 2) and CD2+CD146+ vs. CD2+CD 146 (n = 1) from SE, displayed increased CD146, LAIR2, CXCL13, CD109, IL6ST, IL6R, TNFRsf18, and TNFRsf4 genes, whereas decreased CCR7, CCL5, and cytotoxicity-associated genes including granzymes b, h, and k, perforin were found with the CD146- T-lymphocytes. By QPCR higher mRNA expression of CXCL13, CD146 and CD109 was also noted in the CD146+ subset, compared with the CD146- subset, in PB of healthy individuals and in PB and SE from patients. Our study establishes increased CD146+ T-lymphocytes in diseases with joint effusions, and demonstrates pro-inflammatory gene profiles in these cells. Published 2009 Wiley-Liss, Inc.
C1 [McCoy, J. Philip, Jr.] NHLBI, NIH, Flow Cytometry Core Facil, Bethesda, MD 20892 USA.
[Gourley, Mark] NIAMSD, Bethesda, MD 20892 USA.
[Raghavachari, Nalini; Liu, Poching] NHLBI, Genom Core Facil, Bethesda, MD 20892 USA.
[Liu, Delong] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Mccoy, JP (reprint author), NHLBI, NIH, Flow Cytometry Core Facil, 10 Ctr Dr,MSC 1357,Bldg 10,Rm 8C103D, Bethesda, MD 20892 USA.
EM mccoyjp@nhlbi.nih.gov
FU Intramural Research Programs; National Heart, Lung, and Blood Institute;
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(National Institutes of Health)
FX Grant sponsors: Intramural Research Programs, National Heart, Lung, and
Blood Institute; National Institute of Arthritis and Musculoskeletal and
Skin Diseases (National Institutes of Health).
NR 27
TC 13
Z9 14
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD MAR
PY 2010
VL 78B
IS 2
BP 88
EP 95
DI 10.1002/cyto.b.20502
PG 8
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 578BE
UT WOS:000276267500003
PM 19834966
ER
PT J
AU Rich, BA
Holroyd, T
Carver, FW
Onelio, LM
Mendoza, JK
Cornwell, BR
Fox, NA
Pine, DS
Coppola, R
Leibenluft, E
AF Rich, Brendan A.
Holroyd, Tom
Carver, Frederick W.
Onelio, Laura M.
Mendoza, Jennifer K.
Cornwell, Brian R.
Fox, Nathan A.
Pine, Daniel S.
Coppola, Richard
Leibenluft, Ellen
TI A PRELIMINARY STUDY OF THE NEURAL MECHANISMS OF FRUSTRATION IN PEDIATRIC
BIPOLAR DISORDER USING MAGNETOENCEPHALOGRAPHY
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE irritability; attention; neuroimaging; anterior cingulate cortex;
parietal lobe; theta
ID MAJOR DEPRESSIVE DISORDER; FRONTAL MIDLINE THETA; SPATIALLY-FILTERED
MAGNETOENCEPHALOGRAPHY; EVENT-RELATED SYNCHRONIZATION; ROSTRAL ANTERIOR
CINGULATE; SUBCORTICAL BRAIN-REGIONS; RESPONSE-INHIBITION; PREFRONTAL
CORTEX; GO/NOGO TASK; BEHAVIORAL-RESPONSES
AB Background: Irritability is prevalent and impairing in pediatric bipolar disorder (BD) but has been minimally studied using neuroimaging techniques We used magnetoencephalograpby (MEG) to study theta band oscillations in the anterior cingulate cortex (ACC) during frustration in BD youth. ACC theta power is associated with attention to emotional stimuli, and the A CC may mediate responses to frustrating stimuli. Methods: We used the affective Posner task, an attention paradigm that uses rigged feedback to induce frustration, to compare 20 medicated BD youth (14.9 +/- 2.0 years; 45% male) and 20 healthy controls (14.7 +/- 1.7 years; 45% male). AIEG measured neuronal activity after negative and positive feedback; we also compared groups on reaction time, response accuracy, and self-reported affect Patients met strict DSM-IV BD criteria and were euthymic Controls bad no psychiatric history. Results: BD youth reported more negative affective responses than controls. After negative feedback, BD subject, relative to controls, displayed greater theta power in the right ACC and bilateral parietal lobe. After positive feedback, BD subjects displayed lower theta power in the left A CC than did controls. Correlations between MEG, behavior, and affect were nonsignificant. Conclusion: In this first MEG study of BD youth, BD youth displayed patterns of theta oscillations in the A CC and parietal lobe in response to frustration-inducing negative feedback that differed from healthy controls. These data suggest that BD youth may display heightened processing of negative feedback and exaggerated self-monitoring after frustrating emotional stimuli Future studies are needed with unmedicated bipolar youth, and comparison ADHD and anxiety groups. Depression and Anxiety 27:276-286, 2010. (C) 2009 Wiley-Liss, Inc.
C1 [Rich, Brendan A.] Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA.
[Holroyd, Tom; Carver, Frederick W.; Coppola, Richard] NIMH, MEG Core Facil, Bethesda, MD 20892 USA.
[Onelio, Laura M.; Mendoza, Jennifer K.; Cornwell, Brian R.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Fox, Nathan A.] Univ Maryland, Child Dev Lab, College Pk, MD 20742 USA.
RP Rich, BA (reprint author), Catholic Univ Amer, Dept Psychol, 4001 Harewood Rd NE,327 OBoyle Hall, Washington, DC 20064 USA.
EM richb@cua.edu
FU Intramural Research Program of the NIH; NIMH
FX This research was supported by the Intramural Research Program of the
NIH, NIMH. This funding organization was not involved in research
aspects, such as study design and conduct, data collection, analysis, or
interpretation, nor manuscript preparation or approval. We acknowledge
the subjects and families of patients and controls whose participation
enabled this research. We also thank the staff of the Section on Bipolar
Spectrum Disorders at the NIMH.
NR 120
TC 15
Z9 15
U1 6
U2 9
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD MAR
PY 2010
VL 27
IS 3
BP 276
EP 286
DI 10.1002/da.20649
PG 11
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 563BU
UT WOS:000275101400008
PM 20037920
ER
PT J
AU Bornstein, MH
Arterberry, ME
AF Bornstein, Marc H.
Arterberry, Martha E.
TI The Development of Object Categorization in Young Children: Hierarchical
Inclusiveness, Age, Perceptual Attribute, and Group Versus Individual
Analyses
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
DE categorization; sequential touching; toddlers
ID BASIC-LEVEL; INFANTS CATEGORIZATION; DEPENDENT CATEGORIZATION; INDUCTIVE
INFERENCE; SEMANTIC MEMORY; FOLK BIOLOGY; SCALE ERRORS; REAL OBJECTS;
SIMILARITY; KNOWLEDGE
AB Multiple levels of category inclusiveness in 4 object domains (animals, vehicles, fruit, and furniture) were examined using a sequential touching procedure and assessed in both individual and group analyses in eighty 12-, 18-, 24-, and 30-month-olds. The roles of stimulus discriminability and child motor development, fatigue, and actions were also investigated. More inclusive levels of categorization systematically emerged before less inclusive levels, and a consistent advantage for categorizing high versus low perceptual contrasts was found. Group and individual analyses generally converged, but individual analyses added information about child categorization over group analyses. The development of object categorization in young children is discussed in light of efficiency of processing and similarity-differentiation theories.
C1 [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurosci, NIH, Publ Hlth Serv, Bethesda, MD 20892 USA.
[Arterberry, Martha E.] Colby Coll, Waterville, ME 04901 USA.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurosci, NIH, Publ Hlth Serv, Rockledge 1,Suite 8030,6705 Rockledge Dr,MSC 7971, Bethesda, MD 20892 USA.
EM Marc_H_Bornstein@nih.gov
FU Intramural NIH HHS [ZIA HD001119-22, Z01 HD001119-20]
NR 137
TC 20
Z9 21
U1 6
U2 10
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0012-1649
J9 DEV PSYCHOL
JI Dev. Psychol.
PD MAR
PY 2010
VL 46
IS 2
BP 350
EP 365
DI 10.1037/a0018411
PG 16
WC Psychology, Developmental
SC Psychology
GA 566PQ
UT WOS:000275385400005
PM 20210495
ER
PT J
AU Um, JH
Park, SJ
Kang, H
Yang, ST
Foretz, M
McBurney, MW
Kim, MK
Viollet, B
Chung, JH
AF Um, Jee-Hyun
Park, Sung-Jun
Kang, Hyeog
Yang, Shutong
Foretz, Marc
McBurney, Michael W.
Kim, Myung K.
Viollet, Benoit
Chung, Jay H.
TI AMP-Activated Protein Kinase-Deficient Mice Are Resistant to the
Metabolic Effects of Resveratrol
SO DIABETES
LA English
DT Article
ID SKELETAL-MUSCLE; LIFE-SPAN; MITOCHONDRIAL BIOGENESIS; DIETARY
RESTRICTION; INSULIN-RESISTANCE; RAT-LIVER; C-ELEGANS; SIRT1; EXERCISE;
PGC-1-ALPHA
AB OBJECTIVE-Resveratrol, a natural polyphenolic compound that is found in grapes and red wine, increases metabolic rate, insulin sensitivity, mitochondrial biogenesis, and physical endurance and reduces fat accumulation in mice. Although it is thought that resveratrol targets Sirt1, this is controversial because resveratrol also activates 5' AMP-activated protein kinase (AMPK), which also regulates insulin sensitivity and mitochondrial biogenesis. Here, we use mice deficient in AMPK alpha 1 or -alpha 2 to determine whether the metabolic effects of resveratrol are mediated by AMPK.
RESEARCH DESIGN AND METHODS-Mice deficient in the catalytic subunit of AMPK (alpha 1 or alpha 2) and wild-type mice were fed a high-fat diet or high-fat diet supplemented with resveratrol for 13 weeks. Body weight was recorded biweekly and metabolic parameters were measured. We also used mouse embryonic fibroblasts deficient in AMPK to study the role of AMPK in resveratrol-mediated effects in vitro.
RESULTS-Resveratrol increased the metabolic rate and reduced fat mass in wild-type mice but not in AMPK alpha 1(-/-) mice. In the absence of either AMPK alpha 1 or -alpha 2, resveratrol failed to increase insulin sensitivity, glucose tolerance, mitochondrial biogenesis, and physical endurance. Consistent with this, the expression of genes important for mitochondrial biogenesis was not induced by resveratrol in AMPK-deficient mice. In addition, resveratrol increased the NAD-to-NADH ratio in an AMPK-dependent manner, which may explain how resveratrol may activate Sirt1 indirectly.
CONCLUSIONS-We conclude that AMPK, which was thought to be an off-target hit of resveratrol, is the central target for the metabolic effects of resveratrol. Diabetes 59:554-563, 2010
C1 [Um, Jee-Hyun; Park, Sung-Jun; Kang, Hyeog; Yang, Shutong; Kim, Myung K.; Chung, Jay H.] NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA.
[Foretz, Marc; Viollet, Benoit] Univ Paris 05, CNRS, UMR 8104, Inst Cochin, Paris, France.
[Foretz, Marc; Viollet, Benoit] Natl Sante & Rech Med, Paris, France.
[McBurney, Michael W.] Ottawa Hlth Res Inst, Ctr Canc Therapeut, Ottawa, ON, Canada.
RP Chung, JH (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM chungj@nhlbi.nih.gov
FU Intramural Research Program; National Heart, Lung, and Blood Institute;
National Institutes of Health; European Union [LSHM-CT2004-005272]
FX This work was supported by the Intramural Research Program, National
Heart, Lung, and Blood Institute, National Institutes of Health, and by
the European Union FP6 Program (EXGENESIS Integrated Project
LSHM-CT2004-005272).; No potential conflicts of interest relevant to
this article were reported.; We thank Dalton Saunders for his assistance
with animal management.
NR 52
TC 312
Z9 322
U1 4
U2 40
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD MAR
PY 2010
VL 59
IS 3
BP 554
EP 563
DI 10.2337/db09-0482
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 568YQ
UT WOS:000275562900002
PM 19934007
ER
PT J
AU Cowie, CC
Rust, KF
Byrd-Holt, DD
Gregg, EW
Ford, ES
Geiss, LS
Bainbridge, KE
Fradkin, JE
AF Cowie, Catherine C.
Rust, Keith F.
Byrd-Holt, Danita D.
Gregg, Edward W.
Ford, Earl S.
Geiss, Linda S.
Bainbridge, Kathleen E.
Fradkin, Judith E.
TI Prevalence of Diabetes and High Risk for Diabetes Using A1C Criteria in
the US Population in 1988-2006
SO DIABETES CARE
LA English
DT Article
AB OBJECTIVE - We examined prevalences of previously diagnosed diabetes and undiagnosed diabetes and high risk for diabetes using recently Suggested A1C criteria in the U.S. during 2003-2006. We compared these prevalences to those in earlier surveys and those using glucose criteria.
RESEARCH DESIGN AND METHODS - in 2003-2006, the National Health and Nutrition Examination Survey included a probability sample of 14,611 individuals aged >= 12 years. Participants were classified on glycemic status by interview for diagnosed diabetes and by A1C, fasting, and 2-h glucose challenge values measured in subsamples.
RESULTS - Using A1C criteria, the crude prevalence of total diabetes in adults aged >= 20 years was 9.6% (20.4 million), of which 19.0% was undiagnosed (7.8% diagnosed, 1.8% undiagnosed Using A1C >= 6.5%). Another 3.5% of adults (7.4 million) were at high risk for diabetes (A1C 6.0 to <6.5%). Prevalences were disproportionately high in the elderly. Age-/sex-standardized prevalence was more than two Limes higher in non-Hispanic blacks and Mexican Americans versus non-Hispanic whites for diagnosed, undiagnosed, and total diabetes (P < 0.003); standardized prevalence at high risk for diabetes was more than two times higher in non-Hispanic blacks Versus non-Hispanic whites and Mexican Americans (P < 0.00001. Since 1988-1994, diagnosed diabetes generally increased, while the percent of diabetes that was undiagnosed and the percent at high risk of diabetes generally decreased. Using A1C Criteria, prevalences of undiagnosed diabetes and high risk of diabetes were one-third that and one-tenth that, respectively, using glucose criteria.
CONCLUSIONS - Although A1C detects much lower prevalences than glucose criteria, hyperglycemic conditions remain high in the U.S., and elderly and minority groups are disproportionately affected.
C1 [Cowie, Catherine C.; Fradkin, Judith E.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Rust, Keith F.] WESTAT Corp, Rockville, MD 20850 USA.
[Byrd-Holt, Danita D.; Bainbridge, Kathleen E.] Social & Sci Syst, Silver Spring, MD USA.
[Gregg, Edward W.; Geiss, Linda S.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA.
[Ford, Earl S.] Ctr Dis Control & Prevent, Div Adult & Community Hlth, Atlanta, GA USA.
RP Cowie, CC (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM cowie@nih.gov
NR 14
TC 290
Z9 295
U1 0
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 MAR
PY 2010
VL 33
IS 3
BP 562
EP 568
DI 10.2337/dc09-1524
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 568YO
UT WOS:000275562700021
PM 20067953
ER
PT J
AU Menjoge, AR
Kannan, RM
Tomalia, DA
AF Menjoge, Anupa R.
Kannan, Rangaramanujam M.
Tomalia, Donald A.
TI Dendrimer-based drug and imaging conjugates: design considerations for
nanomedical applications
SO DRUG DISCOVERY TODAY
LA English
DT Review
ID POLYAMIDOAMINE PAMAM DENDRIMERS; MAGNETIC RESONANCE LYMPHANGIOGRAPHY;
CACO-2 CELL MONOLAYERS; MR CONTRAST AGENT; IN-VITRO; POLY(AMIDOAMINE)
DENDRIMERS; SURFACE MODIFICATION; BIOLOGICAL EVALUATION; STARBURST
DENDRIMERS; STEALTH DENDRIMERS
AB Dendrimers are members of a versatile fourth new class of polymer, architecture (i.e. dendritic polymers after traditional linear crosslinked, and branched types) [1]. Typically, dendrimers are used as well-defined scaffolding or nanocontainers to conjugate, complex or encapsulate therapeutic drugs or imaging moieties. As a delivery vector, the dendrimer conjugate linker or spacer chemistry plays a crucial part in determining optimum drug delivery to disease sites by conserving active drug efficacy while influencing appropriate release patterns. This review focuses oil several crucial issues related to those dendrimer features, namely the role of dendrimers as nanoscaffolding and nanocontainers, crucial principles that might be invoked for improving dendrimer cytotoxicity properties, understanding dendrimer cellular transport mechanisms and the exciting role of dendrimers as high-contrast MRI imaging agents. The review concludes with a brief survey of translational efforts from research and development phases to clinical trials that are actively emerging.
C1 [Tomalia, Donald A.] Cent Michigan Univ, Dept Chem, Natl Dendrimer & Nanotechnol Ctr, Mt Pleasant, MI 48859 USA.
[Menjoge, Anupa R.; Kannan, Rangaramanujam M.] Wayne State Univ, Dept Chem Engn & Mat Sci & Biomed Engn, Detroit, MI 48202 USA.
[Menjoge, Anupa R.; Kannan, Rangaramanujam M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NICHD, NIH,DHHS, Detroit, MI 48201 USA.
RP Tomalia, DA (reprint author), Cent Michigan Univ, Dept Chem, Natl Dendrimer & Nanotechnol Ctr, Mt Pleasant, MI 48859 USA.
EM rkannan@eng.wayne.edu; donald.tomalia@cmich.edu
FU Intramural NIH HHS
NR 114
TC 374
Z9 381
U1 19
U2 203
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1359-6446
J9 DRUG DISCOV TODAY
JI Drug Discov. Today
PD MAR
PY 2010
VL 15
IS 5-6
BP 171
EP 185
DI 10.1016/j.drudis.2010.01.009
PG 15
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 573IU
UT WOS:000275906900003
PM 20116448
ER
PT J
AU Hoelbl, A
Schuster, C
Kovacic, B
Zhu, BM
Wickre, M
Hoelzl, MA
Fajmann, S
Grebien, F
Warsch, W
Stengl, G
Hennighausen, L
Poli, V
Beug, H
Moriggl, R
Sexl, V
AF Hoelbl, Andrea
Schuster, Christian
Kovacic, Boris
Zhu, Bingmei
Wickre, Mark
Hoelzl, Maria A.
Fajmann, Sabine
Grebien, Florian
Warsch, Wolfgang
Stengl, Gabriele
Hennighausen, Lothar
Poli, Valeria
Beug, Hartmut
Moriggl, Richard
Sexl, Veronika
TI Stat5 is indispensable for the maintenance of bcr/abl-positive leukaemia
SO EMBO MOLECULAR MEDICINE
LA English
DT Article
DE Bcr/Abl; leukaemia; leukaemic stem cells; Stat5
ID HEMATOPOIETIC STEM-CELLS; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS
LEUKEMIA; DNA-BINDING ACTIVITY; BCR-ABL; MYELOPROLIFERATIVE DISORDERS;
TYROSINE KINASE; CONSTITUTIVE ACTIVATION; BLAST-CRISIS;
LYMPHOPROLIFERATIVE DISEASE
AB Tumourigenesis caused by the Bcr/Abl oncoprotein is a multi-step process proceeding from initial to tumour-maintaining events and finally results in a complex tumour-supporting network. A key to successful cancer therapy is the identification of critical functional nodes in an oncogenic network required for disease maintenance. So far, the transcription factors Stat3 and Stat5a/b have been implicated in bcr/abl-induced initial transformation. However, to qualify as a potential drug target, a signalling pathway must be required for the maintenance of the leukaemic state. Data on the roles of Stat3 or Stat5a/b in leukaemia maintenance are elusive. Here, we show that both, Stat3 and Stat5 are necessary for initial transformation. However, Stat5- but not Stat3-deletion induces G(0)/G(1) cell cycle arrest and apoptosis of imatinib-sensitive and imatinib-resistant stable leukaemic cells in vitro. Accordingly, Stat5-abrogation led to effective elimination of myeloid and lymphoid leukaemia maintenance in vivo. Hence, we identified Stat5 as a vulnerable point in the oncogenic network downstream of Bcr/Abl representing a case of non-oncogene addiction (NOA).
C1 [Hoelbl, Andrea; Schuster, Christian; Hoelzl, Maria A.; Fajmann, Sabine; Warsch, Wolfgang; Sexl, Veronika] MUV, Inst Pharmacol, Ctr Biomol Med & Pharmacol, Vienna, Austria.
[Kovacic, Boris; Stengl, Gabriele; Beug, Hartmut] Res Inst Mol Pathol IMP, Vienna, Austria.
[Zhu, Bingmei; Wickre, Mark; Hennighausen, Lothar] NIH, Bethesda, MD 20892 USA.
[Grebien, Florian] MUV, MFPL, Vienna, Austria.
[Poli, Valeria] Univ Turin, Ctr Mol Biotechnol, Turin, Italy.
[Moriggl, Richard] Ludwig Boltzmann Inst Canc Res, Vienna, Austria.
RP Sexl, V (reprint author), MUV, Inst Pharmacol, Ctr Biomol Med & Pharmacol, Vienna, Austria.
EM veronika.sexl@meduniwien.ac.at
RI Poli, Valeria/A-9215-2012; Kovacic, Boris/J-1871-2016;
OI Poli, Valeria/0000-0002-3739-3966; Kovacic, Boris/0000-0002-1148-4149;
Hoelbl-Kovacic, Andrea/0000-0001-6219-8794; Grebien,
Florian/0000-0003-4289-2281; Moriggl, Richard/0000-0003-0918-9463
FU Austrian Research fund [FWF-SFB-28]; Vienna Science and Technology Fund
[WWTF-LS07-037]; GEN-AU-program DRAGON
FX We are deeply indebted to M. Freissmuth, M. Busslinger, P. Valent, O.
Hantschel, G. Superti-Furga and T. Decker for continuous discussion and
scientific input. We also thank M. Mayerhofer for providing the
Bcr/Ablp210T315I mutant. This work was made possible by
financial support from the Austrian Research fund (FWF-SFB-28), the
Vienna Science and Technology Fund (WWTF-LS07-037) and the
GEN-AU-program DRAGON.
NR 69
TC 108
Z9 115
U1 1
U2 14
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1757-4676
J9 EMBO MOL MED
JI EMBO Mol. Med.
PD MAR
PY 2010
VL 2
IS 3
BP 98
EP 110
DI 10.1002/emmm.201000062
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 572IN
UT WOS:000275822700004
PM 20201032
ER
PT J
AU Risi, GF
Bloom, ME
Hoe, NP
Arminio, T
Carlson, P
Powers, T
Feldmann, H
Wilson, D
AF Risi, George F.
Bloom, Marshall E.
Hoe, Nancy P.
Arminio, Thomas
Carlson, Paul
Powers, Tamara
Feldmann, Heinz
Wilson, Deborah
TI Preparing a Community Hospital to Manage Work-related Exposures to
Infectious Agents in BioSafety Level 3 and 4 Laboratories
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID IMPORTED LASSA FEVER; EBOLA-VIRUS; HEMORRHAGIC-FEVER; BIOTERRORISM;
GERMANY; PATIENT; RISK
AB Construction of new BioSafety Level (BSL) 3 and 4 laboratories has raised concerns regarding provision of care to exposed workers because of healthcare worker (HCW) unfamiliarity with precautions required. When the National Institutes of Health began construction of a new BSL-4 laboratory in Hamilton, Montana, USA, in 2005, they contracted with St. Patrick Hospital in Missoula, Montana, for care of those exposed. A care and isolation unit is described. We developed a training program for HCWs that emphasized the optimal use of barrier precautions and used pathogen-specific modules and simulations with mannequins and fluorescent liquids that represented infectious body fluids. The facility and training led to increased willingness among HCWs to care for patients with all types of communicable diseases. This model may be useful for other hospitals, whether they support a BSL-4 facility, are in the proximity of a BSL-3 facility, or are interested in upgrading their facilities to prepare for exotic and novel infectious diseases.
C1 [Powers, Tamara] St Patricks Hosp, Missoula, MT USA.
[Powers, Tamara] Hlth Sci Ctr, Missoula, MT USA.
[Risi, George F.; Hoe, Nancy P.; Arminio, Thomas; Carlson, Paul; Wilson, Deborah] NIH, Bethesda, MD 20892 USA.
[Bloom, Marshall E.; Feldmann, Heinz] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Risi, GF (reprint author), 614 W Spruce St, Missoula, MT 59802 USA.
EM grisi@mail.nih.gov
FU NIH Division of Occupational Health and Safety; NIAID Division of
Intramural Research
FX This work was supported by the NIH Division of Occupational Health and
Safety (G.R., N.H., T.A., P.C., D.W.), and the NIAID Division of
Intramural Research (M.B., H.F.).
NR 33
TC 6
Z9 6
U1 1
U2 14
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 MAR
PY 2010
VL 16
IS 3
BP 373
EP 378
DI 10.3201/eid1603.091485
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 566WR
UT WOS:000275404700001
PM 20202409
ER
PT J
AU Aguilera, G
Chen, J
Liu, Y
AF Aguilera, Greti
Chen, Jun
Liu, Ying
TI Epigenetic regulation of hypothalamic-pituitary adrenal axis and
corticotrophin releasing hormone transcription by early life stress
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Aguilera, Greti; Chen, Jun; Liu, Ying] NICHHD, PDEGEN, Sect Endocrine Physiol, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S253
EP S253
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742600251
ER
PT J
AU Al-Attas, O
Al-Daghri, N
Alokail, M
Bamakhramah, A
Sabico, S
Huang, T
McTernan, P
Kumar, S
AF Al-Attas, Omar
Al-Daghri, Nasser
Alokail, Majed
Bamakhramah, Ahmed
Sabico, Shaun
Huang, Terry
McTernan, Philip
Kumar, Sudhesh
TI Telomere length and childhood obesity among Arab youth
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Al-Attas, Omar; Al-Daghri, Nasser; Alokail, Majed; Bamakhramah, Ahmed; Sabico, Shaun] King Saud Univ, Dept Biochem, Riyadh, KSA, Saudi Arabia.
[Huang, Terry] Eunice Kennedy Shriver Natl Inst, Child Hlth & Human Dev, Bethesda, MD USA.
[McTernan, Philip; Kumar, Sudhesh] Univ Warwick, Diabet & Metab Unit, Coventry CV4 7AL, W Midlands, England.
RI Al-Daghri, Nasser/G-7736-2011; Al-okail, Majed/E-5565-2016
OI Al-okail, Majed/0000-0001-8147-3499
NR 0
TC 0
Z9 0
U1 0
U2 4
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S619
EP S619
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742601807
ER
PT J
AU Cheng, SY
AF Cheng, Sheue-yann
TI Regulation of metastasis in follicular carcinoma of the thyroid:
Insights from a mouse model
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Cheng, Sheue-yann] NCI, LMB, CCR, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S277
EP S277
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742600351
ER
PT J
AU Gainer, H
AF Gainer, Harold
TI Recent progress in understanding the regulation of the cell-specific
expression of oxytocin and vasopressin genes in the hypothalamus
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Gainer, Harold] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S256
EP S256
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742600260
ER
PT J
AU Gorden, P
AF Gorden, Phillip
TI The application of adipokine biology to the treatment of human disease
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Gorden, Phillip] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S224
EP S224
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742600125
ER
PT J
AU Hanyu, O
Fuda, H
Higashi, Y
Endo, M
Nakae, H
Kohjitani, A
Miida, T
Aizawa, Y
Strott, CA
AF Hanyu, Osamu
Fuda, Hirotoshi
Higashi, Yuko
Endo, Motohiro
Nakae, Hanako
Kohjitani, Atsushi
Miida, Takashi
Aizawa, Yoshifusa
Strott, Charles A.
TI Cholesterol sulfate regulation of profilaggrin expression: Studies
involving sirna for SULT2B1B and ROR alpha in primary cultures of normal
human epidermal keratinocytes
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Hanyu, Osamu; Aizawa, Yoshifusa] Niigata Univ, Grad Sch Med & Dent Sci, Dept Homeostat Regulat & Dev, Div Endocrinol & Metab, Niigata, Japan.
[Miida, Takashi] Juntendo Univ, Sch Med, Dept Clin Lab Med, Tokyo 113, Japan.
[Fuda, Hirotoshi; Higashi, Yuko; Endo, Motohiro; Nakae, Hanako; Kohjitani, Atsushi; Strott, Charles A.] NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S545
EP S546
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742601509
ER
PT J
AU Kimura, S
AF Kimura, Shioko
TI Stem cells in thyroid carcinomas
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S317
EP S317
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742600514
ER
PT J
AU Kino, T
Hurt, DE
Ichijo, T
Nader, N
Chrousos, GP
AF Kino, Tomoshige
Hurt, Darrell E.
Ichijo, Takamasa
Nader, Nancy
Chrousos, George P.
TI Non-coding RNA Gas5 is a growth arrest/starvation-associated repressor
of the glucocorticoid receptor
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Kino, Tomoshige; Ichijo, Takamasa; Nader, Nancy] Eunice Kennedy Shirver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
[Hurt, Darrell E.] NIAID, Bioinformat & Sci IT Program, Off Technol Informat Syst, Bethesda, MD 20892 USA.
[Chrousos, George P.] Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S544
EP S544
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742601503
ER
PT J
AU Korach, K
AF Korach, Kenneth
TI Estrogen receptor insensitivity: Consequences in endocrine physiology
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Korach, Kenneth] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S263
EP S263
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742600291
ER
PT J
AU Marx, SJ
AF Marx, Stephen J.
TI Multiple endocrine neoplasia type 1 (MEN1)
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Marx, Stephen J.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S211
EP S211
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742600073
ER
PT J
AU Mercado-Asis, LB
Lim-Uy, SW
Galia, AM
Mamba, LAE
Sia-Atanacio, AY
Chu, AL
Lorenzo, ZG
Padua, MLM
Macaballug, AG
Fonte, JS
Robles, JF
Pacak, K
AF Mercado-Asis, Leilani B.
Lim-Uy, Stefanie W.
Galia, Analyza M.
Mamba, Lucy Anne E.
Sia-Atanacio, Aileen Y.
Chu, Albert L.
Lorenzo, Zarina G.
Padua, Ma. Louella M.
Macaballug, Aurora G.
Fonte, Jay S.
Robles, Jeremyjones F.
Pacak, Karel
TI Clinical, hormonal, and genetic profile of filipino patients with
suspected pheochromocytoma (preliminary report)
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Mercado-Asis, Leilani B.; Lim-Uy, Stefanie W.; Galia, Analyza M.; Mamba, Lucy Anne E.; Sia-Atanacio, Aileen Y.; Chu, Albert L.; Lorenzo, Zarina G.; Padua, Ma. Louella M.; Macaballug, Aurora G.; Fonte, Jay S.; Robles, Jeremyjones F.] Univ Santo Tomas Hosp, Sect Endocrinol & Metab, Manila, Philippines.
[Fonte, Jay S.; Robles, Jeremyjones F.; Pacak, Karel] NICHHD, Reprod & Adult Endocrinol Program, Sect Med Neuroendocrinol, Natl Inst Hlth, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S634
EP S634
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742601867
ER
PT J
AU Merke, DP
AF Merke, Deborah P.
TI New aspects of congenital adrenal hyperplasia
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Merke, Deborah P.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S307
EP S307
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742600480
ER
PT J
AU Nieman, LK
AF Nieman, Lynnette K.
TI Diagnostic challenges and medical treatment of Cushing's disease
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S209
EP S209
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742600066
ER
PT J
AU Shamay, A
Feuermann, Y
Klover, P
Yamaji, D
Robinson, GW
Hennighausen, L
AF Shamay, Avi
Feuermann, Yonatan
Klover, Peter
Yamaji, D.
Robinson, G. W.
Hennighausen, Lothar
TI Expression of micro RNA 21 in mammary stem cells is controlled by
cytokine-STAT5 signaling
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Shamay, Avi] Agr Res Org, Volcani Ctr, Inst Anim Sci, IL-50250 Bet Dagan, Israel.
[Shamay, Avi; Feuermann, Yonatan; Klover, Peter; Yamaji, D.; Robinson, G. W.; Hennighausen, Lothar] Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S623
EP S623
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742601824
ER
PT J
AU Sue, M
Nakamura, H
Kawashima, A
Ishido, Y
Wu, H
Akama, T
Tanigawa, K
Kohn, LD
Suzuki, K
AF Sue, Mariko
Nakamura, Hanna
Kawashima, Akira
Ishido, Yuko
Wu, Huhehasi
Akama, Takeshi
Tanigawa, Kazunari
Kohn, Leonard D.
Suzuki, Koichi
TI The effect of anti-thyroid drugs on sodium-iodide-symporter (NIS)
expression in rat thyroid FRTL-5 cells
SO ENDOCRINE JOURNAL
LA English
DT Meeting Abstract
C1 [Sue, Mariko; Kawashima, Akira; Ishido, Yuko; Wu, Huhehasi; Akama, Takeshi; Tanigawa, Kazunari; Suzuki, Koichi] Natl Inst Infect Dis, Leoprosy Res Ctr, Lab Mol Diagnost, Tokyo, Japan.
[Sue, Mariko; Nakamura, Hanna] Toho Univ, Sch Med, Dept Internal Med Omori, Div Diabet Metab & Endocrinol, Tokyo, Japan.
[Nakamura, Hanna; Kohn, Leonard D.; Suzuki, Koichi] NIDDK, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR
PY 2010
VL 57
SU 2
BP S480
EP S480
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 623LV
UT WOS:000279742601243
ER
PT J
AU Dahiya, N
Morin, PJ
AF Dahiya, Neetu
Morin, Patrice J.
TI MicroRNAs in ovarian carcinomas
SO ENDOCRINE-RELATED CANCER
LA English
DT Review
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TARGET MESSENGER-RNAS; TUMOR-SUPPRESSOR;
HUMAN CANCER; EXPRESSION PROFILES; CELL-PROLIFERATION; GENE-EXPRESSION;
DOWN-REGULATION; NUCLEAR EXPORT; MIRNA TARGETS
AB The molecular mechanisms involved in epithelial ovarian cancer initiation and progression are just beginning to be elucidated. In particular, it has become evident that microRNAs (miRNAs or miRs), a class of molecules that post-transcriptionally regulate gene expression, play a major role in ovarian tumorigenesis. Several microRNA profiling studies have identified changes in microRNA patterns that take place during ovarian cancer development. While most deregulated microRNAs are down-regulated in cancer, and may therefore act as tumor suppressors, others are elevated and may represent novel oncogenes in this disease. A number of microRNAs identified as aberrantly expressed in ovarian carcinoma have been shown to have important functional roles in cancer development and may therefore represent targets for therapy. In addition, some of the microRNA patterns may have prognostic significance. The identification of functional targets represents a major hurdle in our understanding of microRNA function in ovarian carcinoma, but significant progress is being made. It is hoped that a better understanding of the microRNA expression and roles in ovarian cancer may provide new avenues for the detection, diagnosis, and therapy of this deadly disease.
C1 [Dahiya, Neetu; Morin, Patrice J.] NIA, Lab Cellular & Mol Biol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Morin, Patrice J.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA.
RP Morin, PJ (reprint author), NIA, Lab Cellular & Mol Biol, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100,Room 6C228, Baltimore, MD 21224 USA.
EM morinp@mail.nih.gov
RI Dahiya, Neetu/E-5208-2011
FU National Institutes of Health, National Institute on Aging
FX This work was supported entirely by the Intramural Research Program of
the National Institutes of Health, National Institute on Aging.
NR 93
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U1 1
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD MAR
PY 2010
VL 17
IS 1
BP F77
EP F89
DI 10.1677/ERC-09-0203
PG 13
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA 570HJ
UT WOS:000275663100033
PM 19903743
ER
PT J
AU Liu, Y
Coello, AG
Grinevich, V
Aguilera, G
AF Liu, Ying
Coello, Ana G.
Grinevich, Valery
Aguilera, Greti
TI Involvement of Transducer of Regulated cAMP Response Element-Binding
Protein Activity on Corticotropin Releasing Hormone Transcription
SO ENDOCRINOLOGY
LA English
DT Article
ID MEDIATED GENE-EXPRESSION; HYPOTHALAMIC CELL-LINE; IN-VIVO; STRESS; CREB;
KINASE; ACTIVATION; COACTIVATORS; RECEPTORS; PHOSPHORYLATION
AB We have recently shown that phospho-cAMP response element-binding protein ( CREB) is essential but not sufficient for activation of CRH transcription, suggesting the requirement of a coactivator. Here, we test the hypothesis that the CREB coactivator, transducer of regulated CREB activity (TORC), is required for activation of CRH transcription, using the cell line 4B and primary cultures of hypothalamic neurons. Immunohistochemistry and Western blot experiments in 4B cells revealed time-dependent nuclear translocation of TORC1, TORC 2, and TORC3 by forskolin [ but not by the phorbol ester, phorbol 12-myristate 13-acetate (PMA)] in a concentration-dependent manner. In reporter gene assays, cotransfection of TORC1 or TORC2 potentiated the stimulatory effect of forskolin on CRH promoter activity but had no effect in cells treated with PMA. Knockout of endogenous TORC using silencing RNA markedly inhibited forskolin-activated CRH promoter activity in 4B cells, as well as the induction of endogenous CRH primary transcript by forskolin in primary neuronal cultures. Coimmunoprecipitation and chromatin immunoprecipitation experiments in 4B cells revealed association of CREB and TORC in the nucleus, and recruitment of TORC2 by the CRH promoter, after 20-min incubation with forskolin. These studies demonstrate a correlation between nuclear translocation of TORC with association to the CRH promoter and activation of CRH transcription. The data suggest that TORC is required for transcriptional activation of the CRH promoter by acting as a CREB coactivator. In addition, cytoplasmic retention of TORC during PMA treatment is likely to explain the failure of phorbolesters to activate CRH transcription in spite of efficiently phosphorylating CREB. ( Endocrinology 151: 1109-1118, 2010)
C1 [Liu, Ying; Coello, Ana G.; Aguilera, Greti] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrine Physiol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Grinevich, Valery] Max Planck Inst Med Res, Dept Mol Neurobiol, D-69120 Heidelberg, Germany.
RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bldg 10,CRC,Room 1E-3330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM greti_aguilera@nih.gov
FU Intramural Research program of the National Institutes of
Health/National Institute of Child Health and Human Development
FX We thank Dr. Marc Montminy (Salk Institute, La Jolla, CA) for providing
the expression vectors for TORC1 and TORC2.; Address all correspondence
and requests for reprints to: Greti Aguilera, M. D, Section on Endocrine
Physiology, Developmental Endocrinology Branch, National Institute of
Child Health and Human Development, National Institutes of Health
Building 10, CRC, Room 1E-3330, 10 Center Drive, Bethesda, Maryland
20892. E-mail: greti_aguilera@nih.gov.; This work was supported by the
Intramural Research program of the National Institutes of
Health/National Institute of Child Health and Human Development.;
Disclosure Summary: The authors have nothing to disclose.
NR 32
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U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAR
PY 2010
VL 151
IS 3
BP 1109
EP 1118
DI 10.1210/en.2009-0963
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 558AF
UT WOS:000274711600031
PM 20080871
ER
PT J
AU Schecter, A
Haffner, D
Colacino, J
Patel, K
Papke, O
Opel, M
Birnbaum, L
AF Schecter, Arnold
Haffner, Darrah
Colacino, Justin
Patel, Keyur
Paepke, Olaf
Opel, Matthias
Birnbaum, Linda
TI Polybrominated Diphenyl Ethers (PBDEs) and Hexabromocyclodecane (HBCD)
in Composite US Food Samples
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE dietary intake; food; HBCD; PBDE; United States
ID BROMINATED FLAME RETARDANTS; TETRABROMOBISPHENOL-A TBBPA;
POLYCHLORINATED-BIPHENYLS; UNITED-STATES; MARKET-BASKET; ADIPOSE-TISSUE;
HUMAN EXPOSURE; DIETARY-INTAKE; HOUSE-DUST; TEMPORAL TREND
AB OBJECTIVES: This study was designed to update previous U.S. market basket surveys of levels and polybrominated diphenyl ether (PBDE) dietary intake calculations. This study also quantifies hexabromocyclododecane (HBCD) levels in U.S.-purchased foods for the first time and estimates U.S. dietary intake of HBCD. This is part of a larger market basket study reported in two companion articles, of current levels of certain persistent organic pollutants (POPs) PBDEs, HBCD, perfluorinated compounds, polychlorinated biphenyls, and pesticides in composite food samples collected in 2008-2009.
METHODS: In this study, we measured concentrations of 24 PBDE congeners and total HBCD in composite samples of 31 food types (310 samples). U.S. dietary intake of PBDEs and HBCD was estimated referencing the most current U.S. Department of Agriculture loss-adjusted food availability report.
RESULTS: Total PBDE concentrations in food varied by food type, ranging from 12 pg/g wet weight (ww) in whole milk to 1,545 pg/g ww in canned sardines and 6,211 pg/g ww in butter. Total HBCD concentrations also varied substantially within and among food groups, ranging from 23 pg/g in canned beef chili to 593 pg/g in canned sardines. HBCD was not detected in any dairy samples. Dietary intake of all PBDE congeners measured was estimated to be 50 ng/day, mostly from dairy consumption but also from meat and fish. HBCD intake was estimated at 16 ng/day, primarily from meat consumption.
CONCLUSION: PBDEs and HBCDs currently contaminate some food purchased in the United States, although PBDE intake estimated in this study is lower than reported in our previous market basket surveys. HBCD is in food at higher levels than expected based on previously reported levels in milk and blood compared with PBDE levels and is comparable to European levels.
C1 [Schecter, Arnold; Patel, Keyur] Univ Texas Dallas, Sch Publ Hlth, Dallas, TX 75390 USA.
[Haffner, Darrah] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Colacino, Justin] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Paepke, Olaf; Opel, Matthias] Eurofins, Hamburg, Germany.
[Birnbaum, Linda] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Schecter, A (reprint author), Univ Texas Dallas, Sch Publ Hlth, 6011 Harry Hines, Dallas, TX 75390 USA.
EM arnold.schecter@utsouthwestern.edu
FU Gustavus and Louise Pfeiffer Research Foundation
FX We acknowledge the Gustavus and Louise Pfeiffer Research Foundation for
their generous funding of this research.
NR 59
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U1 4
U2 58
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 MAR
PY 2010
VL 118
IS 3
BP 357
EP 362
DI 10.1289/ehp.0901345
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 567LX
UT WOS:000275449500026
PM 20064778
ER
PT J
AU D'Aloisio, AA
Baird, DD
DeRoo, LA
Sandler, DP
AF D'Aloisio, Aimee A.
Baird, Donna D.
DeRoo, Lisa A.
Sandler, Dale P.
TI Association of Intrauterine and Early-Life Exposures with Diagnosis of
Uterine Leiomyomata by 35 Years of Age in the Sister Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE diabetes mellitus; diethylstilbestrol; early life; leiomyoma;
phytoestrogens; pregnancy; prenatal exposure delayed effects;
socioeconomic factors; soy formula
ID PHYTOESTROGEN GENISTEIN; IMPRINTED GENES; REPRODUCTIVE FACTORS; NEONATAL
EXPOSURE; INFANT FORMULA; RISK; EXPRESSION; WOMEN; MICE; FIBROIDS
AB BACKGROUND: Early-life exposures to hormonally active compounds and other factors may affect later response to estrogen or progesterone and hence may influence development of uterine leiomyomata (fibroids).
OBJECTIVES: We evaluated associations of in utero and early-life exposures, including soy formula, with self-report of physician-diagnosed fibroids by 35 years of age.
METHODS: Our study included 19,972 non-Hispanic white women who were 35-59 years of age when they enrolled in the Sister Study in 2003-2007. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using log-binomial regression models for fibroid associations with adjustment for participant's age and education, maternal age at participant's birth, birth order, and childhood family income.
RESULTS: Greater risk of early fibroid diagnosis was associated with soy formula during infancy (RR = 1.25; 95% CI, 0.97-1.61), maternal prepregnancy diabetes (RR = 2.05; 95% CI, 1.16-3.63), low childhood socioeconomic status (RR = 1.28; 95% CI, 1.01-1.63), and gestational age at birth (RR = 1.64; 95% CI, 1.27-2.13, for being born at least 1 month early). In utero diethylstilbestrol (DES) exposure was also associated with early fibroid diagnosis (RR = 1.42; 95% CI, 1.13-1.80), but this association was driven by women reporting probable rather than definite exposure.
CONCLUSIONS: There are plausible biological pathways by which these early-life factors could promote fibroid pathogenesis. This is the first epidemiologic study to evaluate such exposures, with the exception of in utero DES, in relation to fibroid risk, and replication of findings in other populations is needed.
C1 [D'Aloisio, Aimee A.; Baird, Donna D.; DeRoo, Lisa A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP D'Aloisio, AA (reprint author), NIEHS, Epidemiol Branch, NIH, US Dept HHS, POB 12233,Mail Drop A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM daloisio@niehs.nih.gov
RI Baird, Donna/D-5214-2017;
OI Baird, Donna/0000-0002-5544-2653; Sandler, Dale/0000-0002-6776-0018
FU Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences [Z01 ES04400509]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences (Z01 ES04400509).
NR 34
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U2 9
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 MAR
PY 2010
VL 118
IS 3
BP 375
EP 381
DI 10.1289/ehp.0901423
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 567LX
UT WOS:000275449500029
PM 20194067
ER
PT J
AU Birnbaum, LS
AF Birnbaum, Linda S.
TI TSCA Reform Under Way in Congress
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
C1 [Birnbaum, Linda S.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda S.] NTP, NIH, US Dept HHS, Res Triangle Pk, NC USA.
RP Birnbaum, LS (reprint author), NIEHS, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM birnbaumls@niehs.nih.gov
NR 0
TC 2
Z9 2
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 MAR
PY 2010
VL 118
IS 3
BP A106
EP A106
DI 10.1289/ehp.1001917
PG 1
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 567LX
UT WOS:000275449500001
PM 20197245
ER
PT J
AU Zavitsanou, A
Malliori, M
Sypsa, V
Petrodaskalaki, M
Psichogiou, M
Rokka, C
Giannopoulos, A
Kalapothaki, V
Whitby, D
Hatzakis, A
AF Zavitsanou, A.
Malliori, M.
Sypsa, V.
Petrodaskalaki, M.
Psichogiou, M.
Rokka, C.
Giannopoulos, A.
Kalapothaki, V.
Whitby, D.
Hatzakis, A.
TI Seroepidemiology of human herpesvirus 8 (HHV-8) infection in injecting
drug users
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Article
DE HHV-8; injecting drug users (IDUs); risk factors; seroepidemiology
ID HIV-1-INFECTED PREGNANT-WOMEN; HUMAN-IMMUNODEFICIENCY-VIRUS;
KAPOSIS-SARCOMA; SEXUAL TRANSMISSION; DNA-SEQUENCES;
HERPESVIRUS-INFECTION; RISK-FACTORS; SEROPREVALENCE; AIDS; BLOOD
AB A cross-sectional study was carried out in injecting drug users (IDUs) from Greece to assess the seroprevalence of human herpesvirus 8 (HHV-8) and to identify potentially associated risk factors. A total of 288 IDUs were tested for K8.1 antibodies to HHV-8 lytic antigen. Associations between HHV-8 serostatus and potential risk factors were examined Using univariate and multivarlate logistic regression analysis. Seroprevalence of HHV-8 was 24.3% (95% CI 19.5-29.7), increasing with age from 19.4% in those aged <30 years to 52.9% in those aged >= 40 years (P for trend = 0.003). No statistically significant associations between HHV-8-positive status and gender, educational level, age at first drug injection, needle sharing, number of imprisonments, complications from drug overdose, HIV and HCV were observed. In the multivariate logistic regression analysis, older age (>= 40 vs. <40 years, OR 3.30, 95 % CI 1.14-9.56) and report of septicaemia/abscess (yes vs. no, OR 1.80, 95% CI 1.01-3.18) were each independently associated with higher HHV-8 seroprevalence. HHV-8 is highly prevalent in the IDU Population in Greece. The independent association between HHV-8 and reported abscess or septicaemia supports the hypothesis that poor hygiene conditions in the setting of drug injection may contribute to HHV-8 transmission.
C1 [Zavitsanou, A.; Sypsa, V.; Petrodaskalaki, M.; Psichogiou, M.; Rokka, C.; Kalapothaki, V.; Hatzakis, A.] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece.
[Malliori, M.] Univ Athens, Sch Med, Eginit Hosp, Dept Psychiat, GR-11527 Athens, Greece.
[Giannopoulos, A.] Univ Athens, Sch Med, Laiko Gen Hosp, Dept Surg 1, GR-11527 Athens, Greece.
[Whitby, D.] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA.
RP Hatzakis, A (reprint author), Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias St, GR-11527 Athens, Greece.
EM ahatzak@med.uoa.gr
FU Hellenic Scientific Society for AIDS and Sexually Transmitted Diseases
FX This project was funded by the Hellenic Scientific Society for AIDS and
Sexually Transmitted Diseases.
NR 39
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U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0950-2688
J9 EPIDEMIOL INFECT
JI Epidemiol. Infect.
PD MAR
PY 2010
VL 138
IS 3
BP 403
EP 408
DI 10.1017/S0950268809990628
PG 6
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 560CD
UT WOS:000274878500014
PM 19698211
ER
PT J
AU Botello-Harbaum, M
Schroeder, JR
Collins, CC
Moolchan, ET
AF Botello-Harbaum, Maria
Schroeder, Jennifer R.
Collins, Charles C.
Moolchan, Eric T.
TI NICOTINE REPLACEMENT THERAPY USE AMONG ADOLESCENT SMOKERS SEEKING
CESSATION TREATMENT
SO ETHNICITY & DISEASE
LA English
DT Article
DE Nicotine Dependence; Adolescents; Nicotine Replacement Therapy;
Treatment; Health Disparities
ID AMERICAN TEENAGE SMOKERS; DISPARITIES; DEPENDENCE; HEALTH; PATCH
AB Objective: To examine the correlates of prior nicotine replacement therapy (NRT) in an urban sample of adolescent smokers seeking smoking cessation treatment.
Design: Adolescents were recruited via radio, TV and print advertisements for participation in treatment studies. Participants completed a structured interview using a prescreeningquestionnaire.
Setting: Data were collected via a telephone interview by trained research personnel.
Participants: A sample (N=1879) cessation treatment-seeking volunteer boys (38.2%) and girls (61.8%) aged 12 to 17 years, from a diverse ethnic background residing in the Baltimore, Maryland metropolitan area.
Interventions: No interventions were used in this observational study.
Main Outcome Measures: Use of NRT in adolescents stratified by age, Fagerstrom Test of Nicotine Dependence (FTND), and race/ethnicity.
Results: The sample had a mean FIND score of 5.7 (SD = 2.2). About 41% smoked 11 to 20 cigarettes per day. Adolescent smokers who had used NRT were statistically but only marginally older than those who had not (15.9 vs 15.7 years; t-test= 2.60, P=0.01). FTND score, a measure of nicotine dependence, was higher among those who had used NRT (6.0 vs 5.6; t-test= 3.37, P=.001). African American adolescents were less likely to have used NRT than their European American counterparts (33.0% vs 61.2%; chi(2)=16.09, P<.003). After stepwise logistic regression analyses, age, FIND and race/ethnicity remained predictors of NRT use.
Conclusion: Our results show differences in NRT use patterns based on age, FTND, and race! ethnicity. European American youths are more likely than their 'other' counterparts to use NRT, after adjusting for age and smoking severity, whereas, African American youth are less likely than their 'other' counterparts to use NRT. These findings suggest racial/ethnic disparities in accessing smoking cessation modalities among adolescents. Further research is needed to fully elucidate factors contributing to these differences in order to facilitate increased smoking cessation rates among all adolescents. (Ethn Dis. 2010;20:180-184)
C1 [Botello-Harbaum, Maria] NICHHD, NIH, Intramural Res Program, Bethesda, MD USA.
[Schroeder, Jennifer R.; Collins, Charles C.; Moolchan, Eric T.] Natl Inst Drug Abuse, NIH, Intramural Res Program, Bethesda, MD USA.
RP Moolchan, ET (reprint author), Alkermes Inc, Clin Sci, 88 Sidney St, Cambridge, MA 02139 USA.
EM eric.moolchan@alkermes.com
FU National Institute on Drug Abuse; Eunice Kennedy Shriver National
Institute of Child Health and Human Development; Health Resources and
Services Administration
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, the Eunice Kennedy Shriver National
Institute of Child Health and Human Development Intramural Research
Program, and the Health Resources and Services Administration. We are
grateful for the recruitment contributions of NOVA Research and the
Matthews Media Group.
NR 23
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U1 1
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PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
J9 ETHNIC DIS
JI Ethn. Dis.
PD SPR
PY 2010
VL 20
IS 2
BP 180
EP 184
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 598EJ
UT WOS:000277815700016
PM 20503900
ER
PT J
AU Walitza, S
Wendland, JR
Gruenblatt, E
Warnke, A
Sontag, TA
Tucha, O
Lange, KW
AF Walitza, Susanne
Wendland, Jens R.
Gruenblatt, Edna
Warnke, Andreas
Sontag, Thomas A.
Tucha, Oliver
Lange, Klaus W.
TI Genetics of early-onset obsessive-compulsive disorder
SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY
LA English
DT Review
DE Obsessive-compulsive disorder; Serotonin; Glutamate transporter gene;
Early onset; Brain-derived neurotrophic factor
ID 5-HT2A PROMOTER POLYMORPHISM; SEROTONIN TRANSPORTER; TRANSMISSION
DISEQUILIBRIUM; PSYCHIATRIC-DISORDERS; PEDIATRIC PROBANDS; FAMILY;
ASSOCIATION; ADOLESCENTS; CHILDREN; LINKAGE
AB Obsessive-compulsive disorder (OCD) is characterized by recurrent, intrusive and disturbing thoughts as well as by repetitive stereotypic behaviors. Epidemiological data are similar in children and adults, i.e., between 1 and 3% of the general population suffer from OCD. Children with OCD are often seriously impaired in their development. OCD, especially of early onset, has been shown to be familial. Several candidate genes of predominantly neurotransmitter systems have been analyzed and a total of three genome-wide linkage scans have been performed until now. Analyses of candidate genes in linkage regions have not provided evidence for their involvement in OCD, with the exception of the glutamate transporter gene SLC1A1 on 9p24. Genome-wide association analyses are in progress and the results will promote further independent replication studies. The consideration of subtypes regarding age of onset, symptom dimensions and/or comorbid disorders is needed.
C1 [Walitza, Susanne; Gruenblatt, Edna] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland.
[Wendland, Jens R.] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA.
[Warnke, Andreas] Univ Wurzburg, Dept Child & Adolescent Psychiat & Psychotherapy, Wurzburg, Germany.
[Sontag, Thomas A.; Lange, Klaus W.] Univ Regensburg, Dept Expt Psychol, Regensburg, Germany.
[Tucha, Oliver] Univ Groningen, Dept Psychol, NL-9712 TS Groningen, Netherlands.
RP Walitza, S (reprint author), Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland.
EM susanne.walitza@kjpdzh.ch
RI Wendland, Jens/A-1809-2012; Grunblatt, Edna/A-6762-2016;
OI Grunblatt, Edna/0000-0001-8505-7265; Walitza,
Susanne/0000-0002-8161-8683
NR 59
TC 36
Z9 37
U1 7
U2 22
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1018-8827
J9 EUR CHILD ADOLES PSY
JI Eur. Child Adolesc. Psych.
PD MAR
PY 2010
VL 19
IS 3
SI SI
BP 227
EP 235
DI 10.1007/s00787-010-0087-7
PG 9
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 569WE
UT WOS:000275632700005
PM 20213231
ER
PT J
AU Scuteri, A
Najjar, SS
Orru', M
Usala, G
Piras, MG
Ferrucci, L
Cao, A
Schlessinger, D
Uda, M
Lakatta, EG
AF Scuteri, Angelo
Najjar, Samer S.
Orru', Marco
Usala, Gianluca
Piras, Maria Grazia
Ferrucci, Luigi
Cao, Antonio
Schlessinger, David
Uda, Manuela
Lakatta, Edward G.
TI The central arterial burden of the metabolic syndrome is similar in men
and women: the SardiNIA Study
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Metabolic syndrome; Ageing; Gender; Arterial stiffness; Carotid IMT
ID EARLY CAROTID ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; RISK-FACTOR;
STIFFNESS; ADULTS; HEALTH; AGE
AB We evaluated whether specific clusters of metabolic syndrome (MetS) components differentially impact on arterial structure and function, and whether the impact is similar in men and in women.
Components of the MetS and arterial properties were assessed in 6148 subjects, aged 14-102 in a cluster of four towns in Sardinia, Italy. MetS was defined in accordance with the ATP III criteria. Age groups were classified as: < 35, 35-49, 50-64, and >= 65 years. Systolic blood pressure (BP), diastolic BP, pulse pressure, common carotid artery (CCA) diameter, intima-media thickness, distensibility, strain, stiffness index, wall stress, and aortic pulse wave velocity were measured. Common carotid artery plaque was defined as focal encroachment of the arterial wall and CCA calcification as acoustic shadowing. In any age group, subjects with MetS presented thicker, stiffer or less distensible, and wider large arteries than controls. The arterial burden of MetS increased as the number of altered MetS components increased. However, not all MetS components were associated with the same changes in arterial properties. In fact, specific clusters of MetS components, i.e. any combination of altered glucose tolerance, elevated BP, and elevated triglycerides (with or without abdominal obesity), dramatically increased age-associated arterial changes. The impact of MetS on arterial function was similar in men and women.
MetS accelerates age-associated arterial changes, even in older persons. However, not all the clusters of MetS components render the same burden on arterial structure and function.
C1 [Scuteri, Angelo; Najjar, Samer S.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Scuteri, Angelo; Orru', Marco; Usala, Gianluca; Piras, Maria Grazia; Cao, Antonio; Uda, Manuela] Cittadella Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Study Sect, NIH, Baltimore, MD 21224 USA.
[Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Scuteri, A (reprint author), IRCCS, INRCA, UO Geriatria, Via Cassia 1167, I-00189 Rome, Italy.
EM angeloelefante@interfree.it
OI piras, maria grazia/0000-0001-9004-0900
FU NIA [NO1-AG-1-2109]
FX The SardiNIA team was supported by Contract NO1-AG-1-2109 from the NIA.
NR 24
TC 39
Z9 40
U1 3
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD MAR
PY 2010
VL 31
IS 5
BP 602
EP 613
DI 10.1093/eurheartj/ehp491
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 564UA
UT WOS:000275241900020
PM 19942601
ER
PT J
AU Yang, HP
Brinton, LA
Platz, EA
Lissowska, J
Lacey, JV
Sherman, ME
Peplonska, B
Garcia-Closas, M
AF Yang, Hannah P.
Brinton, Louise A.
Platz, Elizabeth A.
Lissowska, Jolanta
Lacey, James V., Jr.
Sherman, Mark E.
Peplonska, Beata
Garcia-Closas, Montserrat
TI Active and passive cigarette smoking and the risk of endometrial cancer
in Poland
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Endometrial cancer; Active smoking; Passive smoking
ID NONSMOKING WOMEN; BREAST-CANCER; LUNG-CANCER; TOBACCO; 2-HYDROXYESTRONE;
POPULATION; ESTRADIOL; EXPOSURE; ESTROGEN; STATES
AB Background: Epidemiological studies have consistently reported that active cigarette smoking is inversely associated with endometrial cancer risk. However, dose-response relationships with quantitative measures of active smoking or passive smoking remain less clear.
Methods: Data on lifetime active and passive smoking were collected for 551 endometrial cancer cases and 1925 controls in a population-based case-control study conducted during 2001-2003 in Poland (Warsaw and Lodz).
Results: Compared with never active smokers, active current (odds Ratio (OR) = 0.51, 95% Confidence Interval (CI): 0.39, 0.68) and former smokers (OR = 0.60, 95% CI: 0.45, 0.80) were at a statistically significantly decreased risk. We did not observe statistically significant inverse dose-response relationships with increasing exposure with duration and cumulative measures. However, there was some indication that the highest category of number of years (OR = 0.35, 95% CI: 0.23-0.55), intensity (OR = 0.41, 95% CI: 0.24-0.69), and dose (OR = 0.38, 95% CI: 0.24-0.60) of smoking among current smokers had the greatest inverse association compared to never smokers. Our data did not support the presence of an inverse association with passive smoking among never active smokers (OR = 0.92; 95% CI: 0.65, 1.29).
Conclusion: Our results support that long-term and heavy smoking among current smokers strongly influence endometrial cancer risk. Published by Elsevier Ltd.
C1 [Yang, Hannah P.; Brinton, Louise A.; Lissowska, Jolanta; Lacey, James V., Jr.; Sherman, Mark E.; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Yang, Hannah P.; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Peplonska, Beata] Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland.
RP Yang, HP (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS-5034A, Rockville, MD 20852 USA.
EM yanghan@mail.nih.gov
RI Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015;
Brinton, Louise/G-7486-2015;
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799
FU National Cancer Institute, National Institutes of Health
FX The authors would like to thank Neonila Szeszenia-Dabrowska of the Nofer
Institute of Occupational medicine (Lodz, Poland) and Witold Zatonski of
the M. Sklodowska-Curie institute of Oncology and Cancer Centre (Warsaw,
Poland) for their contribution to the Polish Endometrial Cancer Study.
Pei Chao and Michael Stagner (IMS, Silver Spring, MD, USA) have been
invaluable to the management of the study. This work would not be
possible without the dedicated efforts of the physicians, nurses,
interviewers and study participants. This research was supported by
funds from the intramural programme of the National Cancer Institute,
National Institutes of Health.
NR 30
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U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2010
VL 46
IS 4
BP 690
EP 696
DI 10.1016/j.ejca.2009.11.015
PG 7
WC Oncology
SC Oncology
GA 569KE
UT WOS:000275594500012
PM 20036529
ER
PT J
AU van Cruijsen, H
Voest, EE
Punt, CJA
Hoekman, K
Witteveen, PO
Meijerink, MR
Puchalski, TA
Robertson, J
Saunders, O
Jurgensmeier, JM
van Herpen, CML
Giaccone, G
AF van Cruijsen, Hester
Voest, Emile E.
Punt, Cornelis J. A.
Hoekman, Klaas
Witteveen, Petronella O.
Meijerink, Martijn R.
Puchalski, Thomas A.
Robertson, Jane
Saunders, Owain
Jurgensmeier, Juliane M.
van Herpen, Carla M. L.
Giaccone, Giuseppe
TI Phase I evaluation of cediranib, a selective VEGFR signalling inhibitor,
in combination with gefitinib in patients with advanced tumours
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE VEGFR-1; VEGFR-2; VEGFR-3; EGFR; Angiogenesis inhibitors; Clinical
trial; Phase I
ID ENDOTHELIAL GROWTH-FACTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR;
FACTOR RECEPTOR; SOLID TUMORS; TRIAL; CARCINOMA; BEVACIZUMAB; SUNITINIB;
ERLOTINIB
AB Aim: Cediranib is a highly potent inhibitor of vascular endothelial growth factor receptor (VEGFR) signalling. Preclinical and clinical data suggest that inhibition of the VEGFR and epidermal growth factor receptor (EGFR) pathways may be synergistic. Combination treatment with cediranib and gefitinib, an EGFR signalling inhibitor, was evaluated in patients with advanced solid tumours.
Patients and methods: Ninety patients received treatment in this four-part, open-label study (NCT00502060). The patients received once-daily oral doses of cediranib (20-45 mg) and gefitinib 250 mg (part A1; n = 16) or 500 mg (part B1; n = 44). A cohort expansion phase investigated the potential pharmacokinetic interaction of cediranib 30 mg with gefitinib 250 mg (part A2; n = 15) or 500 mg (part B2; n = 15). The primary objective was to assess the safety and tolerability of cediranib with gefitinib. Secondary assessments included pharmacokinetics, efficacy and pharmacodynamics.
Results: Combination treatment was generally well tolerated; the protocol-defined maximum-tolerated dose of cediranib was 30 mg/day with gefitinib 250 mg/day (part Al) and cediranib 45 mg/day was the maximum dose investigated with gefitinib 500 mg/day (part B1). The most common adverse events were diarrhoea (84 [93%]), anorexia (63 [70%]) and fatigue (60 [67%]). Cediranib pharmacokinetic parameters were not substantially different when given alone or in combination with gefitinib. Gefitinib pharmacokinetic parameters were similar to those seen previously with gefitinib monotherapy. Efficacy results included eight (9%) confirmed partial responses (6 renal; 1 lung; 1 osteosarcoma) and 38 (42%) patients with stable disease. Pharmacodynamic assessments demonstrated changes in levels of VEGF and soluble VEGFR-2 following treatment.
Conclusions: Combination treatment was generally well tolerated and showed encouraging antitumour activity in patients with advanced solid tumours. These results merit further exploration. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [van Cruijsen, Hester; Hoekman, Klaas; Giaccone, Giuseppe] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Amsterdam, Netherlands.
[Meijerink, Martijn R.] Vrije Univ Amsterdam, Med Ctr, Dept Radiol, Amsterdam, Netherlands.
[Voest, Emile E.; Witteveen, Petronella O.] Univ Med Ctr Utrecht, Dept Med Oncol, Utrecht, Netherlands.
[Punt, Cornelis J. A.; van Herpen, Carla M. L.] Radboud Univ Nijmegen, Med Ctr, Dept Med Oncol, NL-6525 ED Nijmegen, Netherlands.
[Puchalski, Thomas A.] AstraZeneca, Wilmington, DE USA.
[Robertson, Jane; Saunders, Owain; Jurgensmeier, Juliane M.] AstraZeneca, Macclesfield, Cheshire, England.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bldg 10,Room 12N226,10 Ctr Dr, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Juergensmeier, Juliane/I-4117-2013; Herpen, Carla/N-3576-2014; Giaccone,
Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; Meijerink,
Martijn/0000-0002-1500-7294
FU AstraZeneca
FX This study, including editorial assistance provided by Dr. Jen Lewis of
Mudskipper Bioscience, was supported financially by AstraZeneca.
NR 42
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U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2010
VL 46
IS 5
BP 901
EP 911
DI 10.1016/j.ejca.2009.12.023
PG 11
WC Oncology
SC Oncology
GA 584MJ
UT WOS:000276755800017
PM 20061136
ER
PT J
AU Nacci, C
Addabbo, F
Tarquinio, M
De Benedictis, L
Carratu, MR
Quon, MJ
Montagnani, M
AF Nacci, C.
Addabbo, F.
Tarquinio, M.
De Benedictis, L.
Carratu, M. R.
Quon, M. J.
Montagnani, M.
TI Globular and full-length adiponectin differentially modulate
overexpression of cyclo-oxygenase 2 in endothelium
SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Meeting Abstract
C1 [Nacci, C.; Addabbo, F.; Tarquinio, M.; De Benedictis, L.; Carratu, M. R.; Montagnani, M.] Dept Pharmacol & Human Physiol, Bari, Italy.
[Quon, M. J.] NIH, NCCAM, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0014-2972
J9 EUR J CLIN INVEST
JI Eur. J. Clin. Invest.
PD MAR
PY 2010
VL 40
SU 1
BP 9
EP 9
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 552BF
UT WOS:000274260200026
ER
PT J
AU Brock, KE
Graubard, BI
Fraser, DR
Weinstein, SJ
Stolzenberg-Solomon, RZ
Lim, U
Tangrea, JA
Virtamo, J
Ke, L
Snyder, K
Albanes, D
AF Brock, K. E.
Graubard, B. I.
Fraser, D. R.
Weinstein, S. J.
Stolzenberg-Solomon, R. Z.
Lim, U.
Tangrea, J. A.
Virtamo, J.
Ke, L.
Snyder, K.
Albanes, D.
TI Predictors of vitamin D biochemical status in a large sample of
middle-aged male smokers in Finland
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE vitamin D (25(OH) D) status; predictors of vitamin D deficiency; vitamin
D intake; fish intake; physical activity; BMI
ID YOUNG FINNISH MEN; 25-HYDROXYVITAMIN D; SERUM-LEVELS; D DEFICIENCY;
CANCER-RISK; PROSTATE-CANCER; SUBSEQUENT RISK; D INSUFFICIENCY; BONE
TURNOVER; POPULATION
AB Background/Objectives: As vitamin D deficiency is considered to be more common in regions with little solar ultraviolet (UV) light in winter, the aim of this study was to analyze predictors of vitamin D status by season within a large sample of male smokers from Finland, a country where there is negligible solar UV light in winter.
Subjects/Methods: Vitamin D ( measured by 25-hydroxyvitamin D (25(OH) D) nmol/l) and other serum constituents were assayed. Measured anthropometry, and self-reported dietary intake and physical activity (PA) were obtained and analyzed using stepwise multiple linear and logistic regression in 2271 middle-aged Finnish male smokers.
Results: In all, 27% of the population in winter and 17% in summer had serum 25( OH) D levels of <25 nmol/l, respectively. In summer, in multiple logistic regression analyses with adjustment for confounding and other predictors, high vitamin D intake ( odds ratios ( OR) 3.6; 95% confidence interval (CI) 1.5-8.5), some leisure time PA ( OR 2.0; 95% CI 1.3-3.1) and having a body mass index (BMI) of >= 21 kg/m(2) compared with <21 kg/m(2) ( OR 2.6; 95% CI 1.3-5.0), were associated with 25(OH) D >= 25 nmol/l. In winter, additional modifiable factors were occupational PA ( OR 1.6; 95% CI 1.1-2.5) and high fish ( OR 3.1; 95% CI 1.7-6.2) or poultry consumption ( OR 1.7; 95% CI 1.2-2.5). Predictors from linear regression analyses of continuous levels of 25( OH) D were similar to the logistic regression analyses of 25( OH) D >= 25 nmol/l.
Conclusion: In this Finnish sample more vitamin D intake, PA and having a BMI of >= 21 may have important modifiable roles in maintaining an adequate vitamin D status. European Journal of Clinical Nutrition ( 2010) 64, 280-288; doi:10.1038/ejcn.2009.137; published online 6 January 2010
C1 [Brock, K. E.] Univ Sydney, Fac Hlth Sci, Sydney, NSW 2141, Australia.
[Graubard, B. I.; Weinstein, S. J.; Stolzenberg-Solomon, R. Z.; Albanes, D.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Fraser, D. R.] Univ Sydney, Fac Vet Sci, Sch Anim Sci, Sydney, NSW 2141, Australia.
[Lim, U.] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA.
[Tangrea, J. A.] NCI, Canc Prevent Div, NIH, DHHS, Bethesda, MD 20892 USA.
[Virtamo, J.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Ke, L.] George Inst, Dept Res & Dev, Beijing, Peoples R China.
[Snyder, K.] Informat Management Serv Inc, Silver Spring, MD USA.
RP Brock, KE (reprint author), Univ Sydney, Fac Hlth Sci, Room G204,POB 170 Lidcombe 1825,East St,Lidcombe, Sydney, NSW 2141, Australia.
EM Kaye.Brock@Sydney.edu.au
RI Albanes, Demetrius/B-9749-2015; Osborne, Nicholas/N-4915-2015
OI Osborne, Nicholas/0000-0002-6700-2284
FU NIH; National Cancer Institute, Department of Health and Human Services
[N01-CN-45165, N01-RC-45035, N01-RC-37004]
FX This research was supported in part by the Intramural Research Program
of the NIH and the National Cancer Institute. In addition, this research
was supported by the US Public Health Service contracts N01-CN-45165,
N01-RC-45035 and N01-RC-37004 from the National Cancer Institute,
Department of Health and Human Services. All authors reviewed the final
paper before submission.
NR 50
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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 0954-3007
J9 EUR J CLIN NUTR
JI Eur. J. Clin. Nutr.
PD MAR
PY 2010
VL 64
IS 3
BP 280
EP 288
DI 10.1038/ejcn.2009.137
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 563WX
UT WOS:000275168400008
PM 20051977
ER
PT J
AU Avery, CL
Mills, KT
Chambless, LE
Chang, PP
Folsom, AR
Mosley, TH
Ni, HY
Rosamond, WD
Wagenknecht, L
Wood, J
Heiss, G
AF Avery, Christy L.
Mills, Katherine T.
Chambless, Lloyd E.
Chang, Patricia P.
Folsom, Aaron R.
Mosley, Thomas H.
Ni, Hanyu
Rosamond, Wayne D.
Wagenknecht, Lynne
Wood, Joy
Heiss, Gerardo
TI Long-term association between self-reported signs and symptoms and heart
failure hospitalizations: the Atherosclerosis Risk In Communities (ARIC)
Study
SO EUROPEAN JOURNAL OF HEART FAILURE
LA English
DT Article
DE Epidemiology; Heart failure; Gothenburg score; Surveillance
ID VENTRICULAR SYSTOLIC DYSFUNCTION; GENERAL-POPULATION; MEN BORN;
PREVALENCE; SURVIVAL; CARE; EPIDEMIOLOGY; CONCORDANCE; VALIDATION;
ROTTERDAM
AB Although studies of the accuracy of heart failure (HF) classification scoring systems are available, few have examined their performance when restricted to self-reported items.
We evaluated the association between a simplified version of the Gothenburg score, a validated HF score comprised of cardiac and pulmonary signs and symptoms and medication use, and incident HF hospitalizations in 15 430 Atherosclerosis Risk in Communities (ARIC) Study participants. Gothenburg scores (range: 0-3) were constructed using self-reported items obtained at study baseline (1987-89). Incident HF hospitalization over 14.7 years of follow-up was defined as the first identified hospitalization with an ICD-9 discharge code of 428 (n = 1668). Self-reported Gothenburg scores demonstrated very high agreement with the original metric comprised of self-reported and clinical measures and were directly associated with incident HF hospitalizations: [score = 1: hazard rate ratio (HRR) = 1.23 (1.07-1.42); score = 2: HRR = 2.17 (1.92-2.43); score = 3: HRR = 3.98 (3.37-4.70)].
In a population-based cohort, self-reported Gothenburg criteria items were associated with hospitalized HF over a prolonged follow-up time. The association was also consistent across groups defined by sex and race, suggesting that this simple score deserves further study as a screening tool for the identification of individuals at high risk of HF in resource-limited settings.
C1 [Avery, Christy L.; Mills, Katherine T.; Rosamond, Wayne D.; Wood, Joy; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Bank Amer Ctr, Chapel Hill, NC 27514 USA.
[Chambless, Lloyd E.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27514 USA.
[Chang, Patricia P.] Univ N Carolina, Dept Med, Chapel Hill, NC 27514 USA.
[Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Mosley, Thomas H.] Univ Mississippi, Dept Med, Jackson, MS 39216 USA.
[Ni, Hanyu] NHLBI, Bethesda, MD 20892 USA.
[Wagenknecht, Lynne] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC USA.
RP Avery, CL (reprint author), Univ N Carolina, Dept Epidemiol, Bank Amer Ctr, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA.
EM christy_avery@unc.edu
FU National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022]
FX This work was supported by National Heart, Lung, and Blood Institute
contracts (grant numbers N01-HC-55015, N01-HC-55016, N01-HC-55018,
N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022).
NR 32
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U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1388-9842
J9 EUR J HEART FAIL
JI Eur. J. Heart Fail.
PD MAR
PY 2010
VL 12
IS 3
BP 232
EP 238
DI 10.1093/eurjhf/hfp203
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 558WG
UT WOS:000274778600006
PM 20097681
ER
PT J
AU Meng, GX
Strober, W
AF Meng, Guangxun
Strober, Warren
TI New insights into the nature of autoinflammatory diseases from mice with
Nlrp3 mutations
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Inflammasome; Inflammation; IL-1; Th17
ID NALP3 INFLAMMASOME; CIAS1 MUTATIONS; INTERLEUKIN-1-BETA RELEASE; P2X(7)
RECEPTOR; KEY PLAYER; CELL-DEATH; T-CELLS; ACTIVATION; CASPASE-1; ATP
AB Mutations in the Nlrp3 (CIAS1, cryopyrin) gene are associated with cryopyrin-associated periodic syndrome, autoinflammatory diseases characterized by excessive IL-1 production and neutrophilia in blood and tissues. Recent studies with gene-targeted mice expressing mutations homologous to those found in cryopyrin-associated periodic syndrome patients have advanced the understanding of NLRP3-associated autoinflammation. In this Viewpoint, we will discuss the mechanisms of NLRP3 inflammasome activation and its induction of Th17-cell-dominant immunologic responses.
C1 [Meng, Guangxun; Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, CRC Bldg 10,Room 5W3940,10 Ctr Dr,9000 Rockville, Bethesda, MD 20892 USA.
EM wstrober@niaid.nih.gov
OI 孟, 广勋/0000-0002-4253-9675
FU Division of Intramural Research; National Institute of Allergy and
Infectious Diseases; National Institutes of Health
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health. We apologize to those authors whose work could not be cited due
to space limitations.
NR 35
TC 9
Z9 9
U1 0
U2 0
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD MAR
PY 2010
VL 40
IS 3
BP 649
EP 653
DI 10.1002/eji.200940191
PG 5
WC Immunology
SC Immunology
GA 573SQ
UT WOS:000275935600015
PM 20201022
ER
PT J
AU Bolinger, B
Engeler, D
Krebs, P
Miller, S
Firner, S
Hoffmann, M
Palmer, DC
Restifo, NP
Tian, YH
Clavien, PA
Ludewig, B
AF Bolinger, Beatrice
Engeler, Daniel
Krebs, Philippe
Miller, Simone
Firner, Sonja
Hoffmann, Matthias
Palmer, Douglas C.
Restifo, Nicholas P.
Tian, Yinghua
Clavien, Pierre-Alain
Ludewig, Burkhard
TI IFN-gamma-receptor signaling ameliorates transplant vasculopathy through
attenuation of CD8(+) T-cell-mediated injury of vascular endothelial
cells
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Chronic rejection; CTL; IFN-gamma-receptor; PD-L1; Transplantation;
Vascular endothelial cells
ID CARDIAC ALLOGRAFT VASCULOPATHY; CORONARY-ARTERY-DISEASE;
VERSUS-HOST-DISEASE; INTERFERON-GAMMA; MOUSE HEARTS; DENDRITIC CELLS;
IMMUNOLOGICAL IGNORANCE; MONOCLONAL-ANTIBODY; ANTIVIRAL IMMUNITY;
GRAFT-REJECTION
AB Occlusive transplant vasculopathy (TV) is the major cause for chronic graft rejection. Since endothelial cells (EC) are the first graft cells encountered by activated host lymphocytes, it is important to delineate the molecular mechanisms that coordinate the interaction of EC with activated T cells. Here, the interaction of CD8(+) T cells with Ag-presenting EC in vivo was examined using a transgenic heart transplantation model with beta-galactosidase (beta-gal) expression exclusively in EC (Tie2-LacZ hearts). We found that priming with beta-gal peptide-loaded DC failed to generate a strong systemic IFN-gamma response, but elicited pronounced TV in both IFN-gamma receptor (IFNGR)-competent, and ifngr(-/-) Tie2-LacZ hearts. In contrast, stimulation of EC-specific CD8(+) T cells with beta-gal-recombinant mouse cytomegalovirus (MCMV-LacZ) in recipients of ifngr(+/+) Tie2-LacZ hearts did not precipitate significant TV. However, MCMV-LacZ infection of recipients of ifngr(-/-) Tie2-LacZ hearts led to massive activation of beta-gal-specific CD8 T cells, and led to development of fulminant TV. Further analyses revealed that the strong systemic IFN-gamma "storm" associated with MCMV infection induced upregulation of programmed death-1 ligand 1 (PD-L1) on EC, and subsequent attenuation of programmed death-1 (PD-1)-expressing EC-specific CD8(+) T cells. Thus, IFNGR signaling in ECs activates a potent peripheral negative feedback circuit that protects vascularized grafts from occlusive TV.
C1 [Hoffmann, Matthias] Hannover Med Sch, Dept Visceral Surg, D-3000 Hannover, Germany.
[Palmer, Douglas C.; Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA.
[Tian, Yinghua; Clavien, Pierre-Alain] Univ Zurich Hosp, Dept Visceral Surg, CH-8091 Zurich, Switzerland.
[Ludewig, Burkhard] Univ Zurich, VetSuisse Fac, Zurich, Switzerland.
[Bolinger, Beatrice; Engeler, Daniel; Krebs, Philippe; Miller, Simone; Firner, Sonja; Ludewig, Burkhard] Kantonal Hosp St Gallen, Inst Immunobiol, St Gallen, Switzerland.
RP Ludewig, B (reprint author), Kantonsspital St Gallen, Inst Immunobiol, Rorschacherstr 95, CH-9007 St Gallen, Switzerland.
EM burkhard.ludewig@kssg.ch
RI Restifo, Nicholas/A-5713-2008; Palmer, Douglas/B-9454-2008; Krebs,
Philippe/A-3449-2012
OI Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas
P./0000-0003-4229-4580; Krebs, Philippe/0000-0003-4918-6654
FU Swiss National Science Foundation; Velux Foundation; Kanton of St.
Gallen
FX We would like to thank Silvia Behnke, Andre Fitsche, and Karin Eugster
for help with immunohistochemistry, and Luisa Cervantes-Barragan and
Tobias Junt for critical reading of the manuscript. The project received
support from the Swiss National Science Foundation (to B. L.), the Velux
Foundation (to B. L.), and the Kanton of St. Gallen (to B. L.).
NR 59
TC 11
Z9 11
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD MAR
PY 2010
VL 40
IS 3
BP 733
EP 743
DI 10.1002/eji.200939706
PG 11
WC Immunology
SC Immunology
GA 573SQ
UT WOS:000275935600026
PM 20049875
ER
PT J
AU Scheidemann, F
Therrien, JP
Vogel, J
Pfutzner, W
AF Scheidemann, Frank
Therrien, Jean-Philippe
Vogel, Jon
Pfuetzner, Wolfgang
TI In vivo synthesis and secretion of erythropoietin by genetically
modified primary human keratinocytes grafted onto immunocompromised mice
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Article
DE erythropoietin; gene therapy; keratinocyte; selection; skin
ID MULTIDRUG-RESISTANCE GENE; PRODUCT P-GLYCOPROTEIN; HEMATOPOIETIC-CELLS;
SYSTEMIC DELIVERY; GROWTH-HORMONE; RENAL-FAILURE;
EPIDERMAL-KERATINOCYTES; MOUSE ERYTHROPOIETIN; BICISTRONIC VECTORS;
HEMOPHILIA-B
AB P>Background:
The skin is an easily accessible tissue with a high blood flow facilitating the distribution of secreted peptides. These features make it a very intriguing target to serve as a biofactory releasing a systemically needed factor, such as erythropoietin (EPO).
Methods:
To evaluate the potential of human keratinocytes (KC) to systemically synthesize EPO, EPO-transduced KC were grafted onto immunocompromised mice and EPO secretion was followed by serum ELISA. Furthermore, we assessed if topical colchicine application would select for enriched percentages of KC expressing the multi-drug resistance (MDR) gene as a selectable gene connected to the EPO gene (measured by fluorescence-activated cell sorting (FACS)-analysis) and result in enhanced EPO production (determined by ELISA).
Results:
Transduced KC showed stable EPO production in vivo during a 6-month observation period, pointing to engraftment of EPO-secreting KC progenitor cells. When adding colchicines the number of EPO/MDR+ KC were significantly enriched, both in skin grafts (in vivo) and in skin equivalents (in vitro). Of note, this did not result in enhanced EPO production. Rather, while EPO secretion was substantially increased in transduced KC grown as monolayers and selected with colchicine, it was reduced by more than 50% in both colchicine-treated skin grafts and skin equivalents.
Conclusion:
Keratinocytes carry the potential to serve as a genetically modified biofactory synthesizing human EPO. In vivo gene selection does not allow to select for increased EPO secretion, most likely because of altered secretory activity of transduced KC in the stratified, differentiated epidermis. Thus, further studies are necessary to optimize the release of EPO by genetically modified KC.
C1 [Pfuetzner, Wolfgang] Univ Marburg, Dept Dermatol & Allergol, D-35037 Marburg, Germany.
[Scheidemann, Frank; Pfuetzner, Wolfgang] Univ Munich, Dept Dermatol & Allergol, Munich, Germany.
[Therrien, Jean-Philippe; Vogel, Jon] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
RP Pfutzner, W (reprint author), Univ Marburg, Dept Dermatol & Allergol, Deutsch Str 9-11, D-35037 Marburg, Germany.
EM wpfuetzn@med.uni-marburg.de
FU DFG [Pf 344/2-2]; Canadian Institutes of Health Research (CIHR)
FX This work was supported by DFG Grant No. Pf 344/2-2. J.-P. Therrien is a
recipient of a postdoctoral fellowship from the Canadian Institutes of
Health Research (CIHR). We thank Daniela Holler-Obrigkeit, Department of
Dermatology, University of Aachen, Germany, for helpful advice
optimizing culture conditions for raft cultures and Ines Nachtigall for
expert technical assistance.
NR 63
TC 2
Z9 2
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2010
VL 19
IS 3
BP 289
EP 296
DI 10.1111/j.1600-0625.2009.00984.x
PG 8
WC Dermatology
SC Dermatology
GA 554RL
UT WOS:000274452000008
PM 19889025
ER
PT J
AU Pascual, I
Larrayoz, IM
Campos, MM
Rodriguez, IR
AF Pascual, Iranzu
Larrayoz, Ignacio M.
Campos, Maria M.
Rodriguez, Ignacio R.
TI Methionine sulfoxide reductase B2 is highly expressed in the retina and
protects retinal pigmented epithelium cells from oxidative damage
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retina; macula; methionine sulfoxide reductase B2; mitochondria;
antioxidant
ID MACULAR DEGENERATION; INDUCED INFLAMMATION; ANTIOXIDANT DEFENSE;
KNOCKOUT MOUSE; LENS CELLS; STRESS; MSRA; GENE; OVEREXPRESSION;
RESISTANCE
AB Methionine sulfoxide reductase B2 (MSRB2) is a mitochondrial enzyme that converts methionine sulfoxide (R) enantiomer back to methionine. This enzyme is suspected of functioning to protect mitochondrial proteins from oxidative damage. In this study we report that the retina is one of the human tissues with highest levels of MSRB2 mRNA expression. Other tissues with high expression were heart, kidney and skeletal muscle. Overexpression of an MSRB2-GFP fusion protein increased the MSR enzymatic activity three-fold in stably transfected cultured RPE cells. This overexpression augmented the resistance of these cells to the toxicity induced by 7-ketocholesterol, tent-butyl hydroperoxide and all-trans retinoic acid. By contrast, knockdown of MSRB2 by a miRNA in stably transfected cells did not convey increased sensitivity to the oxidative stress. In the monkey retina MSRB2 localized to the ganglion cell layer (GLC), the outer plexiform layer (OPL) and the retinal pigment epithelium (RPE). MSRB2 expression is most pronounced in the OPL of the macula and foveal regions suggesting an association with the cone synaptic mitochondria. Our data suggests that MSRB2 plays an important function in protecting cones from multiple type of oxidative stress and may be critical in preserving central vision. (C) Published by Elsevier Ltd.
C1 [Pascual, Iranzu; Larrayoz, Ignacio M.; Rodriguez, Ignacio R.] NEI, Mech Retinal Dis Sect, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Campos, Maria M.] NEI, Image Core Facil, NIH, Bethesda, MD 20892 USA.
RP Rodriguez, IR (reprint author), NEI, Mech Retinal Dis Sect, Retinal Cell & Mol Biol Lab, NIH, 6 Ctr Dr,MSC 0608,Bldg 6,Rm 136, Bethesda, MD 20892 USA.
EM pascuali@nei.nih.gov; larrayozi@nei.nih.gov; camposm@nei.nih.gov;
rodriguezi@nei.nih.gov
RI Larrayoz, Ignacio/I-5613-2012
OI Larrayoz, Ignacio/0000-0003-1629-152X
FU Intramural NIH HHS [ZIA EY000307-15]
NR 54
TC 3
Z9 4
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAR
PY 2010
VL 90
IS 3
BP 420
EP 428
DI 10.1016/j.exer.2009.12.003
PG 9
WC Ophthalmology
SC Ophthalmology
GA 572QO
UT WOS:000275848100008
PM 20026324
ER
PT J
AU Kisby, GE
Kohama, SG
Olivas, A
Churchwell, M
Doerge, D
Spangler, E
de Cabo, R
Ingram, DK
Imhof, B
Bao, GB
Kow, YW
AF Kisby, Glen E.
Kohama, Steven G.
Olivas, Antoinette
Churchwell, Mona
Doerge, Daniel
Spangler, Edward
de Cabo, Rafael
Ingram, Donald K.
Imhof, Barry
Bao, Gaobin
Kow, Yoke W.
TI Effect of caloric restriction on base-excision repair (BER) in the aging
rat brain
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article
DE Exonuclease; Apyrimidinic/apurinic endonuclease (APE); DNA polymerase
beta; DNA ligase III; Frontal/parietal cortex; 8-Oxodeoxyguanosine
ID OXIDATIVE DNA-DAMAGE; SENESCENCE-ACCELERATED MICE; ALZHEIMERS-DISEASE;
DIETARY RESTRICTION; MITOCHONDRIAL-DNA; GENOMIC STABILITY; AGE; STRESS;
MOUSE; ENDONUCLEASE
AB Apyrimidinic/apurinic endonuclease (APE) is a key protein involved in the base-excision DNA repair (BER) pathway of oxidative DNA lesions. Using a novel oligonucleotide substrate, we demonstrate that APE activity in the frontal/parietal cortex (F/PCTX), cerebellum, brainstem, midbrain and hypothalamus declined with age in rats on an ad libitum (AL) diet. In contrast, APE activity for these brain regions was similar to 1.5-3 times higher in young, caloric restricted (CR) rats. Despite continuous CR treatment in all animals since six weeks of age, APE activity in the CR group started to decline by middle-age and continued into old age. However, CR maintained APE activity at a level that was significantly higher than that in AL rats across age and in the brain regions examined. Because Western analysis of APE, DNA polymerase 0 and DNA ligase III levels in the F/PCTX of both CR and AL rats remained unchanged with age, this suggests that the increased APE activity in CR rats is the result of differential post-translational modification of APE. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Kisby, Glen E.; Olivas, Antoinette] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97239 USA.
[Kohama, Steven G.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Portland, OR 97239 USA.
[Churchwell, Mona; Doerge, Daniel] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Spangler, Edward; de Cabo, Rafael; Ingram, Donald K.] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
[Imhof, Barry; Bao, Gaobin; Kow, Yoke W.] Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30322 USA.
RP Kisby, GE (reprint author), Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM kisby@ohsu.edu
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU NIH [CA90860]; NIEHS [PO1 ES011163, RR00163, DAMD 17-98-1-8625]
FX We thank Dr. Vilhelm Bohr for his valuable comments on the manuscript.
This work is supported by NIH CA90860 (YWK), NIEHS PO1 ES011163 (YWK),
RR00163 (SGK) and DAMD 17-98-1-8625 (GK).
NR 48
TC 10
Z9 11
U1 0
U2 0
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 MAR
PY 2010
VL 45
IS 3
BP 208
EP 216
DI 10.1016/j.exger.2009.12.003
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 574KD
UT WOS:000275987100007
PM 20005284
ER
PT J
AU Sun, XP
Seeberger, J
Alberico, T
Wang, CX
Wheeler, CT
Schauss, AG
Zou, S
AF Sun, Xiaoping
Seeberger, Jeanne
Alberico, Thomas
Wang, Chunxu
Wheeler, Charles T.
Schauss, Alexander G.
Zou, Sige
TI Acai palm fruit (Euterpe oleracea Mart.) pulp improves survival of flies
on a high fat diet
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article
DE Lifespan; Aging intervention; Euterpe oleracea Mart; Phytochemical;
Phosphoenolpyruvate carboxykinase; Oxidative stress
ID ABSORBENCY CAPACITY ASSAY; LIFE-SPAN; SUPEROXIDE-DISMUTASE; CALORIE
RESTRICTION; DROSOPHILA; ANTIOXIDANT; CANCER; BERRY; FLUORESCEIN;
POLYPHENOLS
AB Reducing oxidative damage is thought to be an effective aging intervention. Acai, a fruit indigenous to the Amazon, is rich in phytochemicals that possesses high anti-oxidant activities, and has anti-inflammatory, anti-cancer and anti-cardiovascular disease properties. However, little is known about its potential anti-aging properties especially at the organismal level. Here we evaluated the effect of acai pulp on modulating lifespan in Drosophila melanogaster. We found that acai supplementation at 2% in the food increased the lifespan of female flies fed a high fat diet compared to the non-supplemented control. We measured transcript changes induced by acai for age-related genes. Although transcript levels of most genes tested were not altered, acai increased the transcript level of 1(2)efl, a small heat-shock-related protein. and two detoxification genes, GstD1 and MtnA, while decreasing the transcript level of phosphoenolpyruvate carboxykinase (Pepck), a key gene involved in gluconeogenesis. Furthermore, acai increased the lifespan of oxidative stressed females caused by sod1 RNAi. This suggests that acai improves survival of flies fed a high fat diet through activation of stress response pathways and suppression of Pepck expression. Acai has the potential to antagonize the detrimental effect of fat in the diet and alleviate oxidative stress in aging. Published by Elsevier Inc.
C1 [Sun, Xiaoping; Seeberger, Jeanne; Alberico, Thomas; Wang, Chunxu; Wheeler, Charles T.; Zou, Sige] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Schauss, Alexander G.] AIBMR Life Sci Inc, Puyallup, WA 98373 USA.
RP Zou, S (reprint author), NIA, Lab Expt Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM zous@grc.nia.nih.gov
FU National Institute on Aging, National Institutes of Health, USA
FX We thank Edward Spangler and Luc Poirier for critical reading of the
manuscript and valuable comments, and thank the Natural and Medicinal
Products Division of AIBMR Life Sciences, Inc. for generously providing
acai samples. This work was supported by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health, USA.
NR 50
TC 48
Z9 49
U1 1
U2 13
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 MAR
PY 2010
VL 45
IS 3
BP 243
EP 251
DI 10.1016/j.exger.2010.01.008
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 574KD
UT WOS:000275987100010
PM 20080168
ER
PT J
AU Jacobi, A
Thieme, S
Lehmann, R
Ugarte, F
Malech, HL
Koch, S
Thiede, C
Muller, K
Bornhauser, M
Ryser, M
Brenner, S
AF Jacobi, Angela
Thieme, Sebastian
Lehmann, Romy
Ugarte, Fernando
Malech, Harry L.
Koch, Sina
Thiede, Christian
Mueller, Katrin
Bornhaeuser, Martin
Ryser, Martin
Brenner, Sebastian
TI Impact of CXCR4 inhibition on FLT3-ITD-positive human AML blasts
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; STEM-CELLS;
PERIPHERAL-BLOOD; FLT3 MUTATIONS; FLT3-ACTIVATING MUTATIONS;
HEMATOPOIETIC-CELLS; PROGENITOR CELLS; UP-REGULATION; ENGRAFTMENT
AB Objective. Internal tandem duplication (ITD) mutations of the FLT3 receptor are associated with a high incidence of relapse in acute myeloid leukemia (AML). Expression of the CXCR4 receptor in FLT3-ITD-positive AML is correlated with poor outcome, and inhibition of CXCR4 was shown to sensitize AMI, blasts toward chemotherapy. The aim of this study was to evaluate the impact of FLT3-ITD on cell proliferation and CXCR4-dependent migration in human hematopoietic progenitor cells and to investigate their response to CXCR4 inhibition.
Materials and Methods. We use primary blasts from patients with FLT3-ITD or FLT3 wild-type AML. In addition, human CD34(+) hematopoietic progenitor cells were transduced to >70% with retroviral vectors containing human FLT3-ITD.
Results. We found that FLT3-ITD transgene overexpressing human hematopoietic progenitor cells show strongly reduced migration toward stromal-derived factor-1 in vitro and display significantly reduced bone marrow homing in nonobese diabetic severe combined immunodeficient mice. Cocultivation of FLT3-ITD-positive AML blasts or hematopoietic progenitor cells oil bone marrow stromal cells resulted in a strong proliferation advantage and increased early cobblestone area-forming cells compared to FLT3-wild-type AML blasts. Addition of the CXCR4 inhibitor AMD3100 to the coculture significantly reduced both cobblestone area-forming cells and proliferation of FLT3-ITD-positive cells, but did not affect FLT3-wild-type cells-highlighting the critical interaction between CXCR4 and FLT3-ITD.
Conclusion. CXCR4 inhibition to decrease cell proliferation and to control the leukemic burden play provide a novel therapeutic strategy in patients with advanced FLT3-ITD-positive AML. (C) 2010 ISEH - Society for Hematology and Stern Cells. Published by Elsevier Inc.
C1 [Jacobi, Angela; Thieme, Sebastian; Lehmann, Romy; Ugarte, Fernando; Ryser, Martin; Brenner, Sebastian] Univ Clin Carl Gustav Carus Dresden, Dept Pediat, D-01307 Dresden, Germany.
[Thieme, Sebastian; Thiede, Christian; Bornhaeuser, Martin; Brenner, Sebastian] Tech Univ Dresden, DFG Res Ctr & Cluster Excellence Regenerat Therap, Dresden, Germany.
[Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Koch, Sina; Thiede, Christian; Mueller, Katrin; Bornhaeuser, Martin] Univ Clin Carl Gustav Carus Dresden, Med Clin 1, D-01307 Dresden, Germany.
RP Brenner, S (reprint author), Univ Clin Carl Gustav Carus Dresden, Dept Pediat, Bldg 21,Fetscherstr 74, D-01307 Dresden, Germany.
RI Brenner, Sebastian/D-7456-2013;
OI Malech, Harry/0000-0001-5874-5775
FU Deutsche Forschungsgemeinschaft (Bonn, Germany) [SFB 655]
FX This work was supported by the 'Deutsche Forschungsgemeinschaft' (Bonn,
Germany) (SFB 655 to CT, MB and SB)
NR 27
TC 14
Z9 14
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD MAR
PY 2010
VL 38
IS 3
BP 180
EP 190
DI 10.1016/j.exphem.2009.12.003
PG 11
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 566JC
UT WOS:000275364900003
PM 20035824
ER
PT J
AU Wirth, EK
Conrad, M
Winterer, J
Wozny, C
Carlson, BA
Roth, S
Schmitz, D
Bornkamm, GW
Coppola, V
Tessarollo, L
Schomburg, L
Kohrle, J
Hatfield, DL
Schweizer, U
AF Wirth, Eva K.
Conrad, Marcus
Winterer, Jochen
Wozny, Christian
Carlson, Bradley A.
Roth, Stephan
Schmitz, Dietmar
Bornkamm, Georg W.
Coppola, Vincenzo
Tessarollo, Lino
Schomburg, Lutz
Koehrle, Josef
Hatfield, Dolph L.
Schweizer, Ulrich
TI Neuronal selenoprotein expression is required for interneuron
development and prevents seizures and neurodegeneration
SO FASEB JOURNAL
LA English
DT Article
DE selenium; parvalbumin; excitability; schizophrenia; gamma oscillation
ID APOLIPOPROTEIN-E RECEPTOR-2; NEUROLOGICAL DYSFUNCTION; SELENIUM
DEFICIENCY; BRAIN-DEVELOPMENT; TARGET TISSUES; MICE; MOUSE; GENE;
SURVIVAL; SELENOCYSTEINE
AB Cerebral selenium (Se) deficiency is associated with neurological phenotypes including seizures and ataxia. We wanted to define whether neurons require selenoprotein expression and which selenoproteins are most important, and explore the possible pathomechanism. Therefore, we abrogated the expression of all selenoproteins in neurons by genetic inactivation of the tRNA[Ser](Sec) gene. Cerebral expression of selenoproteins was significantly diminished in the mutants, and histological analysis revealed progressive neurodegeneration. Developing interneurons failed to specifically express parvalbumin (PV) in the mutants. Electrophysiological recordings, before overt cell death, showed normal excitatory transmission, but revealed spontaneous epileptiform activity consistent with seizures in the mutants. In developing cortical neuron cultures, the number of PV(+) neurons was reduced on combined Se and vitamin E deprivation, while other markers, such as calretinin (CR) and GAD67, remained unaffected. Because of the synergism between Se and vitamin E, we analyzed mice lacking neuronal expression of the Se-dependent enzyme glutathione peroxidase 4 (GPx4). Although the number of CR(+) interneurons remained normal in Gpx4-mutant mice, the number of PV(+) interneurons was reduced. Since these mice similarly exhibit seizures and ataxia, we conclude that GPx4 is a selenoenzyme modulating interneuron function and PV expression. Cerebral SE deficiency may thus act via reduced GPx4 expression.-Wirth, E. K., Conrad, M., Winterer, J., Wozny, C., Carlson, B. A., Roth, S., Schmitz, D., Bornkamm, G. W., Coppola, V., Tessarollo, L., Schomburg, L., Kohrle, J., Hatfield, D. L., Schweizer, U. Neuronal selenoprotein expression is required for interneuron development and prevents seizures and neurodegeneration. FASEB J. 24, 844-852 (2010). www.fasebj.org
C1 [Schomburg, Lutz; Koehrle, Josef; Schweizer, Ulrich] Charite, Inst Expt Endocrinol, D-13353 Berlin, Germany.
[Winterer, Jochen; Wozny, Christian; Schmitz, Dietmar] Charite, Neurosci Res Ctr, D-13353 Berlin, Germany.
[Conrad, Marcus; Bornkamm, Georg W.] Helmholtz Zentrum Munchen, Inst Clin Mol Biol & Tumour Genet, Munich, Germany.
[Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Coppola, Vincenzo; Tessarollo, Lino] NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21701 USA.
RP Schweizer, U (reprint author), Charite, Inst Expt Endocrinol, Augustenburger Pl 1, D-13353 Berlin, Germany.
EM ulrich.schweizer@charite.de
RI Coppola, Vincenzo/E-2917-2011; Schweizer, Ulrich/E-8105-2013; Wozny,
Christian /A-1498-2015;
OI Coppola, Vincenzo/0000-0001-6163-1779; Wozny, Christian
/0000-0003-4220-2033; Wirth, Eva Katrin/0000-0002-0491-9941; Conrad,
Marcus/0000-0003-1140-5612; Kohrle, Josef/0000-0002-9187-9078;
Schweizer, Ulrich/0000-0003-1380-4780
FU Deutsche Forschungsgemeinschaft [Scho849/2-2, SFB 665/A7, Ko922/11-1];
Charite Universitatsmedizin Berlin; U.S. National Institutes of Health;
National Cancer Institute; Center for Cancer Research
FX The authors thank Dr. Claudia Iserhot, who performed initial
physiological studies. SiJie Zhang performed some of the neuron
cultures. CamK-Cre mice were generously provided by Gunther Schutz
(Deutsches Krebsforschungszentrum, Heidelberg, Germany). The authors
gratefully acknowledge the technical assistance of Vartiter Seher, Anita
Kinne, Silke Kappler, Antje Kretschmer, and Heidi Forster. Dorette
Freyer (Experimental Neurology, Charite Universitatsmedizin Berlin),
initially helped with primary neuron culture. Funding for this study was
provided by Deutsche Forschungsgemeinschaft Scho849/2-2, SFB 665/A7,
Ko922/11-1, and Charite Universitatsmedizin Berlin and in part by the
Intramural Research Program of the U.S. National Institutes of Health,
National Cancer Institute, Center for Cancer Research.
NR 46
TC 74
Z9 75
U1 1
U2 10
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD MAR
PY 2010
VL 24
IS 3
BP 844
EP 852
DI 10.1096/fj.09-143974
PG 9
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 561KE
UT WOS:000274974600020
PM 19890015
ER
PT J
AU Hoashi, T
Tamaki, K
Hearing, VJ
AF Hoashi, Toshihiko
Tamaki, Kunihiko
Hearing, Vincent J.
TI The secreted form of a melanocyte membrane-bound glycoprotein
(Pmel17/gp100) is released by ectodomain shedding
SO FASEB JOURNAL
LA English
DT Article
DE melanosome; glycosylation; proprotein convertase
ID MATRIX PROTEIN PMEL17/GP100; MONOCLONAL-ANTIBODY; MELANOSOME BIOGENESIS;
ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; AMYLOID FORMATION; T-LYMPHOCYTES;
SILVER LOCUS; CLEAVAGE; CELLS
AB Ectodomain shedding is a proteolytic mechanism by which a transmembrane protein is converted into a secreted form. Pmel17/gp100 is a melanocyte-specific membrane-bound glycoprotein that has amyloid characteristics and forms fibrillar structures in melanosomes after a complex sequence of post-translational processing and trafficking events, including cleavage by a furin-like proprotein convertase (PC). A secreted form of Pmel17 (termed sPmel17) was also thought to be released due to cleavage by a PC. We used multidisciplinary approaches to demonstrate that sPmel17 is released by ectodomain shedding at the juxtamembrane and/or intramembrane motif and to show that this is independent of cleavage by a PC. We further show that sPmel17 consists of 2 fragments linked by disulfide bonds and that the shedding is inhibited at low temperature but not by metalloproteinase inhibitors. Moreover, treatment with a phorbol ester or a calmodulin inhibitor induces Pmel17 shedding. We also refine the reactivity of HMB50 and NKI/beteb, 2 monoclonal antibodies commonly used as melanoma-specific markers. The fact that those antibodies require physically separated domains of Pmel17 sheds interesting light on its 3-dimensional conformation. We conclude that sPmel17 is released by regulated proteolytic ectodomain shedding.-Hoashi, T., Tamaki, K., Hearing, V. J. The secreted form of a melanocyte membrane-bound glycoprotein (Pmel17/gp100) is released by ectodomain shedding. FASEB J. 24, 916-930 (2010). www.fasebj.org
C1 [Hoashi, Toshihiko; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Hoashi, Toshihiko; Tamaki, Kunihiko] Univ Tokyo, Dept Dermatol, Fac Med, Tokyo 1138655, Japan.
RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 2132, Bethesda, MD 20892 USA.
EM thoashi-tky@umin.ac.jp; hearingv@nih.gov
FU National Institutes of Health, National Cancer Institute
FX We gratefully thank Dr. Michael S. Marks (University of Pennsylvania,
Philadelphia, PA, USA) for kindly providing the Pmel17-i, Pmel17-l, and
Pmel17-s vectors; Dr. Richard N. Sifers (Baylor College of Medicine,
Houston, TX, USA) for the kind gift of hATM-pcDNA3.1; Dr. Donald F.
Steiner (University of Chicago, Chicago, IL, USA) for the kind gift of
pCMV-furin; Dr. Susan H. Garfield and Dr. Stephen M. Wincovitch for
expert advice on confocal microscopy; and Dr. Motozo Yamashita for
useful suggestions. This research was supported, in part, by the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 67
TC 21
Z9 21
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 MAR
PY 2010
VL 24
IS 3
BP 916
EP 930
DI 10.1096/fj.09-140921
PG 15
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 561KE
UT WOS:000274974600027
PM 19884326
ER
PT J
AU Navarathna, DHMLP
Harris, SD
Roberts, DD
Nickerson, KW
AF Navarathna, Dhammika H. M. L. P.
Harris, Steven D.
Roberts, David D.
Nickerson, Kenneth W.
TI Evolutionary aspects of urea utilization by fungi
SO FEMS YEAST RESEARCH
LA English
DT Article
DE urease; urea amidolyase; DUR1,2; Ni-dependent enzymes; fusel alcohols;
methylcrotonyl CoA carboxylase
ID CANDIDA-ALBICANS; NUTRITIONAL CONTROL; VIRULENCE; AMIDOLYASE;
CEREVISIAE; GROWTH; MUTANT; BIOTIN; MODEL; FORM
AB The higher fungi exhibit a dichotomy with regard to urea utilization. The hemiascomycetes use urea amidolyase (DUR1,2), whereas all other higher fungi use the nickel-containing urease. Urea amidolyase is an energy-dependent biotin-containing enzyme. It likely arose before the Euascomycete/Hemiascomycete divergence c. 350 million years ago by insertion of an unknown gene into one copy of a duplicated methylcrotonyl CoA carboxylase (MccA). The dichotomy between urease and urea amidolyase coincides precisely with that for the Ni/Co transporter (Nic1p), which is present in the higher fungi that use urease and is absent in those that do not. We suggest that the selective advantage for urea amidolyase is that it allowed the hemiascomycetes to jettison all Ni(2+) - and Co(2+) - dependent metabolisms and thus to have two fewer transition metals whose concentrations need to be regulated. Also, the absence of MccA in the hemiascomycetes coincides with and may explain their production of fusel alcohols.
C1 [Navarathna, Dhammika H. M. L. P.; Nickerson, Kenneth W.] Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA.
[Navarathna, Dhammika H. M. L. P.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Harris, Steven D.] Univ Nebraska, Dept Plant Pathol, Lincoln, NE 68588 USA.
RP Nickerson, KW (reprint author), Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA.
EM knickerson1@unl.edu
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU University of Nebraska; John C. and Nettie V. David Memorial Trust Fund;
Ann L. Kelsall and the Farnesol and Candida albicans Research Fund;
University of Nebraska Foundation; NIH, NCI, Center for Cancer Research
FX We thank Donald G. Ahearn, Vadim Gladyshev, and anonymous reviewer #2
for helpful suggestions and discussions. This work was supported by the
University of Nebraska Tobacco Settlement Biomedical Research
Enhancement Fund, the John C. and Nettie V. David Memorial Trust Fund,
Ann L. Kelsall and the Farnesol and Candida albicans Research Fund,
University of Nebraska Foundation, and the Intramural Research Program
of the NIH, NCI, Center for Cancer Research (DDR).
NR 29
TC 19
Z9 19
U1 2
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1567-1356
J9 FEMS YEAST RES
JI FEMS Yeast Res.
PD MAR
PY 2010
VL 10
IS 2
BP 209
EP 213
DI 10.1111/j.1567-1364.2010.00602.x
PG 5
WC Biotechnology & Applied Microbiology; Microbiology; Mycology
SC Biotechnology & Applied Microbiology; Microbiology; Mycology
GA 552VE
UT WOS:000274320900009
PM 20100286
ER
PT J
AU Baechler, MF
Groth, AT
Nesti, LJ
Martin, BD
AF Baechler, Martin F.
Groth, Adam T.
Nesti, Leon J.
Martin, Barry D.
TI Soft Tissue Management of War Wounds to the Foot and Ankle
SO FOOT AND ANKLE CLINICS
LA English
DT Article
DE War; Foot; Ankle; Flap; Reconstruction; Microsurgery
ID OPERATION IRAQI-FREEDOM; THIGH PERFORATOR FLAP; BREVIS MUSCLE FLAP;
MICROSURGICAL RECONSTRUCTION; EXTERNAL FIXATION; ENDURING FREEDOM; OPEN
FRACTURES; DISTAL LEG; SURAL FLAP; THERAPY
AB Reconstruction of the war-wounded foot and ankle is a challenging process requiring endurance, patience, diligence, and many harrowing decisions for the patient and surgeon. These decisions involve reconciling the difficult balance between expectations and feasibility. The reconstructive process does not end with the successful healing of a flap. Indeed, the surgeon must counsel the patient that flap coverage is but one small component of the reconstruction process. Multiple procedures may be necessary before the patient reaches maximum function. Overtime, the patient and the surgeon may consider revisions of a flap to improve shoe wear and weight-bearing of the reconstructed foot and ankle. Also of high importance is the availability of a skilled orthotist for custom fitting of braces and shoe wear in the post-reconstructive period. Ultimately, the patient is the final judge of the outcome of foot and ankle reconstruction. It is not a rare occurrence that the patient and surgeon agree at some point during reconstructive efforts that an amputation is the best option.
C1 [Baechler, Martin F.] Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, Washington, DC 20307 USA.
[Baechler, Martin F.; Martin, Barry D.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA.
[Groth, Adam T.] Tripler Army Med Ctr, Dept Surg, Orthopaed Surg Serv, Honolulu, HI 96859 USA.
[Nesti, Leon J.] McDonald Army Community Hosp, Dept Surg, Orthopaed Surg Serv, Ft Eustis, VA 23604 USA.
[Nesti, Leon J.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Martin, Barry D.] Walter Reed Army Med Ctr, Dept Surg, Integrated Plast Surg Serv, Washington, DC 20307 USA.
RP Baechler, MF (reprint author), Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, 6900 Georgia Ave NW, Washington, DC 20307 USA.
EM martin.baechler@us.army.mil
RI Groth, Adam/P-9366-2016
OI Groth, Adam/0000-0003-2475-6200
FU NIAAA NIH HHS [F30 AA005516-01, F30 AA005516-02, F30 AA005516-03]
NR 67
TC 15
Z9 18
U1 0
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1083-7515
J9 FOOT ANKLE CLIN
JI Foot Ankle Clin.
PD MAR
PY 2010
VL 15
IS 1
BP 113
EP 138
DI 10.1016/j.fcl.2009.10.006
PG 26
WC Orthopedics
SC Orthopedics
GA 745TK
UT WOS:000289189200008
PM 20189120
ER
PT J
AU Zhu, WH
Dahut, WL
AF Zhu, Wenhui
Dahut, William L.
TI Tumor angiogenesis as an early marker of long-term prostate cancer
mortality
SO FUTURE ONCOLOGY
LA English
DT Editorial Material
DE angiogenesis; microvessel density; prostate cancer; prostate
cancer-specific mortality
ID CELLS PREDICT SURVIVAL; BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY;
MICROVESSEL DENSITY; PATHOLOGICAL STAGE; PRETREATMENT NOMOGRAM; PSA
VELOCITY; ANTIGEN ERA; RECURRENCE; BRACHYTHERAPY
AB Evaluation of: Mucci LA, Powolny A, Giovanni E et al.: Prospective study of prostate tumor angiogenesis and cancer-specific mortality in the health professionals follow-up study. J. Clin. Oncol. 27, 5627-5633 (2009). Most prostate cancer patients are diagnosed with localized disease, Long-term prostate cancer mortality is low, and many patients have been overtreated. Better prediction tools are needed to distinguish clinically insignificant, low-risk prostate cancers from lethal diseases. Tumor microvessel density, a marker of angiogenesis, has been shown to be related to the development of prostate cancer metastasis and even mortality. Mucci et al. found that morphologic characteristics of tumor microvessels, such as vessel size and irregularity, from prostatectomy specimen may be better than microvessel density as indicators of active angiogenesis, cancer aggressiveness and metastatic potential, and potentially prostate cancer-specific mortality. Prognostic tools combining angiogenesis biomarkers and clinical features led to marked improvement in the prediction of lethal prostate cancer. If these results are confirmed with studies from prostate biopsy samples, this novel prognosis tool will be of significant importance to guide clinical decision-making for localized prostate cancer,
C1 [Zhu, Wenhui; Dahut, William L.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Dahut, WL (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 10 Ctr Dr,Room 12N226, Bethesda, MD 20892 USA.
EM zhuwen@mail.nih.gov; dahutw@mail.nih.gov
NR 38
TC 2
Z9 2
U1 0
U2 0
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1479-6694
EI 1744-8301
J9 FUTURE ONCOL
JI Future Oncol.
PD MAR
PY 2010
VL 6
IS 3
BP 341
EP 345
DI 10.2217/FON.09.177
PG 5
WC Oncology
SC Oncology
GA 571NQ
UT WOS:000275759700006
PM 20222790
ER
PT J
AU Kucherlapati, MH
Lee, K
Nguyen, AA
Clark, AB
Hou, H
Rosulek, A
Li, H
Yang, K
Fan, KH
Lipkin, M
Bronson, RT
Jelicks, L
Kunkel, TA
Kucherlapati, R
Edelmann, W
AF Kucherlapati, Melanie
Lee, Kyeryoung
Nguyen, Andrew A.
Clark, Alan B.
Hou, Harry, Jr.
Rosulek, Andrew
Li, Hua
Yang, Kan
Fan, Kunhua
Lipkin, Martin
Bronson, Roderick T.
Jelicks, Linda
Kunkel, Thomas A.
Kucherlapati, Raju
Edelmann, Winfried
TI An Msh2 Conditional Knockout Mouse for Studying Intestinal Cancer and
Testing Anticancer Agents
SO GASTROENTEROLOGY
LA English
DT Article
DE Mismatch Repair; Msh2; Tumorigenesis; Chemotherapy
ID DNA MISMATCH REPAIR; NONPOLYPOSIS COLORECTAL-CANCER;
MICROSATELLITE-INSTABILITY; GASTROINTESTINAL-TRACT; APC MUTATIONS;
COLON-CANCER; MICE; INACTIVATION; TUMORS; DEFICIENCY
AB BACKGROUND & AIMS: Mutations in the DNA mismatch repair (MMR) gene MSH2 cause Lynch syndromes I and II and sporadic colorectal cancers. Msh2(null) mice predominantly develop lymphoma and do not accurately recapitulate the colorectal cancer phenotype. METHODS: We generated and examined mice with a conditional Msh2 disruption (Msh2(LoxP)), permitting tissue-specific gene inactivation. ECMsh2(LoxP/LoxP) mice carried an EIIa-Cre transgene, and VCMsh2(LoxP/LoxP) mice carried a Villin-Cre transgene. We combined the VCMsh2(LoxP) allele with either Msh2(Delta 7null) (VCMsh2(LoxP/null)) or Msh2(G674D) mutations (VCMsh2(LoxP/G674D)) to create allelic phase mutants. These mice were given cisplatin or 5-fluorouracil/leucovorin and oxaliplatin (FOLFOX), and their tumors were measured by magnetic resonance imaging. RESULTS: Embryonic fibroblasts from ECMsh2(LoxP/LoxP) mice do not express MSH2 and are MMR deficient. Reverse transcription, polymerase chain reaction, and immunohistochemistry from VCMsh2(LoxP/LoxP) mice demonstrated specific loss of Msh2 messenger RNA and protein from epithelial cells of the intestinal tract. Microsatellite instability was observed in all VCMsh2 strains and limited to the intestinal mucosa. Resulting adenomas and adenocarcinomas had somatic truncation mutations to the adenomatous polyposis coli (Apc) gene. VCMsh2(LoxP/LoxP) mice did not develop lymphoma. Comparison of allelic phase tumors revealed significant differences in multiplicity and size. When treated with cisplatin or FOLFOX, tumor size was reduced in VCMsh2(LoxP/G674D) but not VCMsh2LoxP/null tumors. The apoptotic response to FOLFOX was partially sustained in the intestinal mucosa of VCMsh2(LoxP/G674D) animals. CONCLUSIONS: Msh2(LoxP/LoxP) mice in combination with appropriate Cre recombinase transgenes have excellent potential for preclinical modeling of Lynch syndrome, MMR-deficient tumors of other tissue types, and use in drug development.
C1 [Kucherlapati, Melanie] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA.
[Lee, Kyeryoung; Hou, Harry, Jr.; Edelmann, Winfried] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA.
[Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Li, Hua; Jelicks, Linda] Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10467 USA.
[Yang, Kan; Fan, Kunhua; Lipkin, Martin] Cornell Univ, Weill Med Ctr, Dept Med Gastroenterol, Strang Canc Res Lab, New York, NY 10021 USA.
[Bronson, Roderick T.] Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA.
[Bronson, Roderick T.] Tufts Univ, Sch Vet Med, Dept Pathol, Boston, MA 02111 USA.
RP Kucherlapati, MH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA.
EM mkucherlapati@partners.org; edelmann@aecom.yu.edu
FU NIH [ES11040, CA084301, CA76329, CA93484]; Division of Intramural
Research of the NIH, NIEHS [Z01 ES065089]; [CA13330]
FX Supported by NIH grants ES11040 (to R. K.), CA084301 (to R. K.), CA76329
(to W. E.), and CA93484 (to W. E.); Center grant CA13330 (to Albert
Einstein College of Medicine); and Project Z01 ES065089, Division of
Intramural Research of the NIH, NIEHS (to T. A. K.).
NR 37
TC 29
Z9 30
U1 0
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2010
VL 138
IS 3
BP 993
EP U243
DI 10.1053/j.gastro.2009.11.009
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 563EF
UT WOS:000275109900030
PM 19931261
ER
PT J
AU Sakiani, S
Koh, C
Heller, T
AF Sakiani, Sasan
Koh, Christopher
Heller, Theo
TI Glowing in the Dark: Not Always a Bad Thing
SO GASTROENTEROLOGY
LA English
DT Editorial Material
ID FOCAL NODULAR HYPERPLASIA
C1 [Sakiani, Sasan; Koh, Christopher; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Sakiani, S (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA DK054514-03]
NR 3
TC 0
Z9 0
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2010
VL 138
IS 3
BP E8
EP U536
DI 10.1053/j.gastro.2009.05.065
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 563EF
UT WOS:000275109900056
PM 20123140
ER
PT J
AU Galter, D
Pernold, K
Yoshitake, T
Lindqvist, E
Hoffer, B
Kehr, J
Larsson, NG
Olson, L
AF Galter, D.
Pernold, K.
Yoshitake, T.
Lindqvist, E.
Hoffer, B.
Kehr, J.
Larsson, N. -G.
Olson, L.
TI MitoPark mice mirror the slow progression of key symptoms and L-DOPA
response in Parkinson's disease
SO GENES BRAIN AND BEHAVIOR
LA English
DT Article
DE Cre-loxP system; HPLC; mitochondria; striatum; substantia nigra;
tissue-specific knock-out mice
ID GROUND REACTION FORCES; COMPENSATORY ADJUSTMENTS; TYROSINE-HYDROXYLASE;
ACID DECARBOXYLASE; MESSENGER-RNA; IMPAIRMENTS; NEURONS; RATS;
MITOCHONDRIA; TRANSPORTER
AB The MitoPark mouse, in which the mitochondrial transcription factor Tfam is selectively removed in midbrain dopamine (DA) neurons, is a genetic model for Parkinson's disease (PD) that replicates the slow and progressive development of key symptoms. To further validate this model, we have extended both behavioral and biochemical analyses in these animals. We found that vertical movements decline earlier and faster than horizontal movements, possibly modeling the early occurrence of axial, postural instability in PD. L-DOPA induces different locomotor responses depending on the age: in young MitoPark mice the L-DOPA-induced motor activation is small; middle-aged MitoPark mice respond in a dose-dependent manner to L-DOPA, whereas aged MitoPark mice display a double-peaked locomotor response to a high dose of L-DOPA that includes an intermittent period of very low motor activity, similar to the 'on-off' phenomenon in PD. To correlate behavior with biochemical data, we analyzed monoamine levels in three different brain areas that are highly innervated by the DA system: striatum, anterior cortex and olfactory bulb. DA levels declined earlier and faster in striatum than in cortex; only at the latest time-point analyzed, DA levels were found to be significantly lower than control levels in the olfactory bulb. Interestingly, the ratio between homovanillic acid (HVA) and DA differed between regions over time. In striatum and olfactory bulb, the ratio increased steeply indicating increased DA turnover. In contrast, the ratio decreased over time in cortex, revealing important differences between DA cells in substantia nigra and the ventral tegmental area.
C1 [Hoffer, B.] NIDA, NIH, Baltimore, MD USA.
[Yoshitake, T.; Kehr, J.] Dept Physiol & Pharmacol, Baltimore, MD USA.
[Larsson, N. -G.] Karolinska Inst, Dept Lab Med, S-17177 Stockholm, Sweden.
[Larsson, N. -G.] Max Planck Inst Biol Aging, Cologne, Germany.
RP Galter, D (reprint author), Karolinska Inst, Dept Neurosci, Retzius Vag 8,B2 4, S-17177 Stockholm, Sweden.
EM dagmar.galter@ki.se
RI Galter, Dagmar/C-4826-2011
OI Galter, Dagmar/0000-0001-6485-6244
FU Swedish Research Council; Swedish Brain Foundation and Hallstens
Forskningsstiftelse; Swedish Parkinson Foundation; Swedish Brain Power;
Michael J. Fox Foundation; Karolinska Institutet Funds
FX This study was supported by the Swedish Research Council, the Swedish
Brain Foundation and Hallstens Forskningsstiftelse, The Swedish
Parkinson Foundation, Swedish Brain Power, the Michael J. Fox Foundation
and Karolinska Institutet Funds. Conflict of interest statement: N- G.
L. and L. O. are co-owners of a company owning commercial rights to the
MitoPark mice.
NR 23
TC 29
Z9 29
U1 2
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1601-1848
J9 GENES BRAIN BEHAV
JI Genes Brain Behav.
PD MAR
PY 2010
VL 9
IS 2
BP 173
EP 181
DI 10.1111/j.1601-183X.2009.00542.x
PG 9
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 568JX
UT WOS:000275519700003
PM 20002202
ER
PT J
AU Knutsen, T
Padilla-Nash, HM
Wangsa, D
Barenboim-Stapleton, L
Camps, J
McNeil, N
Difilippantonio, MJ
Ried, T
AF Knutsen, Turid
Padilla-Nash, Hesed M.
Wangsa, Danny
Barenboim-Stapleton, Linda
Camps, Jordi
McNeil, Nicole
Difilippantonio, Michael J.
Ried, Thomas
TI Definitive Molecular Cytogenetic Characterization of 15 Colorectal
Cancer Cell Lines
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID COMPARATIVE GENOMIC HYBRIDIZATION; GENE AMPLIFICATION;
CHROMOSOMAL-ABERRATIONS; TELOMERE CAPTURE; INSTABILITY; TRANSLOCATIONS;
TUMORS; BREAK; MECHANISMS; EVOLUTION
AB In defining the genetic profiles in cancer, cytogenetically aberrant cell lines derived from primary tumors are important tools for the study of carcinogenesis. Here, we present the results of a comprehensive investigation of 15 established colorectal cancer cell lines using spectral karyotyping (SKY), fluorescence in situ hybridization, and comparative genomic hybridization (CGH). Detailed karyotypic analysis by SKY on five of the lines (P53HCT116, T84, NCI-H508, NCI-H716, and SK-CO-I) is described here for the first time. The five lines with karyotypes in the diploid range and that are characterized by defects in DNA mismatch repair had a mean of 4.8 chromosomal abnormalities per line, whereas the 10 aneuploid lines exhibited complex karyotypes and a mean of 30 chromosomal abnormalities. Of the 150 clonal translocations, only eight were balanced and none were recurrent among the lines. We also reviewed the karyotypes of 345 cases of adenocarcinoma of the large intestine listed in the Mitelman Database of Chromosome Aberrations in Cancer. The types of abnormalities observed in the cell lines reflected those seen in primary tumors: there were no recurrent translocations in either tumors or cell lines; isochromosomes were the most common recurrent abnormalities; and breakpoints occurred most frequently at the centromeric/pericentromeric and telomere regions. Of the genomic imbalances detected by array CGH, 87% correlated with chromosome aberrations observed in the SKY studies. The fact that chromosome abnormalities predominantly result in copy number changes rather than specific chromosome or gene fusions suggests that this may be the major mechanism leading to carcinogenesis in colorectal cancer. Published 2009 Wiley-Liss, Inc.dagger
C1 [Knutsen, Turid; Padilla-Nash, Hesed M.; Wangsa, Danny; Barenboim-Stapleton, Linda; Camps, Jordi; McNeil, Nicole; Difilippantonio, Michael J.; Ried, Thomas] NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Knutsen, T (reprint author), NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM knutsent@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX Supported by: Intramural Research program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 42
TC 18
Z9 18
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1045-2257
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD MAR
PY 2010
VL 49
IS 3
BP 204
EP 223
DI 10.1002/gcc.20730
PG 20
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 547ZT
UT WOS:000273929200002
PM 19927377
ER
PT J
AU Miller, HI
AF Miller, Henry I.
TI Tempering Regulation with Common Sense
SO GENETIC ENGINEERING & BIOTECHNOLOGY NEWS
LA English
DT Editorial Material
C1 Stanford Univ, Hoover Inst, Stanford, CA 94305 USA.
[Miller, Henry I.] NIH, Bethesda, MD USA.
[Miller, Henry I.] US FDA, Rockville, MD 20857 USA.
RP Miller, HI (reprint author), Stanford Univ, Hoover Inst, Stanford, CA 94305 USA.
EM henry.miller@stanford.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1935-472X
J9 GENET ENG BIOTECHN N
JI Genet. Eng. Biotechnol. News
PD MAR 1
PY 2010
VL 30
IS 5
BP 6
EP 7
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 668LF
UT WOS:000283270000003
ER
PT J
AU Narlikar, L
Sakabe, NJ
Blanski, AA
Arimura, FE
Westlund, JM
Nobrega, MA
Ovcharenko, I
AF Narlikar, Leelavati
Sakabe, Noboru J.
Blanski, Alexander A.
Arimura, Fabio E.
Westlund, John M.
Nobrega, Marcelo A.
Ovcharenko, Ivan
TI Genome-wide discovery of human heart enhancers
SO GENOME RESEARCH
LA English
DT Article
ID CONSERVED NONCODING SEQUENCES; CIS-REGULATORY MODULES; SERUM RESPONSE
FACTOR; GENE-EXPRESSION; TRANSCRIPTION FACTORS; BINDING-SITE; ZEBRAFISH;
IDENTIFICATION; MUSCLE; CLUSTERS
AB The various organogenic programs deployed during embryonic development rely on the precise expression of a multitude of genes in time and space. Identifying the cis-regulatory elements responsible for this tightly orchestrated regulation of gene expression is an essential step in understanding the genetic pathways involved in development. We describe a strategy to systematically identify tissue-specific cis-regulatory elements that share combinations of sequence motifs. Using heart development as an experimental framework, we employed a combination of Gibbs sampling and linear regression to build a classifier that identifies heart enhancers based on the presence and/or absence of various sequence features, including known and putative transcription factor (TF) binding specificities. In distinguishing heart enhancers from a large pool of random noncoding sequences, the performance of our classifier is vastly superior to four commonly used methods, with an accuracy reaching 92% in cross-validation. Furthermore, most of the binding specificities learned by our method resemble the specificities of TFs widely recognized as key players in heart development and differentiation, such as SRF, MEF2, ETS1, SMAD, and GATA. Using our classifier as a predictor, a genome-wide scan identified over 40,000 novel human heart enhancers. Although the classifier used no gene expression information, these novel enhancers are strongly associated with genes expressed in the heart. Finally, in vivo tests of our predictions in mouse and zebrafish achieved a validation rate of 62%, significantly higher than what is expected by chance. These results support the existence of underlying cis-regulatory codes dictating tissue-specific transcription in mammalian genomes and validate our enhancer classifier strategy as a method to uncover these regulatory codes.
C1 [Sakabe, Noboru J.; Blanski, Alexander A.; Arimura, Fabio E.; Westlund, John M.; Nobrega, Marcelo A.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Narlikar, Leelavati; Ovcharenko, Ivan] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Nobrega, MA (reprint author), Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
EM nobrega@uchicago.edu; ovcharei@ncbi.nlm.nih.gov
RI Sakabe, Noboru/A-8708-2009
FU NIH; National Library of Medicine [HL088393, HG004428]
FX We thank Ryan Vo for helping us compile the set of known heart
enhancers, Andrew McCallion for providing the tol2- EGFP plasmid, and
Robert Ho for generously sharing his zebrafish facility and injection
bays with us. This research was supported by the Intramural Research
Program of the NIH, National Library of Medicine (I. O.), and by grants
HL088393 and HG004428 (M. A. N).
NR 67
TC 72
Z9 74
U1 1
U2 3
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD MAR
PY 2010
VL 20
IS 3
BP 381
EP 392
DI 10.1101/gr.098657.109
PG 12
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 563JJ
UT WOS:000275124600010
PM 20075146
ER
PT J
AU Saadat, L
Dupree, JL
Kilkus, J
Han, XL
Traka, M
Proia, RL
Dawson, G
Popko, B
AF Saadat, Laleh
Dupree, Jeffrey L.
Kilkus, John
Han, Xianlin
Traka, Maria
Proia, Richard L.
Dawson, Glyn
Popko, Brian
TI Absence of Oligodendroglial Glucosylceramide Synthesis does not Result
in CNS Myelin Abnormalities or Alter the Dysmyelinating Phenotype of
CGT-Deficient Mice
SO GLIA
LA English
DT Article
DE oligodendrocyte; glycolipids; mouse models
ID MULTIDIMENSIONAL MASS-SPECTROMETRY; SHOTGUN LIPIDOMICS;
GLYCOSPHINGOLIPID SYNTHESIS; GLYCOPROTEIN MAG; RAT-BRAIN; GANGLIOSIDES;
CERAMIDE; EXPRESSION; SYNTHASE; FRACTION
AB To examine the function of glycosphingolipids (GSLs) in oligodendrocytes, the myelinating cells of the central nervous system (CNS), mice were generated that lack oligodendroglial expression of UDP-glucose ceramide glucosyltransferase (encoded by Ugcg). These mice (Ugcg(flox/flox);Cnp/Cre) did not show any apparent clinical phenotype, their total brain and myelin extracts had normal GSL content, including ganglioside composition, and myelin abnormalities were not detected in their CNS. These data indicate that the elimination of gangliosides from oligodendrocytes is not detrimental to myelination. These mice were also used to asses the potential compensatory effect of hydroxyl fatty acid glucosylceramide (HFA-GlcCer) accumulation in UDP-galactose:ceramide galactosyltransferase (encoded by Cgt, also known as Ugt8a) deficient mice. At postnatal day 18, the phenotypic characteristics of the Ugcg(flox/flox);Cnp/Cre;Cgt(-/-) mutants, including the degree of hypomyelination, were surprisingly similar to that of Cgt(-/-) mice, suggesting that the accumulation of HFA-GlcCer in Qgt(-/-) mice does not modify their phenotype. These studies demonstrate that abundant, structurally intact myelin can form in the absence of glycolipids, which normally represent over 20% of the dry weight of myelin. (C) 2009 Wiley-Liss, Inc.
C1 [Saadat, Laleh; Traka, Maria; Popko, Brian] Univ Chicago, Dept Neurol, Jack Miller Ctr Peripheral Neuropathy, Chicago, IL 60637 USA.
[Dupree, Jeffrey L.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA USA.
[Kilkus, John; Dawson, Glyn] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
[Han, Xianlin] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
[Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA.
RP Popko, B (reprint author), 5841 S Maryland Ave,MC2030, Chicago, IL 60637 USA.
EM bpopko@uchicago.edu
RI Proia, Richard/A-7908-2012
FU National Institutes of Health [NS027336, NS036866]; National Multiple
Sclerosis Society postdoctoral fellowship award; VCU Department of
Anatomy and Neurobiology Microscopy Facility; NIH-NINDS [5P30NS047463];
NIA [AG23168]
FX Grant sponsor: National Institutes of Health; Grant numbers: NS027336
(to B.P.) and NS036866 (to G.D.); Grant sponsor: National Multiple
Sclerosis Society postdoctoral fellowship award (to M.T.). Grant
sponsor: VCU Department of Anatomy and Neurobiology Microscopy Facility
(where microscopy was performed), supported in part with funding from an
NIH-NINDS Center core grant; Grant number: 5P30NS047463. Grant sponsor:
Washington University School of Medicine, supported in part, with
funding from an NIA grant (where mass spectrometric analysis was
performed); Grant number: NIA AG23168.
NR 38
TC 24
Z9 25
U1 1
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0894-1491
J9 GLIA
JI Glia
PD MAR
PY 2010
VL 58
IS 4
BP 391
EP 398
DI 10.1002/glia.20930
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 550YZ
UT WOS:000274172500002
PM 19705459
ER
PT J
AU Kurochkina, N
Yardeni, T
Huizing, M
AF Kurochkina, Natalya
Yardeni, Tal
Huizing, Marjan
TI Molecular modeling of the bifunctional enzyme UDP-GlcNAc
2-epimerase/ManNAc kinase and predictions of structural effects of
mutations associated with HIBM and sialuria
SO GLYCOBIOLOGY
LA English
DT Article
DE GNE; MNK; homology model; missense mutation; protein structure; sialic
acid
ID INCLUSION-BODY MYOPATHY; ACETYLGLUCOSAMINE
2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; ATP-DEPENDENT GLUCOKINASE;
SIALIC-ACID BIOSYNTHESIS; HELIX-HELIX INTERFACES; RIMMED VACUOLES DMRV;
DISTAL MYOPATHY; N-ACETYLGLUCOSAMINE; GNE GENE; CRYSTAL-STRUCTURE
AB The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE/MNK), encoded by the GNE gene, catalyzes the first two committed, rate-limiting steps in the biosynthesis of N-acetylneuraminic acid (sialic acid). GNE/MNK is feedback inhibited by binding of the downstream product, CMP-sialic acid in its allosteric site. GNE mutations can result in two human disorders, hereditary inclusion body myopathy (HIBM) or sialuria. So far, no active site geometry predictions or conformational transitions involved with function are available for mammalian GNE/MNK. The N-terminal GNE domain is homologous to various prokaryotic 2-epimerases, some of which have solved crystallographic structures. The C-terminal MNK domain belongs to the sugar kinases superfamily; its crystallographic structure is solved at 2.84 angstrom and three-dimensional structures have also been reported for several other kinases. In this work, we employed available structural data of GNE/MNK homologs to model the active sites of human GNE/MNK and identify critical amino acid residues responsible for interactions with substrates. In addition, we modeled effects of GNE/MNK missense mutations associated with HIBM or sialuria on helix arrangement, substrate binding, and enzyme action. We found that all reported mutations are associated with the active sites or secondary structure interfaces of GNE/MNK. The Persian-Jewish HIBM founder mutation p.M712T is located at the interface alpha 4 alpha 10 and likely affects GlcNAc, Mg(2+), and ATP binding. This work contributes to further understanding of GNE/MNK function and ligand binding, which may assist future studies for therapeutic options that target misfolded GNE/MNK in HIBM and/or sialuria.
C1 [Kurochkina, Natalya] Sch Theoret Modeling, Dept Biophys, Chevy Chase, MD 20825 USA.
[Yardeni, Tal; Huizing, Marjan] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Yardeni, Tal] Tel Aviv Univ, Sackler Sch Med, Grad Partner Program, Tel Aviv, Israel.
RP Kurochkina, N (reprint author), Sch Theoret Modeling, Dept Biophys, Chevy Chase, MD 20825 USA.
EM info@schtm.org
FU National Human Genome Research Institute, National Institutes of Health,
Bethesda, MD, USA; Research Funds of The School of Theoretical Modeling,
Chevy Chase, MD, USA
FX The Intramural Research programs of the National Human Genome Research
Institute, National Institutes of Health, Bethesda, MD, USA and Research
Funds of The School of Theoretical Modeling, Chevy Chase, MD, USA.
NR 61
TC 10
Z9 11
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD MAR
PY 2010
VL 20
IS 3
BP 322
EP 337
DI 10.1093/glycob/cwp176
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 553CC
UT WOS:000274341300006
PM 19917666
ER
PT J
AU Trimble, EL
Denicoff, AM
Abrams, JS
AF Trimble, Edward L.
Denicoff, Andrea M.
Abrams, Jeffrey S.
TI Strengthening accrual to cancer clinical trials
SO GYNECOLOGIC ONCOLOGY
LA English
DT Editorial Material
ID BARRIERS; IMPACT
C1 [Trimble, Edward L.; Denicoff, Andrea M.; Abrams, Jeffrey S.] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Trimble, EL (reprint author), 6130 Execut Blvd,Suite 7025,MSC 7436, Bethesda, MD 20892 USA.
EM tt6m@nih.gov
NR 11
TC 2
Z9 2
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2010
VL 116
IS 3
BP 291
EP 292
DI 10.1016/j.ygyno.2010.01.015
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 566HF
UT WOS:000275360000001
PM 20152512
ER
PT J
AU Bosquet, JG
Terstriep, SA
Cliby, WA
Brown-Jones, M
Kaur, JS
Podratz, KC
Keeney, GL
AF Bosquet, Jesus Gonzalez
Terstriep, Shelby A.
Cliby, William A.
Brown-Jones, Monica
Kaur, Judith S.
Podratz, Karl C.
Keeney, Gary L.
TI The impact of multi-modal therapy on survival for uterine
carcinosarcomas
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Carcinosarcomas; Treatment outcomes; FIGO staging
ID MIXED MULLERIAN TUMORS; GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III TRIAL;
FEMALE GENITAL-TRACT; PROGNOSTIC-FACTORS; ENDOMETRIAL CANCER; MESODERMAL
TUMORS; HISTOLOGIC TYPES; STAGE-I; UTERUS
AB Objectives. To investigate treatment outcomes of patients with carcinosarcoma of the uterus and to identify parameters predictive of survival. Secondary objectives included (a) the assessment of treatment failures as a function Of histologic subtypes and (b) the impact of the new FIGO staging classification system, Methods. This is a retrospective outcomes analysis of 121 patients diagnosed with primary carcinosarcoma of the uterus. Clinical, surgical and pathological data were reviewed and patients were classified according to the new 2009 FIGO staging system for endometrial carcinoma. Survivorship curves were evaluated with the log-rank test and associations between events and variables with Cox proportional hazards model.
Results. in the multivariate analyses for disease-specific survival (DSS) and disease-free Survival (DFS), the only independent factors were FIGO stage, adjuvant chemotherapy after Surgery and the presence of clear cell histology in the tumor. The 5-year DSS for stages I-II, III and IV was 59%, 22% and 9%, respectively. The administration of platin-based chemotherapy provided a significant benefit with regard to both DFS (OR = 0.28; p = 0.001) and DSS (OR = 0.35; p = 0.01). While radiotherapy (RT) appeared to control vaginal failures in all stages, pelvic RT did not impact DSS. Of importance, the epithelial component was the predominant histology in both the primary extrauterine metastases (94%) and the distant failure sites (82%).
Conclusions. This highly aggressive uterine malignancy warrants comprehensive surgical staging to assess tumor dissemination followed by systemic therapy in patients with both early and advanced stage disease. Published by Elsevier Inc.
C1 [Bosquet, Jesus Gonzalez] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Cliby, William A.; Brown-Jones, Monica; Podratz, Karl C.] Mayo Clin, Dept Obstet & Gynecol, Div Gynecol Oncol, Rochester, MN 55905 USA.
[Keeney, Gary L.] Mayo Clin, Dept Anat Pathol, Rochester, MN 55905 USA.
RP Bosquet, JG (reprint author), Adv Technol Ctr, Lab Translat Genom, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA.
EM gonzalej@mail.nih.gov
NR 33
TC 36
Z9 36
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 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2010
VL 116
IS 3
BP 419
EP 423
DI 10.1016/j.ygyno.2009.10.053
PG 5
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 566HF
UT WOS:000275360000027
ER
PT J
AU Kuo, DYS
Blank, SV
Christos, PJ
Kim, M
Caputo, TA
Pothuri, B
Hershman, D
Goldman, N
Ivy, PS
Runowicz, CD
Muggia, F
Goldberg, GL
Einstein, MH
AF Kuo, Dennis Yi-Shin
Blank, Stephanie V.
Christos, Paul J.
Kim, Mimi
Caputo, Thomas A.
Pothuri, Bhavana
Hershman, Dawn
Goldman, Noah
Ivy, Percy S.
Runowicz, Carolyn D.
Muggia, Franco
Goldberg, Gary L.
Einstein, Mark H.
TI Paclitaxel plus oxaliplatin for recurrent or metastatic cervical cancer:
A New York Cancer Consortium Study
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 40th Annual Meeting on Womens Cancer
CY FEB 05-08, 2009
CL San Antonio, TX
DE Recurrent cervical cancel; Paclitaxel; Oxaliplatin; Response; Toxicity
ID GYNECOLOGIC-ONCOLOGY-GROUP; CELL LUNG-CANCER; PHASE-II; CARCINOMA;
CISPLATIN; CHEMOTHERAPY; PLATINUM
AB Objective. Survival in women with recurrent or metastatic cervical cancer remains poor. More effective and less toxic regimens are needed. Cisplatin is an effective radiosensitizer, but its single agent activity ill recurrent cervical cancer, especially after prior cisplatin exposure, is disappointing, with a response rate of only 13%. Oxaliplatin has preclinical activity in cisplatin-resistant tumors and may have synergic activity when combined with paclitaxel. Our objective is to determine the efficacy and toxicity of paclitaxel and oxaliplatin in patients with recurrent or metastatic cervical cancer.
Methods. patients with histologic confirmation of primary metastatic or recurrent cervical cancer not amenable to surgical management were eligible. Treatment consisted of paclitaxel 175 mg/m(2) IV and oxaliplatin 130 mg/m(2) IV every 21 days. The primary endpoints were toxicity, recorded every cycle, and response, determined by RECIST criteria and were assessed every 9 weeks, with Subsequent confirmation as required. Sample size determinations were made using a Simon's two-stage design with a projected overall response proportion of 13% with cisplatin alone. Survival rates were calculated with Kaplan-Meier methods.
Results. Of the 35 patients enrolled, 32 were evaluable. The median age was 56 (27-78): 30 had had prior-radiation (23 concomitant with cisplatin). Patients completed a mean of 4.2 cycles (1-11). There were 2 complete and 5 Partial responses for a total response rate of 7/32 (22%: 95% CI: 9.3%-40.0%). Eight patients had stable disease For an overall clinical benefit rate of 15/32 (47%; 95% Cl: 29.1%-65.3%). The mean time to best response was 13.5 weeks (95% Cl: 10.6, 16.4). The mean progression-free Survival was 21 weeks (95% Cl: 14.7, 27.2) and mean overall Survival was 52 weeks (95% CI: 39.4, 64.8). A total of 135 cycles were administered. There were 28 (20.1%) grade 3/4 hematologic toxicities and 46 (34.1%) grade 3/4 non-hematologic toxicities, which were predominantly sensory neuropathy. There were 13 treatment delays, 4 dose reductions, and no treatment-related deaths.
Conclusions. The combination of paclitaxel and oxaliplatin is an effective regimen in patients with recurrent or persistent cervical cancer including a majority previously exposed to cisplatin. Further study and comparison with other platinum-based regimens is warranted. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Kuo, Dennis Yi-Shin; Goldberg, Gary L.; Einstein, Mark H.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10461 USA.
[Blank, Stephanie V.; Pothuri, Bhavana; Muggia, Franco] NYU, Sch Med, New York, NY 10003 USA.
[Christos, Paul J.; Caputo, Thomas A.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA.
[Hershman, Dawn] Columbia Univ, New York Presbyterian Hosp, New York, NY 10027 USA.
[Goldman, Noah] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA.
[Ivy, Percy S.] NCI, CTEP, Bethesda, MD 20892 USA.
[Runowicz, Carolyn D.] Univ Connecticut, Ctr Hlth, Storrs, CT 06269 USA.
RP Kuo, DYS (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, 1695 Eastchester Rd Suite 601, Bronx, NY 10461 USA.
EM dykuo@montefiore.org
OI Muggia, Franco/0000-0003-0703-9146
FU NCI NIH HHS [N01 CM062204, N01-CM62204, N01CM62204]
NR 21
TC 7
Z9 11
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2010
VL 116
IS 3
BP 442
EP 446
DI 10.1016/j.ygyno.2009.10.082
PG 5
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 566HF
UT WOS:000275360000031
PM 19931137
ER
PT J
AU Dewdney, S
Kizer, N
Babb, S
Rimmel, B
Andaya, A
Ali, S
O'Malley, D
Mannel, R
Darcy, K
DiSilvestro, P
Lele, S
Pearl, M
Brinton, L
Goodfellow, P
AF Dewdney, S.
Kizer, N.
Babb, S.
Rimmel, B.
Andaya, A.
Ali, S.
O'Malley, D.
Mannel, R.
Darcy, K.
DiSilvestro, P.
Lele, S.
Pearl, M.
Brinton, L.
Goodfellow, P.
TI Uterine serous carcinoma: Increased familial risk for pancreatic cancer
and other Lynch-associated malignancies
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Dewdney, S.; Kizer, N.; Babb, S.; Rimmel, B.; Goodfellow, P.] Washington Univ, Sch Med, St Louis, MO USA.
[Andaya, A.; Brinton, L.] Natl Inst Hlth, Bethesda, MD USA.
[O'Malley, D.] Ohio State Univ, Columbus, OH 43210 USA.
[Mannel, R.] Univ Oklahoma, Oklahoma City, OK USA.
[Lele, S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Ali, S.; Darcy, K.] GOG Stat & Data Ctr, Buffalo, NY USA.
[DiSilvestro, P.] Womens & Infants, Providence, RI USA.
[Pearl, M.] Suny Downstate Med Ctr, St James, NY USA.
RI Brinton, Louise/G-7486-2015; OMalley, David/E-3789-2011
OI Brinton, Louise/0000-0003-3853-8562;
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2010
VL 116
IS 3
SU 1
MA 14
BP S8
EP S9
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 594LA
UT WOS:000277538000016
ER
PT J
AU Kim, K
Tosca, P
Rudge, T
Peggins, J
Broadt, T
Wang, M
Harris, R
Aurigemma, R
Curiel, D
Alvarez, R
AF Kim, K.
Tosca, P.
Rudge, T.
Peggins, J.
Broadt, T.
Wang, M.
Harris, R.
Aurigemma, R.
Curiel, D.
Alvarez, R.
TI Identifying the safety profile of Ad5/3-Delta 24, a novel
infectivity-enhanced conditionally replicative adenovirus, in
anticipation of a phase I clinical trial in patients with ovarian cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Kim, K.; Curiel, D.; Alvarez, R.] Univ Alabama, Birmingham, AL USA.
[Tosca, P.; Peggins, J.; Aurigemma, R.] Natl Canc Inst, Bethesda, MD USA.
[Rudge, T.] Battelle Biomed Res Ctr, W Jefferson, OH USA.
[Broadt, T.] Sci Applicat Int Corp, Washington, DC USA.
[Wang, M.; Harris, R.] Sci Applicat Int Corp, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2010
VL 116
IS 3
SU 1
MA 390
BP S150
EP S151
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 594LA
UT WOS:000277538000378
ER
PT J
AU Kimball, K
Barnes, M
Wang, M
Siegal, G
Wang, W
Harris, R
Aurigemma, R
Preuss, M
Alvarez, R
AF Kimball, K.
Barnes, M.
Wang, M.
Siegal, G.
Wang, W.
Harris, R.
Aurigemma, R.
Preuss, M.
Alvarez, R.
TI Phase I study of a tropism-modified, conditionally replicative
adenovirus (CRAd) for recurrent gynecologic malignancies
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Kimball, K.; Barnes, M.; Wang, M.; Siegal, G.; Wang, W.; Preuss, M.; Alvarez, R.] Univ Alabama, Birmingham, AL USA.
[Harris, R.] Sci Applicat Int Corp, Philadelphia, PA USA.
[Aurigemma, R.] Natl Canc Inst, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2010
VL 116
IS 3
SU 1
MA 282
BP S111
EP S112
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 594LA
UT WOS:000277538000275
ER
PT J
AU Lu, K
Chen, L
Lynch, H
Munsell, M
Cornelison, T
Boyd-Rogers, S
Rubin, M
Daniels, M
Loose, D
Broaddus, R
AF Lu, K.
Chen, L.
Lynch, H.
Munsell, M.
Cornelison, T.
Boyd-Rogers, S.
Rubin, M.
Daniels, M.
Loose, D.
Broaddus, R.
TI A prospective, multicenter randomized study of oral contraceptive versus
Depo-Provera for the prevention of endometrial cancer in women with
Lynch syndrome
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Lu, K.; Munsell, M.; Boyd-Rogers, S.; Daniels, M.; Broaddus, R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Chen, L.; Rubin, M.] UCSF, Ctr Comprehens Canc, San Francisco, CA USA.
[Lynch, H.] Creighton Univ, Sch Med, Omaha, NE 68178 USA.
[Cornelison, T.] Natl Canc Inst, Bethesda, MD USA.
[Loose, D.] Univ Texas Houston, Sch Med, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2010
VL 116
IS 3
SU 1
MA 6
BP S4
EP S5
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 594LA
UT WOS:000277538000008
ER
PT J
AU Mannel, R
Brady, M
Kohn, E
Hanjani, P
Hiura, M
Lee, R
De Geest, K
Cohn, D
Monk, B
Michael, H
AF Mannel, R.
Brady, M.
Kohn, E.
Hanjani, P.
Hiura, M.
Lee, R.
De Geest, K.
Cohn, D.
Monk, B.
Michael, H.
TI GOG 175: A Randomized phase III trial of IV carboplatin (AUC 6) and
paclitaxel 175 mg/m(2) Q 21 days x 3 courses plus low-dose paclitaxel 40
mg/m(2)/wk versus IV carboplatin (AUC 6) and paclitaxel 175 mg/m(2) Q 21
days x 3 courses plus observation in patients with early-stage ovarian
carcinoma
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Mannel, R.] Univ Oklahoma, Oklahoma City, OK USA.
[Brady, M.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Kohn, E.] Natl Canc Inst, Bethesda, MD USA.
[Hanjani, P.] Abington Mem Hosp, Rosenfeld Canc Ctr, Abington, PA 19001 USA.
[Hiura, M.] Shikoku Canc Ctr, Matsuyama, Ehime, Japan.
[Lee, R.] Southwest Gynecol Oncol Associates Inc, Lakewood, WA USA.
[De Geest, K.] Univ Iowa, Iowa City, IA USA.
[Cohn, D.] Ohio State Univ, Columbus, OH 43210 USA.
[Monk, B.] Univ Calif Irvine, Orange, CA 92668 USA.
[Michael, H.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2010
VL 116
IS 3
SU 1
MA 1
BP S2
EP S2
DI 10.1016/j.ygyno.2009.12.013
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 594LA
UT WOS:000277538000003
ER
PT J
AU Mathews, C
Tenney, M
Moxley, K
Stoner, J
Smith, K
Nicolas, W
Wang, S
Gold, M
Landrum, L
Walker, J
AF Mathews, C.
Tenney, M.
Moxley, K.
Stoner, J.
Smith, K.
Nicolas, W.
Wang, S.
Gold, M.
Landrum, L.
Walker, J.
TI Tubal ligation and cervical cancer risk
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Smith, K.; Walker, J.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Nicolas, W.] Natl Canc Inst, Bethesda, MD USA.
[Gold, M.] Vanderbilt Univ, Nashville, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2010
VL 116
IS 3
SU 1
MA 91
BP S36
EP S37
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 594LA
UT WOS:000277538000086
ER
PT J
AU Mok, S
Birrer, M
Donninger, H
Hao, K
Ozbun, L
Samini, G
Vathepadiekal, V
Berkowitz, R
Bonome, T
Wong, K
AF Mok, S.
Birrer, M.
Donninger, H.
Hao, K.
Ozbun, L.
Samini, G.
Vathepadiekal, V.
Berkowitz, R.
Bonome, T.
Wong, K.
TI A gene signature predictive for outcome in advanced ovarian cancer
identifies a novel survival factor: Microfibril-associated glycoprotein
2
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Mok, S.; Wong, K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Birrer, M.; Vathepadiekal, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Donninger, H.; Ozbun, L.; Samini, G.; Bonome, T.] NCI, Bethesda, MD 20892 USA.
[Hao, K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Berkowitz, R.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2010
VL 116
IS 3
SU 1
MA 426
BP S164
EP S164
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 594LA
UT WOS:000277538000413
ER
PT J
AU Pittaluga, S
Jaffe, ES
AF Pittaluga, Stefania
Jaffe, Elaine S.
TI T-cell/histiocyte-rich large B-cell lymphoma
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Editorial Material
ID PREDOMINANT HODGKINS-DISEASE; DISTINCT CLINICOPATHOLOGICAL ENTITY;
DIFFERENTIAL-DIAGNOSIS; FOLLICULAR LYMPHOMA; HISTIOCYTE-RICH;
IMMUNOGLOBULIN; EXPRESSION; PU.1; REARRANGEMENTS; POPULATIONS
C1 [Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD USA.
RP Pittaluga, S (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD USA.
EM elainejaffe@nih.gov
OI Jaffe, Elaine/0000-0003-4632-0301
NR 39
TC 13
Z9 13
U1 0
U2 2
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD MAR
PY 2010
VL 95
IS 3
BP 352
EP 356
DI 10.3324/haematol.2009.016931
PG 5
WC Hematology
SC Hematology
GA 578KK
UT WOS:000276292100003
PM 20207840
ER
PT J
AU Sloand, EM
Olnes, MJ
Weinstein, B
Wu, C
Maciejewski, J
Scheinberg, P
Young, NS
AF Sloand, Elaine M.
Olnes, Matthew J.
Weinstein, Barbara
Wu, Colin
Maciejewski, Jaroslaw
Scheinberg, Phillip
Young, Neal S.
TI Long-term follow-up of patients with moderate aplastic anemia and pure
red cell aplasia treated with daclizumab
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE interleukin-2 receptors; immunosuppression; T-regulatory cells; marrow
failure
ID REGULATORY T-CELLS; RECEPTOR ANTIBODY DACLIZUMAB; RENAL-TRANSPLANTATION;
MYELODYSPLASTIC SYNDROME; MULTIPLE-SCLEROSIS; ACUTE REJECTION;
HOST-DISEASE; CYCLOSPORINE; INDUCTION; THERAPY
AB Background
Pure red cell aplasia and moderate aplastic anemia are marrow failure states with an immune pathogenesis. Previously, we described short-term improvements in blood counts in two pilot studies treating moderate aplastic anemia (mAA) and pure red cell aplasia (PRCA) patients with daclizumab, a humanized monoclonal antibody to the interleukin-2 receptor; we now report our long-term experience with a larger cohort of patients.
Design and Methods
After a median follow-up period of 4.8 years, 19 of 45 (42%) evaluable mAA patients and 10 of 26 (38%) patients with PRCA responded by three months and 2 additional m-AA patients responded by six months following administration of the drug.
Results
Seven of 28 (25%) mAA patients achieved long-term packed red blood cell PRBC transfusion independence, and all PRCA responders achieved long-term transfusion PRBC transfusion independence.
Conclusions
Red cell transfusion-independence prior to treatment in mAA patients predicted response. The only significant adverse treatment-related events were transient rashes and arthralgias. Daclizumab is safe and effective, and produces lengthy remissions in patients with PRCA and mAA.
C1 [Sloand, Elaine M.; Olnes, Matthew J.; Weinstein, Barbara; Wu, Colin; Maciejewski, Jaroslaw; Scheinberg, Phillip; Young, Neal S.] NHLBI, Bethesda, MD 20892 USA.
RP Sloand, EM (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
EM sloande@nih.gov
OI Scheinberg, Phillip/0000-0002-9047-4538
NR 28
TC 14
Z9 18
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD MAR
PY 2010
VL 95
IS 3
BP 382
EP 387
DI 10.3324/haematol.2009.013557
PG 6
WC Hematology
SC Hematology
GA 578KK
UT WOS:000276292100009
PM 20207845
ER
PT J
AU Lamant, L
Pileri, S
Sabattini, E
Brugieres, L
Jaffe, ES
Delsol, G
AF Lamant, Laurence
Pileri, Stefano
Sabattini, Elena
Brugieres, Laurence
Jaffe, Elaine S.
Delsol, Georges
TI Cutaneous presentation of ALK-positive anaplastic large cell lymphoma
following insect bites: evidence for an association in five cases
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE ALK-positive ALCL; NPM-ALK; skin involvement
ID BARR-VIRUS INFECTION; MOSQUITO BITES; BORRELIA-BURGDORFERI;
HYPERSENSITIVITY; KINASE; PATIENT; FUSION; SKIN; INFILTRATION;
EXPRESSION
AB Background
Skin involvement is frequent in ALK-positive anaplastic large cell lymphomas. The role of an insect bite as a triggering event has been postulated but not well documented.
Design and Methods
We retrospectively investigated five cases of ALK-positive anaplastic large cell lymphoma who presented with skin lesions occurring after an insect bite. Biopsies were immunostained with antibodies against CD30, ALK, T- and B-cell antigens.
Results
Persistent skin lesions developed after solitary insect bites in three patients and after multiple bites in two. Regional lymphadenopathy developed within weeks after the bite in three cases. In four cases the correct diagnosis was delayed due to misinterpretation of the findings as a reactive infiltrate in the skin (n=2) or lymph nodes (n=2); all cases subsequently showed small numbers of cells with nuclear and cytoplasmic staining for ALK. The final diagnoses were lymphohistiocytic variant (n=3) and composite common/small cell type (n=2) anaplastic large cell lymphoma. The patients were treated and three were alive at the last follow-up. Two patients died, one of pneumonia and the other of disseminated disease.
Conclusions
In these cases the sequence of events between the insect bites and the occurrence of both skin lesions and satellite lymphadenopathy suggest a direct relationship between the bite and the presentation with anaplastic large cell lymphoma. We postulate that insect bite-associated antigens could result in an influx of T lymphocytes, some bearing the t(2,5). The subsequent release of cytokines at the site of the bite could act as a 'second hit', eliciting activation of the latter cells, which would then express the oncogenic NPM-ALK protein and undergo uncontrolled proliferation.
C1 [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Lamant, Laurence; Delsol, Georges] Univ Toulouse 3, Toulouse, France.
[Lamant, Laurence; Delsol, Georges] Fac Med Toulouse, INSERM, Ctr Physiopathol Toulouse Purpan, U 563, F-31073 Toulouse, France.
[Lamant, Laurence; Delsol, Georges] CHU Purpan, Anat Pathol Lab, Toulouse, France.
[Pileri, Stefano; Sabattini, Elena] Univ Bologna, Unit Haematopathol, Dept Haematol & Oncol Sci L & A Seragnoli, Policlin S Orsola, Bologna, Italy.
[Brugieres, Laurence] Inst Gustave Roussy, Dept Pediat Oncol, Villejuif, France.
RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 2B 42 10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA.
EM elainejaffe@nih.gov
OI Jaffe, Elaine/0000-0003-4632-0301
FU A.I.R.C. (Milan); Center for Cancer Research, National Cancer Institute;
Institut National du Cancer (PAIR lymphomes)
FX Funding: this work was partly supported by A.I.R.C. (Milan), by the
intramural research program of the Center for Cancer Research, National
Cancer Institute and by the Programme d'Action Integree de Recherche sur
les Lymphomes, Institut National du Cancer (PAIR lymphomes).
NR 31
TC 20
Z9 20
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD MAR
PY 2010
VL 95
IS 3
BP 449
EP 455
DI 10.3324/haematol.2009.015024
PG 7
WC Hematology
SC Hematology
GA 578KK
UT WOS:000276292100017
PM 19951975
ER
PT J
AU Hoots, K
AF Hoots, K.
TI A commentary on variant Creutzfeld-Jacob disease
SO HAEMOPHILIA
LA English
DT Editorial Material
C1 NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
RP Hoots, K (reprint author), NHLBI, Div Blood Dis & Resources, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1351-8216
J9 HAEMOPHILIA
JI Haemophilia
PD MAR
PY 2010
VL 16
IS 2
BP 238
EP 239
DI 10.1111/j.1365-2516.2010.02234.x
PG 2
WC Hematology
SC Hematology
GA 560YI
UT WOS:000274941200003
PM 20487441
ER
PT J
AU Friedmann, T
AF Friedmann, Theodore
TI How Close Are We to Gene Doping?
SO HASTINGS CENTER REPORT
LA English
DT Article
ID THERAPY; IMMUNODEFICIENCY
C1 [Friedmann, Theodore] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA.
[Friedmann, Theodore] NIH, Recombinant DNA Advisory Comm, Off Biotechnol Activ, Bethesda, MD USA.
RP Friedmann, T (reprint author), Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA.
NR 10
TC 9
Z9 9
U1 1
U2 14
PU HASTINGS CENTER
PI BRIARCLIFF MANOR
PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA
SN 0093-0334
J9 HASTINGS CENT REP
JI Hastings Cent. Rep.
PD MAR-APR
PY 2010
VL 40
IS 2
BP 20
EP 22
PG 3
WC Ethics; Health Care Sciences & Services; Medical Ethics; Social
Sciences, Biomedical
SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical
Ethics; Biomedical Social Sciences
GA 574MD
UT WOS:000275992600014
PM 20391845
ER
PT J
AU Lonsdorf, AS
Becker, MR
Stockfleth, E
Schakel, K
Ulrich, C
AF Lonsdorf, A. S.
Becker, M. R.
Stockfleth, E.
Schaekel, K.
Ulrich, C.
TI Primary and secondary prevention of skin cancer in organ transplant
recipients
SO HAUTARZT
LA German
DT Article
DE Organ transplantation; Immunosuppression; mTOR-Inhibitor; Skin cancer;
Actinic keratosis
ID TOPICAL PHOTODYNAMIC THERAPY; SQUAMOUS-CELL CARCINOMA; ACTINIC
KERATOSES; 5-PERCENT IMIQUIMOD; CONTROLLED TRIAL; RISK-FACTORS;
DNA-DAMAGE; IMMUNOSUPPRESSION; DISEASE; KIDNEY
AB Skin cancer constitutes the most frequently reported post-transplant malignancy in solid organ transplant recipients (OTR) worldwide. Whereas the risk for malignant melanoma is only moderately increased, non-melanoma skin cancers (NMSC) seem to thrive on chronic immunosuppression and account for up to 95% of post-transplant cutaneous malignancies. Compared to the general population cutaneous squamous cell carcinoma (SCC) and actinic keratoses (AK) characteristically show even higher incidences than basal cell carcinoma (BCC) and act as an indicator for the development of multiple primary cutaneous neoplasias and locally recurrent cancers (field cancerization). Early diagnosis and therapy of pre-malignant cutaneous lesions is crucial for the secondary prophylaxis of further invasive and highly aggressive skin cancers. High quality interdisciplinary care and prophylactic modalities, including consistent and sufficient UV protection, topical immunmodulatory therapies of UV-damaged skin areas, retinoid chemoprevention as well as tapering immunosuppressive treatment or the selection of immunosuppressants with proposed antiangiogenic properties like mTor-inhibitors may help to reduce the multiplicity of subsequent primary skin cancers in high-risk patients. Apart from the continuous need for educational intervention of OTR in the primary prophylaxis of post-transplant skin cancers, dermatologic care occupies a central position within the field of transplantation medicine in terms of pre- and post-transplanation dermatologic evaluation and therapy as well as the implication of timely and effective secondary preventive approaches in the management of this high-risk patient population.
C1 [Lonsdorf, A. S.; Schaekel, K.] Hauttumorzentrum, Univ Hautklin, D-69115 Heidelberg, Germany.
[Becker, M. R.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
[Stockfleth, E.; Ulrich, C.] Charite, Klin Dermatol Venerol & Allergol, D-13353 Berlin, Germany.
RP Lonsdorf, AS (reprint author), Hauttumorzentrum, Univ Hautklin, Vossstr 2, D-69115 Heidelberg, Germany.
EM anke.lonsdorf@med.uni-heidelberg.de
NR 32
TC 5
Z9 5
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0017-8470
J9 HAUTARZT
JI Hautarzt
PD MAR
PY 2010
VL 61
IS 3
BP 195
EP +
DI 10.1007/s00105-009-1858-2
PG 10
WC Dermatology
SC Dermatology
GA 566VL
UT WOS:000275401200007
PM 20177652
ER
PT J
AU Drori-Herishanu, L
Lodish, M
Verma, S
Bimpaki, E
Keil, MF
Horvath, A
Stratakis, CA
AF Drori-Herishanu, L.
Lodish, M.
Verma, S.
Bimpaki, E.
Keil, M. F.
Horvath, A.
Stratakis, C. A.
TI The Growth Hormone Receptor (GHR) Polymorphism in Growth-retarded
Children with Cushing Disease: Lack of Association with Growth and
Measures of the Somatotropic Axis
SO HORMONE AND METABOLIC RESEARCH
LA English
DT Article
DE Cushing syndrome; cortisol; pituitary gland; growth hormone receptor;
genetics
ID GESTATIONAL-AGE CHILDREN; FULL-LENGTH ISOFORMS; INCREASED
RESPONSIVENESS; REPLACEMENT THERAPY; DEFICIENT ADULTS; TURNER SYNDROME;
SHORT STATURE; FINAL HEIGHT; EXON-3; DELETION
AB Pediatric Cushing disease (CD) often presents with short stature, but we have observed significant inter-individual variability in the growth delay caused by endogenous hypercortisolism. Glucocorticoids cause growth retardation by affecting the growth hormone (GH) - insulin-like growth factor-1 (IGF 1) somatotropic axis, but also other, GH-independent sites. Recently, the GH receptor (GHR) gene was found to have a common polymorphism (P) that leads to a deletion (d3) or retention of exon 3. In this study, we tested the hypothesis that the GH receptor polymorphism (GHR-P) maybe one of the significant variants that determines the degree of growth delay among patients with CD. GHR genotyping was performed on 56 children with newly diagnosed CD (24 females, 32 males, mean age of 12.9 +/- 3.3 years) who were followed at our institution between the years 1997-2007. Correlation analysis included genotype, measures of growth and the somatotropic axis, and anthropometrics. Within the group, 31 (12 girls, 19 boys) expressed the full length GHR allele, 10 (4 girls, 6 boys) were d3-GHR homozygotes and 15 (7 girls, 8 boys) were d3-GHR heterozygotes. No significant differences were found between the GHR genotypes and patient's height and/or growth velocity, or any other measures that we evaluated. The presence of a well-studied and common GHR polymorphism does not appear to be responsible for the variability of growth delay observed in patients with Cushing disease.
C1 NIH, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA.
NIH, Pediat Endocrinol Interinst Training Program, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet, Director Pediat Endocrinol Training Program, DEB,NIH, Bldg 10 CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU United States National Institutes of Health, National Institute of Child
Health & Human Development (NICHD) [Z01-HD-000642-04]
FX The described studies were supported by the United States National
Institutes of Health, National Institute of Child Health & Human
Development (NICHD) intramural project Z01-HD-000642-04 to C.A.
Stratakis.
NR 30
TC 2
Z9 2
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0018-5043
J9 HORM METAB RES
JI Horm. Metab. Res.
PD MAR
PY 2010
VL 42
IS 3
BP 194
EP 197
DI 10.1055/s-0029-1242744
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 568CY
UT WOS:000275500600007
PM 20013551
ER
PT J
AU Franceschini, N
Voruganti, VS
Haack, K
Almasy, L
Laston, S
Goring, HHH
Umans, JG
Lee, ET
Best, LG
Fabsitz, RR
MacCluer, JW
Howard, BV
North, KE
Cole, SA
AF Franceschini, Nora
Voruganti, V. Saroja
Haack, Karin
Almasy, Laura
Laston, Sandy
Goering, Harald H. H.
Umans, Jason G.
Lee, Elisa T.
Best, Lyle G.
Fabsitz, Richard R.
MacCluer, Jean W.
Howard, Barbara V.
North, Kari E.
Cole, Shelley A.
TI The association of the MYH9 gene and kidney outcomes in American
Indians: the Strong Heart Family Study
SO HUMAN GENETICS
LA English
DT Article
ID TYPE-2 DIABETES-MELLITUS; STAGE RENAL-DISEASE; AFRICAN-AMERICANS;
LINKAGE DISEQUILIBRIUM; CARDIOVASCULAR-DISEASE; RISK; POLYMORPHISMS;
ALBUMINURIA; COMMITTEE
AB Chronic kidney disease (CKD) is an important public health problem in American Indian populations. Recent research has identified associations of polymorphisms in the myosin heavy chain type II isoform A (MYH9) gene with hypertensive CKD in African-Americans. Whether these associations are also present among American Indian individuals is unknown. To evaluate the role of genetic polymorphisms in the MYH9 gene on kidney disease in American Indians, we genotyped 25 SNPs in the MYH9 gene region in 1,119 comparatively unrelated individuals. Four SNPs failed, and one SNP was monomorphic. We inferred haplotypes using seven SNPs within the region of the previously described E haplotype using Phase v2.1. We studied the association between 20 MYH9 SNPs with kidney function (estimated glomerular filtration rate, eGFR) and CKD (eGFR < 60 ml/min/1.73 m(2) or renal replacement therapy or kidney transplant) using age-, sex- and center-adjusted models and measured genotyped within the variance component models. MYH9 SNPs were not significantly associated with kidney traits in additive or recessive genetic adjusted models. MYH9 haplotypes were also not significantly associated with kidney outcomes. In conclusion, common variants in MYH9 polymorphisms may not confer an increased risk of CKD in American Indian populations. Identification of the actual functional genetic variation responsible for the associations seen in African-Americans will likely help to clarify the lack of replication of this gene in our population of American Indians.
C1 [Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.
[Voruganti, V. Saroja; Haack, Karin; Almasy, Laura; Laston, Sandy; Goering, Harald H. H.; MacCluer, Jean W.; Cole, Shelley A.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA.
[Umans, Jason G.] Georgetown Univ, Med Ctr, Div Nephrol & Hypertens, Washington, DC 20007 USA.
[Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Ctr Amer Indian Hlth Res, Coll Publ Hlth, Oklahoma City, OK USA.
[Best, Lyle G.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA.
[Fabsitz, Richard R.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Umans, Jason G.; Howard, Barbara V.; North, Kari E.] MedStar Res Inst, Washington, DC USA.
[North, Kari E.] Univ N Carolina, Ctr Genome Sci, Chapel Hill, NC USA.
RP Franceschini, N (reprint author), Univ N Carolina, Dept Epidemiol, 137 E Franklin St,Suite 306 CB 8050, Chapel Hill, NC 27514 USA.
EM noraf@unc.edu
FU National Heart, Lung, and Blood Institute, Bethesda, MD [U01-HL65520,
U01-HL41642, U01-HL41652, U01-HL41654, U01-HL65521]; National Institutes
of Health [MH59490]
FX This work was supported by grants U01-HL65520, U01-HL41642, U01-HL41652,
U01-HL41654, and U01-HL65521 from the National Heart, Lung, and Blood
Institute, Bethesda, MD. Development of SOLAR was supported by National
Institutes of Health grant MH59490.
NR 22
TC 13
Z9 13
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD MAR
PY 2010
VL 127
IS 3
BP 295
EP 301
DI 10.1007/s00439-009-0769-8
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 554TE
UT WOS:000274456500003
PM 19921264
ER
PT J
AU Hehr, U
Pineda-Alvarez, DE
Uyanik, G
Hu, P
Zhou, N
Hehr, A
Schell-Apacik, C
Altus, C
Daumer-Haas, C
Meiner, A
Steuernagel, P
Roessler, E
Winkler, J
Muenke, M
AF Hehr, Ute
Pineda-Alvarez, Daniel E.
Uyanik, Goekhan
Hu, Ping
Zhou, Nan
Hehr, Andreas
Schell-Apacik, Chayim
Altus, Carola
Daumer-Haas, Cornelia
Meiner, Annechristin
Steuernagel, Peter
Roessler, Erich
Winkler, Juergen
Muenke, Maximilian
TI Heterozygous mutations in SIX3 and SHH are associated with
schizencephaly and further expand the clinical spectrum of
holoprosencephaly
SO HUMAN GENETICS
LA English
DT Article
ID SONIC HEDGEHOG GENE; GERMLINE MUTATIONS; EMX2; POPULATION; FEATURES
AB Schizencephaly (SCH) is a clinically and etiologically heterogeneous cerebral malformation presenting as unilateral or bilateral hemispheric cleft with direct connection between the inner and outer liquor spaces. The SCH cleft is usually lined by gray matter, which appears polymicrogyric implying an associated impairment of neuronal migration. The majority of SCH patients are sporadic, but familial SCH has been described. An initial report of heterozygous mutations in the homeobox gene EMX2 could not be confirmed in 52 patients investigated in this study in agreement with two independent SCH patient cohorts published previously. SCH frequently occurs with additional cerebral malformations like hypoplasia or aplasia of the septum pellucidum or optic nerve, suggesting the involvement of genes important for the establishment of midline forebrain structures. We therefore considered holoprosencephaly (HPE)-associated genes as potential SCH candidates and report for the first time heterozygous mutations in SIX3 and SHH in a total of three unrelated patients and one fetus with SCH; one of them without obvious associated malformations of midline forebrain structures. Three of these mutations have previously been reported in independent patients with HPE. SIX3 acts directly upstream of SHH, and the SHH pathway is a key regulator of ventral forebrain patterning. Our data indicate that in a subset of patients SCH may develop as one aspect of a more complex malformation of the ventral forebrain, directly result from mutations in the SHH pathway and hence be considered as yet another feature of the broad phenotypic spectrum of holoprosencephaly.
C1 [Hehr, Ute; Hehr, Andreas] Univ Klinikum D3, Ctr Human Genet, D-93053 Regensburg, Germany.
[Hehr, Ute] Univ Regensburg, Dept Human Genet, Regensburg, Germany.
[Pineda-Alvarez, Daniel E.; Hu, Ping; Zhou, Nan; Roessler, Erich; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Uyanik, Goekhan] Univ Regensburg, Dept Neurol, Regensburg, Germany.
[Schell-Apacik, Chayim] Univ Munich, Inst Social Pediat & Adolescent Med, Munich, Germany.
[Daumer-Haas, Cornelia] Prenatal Med Munich, Munich, Germany.
[Steuernagel, Peter] Klinikum Oldenburg, Dept Clin Genet & Cytogenet, Oldenburg, Germany.
[Winkler, Juergen] Univ Hosp Erlangen, Div Mol Neurol, Erlangen, Germany.
RP Hehr, U (reprint author), Univ Klinikum D3, Ctr Human Genet, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany.
EM ute.hehr@humangenetik-regensburg.de
FU Intramural NIH HHS [ZIA HG000209-10]
NR 30
TC 14
Z9 16
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD MAR
PY 2010
VL 127
IS 5
BP 555
EP 561
DI 10.1007/s00439-010-0797-4
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 583HP
UT WOS:000276665000008
PM 20157829
ER
PT J
AU Traherne, JA
Martin, M
Ward, R
Ohashi, M
Pellett, F
Gladman, D
Middleton, D
Carrington, M
Trowsdale, J
AF Traherne, James A.
Martin, Maureen
Ward, Rosemary
Ohashi, Maki
Pellett, Fawnda
Gladman, Dafna
Middleton, Derek
Carrington, Mary
Trowsdale, John
TI Mechanisms of copy number variation and hybrid gene formation in the KIR
immune gene complex
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID IMMUNOGLOBULIN-LIKE RECEPTOR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HUMAN
GENOME; ALLELIC POLYMORPHISM; STRUCTURAL VARIATION; HAPLOTYPES CONTAIN;
CELL-RECEPTOR; HUMAN HISTORY; FINE-SCALE; NK CELLS
AB The fine-scale structure of the majority of copy number variation (CNV) regions remains unknown. The killer immunoglobulin receptor (KIR) gene complex exhibits significant CNV. The evolutionary plasticity of the KIRs and their broad biomedical relevance makes it important to understand how these immune receptors evolve. In this paper, we describe haplotype re-arrangement creating novel loci at the KIR complex. We completely sequenced, after fosmid cloning, two rare contracted haplotypes. Evidence of frequent hybrid KIR genes in samples from many populations suggested that re-arrangements may be frequent and selectively advantageous. We propose mechanisms for formation of novel hybrid KIR genes, facilitated by protrusive non-B DNA structures at transposon recombination sites. The heightened propensity to generate novel hybrid KIR receptors may provide a proactive evolutionary measure, to militate against pathogen evasion or subversion. We propose that CNV in KIR is an evolutionary strategy, which KIR typing for disease association must take into account.
C1 [Traherne, James A.; Ward, Rosemary; Ohashi, Maki; Trowsdale, John] Univ Cambridge, Dept Pathol, Div Immunol, Cambridge CB2 1QP, England.
[Martin, Maureen; Carrington, Mary] SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, NCI Frederick, Frederick, MD 21702 USA.
[Martin, Maureen; Carrington, Mary] MIT & Harvard, Ragon Inst MGH, Boston, MA 02129 USA.
[Middleton, Derek] Univ Liverpool, Liverpool Univ Hosp, Liverpool L69 3BX, Merseyside, England.
[Middleton, Derek] Univ Liverpool, Sch Infect & Host Def, Liverpool L69 3BX, Merseyside, England.
[Pellett, Fawnda; Gladman, Dafna] Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada.
RP Traherne, JA (reprint author), Univ Cambridge, Dept Pathol, Div Immunol, Tennis Court Rd, Cambridge CB2 1QP, England.
EM jat51@cam.ac.uk
FU MRC; National Cancer Institute; National Institutes of Health
[HHSN261200800001E]
FX This work was supported by the MRC (www. mrc. ac. uk). This project has
been funded in part with federal funds from the National Cancer
Institute, National Institutes of Health, under Contract No.
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products or
organizations imply endorsement by the US Government. This Research was
supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. The funders had
no role in study design, data collection and analysis, decision to
publish or preparation of the manuscript.
NR 53
TC 46
Z9 46
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 MAR 1
PY 2010
VL 19
IS 5
BP 737
EP 751
DI 10.1093/hmg/ddp538
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 553CD
UT WOS:000274341400001
PM 19959527
ER
PT J
AU Rhee, DB
Wang, YS
Mizesko, M
Zhou, F
Haneline, L
Liu, Y
AF Rhee, David B.
Wang, Yisong
Mizesko, Melissa
Zhou, Fang
Haneline, Laura
Liu, Yie
TI FANCC suppresses short telomere-initiated telomere sister chromatid
exchange
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ABERRANT HOMOLOGOUS RECOMBINATION; DNA-DAMAGE RESPONSE; STEM-CELLS;
REPOPULATING ABILITY; DEFICIENT MOUSE; ALT CELLS; ANEMIA; MICE; LENGTH;
REPAIR
AB Telomere shortening has been linked to rare human disorders that present with bone marrow failure including Fanconi anemia (FA). FANCC is one of the most commonly mutated FA genes in FA patients and the FANCC subtype tends to have a relatively early onset of bone marrow failure and hematologic malignancies. Here, we studied the role of Fancc in telomere length regulation in mice. Deletion of Fancc (Fancc(-/-)) did not affect telomerase activity, telomere length or telomeric end-capping in a mouse strain possessing intrinsically long telomeres. However, ablation of Fancc did exacerbate telomere attrition when murine bone marrow cells experienced high cell turnover after serial transplantation. When Fancc(-/-) mice were crossed into a telomerase reverse transcriptase heterozygous or null background (Tert(+/-) or Tert(-/-)) with short telomeres, Fancc deficiency led to an increase in the incidence of telomere sister chromatid exchange. In contrast, these phenotypes were not observed in Tert mutant mice with long telomeres. Our data indicate that Fancc deficiency accelerates telomere shortening during high turnover of hematopoietic cells and promotes telomere recombination initiated by short telomeres.
C1 [Mizesko, Melissa; Haneline, Laura] Indiana Univ, Sch Med, Dept Pediat, Herman B Wells Ctr, Indianapolis, IN 46202 USA.
[Mizesko, Melissa; Haneline, Laura] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Herman B Wells Ctr, Indianapolis, IN 46202 USA.
[Rhee, David B.; Zhou, Fang; Liu, Yie] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Wang, Yisong] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN USA.
RP Haneline, L (reprint author), Indiana Univ, Sch Med, Dept Pediat, Herman B Wells Ctr, R4-476,1044 W Walnut St, Indianapolis, IN 46202 USA.
EM lhanelin@iupui.edu; liuyie@mail.nih.gov
FU Intramural Research Program of the NIA; National Institutes of Health;
U. S. Public Health Services [R01 HL077175, P30 CA82709, T32 DK07519];
Riley Children's Foundation
FX This study was supported by the Intramural Research Program of the NIA,
National Institutes of Health (Y. L.), U. S. Public Health Services
Grants R01 HL077175 (L. H.), P30 CA82709 (L. H.), T32 DK07519 (M. M.)
and the Riley Children's Foundation (L. H.).
NR 54
TC 17
Z9 18
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAR 1
PY 2010
VL 19
IS 5
BP 879
EP 887
DI 10.1093/hmg/ddp556
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 553CD
UT WOS:000274341400012
PM 20022886
ER
PT J
AU Tom, SE
Cooper, R
Kuh, D
Guralnik, JM
Hardy, R
Power, C
AF Tom, Sarah E.
Cooper, Rachel
Kuh, Diana
Guralnik, Jack M.
Hardy, Rebecca
Power, Chris
TI Fetal environment and early age at natural menopause in a British birth
cohort study
SO HUMAN REPRODUCTION
LA English
DT Article
DE menopause; fetal environment; birth cohort; birthweight; fetal growth
ID CAUSE-SPECIFIC MORTALITY; SYSTOLIC BLOOD-PRESSURE; LIFE-STYLE FACTORS;
INTRAUTERINE GROWTH; GESTATIONAL-AGE; HEART-DISEASE; RISK-FACTORS;
SWEDISH MEN; WOMEN; WEIGHT
AB Early life development may influence the timing of natural menopause through association with size of the initial follicle pool or early follicular loss. This study examines the relationships of birthweight, gestational age and birthweight standardized by gestational age with early menopause in the 1958 British birth cohort study.
Study participants were over 2900 women with data on birthweight, gestational age (obtained at birth), menopausal status at age 44-45 years and potential confounding factors. Logistic regression was used to study relationships of birthweight, gestational age and birthweight standardized by gestational age with post-menopausal status by 44-45 years, with and without adjustments for confounding factors.
There was a U-shaped association between birthweight and menopausal status at 44-45 years: women at either extremes of birthweight (< 2.5 and >= 4.0 kg) had increased odds of post-menopausal status compared with those weighing 3.0-3.49 kg [odds ratio (OR) = 1.91, 95% confidence interval (CI) 1.08, 3.38; 1.81, 95% CI 1.11, 2.97, respectively]. Women with higher birthweight standardized by gestational age (which indicates faster fetal growth rate) also had increased odds of being post-menopausal by 44-45 years (OR for fastest quarter versus second fastest quarter = 1.80; 95% CI 1.16, 2.81). These associations persisted after adjustment for socioeconomic position at birth, adult smoking status and use of oral contraceptives.
These findings suggest that variations in fetal environment may be associated with the timing of menopause. Given that extremes of birthweight and higher birthweight standardized by gestational age were associated with earlier age at menopause, mechanisms related to these characteristics that also regulate ovarian function should be investigated further.
C1 [Tom, Sarah E.] Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Cooper, Rachel; Kuh, Diana; Hardy, Rebecca] MRC, Unit Lifelong Hlth & Ageing, London WC1B 5JU, England.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Power, Chris] UCL, Inst Child Hlth, MRC, Ctr Epidemiol Child Hlth, London WC1N 1EH, England.
RP Tom, SE (reprint author), Grp Hlth Res Inst, 1730 Minor Aveue,Suite 1600, Seattle, WA 98101 USA.
EM tom.s@ghc.org
OI Cooper, Rachel/0000-0003-3370-5720
FU National Institute on Aging, National Institutes of Health; Medical
Research Council [G0000934]
FX S. E. T. and J. G. were funded by the Intramural Research Program at the
National Institute on Aging, National Institutes of Health. R. C., D. K.
and R. H. were funded by the Medical Research Council. The biomedical
examination of the 1958 cohort was funded by the Medical Research
Council(grant G0000934 awarded under the Health of the Public
Initiative). The Great Ormond Street Hospital/UCL Institute of Child
Health receives a proportion of funding from the Department of Health's
NIHR Biomedical Research Centres funding scheme. The Centre for
Paediatric Epidemiology and Biostatistics also benefits from the funding
support from the Medical Research Council in its capacity as the MRC
Centre of Epidemiology for Child Health.
NR 51
TC 22
Z9 22
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD MAR
PY 2010
VL 25
IS 3
BP 791
EP 798
DI 10.1093/humrep/dep451
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 555EL
UT WOS:000274490700032
PM 20047935
ER
PT J
AU Esona, MD
Foytich, K
Wang, YH
Shin, G
Wei, G
Gentsch, JR
Glass, RI
Jiang, BM
AF Esona, Mathew D.
Foytich, Kimberly
Wang, Yuhuan
Shin, Gary
Wei, Gang
Gentsch, Jon R.
Glass, Roger I.
Jiang, Baoming
TI Molecular characterization of human rotavirus vaccine strain CDC-9
during sequential passages in Vero cells
SO HUMAN VACCINES
LA English
DT Article
DE rotavirus; rotavirus vaccine; CDC-9
ID NONSTRUCTURAL GLYCOPROTEIN NSP4; POLYMERASE CHAIN-REACTION; GROUP-A;
PORCINE ROTAVIRUS; ATTENUATED VACCINE; NUCLEIC-ACID; VIRUS; GENE;
IDENTIFICATION; DIARRHEA
AB We have developed several candidate human rotavirus vaccine strains with common serotypes via adaptation in Vero cells, adhering to the Good Laboratory Practice (GLP) guidelines. We sequenced the entire genome of a G1P[8] strain CDC-9 in original stool and passaged materials from Vero cells and examined its genetic relatedness to the prototype human rotavirus KU and other strains. With the exception of VP3 gene which was closely related to that of strain DS-1, the culture-adapted CDC-9 strain shared moderate to high nt (range 83.4%-95.1%) and deduced aa (range 81.3%-97.9%) sequence identities with the KU and other G1P[8] strains. Alignments of the deduced aa sequences of 11 gene segments of the wild-type and culture-adapted CDC-9 showed complete sequence identity in genes encoding NSP2, NSP3, NSP4, VP1, VP2, VP3 and VP7, a single aa change in genes coding for NSP1, NSP5 and VP6 and several scattered aa changes in the VP4 gene during the passage in Vero cells. Two of the VP4 aa substitutions (385 and 388) are within sites associated with neutralization resistant mutants selected by cross-reactive monoclonal antibodies. Although some sequence changes were evident, we do not know if these changes contribute to the possible attenuation of this strain. Further testing of this vaccine strain in clinical trials is justified.
C1 [Esona, Mathew D.; Foytich, Kimberly; Wang, Yuhuan; Shin, Gary; Wei, Gang; Gentsch, Jon R.; Glass, Roger I.; Jiang, Baoming] Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA 30333 USA.
[Glass, Roger I.] NIH, Fogerty Int Ctr, Bethesda, MD 20892 USA.
RP Jiang, BM (reprint author), Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA 30333 USA.
EM bxj4@cdc.gov
FU Cooperative Research and Development Agreement with Sanofi Pasteur,
Lyon, France
FX We thank Charles Humphrey for performing electron microscope analysis.
This study was supported in part by a Cooperative Research and
Development Agreement with Sanofi Pasteur, Lyon, France.
NR 51
TC 8
Z9 9
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8600
J9 HUM VACCINES
JI Hum. Vaccines
PD MAR
PY 2010
VL 6
IS 3
BP 247
EP 253
PG 7
WC Biotechnology & Applied Microbiology; Immunology
SC Biotechnology & Applied Microbiology; Immunology
GA 589VZ
UT WOS:000277183600011
ER
PT J
AU Wang, KL
Cheng, HM
Sung, SH
Chuang, SY
Li, CH
Spurgeon, HA
Ting, CT
Najjar, SS
Lakatta, EG
Yin, FCP
Chou, P
Chen, CH
AF Wang, Kang-Ling
Cheng, Hao-Min
Sung, Shih-Hsien
Chuang, Shao-Yuan
Li, Cheng-Hung
Spurgeon, Harold A.
Ting, Chih-Tai
Najjar, Samer S.
Lakatta, Edward G.
Yin, Frank C. P.
Chou, Pesus
Chen, Chen-Huan
TI Wave Reflection and Arterial Stiffness in the Prediction of 15-Year
All-Cause and Cardiovascular Mortalities A Community-Based Study
SO HYPERTENSION
LA English
DT Article
DE wave reflection; pulse wave velocity; arterial stiffness; vascular
aging; mortality; epidemiology
ID LEFT-VENTRICULAR MASS; BLOOD-PRESSURE; AUGMENTATION INDEX; AORTIC
STIFFNESS; PULSE PRESSURE; HEART-DISEASE; UPPER-LIMB; VELOCITY; EVENTS;
WOMEN
AB The value of increased arterial wave reflection, usually assessed by the transit time-dependent augmentation index and augmented pressure (Pa), in the prediction of cardiovascular events may have been underestimated. We investigated whether the transit time-independent measures of reflected wave magnitude predict cardiovascular outcomes independent of arterial stiffness indexed by carotid-femoral pulse wave velocity. A total of 1272 participants (47% women; mean age: 52 +/- 13 years; range: 30 to 79 years) from a community-based survey were studied. Carotid pressure waveforms derived by tonometry were decomposed into their forward wave amplitudes, backward wave amplitudes (Pb), and a reflection index (=[Pb/(forward wave amplitude + Pb)]), in addition to augmentation index, Pa, and reflected wave transit time. During a median follow-up of 15 years, 225 deaths occurred (17.6%), including 64 cardiovascular origins (5%). In univariate Cox proportional hazard regression analysis, pulse wave velocity, Pa, and Pb predicted all-cause and cardiovascular mortality in both men and women, whereas augmentation index, reflected wave transit time, and reflection index were predictive only in men. In multivariate analysis accounting for age, height, and heart rate, Pb predicted cardiovascular mortality in both men and women, whereas Pa was predictive only in men. Per 1-SD increment (6 mm Hg), Pb predicted 15-year cardiovascular mortality independent of brachial but not central pressure, pulse wave velocity, augmentation index, Pa, and conventional cardiovascular risk factors with hazard ratios of approximate to 1.60 (all P<0.05). In conclusion, Pb, a transit time-independent measure of reflected wave magnitude, predicted long-term cardiovascular mortality in men and women independent of arterial stiffness. (Hypertension. 2010; 55: 799-805.)
C1 [Chen, Chen-Huan] Taipei Vet Gen Hosp, Div Cardiol, Dept Med Res & Educ, Taipei, Taiwan.
[Wang, Kang-Ling; Sung, Shih-Hsien; Li, Cheng-Hung] Taipei Vet Gen Hosp, Dept Med, Taipei, Taiwan.
[Chuang, Shao-Yuan] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
[Ting, Chih-Tai] Taichung Vet Gen Hosp, Ctr Cardiovasc, Taichung, Taiwan.
[Spurgeon, Harold A.; Najjar, Samer S.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Yin, Frank C. P.] Washington Univ, Dept Biomed Engn, St Louis, MO USA.
[Chen, Chen-Huan] Natl Yang Ming Univ, Cardiovasc Res Ctr, Taipei 112, Taiwan.
[Chou, Pesus; Chen, Chen-Huan] Natl Yang Ming Univ, Dept Publ Hlth, Taipei 112, Taiwan.
RP Chen, CH (reprint author), Taipei Vet Gen Hosp, Div Cardiol, Dept Med Res & Educ, 201 Sec 2,Shih Pai Rd, Taipei, Taiwan.
EM chench@vghtpe.gov.tw
RI Chuang, Shao-Yuan/B-3478-2011
FU National Science Council (NSC) [96-2314-B-010-035-MY3]; Taipei Veterans
General Hospital [V98C1-028]; Research Foundation of Cardiovascular
Medicine (Taipei, Taiwan, Republic of China) [NO1-AG-1-2118]; National
Institute on Aging, National Institutes of Health
FX This work was supported in part by a grant from the National Science
Council (NSC 96-2314-B-010-035-MY3), an intramural grant from the Taipei
Veterans General Hospital (grant V98C1-028), Grants-in-Aid from the
Research Foundation of Cardiovascular Medicine (Taipei, Taiwan, Republic
of China), Research and Development contract NO1-AG-1-2118, and the
Intramural Research Program of the National Institute on Aging, National
Institutes of Health.
NR 36
TC 170
Z9 175
U1 4
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD MAR 1
PY 2010
VL 55
IS 3
BP 799
EP 805
DI 10.1161/HYPERTENSIONAHA.109.139964
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 557GV
UT WOS:000274658500032
PM 20065155
ER
PT J
AU Grainger, JR
Hall, JA
Bouladoux, N
Oldenhove, G
Belkaid, Y
AF Grainger, John R.
Hall, Jason A.
Bouladoux, Nicolas
Oldenhove, Guillaume
Belkaid, Yasmine
TI Microbe-dendritic cell dialog controls regulatory T-cell fate
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE dendritic cell; regulatory T cell; Foxp3+; microbe; commensal
ID TOLL-LIKE RECEPTORS; TRANSCRIPTION FACTOR FOXP3; EXCRETORY-SECRETORY
PRODUCTS; INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE;
STIMULATORY CPG MOTIFS; TRANS-RETINOIC ACID; GROWTH-FACTOR-BETA;
TGF-BETA; CROHNS-DISEASE
AB Each microenvironment is controlled by a specific set of regulatory elements that have to be finely and constantly tuned to maintain local homeostasis. These environments could be site specific, such as the gut environment, or induced by chronic exposure to microbes. Various populations of dendritic cells are central to the orchestration of this control. In this review, we discuss some new findings associating dendritic cells from defined compartments with the induction and control of regulatory T cells in the context of exposure to both commensal and pathogenic microbes.
C1 [Grainger, John R.; Hall, Jason A.; Bouladoux, Nicolas; Oldenhove, Guillaume; Belkaid, Yasmine] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, Bethesda, MD 20894 USA.
RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, Parasit Dis Lab, 4 Ctr Dr,B1-28, Bethesda, MD 20894 USA.
EM ybelkaid@niaid.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 Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health. We apologize to those authors whose work we were unable to cite
because of space limitations.
NR 135
TC 27
Z9 28
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD MAR
PY 2010
VL 234
BP 305
EP 316
PG 12
WC Immunology
SC Immunology
GA 559HC
UT WOS:000274813200020
PM 20193027
ER
PT J
AU Padhan, K
Varma, R
AF Padhan, Kartika
Varma, Rajat
TI Immunological synapse: a multi-protein signalling cellular apparatus for
controlling gene expression
SO IMMUNOLOGY
LA English
DT Review
DE immune synapses; signalling; signal transduction; systems biology;
T-cell receptor; transcription factors (gene regulation)
ID NF-KAPPA-B; CD4(+) T-CELLS; ALLERGIC AIRWAY INFLAMMATION;
GLYCOGEN-SYNTHASE KINASE-3; LACKING C-FOS; TRANSCRIPTION FACTOR;
NUCLEAR-LOCALIZATION; IMMUNE-RESPONSES; MICE LACKING; IN-VIVO
AB P>The interaction of T cells with antigen-presenting cells is the hallmark of adaptive immunity. In vitro studies have described the formation of an immunological synapse between these cells, and intra-vital imaging has described in great detail the dynamics of these interactions. The immunological synapse has become a paradigm to study signals exchanged between the two cells. A wealth of information has been amassed regarding the localization of signalling molecules, their kinetics and the transcription factors they activate. We continue to discover mechanisms that cause receptors and signalling molecules to compartmentalize in the cell; however, the emerging challenge lies in understanding how the immunological synapse contributes to differentiation. Here, we review some of the transcription factors activated downstream of T-cell receptor signalling and discuss mechanisms by which antigen dose and affinity may influence differentiation. Antigen affinity might change the kind of transcription factors that are activated whereas antigen dose is likely to influence the temporal dynamics of the transcription factors. The immunological synapse is therefore likely to influence differentiation by modulating the trafficking of transcription factors and by promoting asymmetric cell division, an emerging concept.
C1 [Padhan, Kartika; Varma, Rajat] NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Varma, R (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA.
EM varmarajat@mail.nih.gov
RI Varma, Rajat/I-1209-2012
OI Varma, Rajat/0000-0001-5131-0402
NR 105
TC 13
Z9 13
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD MAR
PY 2010
VL 129
IS 3
BP 322
EP 328
DI 10.1111/j.1365-2567.2009.03241.x
PG 7
WC Immunology
SC Immunology
GA 551WF
UT WOS:000274242500002
PM 20409153
ER
PT J
AU Paul, WE
AF Paul, William E.
TI What determines Th2 differentiation, in vitro and in vivo?
SO IMMUNOLOGY AND CELL BIOLOGY
LA English
DT Review
DE IL-4; IL-13; GATA3; Th1/Th2; basophils; STAT5
ID T-CELL DIFFERENTIATION; IMMUNE-RESPONSES; INTERFERON-GAMMA; DENDRITIC
CELLS; IL-4; BASOPHILS; CYTOKINE; ANTIGEN; GATA-3; TSLP
AB We have known since 1991 how to induce naive CD4 T cells to differentiate in vitro into Th2 cells and, over the ensuing years, a comprehensive picture of the molecules involved in this important process has emerged. GATA3 and STAT5 are both essential for in vitro differentiation, stimulating naive cells through a process involving induction, which is T-cell receptor (TCR) dependent but interleukin (IL)-4 independent, and commitment, which is IL-4 dependent. Th2 differentiation in vivo appears more complex. GATA3 and probably STAT5 are required in vivo but, at least for certain helminth infections, the IL-4/IL-4Ra/STAT6 pathway is dispensable. The role of thymic stromal lymphopoietin and of low TCR signal strength and the participation of basophils in establishing a Th2-baising in vivo environment have achieved considerable attention. Here I discuss the major players in Th2 differentiation particularly as they may exert their effects in vivo. Immunology and Cell Biology (2010) 88, 236-239; doi: 10.1038/icb.2010.2; published online 16 February 2010
C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room IIN311, Bethesda, MD 20892 USA.
EM wpaul@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, USA
FX The work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, USA.
NR 38
TC 41
Z9 43
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0818-9641
J9 IMMUNOL CELL BIOL
JI Immunol. Cell Biol.
PD MAR-APR
PY 2010
VL 88
IS 3
BP 236
EP 239
DI 10.1038/icb.2010.2
PG 4
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 575OM
UT WOS:000276076800003
PM 20157328
ER
PT J
AU Forbes, E
van Panhuys, N
Min, B
Le Gros, G
AF Forbes, Elizabeth
van Panhuys, Nicholas
Min, Booki
Le Gros, Graham
TI Differential requirements for IL-4/STAT6 signalling in CD4 T-cell fate
determination and Th2-immune effector responses
SO IMMUNOLOGY AND CELL BIOLOGY
LA English
DT Review
DE Th2; IL-4; STAT6; differentiation; effector response
ID ACTIVATED PROTEIN-KINASE; ANTIGEN-PRESENTING CELLS; TH2
IMMUNE-RESPONSES; VIVO IL-4 RESPONSES; IN-VIVO; DENDRITIC CELLS; CUTTING
EDGE; NIPPOSTRONGYLUS-BRASILIENSIS; AIRWAYS HYPERREACTIVITY;
EXPERIMENTAL ASTHMA
AB Improved analytical tools have revealed that the development and expression of a Th2 immune response can be broken down into distinct stages with respect to the cytokine microenvironment that is required. Although IL-4 and its STAT6-signalling pathway are critical for the expression of Th2 effector immune responses in peripheral tissues such as the skin, lung and gut, IL-4 and STAT6 signalling are not required for the initial generation of IL-4-producing Th2 cells in the lymph node. This finding reveals that we have yet to identify the key cytokine or microenvironment that stimulates the development of this most intriguing CD4(+) T-helper subset and emphasises the tissue specificity and timing of IL-4/STAT6-dependent Th2 effector responses. Immunology and Cell Biology (2010) 88, 240-243; doi: 10.1038/icb.2009.101; published online 15 December 2009
C1 [Forbes, Elizabeth; Le Gros, Graham] Malaghan Inst Med Res, Wellington 6242, New Zealand.
[van Panhuys, Nicholas] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Min, Booki] Lerner Res Inst, Dept Immunol, Cleveland, OH USA.
RP Le Gros, G (reprint author), Malaghan Inst Med Res, POB 7060, Wellington 6242, New Zealand.
EM glegros@malaghan.org.nz
RI Le Gros, Graham/C-6725-2011; Forbes-Blom, Elizabeth/I-3648-2013; van
Panhuys, Nicholas/E-1812-2011;
OI van Panhuys, Nicholas/0000-0003-2199-852X
FU Health Research Council of New Zealand; Marjorie Barclay Trust; Marsden
Fund; AMI Insurance Ltd
FX This research was supported by Program Grant funding from the Health
Research Council of New Zealand, the Marjorie Barclay Trust, the Marsden
Fund and AMI Insurance Ltd.
NR 73
TC 20
Z9 22
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0818-9641
J9 IMMUNOL CELL BIOL
JI Immunol. Cell Biol.
PD MAR-APR
PY 2010
VL 88
IS 3
BP 240
EP 243
DI 10.1038/icb.2009.101
PG 4
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 575OM
UT WOS:000276076800004
PM 20010912
ER
PT J
AU Zhu, JF
AF Zhu, Jinfang
TI Transcriptional regulation of Th2 cell differentiation
SO IMMUNOLOGY AND CELL BIOLOGY
LA English
DT Review
DE T-cell differentiation; transcription factors; cytokines
ID LOCUS-CONTROL REGION; CD4(+) T-CELLS; NF-KAPPA-B; ALLERGIC AIRWAY
INFLAMMATION; THYMIC STROMAL LYMPHOPOIETIN; ANTIGEN-PRESENTING CELLS;
HELPER TYPE-1 CELLS; IN-VIVO; IL-4 PRODUCTION; CYTOKINE PRODUCTION
AB CD4 T helper 2 (Th2) cells have critical functions in immune responses against extracellular parasites and are involved in asthma and other allergic diseases. The differentiation of naive CD4 T cells into Th2 cells is initiated from T-cell receptor and cytokine-mediated signaling followed by upregulation of GATA3 and activation of signal transducer and activator of transcription 5 (STAT5), two indispensable events for this differentiation process. In this review, regulation of GATA3 expression and STAT5 activation and functions of these two transcription factors in inducing the expression of Th2 cytokines, cytokine receptors as well as epigenetic modification at Th2 cytokine locus are summarized. Furthermore, I present positive and negative regulatory networks important for Th2 cell commitment, selective growth of committed Th2 cells and suppression of alternative lineage fates. Finally, the difference between in vitro and in vivo Th2 differentiation is discussed. Immunology and Cell Biology (2010) 88, 244-249; doi: 10.1038/icb.2009.114; published online 12 January 2010
C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 11N323, Bethesda, MD 20892 USA.
EM jfzhu@niaid.nih.gov
RI Zhu, Jinfang/B-7574-2012
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, USA
FX The work is supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, USA.
NR 118
TC 21
Z9 24
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0818-9641
J9 IMMUNOL CELL BIOL
JI Immunol. Cell Biol.
PD MAR-APR
PY 2010
VL 88
IS 3
BP 244
EP 249
DI 10.1038/icb.2009.114
PG 6
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 575OM
UT WOS:000276076800005
PM 20065998
ER
PT J
AU Cunha, N
Matsunaga, G
Oliveira, P
Lima, T
Murad, A
Araujo, AC
Brigido, M
Waters, M
Fontes, A
Silva, L
Souza, G
Bloch, C
O'Keefe, B
Saucedo, C
Lewis, R
Old, L
Caballero, O
Simpson, A
Ritter, G
Vianna, G
Rech, E
AF Cunha, Nicolau
Matsunaga, Gabriela
Oliveira, Paula
Lima, Thaina
Murad, Andre
Araujo, Ana Claudia
Brigido, Marcelo
Waters, Michael
Fontes, Aparecida
Silva, Luciano
Souza, Gustavo
Bloch, Carlos
O'Keefe, Barry
Saucedo, Carrie
Lewis, Randolph
Old, Lloyd
Caballero, Otavia
Simpson, Andrew
Ritter, Gerd
Vianna, Giovanni
Rech, Elibio
TI Recombinant Proteins in Soybean Seeds Under Control of Legumes Storage
Proteins Regulatory Sequences
SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
LA English
DT Meeting Abstract
C1 [Cunha, Nicolau; Matsunaga, Gabriela; Oliveira, Paula; Lima, Thaina; Murad, Andre; Araujo, Ana Claudia; Silva, Luciano; Bloch, Carlos; Vianna, Giovanni; Rech, Elibio] Embrapa Genet Resources & Biotechnol, Parque Estacao Biol, BR-70770917 Brasilia, DF, Brazil.
[Cunha, Nicolau; Matsunaga, Gabriela; Oliveira, Paula; Lima, Thaina; Brigido, Marcelo] Univ Brasilia, Dept Cellular Biol, BR-70910900 Brasilia, DF, Brazil.
[Waters, Michael] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
[Waters, Michael] Univ Queensland, Sch Biomed Sci, St Lucia, Qld 4072, Australia.
[Fontes, Aparecida] Ctr Cellular Therapy FMRP USP, Blood Ctr Ribeirao Preto, BR-14051140 Ribeirao Preto, SP, Brazil.
[Souza, Gustavo] Waters Corp, Mass Spectrometry Applicat Res & Dev Lab, BR-06455020 Sao Paulo, Brazil.
[O'Keefe, Barry; Saucedo, Carrie] NCI, Mol Targets Dev Program, Frederick, MD 21702 USA.
[Lewis, Randolph] Univ Wyoming, Dept Mol Biol, Dept 3944, Laramie, WY 82071 USA.
[Old, Lloyd; Caballero, Otavia; Simpson, Andrew; Ritter, Gerd] Ludwig Inst Canc Res Ltd, Mem Sloan Kettering Canc Ctr, New York Branch Human Canc Immunol, New York, NY 10065 USA.
RI Brigido, Marcelo/A-1972-2015
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 SPR
PY 2010
VL 46
SU S
BP S63
EP S64
PG 2
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 695JX
UT WOS:000285367500140
ER
PT J
AU Felek, S
Muszynski, A
Carlson, RW
Tsang, TM
Hinnebusch, BJ
Krukonis, ES
AF Felek, Suleyman
Muszynski, Artur
Carlson, Russell W.
Tsang, Tiffany M.
Hinnebusch, B. Joseph
Krukonis, Eric S.
TI Phosphoglucomutase of Yersinia pestis Is Required for Autoaggregation
and Polymyxin B Resistance
SO INFECTION AND IMMUNITY
LA English
DT Article
ID GENE-ENCODING PHOSPHOMANNOMUTASE; ESCHERICHIA-COLI K-12;
FUNCTIONAL-ANALYSIS; LIPOPOLYSACCHARIDE BIOSYNTHESIS; TRANSCRIPTIONAL
REGULATION; ALPHA-PHOSPHOGLUCOMUTASE; CYCLIC BETA-1,2-GLUCAN;
SALMONELLA-TYPHIMURIUM; PATHOGENIC YERSINIAE; BIOFILM FORMATION
AB Yersinia pestis, the causative agent of plague, autoaggregates within a few minutes of cessation of shaking when grown at 28 degrees C. To identify the autoaggregation factor of Y. pestis, we performed mariner-based transposon mutagenesis. Autoaggregation-defective mutants from three different pools were identified, each with a transposon insertion at a different position within the gene encoding phosphoglucomutase (pgmA; y1258). Targeted deletion of pgmA in Y. pestis KIM5 also resulted in loss of autoaggregation. Given the previously defined role for phosphoglucomutase in antimicrobial peptide resistance in other organisms, we tested the KIM5 Delta pgmA mutant for antimicrobial peptide sensitivity. The Delta pgmA mutant displayed > 1,000-fold increased sensitivity to polymyxin B compared to the parental Y. pestis strain, KIM5. This sensitivity is not due to changes in lipopolysaccharide (LPS) since the LPSs from both Y. pestis KIM5 and the Delta pgmA mutant are identical based on a comparison of their structures by mass spectrometry ( MS), tandem MS, and nuclear magnetic resonance analyses. Furthermore, the ability of polymyxin B to neutralize LPS toxicity was identical for LPS purified from both KIM5 and the Delta pgmA mutant. Our results indicate that increased polymyxin B sensitivity of the Delta pgmA mutant is due to changes in surface structures other than LPS. Experiments with mice via the intravenous and intranasal routes did not demonstrate any virulence defect for the Delta pgmA mutant, nor was flea colonization or blockage affected. Our findings suggest that the activity of PgmA results in modification and/or elaboration of a surface component of Y. pestis responsible for autoaggregation and polymyxin B resistance.
C1 [Felek, Suleyman; Krukonis, Eric S.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
[Muszynski, Artur; Carlson, Russell W.] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA.
[Tsang, Tiffany M.; Krukonis, Eric S.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
[Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Krukonis, ES (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, 1011 N Univ,Dent Bldg,RM 3204, Ann Arbor, MI 48109 USA.
EM ekrukoni@umich.edu
OI Muszynski, Artur/0000-0003-3497-9977
FU Biomedical Research Council at the University of Michigan School of
Medicine; University of Michigan's Office of the Vice President for
Research; Rackham School of Graduate Studies; Department of Energy
[FG02-93ER20097]
FX We thank Stephen Trent for helpful discussions concerning this work,
Clayton Jarrett for assistance with the flea experiments, and J. Chris
Fenno for critical reading of the manuscript.; This study was supported
by a grant from the Biomedical Research Council at the University of
Michigan School of Medicine and by grants from the University of
Michigan's Office of the Vice President for Research and the Rackham
School of Graduate Studies. This work was also partially supported by
Department of Energy Grant FG02-93ER20097 to the Complex Carbohydrate
Research Center.
NR 79
TC 14
Z9 16
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD MAR
PY 2010
VL 78
IS 3
BP 1163
EP 1175
DI 10.1128/IAI.00997-09
PG 13
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 557FE
UT WOS:000274654200027
PM 20028810
ER
PT J
AU Sutten, EL
Norimine, J
Beare, PA
Heinzen, RA
Lopez, JE
Morse, K
Brayton, KA
Gillespie, JJ
Brown, WC
AF Sutten, Eric L.
Norimine, Junzo
Beare, Paul A.
Heinzen, Robert A.
Lopez, Job E.
Morse, Kaitlyn
Brayton, Kelly A.
Gillespie, Joseph J.
Brown, Wendy C.
TI Anaplasma marginale Type IV Secretion System Proteins VirB2, VirB7,
VirB11, and VirD4 Are Immunogenic Components of a Protective Bacterial
Membrane Vaccine
SO INFECTION AND IMMUNITY
LA English
DT Article
ID T-CELL RESPONSES; AGROBACTERIUM-TUMEFACIENS VIRB7; COMPLEX TRANSPORT
APPARATUS; LYMPHOCYTE RESPONSES; PERIPLASMIC SURFACE; GENE CONVERSION;
OUTER MEMBRANES; MOLECULAR-BASIS; CHALLENGE; PHAGOCYTOPHILUM
AB Anaplasma and related Ehrlichia spp. are important tick-borne, Gram-negative bacterial pathogens of livestock and humans that cause acute infection and disease and can persist. Immunization of cattle with an Anaplasma marginale fraction enriched in outer membranes (OM) can provide complete protection against disease and persistent infection. Serological responses of OM vaccinees to the OM proteome previously identified over 20 antigenic proteins, including three type IV secretion system (T4SS) proteins, VirB9-1, VirB9-2, and VirB10. Subsequent studies showed that these three proteins also stimulated CD4(+) T-cell responses in OM vaccinees. The T4SS, composed of a complex of proteins spanning the inner and outer membranes of certain bacteria, is an important virulence factor but is relatively unexplored as a vaccine target. The goal of this study was to determine if additional T4SS proteins are immunogenic for animals immunized with the protective OM fraction of A. marginale. T4SS proteins expressed by in vitro transcription and translation were screened for stimulating proliferation of T cells from OM vaccinees, and immunogenic proteins were expressed as recombinant proteins in Escherichia coli and their immunogenicity was verified. VirB2, a putative VirB7, VirB11, and VirD4 were immunogenic for OM vaccinees expressing several common major histocompatibility complex (MHC) class II haplotypes. VirB2 is encoded by multiple genes that share a conserved central region, and epitope mapping revealed T-cell epitopes in this region. The discovery of novel immunogenic T4SS proteins recognized by outbred individuals with common MHC haplotypes further justifies evaluating the T4SS as a potential vaccine candidate for pathogenic bacteria.
C1 [Sutten, Eric L.; Norimine, Junzo; Lopez, Job E.; Morse, Kaitlyn; Brayton, Kelly A.; Brown, Wendy C.] Washington State Univ, Dept Vet Microbiol & Pathol, Pullman, WA 99164 USA.
[Beare, Paul A.; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA.
[Lopez, Job E.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Gillespie, Joseph J.] Virginia Tech, Bioinformat Facil, Virginia Bioinformat Inst 0477, Blacksburg, VA 24061 USA.
[Gillespie, Joseph J.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
RP Brown, WC (reprint author), Washington State Univ, Dept Vet Microbiol & Pathol, Pullman, WA 99164 USA.
EM wbrown@vetmed.wsu.edu
OI Morse, Kaitlyn/0000-0002-3077-2832; Gillespie,
Joseph/0000-0002-5447-7264
FU National Institutes of Health (NIH) National Institutes of Allergy and
Infectious Diseases (NIAID) [AI053692]; NIAID [R01AI017828, R01AI59118,
HHSN266200400035C]
FX We thank Shelley Whidbee, Emma Karel, and Ralph Horn for excellent
technical assistance and Heather Fallquist for providing A. marginale
RNA.; This research was supported by National Institutes of Health (NIH)
National Institutes of Allergy and Infectious Diseases (NIAID) grant
AI053692 (W. C. B.) and the Intramural Research Program at NIH, NIAID
(R. A. H., P. A. B., and J. E. L.). J. J. G. acknowledges support from
NIAID awards R01AI017828 and R01AI59118 to Abdu Azad (University of
Maryland) and contract HHSN266200400035C to Bruno Sobral (Virginia
Bioinformatics Institute at Virginia Tech).
NR 75
TC 26
Z9 27
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD MAR
PY 2010
VL 78
IS 3
BP 1314
EP 1325
DI 10.1128/IAI.01207-09
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 557FE
UT WOS:000274654200043
PM 20065028
ER
PT J
AU Henderson, DK
Dembry, L
Fishman, NO
Grady, C
Lundstrom, T
Palmore, TN
Sepkowitz, KA
Weber, DJ
AF Henderson, David K.
Dembry, Louise
Fishman, Neil O.
Grady, Christine
Lundstrom, Tammy
Palmore, Tara N.
Sepkowitz, Kent A.
Weber, David J.
CA Soc Healthcare Epidemiology Amer
TI SHEA Guideline for Management of Healthcare Workers Who Are Infected
with Hepatitis B Virus, Hepatitis C Virus, and/or Human Immunodeficiency
Virus
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Review
ID TO-PATIENT TRANSMISSION; HBV DNA LEVELS; HIV TRANSMISSION; PERCUTANEOUS
INJURIES; SURGICAL-PROCEDURES; ORTHOPEDIC SURGEON; GLOVE PERFORATION;
E-ANTIGEN; OCCUPATIONAL EXPOSURES; PUNCTURE RESISTANCE
AB This guideline provides the updated recommendations of the Society for Healthcare Epidemiology of America (SHEA) regarding the management of healthcare providers who are infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and/or the human immunodeficiency virus (HIV). For the reasons cited in the guideline, SHEA continues to recommend that, although some aspects of the approach to and administrative management of each of these infectious syndromes in healthcare providers are similar, separate management strategies for healthcare workers who are infected with these unrelated viruses remain appropriate. As we did in both prior iterations of this document, SHEA emphasizes the use of appropriate infection control procedures to minimize exposure of patients or providers to blood, emphasizes that transfers of blood from patients to providers and from providers to patients should be avoided, and recommends that infected healthcare providers should not be totally prohibited from participating in patient-care activities solely on the basis of a bloodborne pathogen infection. The types of procedures assessed by the panel as associated with an increased risk for provider-to-patient transmission of these pathogens are discussed in detail. For each pathogen, recommendations are graduated according to the relative viral load level of the infected provider (Tables 1 and 2). However, SHEA emphasizes that, because of the complexity of these cases, each such case will be slightly different from the next, and each should be independently considered in context.
C1 [Henderson, David K.; Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Dembry, Louise] Yale New Haven Med Ctr, Dept Qual Improvement Support Serv, New Haven, CT 06504 USA.
[Fishman, Neil O.] Univ Penn, Sch Med, Div Infect Dis, Philadelphia, PA 19104 USA.
[Lundstrom, Tammy] Providence Hosp & Med Ctr, Infect Dis Sect, Detroit, MI USA.
[Palmore, Tara N.] NIH, Infect Dis Fellowship Training Program, Ctr Clin, Bethesda, MD 20892 USA.
[Sepkowitz, Kent A.] Mem Sloan Kettering Canc Ctr, Infect Dis Serv, New York, NY 10021 USA.
[Weber, David J.] Univ N Carolina, Div Infect Dis, Chapel Hill, NC USA.
RP Henderson, DK (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Rm 6-1480,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dkh@nih.gov
NR 157
TC 48
Z9 51
U1 0
U2 5
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
EI 1559-6834
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD MAR
PY 2010
VL 31
IS 3
BP 203
EP 232
DI 10.1086/650298
PG 30
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 549UJ
UT WOS:000274079500001
PM 20088696
ER
PT J
AU Kato, H
Jochim, RC
Gomez, EA
Sakoda, R
Iwata, H
Valenzuela, JG
Hashiguchi, Y
AF Kato, Hirotomo
Jochim, Ryan C.
Gomez, Eduardo A.
Sakoda, Ryo
Iwata, Hiroyuki
Valenzuela, Jesus G.
Hashiguchi, Yoshihisa
TI A repertoire of the dominant transcripts from the salivary glands of the
blood-sucking bug, Triatoma dimidiata, a vector of Chagas disease
SO INFECTION GENETICS AND EVOLUTION
LA English
DT Article
DE Triatoma dimidiata; Saliva; Transcriptome; Bioinformatics; cDNA library
ID ADULT FEMALE MOSQUITO; PLATELET-AGGREGATION INHIBITOR; ANTIGENIC
CROSS-REACTIVITY; BLOOD-FEEDING ARTHROPODS; RHODNIUS-PROLIXUS;
RECOMBINANT EXPRESSION; SEQUENCE ALIGNMENT; ANOPHELES-GAMBIAE; BINDING
PROTEIN; IDENTIFICATION
AB Triatoma (T.) dimidiata is a hematophagous Hemiptera and a main vector of Chagas disease. The saliva of this and other blood-sucking insects contains potent pharmacologically active components that assist them in counteracting the host hemostatic and inflammatory systems during blood feeding. To describe the repertoire of potential bioactive salivary molecules from this insect, a number of randomly selected transcripts from the salivary gland cDNA library of T. dimidiata were sequenced and analyzed. This analysis showed that 77.5% of the isolated transcripts coded for putative secreted proteins, and 89.9% of these coded for variants of the lipocalin family proteins. The most abundant transcript was a homologue of procalin, the major allergen of T. protracta saliva, and contributed more than 50% of the transcripts coding for putative secreted proteins, suggesting that it may play an important role in the blood-feeding process. Other salivary transcripts encoding lipocalin family proteins had homology to triabin (a thrombin inhibitor), triafestin (an inhibitor of kallikrein-kinin system), pallidipin (an inhibitor of collagen-induced platelet aggregation) and others with unknown function. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Kato, Hirotomo; Sakoda, Ryo; Iwata, Hiroyuki] Yamaguchi Univ, Fac Agr, Dept Vet Hyg, Yamaguchi 7538515, Japan.
[Jochim, Ryan C.; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD USA.
[Hashiguchi, Yoshihisa] Kochi Univ, Dept Parasitol, Kochi Med Sch, Kochi 780, Japan.
RP Kato, H (reprint author), Yamaguchi Univ, Fac Agr, Dept Vet Hyg, 1677-1 Yoshida, Yamaguchi 7538515, Japan.
EM katoh@yamaguchi-u.ac.jp
RI Kato, Hirotomo/A-4820-2012; Jochim, Ryan/C-6756-2013
OI Kato, Hirotomo/0000-0001-5429-9536;
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) of
Japan [18256004, 18780230]; Inamori Foundation; Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX We are grateful to Dr. Jose M.C. Ribeiro (Vector Biology Section,
Laboratory of Malaria and Vector Research, NIAID, NIH, USA) for the
development and training of all custom bioinformatics programs used in
this research. We also thank Dr. Cesar Suarez and Mrs. Erika Sanchez
(Laboratory of Medical Entomology, National Institute of Health and
Tropical Medicine, Ecuador) for providing T. dimidiata. This study was
supported by the Ministry of Education, Culture, Sports, Science and
Technology (MEXT) of Japan (Grant Nos. 18256004 and 18780230) and by the
grant from the Inamori Foundation. Because R.C.J. and J.G.V. are
government employees and part of this is a government work, the work is
in the public domain in the United States. 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.
NR 60
TC 17
Z9 18
U1 1
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-1348
J9 INFECT GENET EVOL
JI Infect. Genet. Evol.
PD MAR
PY 2010
VL 10
IS 2
BP 184
EP 191
DI 10.1016/j.meegid.2009.10.012
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA 573PJ
UT WOS:000275926400003
PM 19900580
ER
PT J
AU Goldstein, E
Miller, JC
O'Hagan, JJ
Lipsitch, M
AF Goldstein, Edward
Miller, Joel C.
O'Hagan, Justin J.
Lipsitch, Marc
TI Pre-dispensing of antivirals to high-risk individuals in an influenza
pandemic
SO INFLUENZA AND OTHER RESPIRATORY VIRUSES
LA English
DT Review
DE Antivirals; high-risk individuals; influenza; pre-dispensing
ID RESPIRATORY-FAILURE; OSELTAMIVIR
AB We consider the net benefits of pre-dispensing antivirals to high-risk individuals during an influenza pandemic, where the measure of the benefit is the number of severe outcomes (such as deaths or hospitalizations) prevented by antivirals in the whole population. One potential benefit of pre-dispensing is that individuals to whom antivirals have been pre-dispensed may be able to initiate treatment earlier than if they had to wait to obtain and fill a prescription, reducing their risk of progression to severe disease. If this benefit exceeds the side effects of misuse for the category of individuals to whom antivirals were pre-dispensed, and if antiviral supply exceeds overall population demand (which appears relevant for several countries including US in the 2009 H1N1 pandemic), pre-dispensing a quantity of antivirals not exceeding the difference between supply and demand is always beneficial. In this study, we consider the net benefits of pre-dispensing antivirals under various scenarios, including demand exceeding supply, and derive mathematical conditions under which antiviral pre-dispensing is advantageous on balance. For individuals whose relative risk of severe outcome is high enough, such as immunosuppressed individuals (particularly children) and possibly individuals with neurological disorders, pre-dispensing is always beneficial at a given level of antiviral stockpile with modest assumptions on the relative benefit of early treatment by a pre-dispensed course, regardless of the overall population demand for antivirals during the course of an epidemic. Making additional assumptions on either the overall population demand for antivirals (which appear relevant for the 2009 H1N1 pandemic) or on the relative benefit of pre-dispensing would make pre-dispensing net beneficial with inclusion of a larger number of persons such as pregnant women and morbidly obese adults.
C1 [Goldstein, Edward; Miller, Joel C.; O'Hagan, Justin J.; Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
[Miller, Joel C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Goldstein, E (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, 677 Huntington Ave, Boston, MA 02115 USA.
EM egoldste@hsph.harvard.edu
RI Miller, Joel/C-4229-2015;
OI Miller, Joel/0000-0003-4426-0405; Lipsitch, Marc/0000-0003-1504-9213
FU US National Institutes of Health Models of Infectious Disease Agent
Study [5U01GM076497, 1U54GM088588]; RAPIDD; Department of Homeland
Security, and the Fogarty International Center; National Institutes of
Health (JCM)
FX We thank Richard Hatchett for helpful discussions. The MIDAS High Risk
Segmentation Group (D. Wagener, R. Zimmerman, D. Lauderdale) kindly
shared their the data. This work was funded by the US National
Institutes of Health Models of Infectious Disease Agent Study
Cooperative Agreements 5U01GM076497 and 1U54GM088588 to ML for the
Harvard Center for Communicable Disease Dynamics (ML,EG,JO), and by the
RAPIDD program of the Science & Technology Directorate, Department of
Homeland Security, and the Fogarty International Center, National
Institutes of Health (JCM). An earlier version of this paper appeared
online in PLoS Currents:Influenza.31
NR 29
TC 4
Z9 4
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1750-2640
J9 INFLUENZA OTHER RESP
JI Influenza Other Respir. Viruses
PD MAR
PY 2010
VL 4
IS 2
BP 101
EP 112
DI 10.1111/j.1750-2659.2009.00128.x
PG 12
WC Infectious Diseases; Virology
SC Infectious Diseases; Virology
GA 554BR
UT WOS:000274411000007
PM 20167050
ER
PT J
AU de la Lande, A
Maddaluno, J
Parisel, O
Darden, TA
Piquemal, JP
AF de la Lande, A.
Maddaluno, J.
Parisel, O.
Darden, T. A.
Piquemal, J-P
TI Study of the Docking of Competitive Inhibitors at a Model of Tyrosinase
Active Site: Insights from Joint Broken-Symmetry/Spin-Flip DFT
Computations and ELF Topological Analysis
SO INTERDISCIPLINARY SCIENCES-COMPUTATIONAL LIFE SCIENCES
LA English
DT Article
DE Density Functional Theory; Spin-Flip TD-DFT; copper; oxygenase;
tyrosinase; competitive inhibition
AB Following our previous study (Piquemal et al., 2003), we present here a DFT study of the inhibition of the Tyrosinase enzyme. Broken-symmetry DFT computations are supplemented with Spin-Flip TD-DFT calculations, which, for the first time, are applied to such a dicopper enzyme. The chosen biomimetic model encompasses a dioxygen molecule, two Cu(II) cations, and six imidazole rings. The docking energy of a natural substrate, namely phenolate, together with those of several inhibitor and non-inhibitor compounds, are reported and show the ability of the model to rank the most potent inhibitors in agreement with experimental data. With respect to broken-symmetry calculations, the Spin-Flip TD-DFT approach reinforces the possibility for theory to point out potent inhibitors: the need for the deprotonation of the substrates, natural or inhibitors, is now clearly established. Moreover, Electron Localization Function (ELF) topological analysis computations are used to deeply track the particular electronic distribution of the Cu-O-Cu three-center bonds involved in the enzymatic Cu2O2 metallic core (Piquemal and Pilme, 2006). It is shown that such bonds exhibit very resilient out-of-plane density expansions that play a key role in docking interactions: their 3D-orientation could be the topological electronic signature of oxygen activation within such systems.
C1 [de la Lande, A.; Parisel, O.; Piquemal, J-P] UPMC Univ Paris 06, UMR 7616, Chim Theor Lab, F-75005 Paris, France.
[de la Lande, A.; Parisel, O.; Piquemal, J-P] CNRS, Chim Theor Lab, UMR 7616, F-75005 Paris, France.
[de la Lande, A.] Univ Calgary, Inst Biocomplex & Informat, Calgary, AB T2N 1N4, Canada.
[Maddaluno, J.] Univ Rouen, CNRS, UMR 6014, Inst Rech Chim Organ Fine, F-76821 Mont St Aignan, France.
[Darden, T. A.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
RP Piquemal, JP (reprint author), UPMC Univ Paris 06, UMR 7616, Chim Theor Lab, Case Courrier 137,4 Pl Jussieu, F-75005 Paris, France.
EM jpp@lct.jussieu.fr
RI Piquemal, Jean-Philip/B-9901-2009; de la Lande, Aurelien/P-5656-2016
OI Piquemal, Jean-Philip/0000-0001-6615-9426;
FU CRIHAN (Saint-Etienne-du-Rouvray, France) [2008011]; Intramural Research
program of the NIH; NIEHS (USA)
FX The computations were performed at CRIHAN (Saint-Etienne-du-Rouvray,
France) on project 2008011, IDRIS (Orsay, France) and NIEHS (RTP, NC,
USA). This research was supported by the Intramural Research program of
the NIH and NIEHS (USA). The authors are deeply indebted to Dr Claude
Giessner-Prettre who initiated the project.
NR 52
TC 7
Z9 7
U1 1
U2 13
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1913-2751
J9 INTERDISCIP SCI
JI Interdiscip. Sci.
PD MAR
PY 2010
VL 2
IS 1
SI SI
BP 3
EP 11
DI 10.1007/s12539-010-0096-8
PG 9
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA V28VT
UT WOS:000208709000002
PM 20396590
ER
PT J
AU Balansky, R
Ganchev, G
Iltcheva, M
Steele, VE
De Flora, S
AF Balansky, Roumen
Ganchev, Gancho
Iltcheva, Marietta
Steele, Vernon E.
De Flora, Silvio
TI Prevention of cigarette smoke-induced lung tumors in mice by budesonide,
phenethyl isothiocyanate, and N-acetylcysteine
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE mainstream cigarette smoke; lung cancer; budesonide; phenethyl
isothiocyanate; N-acetyl-L-cysteine
ID CANCER CHEMOPREVENTIVE AGENTS; TOBACCO-SMOKE; INHALATION EXPOSURE;
BETA-CAROTENE; END-POINTS; A/J MOUSE; MODULATION; CARCINOGENESIS; RATS;
DNA
AB Lung cancer is the most important cause of death among neoplastic diseases worldwide, and cigarette smoke (CS) is the major risk factor for cancer. Complementarity to avoidance of exposure to CS, chemoprevention will lower the risk of cancer in passive smokers, ex-smokers, and addicted current smokers who fait to quit smoking. Unfortunately, chemoprevention clinical trials have produced disappointing results to date and, until recently, a suitable animal model evaluating CS carcinogenicity was not available. We previously demonstrated that mainstream CS induces a potent carcinogenic response when exposure of mice starts at birth. In the present study, neonatal mice (strain H) were exposed to CS for 120 consecutive days, starting at birth. The chemopreventive agents budesonide (2.4 mg/kg diet), phenethyl isothiocyanate (PEITC, 1,000 mg/kg diet), and N-acetyl-L-cysteine (NAC, 1,000 mg/kg body weight) were administered orally according to various protocols. The experiment was stopped after 210 days. Exposure to CS resulted in a high incidence and multiplicity of benign lung tumors and in significant increases of malignant lung tumors and other histopathological alterations. All three chemopreventive agents, administered to current smokers after weaning, were quite effective in protecting both mate and female mice from CS pulmonary carcinogenicity. When given to ex-smokers after withdrawal of exposure to CS, the protective capacity of budesonide was unchanged, while PEITC lost part of its cancer chemopreventive activity. In conclusion, the proposed experimental model provides convincing evidence that it is possible to prevent CS-induced lung cancer by means of dietary and pharmacological agents.
C1 [Balansky, Roumen; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy.
[Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta] Natl Oncol Ctr, BU-1157 Sofia, Bulgaria.
[Steele, Vernon E.] NCI, Rockville, MD USA.
RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via Pastore 1, I-16132 Genoa, Italy.
EM sdf@unige.it
FU Bulgarian Ministry of Education and Science; U.S. National Cancer
Institute [N01-CN53301]
FX Grant sponsor: The Bulgarian Ministry of Education and Science;; Grant
sponsor: The U.S. National Cancer Institute; Grant number: N01-CN53301
NR 42
TC 31
Z9 31
U1 0
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 1
PY 2010
VL 126
IS 5
BP 1047
EP 1054
DI 10.1002/ijc.24942
PG 8
WC Oncology
SC Oncology
GA 547PU
UT WOS:000273902300003
PM 19816928
ER
PT J
AU Pinheiro, AP
Raney, TJ
Thornton, LM
Fichter, MM
Berrettini, WH
Goldman, D
Halmi, KA
Kaplan, AS
Strober, M
Treasure, J
Woodside, DB
Kaye, WH
Bulik, CM
AF Pinheiro, Andrea Poyastro
Raney, T. J.
Thornton, Laura M.
Fichter, Manfred M.
Berrettini, Wade H.
Goldman, David
Halmi, Katherine A.
Kaplan, Allan S.
Strober, Michael
Treasure, Janet
Woodside, D. Blake
Kaye, Walter H.
Bulik, Cynthia M.
TI Sexual Functioning in Women with Eating Disorders
SO INTERNATIONAL JOURNAL OF EATING DISORDERS
LA English
DT Article
DE anorexia nervosa; eating disorders; sexual behavior; sexual dysfunction
ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA; STRUCTURED INTERVIEW; LONGITUDINAL
DATA; BODY-IMAGE; REPRODUCTION; DYSFUNCTION; DEPRESSION; EXPERIENCE;
PROFILES
AB Objective: To describe sexual functioning in women with eating disorders
Method: We assessed physical intimacy, libido, sexual anxiety, partner status. and sexual relationships in 242 women from the international Price Foundation Genetic Studies relative to normative data
Results: Intercourse (55 3%), having a partner (52 7%). decreased sexual desire (66 9%), and increased sexual anxiety (59 2%) were common Women with restricting and purging anorexia nervosa had a higher prevalence of loss of libido than women with bulimia nervosa and eating disorder not otherwise specified (75%, 74 6%, 39%, and 45 4%, respectively) Absence of sexual relationships was associated with lower minimum lifetime body mass index (BMI) and earlier age of onset. loss of libido with lower lifetime BMI. higher interoceptive awareness and trait anxiety, and sexual anxiety with lower lifetime BMI, higher harm avoidance and ineffectiveness Sexual dysfunction in eating disorders was higher than in the normative sample
Discussion: Sexual dysfunction, Is common across eating disorders subtypes Low BMI is associated with loss of libido, sexual anxiety, and avoidance of Sexual relationships (C) 2009 by Wiley Periodicals, Inc
C1 [Pinheiro, Andrea Poyastro; Raney, T. J.; Thornton, Laura M.; Bulik, Cynthia M.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
[Fichter, Manfred M.] Univ Munich, D-80539 Munich, Germany.
[Berrettini, Wade H.] Univ Penn, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA.
[Goldman, David] Natl Inst Alcohol Abuse & Alcoholism, Rockville, MD USA.
[Halmi, Katherine A.] Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Westchester Div, White Plains, NY USA.
[Kaplan, Allan S.] Toronto Hosp, Dept Psychiat, Toronto, ON M5T 2S8, Canada.
[Strober, Michael] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
[Treasure, Janet] Kings Coll London, Inst Psychiat, London WC2R 2LS, England.
[Kaye, Walter H.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Kaye, Walter H.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Bulik, Cynthia M.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.
RP Bulik, CM (reprint author), Univ N Carolina, Dept Psychiat, 101 Manning Dr,CB 7160, Chapel Hill, NC 27599 USA.
RI Goldman, David/F-9772-2010;
OI Goldman, David/0000-0002-1724-5405; Treasure, Janet/0000-0003-0871-4596
FU National Institutes of Health, Bethesda [MH66117]; Franklin Mint Endowed
Chair in Eating Disorders
FX Supported by MH66117 from the National Institutes of Health, Bethesda.
MD Or Strober is supported in part by the Franklin Mint Endowed Chair in
Eating Disorders
NR 43
TC 28
Z9 30
U1 1
U2 12
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0276-3478
J9 INT J EAT DISORDER
JI Int. J. Eating Disord.
PD MAR
PY 2010
VL 43
IS 2
BP 123
EP 129
PG 7
WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology
SC Psychology; Nutrition & Dietetics; Psychiatry
GA 562CD
UT WOS:000275025900003
PM 19260036
ER
PT J
AU Jiang, LY
Malpica, A
Deavers, MT
Guo, M
Villa, LL
Nuovo, G
Merino, MJ
Silva, EG
AF Jiang, Liuyan
Malpica, Anais
Deavers, Michael T.
Guo, Ming
Villa, Luisa Lina
Nuovo, Gerard
Merino, Maria J.
Silva, Elvio G.
TI Endometrial Endometrioid Adenocarcinoma of the Uterine Corpus Involving
the Cervix: Some Cases Probably Represent Independent Primaries
SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY
LA English
DT Article
DE Endometrial adenocarcinoma; Endocervical adenocarcinoma; Endometrioid
type; Microcystic pattern
ID ENDOCERVICAL ADENOCARCINOMAS; PROGNOSTIC-SIGNIFICANCE; CARCINOMA;
INVOLVEMENT; SURVIVAL; CANCER; STAGE; DISTINCTION; PATTERN; VULVA
AB The majority of endometrial endometrioid adenocarcinomas involving the cervix have tumor morphology that is similar in the endometrium and the endocervix. There are, however, some cases in which the morphology of the tumor in the endocervix is different from the endometrial carcinoma, in which it is more invasive than the endometrial carcinoma, or in which invasion only occurs in the endocervix while there is no or only minimal myometrial invasion. The goal of this study was to investigate whether tumors involving the endometrium and the endocervix are similar or 2 independent primaries by hematoxylin and eosin stain, immunohistochemistry (IHC), human papillomavirus (HPV) DNA in situ hybridization, RNA reverse transcriptase in situ polymerase chain reaction (PCR) analyses to reveal HPV, and DNA clonality studies. We selected 14 cases of endometrial endometrioid adenocarcinomas involving the cervix with complete pathology material available from the years between 1968 and 2004. Immunohistochemical studies for vimentin, carcinoembryonic antigen, estrogen receptor, progesterone receptor, and p16 were performed in 12 cases; HPV DNA/RNA analyses in 4 cases; and clonality studies in 9 cases. The patients' ages ranged from 42 to 81 years (mean: 62 y). Follow-up information was obtained in 11 patients. Histologic features varied between the tumors in the endometrium and the endocervix in 8 cases, and 5 of these cases had uniform, dilated glands having a microcystic appearance in the cervix. In 6 cases, the tumors in the endometrium and the endocervix had similar histologic features. The immunohistochemical studies showed some differences between the endometrial and endocervical adenocarcinomas in 8 of the 12 cases, independent of differing or similar histologic features. HPV testing in 4 of the cases (3 with similar and 1 with different histology) yielded similar results in the endometrium and endocervix: 2 cases were negative, 1 was positive and 1 was equivocal for HPV DNA/RNA analyses. Clonality studies showed differences between the adenocarcinoma in the endometrium and the endocervix in 7 cases, including 5 cases with different histologic appearances; 2 cases had similar loss of heterozygosity patterns. In conclusion, as suggested by clonality studies, coexisting endometrial and endocervical carcinomas with different histologic features are most likely independent neoplasms. Endometrial and endocervical carcinomas that have similar appearances can represent either the same neoplasm or independent primaries. Clonality tests may help determine their relationship. IHC studies may not be helpful for synchronous endometrial and endocervical tumors, especially those of endometrioid type. It is possible that IHC identifies cell differentiation, rather than site of origin. HPV studies are important to identify endocervical tumors associated with high-risk HPV. However, endometrial tumors involving the cervix and endocervical tumors unrelated to HPV are both negative for high-risk HPV.
C1 [Jiang, Liuyan; Merino, Maria J.] NCI, Dept Pathol, Bethesda, MD 20892 USA.
[Malpica, Anais; Deavers, Michael T.; Guo, Ming; Silva, Elvio G.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA.
[Villa, Luisa Lina] Ludwig Inst Canc Res, Sao Paulo, Brazil.
[Nuovo, Gerard] Ohio Univ, Dept Pathol, Columbus, OH USA.
RP Silva, EG (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA.
EM esilva@mdanderson.org
NR 18
TC 6
Z9 6
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-1691
J9 INT J GYNECOL PATHOL
JI Int. J. Gynecol. Pathol.
PD MAR
PY 2010
VL 29
IS 2
BP 146
EP 156
DI 10.1097/PGP.0b013e3181b8e951
PG 11
WC Obstetrics & Gynecology; Pathology
SC Obstetrics & Gynecology; Pathology
GA 586KN
UT WOS:000276907200007
PM 20173500
ER
PT J
AU Bedognetti, D
Zoppoli, G
Sertoli, MR
Zanardi, E
Blandini, P
Uccellini, L
Boccardo, F
Andreoli, GB
Ghio, R
Racchi, O
Ferrarini, M
De Maria, A
AF Bedognetti, Davide
Zoppoli, Gabriele
Sertoli, Mario Roberto
Zanardi, Elisa
Blandini, Pietro
Uccellini, Lorenzo
Boccardo, Francesco
Andreoli, Giovanni Battista
Ghio, Riccardo
Racchi, Omar
Ferrarini, Manlio
De Maria, Andrea
TI Relevance of HBV/HBcAb screening in lymphoma patients treated in the
Rituximab era
SO INTERNATIONAL JOURNAL OF HEMATOLOGY
LA English
DT Letter
ID HEPATITIS-B; MALIGNANT-LYMPHOMA; REACTIVATION
C1 [Bedognetti, Davide; Uccellini, Lorenzo] Natl Inst Hlth, Infect Dis & Immunogenet Sect, Dept Transfus Med, Bethesda, MD 20892 USA.
[Bedognetti, Davide; Sertoli, Mario Roberto; Zanardi, Elisa; Boccardo, Francesco; Racchi, Omar; Ferrarini, Manlio] Univ Genoa, Dept Oncol Biol & Genet, I-16132 Genoa, Italy.
[Zoppoli, Gabriele; Blandini, Pietro; Ghio, Riccardo; De Maria, Andrea] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy.
[Zoppoli, Gabriele] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Sertoli, Mario Roberto; Boccardo, Francesco; Ferrarini, Manlio; De Maria, Andrea] Natl Inst Canc Res, Dept Med Oncol, Genoa, Italy.
[Andreoli, Giovanni Battista] Natl Inst Canc Res, Direz Sanit, Genoa, Italy.
[Racchi, Omar] Villa Scassi Hosp, Dept Internal Med, Genoa, Italy.
[De Maria, Andrea] Natl Inst Canc Res, Infect Dis Sect, Genoa, Italy.
RP Bedognetti, D (reprint author), Natl Inst Hlth, Infect Dis & Immunogenet Sect, Dept Transfus Med, Bldg 10,Room 1 N-224,10 Ctr Dr, Bethesda, MD 20892 USA.
EM Davide.Bedognetti@nih.gov
RI Bedognetti, Davide/A-9090-2012; Zoppoli, Gabriele/B-6935-2016; de maria,
andrea/F-7116-2016;
OI Zoppoli, Gabriele/0000-0003-3890-5588; de maria,
andrea/0000-0001-5782-333X; Bedognetti, Davide/0000-0002-5857-773X;
Ferrarini, Manlio/0000-0002-6154-2570
NR 12
TC 6
Z9 7
U1 0
U2 0
PU SPRINGER TOKYO
PI TOKYO
PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN
SN 0925-5710
J9 INT J HEMATOL
JI Int. J. Hematol.
PD MAR
PY 2010
VL 91
IS 2
BP 342
EP 344
DI 10.1007/s12185-010-0522-z
PG 3
WC Hematology
SC Hematology
GA 580OX
UT WOS:000276459900032
PM 20191334
ER
PT J
AU Bertherat, E
England, K
AF Bertherat, E.
England, K.
TI What is the current situation with plague in North Africa?
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Bertherat, E.] WHO, CH-1211 Geneva, Switzerland.
[England, K.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD MAR
PY 2010
VL 14
SU 1
BP E374
EP E375
DI 10.1016/j.ijid.2010.02.454
PG 2
WC Infectious Diseases
SC Infectious Diseases
GA 578MQ
UT WOS:000276298201414
ER
PT J
AU Brown, J
AF Brown, J.
TI Indexing infectious disease information into a relational database for
useful queries on the World Wide Web
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Brown, J.] Natl Lib Med, Tacoma, WA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD MAR
PY 2010
VL 14
SU 1
BP E273
EP E273
DI 10.1016/j.ijid.2010.02.2093
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA 578MQ
UT WOS:000276298201182
ER
PT J
AU Cuellar, J
AF Cuellar, J.
TI Tropical Infections in Solid Organ Transplant Recipients
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Cuellar, J.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD MAR
PY 2010
VL 14
SU 1
BP E328
EP E328
DI 10.1016/j.ijid.2010.02.2219
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA 578MQ
UT WOS:000276298201306
ER
PT J
AU Morens, D
AF Morens, D.
TI Historical perspective: Lessons Learned from past Pandemics
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Morens, D.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD MAR
PY 2010
VL 14
SU 1
BP E20
EP E21
DI 10.1016/j.ijid.2010.02.1531
PG 2
WC Infectious Diseases
SC Infectious Diseases
GA 578MQ
UT WOS:000276298200053
ER
PT J
AU Uhlenhaut, C
McClenahan, SD
Sosnovtsev, S
Bok, K
Kapikian, AZ
Green, KY
Krause, PR
AF Uhlenhaut, C.
McClenahan, S. D.
Sosnovtsev, S.
Bok, K.
Kapikian, A. Z.
Green, K. Y.
Krause, P. R.
TI Enteric virus detection and identification with a universal virus
discovery assay
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Uhlenhaut, C.; McClenahan, S. D.; Krause, P. R.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Sosnovtsev, S.; Bok, K.; Kapikian, A. Z.] NIH, Bethesda, MD 20892 USA.
[Green, K. Y.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD MAR
PY 2010
VL 14
SU 1
BP E188
EP E189
DI 10.1016/j.ijid.2010.02.1907
PG 2
WC Infectious Diseases
SC Infectious Diseases
GA 578MQ
UT WOS:000276298200425
ER
PT J
AU Green, JG
Avenevoli, S
Finkelman, M
Gruber, MJ
Kessler, RC
Merikangas, KR
Sampson, NA
Zaslavsky, AM
AF Green, Jennifer Greif
Avenevoli, Shelli
Finkelman, Matthew
Gruber, Michael J.
Kessler, Ronald C.
Merikangas, Kathleen R.
Sampson, Nancy A.
Zaslavsky, Alan M.
TI Attention deficit hyperactivity disorder. concordance of the adolescent
version of the Composite International Diagnostic Interview Version 3.0
(CIDI) with the K-SADS in the US National Comorbidity Survey Replication
Adolescent (NCS-A) supplement
SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH
LA English
DT Article
DE attention deficit hyperactivity disorder; WHO Composite International
Diagnostic Interview (CIDI); validity; National Comorbidity Survey
Replication Adolescent Supplement (NCS-A)
ID PERFORMANCE-TEST PERFORMANCE; DEFICIT/HYPERACTIVITY-DISORDER;
RATING-SCALES; CHILDREN; ADHD; SYMPTOMS; AGREEMENT; SCHEDULE; VALIDITY;
SAMPLE
AB This paper evaluates the internal consistency reliability and concurrent validity of the assessment of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) attention deficit hyperactivity disorder (ADHD) in the adolescent version of the World Health Organization (WHO) Composite International Diagnostic Interview Version 3.0 (CIDI). The CIDI is a lay-administered diagnostic interview that was carried out in con unction with the US National Comorbidity Survey Adolescent Supplement,) a US nationally representative survey of 10,148 adolescents and their parents. Internal consistency reliability was evaluated using factor and item response theory analyses. Concurrent validity was evaluated against diagnoses based on blinded clinician-administered interviews. Inattention and hyperactivity-impulsivity items loaded on separate but correlated factors, with hyperactivity and impulsivity items forming a single factor in parent reports but separate factors in Youth reports. We were able to differentiate hyperactivity and impulsivity factors for parents its well by eliminating a subset who endorsed zero ADHD items from the factor analysis. Although concurrent validity was relatively weak, de-composition showed that this was due to low validity of adolescent reports. A modified CIDI diagnosis based exclusively on parent reports generated a diagnosis that had good concordance with clinical diagnoses [area tinder the curve (AUC) = 0.78]. Implications for assessing ADHD using the CIDI and the effect of different informants on measurement are discussed. Copyright (C) 2010 John Wiley & Sons, Ltd
C1 [Green, Jennifer Greif; Gruber, Michael J.; Kessler, Ronald C.; Sampson, Nancy A.; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Avenevoli, Shelli] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA.
[Finkelman, Matthew] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA.
[Merikangas, Kathleen R.] NIMH, Intramural Res Program, Genet Epidemiol Branch, Bethesda, MD 20892 USA.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM Kessler@hcp.medharvard.edu
FU NIMH [IZOI-MI-1070884, R13-MH066849, ROI-MHO69864, ROI-MI-1077883]
FX The WMH Data Coordination Centres have received support from NIMH
(IZOI-MI-1070884, R13-MH066849, ROI-MHO69864, ROI-MI-1077883),
NR 41
TC 14
Z9 14
U1 5
U2 8
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1049-8931
J9 INT J METH PSYCH RES
JI Int. J. Methods Psychiatr. Res.
PD MAR
PY 2010
VL 19
IS 1
BP 34
EP 49
DI 10.1002/mpr303
PG 16
WC Psychiatry
SC Psychiatry
GA 571YY
UT WOS:000275793700003
PM 20191660
ER
PT J
AU Daly, KA
Hoffman, HJ
Kvaerner, KJ
Kvestad, E
Casselbrant, ML
Homoe, P
Rovers, MM
AF Daly, Kathleen A.
Hoffman, Howard J.
Kvaerner, Kari Jorunn
Kvestad, Ellen
Casselbrant, Margaretha L.
Homoe, Preben
Rovers, Maroeska M.
TI Epidemiology, natural history, and risk factors: Panel report from the
Ninth International Research Conference on Otitis Media
SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY
LA English
DT Review
DE Otitis media; Epidemiology; Natural history; Risk factors
ID RESPIRATORY-TRACT INFECTIONS; RANDOMIZED CONTROLLED-TRIAL; MIDDLE-EAR
DISEASE; PRESCHOOL-CHILDREN; WESTERN-AUSTRALIA; YOUNG-CHILDREN;
DAY-CARE; EFFUSION; SCHOOLCHILDREN; INTERVENTION
AB The 2007 Recent Advances in Otitis Media Research Conference Panel Report provides an update on otitis media (OM) research published from 2003 to 2007 This report summarizes important trends in disease incidence and prevalence, describes established and newly identified risk factors for acute and chronic OM and OM with effusion, and conveys information on newly discovered genetic factors In this report, researchers have described declining rates of OM diagnosis, antibiotic prescriptions, offices visits for OM, and middle car Surgery since the licensure and routine use of pneumococcal conjugate vaccine in infants The panel report also recommends short and long term goals for current and future OM research (C) 2009 Elsevier Ireland Ltd All rights reserved.
C1 [Daly, Kathleen A.] Univ Minnesota, Dept Otolaryngol, Minneapolis, MN 55435 USA.
[Daly, Kathleen A.] Univ Minnesota, Div Epidemiol, Minneapolis, MN 55435 USA.
[Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders NIDCD, Epidemiol & Biostat Program, NIH, Bethesda, MD 20892 USA.
[Kvaerner, Kari Jorunn] Univ Oslo, Inst Special Needs, Oslo, Norway.
[Kvestad, Ellen] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway.
[Casselbrant, Margaretha L.] Univ Pittsburgh, Sch Med, Div Pediat Otolaryngol, Childrens Hosp, Pittsburgh, PA USA.
[Homoe, Preben] Univ Copenhagen, Rigshosp, Dept Otorhinolaryngol Head & Neck Surg, DK-2100 Copenhagen, Denmark.
[Rovers, Maroeska M.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands.
RP Daly, KA (reprint author), Univ Minnesota, Dept Otolaryngol, Minneapolis, MN 55435 USA.
RI Rovers, Maroeska/F-2969-2014
OI Rovers, Maroeska/0000-0002-3095-170X
FU National Institute on Deafness and Other Communication Disorders
(NIDCD), NIH [1R13-DC-008950-01]
FX The Post-Symposium Otitis Media Research Conference was made possible
through funding by The National Institute on Deafness and Other
Communication Disorders (NIDCD), NIH, of conference grant:
1R13-DC-008950-01 (PI - Dr. David Lim). We gratefully acknowledge Dr.
Lim for his tireless efforts in organizing and Implementing the
Post-Symposium OM Research Conference, as well as the preceding 9th
International Symposium on Recent Advances in Otitis Media.
NR 83
TC 40
Z9 43
U1 3
U2 14
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-5876
J9 INT J PEDIATR OTORHI
JI Int. J. Pediatr. Otorhinolaryngol.
PD MAR
PY 2010
VL 74
IS 3
BP 231
EP 240
DI 10.1016/j.ijporl.2009.09.006
PG 10
WC Otorhinolaryngology; Pediatrics
SC Otorhinolaryngology; Pediatrics
GA 569QF
UT WOS:000275612400001
PM 19836843
ER
PT J
AU Darby, SC
Cutter, DJ
Boerma, M
Constine, LS
Fajardo, LF
Kodama, K
Mabuchi, K
Marks, LB
Mettler, FA
Pierce, LJ
Trott, KR
Yeh, ETH
Shore, RE
AF Darby, Sarah C.
Cutter, David J.
Boerma, Marjan
Constine, Louis S.
Fajardo, Luis F.
Kodama, Kazunori
Mabuchi, Kiyohiko
Marks, Lawrence B.
Mettler, Fred A.
Pierce, Lori J.
Trott, Klaus R.
Yeh, Edward T. H.
Shore, Roy E.
TI RADIATION-RELATED HEART DISEASE: CURRENT KNOWLEDGE AND FUTURE PROSPECTS
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Review
ID ATOMIC-BOMB SURVIVORS; BREAST-CANCER RADIOTHERAPY; LONG-TERM SURVIVORS;
HODGKINS-DISEASE; MEDIASTINAL IRRADIATION; IONIZING-RADIATION;
RANDOMIZED-TRIALS; CARDIAC DAMAGE; LATE MORTALITY; RAT-HEART
C1 [Darby, Sarah C.; Cutter, David J.] Clin Trial Serv Unit, Oxford OX3 7LF, England.
[Boerma, Marjan] Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR 72205 USA.
[Constine, Louis S.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA.
[Constine, Louis S.] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA.
[Fajardo, Luis F.] Stanford Univ, Sch Med & Vet Healthcare Syst, Dept Pathol, Palo Alto, CA 94304 USA.
[Kodama, Kazunori; Shore, Roy E.] Radiat Effects Res Fdn, Hiroshima, Japan.
[Mabuchi, Kiyohiko] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Marks, Lawrence B.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC USA.
[Mettler, Fred A.] New Mexico Vet Affairs Hlth Care Syst, Radiol & Nucl Med Serv, Albuquerque, NM USA.
[Pierce, Lori J.] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI 48109 USA.
[Trott, Klaus R.] UCL, Inst Canc, London, England.
[Yeh, Edward T. H.] Univ Texas MD Anderson Canc Ctr, Dept Cardiol, Houston, TX 77030 USA.
RP Darby, SC (reprint author), Clin Trial Serv Unit, Richard Doll Bldg, Oxford OX3 7LF, England.
EM sarah.darby@ctsu.ox.ac.uk
FU Intramural NIH HHS [ZIA CP010134-18]; Medical Research Council
[MC_U137686858]; NCI NIH HHS [R01 CA069579]
NR 54
TC 159
Z9 170
U1 0
U2 19
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 1
PY 2010
VL 76
IS 3
BP 656
EP 665
DI 10.1016/j.ijrobp.2009.09.064
PG 10
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 562RT
UT WOS:000275072200002
PM 20159360
ER
PT J
AU Kapetanovic, IM
Horn, TL
Johnson, WD
Cwik, MJ
Detrisac, CJ
McCormick, DL
AF Kapetanovic, Izet M.
Horn, Thomas L.
Johnson, William D.
Cwik, Michael J.
Detrisac, Carol J.
McCormick, David L.
TI Murine Oncogenicity and Pharmacokinetics Studies of 9-cis-UAB30, an RXR
Agonist, for Breast Cancer Chemoprevention
SO INTERNATIONAL JOURNAL OF TOXICOLOGY
LA English
DT Article
DE 9-cis-UAB30; retinoid; cancer chemopreventive agent; pharmacokinetics;
oncogenicity; p53((+/-)) mouse
ID RETINOIC ACID ANALOGS; 9-CIS-RETINOIC ACID; PREVENTION; 9CUAB30;
BEXAROTENE; INDUCTION; REXINOIDS; TAMOXIFEN; THERAPY; ENZYMES
AB The synthetic retinoic acid analog, 9-cis-UAB30 [(2E,4E,6Z,8E)-8-(3',4'-dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid], is a specific ligand for the retinoid X receptor. Murine oncogenicity and pharmacokinetics studies were performed as part of the preclinical development of 9-cis-UAB30 for breast cancer chemoprevention. In the oncogenicity study, TSG-p53((+/-)) (p53 knockout) mice (25 per sex per group) received daily gavage exposure to 9-cis-UAB30 doses of 0 (control), 30, 100, or 300 mg/kg/d for 6 months. Positive controls received p-cresidine (400 mg/kg/d) for 6 months. 9-cis-UAB30 had no biologically significant effects on survival, body weight, body weight gain, clinical signs, hematology, or clinical chemistry but induced dose-related hepatomegaly in both sexes and decreased thymus weights in high-dose females. Gross and microscopic pathology provided no evidence of 9-cis-UAB30 toxicity or oncogenicity; by contrast, p-cresidine induced urinary bladder neoplasms in more than 60% of male and female mice. It was concluded that 9-cis-UAB30 is not oncogenic in p53((+/-)) mice. In the pharmacokinetics study, C57BL/6 mice received daily gavage exposure to 9-cis-UAB30 (100 or 300 mg/kg/d) for 1 or 7 days. Pharmacokinetic parameters were similar after 1 and 7 days of dosing. Dose-related peak plasma levels of 9-cis-UAB30 were seen between 0.25 and 3 hours; volume of distribution was comparable at both dose levels. Increases in area under the curve were less than proportional to dose and were associated with an increased rate of apparent clearance and decreased elimination half-life. These results suggest decreased absorption and/or possible induction of clearance mechanisms. Enzyme induction may underlie the hepatomegaly seen in mice treated with 9-cis-UAB30 for 6 months in the oncogenicity study.
C1 [Horn, Thomas L.; Johnson, William D.; Cwik, Michael J.; McCormick, David L.] IIT, Res Inst, Chicago, IL 60616 USA.
[Kapetanovic, Izet M.] NCI, Bethesda, MD 20892 USA.
[Detrisac, Carol J.] Pathol Associates Inc, Chicago, IL USA.
RP McCormick, DL (reprint author), IIT, Res Inst, 10 W 35th St, Chicago, IL 60616 USA.
EM dmccormick@iitri.org
FU Chemopreventive Agent Development Research Group, Division of Cancer
Prevention, National Cancer Institute [N01-CN-43304]
FX The author(s) disclosed receipt of the following financial support for
the research and/or authorship of this article: contract N01-CN-43304
from the Chemopreventive Agent Development Research Group, Division of
Cancer Prevention, National Cancer Institute.
NR 26
TC 6
Z9 6
U1 0
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1091-5818
J9 INT J TOXICOL
JI Int. J. Toxicol.
PD MAR
PY 2010
VL 29
IS 2
BP 157
EP 164
DI 10.1177/1091581809360070
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 577XP
UT WOS:000276257600002
PM 20335511
ER
PT J
AU Amaral, J
Becerra, SP
AF Amaral, Juan
Becerra, S. Patricia
TI Effects of Human Recombinant PEDF Protein and PEDF-Derived Peptide
34-mer on Choroidal Neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT-EPITHELIUM; GENE-TRANSFER;
ANTIANGIOGENIC ACTIVITY; NEUROTROPHIC ACTIVITY; MACULAR DEGENERATION;
BINDING-SITE; NONINHIBITORY SERPIN; ANGIOGENIC FACTOR; TUMOR-GROWTH
AB PURPOSE. Pigment epithelium-derived factor (PEDF) is a serpin with antiangiogenic properties. Previously, the authors showed that PEDF injected into the subconjunctiva reaches the choroid. Here, they examined the effects of PEDF polypeptide fragments on vessel sprouting and on choroidal neovascularization (CNV) after subconjunctival administration.
METHODS. Recombinant human PEDF (rhuPEDF) was cleaved at its serpin-exposed loop by limited chymotrypsin proteolysis. Synthetic PEDF peptides 34-mer (Asp(44)-Asn(77)) and 44-mer (Val(78)-Thr(121)) were used. Ex vivo chick aortic vessel sprouting assays were performed. CNV was induced in rats by laser injury of Bruch's membrane. Daily subconjunctival injections (0.01-10 pmol/d protein) were performed for 5 days starting at day of injury or at the seventh day after injury. New vessel volumes were quantified using optical sections of choroid/RPE flat-mounts labeled with isolectin-Ib4. PEDF distribution was evaluated by immunofluorescence of choroid/RPE/retina cross-sections.
RESULTS. Full-length rhuPEDF, cleaved rhuPEDF, or peptide 34-mer exhibited ex vivo antiangiogenic activity, but peptide 44-mer was inefficient. PEDF immunostaining around CNV lesions diminished after laser injury. Subconjunctival administration of rhuPEDF or 34-mer at 0.1 pmol/d decreased CNV lesion volumes by 52% and 47%, respectively, whereas those of 44-mer were similar to vehicle injections. Doses of 0.1 and 1 pmol/d rhuPEDF decreased fully developed CNV complex volumes by 45% and 50%, respectively, compared with vehicle injections.
CONCLUSIONS. A functional region for the inhibition of vessel sprouting and CNV resides within the 34-mer region of PEDF. Furthermore, subconjunctival administration of optimal range dosages of rhuPEDF or 34-mer can suppress and regress rat CNV lesions, demonstrating that these agents reach the choroid/RPE complex as functionally active molecules. (Invest Ophthalmol Vis Sci. 2010;51:1318-1326) DOI:10.1167/iovs.09-4455
C1 [Amaral, Juan; Becerra, S. Patricia] NEI, Sect Prot Struct & Funct, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Becerra, SP (reprint author), NEI, Sect Prot Struct & Funct, Retinal Cell & Mol Biol Lab, NIH, Bldg 6,Room 134,6 Ctr Dr,MSC 0608, Bethesda, MD 20892 USA.
EM becerrap@nei.nih.gov
FU Intramural Research Program of the National Eye Institute; National
Institutes of Health
FX Supported by the Intramural Research Program of the National Eye
Institute, National Institutes of Health.
NR 55
TC 32
Z9 34
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2010
VL 51
IS 3
BP 1318
EP 1326
DI 10.1167/iovs.09-4455
PG 9
WC Ophthalmology
SC Ophthalmology
GA 563VW
UT WOS:000275164300013
PM 19850839
ER
PT J
AU Turkbey, EB
McClelland, RL
Kronmal, RA
Burke, GL
Bild, DE
Tracy, RP
Arai, AE
Lima, JAC
Bluemke, DA
AF Turkbey, Evrim B.
McClelland, Robyn L.
Kronmal, Richard A.
Burke, Gregory L.
Bild, Diane E.
Tracy, Russell P.
Arai, Andrew E.
Lima, Joao A. C.
Bluemke, David A.
TI The Impact of Obesity on the Left Ventricle The Multi-Ethnic Study of
Atherosclerosis (MESA)
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE cardiac magnetic resonance; cardiac morphology; epidemiology; left
ventricular function; obesity
ID CARDIOVASCULAR MAGNETIC-RESONANCE; BODY-MASS INDEX; HEART-FAILURE;
2-DIMENSIONAL ECHOCARDIOGRAPHY; EJECTION FRACTION; RISK-FACTORS;
HYPERTROPHY; ASSOCIATION; GEOMETRY; DISEASE
AB OBJECTIVES The purpose of this study was to evaluate the relationship of left ventricular (LV) remodeling assessed by cardiac magnetic resonance to various measures of obesity in a large population-based study.
BACKGROUND Obesity is a well-known risk factor for cardiovascular disease, yet its relationship with LV size and function is poorly understood.
METHODS A total of 5,098 participants (age 45 to 84 years; 48% men) in the Multi-Ethnic Study of Atherosclerosis who were free of clinically apparent cardiovascular disease underwent cardiac magnetic resonance to assess LV size and function as well as measures of obesity, including body mass index, waist-to-hip ratio and waist circumference, and cardiovascular risk factors. Fat mass (FM) was estimated based on height-weight models derived from bioelectrical impedance studies. The associations of obesity measures with LV size and function were evaluated using linear spline regression models for body mass index and multivariable regression models for other measures of obesity; they were displayed graphically using generalized additive models.
RESULTS LV mass and end-diastolic volume were positively associated with measures of obesity in both sexes after adjustment for risk factors (e. g., 5.7-g and 6.9-g increase in LV mass per 10-kg increase in FM in women and men, respectively [p < 0.001]). LV mass-to-volume ratio was positively associated with increased body mass index, waist-to-hip ratio, waist circumference, and estimated FM (e. g., 0.02-g/ml and 0.06-g/ml increase in mass-to-volume ratio per 10-kg increase in FM in women and men, respectively [p < 0.001]). The increased mass-to-volume ratio was due to a greater increase in LV mass relative to LV end-diastolic volume. All associations were stronger for men than for women. Ejection fraction showed no significant association with measures of obesity.
CONCLUSIONS Obesity was associated with concentric LV remodeling without change in ejection fraction in a large, multiethnic cohort study. (J Am Coll Cardiol Img 2010; 3: 266-74) (C) 2010 by the American College of Cardiology Foundation
C1 [Turkbey, Evrim B.; Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[McClelland, Robyn L.; Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Burke, Gregory L.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC USA.
[Bild, Diane E.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Arai, Andrew E.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
[Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, VT USA.
[Tracy, Russell P.] Univ Vermont, Dept Biochem, Colchester, VT USA.
[Lima, Joao A. C.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA.
RP Bluemke, DA (reprint author), NIH, Ctr Clin, 9000 Rockville Pike,Bldg 10,Room 1C355, Bethesda, MD 20892 USA.
EM bluemked@nih.gov
OI Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169]
FX This research was supported by contracts N01-HC-95159 through
N01-HC-95169 from the National Heart, Lung, and Blood Institute.
NR 21
TC 111
Z9 115
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD MAR
PY 2010
VL 3
IS 3
BP 266
EP 274
DI 10.1016/j.jcmg.2009.10.012
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 647NS
UT WOS:000281625800006
PM 20223423
ER
PT J
AU Osinusi, A
Rasimas, JJ
Bishop, R
Proschan, M
McLaughlin, M
Murphy, A
Cortez, KJ
Polis, MA
Masur, H
Rosenstein, D
Kottilil, S
AF Osinusi, Anu
Rasimas, Joseph J.
Bishop, Rachel
Proschan, Michael
McLaughlin, Mary
Murphy, Alison
Cortez, Karoll J.
Polis, Michael A.
Masur, Henry
Rosenstein, Donald
Kottilil, Shyam
TI HIV/Hepatitis C Virus-Coinfected Virologic Responders to Pegylated
Interferon and Ribavirin Therapy More Frequently Incur
Interferon-Related Adverse Events Than Nonresponders Do
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE adverse events; HCV; HIV; Peg-interferon alpha; psychiatric toxicity
ID CHRONIC HEPATITIS-C; HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS
RIBAVIRIN; HIV-INFECTED PATIENTS; INDUCED DEPRESSION; MANAGEMENT;
CANCER; PEGINTERFERON-ALPHA-2B; COMPLICATIONS; PREDICTION
AB Background: This study aimed to assess the relationship between interferon (IFN)-related adverse effects and Hepatitis C virus (HCV) virologic response in HIV/HCV-coinfected individuals treated with pegylated interferon and ribavirin.
Methods: We conducted 2 prospective, open-label trials treating HIV/HCV-coinfected individuals with pegylated interferon alpha-2b or alpha-2a and ribavirin for 48 weeks. Safety laboratories, HCV RNA, psychiatric, and ophthalmologic evaluations were performed at baseline and monthly until week 72.
Results: Responders were defined as those with HCV RNA decline of >= 2-log drop from baseline and nonresponders were those who did not. Remarkably, of the 27 patients (50%) who developed psychiatric toxicities, 26 patients were responders, although only 1 of 14 virologic nonresponders experienced psychiatric toxicity. Other adverse effects, such as anemia and ophthalmologic toxicities, were also more frequent in responders compared with nonresponders. Decline in CD4(+) T-cell counts strongly correlated with HCV viral decline.
Conclusions: Our study demonstrates coupling of antiviral effect and occurrence of adverse events in HIV/HCV-coinfected patients. These patients with IFN-related adverse effects need a multidisciplinary treatment approach, hence, they are more likely to achieve sustained virologic response. Future studies are needed to evaluate the factors that predict the development of IFN-alpha-dependent adverse events before therapy.
C1 [Kottilil, Shyam] NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Rasimas, Joseph J.; Rosenstein, Donald] NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Bishop, Rachel] NEI, NIH, Bethesda, MD 20892 USA.
[Proschan, Michael] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Cortez, Karoll J.; Masur, Henry] NIH, Dept Crit Care Med, Clin Res Ctr, Bethesda, MD 20892 USA.
[Cortez, Karoll J.; Masur, Henry] NIH, CCMD, CC, Bethesda, MD 20892 USA.
RP Kottilil, S (reprint author), NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11N204, Bethesda, MD 20892 USA.
EM skottilil@niaid.nih.gov
OI Polis, Michael/0000-0002-9151-2268
FU National Institutes of Health
FX Supported in whole by the Intramural Research Program of the National
Institutes of Health (National Institute of Allergy and Infectious
Diseases, National Institute of Mental Health, and the National Eye
Institute).
NR 33
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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 MAR 1
PY 2010
VL 53
IS 3
BP 357
EP 363
DI 10.1097/QAI.0b013e3181c7a29d
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 565VX
UT WOS:000275324500010
PM 20101190
ER
PT J
AU Limb, CJ
Molloy, AT
Jiradejvong, P
Braun, AR
AF Limb, Charles J.
Molloy, Anne T.
Jiradejvong, Patpong
Braun, Allen R.
TI Auditory Cortical Activity During Cochlear Implant-Mediated Perception
of Spoken Language, Melody, and Rhythm
SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
LA English
DT Article
DE music; PET; neuroimaging; cochlear implant; melody; rhythm; language
ID POSITRON-EMISSION-TOMOGRAPHY; NORMAL-HEARING SUBJECTS; MUSIC PERCEPTION;
SPEECH; USERS; PET; CORTEX; RECOGNITION; ACTIVATION; PLASTICITY
AB Despite the significant advances in language perception for cochlear implant (CI) recipients, music perception continues to be a major challenge for implant-mediated listening. Our understanding of the neural mechanisms that underlie successful implant listening remains limited. To our knowledge, this study represents the first neuroimaging investigation of music perception in CI users, with the hypothesis that CI subjects would demonstrate greater auditory cortical activation than normal hearing controls. H(2) (15)O positron emission tomography (PET) was used here to assess auditory cortical activation patterns in ten postlingually deafened CI patients and ten normal hearing control subjects. Subjects were presented with language, melody, and rhythm tasks during scanning. Our results show significant auditory cortical activation in implant subjects in comparison to control subjects for language, melody, and rhythm. The greatest activity in CI users compared to controls was seen for language tasks, which is thought to reflect both implant and neural specializations for language processing. For musical stimuli, PET scanning revealed significantly greater activation during rhythm perception in CI subjects (compared to control subjects), and the least activation during melody perception, which was the most difficult task for CI users. These results may suggest a possible relationship between auditory performance and degree of auditory cortical activation in implant recipients that deserves further study.
C1 [Limb, Charles J.] Johns Hopkins Univ, Peabody Inst Mus, Baltimore, MD 21202 USA.
[Limb, Charles J.; Molloy, Anne T.; Braun, Allen R.] NIDCD, NIH, Language Sect, Rockville, MD 20892 USA.
[Limb, Charles J.; Jiradejvong, Patpong] Johns Hopkins Univ Hosp, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA.
RP Limb, CJ (reprint author), Johns Hopkins Univ, Peabody Inst Mus, Baltimore, MD 21202 USA.
EM climb@jhmi.edu
FU NIDCD/NIH
FX This work was supported by the Division of Intramural Research of the
NIDCD/NIH.
NR 35
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U1 2
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1525-3961
J9 JARO-J ASSOC RES OTO
JI JARO
PD MAR
PY 2010
VL 11
IS 1
BP 133
EP 143
DI 10.1007/s10162-009-0184-9
PG 11
WC Neurosciences; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 554LP
UT WOS:000274436800011
PM 19662456
ER
PT J
AU Murray, MM
Savage, C
AF Murray, Margaret M.
Savage, Christine
TI The NIAAA BSN Nursing Education Curriculum: A Rationale and Overview
SO JOURNAL OF ADDICTIONS NURSING
LA English
DT Editorial Material
ID INTERVENTION
C1 [Murray, Margaret M.] NIAAA, Bethesda, MD USA.
[Savage, Christine] Univ Cincinnati, Acad Hlth Ctr, Cincinnati, OH USA.
RP Murray, MM (reprint author), NIAAA, Bethesda, MD USA.
NR 14
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Z9 7
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1088-4602
J9 J ADDICT NURS
JI J. Addict. Nurs.
PD MAR
PY 2010
VL 21
IS 1
BP 3
EP 5
DI 10.3109/10884601003594488
PG 3
WC Substance Abuse; Nursing
SC Substance Abuse; Nursing
GA 569GU
UT WOS:000275585400001
ER
PT J
AU Szefler, SJ
Gergen, PJ
Mitchell, H
Morgan, W
AF Szefler, Stanley J.
Gergen, Peter J.
Mitchell, Herman
Morgan, Wayne
TI Achieving asthma control in the inner city: Do the National Institutes
of Health Asthma Guidelines really work?
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Review
DE Asthma; childhood asthma; inner-city asthma; exhaled nitric oxide;
asthma guidelines
ID URBAN CHILDREN; MANAGEMENT; DISEASE; DISPARITIES; ADHERENCE; MORBIDITY;
BELIEFS; ADULTS; TRIAL; CARE
AB For children living in inner cities, asthma tends to be more frequent and severe. To characterize, understand, and treat children with asthma living in the inner city more effectively, the National Institute of Allergy and Infectious Diseases established an Inner-City Asthma Program in 1991. In addition, the revised National Asthma Education and Prevention Program Expert Panel 3 report was introduced with new concepts for asthma management that are now centered on asthma control. The purpose of this review is to highlight features of the National Institute of Allergy and Infectious Diseases Inner-City Asthma Consortium Asthma Control Evaluation study that enhance our knowledge regarding the application of the asthma guidelines and to provide a summary of lessons learned from that important study. We recognized that asthma symptoms and exacerbations are theoretically linked to underlying inflammation of airways but are not direct indicators of inflammation. Based on the observations from the Asthma Control Evaluation study, we were impressed that a systematic guidelines-based approach improved asthma control significantly over the course of the 1-year treatment period. (J Allergy Clin Immunol 2010;125:521-6.)
C1 [Szefler, Stanley J.] Natl Jewish Hlth, Div Pediat Clin Pharmacol, Dept Pediat, Denver, CO 80206 USA.
[Szefler, Stanley J.] Natl Jewish Hlth, Div Allergy & Immunol, Dept Pediat, Denver, CO 80206 USA.
[Szefler, Stanley J.] Univ Colorado, Denver Sch Med, Boulder, CO 80309 USA.
[Gergen, Peter J.] NIAID, NIH, Bethesda, MD 20892 USA.
[Mitchell, Herman] Rho Inc, Chapel Hill, NC USA.
[Morgan, Wayne] Univ Arizona, Coll Med, Dept Pediat, Tucson, AZ 85721 USA.
RP Szefler, SJ (reprint author), Natl Jewish Hlth, Div Pediat Clin Pharmacol, Dept Pediat, 1400 Jackson St,Room J304 Molly Blank Bldg, Denver, CO 80206 USA.
EM szeflers@njhealth.org
FU NIH/NHLBI Childhood Management Program (CAMP); NHLBI Childhood Asthma
Research and Education (CARE); NIH/NHLBI Asthma Clin Res Network (ACRN);
NIH/NIAID Inner City Asthma Consortium (ICAC); GlaxoSmithKline;
NJH.NHLBI Asthma Net; NEEHS/EPA Childhood Environmental Health Center;
NIH/NIAID; NIH/University of Wisconsin and Novartis; Public Health
Services [HR-16048, HL64288, HL 51834, AI-25496, HL081335, HL075416];
National Institutes of Health and National Center for Research Resources
[1 UL1 RR025780]; Colorado Cancer, Cardiovascular, and Pulmonary Disease
Program
FX Companies/Organizations: S. J. Szefler is a consultant for
GlaxoSmithKline, Genentech, Merck, Boehringer-Ingelheim, Novartis,
Schering Plough; and has received research support from the NIH/NHLBI
Childhood Management Program (CAMP), NHLBI Childhood Asthma Research and
Education (CARE), NIH/NHLBI Asthma Clin Res Network (ACRN), NIH/NIAID
Inner City Asthma Consortium (ICAC), GlaxoSmithKline, NJH.NHLBI Asthma
Net, and NEEHS/EPA Childhood Environmental Health Center grant. P. J.
Gergen declares he has no conflicts of interest. H. Mitchell has
received research support from the NIH/NIAID. W. Morgan is a consultant,
and is Chair for the Data Safety Monitoring Board for the Cystic
Fibrosis Foundation; is a consultant and is Chair for the North American
Scientific Advisory Group for the Epidemiologic Study of Cystic Fibrosis
for Genentech; is a consultant for Novartis; and has received research
support from the NIH/University of Wisconsin and Novartis.; Supported in
part by Public Health Services research grants HR-16048, HL64288, HL
51834, AI-25496, HL081335, and HL075416; the Colorado CTSA grant 1 UL1
RR025780 from the National Institutes of Health and National Center for
Research Resources; and the Colorado Cancer, Cardiovascular, and
Pulmonary Disease Program.
NR 27
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U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2010
VL 125
IS 3
BP 521
EP 526
DI 10.1016/j.jaci.2010.01.025
PG 6
WC Allergy; Immunology
SC Allergy; Immunology
GA 573BK
UT WOS:000275883200003
PM 20226288
ER
PT J
AU Togias, A
Fenton, MJ
Gergen, PJ
Rotrosen, D
Fauci, AS
AF Togias, Alkis
Fenton, Matthew J.
Gergen, Peter J.
Rotrosen, Daniel
Fauci, Anthony S.
TI Asthma in the inner city: The perspective of the National Institute of
Allergy and Infectious Diseases
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Inner-city asthma; asthma research funding; cockroach allergy
ID ENVIRONMENTAL INTERVENTION; CHILDREN; IMMUNOTHERAPY; MORBIDITY;
RHINITIS; TRIAL; CARE
AB Since 1991, the National Institute of Allergy and Infectious Diseases (NIAID) has funded four consecutive research initiatives to investigate the problem of high asthma prevalence, morbidity and mortality in poor urban communities. The multi-site studies conducted under these initiatives have identified key risk factors for asthma morbidity and novel interventions to improve asthma control. NIAID focuses its asthma and allergy programs on understanding the interaction of the immune system with allergens and infectious agents and identifying genetic and epigenetic elements that influence the immune system. A key goal in this field is to define mechanisms of immune system deviation and immune tolerance and apply this knowledge to generate improvements in asthma care and allergen immunotherapy. A related goal is to further understand the environmental, social, and immunological elements that impact on the development of inner-city asthma through in-depth characterization and longitudinal follow-up of inner-city children from the time of birth. In the past 5 years, NIH budgetary constraints have imposed many challenges for the academic research community. Despite these constraints, NIAID has maintained its support of a highly productive asthma and allergy research program. (J Allergy Clin Immunol 2010;125:540-4.)
C1 [Togias, Alkis] NIAID, AAIB, DAIT, NIH, Bethesda, MD 20892 USA.
RP Togias, A (reprint author), NIAID, AAIB, DAIT, NIH, 6610 Rockledge Dr, Bethesda, MD 20892 USA.
EM togiasa@niaid.nih.gov
NR 25
TC 33
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U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2010
VL 125
IS 3
BP 540
EP 544
DI 10.1016/j.jaci.2010.01.040
PG 5
WC Allergy; Immunology
SC Allergy; Immunology
GA 573BK
UT WOS:000275883200005
PM 20226290
ER
PT J
AU Kattan, M
Kumar, R
Bloomberg, GR
Mitchell, HE
Calatroni, A
Gergen, PJ
Kercsmar, CM
Visness, CM
Matsui, EC
Steinbach, SF
Szefler, SJ
Sorkness, CA
Morgan, WJ
Teach, SJ
Gan, VN
AF Kattan, Meyer
Kumar, Rajesh
Bloomberg, Gordon R.
Mitchell, Herman E.
Calatroni, Agustin
Gergen, Peter J.
Kercsmar, Carolyn M.
Visness, Cynthia M.
Matsui, Elizabeth C.
Steinbach, Suzanne F.
Szefler, Stanley J.
Sorkness, Christine A.
Morgan, Wayne J.
Teach, Stephen J.
Gan, Vanthaya N.
TI Asthma control, adiposity, and adipokines among inner-city adolescents
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Obesity; asthma; adipokines; leptin; adiponectin
ID BODY-MASS INDEX; QUALITY-OF-LIFE; AIRWAY INFLAMMATION; PROSPECTIVE
COHORT; EMERGENCY-DEPARTMENT; CHILDHOOD OBESITY; NONOBESE CHILDREN;
INCIDENT ASTHMA; SEX-DIFFERENCES; PLASMA-PROTEIN
AB Background: There is an association between adiposity and asthma prevalence, but the relationship to asthma control is unclear.
Objectives: We sought to understand the relationships among adiposity, sex, and asthma control in inner-city adolescents with asthma.
Methods: We prospectively followed 368 adolescents with moderate-to-severe asthma (ages 12-20 years) living in 10 urban areas for 1 year. Asthma symptoms and exacerbations were recorded, and pulmonary function and exhaled nitric oxide levels were measured every 6 weeks. Adiposity measures (body mass index [BMI] and dual-energy X-ray absorptiometric scans) were made, and blood was collected for measurement of allergy markers, adiponectin, leptin, TNF-alpha, IL-6, and C-reactive protein levels.
Results: More than 60% of female subjects and 50% of male subjects were above the 85th percentile of BMI for age. Higher BMI was associated with more symptom days (R = 0.18, P = .02) and exacerbations (R = 0.18, P = .06) among female subjects only. Adiponectin was inversely related to asthma symptoms (R = 0.18, P < .05) and exacerbations (R = 0.20, P < .05) and positively with FEN/1/forced vital capacity ratio (R = 0.15, P < .05) in male subjects only independent of body size. There was no relationship between adiposity or adipokines and total IgE levels, blood eosinophil counts, and exhaled nitric oxide levels. Dual-energy X-ray absorptiometry provided little additional value in relating adiposity to asthma outcome in this population of adolescents.
Conclusion: Adiposity is associated with poorer asthma control in female subjects. Adiponectin is associated with improved asthma control in male subjects. (J Allergy Clin Immunol 2010;125:584-92.)
C1 [Kattan, Meyer] Columbia Univ, Med Ctr, Coll Phys & Surg, Dept Pediat Pulmonol, New York, NY 10032 USA.
[Kumar, Rajesh] Childrens Mem Hosp, Div Allergy Immunol, Chicago, IL 60614 USA.
[Bloomberg, Gordon R.] Washington Univ, Dept Pediat, Div Allergy Immunol & Pulm Med, St Louis, MO 63130 USA.
[Mitchell, Herman E.; Calatroni, Agustin; Visness, Cynthia M.] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Gergen, Peter J.] NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA.
[Kercsmar, Carolyn M.] Cincinnati Childrens Hosp, Dept Pediat, Div Pulm Med, Ctr Med, Cincinnati, OH 45229 USA.
[Matsui, Elizabeth C.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA.
[Steinbach, Suzanne F.] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA.
[Szefler, Stanley J.] Univ Colorado Hlth Sci, Denver, CO USA.
[Szefler, Stanley J.] Natl Jewish Hlth, Dept Pediat, Div Allergy & Immunol, Denver, CO USA.
[Szefler, Stanley J.] Natl Jewish Hlth, Dept Pediat, Div Pediat Clin Pharmacol, Denver, CO USA.
[Sorkness, Christine A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Allergy Pulm & Crit Care Med, Madison, WI 53706 USA.
[Sorkness, Christine A.] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA.
[Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA.
[Morgan, Wayne J.] Univ Arizona, Coll Med, Dept Pediat, Tucson, AZ USA.
[Gan, Vanthaya N.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
RP Kattan, M (reprint author), Columbia Univ, Med Ctr, Coll Phys & Surg, Dept Pediat Pulmonol, 3959 Broadway,CHC 7-701, New York, NY 10032 USA.
EM mk2833@columbia.edu
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [NO1-AI-25496, NO1-JAI-25482]; National Center for
Research Resources, National Institutes of Health [RR00052, M01RR00533,
MO1RR00071, 5UL1RR024992-02, 5M01RR020359-04]; National Heart, Lung. and
Blood Institute; National Institutes of Health/National Institute of
Allergy and Infectious Diseases; Sepracor; NIH/NHLBI Childhood
Management Program (CAMP); NHLBI Childhood Asthma Research and Education
(CARE); NIH/NHLBI Asthma Clin Res Network (ACRN); NIH/NIAID Inner City
Asthma Consortium (ICAC); GlaxoSmithKline; NJH/NHLBI Asthma Net;
NEEHS/EPA Childhood Environmental Health Center; Schering Plough;
Sanofi; NIH/University of Wisconsin; Novartis; Baylor College of
Medicine/Texas Department of State Health Services
FX This project has been funded in whole or in part with Federal funds from
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health, under contract numbers NO1-AI-25496 and
NO1-JAI-25482 and from the National Center for Research Resources,
National Institutes of Health, under grants RR00052, M01RR00533,
MO1RR00071, 5UL1RR024992-02, and 5M01RR020359-04.; Disclosure of
potential conflict of interest: J. Kumar has received research support
from the National Heart, Lung. and Blood Institute; is President of the
Illinois Society of Allergy, Asthma. and Immunology; and is a member of
the American Thoracic Society. G. R. Bloomberg has received research
support from the National Institutes of Health/National Institute of
Allergy and Infectious Diseases. H. Mitchell has received research
support from the National Institutes of Health/National Institute of
Allergy and Infectious Diseases. C. M. Kercsmar is on the Speakers'
Bureau for Merck; and has received research support from Sepracor. E.
Matsui has received research support from the National Institutes of
Health. S. Steinback has received research support from the National
Institutes of Health/National Institute of Allergy and Infectious
Diseases; and has served as an expert witness on the topic of
bronchiolitis. S. J. Szefler is a Consultant for GlaxoSmithKline,
Genentech, Merck, Boeringher-Ingelheim, Novartis, and Schering Plough;
has received research support from the NIH/NHLBI Childhood Management
Program (CAMP), NHLBI Childhood Asthma Research and Education (CARE),
NIH/NHLBI Asthma Clin Res Network (ACRN), NIH/NIAID Inner City Asthma
Consortium (ICAC), GlaxoSmithKline, NJH/NHLBI Asthma Net, and NEEHS/EPA
Childhood Environmental Health Center Grant. C. A. Sorkness is on the
Advisory Board for GlaxoSmithKline, Schering Plough, AstraZeneca, and
Novartis; and has received research support from Schering Plough and
Sanofi. W. J. Morgan is a consultant for, and Chair of the Data Safety
Monitoring Board for the Cystic Fibrosis Foundation; is a Consultant and
Chair of the North American Scientific Advisory Group for the
Epidemiologic Study of Cystic Fibrosis for Genentech; is a Consultant
for Novartis; has received research support from the NIH/University of
Wisconsin and Novartis. S. J. Teach has received research support from
Novartis; has served as an expert witness on the topics of wheezing,
pneumonia, and dehydration; and is a volunteer for the NIAID Food
Allergy Guidelines. V. N. Gan has received research support from Baylor
College of Medicine/Texas Department of State Health Services. The other
authors declare they have no conflicts of interest.
NR 66
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U1 1
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2010
VL 125
IS 3
BP 584
EP 592
DI 10.1016/j.jaci.2010.01.053
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA 573BK
UT WOS:000275883200012
PM 20226295
ER
PT J
AU Pongracic, JA
O'Connor, GT
Muilenberg, ML
Vaughn, B
Gold, DR
Kattan, M
Morgan, WJ
Gruchalla, RS
Smartt, E
Mitchell, HE
AF Pongracic, Jacqueline A.
O'Connor, George T.
Muilenberg, Michael L.
Vaughn, Ben
Gold, Diane R.
Kattan, Meyer
Morgan, Wayne J.
Gruchalla, Rebecca S.
Smartt, Ernestine
Mitchell, Herman E.
TI Differential effects of outdoor versus indoor fungal spores on asthma
morbidity in inner-city children
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma; inner city; airborne fungi; indoor fungi; outdoor fungi; fungal
allergens; children
ID RESPIRATORY SYMPTOMS; RESIDENTIAL CHARACTERISTICS; ENVIRONMENTAL
INTERVENTION; ASPERGILLUS-FUMIGATUS; URBAN COMMUNITIES; HOUSE DUST; 1ST
YEAR; F-I; ALLERGENS; EXPOSURE
AB Background: Although sensitization to fungal allergens is prevalent in inner-city children with asthma, the relationship between fungal exposure and morbidity is poorly understood.
Objective: We examined relationships between fungal sensitization, exposure, and asthma morbidity in inner-city children.
Methods: Participants were 5 to 11 years old and enrolled in the Inner-City Asthma Study. This report includes the subset of children with at least 1 positive skin test (PST) response to a fungal allergen extract; for these children, indoor and outdoor airborne culturable fungi levels were measured at baseline and throughout the 2-year study. Asthma morbidity measures were collected prospectively. The primary outcome was symptom days per 2 weeks.
Results: At baseline, children with a PST response to a fungal allergen extract had significantly more symptom days compared with those without a PST response to any fungal allergen extract (6.3 vs 5.7 days per 2 weeks, P = .04). During the study, increases in total fungal exposure and indoor Penicillium species exposure were associated with increases in symptom days and asthma-related unscheduled visits. Indoor exposures to total fungi and to Penicillium species were associated with significant increases in unscheduled visits, even after controlling for outdoor fungal levels. Adverse effects associated with exposure to a specific fungus were stronger among children with PST responses to that fungal allergen extract compared with those seen in children with negative skin test responses.
Conclusion: Outdoor fungal exposure is primarily associated with increased asthma symptoms and increased risk of exacerbations in this population. (J Allergy Clin Immunol 2010;125:593-9.)
C1 [Pongracic, Jacqueline A.] Northwestern Univ, Feinburg Sch Med, Childrens Mem Hosp, Chicago, IL 60611 USA.
[O'Connor, George T.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Muilenberg, Michael L.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA.
[Vaughn, Ben; Mitchell, Herman E.] Rho Inc, Chapel Hill, NC USA.
[Gold, Diane R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Kattan, Meyer] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Morgan, Wayne J.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA.
[Gruchalla, Rebecca S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Smartt, Ernestine] NIAID, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Pongracic, JA (reprint author), 2300 Childrens Plaza,60, Chicago, IL 60614 USA.
EM j-pongracic@northwestern.edu
OI O'Connor, George/0000-0002-6476-3926
FU National Institute of Allergy and Infectious Diseases [AI/ES-39769,
AI/ES-39900, AI/ES39902, AI/ES-39789, AI/ES-39901, AI/ES-39761,
AI/ES-39785, AI/ES-39776]; National Institutes of Environmental Health
Sciences; National Institutes of Health, Department of Health and Human
Services; National Center for Research Resources, National Institutes of
Health, Department of Health and Human Services [M01 RR00533]; National
Institute of Allergy and Infectious Diseases and the Food Allergy
Project; National Institutes of Health; US Environmental Protection
Agency; Novartis
FX Supported by National Institutes of Health grants AI/ES-39769,
AI/ES-39900, AI/ES39902, AI/ES-39789, AI/ES-39901, AI/ES-39761,
AI/ES-39785, and AI/ES-39776 from the National Institute of Allergy and
Infectious Diseases and the National Institutes of Environmental Health
Sciences. National Institutes of Health, Department of Health and Human
Services, and by grant M01 RR00533 front the National Center for
Research Resources, National Institutes of Health, Department of Health
and Human Services.; Disclosure of potential conflict of interest: J. A.
Pongracic receives research support front the National Institute of
Allergy and Infectious Diseases and the Food Allergy Project. G. T.
O'Connor is a consultant for Sepracor, Inc, and Pulmatrix, Inc. M. L.
Muilenberg receives research support from the National Institutes of
Health. B. Vaughn is employed by Rho, Inc. D. R. Gold receives grant
support from the National Institutes of Health and the US Environmental
Protection Agency. W. J. Morgan is a consultant for the Cystic Fibrosis
Foundation and Genentech. Inc, and receives grant support from the
National Institutes of Health. R. S. Gruchalla is a consultant for
GlaxoSmithKline, receives research support front Novartis, and is on the
Board of Directors for ABAI. H. E. Mitchell is employed by Rho, Inc, and
receives research support from the National Institute of Allergy and
Infectious Diseases and the National Institutes of Environmental Health
Sciences. The rest of the authors have declared that they have no
conflict of interest.
NR 37
TC 46
Z9 48
U1 0
U2 7
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2010
VL 125
IS 3
BP 593
EP 599
DI 10.1016/j.jaci.2009.10.036
PG 7
WC Allergy; Immunology
SC Allergy; Immunology
GA 573BK
UT WOS:000275883200013
PM 20132971
ER
PT J
AU van der Kleij, H
Charles, N
Karimi, K
Mao, YK
Foster, J
Janssen, L
Yang, PC
Kunze, W
Rivera, J
Bienenstock, J
AF van der Kleij, Hanneke
Charles, Nicolas
Karimi, Khalil
Mao, Yu-Kang
Foster, Jane
Janssen, Luke
Yang, Ping Chang
Kunze, Wolfgang
Rivera, Juan
Bienenstock, John
TI Evidence for neuronal expression of functional Fc (epsilon and gamma)
receptors
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID SENSORY NEURONS; ACTIVATION; CELLS; MICE; RIV
C1 [van der Kleij, Hanneke; Mao, Yu-Kang; Foster, Jane; Janssen, Luke; Yang, Ping Chang; Kunze, Wolfgang; Bienenstock, John] McMaster Univ, Brain Body Inst, St Josephs Healthcare Hamilton, Hamilton, ON L8S 4L8, Canada.
[van der Kleij, Hanneke; Karimi, Khalil; Mao, Yu-Kang; Foster, Jane; Janssen, Luke; Yang, Ping Chang; Kunze, Wolfgang; Bienenstock, John] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8S 4L8, Canada.
[Charles, Nicolas; Rivera, Juan] NIAMSD, Lab Immune Cell Signaling, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP van der Kleij, H (reprint author), McMaster Univ, Brain Body Inst, St Josephs Healthcare Hamilton, Hamilton, ON L8S 4L8, Canada.
EM bienens@mcmaster.ca
RI Charles, Nicolas/P-5430-2014
OI Charles, Nicolas/0000-0002-5416-5834
FU Intramural NIH HHS [Z01 AR041101-15]
NR 9
TC 23
Z9 23
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2010
VL 125
IS 3
BP 757
EP 760
DI 10.1016/j.jaci.2009.10.054
PG 4
WC Allergy; Immunology
SC Allergy; Immunology
GA 573BK
UT WOS:000275883200041
PM 20132972
ER
PT J
AU Salo, PM
Zeldin, DC
AF Salo, Paeivi M.
Zeldin, Darryl C.
TI Cats and dogs: An attractive remedy versus atopy? Reply
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID ALLERGEN; HOMES
C1 [Salo, Paeivi M.; Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Natl Inst Hlth, Res Triangle Pk, NC USA.
RP Salo, PM (reprint author), Natl Inst Environm Hlth Sci, Natl Inst Hlth, Res Triangle Pk, NC USA.
EM zeldin@niehs.nih.gov
NR 9
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2010
VL 125
IS 3
BP 765
EP 766
DI 10.1016/j.jaci.2009.11.012
PG 2
WC Allergy; Immunology
SC Allergy; Immunology
GA 573BK
UT WOS:000275883200046
PM 20138349
ER
PT J
AU Smith, ML
Shimomura, E
Paul, BD
Cone, EJ
Darwin, WD
Huestis, MA
AF Smith, Michael L.
Shimomura, Eric
Paul, Buddha D.
Cone, Edward J.
Darwin, W. David
Huestis, Marilyn A.
TI Urinary Excretion of Ecgonine and Five Other Cocaine Metabolites
Following Controlled Oral, Intravenous, Intranasal, and Smoked
Administration of Cocaine
SO JOURNAL OF ANALYTICAL TOXICOLOGY
LA English
DT Article
C1 [Darwin, W. David; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 20892 USA.
[Smith, Michael L.; Shimomura, Eric; Paul, Buddha D.] Armed Forces Inst Pathol, Div Forens Toxicol, Armed Forces Med Examiner Syst, Rockville, MD USA.
[Cone, Edward J.] Johns Hopkins Sch Med, Baltimore, MD USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD 20892 USA.
EM mhuestis@intra.nida.nih.gov
FU National Institutes of Health, National Institute on Drug Abuse
FX The authors thank the American Registry of Pathology and the Intramural
Research Program, National Institutes of Health, National Institute on
Drug Abuse for support.
NR 10
TC 11
Z9 12
U1 0
U2 5
PU PRESTON PUBL INC
PI NILES
PA 6600 W TOUHY AVE, NILES, IL 60714-4588 USA
SN 0146-4760
J9 J ANAL TOXICOL
JI J. Anal. Toxicol.
PD MAR
PY 2010
VL 34
IS 2
BP 57
EP 63
PG 7
WC Chemistry, Analytical; Toxicology
SC Chemistry; Toxicology
GA 580OO
UT WOS:000276459000001
PM 20223096
ER
PT J
AU Maggio, M
Lauretani, F
Ceda, GP
Bandinelli, S
Basaria, S
Paolisso, G
Giumelli, C
Luci, M
Najjar, SS
Metter, EJ
Valenti, G
Guralnik, J
Ferrucci, L
AF Maggio, Marcello
Lauretani, Fulvio
Ceda, Gian Paolo
Bandinelli, Stefania
Basaria, Shehzad
Paolisso, Giuseppe
Giumelli, Claudio
Luci, Michele
Najjar, Samer S.
Metter, E. Jeffrey
Valenti, Giorgio
Guralnik, Jack
Ferrucci, Luigi
TI Estradiol and Metabolic Syndrome in Older Italian Men: The InCHIANTI
Study
SO JOURNAL OF ANDROLOGY
LA English
DT Article
DE Androgen; andropause
ID ENDOGENOUS SEX-HORMONES; ELDERLY-MEN; CARDIOVASCULAR-DISEASE; OBESE MEN;
TESTOSTERONE; ASSOCIATION; SERUM; AGE; RISK; POPULATION
AB The increasing prevalence of metabolic syndrome (MS) with age in older men has been linked with decreasing testosterone levels. Interestingly, while testosterone levels decline with age, estradiol (E2) levels remain relatively stable, resulting in a decreased testosterone:E2 ratio. Because E2 levels tend to be elevated in morbid obesity, insulin resistance, and diabetes, it is reasonable to hypothesize that high E2 levels are associated with MS in older men. We studied the relationship of total and free E2 with MS after adjustment for multiple confounders, including age, BMI, smoking, alcohol consumption, physical activity, interleukin-6 (IL-6), fasting insulin, and testosterone. Men 65 years or older (age range, 65-96; n = 452) had complete data on E2, testosterone, fasting insulin, sex hormone binding globulin, IL-6, and albumin. Concentrations of free E2 and free testosterone were calculated using the mass action equations. MS was defined according to Adult Treatment Panel III (ATP-III). Participants with MS had significantly higher serum free and total E2 (P < .001) (P = .003). After adjusting for confounders, including age, smoking, alcohol consumption, physical activity, log(IL-6), and log(insulin), participants with higher log(total E2) (odds ratio [OR], 2.31; 95% confidence interval [95% CI], 1.39-4.70; P = .02) and higher log(free E2) (OR, 2.69; 1.38-5.24; P < .001) had an increased risk of having MS. Log(free E2) (P = .04) maintained significant correlation with MS, even after further adjustment for BMI. In older men, high E2 is independently associated with MS. Whether confirmed in other studies, assessment of E2 should be also considered in older men. Whether changes in this hormonal pattern play a role in the development of MS should be further tested in longitudinal studies.
C1 [Maggio, Marcello; Ceda, Gian Paolo; Giumelli, Claudio; Luci, Michele; Valenti, Giorgio] Univ Parma, Sect Geriatr, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy.
[Maggio, Marcello; Basaria, Shehzad; Metter, E. Jeffrey; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Najjar, Samer S.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
[Lauretani, Fulvio] Tuscany Reg Hlth Agcy, Florence, Italy.
[Bandinelli, Stefania] ASF Florence, Geriatr Rehabil Unit, Florence, Italy.
[Basaria, Shehzad] Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Div Endocrinol,Dept Med, Baltimore, MD USA.
[Paolisso, Giuseppe] Univ Naples Federico II, Dept Geriatr Med & Metab Dis 2, I-80138 Naples, Italy.
[Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
RP Maggio, M (reprint author), Univ Parma, Sect Geriatr, Dept Internal Med & Biomed Sci, Via Gramsci 14, I-43100 Parma, Italy.
EM marcellomaggio2001@yahoo.it; ferruccilu@grc.nia.nih.gov
RI Lauretani, Fulvio/K-5115-2016
OI Ceda, Gian Paolo/0000-0002-9648-8295; Paolisso,
Giuseppe/0000-0002-2137-455X; Lauretani, Fulvio/0000-0002-5287-9972
FU Italian Ministry of Health; US National Institute on Aging
[N01-AG-916413, N01-AG-821336, 263 MD 916413, 263 MD 821336]
FX The InCHIANTI Study was supported as a "targeted project" (ICS
110.1/RS97.71) by the Italian Ministry of Health and, in part, by the US
National Institute on Aging (contracts N01-AG-916413 and N01-AG-821336)
and by the Intramural Research Program of the US National Institute on
Aging (contracts 263 MD 916413 and 263 MD 821336). The funding
institutes had no role in the design, methods, subject recruitment, data
collection, analysis, or preparation of manuscript or in the decision to
submit the manuscript for publication.
NR 40
TC 24
Z9 25
U1 1
U2 1
PU AMER SOC ANDROLOGY, INC
PI LAWRENCE
PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA
SN 0196-3635
EI 1939-4640
J9 J ANDROL
JI J. Androl.
PD MAR-APR
PY 2010
VL 31
IS 2
BP 155
EP 162
DI 10.2164/jandrol.108.006098
PG 8
WC Andrology
SC Endocrinology & Metabolism
GA 573NH
UT WOS:000275920100009
PM 19059904
ER
PT J
AU Moldenhauer, JS
Lai, YL
Schatz, M
Wise, R
Landon, MB
Newman, RB
Rouse, DJ
Simhan, HN
Leveno, KJ
Miodovnik, M
Lindheimer, MD
Wapner, RJ
Varner, MW
O'Sullivan, MJ
Conway, DL
AF Moldenhauer, Julie S.
Lai, Yinglei
Schatz, Michael
Wise, Robert
Landon, Mark B.
Newman, Roger B.
Rouse, Dwight J.
Simhan, Hyagriv N.
Leveno, Kenneth J.
Miodovnik, Menachem
Lindheimer, Marshall D.
Wapner, Ronald J.
Varner, Michael W.
O'Sullivan, Mary Jo
Conway, Deborah L.
CA Eunice Kennedy Shriver Natl Inst C
TI Influence of Maternal Asthma and Asthma Severity on Newborn Morphometry
SO JOURNAL OF ASTHMA
LA English
DT Article
DE asthma; neonatal morphometry; pregnancy
ID BIRTH-WEIGHT; PERINATAL OUTCOMES; HIGH-ALTITUDE; PREGNANCY; GROWTH;
WOMEN
AB Objective. To determine if maternal asthma or asthma severity affects newborn morphometry. Study Design. A secondary analysis was performed on data collected in a multicenter prospective observational cohort study of asthma in pregnancy. Patients enrolled included women with asthma stratified by severity of disease and controls. Asthma severity was defined according to the classification proposed by the National Asthma Education Program (NAEP) Report of the Working Group on Asthma and Pregnancy, modified to include medication requirements. Newborn morphometry measurements included birth weight (BW) and multiples of the median birth weight (BW-MOM), head circumference (HC), length (L), HC:BW ratio, and ponderal index (PI). Results. Of 2480 patients there were 828 nonasthmatic controls, 828 with mild, 775 with moderate, and 49 with severe disease. Comparing all groups, there were statistically significant differences in maternal age (p < .001), race (p = .005), parity (p = .006), prepregnancy weight (p = .028), and medical care source (p = .001), with the severe asthma group having the highest mean maternal age (25.7 years), and proportion of African Americans (71.4%), proportion of multiparous patients (63.3%), and proportion of patients receiving government assistance (85.7%). When the control group was excluded from the comparisons, differences in prepregnancy weight and medical care source were no longer significant. BW-MOM and L did not differ between groups. The HC:BW ratio increased with asthma severity (p = .029) and was increased compared to controls (p = .010). This remained significant after controlling for confounding variables (both p <.001). HC was statistically significantly different between all groups (p = .032), as well as among women with varying degrees of asthma severity (p = .013), which was not clinically significant. After covariates adjustment, HC was not significantly different among all groups (p = .228), nor the asthma groups (p = .144). Conclusion. Asthma severity is associated with an increased HC:BW ratio. Severity was not found to impact HC, BW-MOM, L, or PI independently. However, the magnitudes of the effects were too small to suggest a clinically significant effect of asthma on neonatal morphometry in this large prospectively studied sample. 0.01). White and Asian BCS reported more endoscopic examinations (58.9% versus 46.5%; P < 0.001; 61.2% versus 38.4%; P < 0.05) than the comparison population. After adjustment for demographic, socioeconomic, and health status differences, screening rates for BCS showed higher mammography use (odds ratio [OR] 1.97; 95% confidence interval [95% CI] 1.58-2.46), Pap test (OR 1.44; 95% CI 1.22-1.70), and endoscopic use (OR 1.35; 95% CI 1.16-1.58), but not higher for FOBT.
Conclusions Even though BCS generally had higher cancer screening rates than women without a cancer history, racial/ethnic differences exist among the type of test received. Narrowing these differences is essential to lessen disparities.
Implications for cancer survivors The need for screening guidelines for BCS remains a high priority. Survivors would benefit from the frequency of screening for all cancers post-treatment.
C1 [Breslau, Erica S.; Moser, Richard P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Jeffery, Diana D.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Davis, William W.] NCI, Stat Res & Applicat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[McNeel, Timothy S.] Informat Management Serv Inc, Silver Spring, MD USA.
[Hawley, Sarah] Univ Michigan, Div Gen Med, Ann Arbor, MI 48109 USA.
RP Breslau, ES (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM breslaue@mail.nih.gov
NR 62
TC 11
Z9 11
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1932-2259
J9 J CANCER SURVIV
JI J. Cancer Surviv.-Res. Pract.
PD MAR
PY 2010
VL 4
IS 1
BP 1
EP 14
DI 10.1007/s11764-009-0102-5
PG 14
WC Oncology; Social Sciences, Biomedical
SC Oncology; Biomedical Social Sciences
GA 788TV
UT WOS:000292468200001
PM 19882379
ER
PT J
AU Keteyian, SJ
Pina, IL
Hibner, BA
Fleg, JL
AF Keteyian, Steven J.
Pina, Ileana L.
Hibner, Brooks A.
Fleg, Jerome L.
TI Clinical Role of Exercise Training in the Management of Patients With
Chronic Heart Failure
SO JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION
LA English
DT Review
DE cardiac rehabilitation; exercise training; heart failure; HF-ACTION
ID RANDOMIZED CONTROLLED-TRIAL; LEFT-VENTRICULAR DYSFUNCTION;
SKELETAL-MUSCLE FUNCTION; RESISTANCE EXERCISE; HF-ACTION; PROGRAM;
INTOLERANCE; REHABILITATION; PERFORMANCE; PRESCRIPTION
AB Prior exercise research and the recently completed HF-ACTION (Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training) trial indicate that regular exercise represents an effective therapy in the management of patients with stable chronic heart failure (HF) due to left ventricular systolic dysfunction. This review summarizes the results from these studies and provides a guide for prescribing exercise. Regular aerobic-type exercise training improves exercise capacity; does not worsen and may, in fact, mildly improve cardiac function; and partially improves other physiological abnormalities that develop because of chronic HF (eg, autonomic and skeletal muscle function). Regular exercise is safe, improves health status, and modestly reduces (similar to 15%) combined risk for cardiovascular death or HF-related hospitalization. Even greater physiological and clinical benefits appear likely in patients with HF who adhere to a higher volume of exercise (eg, 6 MET-hr per week). The exercise regimen should include an aerobic-type activity performed at least 30 minutes, 5 or more days per week, and at an intensity approximating 55% to 80% of heart rate reserve. Resistance training should be considered for patients who first demonstrate they are able to tolerate aerobic exercise training. Common to other interventions that also rely on human behavior, long-term adherence to exercise in patients with HF remains a challenge and requires additional research to determine strategies aimed at improving compliance. Areas of needed research include identifying which patient subgroup(s) benefits the most and determination of the optimal intensity, duration, and frequency of exercise needed to maximize clinical benefits and attenuate fatigue.
C1 [Keteyian, Steven J.; Hibner, Brooks A.] Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA.
[Pina, Ileana L.] Case Western Univ, Sch Med, Vet Adm Med Ctr, Cleveland, OH USA.
[Fleg, Jerome L.] NHLBI, Div Cardiovasc Dis, Bethesda, MD 20892 USA.
RP Keteyian, SJ (reprint author), Henry Ford Hosp, Dept Med, 6525 2nd Ave, Detroit, MI 48202 USA.
EM sketeyi1@hfhs.org
NR 67
TC 30
Z9 40
U1 1
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1932-7501
J9 J CARDIOPULM REHABIL
JI J. Cardiopulm. Rehabil. Prev.
PD MAR-APR
PY 2010
VL 30
IS 2
BP 67
EP 76
DI 10.1097/HCR.0b013e3181d0c1c1
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 575HH
UT WOS:000276057600001
PM 20216359
ER
PT J
AU Dikovskaya, D
Li, ZY
Newton, IP
Davidson, I
Hutchins, JRA
Kalab, P
Clarke, PR
Nathke, IS
AF Dikovskaya, Dina
Li, Zhuoyu
Newton, Ian P.
Davidson, Iain
Hutchins, James R. A.
Kalab, Petr
Clarke, Paul R.
Naethke, Inke S.
TI Microtubule assembly by the Apc protein is regulated by
importin-beta-RanGTP
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Adenomatous polyposis coli; Importin-beta; Microtubules; Mitotic spindle
ID TUMOR-SUPPRESSOR PROTEIN; POLYPOSIS-COLI PROTEIN; GUANINE-NUCLEOTIDE
EXCHANGE; MITOTIC SPINDLE; CELL-MIGRATION; NUCLEAR IMPORT; IN-VITRO;
BINDING; IDENTIFICATION; MITOSIS
AB Mutations in the tumour suppressor Adenomatous polyposis coli (Apc) initiate most sporadic colorectal cancers. Apc is implicated in regulating microtubule (MT) dynamics in interphase and mitosis. However, little is known about the underlying mechanism or regulation of this Apc function. We identified importin-beta as a binding partner of Apc that regulates its effect on MTs. Apc binds importin-beta in vitro and in Xenopus egg extracts, and RanGTP inhibits this interaction. The armadillo-like repeat domain of importin-beta binds to the middle of Apc, where it can compete with beta-catenin. In addition, two independent sites in the C terminus of Apc bind the N-terminal region of importin-beta. Binding to importin-beta reduces the ability of Apc to assemble and bundle MTs in vitro and to promote assembly of microtubule asters in Xenopus egg extracts, but does not affect the binding of Apc to MTs or to EB1. Depletion of Apc decreases the formation of cold-stable spindles in Xenopus egg extracts. Importantly, the ability of purified Apc to rescue this phenotype was reduced when it was constitutively bound to importin-beta. Thus, importin-beta binds to Apc and negatively regulates the MT-assembly and spindle-promoting activity of Apc in a Ran-regulatable manner.
C1 [Dikovskaya, Dina; Li, Zhuoyu; Newton, Ian P.; Davidson, Iain; Naethke, Inke S.] Univ Dundee, Div Cell & Dev Biol, Coll Life Sci, Dundee DD1 5EH, Scotland.
[Hutchins, James R. A.; Clarke, Paul R.] Univ Dundee, Biomed Res Inst, Coll Med Dent & Nursing, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Scotland.
[Kalab, Petr] NCI, Bethesda, MD 20892 USA.
RP Dikovskaya, D (reprint author), Univ Dundee, Div Cell & Dev Biol, Coll Life Sci, Dundee DD1 5EH, Scotland.
EM d.dikovskaya@dundee.ac.uk
RI Clarke, Paul/B-1684-2009; Kalab, Petr/B-2478-2009
FU Cancer Research UK
FX We thank Ewan Morrison for providing the EB1 expression construct, Bill
Hunter and members of the Nathke laboratory for helpful discussions,
Paul Appleton for help with imaging, Holly Goodson for advice with the
light scattering assay, and Alan Fairlamb for providing a
spectrophotometer. This work was funded by a program grant from Cancer
Research UK to I. S. N.
NR 38
TC 15
Z9 15
U1 0
U2 2
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD MAR 1
PY 2010
VL 123
IS 5
BP 736
EP 746
DI 10.1242/jcs.060806
PG 11
WC Cell Biology
SC Cell Biology
GA 556MH
UT WOS:000274594700011
PM 20144988
ER
PT J
AU Peters, N
Perez, DE
Song, MH
Liu, Y
Muller-Reichert, T
Caron, C
Kemphues, KJ
O'Connell, KF
AF Peters, Nathaniel
Perez, Dahlia E.
Song, Mi Hye
Liu, Yan
Mueller-Reichert, Thomas
Caron, Cathy
Kemphues, Kenneth J.
O'Connell, Kevin F.
TI Control of mitotic and meiotic centriole duplication by the Plk4-related
kinase ZYG-1
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Centrosome amplification; Meiosis; ZYG-1; C. elegans
ID SEX-DETERMINATION GENE; CAENORHABDITIS-ELEGANS; CENTROSOME DUPLICATION;
C-ELEGANS; CELL-CYCLE; PROTEIN-SYNTHESIS; DROSOPHILA SPD-2;
SPERMATOGENESIS; RECRUITMENT; BIOGENESIS
AB Centriole duplication is of crucial importance during both mitotic and male meiotic divisions, but it is currently not known whether this process is regulated differently during the two modes of division. In Caenorhabditis elegans, the kinase ZYG-1 plays an essential role in both mitotic and meiotic centriole duplication. We have found that the C-terminus of ZYG-1 is necessary and sufficient for targeting to centrosomes and is important for differentiating mitotic and meiotic centriole duplication. Small truncations of the C-terminus dramatically lower the level of ZYG-1 at mitotic centrosomes but have little effect on the level of ZYG-1 at meiotic centrosomes. Interestingly, truncation of ZYG-1 blocks centrosome duplication in the mitotic cycle but leads to centrosome amplification in the meiotic cycle. Meiotic centriole amplification appears to result from the overduplication of centrioles during meiosis I and leads to the formation of multipolar meiosis II spindles. The extra centrioles also disrupt spermatogenesis by inducing the formation of supernumerary fertilization-competent spermatids that contain abnormal numbers of chromosomes and centrioles. Our data reveal differences in the regulation of mitotic and meiotic centrosome duplication, particularly with regard to ZYG-1 activity, and reveal an important role for centrosomes in spermatid formation.
C1 [Peters, Nathaniel; Perez, Dahlia E.; Song, Mi Hye; Liu, Yan; O'Connell, Kevin F.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
[Mueller-Reichert, Thomas] Max Planck Inst Mol Cell Biol & Genet MPI CBG, D-01307 Dresden, Germany.
[Caron, Cathy; Kemphues, Kenneth J.] Cornell Univ, Sect Genet & Dev, Ithaca, NY 14853 USA.
RP O'Connell, KF (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
EM kevino@intra.niddk.nih.gov
OI Song, Mi Hye/0000-0001-8326-6602
FU NIH National Center for Research Resources (NCRR); Shohei Mitani and the
National Bioresource Project-Japan; National Institutes Health (NIH);
National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank Jenny Hinshaw and Jurgen Heymann for help with electron
microscopy, Nina Peel, Nicholas Miliaras, and Andy Golden for comments
on the manuscript, and Catherine Kemp for technical assistance. Strains
were provided by the Caenorhabditis Genetics Center, which is funded by
the NIH National Center for Research Resources (NCRR), and by Shohei
Mitani and the National Bioresource Project-Japan. This work was
supported by the Intramural Research Program of the National Institutes
Health (NIH) and by the National Institute of Diabetes and Digestive and
Kidney Diseases. Deposited in PMC for release after 12 months.
NR 53
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Z9 19
U1 0
U2 3
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD MAR 1
PY 2010
VL 123
IS 5
BP 795
EP 805
DI 10.1242/jcs.050682
PG 11
WC Cell Biology
SC Cell Biology
GA 556MH
UT WOS:000274594700017
PM 20144993
ER
PT J
AU Clark, K
Howe, JD
Pullar, CE
Green, JA
Artym, VV
Yamada, KM
Critchley, DR
AF Clark, Katherine
Howe, Jonathan D.
Pullar, Christine E.
Green, J. Angelo
Artym, Vira V.
Yamada, Kenneth M.
Critchley, David R.
TI Tensin 2 Modulates Cell Contractility in 3D Collagen Gels Through the
RhoGAP DLC1
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE TENSIN; FIBRONECTIN MATRIX ASSEMBLY; FIBRILLAR ADHESION; COLLAGEN
CONTRACTION; DLC1; RhoGAP
ID FIBRONECTIN MATRIX DEPOSITION; CYTOPLASMIC DOMAIN; TYROSINE
PHOSPHORYLATION; BINDING DOMAINS; FAMILY-MEMBER; PTB DOMAIN; PROTEIN;
ADHESIONS; MIGRATION; IDENTIFICATION
AB Cytoskeletal proteins of the tensin family couple integrins to the actin cytoskeleton. They are found in both focal adhesions and the fibrillar adhesions formed between cells and the fibronectin matrix. There are four tensin genes which encode three large (similar to 200 kDa) tensin isoforms (tensin 1, 2, 3) and one short isoform (cten). However, the subcellular localization and function of the individual isoforms is poorly understood. Using human foreskin fibroblasts (HFFs), and imaging on both fixed and live cells, we show that GFP-tensin 2 is enriched in dynamic focal adhesions at the leading edge of the cell, whereas GFP-tensin 3 translocates rearward, and is enriched in fibrillar adhesions. To investigate the possible role of tensins in cell-matrix remodeling, we used siRNAs to knockdown each tensin isoform. We discovered that tensin 2 knockdown significantly reduced the ability of HFFs to contract 31) collagen gels, whilst no effect on fibronectin fibrillogenesis was observed. This inhibition of collagen gel contraction was associated with a substantial reduction in Rho activity, and it was reversed by depletion of DLC1, a RhoGAP that binds to tensin in focal adhesions. These findings suggest that focal adhesion localized tensin 2 negatively regulates DLC1 to percent Rho-mediated actomyosin contraction and remodeling of collagen fibers. J. Cell. Biochem. 109: 808-817, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Clark, Katherine; Howe, Jonathan D.; Critchley, David R.] Univ Leicester, Dept Biochem, Leicester LE1 9HN, Leics, England.
[Clark, Katherine; Pullar, Christine E.] Univ Leicester, Dept Cell Physiol & Pharmacol, Leicester LE1 9HN, Leics, England.
[Green, J. Angelo; Artym, Vira V.; Yamada, Kenneth M.] NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Artym, Vira V.] Georgetown Univ, Sch Med, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
RP Critchley, DR (reprint author), Univ Leicester, Dept Biochem, Leicester LE1 9HN, Leics, England.
EM drc@le.ac.uk
OI Yamada, Kenneth/0000-0003-1512-6805
FU Wellcome Trust; NIH
FX Grant sponsor: Wellcome Trust and the Intramural Research Program of the
NIH.
NR 46
TC 21
Z9 21
U1 1
U2 10
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD MAR 1
PY 2010
VL 109
IS 4
BP 808
EP 817
DI 10.1002/jcb.22460
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 568XH
UT WOS:000275559000020
PM 20069572
ER
PT J
AU Major, JM
Laughlin, GA
Kritz-Silverstein, D
Wingard, DL
Barrett-Connor, E
AF Major, Jacqueline M.
Laughlin, Gail A.
Kritz-Silverstein, Donna
Wingard, Deborah L.
Barrett-Connor, Elizabeth
TI Insulin-Like Growth Factor-I and Cancer Mortality in Older Men
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID IGF-BINDING PROTEIN-3; FACTOR (IGF)-I; CIRCULATING LEVELS;
PANCREATIC-CANCER; PLASMA-LEVELS; RISK; WOMEN; IGFBP-3; HORMONE; COHORT
AB Context: Although numerous studies have explored the relation of IGF-I with cancer incidence, few have investigated the association between IGF-I and cancer mortality.
Objective: This study examined the association of serum IGF-I levels with cancer mortality in older community-dwelling men.
Design, Setting, and Participants: We conducted a prospective, population-based study of 633 men aged 50 yr and older (mean = 73) who attended a 1988-1991 research clinic visit when blood was obtained for measurement of IGF-I. Participants were followed for vital status through July 2006.
Main Outcome Measure: All-cancer mortality was assessed.
Results: Median IGF-I was 96 ng/ml. During the 18-yr follow-up, 368 deaths occurred; 74 (20%) were due to cancer. Cox regression analyses showed a significant quadratic association between IGF-I and all-cancer mortality (P = 0.039). Higher levels of IGF-I were associated with progressively higher risk of cancer death after adjusting for age, IGF-binding protein-1, adiposity, exercise, current smoking, and previous cancer. The adjusted risk of cancer death was statistically significant for IGF-I levels above 120 ng/ml, with magnitudes of effect ranging from 1.61 [95% confidence interval (CI) = 1.28-2.02] to 2.61 (95% CI = 1.46-4.64). For the 46% of men with IGF-I above 100 ng/ml, the risk of fatal cancer was 1.82 (95% CI = 1.11-2.96) compared to the risk with lower levels.
Conclusions: Higher serum IGF-I in older men is associated with increased risk of cancer death, independent of age, adiposity, lifestyle, and cancer history. These results suggest caution in the use of IGF-I-enhancing therapies to slow the adverse effects of aging. (J Clin Endocrinol Metab 95: 1054-1059, 2010)
C1 [Major, Jacqueline M.; Laughlin, Gail A.; Kritz-Silverstein, Donna; Wingard, Deborah L.; Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, Sch Med, La Jolla, CA 92093 USA.
[Major, Jacqueline M.] NCI, Div Canc, Bethesda, MD 20852 USA.
RP Laughlin, GA (reprint author), Univ Calif San Diego, Dept Family & Prevent Med, Sch Med, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM glaughlin@ucsd.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of Aging [AG028507, AG018339]
FX This work was supported by Grant DK007386-28 from the National Institute
of Diabetes and Digestive and Kidney Diseases and National Institute of
Aging Grants AG028507 and AG018339.
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PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2010
VL 95
IS 3
BP 1054
EP 1059
DI 10.1210/jc.2009-1378
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 564FA
UT WOS:000275197500009
PM 20080855
ER
PT J
AU Bechlioulis, A
Kalantaridou, SN
Naka, KK
Chatzikyriakidou, A
Calis, KA
Makrigiannakis, A
Papanikolaou, O
Kaponis, A
Katsouras, C
Georgiou, I
Chrousos, GP
Michalis, LK
AF Bechlioulis, Aris
Kalantaridou, Sophia N.
Naka, Katerina K.
Chatzikyriakidou, Anthoula
Calis, Karim A.
Makrigiannakis, Antonis
Papanikolaou, Odysseas
Kaponis, Apostolos
Katsouras, Christos
Georgiou, Ioannis
Chrousos, George P.
Michalis, Lampros K.
TI Endothelial Function, But Not Carotid Intima-Media Thickness, Is
Affected Early in Menopause and Is Associated with Severity of Hot
Flushes
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ESTROGEN-RECEPTOR-ALPHA; CARDIOVASCULAR RISK-FACTORS; POSTMENOPAUSAL
WOMEN; GENE POLYMORPHISMS; MYOCARDIAL-INFARCTION; VASOMOTOR FUNCTION;
HORMONE-THERAPY; DYSFUNCTION; DISEASE; HEART
AB Context: The effect of early menopause on indices of vascular function has been little studied.
Objective: The objective of the study was to investigate the effect of early menopause on indices of subclinical atherosclerosis and identify predictors of those indices in early menopausal women.
Design, Setting, and Participants: This was a cross-sectional study that included 120 early menopausal women (age range 42-55 yr, <3 yr in menopause) recruited from the menopause outpatient clinic of an academic hospital and 24 age-matched premenopausal women.
Main Outcome Measures: Brachial artery flow-mediated dilation (FMD) and common carotid intima-media thickness (IMT) were studied. Estrogen receptor (ER)-alpha (rs2234693 T-->C and rs9340799 A-->G) and ER beta (rs4986938 A-->G) polymorphisms were studied in menopausal women.
Results: FMD was significantly lower in early menopausal women compared with controls (5.43 +/- 2.53 vs. 8.74 +/- 3.17%, P < 0.001), whereas IMT did not differ between groups (P > 0.8). Severity of hot flushes was the most important independent predictor for FMD (P < 0.001) in menopausal women. Women with moderate/severe/very severe hot flushes had impaired FMD in contrast to women with no/mild hot flushes or controls. Women with no/mild hot flushes did not differ compared with controls. Age and systolic blood pressure were the main determinants of IMT (both P = 0.004). ER polymorphisms were not associated with vascular parameters.
Conclusions: Impairment of endothelial function is present in the early menopausal years, whereas carotid IMT is not affected. Severity of hot flushes is the main determinant of endothelial dysfunction in early menopausal women. The studied ER polymorphisms do not offer important information on vascular health in early menopause. (J Clin Endocrinol Metab 95: 1199-1206, 2010)
C1 [Naka, Katerina K.; Katsouras, Christos; Michalis, Lampros K.] Univ Ioannina, Dept Cardiol, GR-45110 Ioannina, Greece.
[Chatzikyriakidou, Anthoula; Georgiou, Ioannis] Univ Ioannina, Dept Obstet & Gynecol, Genet Unit, GR-45110 Ioannina, Greece.
[Bechlioulis, Aris; Naka, Katerina K.; Katsouras, Christos; Michalis, Lampros K.] Univ Ioannina, Michaelid Cardiac Ctr, GR-45110 Ioannina, Greece.
[Papanikolaou, Odysseas; Kaponis, Apostolos] Univ Hosp Ioannina, Dept Obstet & Gynecol, Ioannina 45110, Greece.
[Makrigiannakis, Antonis] Univ Crete, Dept Obstet & Gynecol, Iraklion 71409, Greece.
[Chrousos, George P.] Univ Athens, Dept Pediat 1, Athens 15784, Greece.
[Calis, Karim A.] NIH, Dept Pharm, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Michalis, LK (reprint author), Univ Ioannina, Dept Cardiol, GR-45110 Ioannina, Greece.
EM lmihalis@cc.uoi.gr
RI Bechlioulis, Aris/D-4814-2011;
OI Kaponis, Apostolos/0000-0002-4738-2582
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U1 0
U2 3
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2010
VL 95
IS 3
BP 1199
EP 1206
DI 10.1210/jc.2009-2262
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 564FA
UT WOS:000275197500027
PM 20080857
ER
PT J
AU Zemskova, MS
Gundabolu, B
Sinaii, N
Chen, CC
Carrasquillo, JA
Whatley, M
Chowdhury, I
Gharib, AM
Nieman, LK
AF Zemskova, Marina S.
Gundabolu, Bhaskar
Sinaii, Ninet
Chen, Clara C.
Carrasquillo, Jorge A.
Whatley, Millie
Chowdhury, Iffat
Gharib, Ahmed M.
Nieman, Lynnette K.
TI Utility of Various Functional and Anatomic Imaging Modalities for
Detection of Ectopic Adrenocorticotropin-Secreting Tumors
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; SOMATOSTATIN RECEPTOR SCINTIGRAPHY;
CUSHINGS-SYNDROME; CARCINOID-TUMORS; DIFFERENTIAL-DIAGNOSIS;
NEUROENDOCRINE TUMORS; F-18-DOPA PET/CT; HORMONE SYNDROME; LOCALIZATION;
CORTICOTROPIN
AB Context: Because ectopic ACTH-secreting (EAS) tumors are often occult, improved imaging is needed.
Objective: Our objective was to evaluate the utility of [(111)In-DTPA-D-Phe]pentetreotide scintigraphy [octreotide (OCT)] imaging at 6 mCi [low OCT (LOCT)] and 18 mCi [high OCT (HOCT)], [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) and [(18)F]L-3,4-dihydroxyphenylalanine (F-DOPA)-PET scans, computed tomography (CT), and magnetic resonance imaging (MRI).
Design and Setting: The study was a prospective evaluation at a clinical research center.
Patients: Forty-one subjects participated, 30 (17 female) with resected EAS tumors and 11 (three female) with occult EAS, based on inferior petrosal sinus sampling results and imaging studies.
Intervention: Intervention included CT and MRI of neck, chest, abdomen, LOCT (with or without HOCT) and FDG- or F-DOPA-PET without CT every 6-12 months.
Main Outcome Measure: Tumor identification was the main outcome measure.
Results: Most recent results were analyzed. Eighteen patients had tumor resected on the first visit; otherwise, surgery occurred 33 +/- 25 (9-99) months later. Tumor size was 1.9 +/- 1.7 (0.8-8.0) cm; 83% were intrathoracic. CT, MRI, LOCT, HOCT, FDG-PET, and F-DOPA-PET had sensitivities per patient of 93% [95% confidence interval (CI) = 79-98%], 90% (95% CI = 74-96%), 57% (95% CI = 39-73%), 50% (95% CI = 25-75%), 64% (95% CI = 35-85%), and 55% (95% CI = 28-79%) and positive predictive values (PPV) per lesion of 66, 74, 79, 89, 53, and 100%, respectively. LOCT and PET detected only lesions seen by CT/MRI; abnormal LOCT or F-DOPA-PET improved PPV of CT/MRI. By modality, the fraction of patients with one or more false-positive findings was 50% by CT, 31% by MRI, 18% by L/HOCT, and 18% by FDG-PET. Eight occult EAS patients had 64 +/- 58 (9-198) months follow-up; others had none.
Conclusions: High sensitivity and PPV suggest thoracic CT/MRI plus LOCT scans for initial imaging, with lesion confirmation by two modalities. (J Clin Endocrinol Metab 95: 1207-1219, 2010)
C1 [Zemskova, Marina S.; Gundabolu, Bhaskar; Chowdhury, Iffat; Nieman, Lynnette K.] NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA.
[Sinaii, Ninet] NIDDKD, Biostat & Clin Epidemiol Serv, NIH, Bethesda, MD 20892 USA.
[Chen, Clara C.; Carrasquillo, Jorge A.; Whatley, Millie] NIDDKD, Div Nucl Med, Radiol & Imaging Sci Dept, NIH, Bethesda, MD 20892 USA.
[Gharib, Ahmed M.] NIDDKD, Dept Diagnost Radiol, NIH, Bethesda, MD 20892 USA.
RP Nieman, LK (reprint author), Bldg 10,CRC,1 E,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM NiemanL@nih.gov
RI Carrasquillo, Jorge/E-7120-2010; Gharib, Ahmed/O-2629-2016;
OI Gharib, Ahmed/0000-0002-2476-481X; Carrasquillo,
Jorge/0000-0002-8513-5734
FU Intramural Research Program in Reproductive and Adult Endocrinology;
Eunice Kennedy Shriver National Institute of Child Health and
Development; National Institutes of Health
FX This work was supported, in part, by the Intramural Research Program in
Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National
Institute of Child Health and Development, National Institutes of
Health.
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U2 2
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2010
VL 95
IS 3
BP 1207
EP 1219
DI 10.1210/jc.2009-2282
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 564FA
UT WOS:000275197500028
PM 20089611
ER
PT J
AU Zemel, BS
Leonard, MB
Kelly, A
Lappe, JM
Gilsanz, V
Oberfield, S
Mahboubi, S
Shepherd, JA
Hangartner, TN
Frederick, MM
Winer, KK
Kalkwarf, HJ
AF Zemel, Babette S.
Leonard, Mary B.
Kelly, Andrea
Lappe, Joan M.
Gilsanz, Vicente
Oberfield, Sharon
Mahboubi, Soroosh
Shepherd, John A.
Hangartner, Thomas N.
Frederick, Margaret M.
Winer, Karen K.
Kalkwarf, Heidi J.
TI Height Adjustment in Assessing Dual Energy X-Ray Absorptiometry
Measurements of Bone Mass and Density in Children
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID MINERAL CONTENT; COMPUTED-TOMOGRAPHY; ADOLESCENT GIRLS;
HEALTHY-CHILDREN; AGE; DISEASE; PUBERTY; DENSITOMETRY; ACQUISITION;
CHILDHOOD
AB Context: In children, bone mineral content (BMC) and bone mineral density (BMD) measurements by dual-energy x-ray absorptiometry (DXA) are affected by height status. No consensus exists on how to adjust BMC or BMD (BMC/BMD) measurements for short or tall stature.
Objective: The aim of this study was to compare various methods to adjust BMC/BMD for height in healthy children.
Design: Data from the Bone Mineral Density in Childhood Study (BMDCS) were used to develop adjustment methods that were validated using an independent cross-sectional sample of healthy children from the Reference Data Project (RDP).
Setting: We conducted the study in five clinical centers in the United States.
Participants: We included 1546 BMDCS and 650 RDP participants (7 to 17 yr of age, 50% female).
Intervention: No interventions were used.
Main Outcome Measures: We measured spine and whole body (WB) BMC and BMD Z-scores for age (BMC/BMD(age)), height age(BMC/BMD(height age)), height(BMC(height)), bone mineral apparent density (BMAD(age)), and height-for-age Z-score (HAZ) (BMC/BMD(haz)).
Results: Spine and WB BMC/BMD(age)Z and BMAD(age)Z were positively (P < 0.005; r = 0.11 to 0.64) associated with HAZ. Spine BMD(haz) and BMC(haz)Z were not associated with HAZ; WB BMC(haz)Z was modestly associated with HAZ (r = 0.14; P = 0.0003). All other adjustment methods were negatively associated with HAZ (P = 0.005; r = -0.20 to -0.34). The deviation between adjusted and BMC/BMD(age) Z-scores was associated with age for most measures (P < 0.005) except for BMC/BMD(haz).
Conclusions: Most methods to adjust BMC/BMD Z-scores for height were biased by age and/or HAZ. Adjustments using HAZ were least biased relative to HAZ and age and can be used to evaluate the effect of short or tall stature on BMC/BMD Z-scores. (J Clin Endocrinol Metab 95: 1265-1273, 2010)
C1 [Zemel, Babette S.; Leonard, Mary B.; Kelly, Andrea; Mahboubi, Soroosh] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Lappe, Joan M.] Creighton Univ, Omaha, NE 68131 USA.
[Gilsanz, Vicente] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Oberfield, Sharon] Columbia Univ, New York, NY 10032 USA.
[Shepherd, John A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hangartner, Thomas N.] Wright State Univ, Dayton, OH 45435 USA.
[Frederick, Margaret M.] Clin Trials & Surveys Corp, Baltimore, MD 21117 USA.
[Winer, Karen K.] NICHHD, Bethesda, MD 20892 USA.
[Kalkwarf, Heidi J.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA.
RP Zemel, BS (reprint author), Childrens Hosp Philadelphia, 3535 Market St,Room 1560, Philadelphia, PA 19104 USA.
EM zemel@email.chop.edu
FU National Institute of Child Health and Human Development [NO1-HD-1-3228,
NO1-HD-1-3329, NO1-HD-1-3330, NO1-HD-1-3331, NO1-HD-1-3332,
NO1-HD-1-3333]; General Clinical Research Center [5-MO1-RR-000240];
Clinical and Translational Research Center of The Children's Hospital of
Philadelphia/University of Pennsylvania [UL1-RR024134]; Research
Institute of The Children's Hospital of Philadelphia
FX This work was supported by the National Institute of Child Health and
Human Development contracts NO1-HD-1-3228, -3329, -3330, -3331, -3332,
and -3333; the General Clinical Research Center (5-MO1-RR-000240); the
Clinical and Translational Research Center of The Children's Hospital of
Philadelphia/University of Pennsylvania (UL1-RR024134); and the Research
Institute of The Children's Hospital of Philadelphia.
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U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2010
VL 95
IS 3
BP 1265
EP 1273
DI 10.1210/jc.2009-2057
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 564FA
UT WOS:000275197500034
PM 20103654
ER
PT J
AU Danielian, S
Basile, N
Rocco, C
Prieto, E
Rossi, J
Barsotti, D
Roche, PA
Bernasconi, A
Oleastro, M
Zelazko, M
Braier, J
AF Danielian, Silvia
Basile, Natalia
Rocco, Carlos
Prieto, Emma
Rossi, Jorge
Barsotti, Dario
Roche, Paul A.
Bernasconi, Andrea
Oleastro, Matias
Zelazko, Marta
Braier, Jorge
TI Novel Syntaxin 11 Gene (STX11) Mutation in Three Argentinean Patients
with Hemophagocytic Lymphohistiocytosis
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE Familial hemophagocytic lymphohistiocytosis; primary immunodeficiency;
syntaxin 11 gene; founder mutation
ID TRANS-GOLGI NETWORK; DISEASE; CYTOTOXICITY; MUNC13-4; LINKAGE; PRF1; FHL
AB Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease with major diagnostic and therapeutic difficulties, basically comprising two different conditions: primary and secondary forms. Recent advances regarding molecular diagnosis may be useful to distinguish from one another, especially in sporadic cases starting in early infancy.
In this report, we evaluated three Argentinean patients with clinical suspicion of HLH, but without family history. We excluded mutations in the perforin gene but identified in the three patients a novel homozygous deletion (c. 581_584delTGCC; p.Leu194ProfsX2) in the gene-encoding syntaxin 11 (STX11), causing a premature termination codon.
Each parent from the three unrelated families resulted heterozygous for this deletion confirming the diagnosis of familial hemophagocytic lymphohistiocytosis type 4. Patients shared the same single-nucleotide polymorphism profile in STX11 gene, and genotyping at ten microsatellites surrounding this gene support the presence of a single-haplotype block carrying the novel mutation.
C1 [Danielian, Silvia; Basile, Natalia; Prieto, Emma; Rossi, Jorge; Bernasconi, Andrea; Oleastro, Matias; Zelazko, Marta] Hosp Pediat Juan P Garrahan, Serv Inmunol & Reumatol, Buenos Aires, DF, Argentina.
[Barsotti, Dario; Braier, Jorge] Hosp Pediat Juan P Garrahan, Serv Hematol Oncol, Buenos Aires, DF, Argentina.
[Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Rocco, Carlos] Hosp Pediat Juan P Garrahan, Lab Biol Celular & Retrovirus, Buenos Aires, DF, Argentina.
RP Danielian, S (reprint author), Hosp Pediat Juan P Garrahan, Serv Inmunol & Reumatol, Buenos Aires, DF, Argentina.
EM danielian.silvia@gmail.com
FU Agencia Nacional de Promocion Cientifica y Tecnologica [21235]
FX The study was supported by Agencia Nacional de Promocion Cientifica y
Tecnologica (PICT2004 No. 21235). We wish to thank Veronica Goris for
the expert handling of patient samples and Marianela Sanz for technical
assistance in the detection of NK activity and CD107a.
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U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD MAR
PY 2010
VL 30
IS 2
SI SI
BP 330
EP 337
DI 10.1007/s10875-009-9350-4
PG 8
WC Immunology
SC Immunology
GA 572AP
UT WOS:000275798900019
PM 19967551
ER
PT J
AU Kantoff, PW
Schuetz, TJ
Blumenstein, BA
Glode, LM
Bilhartz, DL
Wyand, M
Manson, K
Panicali, DL
Laus, R
Schlom, J
Dahut, WL
Arlen, PM
Gulley, JL
Godfrey, WR
AF Kantoff, Philip W.
Schuetz, Thomas J.
Blumenstein, Brent A.
Glode, L. Michael
Bilhartz, David L.
Wyand, Michael
Manson, Kelledy
Panicali, Dennis L.
Laus, Reiner
Schlom, Jeffrey
Dahut, William L.
Arlen, Philip M.
Gulley, James L.
Godfrey, Wayne R.
TI Overall Survival Analysis of a Phase II Randomized Controlled Trial of a
Poxviral-Based PSA-Targeted Immunotherapy in Metastatic
Castration-Resistant Prostate Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID COLONY-STIMULATING FACTOR; COSTIMULATORY MOLECULES; CLINICAL-TRIALS;
ANTIGEN; THERAPY; VACCINES
AB Purpose
Therapeutic prostate-specific antigen (PSA)-targeted poxviral vaccines for prostate cancer have been well tolerated. PROSTVAC-VF treatment was evaluated for safety and for prolongation of progression-free survival (PFS) and overall survival (OS) in a randomized, controlled, and blinded phase II study.
Patients and Methods
In total, 125 patients were randomly assigned in a multicenter trial of vaccination series. Eligible patients had minimally symptomatic castration-resistant metastatic prostate cancer (mCRPC). PROSTVAC-VF comprises two recombinant viral vectors, each encoding transgenes for PSA, and three immune costimulatory molecules (B7.1, ICAM-1, and LFA-3). Vaccinia-based vector was used for priming followed by six planned fowlpox-based vector boosts. Patients were allocated (2:1) to PROSTVAC-VF plus granulocyte-macrophage colony-stimulating factor or to control empty vectors plus saline injections.
Results
Eighty-two patients received PROSTVAC-VF and 40 received control vectors. Patient characteristics were similar in both groups. The primary end point was PFS, which was similar in the two groups (P = .6). However, at 3 years post study, PROSTVAC-VF patients had a better OS with 25 (30%) of 82 alive versus 7 (17%) of 40 controls, longer median survival by 8.5 months (25.1 v 16.6 months for controls), an estimated hazard ratio of 0.56 (95% CI, 0.37 to 0.85), and stratified log-rank P = .0061.
Conclusion
PROSTVAC-VF immunotherapy was well tolerated and associated with a 44% reduction in the death rate and an 8.5-month improvement in median OS in men with mCRPC. These provocative data provide preliminary evidence of clinically meaningful benefit but need to be confirmed in a larger phase III study. J Clin Oncol 28:1099-1105. (C) 2010 by American Society of Clinical Oncology
C1 [Godfrey, Wayne R.] BN Immunotherapeut, Mountain View, CA 94043 USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Therion Biol, Cambridge, MA USA.
Trial Architecture Consulting, Washington, DC USA.
Univ Colorado, Aurora, CO USA.
Urol Associates, Nashville, TN USA.
NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Godfrey, WR (reprint author), BN Immunotherapeut, 2425 Garcia Ave, Mountain View, CA 94043 USA.
EM wayne.godfrey@bn-it.com
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU National Cancer Institute; Center for Cancer Research; National
Institutes of Health; Laboratory of Tumor Immunology and Biology
FX Supported by the Intramural Research Program of the National Cancer
Institute, Center for Cancer Research, National Institutes of Health.
Additional support was provided by the Laboratory of Tumor Immunology
and Biology, via the National Cancer Institute, which had a
Collaborative Research and Development Agreement with Therion Biologics
and currently has one with BN ImmunoTherapeutics.
NR 22
TC 491
Z9 502
U1 3
U2 37
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 MAR 1
PY 2010
VL 28
IS 7
BP 1099
EP 1105
DI 10.1200/JCO.2009.25.0597
PG 7
WC Oncology
SC Oncology
GA 560HG
UT WOS:000274892500006
PM 20100959
ER
PT J
AU Wick, W
Puduvalli, VK
Chamberlain, MC
van den Bent, MJ
Carpentier, AF
Cher, LM
Mason, W
Weller, M
Hong, S
Musib, L
Liepa, AM
Thornton, DE
Fine, HA
AF Wick, Wolfgang
Puduvalli, Vinay K.
Chamberlain, Marc C.
van den Bent, Martin J.
Carpentier, Antoine F.
Cher, Lawrence M.
Mason, Warren
Weller, Michael
Hong, Shengyan
Musib, Luna
Liepa, Astra M.
Thornton, Donald E.
Fine, Howard A.
TI Phase III Study of Enzastaurin Compared With Lomustine in the Treatment
of Recurrent Intracranial Glioblastoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; MALIGNANT GLIOMA;
BRAIN-TUMORS; TRIAL; CHEMOTHERAPY; TEMOZOLOMIDE; MULTIFORME; THERAPY;
CANCER
AB Purpose
This phase III open-label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma (WHO grade 4).
Patients and Methods
Patients were randomly assigned 2:1 to receive 6-week cycles of enzastaurin 500 mg/d (1,125-mg loading dose, day 1) or lomustine (100 to 130 mg/m(2), day 1). Assuming a 45% improvement in progression-free survival (PFS), 397 patients were required to provide 80% power to achieve statistical significance at a one-sided level of .025.
Results
Enrollment was terminated at 266 patients (enzastaurin, n = 174; lomustine, n = 92) after a planned interim analysis for futility. Patient characteristics were balanced between arms. Median PFS (1.5 v 1.6 months; hazard ratio [HR] = 1.28; 95% CI, 0.97 to 1.70), overall survival (6.6 v 7.1 months; HR = 1.20; 95% CI, 0.88 to 1.65), and 6-month PFS rate (P = .13) did not differ significantly between enzastaurin and lomustine, respectively. Stable disease occurred in 38.5% and 35.9% of patients and objective response occurred in 2.9% and 4.3% of patients, respectively. Time to deterioration of physical and functional well-being and symptoms did not differ between arms (HR = 1.12; P = .54). Four patients discontinued enzastaurin because of drug-related serious adverse events (AEs). Eleven patients treated with enzastaurin died on study (four because of AEs; one was drug-related). All four deaths that occurred in patients receiving lomustine were disease-related. Grade 3 to 4 hematologic toxicities were significantly higher with lomustine (46 events) than with enzastaurin (one event; P <= .001).
Conclusion
Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma. J Clin Oncol 28: 1168-1174. (C) 2010 by American Society of Clinical Oncology
C1 [Wick, Wolfgang] Univ Heidelberg, Dept Neurooncol, D-69120 Heidelberg, Germany.
Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
Erasmus MC, Rotterdam, Netherlands.
Hop La Pitie Salpetriere, Paris, France.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
Univ Toronto, Toronto, ON, Canada.
Eli Lilly & Co, Indianapolis, IN 46285 USA.
NCI, Neurooncol Branch, Bethesda, MD 20892 USA.
RP Wick, W (reprint author), Univ Heidelberg, Dept Neurooncol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany.
EM wolfgang.wick@med.uni-heidelberg.de
RI Puduvalli, Vinay/A-2411-2016
FU Eli Lilly and Company
FX Supported by Eli Lilly and Company.
NR 45
TC 198
Z9 201
U1 0
U2 11
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 MAR 1
PY 2010
VL 28
IS 7
BP 1168
EP 1174
DI 10.1200/JCO.2009.23.2595
PG 7
WC Oncology
SC Oncology
GA 560HG
UT WOS:000274892500016
PM 20124186
ER
PT J
AU Preston, G
Anderson, E
Silva, C
Goldberg, T
Wassermann, EM
AF Preston, Gilbert
Anderson, Erik
Silva, Claudio
Goldberg, Terry
Wassermann, Eric M.
TI Effects of 10 Hz rTMS on the Neural Efficiency of Working Memory
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID TRANSCRANIAL MAGNETIC STIMULATION; CORTICAL OSCILLATORY ACTIVITY; LEFT
PREFRONTAL CORTEX; EVENT-RELATED FMRI; AUDITORY HALLUCINATIONS;
POSTERIOR PARIETAL; THETA-OSCILLATIONS; TELL US; PERFORMANCE;
SCHIZOPHRENIA
AB Working memory (WM) has been described as short-term retention of information that is no longer accessible in the environment, and the manipulation of this information for subsequent use in guiding behavior. WM is viewed as a cognitive process underlying higher-order cognitive functions. Evidence supports a critical role for PFC in mediating WM performance. Studies show psychomotor processing speed and accuracy account for considerable variance in neural efficiency (Ne). This study compared the relative effects of active and sham 10 Hz rTMS applied to dorsolateral prefrontal cortex (DLPFC) on indices of Ne in healthy participants performing a WM paradigm that models the association between WM load and task behavior [Sternberg, S. High-speed scanning in human memory. Science, 153, 652-654, 1966]. Previous studies identified a relationship between diminished Ne and impaired WM across a broad array of clinical disorders. In the present study, the authors predicted there would be a main effect of stimulation group (STM) on accuracy (SCR) and processing speed (RT), hence, Ne. We observed a main effect of STM for RT without an effect on SCR; even so, there was a robust effect of STMon Ne.
C1 [Preston, Gilbert] Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT 84132 USA.
[Goldberg, Terry] Hillside Zucker Hosp, Glen Oaks, NY USA.
[Wassermann, Eric M.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
RP Preston, G (reprint author), Univ Utah, Sch Med, Dept Psychiat, 30 North 1900 East, Salt Lake City, UT 84132 USA.
EM gilbert.preston@hsc.utah.edu
FU NARSAD Young Investigator Award; L. C. Tanner Family Foundation;
Intramural NINDS; DARPA; National Science Foundation [IIS-0513692,
CCF-0401498, EIA-0323604, CNS-0514485, IIS-0534628, CNS-0528201,
OISE-0405402]; Department of Energy; IBM Faculty Award
FX This study was supported by the NARSAD Young Investigator Award (to G.
P.), the L. C. Tanner Family Foundation (to G. P.), and Intramural
NINDS, DARPA (to E. W.). National Science Foundation (IIS-0513692 to C.
S., CCF-0401498 to C. S., EIA-0323604 to C. S., CNS-0514485 to C. S.,
IIS-0534628 to C. S., CNS-0528201 to C. S., OISE-0405402 to C. S.);
Department of Energy (to C. S.); IBM Faculty Award (to C. S.).
NR 51
TC 11
Z9 11
U1 0
U2 10
PU M I T PRESS
PI CAMBRIDGE
PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA
SN 0898-929X
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD MAR
PY 2010
VL 22
IS 3
BP 447
EP 456
DI 10.1162/jocn.2009.21209
PG 10
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 565QO
UT WOS:000275309500004
PM 19309294
ER
PT J
AU Cho, CH
Neuenswander, B
Larock, RC
AF Cho, Chul-Hee
Neuenswander, Benjamin
Larock, Richard C.
TI Diverse Methyl Sulfone-Containing Benzo[b]thiophene Library via
Iodocyclization and Palladium-Catalyzed Coupling
SO JOURNAL OF COMBINATORIAL CHEMISTRY
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ESTROGEN-RECEPTOR MODULATORS;
SELECTIVE COX-2 INHIBITORS; CYCLOOXYGENASE-2 INHIBITORS; BIOLOGICAL
EVALUATION; PROSTAGLANDIN SYNTHESIS; TUBULIN POLYMERIZATION;
PARKINSONS-DISEASE; POTENT; DERIVATIVES
AB Parallel solution-phase methods for the synthesis of a 72-membered benzo[b]thiophene library are reported. Medicinally interesting, drug-like, methyl sulfone-substituted benzo[b]thiophenes have been prepared by the palladium-catalyzed substitution Of 3-iodobenzo[b]thiophenes by Suzuki-Miyaura, Sonogashira, Heck, carboalkoxylation, and aminocarbonylation chemistry, The key intermediates for library generation, methyl sulfone-containing 3-iodobenzo[b]thiophenes, are readily prepared by iodocyclization and oxidation methodologies from readily available alkynes.
C1 [Cho, Chul-Hee; Larock, Richard C.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
[Neuenswander, Benjamin] Univ Kansas, NIH, Ctr Excellence Chem Methodol & Lib Dev, Lawrence, KS 66047 USA.
RP Larock, RC (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
EM larock@iastate.edu
FU National Institute of General Medical Sciences [GM070620, GM079593];
National Institutes of Health Kansas University Chemical Methodologies
and Library Development Center of Excellence [GM069663]
FX We would like to thank Dr. Gerald H. Lushington of Kansas University for
all calculations for the compounds. We thank the National Institute of
General Medical Sciences (GM070620 and GM079593) and the National
Institutes of Health Kansas University Chemical Methodologies and
Library Development Center of Excellence (GM069663) for support of this
research: Johnson Matthey, Inc. and Kawaken Fine Chemicals Co., Ltd. for
donations of palladium catalysts and Frontier Scientific and Synthonix
for donations of boronic acids.
NR 58
TC 40
Z9 40
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-4766
J9 J COMB CHEM
JI J. Comb. Chem.
PD MAR-APR
PY 2010
VL 12
IS 2
BP 278
EP 285
DI 10.1021/cc900172u
PG 8
WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary
SC Chemistry; Pharmacology & Pharmacy
GA 563VZ
UT WOS:000275164600012
PM 20055500
ER
PT J
AU Vilar, S
Karpiak, J
Costanzi, S
AF Vilar, Santiago
Karpiak, Joel
Costanzi, Stefano
TI Ligand and Structure-Based Models for the Prediction of Ligand-Receptor
Affinities and Virtual Screenings: Development and Application to the
beta(2)-Adrenergic Receptor
SO JOURNAL OF COMPUTATIONAL CHEMISTRY
LA English
DT Article
DE docking; QSAR; CoMFA; CoMSIA; statistical analysis; G protein-coupled
receptors; beta(2)-adrenergic receptor; virtual screening
ID PROTEIN-COUPLED RECEPTOR; MULTIPLE LINEAR-REGRESSION; CRYSTAL-STRUCTURE;
DRUG DISCOVERY; IN-SILICO; BETA-2-ADRENERGIC RECEPTOR;
BIOLOGICAL-ACTIVITY; LEAD OPTIMIZATION; BINDING-SITE; 3D STRUCTURE
AB In this study, we evaluated the applicability of ligand-based and structure-based models to quantitative affinity predictions and virtual screenings for ligands of the beta(2)-adrenergic receptor, a G protein-coupled receptor (GPCR). We also devised and evaluated a number of consensus models obtained through partial least square regressions, to combine the strengths of the individual components. In all cases, the bioactive conformation of each ligand was derived from molecular docking at the crystal structure of the receptor. We identified the most effective models applicable to the different scenarios, in the presence or in the absence of a training set. For ranking the affinity of closely related analogs when a training set is available, a ligand-based consensus model (LI-CM) seems to be the best choice, while the structure-based MM-GBSA score seems the best alternative in the absence of a training set. For virtual screening purposes, the structure-based MM-GBSA score was found to be the method of choice. Consensus models consistently had performances superior or close to those of the best individual components, and were endowed with a significantly increased robustness. Given multiple models with no a priori knowledge of their predictive capabilities, constructing a consensus model ensures results very close to those that the best model alone would have yielded. (C) 2009 Wiley Periodicals, Inc.* J Comput Chem 31: 707-720, 2010
C1 [Vilar, Santiago; Karpiak, Joel; Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, DHHS, Bethesda, MD 20892 USA.
RP Costanzi, S (reprint author), NIDDK, Lab Biol Modeling, NIH, DHHS, Bethesda, MD 20892 USA.
EM stefanoc@mail.nih.gov
RI Costanzi, Stefano/G-8990-2013;
OI Costanzi, Stefano/0000-0003-3183-7332; Vilar Varela,
Santiago/0000-0003-2663-4370
FU NIH, NIDDK
FX This research was supported by Intramural Research Program of the NIH,
NIDDK.
NR 55
TC 29
Z9 29
U1 1
U2 15
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0192-8651
J9 J COMPUT CHEM
JI J. Comput. Chem.
PD MAR
PY 2010
VL 31
IS 4
BP 707
EP 720
DI 10.1002/jcc.21346
PG 14
WC Chemistry, Multidisciplinary
SC Chemistry
GA 560SG
UT WOS:000274922000004
PM 19569204
ER
PT J
AU Bechert, CJ
Stern, JB
AF Bechert, Charles J.
Stern, Jere B.
TI Basal cell carcinoma with perineural invasion: reexcision perineural
invasion?
SO JOURNAL OF CUTANEOUS PATHOLOGY
LA English
DT Article
ID MALIGNANCY
AB Background: Perineural invasion (PI) in basal cell and squamous cell carcinomas, especially of the head and neck, has been reported to indicate an increased morbidity. Reexcision perineural invasion (RPI), a benign mimic of tumoral perineural invasion, may present a difficult histologic differential diagnosis.
Methods: We surveyed the medical literature for PI occurring in basal cell carcinomas to investigate the degree to which the reported cases occurred in reexcision specimens vs. primary biopsy specimens.
Results: We found large retrospective studies of 14,120 basal cell carcinomas evaluated for PI in which 310 cases of PI were identified (2.2%), and 20 sporadic case reports of basal cell carcinomas with PI. Of 310 cases of basal cell carcinoma with PI, 196 (63%) were in reexcision specimens. Of 20 sporadic reports, 17 (85%) were in reexcision specimens.
Conclusion: The high percentage of PI occurring in reexcision specimens vs. primary excisions may indicate that many of the reported cases of basal cell carcinomas with PI are actually examples of RPI.
C1 [Bechert, Charles J.] Univ Texas Med Branch, Dept Pathol, Galveston, TX USA.
[Stern, Jere B.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Stern, Jere B.] Dermatopathol Consultat Serv, Baltimore, MD USA.
RP Bechert, CJ (reprint author), Univ Texas Med Branch, Dept Pathol, Galveston, TX USA.
EM cjbecher@utmb.edu
NR 16
TC 8
Z9 8
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0303-6987
J9 J CUTAN PATHOL
JI J. Cutan. Pathol.
PD MAR
PY 2010
VL 37
IS 3
BP 376
EP 379
DI 10.1111/j.1600-0560.2009.01331.x
PG 4
WC Dermatology; Pathology
SC Dermatology; Pathology
GA 547KX
UT WOS:000273887600013
PM 19615028
ER
PT J
AU Katoh, A
Fujihara, H
Ohbuchi, T
Onaka, T
Young, WS
Dayanithi, G
Yamasaki, Y
Kawata, M
Suzuki, H
Otsubo, H
Suzuki, H
Murphy, D
Ueta, Y
AF Katoh, Akiko
Fujihara, Hiroaki
Ohbuchi, Toyoaki
Onaka, Tatsushi
Young, W. Scott, III
Dayanithi, Govindan
Yamasaki, Yuka
Kawata, Mitsuhiro
Suzuki, Hitoshi
Otsubo, Hiroki
Suzuki, Hideaki
Murphy, David
Ueta, Yoichi
TI Specific expression of an oxytocin-enhanced cyan fluorescent protein
fusion transgene in the rat hypothalamus and posterior pituitary
SO JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID SUPRAOPTIC NUCLEUS; NERVE-TERMINALS; MAGNOCELLULAR NEURONS;
NEUROSECRETORY-CELLS; HORMONE NEURONS; IN-VIVO; VASOPRESSIN; RELEASE;
GENE; CALCIUM
AB We have generated rats bearing an oxytocin (OXT)-enhanced cyan fluorescent protein (eCFP) fusion transgene designed from a murine construct previously shown to be faithfully expressed in transgenic mice. In situ hybridisation histochemistry revealed that the Oxt-eCfp fusion gene was expressed in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) in these rats. The fluorescence emanating from eCFP was observed only in the SON, the PVN, the internal layer of the median eminence and the posterior pituitary (PP). In in vitro preparations, freshly dissociated cells from the SON and axon terminals showed clear eCFP fluorescence. Immunohistochemistry for OXT and arginine vasopressin (AVP) revealed that the eCFP fluorescence co-localises with OXT immunofluorescence, but not with AVP immunofluorescence in the SON and the PVN. Although the expression levels of the Oxt-eCfp fusion gene in the SON and the PVN showed a wide range of variations in transgenic rats, eCFP fluorescence was markedly increased in the SON and the PVN, but decreased in the PP after chronic salt loading. The expression of the Oxt gene was significantly increased in the SON and the PVN after chronic salt loading in both non-transgenic and transgenic rats. Compared with wild-type animals, euhydrated and salt-loaded male and female transgenic rats showed no significant differences in plasma osmolality, sodium concentration and OXT and AVP levels, suggesting that the fusion gene expression did not disturb any physiological processes. These results suggest that our new transgenic rats are a valuable new tool to identify OXT-producing neurones and their terminals. Journal of Endocrinology (2010) 204, 275-285
C1 [Katoh, Akiko; Fujihara, Hiroaki; Ohbuchi, Toyoaki; Suzuki, Hitoshi; Otsubo, Hiroki; Ueta, Yoichi] Univ Occupat & Environm Hlth, Dept Physiol, Yahatanishi Ku, Kitakyushu, Fukuoka 8078555, Japan.
[Katoh, Akiko; Fujihara, Hiroaki; Ohbuchi, Toyoaki; Suzuki, Hitoshi; Otsubo, Hiroki; Ueta, Yoichi] Univ Occupat & Environm Hlth, Dept Otorhynolaryngol, Sch Med, Yahatanishi Ku, Kitakyushu, Fukuoka 8078555, Japan.
[Onaka, Tatsushi] Jichi Med Sch, Dept Physiol, Shimotsuke, Tochigi 3290498, Japan.
[Young, W. Scott, III] NIMH, Sect Neural Gene Express, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Dayanithi, Govindan] Acad Sci Czech Republic, Inst Expt Med, Dept Cellular Neurophysiol, EU Res Ctr Excellence, CZ-14220 Prague, Czech Republic.
[Yamasaki, Yuka; Kawata, Mitsuhiro] Kyoto Prefectural Univ Med, Dept Anat & Neurobiol, Kyoto 6028566, Japan.
[Murphy, David] Univ Bristol, Mol Neuroendocrinol Res Grp, Henry Wellcome Labs Integrat Neurosci & Endocrino, Bristol BS1 3NY, Avon, England.
RP Ueta, Y (reprint author), Univ Occupat & Environm Hlth, Dept Physiol, Yahatanishi Ku, 1-1 Iseigaoka, Kitakyushu, Fukuoka 8078555, Japan.
EM yoichi@med.uoeh-u.ac.jp
RI Murphy, David/C-3967-2012; Young, W Scott/A-9333-2009; Onaka,
Tatsushi/I-7115-2012; Dayanithi, Govindan/H-3131-2014; Dayanithi,
Govindan/F-6068-2016
OI Murphy, David/0000-0003-2946-0353; Young, W Scott/0000-0001-6614-5112;
Dayanithi, Govindan/0000-0002-1009-7809; Dayanithi,
Govindan/0000-0002-1009-7809
FU Biotechnology and Biological Sciences Research Council [BB/G006156/1];
Intramural NIH HHS [ZIA MH002498-20]; Medical Research Council
[G0700954]; NIMH NIH HHS [Z01 MH002498, Z01-MH-002498-20]
NR 37
TC 11
Z9 11
U1 2
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0022-0795
J9 J ENDOCRINOL
JI J. Endocrinol.
PD MAR
PY 2010
VL 204
IS 3
BP 275
EP 285
DI 10.1677/JOE-09-0289
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 568ND
UT WOS:000275528200006
PM 20026620
ER
PT J
AU Lakind, JS
Birnbaum, LS
AF Lakind, Judy S.
Birnbaum, Linda S.
TI Out of the frying pan and out of the fire: the indispensable role of
exposure science in avoiding risks from replacement chemicals
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Editorial Material
C1 [Lakind, Judy S.] LaKind Associates LLC, Catonsville, MD USA.
[Lakind, Judy S.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
[Lakind, Judy S.] Penn State Coll Med, Dept Pediat, Hershey, PA USA.
[Birnbaum, Linda S.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Lakind, JS (reprint author), LaKind Associates LLC, Catonsville, MD USA.
EM lakindassoc@comcast.net
NR 5
TC 5
Z9 5
U1 0
U2 3
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 MAR-APR
PY 2010
VL 20
IS 2
BP 115
EP 116
DI 10.1038/jes.2009.71
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 557DQ
UT WOS:000274649700002
PM 20160736
ER
PT J
AU Thomas, KW
Dosemeci, M
Hoppin, JA
Sheldon, LS
Croghan, CW
Gordon, SM
Jones, ML
Reynolds, SJ
Raymer, JH
Akland, GG
Lynch, CF
Knott, CE
Sandler, DP
Blair, AE
Alavanja, MC
AF Thomas, Kent W.
Dosemeci, Mustafa
Hoppin, Jane A.
Sheldon, Linda S.
Croghan, Carry W.
Gordon, Sydney M.
Jones, Martin L.
Reynolds, Stephen J.
Raymer, James H.
Akland, Gerald G.
Lynch, Charles F.
Knott, Charles E.
Sandler, Dale P.
Blair, Aaron E.
Alavanja, Michael C.
TI Urinary biomarker, dermal, and air measurement results for 2,4-D and
chlorpyrifos farm applicators in the Agricultural Health Study
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Article
DE 2,4-D; chlorpyrifos; exposure measurement; farm applicator; occupational
exposure; Agricultural Health Study
ID 2,4-DICHLOROPHENOXYACETIC ACID; PESTICIDE APPLICATORS; HUMAN VOLUNTEERS;
CUSTOM APPLICATORS; DIMETHYLAMINE SALT; EXPOSURE; CANCER; WORKERS;
ABSORPTION; FORESTRY
AB A subset of private pesticide applicators in the Agricultural Health Study (AHS) epidemiological cohort was monitored around the time of their agricultural use of 2,4-dichlorophenoxyacetic acid (2,4-D) and O,O-diethyl-O-3,5,6-trichloro-2-pyridyl phosphorothioate (chlorpyrifos) to assess exposure levels and potential determinants of exposure. Measurements included pre- and post-application urine samples, and patch, hand wipe, and personal air samples. Boom spray or hand spray application methods were used by applicators for 2,4-D products. Chlorpyrifos products were applied using spray applications and in-furrow application of granular products. Geometric mean (GM) values for 69 2,4-D applicators were 7.8 and 25 mg/l in pre- and post-application urine, respectively (P<0.05 for difference); 0.39mg for estimated hand loading; 2.9 mg for estimated body loading; and 0.37 mu g/m(3) for concentration in personal air. Significant correlations were found between all media for 2,4-D. GM values for 17 chlorpyrifos applicators were 11 mu g/l in both pre- and post-application urine for the 3,5,6-trichloro-2-pyridinol metabolite, 0.28 mg for body loading, and 0.49 mu g/m(3) for air concentration. Only 53% of the chlorpyrifos applicators had measurable hand loading results; their median hand loading being 0.02 mg. Factors associated with differences in 2,4-D measurements included application method and glove use, and, for hand spray applicators, use of adjuvants, equipment repair, duration of use, and contact with treated vegetation. Spray applications of liquid chlorpyrifos products were associated with higher measurements than in-furrow granular product applications. This study provides information on exposures and possible exposure determinants for several application methods commonly used by farmers in the cohort and will provide information to assess and refine exposure classification in the AHS. Results may also be of use in pesticide safety education for reducing exposures to pesticide applicators. Journal of Exposure Science and Environmental Epidemiology (2010) 20, 119-134; doi: 10.1038/jes.2009.6; published online 25 February 2009
C1 [Thomas, Kent W.; Sheldon, Linda S.; Croghan, Carry W.] US EPA, Natl Exposure Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
[Dosemeci, Mustafa; Blair, Aaron E.; Alavanja, Michael C.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA.
[Hoppin, Jane A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Gordon, Sydney M.] Battelle Mem Inst, Columbus, OH 43201 USA.
[Jones, Martin L.; Reynolds, Stephen J.] Univ Iowa, Dept Occupat & Environm Med, Iowa City, IA USA.
[Raymer, James H.; Akland, Gerald G.] RTI Int, Res Triangle Pk, NC USA.
[Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Knott, Charles E.] Battelle Ctr Publ Hlth Res & Evaluat, Durham, NC USA.
RP Thomas, KW (reprint author), US EPA, Natl Exposure Res Lab, Off Res & Dev, MD-E205-04, Res Triangle Pk, NC 27711 USA.
EM thomas.kent@epa.gov
OI Sandler, Dale/0000-0002-6776-0018
FU The United States Environmental Protection Agency through its Office of
Research and Development [68-D99-011, 68-D99-012]; NIH, National Cancer
Institute [DW-75-93912801-0, Z01-CP010119-12]; National Institute of
Environmental Health Sciences [Z01-ES049030-1]
FX We thank the AHS cohort members participating in this study for their
considerable time and effort. Several EPA researchers, including Ross
Highsmith, William Steen, Miles Okino, and Ruth Allen, provided
significant contributions to the study design. Paul Jones at EPA
provided statistical support and Guadalupe Chapa assisted in data
analysis. Joy Herrington, Nyla Logsden-Sackett, and Patti Gillette at
the AHS Field Stations in IA and NC led participant screening
activities. We thank Marcia Nishioka (Battelle Memorial Institute),
Robin Helburn (RTI International) and David Camann and Jackie Clothier
(Southwest Research Institute) for leading sample analyses and for hand
wipe method development. The United States Environmental Protection
Agency through its Office of Research and Development partially funded
and collaborated in the research described here under contracts
68-D99-011 to Battelle and 68-D99-012 to RTI International, and through
Interagency Agreement DW-75-93912801-0 to the National Cancer Institute.
It has been subjected to agency administrative review and approved for
publication. Mention of trade names or commercial products does not
constitute endorsement or recommendation for use. This study has been
supported in part by the Intramural Research Program of the NIH,
National Cancer Institute (Z01-CP010119-12), and National Institute of
Environmental Health Sciences (Z01-ES049030-1).
NR 39
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1559-0631
EI 1559-064X
J9 J EXPO SCI ENV EPID
JI J. Expo. Sci. Environ. Epidemiol.
PD MAR-APR
PY 2010
VL 20
IS 2
BP 119
EP 134
DI 10.1038/jes.2009.6
PG 16
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 557DQ
UT WOS:000274649700004
PM 19240759
ER
PT J
AU Bhatti, P
Blair, A
Bell, EM
Rothman, N
Lan, Q
Barr, DB
Needham, LL
Portengen, L
Figgs, LW
Vermeulen, R
AF Bhatti, Parveen
Blair, Aaron
Bell, Erin M.
Rothman, Nathaniel
Lan, Qing
Barr, Dana B.
Needham, Larry L.
Portengen, Lutzen
Figgs, Larry W.
Vermeulen, Roel
TI Predictors of 2,4-dichlorophenoxyacetic acid exposure among herbicide
applicators
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Article
DE 2,4-D; biomonitoring; herbicide; exposure determinants
ID PROFESSIONAL TURF APPLICATORS; HUMAN URINE; METABOLITES; PESTICIDES;
MODELS
AB To determine the major factors affecting the urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) among county noxious weed applicators in Kansas, we used a regression technique that accounted for multiple days of exposure. We collected 136 12-h urine samples from 31 applicators during the course of two spraying seasons (April to August of 1994 and 1995). Using mixed-effects models, we constructed exposure models that related urinary 2,4-D measurements to weighted self-reported work activities from daily diaries collected over 5 to 7 days before the collection of the urine sample. Our primary weights were based on an earlier pharmacokinetic analysis of turf applicators; however, we examined a series of alternative weighting schemes to assess the impact of the specific weights and the number of days before urine sample collection that were considered. The derived models accounting for multiple days of exposure related to a single urine measurement seemed robust with regard to the exact weights, but less to the number of days considered; albeit the determinants from the primary model could be fitted with marginal losses of fit to the data from the other weighting schemes that considered a different numbers of days. In the primary model, the total time of all activities (spraying, mixing, other activities), spraying method, month of observation, application concentration, and wet gloves were significant determinants of urinary 2,4-D concentration and explained 16% of the between-worker variance and 23% of the within-worker variance of urinary 2,4-D levels. As a large proportion of the variance remained unexplained, further studies should be conducted to try to systematically assess other exposure determinants. Journal of Exposure Science and Environmental Epidemiology (2010) 20, 160-168; doi: 10.1038/jes.2009.14; published online 25 March 2009
C1 [Bhatti, Parveen; Blair, Aaron; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Bell, Erin M.] SUNY Albany, Dept Epidemiol, Sch Publ Hlth, Rensselaer, NY USA.
[Barr, Dana B.; Needham, Larry L.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA.
[Portengen, Lutzen; Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Figgs, Larry W.] Univ Kentucky, Dept Prevent Med & Environm Hlth, Coll Publ Hlth, Lexington, KY USA.
[Vermeulen, Roel] Univ Med Ctr Utrecht, Julius Ctr, Utrecht, Netherlands.
RP Bhatti, P (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7049,MSC 7238, Bethesda, MD 20892 USA.
EM bhattip@mail.nih.gov
RI Needham, Larry/E-4930-2011; Barr, Dana/E-6369-2011; Barr,
Dana/E-2276-2013; Vermeulen, Roel/F-8037-2011
OI Vermeulen, Roel/0000-0003-4082-8163
FU Intramural NIH HHS [Z01 CP010119-12]
NR 11
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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 MAR-APR
PY 2010
VL 20
IS 2
BP 160
EP 168
DI 10.1038/jes.2009.14
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 557DQ
UT WOS:000274649700007
PM 19319162
ER
PT J
AU Baird, DD
Saldana, TM
Nepomnaschy, PA
Hoppin, JA
Longnecker, MP
Weinberg, CR
Wilcox, AJ
AF Baird, Donna Day
Saldana, Tina M.
Nepomnaschy, Pablo A.
Hoppin, Jane A.
Longnecker, Matthew P.
Weinberg, Clarice R.
Wilcox, Allen J.
TI Within-person variability in urinary phthalate metabolite
concentrations: measurements from specimens after long-term frozen
storage
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Article
DE biomarker; phthalate; reproducibility; menstrual cycle; temporal
variability
ID TEMPORAL VARIABILITY; PREGNANT-WOMEN; MALE-RAT; EXPOSURE; POPULATION;
HEALTH; ESTERS; DEHP; MONOESTERS; CHILDREN
AB Laboratory studies show that exposure to phthalates during development can cause adverse effects, especially for males. Studies in humans would be facilitated by collection of urine during pregnancy, long-term storage, and measurement of phthalate metabolites at the time that offspring health is assessed. Our aims were to measure urinary phthalate metabolites after long-term freezer storage, to use those measurements to evaluate within-woman variability over 2- and 4-week intervals, and to determine whether the phases of the menstrual cycle affect metabolite levels. Samples were selected from daily first-morning urine specimens collected by 60 women and stored frozen since 1983-1985. Three specimens per woman were selected at approximately 2-week intervals to include both follicular and luteal phase samples. Seven metabolites of five phthalates were measured by mass spectrometry. Statistical analyses were conducted with correlation, mixed model regression, and the Wilcoxon signed rank test. Creatinine-corrected urinary phthalate metabolite concentrations measured in samples after long-term storage tended to have a similar right-skewed distribution, though with somewhat higher concentrations than those reported for recently collected US samples. The concentrations of three metabolites of di(2-ethylhexyl) phthalate in the same specimen were very highly correlated (Pearson r=0.85-0.97). Reproducibility over a 4-week interval was moderate for the metabolites of diethyl phthalate and benzylbutyl phthalate (intraclass correlation coefficients, ICCs, 0.48 and 0.53, respectively), whereas five other metabolites had lower ICCs (0.21-0.37). Menstrual phase was not related to metabolite concentrations. Although the same samples have not been measured both before and after long-term storage, results suggest that the measurement of phthalate metabolites after long-term sample storage yield generally similar distributions and temporal reliability as those reported for recently collected specimens. These findings support the use of stored urine specimens collected during the relevant stage of human pregnancy to investigate the influence of phthalate exposures on later outcomes. Journal of Exposure Science and Environmental Epidemiology (2010) 20, 169-175; doi: 10.1038/jes.2009.17; published online 11 March 2009
C1 [Baird, Donna Day; Hoppin, Jane A.; Longnecker, Matthew P.; Wilcox, Allen J.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Saldana, Tina M.] Social & Sci Syst Inc, Durham, NC USA.
[Nepomnaschy, Pablo A.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada.
[Weinberg, Clarice R.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Baird, DD (reprint author), NIEHS, Epidemiol Branch, NIH, MD A3-05 NIEHS,POB 12233, Res Triangle Pk, NC 27709 USA.
EM baird@niehs.nih.gov
RI Baird, Donna/D-5214-2017;
OI Baird, Donna/0000-0002-5544-2653; Longnecker,
Matthew/0000-0001-6073-5322; Wilcox, Allen/0000-0002-3376-1311
FU National Institute of Environmental Health Sciences, National Institutes
of Health, HHS
FX The field manager of the North Carolina Early Pregnancy Study was Joy
Pierce, and D. Robert McConnaughey manages the study data files. This
research was funded by the intramural program at the National Institute
of Environmental Health Sciences, National Institutes of Health, HHS. We
thank AXYS Analytical Services Ltd from Sidney, BC Canada, for their
assistance with this project including their detailed description of the
analytic methods. An earlier version of the manuscript was reviewed by
Drs. Freya Kamel and Yang Cao.
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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 MAR-APR
PY 2010
VL 20
IS 2
BP 169
EP 175
DI 10.1038/jes.2009.17
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 557DQ
UT WOS:000274649700008
PM 19277068
ER
PT J
AU Takikawa, S
Engle, RE
Faulk, KN
Emerson, SU
Purcell, RH
Bukh, J
AF Takikawa, Shingo
Engle, Ronald E.
Faulk, Kristina N.
Emerson, Suzanne U.
Purcell, Robert H.
Bukh, Jens
TI Molecular evolution of GB virus B hepatitis virus during acute resolving
and persistent infections in experimentally infected tamarins
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID C VIRUS; IN-VIVO; CHIMPANZEES; CLONE; PROTEIN; AGENT; REGION; STRAIN;
SERUM; MODEL
AB GB virus B (GBV-B) causes acute hepatitis in experimentally infected tamarins. We compared evolutionary features in acute resolving and persistent GBV-B infection. We detected no evidence of evolution in four animals with clearance during weeks 9-12, whereas three animals with clearance during weeks 13-26 had several substitutions in their polyprotein sequence. A single tamarin had long-term GBV-B viraemia; analysis of virus recovered at weeks 2, 5, 12, 20, 26, 52 and 104 demonstrated that mutations accumulated over time, Overall, the amino acid substitution rate was 3.5 x 10(-3) and 1.1 x 10(-3) substitutions per site year(-1) during weeks 1-52 and 53-104, respectively. Thus, there was a significant decrease in evolution over time, as found for hepatitis C virus. The rate of non-synonymous substitution per non-synonymous site compared with that of synonymous substitution per synonymous site decreased over time, suggesting reduction of positive selective pressure. These data demonstrate that prolonged GBV-B infection is associated with viral evolution.
C1 [Takikawa, Shingo; Engle, Ronald E.; Faulk, Kristina N.; Emerson, Suzanne U.; Purcell, Robert H.; Bukh, Jens] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Takikawa, Shingo; Engle, Ronald E.; Faulk, Kristina N.; Emerson, Suzanne U.; Purcell, Robert H.; Bukh, Jens] NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Bukh, Jens] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, Copenhagen N, Denmark.
[Bukh, Jens] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis Program C, Hvidovre, Denmark.
[Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark.
RP Bukh, J (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jbukh@niaid.nih.gov
FU Lundbeck Foundation; National Institute of Allergy and Infectious
Diseases, National Institutes of Health
FX J. B. is the recipient of a professorship at the University of
Copenhagen with external funding from the Lundbeck Foundation. This
research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 17
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U1 0
U2 0
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD MAR
PY 2010
VL 91
BP 727
EP 733
DI 10.1099/vir.0.015750-0
PN 3
PG 7
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 569HM
UT WOS:000275587200016
PM 19906942
ER
PT J
AU Bailey, D
Kaiser, WJ
Hollinshead, M
Moffat, K
Chaudhry, Y
Wileman, T
Sosnovtsev, SV
Goodfellow, IG
AF Bailey, Dalan
Kaiser, William J.
Hollinshead, Mike
Moffat, Katy
Chaudhry, Yasmin
Wileman, Thomas
Sosnovtsev, Stanislav V.
Goodfellow, Ian G.
TI Feline calicivirus p32, p39 and p30 proteins localize to the endoplasmic
reticulum to initiate replication complex formation
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID MOUTH-DISEASE VIRUS; VESICULAR STOMATITIS-VIRUS; TO-GOLGI TRANSPORT;
POLIOVIRUS REPLICATION; SECRETORY PATHWAY; INFECTED-CELLS; NONSTRUCTURAL
POLYPROTEIN; MEMBRANE-PROTEINS; PHASE-SEPARATION; CULTURED-CELLS
AB In common with other positive-strand RNA viruses, replication of feline calicivirus (FCV) results in rearrangement of intracellular membranes and production of numerous membrane-bound vesicular structures on which viral genome replication is thought to occur. In this study, bioinformatics approaches have identified three of the FCV non-structural proteins, namely p32, p39 and p30, as potential transmembrane proteins. These proteins were able to target enhanced cyan fluorescent protein to membrane fractions where they behaved as integral membrane proteins. Immunofluorescence microscopy of these proteins expressed in cells showed colocalization with endoplasmic reticulum (ER) markers. Further electron microscopy analysis of cells co-expressing FCV p39 or p30 with a horseradish peroxidase protein containing the KDEL ER retention motif demonstrated gross morphological changes to the ER. Similar reorganization patterns, especially for those produced by p30, were observed in naturally infected Crandel-Rees feline kidney cells. Together, the data demonstrate that the p32, p39 and p30 proteins of FCV locate to the ER and lead to reorganization of ER membranes. This suggests that they may play a role in the generation of FCV replication complexes and that the endoplasmic reticulum may represent the potential source of the membrane vesicles induced during FCV infection.
C1 [Bailey, Dalan; Hollinshead, Mike; Chaudhry, Yasmin; Goodfellow, Ian G.] Univ London Imperial Coll Sci Technol & Med, Dept Virol, London W2 1PG, England.
[Kaiser, William J.] Univ Reading, Sch Biol Sci, Reading RG6 6AJ, Berks, England.
[Moffat, Katy] AFRC, Inst Anim Hlth, Guildford GU24 0NF, Surrey, England.
[Wileman, Thomas] Univ E Anglia, Sch Med, Norwich NR4 7TJ, Norfolk, England.
[Sosnovtsev, Stanislav V.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Bailey, D (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Virol, Norfolk Pl, London W2 1PG, England.
EM d.bailey@imperial.ac.uk; i.goodfellow@imperial.ac.uk
OI Bailey, Dalan/0000-0002-5640-2266; Goodfellow, Ian/0000-0002-9483-510X
FU Wellcome Trust
FX This work was supported by funding from the Wellcome Trust. I. G. G. is
a Wellcome Senior Fellow.
NR 58
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U1 0
U2 2
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD MAR
PY 2010
VL 91
BP 739
EP 749
DI 10.1099/vir.0.016279-0
PN 3
PG 11
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 569HM
UT WOS:000275587200018
PM 19906938
ER
EF