FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Moody, TW
Sancho, V
di Florio, A
Nuche-Berenguer, B
Mantey, S
Jensen, RT
AF Moody, Terry W.
Sancho, Veronica
di Florio, Alessia
Nuche-Berenguer, Bernardo
Mantey, Samuel
Jensen, Robert T.
TI Bombesin receptor subtype-3 agonists stimulate the growth of lung cancer
cells and increase EGF receptor tyrosine phosphorylation
SO PEPTIDES
LA English
DT Article
DE Bombesin receptor subtype-3; Epidermal growth factor receptor; Tyrosine
phosphorylation; Lung cancer; Proliferation
ID GASTRIN-RELEASING-PEPTIDE; HUMAN ORPHAN RECEPTOR; HIGH-AFFINITY;
NECK-CANCER; ACTIVATION; EXPRESSION; LINES; GEFITINIB; PHARMACOLOGY;
SELECTIVITY
AB The effects of bombesin receptor subtype-3 (BRS-3) agonists were investigated on lung cancer cells. The BRS-3 agonist (DTyr(6), (Ala(11), Phe(13), Nle(14)) bombesin(6-14) (BA1), but not gastrin releasing peptide (GRP) or neuromedin B (NMB) increased significantly the clonal growth of NCI-H1299 cells stably transfected with BRS-3 (NCI-H1299-BRS-3). Also, BA1 addition to NCI-H727 or NCI-H1299-BRS-3 cells caused Tyr(1068) phosphorylation of the epidermal growth factor receptor (EGFR). Similarly, (DTyr(6), R-Apa(11), Phe(13), Nle(14)) bombesin(6-14) (BA2) and (DTyr(6), R-Apa(11), 4-Cl,Phe(13), Nle(14)) bombesin(6-14) (BA3) but not gastrin releasing peptide (GRP) or neuromedin B (NMB) caused EGFR transactivation in NCI-H1299-BRS-3 cells. BA1-induced EGFR or ERK tyrosine phosphorylation was not inhibited by addition of BW2258U89 (BB(2)R antagonist) or PD168368 (BB(1)R antagonist) but was blocked by (DNal-Cys-Tyr-DTrp-Lys-Val-CysNal)NH(2) (BRS-3 ant.). The BRS-3 ant. reduced clonal growth of NCI-H1299-BRS-3 cells. BA1, BA2, BA3 and BRS-3 ant. inhibit specific (126)I-BA1 binding to NCI-H1299-BRS-3 cells with an IC(50) values of 1.1, 21, 15 and 750 nM, respectively. The ability of BRS-3 to regulate EGFR transactivation in NCI-H1299-BRS-3 cells was reduced by AG1478 or gefitinib (EGFR tyrosine kinase inhibitors), GM6001 (matrix metalloprotease inhibitor), PP2 (Src inhibitor), N-acetylcysteine (anti-oxidant), Tiron (superoxide scavenger) and DPI (NADPH oxidase inhibitor). These results demonstrate that BRS-3 agonists may stimulate lung cancer growth as a result of EGFR transactivation and that the transactivation is regulated by BRS-3 in a Src-, reactive oxygen and matrix metalloprotease-dependent manner. Published by Elsevier Inc.
C1 [Moody, Terry W.] NCI, Dept Hlth & Human Serv, Ctr Canc Res, Off Director, Bethesda, MD 20892 USA.
[Sancho, Veronica; di Florio, Alessia; Nuche-Berenguer, Bernardo; Mantey, Samuel; Jensen, Robert T.] NIDDKD, Digest Dis Branch, Bethesda, MD 20892 USA.
RP Moody, TW (reprint author), NCI, Off Director, CCR, Bldg 31,Rm 4A48,31 Ctr Dr, Bethesda, MD 20892 USA.
EM moodyt@mail.nih.gov
FU NIDDK; NCI, of NIH
FX This research is partially supported by the intramural research program
of the NIDDK and NCI, of NIH.
NR 52
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U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-9781
J9 PEPTIDES
JI Peptides
PD AUG
PY 2011
VL 32
IS 8
BP 1677
EP 1684
DI 10.1016/j.peptides.2011.06.011
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
GA 816BD
UT WOS:000294572800016
PM 21712056
ER
PT J
AU Uehara, H
Gonzalez, N
Sancho, V
Mantey, SA
Nuche-Berenguer, B
Pradhan, T
Coy, DH
Jensen, RT
AF Uehara, Hirotsugu
Gonzalez, Nieves
Sancho, Veronica
Mantey, Samuel A.
Nuche-Berenguer, Bernardo
Pradhan, Tapas
Coy, David H.
Jensen, Robert T.
TI Pharmacology and selectivity of various natural and synthetic bombesin
related peptide agonists for human and rat bombesin receptors differs
SO PEPTIDES
LA English
DT Article
DE Bombesin; Neuromedin B; Gastrin-releasing peptide; Bombesin receptor;
Gastrin-releasing peptide receptor; BRS-3; Neuromedin B receptor;
Satiety; Peptide mediated cytotoxicity; Tumor imaging; PRRT
ID GASTRIN-RELEASING-PEPTIDE; LUNG-CANCER CELLS; NEUROMEDIN-B RECEPTORS;
HUMAN ORPHAN RECEPTOR; SMOOTH-MUSCLE PREPARATIONS;
CENTRAL-NERVOUS-SYSTEM; SWISS 3T3 CELLS; HIGH-AFFINITY; MOLECULAR-BASIS;
STRUCTURAL REQUIREMENTS
AB The mammalian bombesin (Bn)-receptor family [gastrin-releasing peptide-receptor (GRPR-receptor), neuromedin B-receptor (NMB receptor)], their natural ligands, GRP/NMB, as well as the related orphan receptor, BRS-3, are widely distributed, and frequently overexpressed by tumors. There is increased interest in agonists for this receptor family to explore their roles in physiological/pathophysiological processes, and for receptor-imaging/cytotoxicity in tumors. However, there is minimal data on human pharmacology of Bn receptor agonists and most results are based on nonhuman receptor studies, particular rodent-receptors, which with other receptors frequently differ from human-receptors. To address this issue we compared hNMB-/GRP-receptor affinities and potencies/efficacies of cell activation (assessing phospholipase C activity) for 24 putative Bn-agonists (12 natural, 12 synthetic) in four different cells with these receptors, containing native receptors or receptors expressed at physiological densities, and compared the results to native rat GRP-receptor containing cells (AR42J-cells) or rat NMB receptor cells (C6-glioblastoma cells). There were close correlations (r=0.92-99, p<0.0001) between their affinities/potencies for the two hGRP- or hNMB-receptor cells. Twelve analogs had high affinities (<= 1 nM) for hGRP receptor with 15 selective for it (greatest=GRP, NMC), eight had high affinity/potencies for hNMB receptors and four were selective for it. Only synthetic Bn analogs containing beta-alanine(11) had high affinity for hBRS-3, but also had high affinities/potencies for all GRP-/hNMB-receptor cells. There was no correlation between affinities for human GRP receptors and rat GRP receptors (r=0.131, p=0.54), but hNMB receptor results correlated with rat NMB receptor (r=0.71, p<0.0001). These results elucidate the human and rat GRP-receptor pharmacophore for agonists differs markedly, whereas they do not for NMB receptors, therefore potential GRP-receptor agonists for human studies (such as En receptor-imaging/cytotoxicity) must be assessed on human Bn receptors. The current study provides affinities/potencies on a large number of potential agonists that might be useful for human studies. Published by Elsevier Inc.
C1 [Uehara, Hirotsugu; Gonzalez, Nieves; Sancho, Veronica; Mantey, Samuel A.; Nuche-Berenguer, Bernardo; Pradhan, Tapas; Jensen, Robert T.] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
[Coy, David H.] Tulane Hlth Sci Ctr, Dept Med, Peptide Res Labs, New Orleans, LA 70112 USA.
RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA.
EM robertj@bdg10.niddk.nih.gov
RI Gonzalez, Nieves/N-2199-2014
OI Gonzalez, Nieves/0000-0002-1551-2872
FU NIDDK, NIH
FX This work was partial supported by intramural funds of the NIDDK, NIH.
NR 99
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-9781
J9 PEPTIDES
JI Peptides
PD AUG
PY 2011
VL 32
IS 8
BP 1685
EP 1699
DI 10.1016/j.peptides.2011.06.017
PG 15
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
GA 816BD
UT WOS:000294572800017
PM 21729729
ER
PT J
AU Bell, DW
Sikdar, N
Lee, KY
Price, JC
Chatterjee, R
Park, HD
Fox, J
Ishiai, M
Rudd, ML
Pollock, LM
Fogoros, SK
Mohamed, H
Hanigan, CL
Zhang, SY
Cruz, P
Renaud, G
Hansen, NF
Cherukuri, PF
Borate, B
McManus, KJ
Stoepel, J
Sipahimalani, P
Godwin, AK
Sgroi, DC
Merino, MJ
Elliot, G
Elkahloun, A
Vinson, C
Takata, M
Mullikin, JC
Wolfsberg, TG
Hieter, P
Lim, DS
Myung, K
AF Bell, Daphne W.
Sikdar, Nilabja
Lee, Kyoo-young
Price, Jessica C.
Chatterjee, Raghunath
Park, Hee-Dong
Fox, Jennifer
Ishiai, Masamichi
Rudd, Meghan L.
Pollock, Lana M.
Fogoros, Sarah K.
Mohamed, Hassan
Hanigan, Christin L.
Zhang, Suiyuan
Cruz, Pedro
Renaud, Gabriel
Hansen, Nancy F.
Cherukuri, Praveen F.
Borate, Bhavesh
McManus, Kirk J.
Stoepel, Jan
Sipahimalani, Payal
Godwin, Andrew K.
Sgroi, Dennis C.
Merino, Maria J.
Elliot, Gene
Elkahloun, Abdel
Vinson, Charles
Takata, Minoru
Mullikin, James C.
Wolfsberg, Tyra G.
Hieter, Philip
Lim, Dae-Sik
Myung, Kyungjae
CA NISC Comparative Sequencing Progra
TI Predisposition to Cancer Caused by Genetic and Functional Defects of
Mammalian Atad5
SO PLOS GENETICS
LA English
DT Article
ID REPLICATION-FACTOR-C; COMPARATIVE GENOMIC HYBRIDIZATION; GROSS
CHROMOSOMAL REARRANGEMENTS; DNA-POLYMERASE-ETA;
SACCHAROMYCES-CEREVISIAE; HOMOLOGOUS RECOMBINATION; ENDOMETRIAL
CARCINOMA; XERODERMA-PIGMENTOSUM; CELL-LINE; INSTABILITY
AB ATAD5, the human ortholog of yeast Elg1, plays a role in PCNA deubiquitination. Since PCNA modification is important to regulate DNA damage bypass, ATAD5 may be important for suppression of genomic instability in mammals in vivo. To test this hypothesis, we generated heterozygous (Atad5(+/m)) mice that were haploinsuffficient for Atad5. Atad5(+/m) mice displayed high levels of genomic instability in vivo, and Atad5(+/m) mouse embryonic fibroblasts (MEFs) exhibited molecular defects in PCNA deubiquitination in response to DNA damage, as well as DNA damage hypersensitivity and high levels of genomic instability, apoptosis, and aneuploidy. Importantly, 90% of haploinsufficient Atad5(+/m) mice developed tumors, including sarcomas, carcinomas, and adenocarcinomas, between 11 and 20 months of age. High levels of genomic alterations were evident in tumors that arose in the Atad5(+/m) mice. Consistent with a role for Atad5 in suppressing tumorigenesis, we also identified somatic mutations of ATAD5 in 4.6% of sporadic human endometrial tumors, including two nonsense mutations that resulted in loss of proper ATAD5 function. Taken together, our findings indicate that loss-of-function mutations in mammalian Atad5 are sufficient to cause genomic instability and tumorigenesis.
C1 [Bell, Daphne W.; Price, Jessica C.; Rudd, Meghan L.; Pollock, Lana M.; Fogoros, Sarah K.; Mohamed, Hassan; Hanigan, Christin L.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Sikdar, Nilabja; Lee, Kyoo-young; Park, Hee-Dong; Fox, Jennifer; Lim, Dae-Sik; Myung, Kyungjae] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Chatterjee, Raghunath; Merino, Maria J.; Vinson, Charles] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Park, Hee-Dong; Lim, Dae-Sik] Korea Adv Inst Sci & Technol, Natl Res Lab Genom Stabil, Dept Biol Sci, Taejon 305701, South Korea.
[Ishiai, Masamichi; Takata, Minoru] Kyoto Univ, Ctr Radiat Biol, Lab DNA Damage Signaling, Dept Late Effect Studies,Sakyo Ku, Kyoto 606, Japan.
[NISC Comparative Sequencing Progra] NIH, NIH Intramural Sequencing Ctr, Bethesda, MD 20892 USA.
[Zhang, Suiyuan; Cruz, Pedro; Renaud, Gabriel; Hansen, Nancy F.; Cherukuri, Praveen F.; Borate, Bhavesh; Elkahloun, Abdel; Mullikin, James C.; Wolfsberg, Tyra G.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[McManus, Kirk J.; Stoepel, Jan; Sipahimalani, Payal; Hieter, Philip] Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA.
[Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA.
[Elliot, Gene] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP Bell, DW (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
EM belldaph@mail.nih.gov; kmyung@mail.nih.gov
OI Stoepel, Jan/0000-0002-1559-3852
FU NHGRI, NIH; NCI, NIH; Ministry of Education, Science, Sports, and
Culture of Japan; Canadian Institutes of Health Research (CIHR)
[MOP-38096]; Korean Research Foundation; NIH [R01 CA140323,
RO1-1CA112021-01]; Ovarian Cancer Research Fund; NCI SPORE in breast
cancer at Massachusetts General Hospital; Avon Foundation; [U01
CA113916]
FX This research was supported by the intramural research program of the
NHGRI, NIH, to DWB and KM; the intramural research program of the NCI,
NIH, to CV; the Ministry of Education, Science, Sports, and Culture of
Japan grant to MT and MI; Canadian Institutes of Health Research (CIHR)
grant MOP-38096 (PH); the Korean Research Foundation (KL); NIH R01
CA140323 (AKG); U01 CA113916 (AKG); the Ovarian Cancer Research Fund
(AKG); NIH RO1-1CA112021-01 (DCS); the NCI SPORE in breast cancer at
Massachusetts General Hospital (DCS); and the Avon Foundation (DCS). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 52
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD AUG
PY 2011
VL 7
IS 8
AR e1002245
DI 10.1371/journal.pgen.1002245
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 812MG
UT WOS:000294297000038
PM 21901109
ER
PT J
AU Hamza, TH
Chen, HL
Hill-Burns, EM
Rhodes, SL
Montimurro, J
Kay, DM
Tenesa, A
Kusel, VI
Sheehan, P
Eaaswarkhanth, M
Yearout, D
Samii, A
Roberts, JW
Agarwal, P
Bordelon, Y
Park, Y
Wang, LY
Gao, JJ
Vance, JM
Kendler, KS
Bacanu, SA
Scott, WK
Ritz, B
Nutt, J
Factor, SA
Zabetian, CP
Payami, H
AF Hamza, Taye H.
Chen, Honglei
Hill-Burns, Erin M.
Rhodes, Shannon L.
Montimurro, Jennifer
Kay, Denise M.
Tenesa, Albert
Kusel, Victoria I.
Sheehan, Patricia
Eaaswarkhanth, Muthukrishnan
Yearout, Dora
Samii, Ali
Roberts, John W.
Agarwal, Pinky
Bordelon, Yvette
Park, Yikyung
Wang, Liyong
Gao, Jianjun
Vance, Jeffery M.
Kendler, Kenneth S.
Bacanu, Silviu-Alin
Scott, William K.
Ritz, Beate
Nutt, John
Factor, Stewart A.
Zabetian, Cyrus P.
Payami, Haydeh
TI Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene
GRIN2A as a Parkinson's Disease Modifier Gene via Interaction with
Coffee
SO PLOS GENETICS
LA English
DT Article
ID RISK-FACTORS; ASSOCIATION; SMOKING; CAFFEINE; MODEL; TRIAL; ONSET;
ISTRADEFYLLINE; METAANALYSIS; VARIANTS
AB Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P(2df)=10(-6), GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6x10(-7)) but not in light coffee-drinkers. The a priori Replication hypothesis that "Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers" was confirmed: OR(Replication) = 0.59, P(Replication) = 10(-3); OR(Pooled) = 0.51, P(Pooled) = 7x10(-8). Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3x10(-3)), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6x10(-13)). Imputation revealed a block of SNPs that achieved P(2df)<5x10(-8) in GWAIS, and OR = 0.41, P = 3x10(-8) in heavy coffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify genes that are missed in GWAS. Both adenosine antagonists (caffeine-like) and glutamate antagonists (GRIN2A-related) are being tested in clinical trials for treatment of PD. GRIN2A may be a useful pharmacogenetic marker for subdividing individuals in clinical trials to determine which medications might work best for which patients.
C1 [Hamza, Taye H.; Hill-Burns, Erin M.; Montimurro, Jennifer; Kay, Denise M.; Kusel, Victoria I.; Sheehan, Patricia; Eaaswarkhanth, Muthukrishnan; Yearout, Dora; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
[Chen, Honglei; Gao, Jianjun] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Rhodes, Shannon L.; Ritz, Beate] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Tenesa, Albert] Univ Edinburgh, Roslin Inst, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Yearout, Dora; Samii, Ali; Zabetian, Cyrus P.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
[Yearout, Dora; Samii, Ali; Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA.
[Agarwal, Pinky] Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA.
[Bordelon, Yvette; Ritz, Beate] Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA.
[Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol, Bethesda, MD 20892 USA.
[Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Genet, Bethesda, MD 20892 USA.
[Wang, Liyong; Vance, Jeffery M.; Scott, William K.] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL 33136 USA.
[Wang, Liyong; Vance, Jeffery M.; Scott, William K.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL 33136 USA.
[Kendler, Kenneth S.; Bacanu, Silviu-Alin] Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA.
[Ritz, Beate] Univ Calif Los Angeles, Sch Publ Hlth, Ctr Occupat & Environm Hlth, Dept Environm Hlth Sci, Los Angeles, CA 90024 USA.
[Nutt, John] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
RP Hamza, TH (reprint author), New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
EM hpayami@wadsworth.org
RI Ritz, Beate/E-3043-2015;
OI Kay, Denise/0000-0002-9928-2698; Zabetian, Cyrus/0000-0002-7739-4306;
Eaaswarkhanth, Muthukrishnan/0000-0001-9631-8555; Chen,
Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X
FU National Institute of Neurological Disorders and Stroke (NINDS) [R01
NS36960, R01 NS067469]; Michael J. Fox Foundation; Department of
Veterans Affairs [1I01BX000531]; Close to a Cure Foundation, Research of
Foundation for the Carolinas; National Institutes of Health
[HHSN268200782096C]; National Institute of Environmental Health Sciences
(NIEHS) [R01 ES010544, P01 ES016732]; UCLA Center for Neurodegeneration
Science; NINDS [P50 NS038367, P50 NS039764]; NIEHS [Z01-ES-101986];
National Cancer Institute [Z01 CP010196-02]
FX NGRC was supported by grants from the National Institute of Neurological
Disorders and Stroke (NINDS) R01 NS36960 and R01 NS067469
(http://www.ninds.nih.gov/) and from the Michael J. Fox Foundation
(Edmond J. Safra Global Genetics Consortia)
(http://www.michaeljfox.org/). Additional support for subject
recruitment was provided by the Department of Veterans Affairs
(1I01BX000531) and The Close to a Cure Foundation: A Fund for
Parkinson's Research of Foundation for the Carolinas. Genome-wide
genotyping was performed at CIDR and funded by the National Institutes
of Health (HHSN268200782096C). The PEG study was funded by National
Institute of Environmental Health Sciences (NIEHS R01 ES010544 and P01
ES016732), UCLA Center for Neurodegeneration Science, and NINDS (P50
NS038367). The PAGE study was supported by NIEHS (Z01-ES-101986) and the
National Cancer Institute (Z01 CP010196-02). HIHG was supported by NINDS
(P50 NS039764). Some of the HIHG samples were collected while JMV and
WKS were faculty members at Duke University. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the funding agencies. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
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PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD AUG
PY 2011
VL 7
IS 8
AR e1002237
DI 10.1371/journal.pgen.1002237
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 812MG
UT WOS:000294297000032
PM 21876681
ER
PT J
AU Lewis, A
Wilson, N
Stearns, G
Johnson, N
Nelson, R
Brockerhoff, SE
AF Lewis, Alaron
Wilson, Neil
Stearns, George
Johnson, Nicolas
Nelson, Ralph
Brockerhoff, Susan E.
TI Celsr3 Is Required for Normal Development of GABA Circuits in the Inner
Retina
SO PLOS GENETICS
LA English
DT Article
ID 7-PASS TRANSMEMBRANE CADHERIN; IN-SITU HYBRIDIZATION; OPTOKINETIC
RESPONSE; TRANSGENIC ZEBRAFISH; BEHAVIORAL SCREEN; VIVO DEVELOPMENT;
BIPOLAR CELLS; FLAMINGO; DROSOPHILA; RECEPTORS
AB The identity of the specific molecules required for the process of retinal circuitry formation is largely unknown. Here we report a newly identified zebrafish mutant in which the absence of the atypical cadherin, Celsr3, leads to a specific defect in the development of GABAergic signaling in the inner retina. This mutant lacks an optokinetic response (OKR), the ability to visually track rotating illuminated stripes, and develops a super-normal b-wave in the electroretinogram (ERG). We find that celsr3 mRNA is abundant in the amacrine and ganglion cells of the retina, however its loss does not affect synaptic lamination within the inner plexiform layer (IPL) or amacrine cell number. We localize the ERG defect pharmacologically to a late-stage disruption in GABAergic modulation of ON-bipolar cell pathway and find that the DNQX-sensitive fast b1 component of the ERG is specifically affected in this mutant. Consistently, we find an increase in GABA receptors on mutant ON-bipolar terminals, providing a direct link between the observed physiological changes and alterations in GABA signaling components. Finally, using blastula transplantation, we show that the lack of an OKR is due, at least partially, to Celsr3-mediated defects within the brain. These findings support the previously postulated inner retina origin for the b1 component and reveal a new role for Celsr3 in the normal development of ON visual pathway circuitry in the inner retina.
C1 [Lewis, Alaron; Wilson, Neil; Stearns, George; Johnson, Nicolas; Brockerhoff, Susan E.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Nelson, Ralph] NINDS, Basic Neurosci Program, NIH, Rockville, MD USA.
RP Lewis, A (reprint author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
EM sbrocker@uw.edu
FU National Institute of Neurological Disorders and Stroke; NIH NEI
[EY015165, EY018814]; NRSA [EY019210]; UW Vision Core facility
[P3OEY01733]
FX This research was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke (RN), NIH NEI
grants EY015165 and EY018814 (SEB), an NRSA postdoctoral fellowship
EY019210 (AL), and the UW Vision Core facility (P3OEY01733). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
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PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD AUG
PY 2011
VL 7
IS 8
AR e1002239
DI 10.1371/journal.pgen.1002239
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 812MG
UT WOS:000294297000034
PM 21852962
ER
PT J
AU Pandrea, I
Gaufin, T
Gautam, R
Kristoff, J
Mandell, D
Montefiori, D
Keele, BF
Ribeiro, RM
Veazey, RS
Apetrei, C
AF Pandrea, Ivona
Gaufin, Thaidra
Gautam, Rajeev
Kristoff, Jan
Mandell, Daniel
Montefiori, David
Keele, Brandon F.
Ribeiro, Ruy M.
Veazey, Ronald S.
Apetrei, Cristian
TI Functional Cure of SIVagm Infection in Rhesus Macaques Results in
Complete Recovery of CD4(+) T Cells and Is Reverted by CD8(+) Cell
Depletion
SO PLOS PATHOGENS
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; AFRICAN-GREEN MONKEYS; IN-VIVO
REPLICATION; ANTIRETROVIRAL THERAPY; HIV-1 INFECTION;
GASTROINTESTINAL-TRACT; LONG-TERM; PIGTAILED MACAQUES; VIRAL
REPLICATION; CORECEPTOR USAGE
AB Understanding the mechanism of infection control in elite controllers (EC) may shed light on the correlates of control of disease progression in HIV infection. However, limitations have prevented a clear understanding of the mechanisms of elite controlled infection, as these studies can only be performed at randomly selected late time points in infection, after control is achieved, and the access to tissues is limited. We report that SIVagm infection is elite-controlled in rhesus macaques (RMs) and therefore can be used as an animal model for EC HIV infection. A robust acute infection, with high levels of viral replication and dramatic mucosal CD4(+) T cell depletion, similar to pathogenic HIV-1/SIV infections of humans and RMs, was followed by complete and durable control of SIVagm replication, defined as: undetectable VLs in blood and tissues beginning 72 to 90 days postinoculation (pi) and continuing at least 4 years; seroreversion; progressive recovery of mucosal CD4+ T cells, with complete recovery by 4 years pi; normal levels of T cell immune activation, proliferation, and apoptosis; and no disease progression. This "functional cure" of SIVagm infection in RMs could be reverted after 4 years of control of infection by depleting CD8 cells, which resulted in transient rebounds of VLs, thus suggesting that control may be at least in part immune mediated. Viral control was independent of MHC, partial APOBEC restriction was not involved in SIVagm control in RMs and Trim5 genotypes did not impact viral replication. This new animal model of EC lentiviral infection, in which complete control can be predicted in all cases, permits research on the early events of infection in blood and tissues, before the defining characteristics of EC are evident and when host factors are actively driving the infection towards the EC status.
C1 [Pandrea, Ivona; Veazey, Ronald S.] Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA 70433 USA.
[Pandrea, Ivona] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA.
[Pandrea, Ivona; Kristoff, Jan; Apetrei, Cristian] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15213 USA.
[Gaufin, Thaidra; Gautam, Rajeev; Mandell, Daniel; Apetrei, Cristian] Tulane Natl Primate Res Ctr, Div Microbiol, Covington, LA USA.
[Montefiori, David] Duke Univ, Dept Surg, Durham, NC USA.
[Keele, Brandon F.] NCI, SAIC Frederick Inc, NIH, Frederick, MD 21701 USA.
[Ribeiro, Ruy M.] Los Alamos Natl Lab, Los Alamos, NM USA.
[Apetrei, Cristian] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA.
RP Pandrea, I (reprint author), Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA 70433 USA.
EM apetreic@cvr.pitt.edu
OI Ribeiro, Ruy/0000-0002-3988-8241
FU NIH/NIAID/NCRR [RO1 AI064066, R21AI069935, R01 AI065325, R01 RR025781,
RR-00168]; Tulane Research Enhancement Fund; American Foundation for
AIDS Research (AMFAR) [107151-44 RGRL]; National Cancer Institute,
National Institutes of Health [HHSN266200400088C]
FX This work was supported by NIH/NIAID/NCRR grants RO1 AI064066 and
R21AI069935 (IP), R01 AI065325 (CA), R01 RR025781 (CA/IP) and RR-00168
(TNPRC). The study was also supported by the Tulane Research Enhancement
Fund and grant 107151-44 RGRL from the American Foundation for AIDS
Research (AMFAR). Portions of this work were supported with federal
funds from the National Cancer Institute, National Institutes of Health
under contract HHSN266200400088C. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 57
TC 38
Z9 38
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2011
VL 7
IS 8
AR e1002170
DI 10.1371/journal.ppat.1002170
PG 15
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 812MR
UT WOS:000294298100013
PM 21829366
ER
PT J
AU Wilson, MS
Cheever, AW
White, SD
Thompson, RW
Wynn, TA
AF Wilson, Mark S.
Cheever, Allen W.
White, Sandra D.
Thompson, Robert W.
Wynn, Thomas A.
TI IL-10 Blocks the Development of Resistance to Re-Infection with
Schistosoma mansoni
SO PLOS PATHOGENS
LA English
DT Article
ID REGULATORY T-CELLS; OCCUPATIONALLY EXPOSED ADULTS; T-HELPER-2 CYTOKINE
RESPONSES; IMMUNE-RESPONSES; GRANULOMA-FORMATION; LEISHMANIA-MAJOR;
IN-VIVO; ANTISCHISTOSOMAL DRUGS; MURINE SCHISTOSOMIASIS; HAEMATOBIUM
INFECTION
AB Despite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high. Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals. Using a well-established and highly permissive mouse model, we investigated whether immunoregulatory mechanisms influence the development of resistance. Following Praziquantel (PZQ) treatment of S. mansoni infected mice we observed a significant and mixed anti-worm response, characterized by Th1, Th2 and Th17 responses. Despite the elevated anti-worm response in PBMC's, liver, spleen and mesenteric lymph nodes, this did not confer any protection from a secondary challenge infection. Because a significant increase in IL-10-producing CD4(+)CD44(+)CD25(+)GITR(+) lymphocytes was observed, we hypothesised that IL-10 was obstructing the development of resistance. Blockade of IL-10 combined with PZQ treatment afforded a greater than 50% reduction in parasite establishment during reinfection, compared to PZQ treatment alone, indicating that IL-10 obstructs the development of acquired resistance. Markedly enhanced Th1, Th2 and Th17 responses, worm-specific IgG1, IgG2b and IgE and circulating eosinophils characterized the protection. This study demonstrates that blocking IL-10 signalling during PZQ treatment can facilitate the development of protective immunity and provide a highly effective strategy to protect against reinfection with S. mansoni.
C1 [Wilson, Mark S.; White, Sandra D.; Thompson, Robert W.; Wynn, Thomas A.] NIAID, Immunopathogensis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Cheever, Allen W.] Biomed Res Inst, Rockville, MD 20852 USA.
RP Wilson, MS (reprint author), NIAID, Immunopathogensis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mwilson@nimr.mrc.ac.uk
RI Wynn, Thomas/C-2797-2011
FU NIAID/NIH
FX The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The research
presented was supported by the Intramural Research Program, NIAID/NIH.
NR 87
TC 35
Z9 36
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD AUG
PY 2011
VL 7
IS 8
AR e1002171
DI 10.1371/journal.ppat.1002171
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 812MR
UT WOS:000294298100014
PM 21829367
ER
PT J
AU Gaiser, T
Berroa-Garcia, L
Kemmerling, R
Dutta, A
Ried, T
Heselmeyer-Haddad, K
AF Gaiser, Timo
Berroa-Garcia, Lissa
Kemmerling, Ralf
Dutta, Aparajita
Ried, Thomas
Heselmeyer-Haddad, Kerstin
TI Automated analysis of protein expression and gene amplification within
the same cells of paraffin-embedded tumour tissue
SO CELLULAR ONCOLOGY
LA English
DT Article
DE Automated image analysis; Fluorescence in situ hybridization;
Immunofluorescence; Image relocation
ID COMPARATIVE GENOMIC HYBRIDIZATION; BREAST-CANCER; CHROMOSOMAL GAINS;
COMBINED FISH; COLON-CANCER; GUIDELINES; HER2; IMMUNOHISTOCHEMISTRY;
HETEROGENEITY; CARCINOMA
AB The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining. Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell.
Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion.
Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217. There was no significant difference between CD133 positive tumour and CD133 negative tumour cells.
The technique and algorithm presented here enables an easy and reproducible combination of IHC and FISH based on a novel automated algorithm using relocation and automated spot counting.
C1 [Gaiser, Timo; Berroa-Garcia, Lissa; Ried, Thomas; Heselmeyer-Haddad, Kerstin] NCI, Sect Canc Genom, NIH, Bethesda, MD 20892 USA.
[Kemmerling, Ralf] Paracelsus Med Univ, Inst Pathol, A-5020 Salzburg, Austria.
[Dutta, Aparajita] MetaSystems, Waltham, MA 02451 USA.
RP Ried, T (reprint author), NCI, Sect Canc Genom, NIH, Bldg 50,Room 1408,50 South Dr, Bethesda, MD 20892 USA.
EM riedt@mail.nih.gov
FU NIH, National Cancer Institute; Mildred Scheel Foundation
FX Timo Gaiser is supported by a fellowship within the post doctorate
program of the Mildred Scheel Foundation. The study was supported by the
Intramural Research Program by the NIH, National Cancer Institute.
NR 26
TC 1
Z9 1
U1 2
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 2211-3428
J9 CELL ONCOL
JI Cell. Oncol.
PD AUG
PY 2011
VL 34
IS 4
BP 337
EP 342
DI 10.1007/s13402-011-0032-x
PG 6
WC Oncology; Cell Biology; Pathology
SC Oncology; Cell Biology; Pathology
GA 813EV
UT WOS:000294350500007
PM 21656271
ER
PT J
AU Denardo, SJ
Wen, XR
Handberg, EM
Merz, CNB
Sopko, GS
Cooper-DeHoff, RM
Pepine, CJ
AF Denardo, Scott J.
Wen, Xuerong
Handberg, Eileen M.
Merz, C. Noel Bairey
Sopko, George S.
Cooper-DeHoff, Rhonda M.
Pepine, Carl J.
TI Effect of Phosphodiesterase Type 5 Inhibition on Microvascular Coronary
Dysfunction in Women: A Women's Ischemia Syndrome Evaluation (WISE)
Ancillary Study
SO CLINICAL CARDIOLOGY
LA English
DT Article
ID CHEST-PAIN; ENDOTHELIAL DYSFUNCTION; ARTERY-DISEASE; FOLLOW-UP;
CARDIOVASCULAR-DISEASE; MYOCARDIAL-ISCHEMIA; SILDENAFIL CITRATE;
NATIONAL-HEART; ANGINA; GENDER
AB Background: Microvascular coronary dysfunction (MCD) is associated with symptoms and signs of ischemia, and also adverse outcomes in women without macrovascular obstructive coronary artery disease (M-CAD). Although MCD can be quantified using coronary flow reserve (CFR), treatment is poorly defined.
Hypothesis: Phosphodiesterase type 5 (PDE-5) inhibition acutely improves MCD in these women.
Methods: The subjects were 23 symptomatic women (age 54 +/- 11 y) participating in an ancillary study of the Women's lschemia Syndrome Evaluation with baseline CFR <= 3.0 (Doppler flow wire and intracoronary adenosine) and without M-CAD. Coronary flow reserve was remeasured 45 minutes after PDE-5 inhibition (100 mg oral sildenafil). The primary measure of interest was change in CFR adjusted for baseline variables.
Results: The relationship between log(2)-transformed CFR post PDE-5 inhibition (adjusted) and baseline was different from the line of identity (slope: 0.55 vs 1.0, P = 0.008; intercept: 0.73 vs 0.0, P = 0.01), indicating that PDE-5 inhibition improves CFR and the lower the baseline CFR, the greater the response. Among women with baseline CFR <= 2.5 (n = 11)CFR increased from 2.1 +/- 0.2 to 2.7 +/- 0.6 (P = 0.006). For women with baseline CFR > 2.5 (n =12), CFR did not change (3.1 +/- 0.3 to 3.0 +/- 0.6; P = 0.70).
Conclusions: For women with symptoms and signs of ischemia and no M-CAD, PDE-5 inhibition is associated with acute improvement in CFR, and the effect concentrates among those with CFR <= 2.5. If these acute effects are sustained, then PDE-5 inhibition would provide a rational strategy for management of MCD in symptomatic women without M-CAD. The longer-term effects warrant study in a randomized trial using a sustained-acting PDE-5 inhibitor.
C1 [Denardo, Scott J.] Duke Univ, Med Ctr, Div Cardiovasc Med, Durham, NC USA.
[Wen, Xuerong; Handberg, Eileen M.; Pepine, Carl J.] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA.
[Merz, C. Noel Bairey] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA.
[Sopko, George S.] NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA.
[Cooper-DeHoff, Rhonda M.] Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA.
RP Pepine, CJ (reprint author), 1600 SW Archer Rd,POB 100277, Gainesville, FL 32610 USA.
EM carl.pepine@medicine.ufl.edu
FU NCRR NIH HHS [5-UL1RR025208-02, MO1-RR00425, M01 RR000425, UL1 RR029890,
5 UL1 RR029890-02]; NHLBI NIH HHS [N01HV68163, U01 HL064829-01A1,
N01HV68162, N01 HV068161, 5 R01 HL091005-03, U01 HL649241, U01 HL087366,
T32HL69751, N01 HV068163, N01-HV-68162, N01 HV068162, T32 HL069751,
U01HL649141, N01-HV-68163, U01 HL064829, 5 R01 HL090957-03, 5 U01
HL087366-04, R01 HL091005, N01 HV068164, R01 HL090957]; NIA NIH HHS [U01
AG022376, 3 U01 AG022376-05A2S1]; NIGMS NIH HHS [U01 GM074492, 2 U01
GM074492-06]; PHS HHS [U0164829]
NR 29
TC 11
Z9 11
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0160-9289
J9 CLIN CARDIOL
JI Clin. Cardiol.
PD AUG
PY 2011
VL 34
IS 8
BP 483
EP 487
DI 10.1002/clc.20935
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 815CZ
UT WOS:000294505000004
PM 21780138
ER
PT J
AU Szebeni, A
Szentandrassy, N
Pacher, P
Simko, J
Nanasi, PP
Kecskemeti, V
AF Szebeni, A.
Szentandrassy, N.
Pacher, P.
Simko, J.
Nanasi, P. P.
Kecskemeti, V.
TI Can the Electrophysiological Action of Rosiglitazone Explain its Cardiac
Side Effects?
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE Antidiabetic agents; rosiglitazone; action potential; ion currents
ID PROLIFERATOR-ACTIVATED-RECEPTOR; TYPE-2 DIABETES-MELLITUS;
CONGESTIVE-HEART-FAILURE; PPAR-GAMMA AGONISTS; ZUCKER FATTY RATS;
VENTRICULAR MYOCYTES; CALCIUM CURRENTS; BLOOD-PRESSURE; K+ CURRENTS;
THIAZOLIDINEDIONE DRUGS
AB Recent large clinical trials found an association between the antidiabetic drug rosiglitazone therapy and increased risk of cardiovascular adverse events. The aim of this report is to elucidate the cardiac electrophysiological properties of rosiglitazone (R) on isolated rat and murine ventricular papillary muscle cells and canine ventricular myocytes using conventional microelectrode, whole cell voltage clamp, and action potential (AP) voltage clamp techniques.
In histidine-decarboxylase knockout mice as well as in their wild types R (1-30 mu M) shortened AP duration at 90% level of repolarization (APD(90)) and increased the AP amplitude (APA) in a concentration-dependent manner. In rat ventricular papillary muscle cells R (1-30 mu M) caused a significant reduction of APA and maximum velocity of depolarization (V-max) which was accompanied by lengthening of APD(90).
In single canine ventricular myocytes at concentrations >= 10 mu M R decreased the amplitude of phase-1 repolarization, the plateau potential and reduced V-max. R suppressed several ion currents in a concentration-dependent manner under voltage clamp conditions. The EC50 value for this inhibition was 25.2 +/- 2.7 mu M for the transient outward K+ current (I-to), 72.3 +/- 9.3 mu M for the rapid delayed rectifier K+ current (I-Kr), and 82.5 +/- 9.4 mu M for the L-type Ca2+ current (I-Ca) with Hill coefficients close to unity. The inward rectifier K+ current (I-K1) was not affected by R up to concentrations of 100 mu M. Suppression of I-to, I-Kr, and I-Ca has been confirmed under action potential voltage clamp conditions as well.
The observed alterations in the AP morphology and densities of ion currents may predict serious proarrhythmic risk in case of intoxication with R as a consequence of overdose or decreased elimination of the drug, particularly in patients having multiple cardiovascular risk factors, such as elderly diabetic patients.
C1 [Szebeni, A.; Kecskemeti, V.] Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, H-1445 Budapest, Hungary.
[Szentandrassy, N.; Nanasi, P. P.] Univ Debrecen, Dept Physiol, Debrecen, Hungary.
[Pacher, P.] Natl Inst Alcohol Abuse & Alcoholism, Lab Physiol Studies, Bethesda, MD USA.
[Simko, J.] Semmelweis Hlth Care Ctr, Dept Cardiol, Inst Med, Miskolc, Hungary.
RP Kecskemeti, V (reprint author), Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, Nagyvarad Ter 4 ,POB 370, H-1445 Budapest, Hungary.
EM kecsval@pharma.sote.hu
RI Pacher, Pal/B-6378-2008
OI Pacher, Pal/0000-0001-7036-8108
FU Hungarian Research Foundation [OTKA K68457, CNK-77855]; NIH/NAAA
FX This work was supported by the Hungarian Research Foundation (OTKA
K68457, CNK-77855) and by Intramural Research Program of NIH/NAAA to P.
Pacher.
NR 88
TC 4
Z9 4
U1 0
U2 10
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 AUG
PY 2011
VL 18
IS 24
BP 3720
EP 3728
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 814AR
UT WOS:000294414700011
PM 21774756
ER
PT J
AU Edlich, F
Lucke, C
AF Edlich, Frank
Luecke, Christian
TI From cell death to viral replication: the diverse functions of the
membrane-associated FKBP38
SO CURRENT OPINION IN PHARMACOLOGY
LA English
DT Article
ID BCL-2 REGULATOR FKBP38; C-VIRUS NS5A; NEURAL-TUBE; SONIC HEDGEHOG;
INHIBITS APOPTOSIS; MAMMALIAN TARGET; RAPAMYCIN; CALCINEURIN; COMPLEX;
FAMILY
AB FKBP38 is in many ways an exceptional member of the FK506-binding proteins. The calmodulin-regulated activity of FKBP38 for instance is unique within this protein family. The activated FKBP38 participates in apoptosis signaling by inhibiting the anti-apoptotic Bcl-2. Beyond this role in programmed cell death, FKBP38 seems to be involved in very different cellular processes that do not necessarily depend on the FKBP domain. These functions involve regulation of the kinase mTOR, regulation of neural tube formation, regulation of cellular hypoxia response, but also Hepatitis C virus replication. Pharmacological targeting of FKBP38 might therefore prove a successful strategy for intervention in different FKBP38-dependent processes, including programmed cell death in cancer or neurodegenerative diseases.
C1 [Luecke, Christian] Max Planck Res Unit Enzymol Prot Folding, D-06120 Halle, Saale, Germany.
[Edlich, Frank] NINDS, NIH, Surg Neurol Branch, Bethesda, MD 20892 USA.
RP Lucke, C (reprint author), Max Planck Res Unit Enzymol Prot Folding, Weinbergweg 22, D-06120 Halle, Saale, Germany.
EM luecke@enzyme-halle.mpg.de
NR 49
TC 13
Z9 13
U1 0
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4892
J9 CURR OPIN PHARMACOL
JI Curr. Opin. Pharmacol.
PD AUG
PY 2011
VL 11
IS 4
BP 348
EP 353
DI 10.1016/j.coph.2011.03.011
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 812SM
UT WOS:000294313200012
PM 21514222
ER
PT J
AU Simon, R
AF Simon, Richard
TI Genomic biomarkers in predictive medicine. An interim analysis
SO EMBO MOLECULAR MEDICINE
LA English
DT Editorial Material
DE biomarkers; early detection; genomics; personalized medicine;
translational research
ID TRANSLATIONAL RESEARCH; BREAST-CANCER; CLINICAL-RESEARCH; TUMOR
EVOLUTION; OVARIAN-CANCER; ADDICTION
C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
RP Simon, R (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
EM rsimon@nih.gov
NR 30
TC 13
Z9 14
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1757-4676
J9 EMBO MOL MED
JI EMBO Mol. Med.
PD AUG
PY 2011
VL 3
IS 8
BP 429
EP 435
DI 10.1002/emmm.201100153
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 813IG
UT WOS:000294359400001
PM 21744497
ER
PT J
AU Eggesbo, M
Thomsen, C
Jorgensen, JV
Becher, G
Odland, JO
Longnecker, MP
AF Eggesbo, Merete
Thomsen, Cathrine
Jorgensen, Jens V.
Becher, Georg
Odland, Jon Oyvind
Longnecker, Matthew P.
TI Associations between brominated flame retardants in human milk and
thyroid-stimulating hormone (TSH) in neonates
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Brominated flame retardants; BDE-209; HBCD; Thyroid-stimulating hormone;
TSH; Infants
ID POLYBROMINATED DIPHENYL ETHERS; POLYCHLORINATED-BIPHENYLS PCBS; PRETERM
INFANTS; 2,2',4,4',5-PENTABROMODIPHENYL ETHER; BRAIN-DEVELOPMENT;
GESTATIONAL-AGE; PLASMA-LEVELS; BREAST-MILK; MICE; PBDES
AB Background: Brominated flame retardants (BERs) have been in widespread use in a vast array of consumer products since the 1970s. The metabolites of some BFRs show a structural similarity to thyroid hormones and experimental animal studies have confirmed that they may interfere with thyroid hormone homeostasis. A major concern has been whether intrauterine exposure to BFRs may disturb thyroid homeostasis since the fetal brain is particularly susceptible to alterations in thyroid hormones. However, few reports on newborns have been published to date.
Objectives: To evaluate the association between BFRs and neonatal thyroid-stimulating hormone (TSH). Methods: We studied six polybrominated diphenyl ethers (PBDEs) measured in milk samples from 239 women who were part of the "Norwegian Human Milk Study" (HUMIS), 2003-2006. Hexabromocyclododecane (HBCD) and BDE-209 were measured in a subset of the women (193 and 46 milk samples, respectively). The milk was sampled at a median of 33 days after delivery. TSH was measured in babies three days after delivery as part of the routine national screening program for early detection of congenital hypothyroidism. Additional information was obtained through the Medical Birth Registry and questionnaires to the mothers.
Results: The PBDE concentrations in human milk in Norway were comparable to concentrations reported from other European countries and Asia, but not the US and Canada where levels are approximately one order of higher magnitude. We observed no statistically significant associations between BDE-47, 99, 153, 154, 209 and HBCD in human milk and TSH in models adjusted for possible confounders and other environmental toxicants including polychlorinated biphenyls (PCBs).
Conclusions: We did not observe an association between TSH and exposure to HBCD and PBDEs within the exposure levels observed. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Eggesbo, Merete] Norwegian Inst Publ Hlth, Dept Genes & Environm, Div Epidemiol, N-0403 Oslo, Norway.
[Eggesbo, Merete; Longnecker, Matthew P.] Natl Inst Environm Hlth Sci, NIH, US Dept HHS, Res Triangle Pk, NC USA.
[Thomsen, Cathrine; Becher, Georg] Norwegian Inst Publ Hlth, Div Environm Med, Oslo, Norway.
[Jorgensen, Jens V.] Univ Oslo, Rikshosp, Oslo Univ Hosp, Dept Pediat Res, N-0027 Oslo, Norway.
[Odland, Jon Oyvind] Univ Tromso, Inst Community Med, N-9001 Tromso, Norway.
RP Eggesbo, M (reprint author), Norwegian Inst Publ Hlth, Dept Genes & Environm, Div Epidemiol, POB 4404 Nydalen, N-0403 Oslo, Norway.
EM merete.eggesbo@fhi.no
OI Longnecker, Matthew/0000-0001-6073-5322; Eggesbo,
Merete/0000-0002-0006-5336; Odland, Jon Oyvind/0000-0002-2756-0732
FU European Community [227391]; National Institute of Environmental Health
Sciences
FX This research was supported by a grant from the European Community's
Seventh Framework Program [FP7/2007-2013] under grant agreement OBELIX
no. 227391 and the intramural research program of the National Institute
of Environmental Health Sciences.
NR 45
TC 23
Z9 24
U1 1
U2 29
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
J9 ENVIRON RES
JI Environ. Res.
PD AUG
PY 2011
VL 111
IS 6
BP 737
EP 743
DI 10.1016/j.envres.2011.05.004
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 804RI
UT WOS:000293671300001
PM 21601188
ER
PT J
AU Sepeta, L
Zimmaro, LA
Duke, ES
Berl, MM
VanMeter, J
Vaidya, CJ
Yerys, B
Gaillard, WD
AF Sepeta, L.
Zimmaro, L. A.
Duke, E. S.
Berl, M. M.
VanMeter, J.
Vaidya, C. J.
Yerys, B.
Gaillard, W. D.
TI FUNCTIONAL CONNECTIVITY OF LANGUAGE ACTIVATION IN CHILDHOOD FOCAL
EPILEPSY
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 29th International Epilepsy Congress
CY AUG 28-SEP 01, 2011
CL Rome, ITALY
C1 [Sepeta, L.; Zimmaro, L. A.; Duke, E. S.; Berl, M. M.; Vaidya, C. J.; Yerys, B.; Gaillard, W. D.] Childrens Natl, Washington, DC USA.
[Zimmaro, L. A.; Gaillard, W. D.] NINDS, NIH, Bethesda, MD 20892 USA.
[VanMeter, J.] Georgetown Univ, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD AUG
PY 2011
VL 52
SU 6
SI SI
BP 4
EP 5
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 811NE
UT WOS:000294217200004
ER
PT J
AU Hirvonen, J
Kreisl, WC
Fujita, M
Dustin, I
Khan, O
Appel, S
Zhang, Y
Morse, C
Pike, VW
Innis, RB
Theodore, WH
AF Hirvonen, J.
Kreisl, W. C.
Fujita, M.
Dustin, I
Khan, O.
Appel, S.
Zhang, Y.
Morse, C.
Pike, V. W.
Innis, R. B.
Theodore, W. H.
TI INCREASED IN VIVO EXPRESSION OF AN INFLAMMATORY MARKER IN TEMPORAL LOBE
EPILEPSY
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 29th International Epilepsy Congress
CY AUG 28-SEP 01, 2011
CL Rome, ITALY
C1 [Hirvonen, J.; Kreisl, W. C.; Fujita, M.; Zhang, Y.; Morse, C.; Pike, V. W.; Innis, R. B.] NIMH, NIH, Bethesda, MD 20892 USA.
[Dustin, I; Khan, O.; Appel, S.; Theodore, W. H.] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD AUG
PY 2011
VL 52
SU 6
SI SI
BP 175
EP 175
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA 811NE
UT WOS:000294217200564
ER
PT J
AU Lieb, W
Pencina, MJ
Jacques, PF
Wang, TJ
Larson, MG
Levy, D
Kannel, WB
Vasan, RS
AF Lieb, Wolfgang
Pencina, Michael J.
Jacques, Paul F.
Wang, Thomas J.
Larson, Martin G.
Levy, Daniel
Kannel, William B.
Vasan, Ramachandran S.
TI Higher aldosterone and lower N-terminal proatrial natriuretic peptide as
biomarkers of salt sensitivity in the community
SO EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION & REHABILITATION
LA English
DT Article
DE Salt sensitivity; aldosterone; N-terminal proatrial natriuretic peptide;
ANP
ID FOOD FREQUENCY QUESTIONNAIRE; METABOLIC RISK-FACTORS; BLOOD-PRESSURE;
GLOMERULAR-FILTRATION; SODIUM-INTAKE; HYPERTENSION; ASSOCIATION;
POTASSIUM; PLASMA; MICE
AB Background: Salt sensitivity, a trait characterized by a pressor blood pressure response to increased dietary salt intake, has been associated with higher rates of cardiovascular target organ damage and cardiovascular disease events. Recent experimental studies have highlighted the potential role of the natriuretic peptides and aldosterone in mediating salt sensitivity.
Design: Prospective cohort study.
Methods: We evaluated 1575 non-hypertensive Framingham Offspring cohort participants (mean age 55 +/- 9 years, 58% women) who underwent routine measurements of circulating aldosterone and N-terminal proatrial natriuretic peptide (NT-ANP) and assessment of dietary sodium intake. Participants were categorized as potentially 'salt sensitive' if their serum aldosterone was > sex-specific median but plasma NT-ANP was <= sex-specific median value. Dietary sodium intake was categorized as lower versus higher (dichotomized at the sex-specific median). We used multivariable linear regression to relate presence of salt sensitivity (as defined above) to longitudinal changes (Delta) in systolic and diastolic blood pressure on follow-up (median four years).
Results: Participants who were 'salt sensitive' (N=437) experienced significantly greater increases in blood pressure (Delta systolic, +4.4 and +2.3 mmHg; Delta diastolic, +1.9 and -0.3 mmHg; on a higher versus lower sodium diet, respectively) as compared to the other participants (Delta systolic, +2.8 and +1.0 mmHg; Delta diastolic, +0.5 and -0.2 mmHg; on higher versus lower sodium diet, respectively; P=0.033 and P=0.0127 for differences between groups in Delta systolic and Delta diastolic blood pressure, respectively).
Conclusions: Our observational data suggest that higher circulating aldosterone and lower NT-ANP concentrations may be markers of salt sensitivity in the community. Additional studies are warranted to confirm these observations.
C1 [Lieb, Wolfgang; Levy, Daniel; Kannel, William B.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.
[Pencina, Michael J.; Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Jacques, Paul F.] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA.
[Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
EM vasan@bu.edu
RI Lieb, Wolfgang/C-1990-2012;
OI Larson, Martin/0000-0002-9631-1254; Ramachandran,
Vasan/0000-0001-7357-5970
FU NHLBI [N01-HC-25195, 2 K24 HL04334]; US Department of Agriculture,
Agricultural Research Service [58-1950-7-707]
FX This work was supported by NHLBI Contract N01-HC-25195 and 2 K24 HL04334
(to RSV); and the US Department of Agriculture, Agricultural Research
Service, agreement No. 58-1950-7-707.
NR 38
TC 3
Z9 5
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1741-8267
J9 EUR J CARDIOV PREV R
JI Eur. J. Cardiovasc. Prev. Rehabil.
PD AUG
PY 2011
VL 18
IS 4
BP 664
EP 673
DI 10.1177/1741826710389406
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 813ON
UT WOS:000294376900018
PM 21450637
ER
PT J
AU Chun, JH
Lu, SY
Pike, VW
AF Chun, Joong-Hyun
Lu, Shuiyu
Pike, Victor W.
TI Rapid and Efficient Radiosyntheses of meta-Substituted
[F-18]Fluoroarenes from [F-18]Fluoride Ion and Diaryliodonium Tosylates
within a Microreactor
SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
DE Isotopic labeling; Fluorine-18; Hypervalent compounds; Microreactors;
Iodonium salts
ID POSITRON-EMISSION-TOMOGRAPHY; DRUG DEVELOPMENT; IODONIUM SALTS; F-18;
PET; (DIACETOXYIODO)ARENES; IODOARENES; OXIDANT; REACTOR; ROUTE
AB Effective methods for the introduction of the short-lived positron-emitter fluorine-18 (t(1/2) = 109.7 min) at high specific radioactivity into fluoroarenes are valuable for the development of radiotracers for molecular imaging with positron emission tomography. We have explored the scope of the radiofluorination of diaryliodonium salts with no-carrier-added (NCA) [F-18]fluoride ion for the preparation of otherwise difficult to access meta-substituted [F-18] fluoroarenes. A microfluidic reaction platform was used to establish optimal radiochemical yields. Rapid, high yielding and selective radiofluorinations were achieved in unsymmetrical diaryliodonium to-sylates (ArI+Ar'TsO-), in which Ar carried either a meta electron-withdrawing (CN, NO2, CF3) or electron-donating (Me or MeO) group, and in which the partner aryl group (Ar') was relatively electron-rich, such as Ph, 3-MeC6H4, 4-Me-OC6H4, 2-thienyl, or 5-Me-2-thienyl. The radiofluorination of appropriate diaryliodonium tosylates is therefore a generally useful method for the preparation of simple [F-18]m-fluoroarenes ([F-18]ArF).
C1 [Chun, Joong-Hyun; Lu, Shuiyu; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr,Bldg 10,Room B3 C346A, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
FU National Institutes of Health (NIMH)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIMH). The authors are grateful to the
NIH Clinical Center PET Department (Chief, Dr. Peter Herscovitch) for
the cyclotron production of fluorine-18.
NR 45
TC 24
Z9 24
U1 1
U2 16
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1434-193X
J9 EUR J ORG CHEM
JI Eur. J. Org. Chem.
PD AUG
PY 2011
IS 23
BP 4439
EP 4447
DI 10.1002/ejoc.201100382
PG 9
WC Chemistry, Organic
SC Chemistry
GA 813DR
UT WOS:000294347500021
PM 22016665
ER
PT J
AU Volkow, ND
Montaner, J
AF Volkow, Nora D.
Montaner, Julio
TI The Urgency Of Providing Comprehensive And Integrated Treatment For
Substance Abusers With HIV
SO HEALTH AFFAIRS
LA English
DT Article
ID INJECTION-DRUG USERS; SEXUALLY-TRANSMITTED INFECTIONS; ACTIVE
ANTIRETROVIRAL THERAPY; US METROPOLITAN-AREAS; C VIRUS-INFECTION;
UNITED-STATES; STRUCTURAL INTERVENTIONS; HEPATITIS-C; TREATMENT
PROGRAMS; PUBLIC-HEALTH
AB Substance abuse is linked to many new cases of HIV infection. Barriers such as the myth that drug users cannot adhere to HIV/AIDS treatment block progress in curbing the spread of HIV in that population. In this article we explain the need to aggressively seek out high-risk, hard-to-reach substance abusers and to offer them HIV testing, access to treatment, and the necessary support to remain in treatment-both for HIV and for substance abuse. We summarize evidence showing that injection drug users can successfully undergo HIV treatment; that many substance abusers adhere to antiretroviral therapy as well as do people who don't inject drugs; and that injection drug users who undergo substance abuse treatment are more likely to obtain and stay in treatment for their HIV infection. This evidence makes a strong case for integrating substance abuse treatment with HIV treatment programs and providing substance abusers with universal access to HIV treatment. But an integrated strategy will require changes in the health care system to overcome lingering obstacles that inhibit the merging of substance abuse treatment with HIV programs.
C1 [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA.
[Montaner, Julio] HIV AIDS, British Columbia Ctr Excellence, Burnaby, BC, Canada.
[Montaner, Julio] Univ British Columbia Vancouver, Vancouver, BC, Canada.
RP Volkow, ND (reprint author), Natl Inst Drug Abuse, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
FU Intramural NIH HHS [Z99 DA999999]; NIDA NIH HHS [DP1 DA026182]
NR 69
TC 29
Z9 29
U1 1
U2 6
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD AUG
PY 2011
VL 30
IS 8
BP 1411
EP 1419
DI 10.1377/hlthaff.2011.0663
PG 9
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 803BW
UT WOS:000293556100004
PM 21821558
ER
PT J
AU Faia, LJ
Sen, HN
Li, ZQ
Yeh, S
Wroblewski, KJ
Nussenblatt, RB
AF Faia, Lisa J.
Sen, H. Nida
Li, Zhuqing
Yeh, Steven
Wroblewski, Keith J.
Nussenblatt, Robert B.
TI Treatment of Inflammatory Macular Edema with Humanized Anti-CD11a
Antibody Therapy
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article; Proceedings Paper
CT Meeting of the American-Academy-of-Ophthalmology
CY AUG, 2008
CL Atlanta, GA
SP Amer Acad Ophthalmol
ID NATURAL-KILLER-CELLS; IMMUNOSUPPRESSIVE DRUGS; MONOCLONAL-ANTIBODIES;
PLAQUE PSORIASIS; EXPERT PANEL; NK CELLS; IN-VIVO; EFALIZUMAB; UVEITIS;
EXPRESSION
AB PURPOSE. To evaluate the safety and efficacy of treating macular edema, secondary to noninfectious uveitis, with a humanized anti-CD11a antibody.
METHODS. Six patients received weekly subcutaneous treatments for 16 weeks according to this open-label, prospective, noncomparative phase I/II trial. Best corrected visual acuity (BCVA) and central macular thickness (CMT) were compared to baseline. Adverse events were recorded and assessed. Blood was sampled to assess the levels of CD56(bright) regulatory NK cells before initiation and after termination of the study.
RESULTS. No serious adverse events were reported by the patients. Patients' ages ranged from 22 to 82 years. Mean BCVA improvements were 6.7 +/- 6.9 ETDRS letters in the worse eye and 1.7 +/- 5.2 letters in the better eye. Mean CMT reductions were 128 +/- 105 mu m in the worse eye and 57 +/- 68 mu m in the better eye. Anti-CD11a antibody treatments resulted in an increase in the CD56(bright) regulatory NK cell population in the peripheral blood of the patients.
CONCLUSIONS. Anti-CD11a treatment improved visual function, reduced macular thickness, and increased the level of CD56(bright) regulatory NK cells in patients with uveitic macular edema refractory to other immunosuppressive medications. Targeting CD11a may be beneficial in treating other causes of macular edema. (ClinicalTrials.gov number, NCT00280826.) (Invest Ophthalmol Vis Sci. 2011;52:6919-6924) DOI:10.1167/iovs.10-5896
C1 [Faia, Lisa J.; Sen, H. Nida; Li, Zhuqing; Yeh, Steven; Wroblewski, Keith J.; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Faia, Lisa J.] Associated Retinal Consultants PC, Royal Oak, MI USA.
[Yeh, Steven] Casey Eye Inst, Portland, OR USA.
[Wroblewski, Keith J.] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
RP Sen, HN (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10 N 112, Bethesda, MD 20892 USA.
EM senh@nei.nih.gov
FU Intramural NIH HHS
NR 25
TC 6
Z9 6
U1 0
U2 0
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 AUG
PY 2011
VL 52
IS 9
BP 6919
EP 6924
DI 10.1167/iovs.10-5896
PG 6
WC Ophthalmology
SC Ophthalmology
GA 815SI
UT WOS:000294548300071
PM 21498606
ER
PT J
AU Yu, CR
Mahdi, RR
Oh, HM
Amadi-Obi, A
Levy-Clarke, G
Burton, J
Eseonu, A
Lee, Y
Chan, CC
Egwuagu, CE
AF Yu, Cheng-Rong
Mahdi, Rashid R.
Oh, Hyun-Mee
Amadi-Obi, Ahjoku
Levy-Clarke, Grace
Burton, Jenna
Eseonu, Amarachi
Lee, YongJun
Chan, Chi-Chao
Egwuagu, Charles E.
TI Suppressor of Cytokine Signaling-1 (SOCS1) Inhibits Lymphocyte
Recruitment into the Retina and Protects SOCS1 Transgenic Rats and Mice
from Ocular Inflammation
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; CD4(+) T-CELLS; INDUCED STAT
INHIBITOR; GAMMA-INTERFERON; CD154 EXPRESSION; GENE-EXPRESSION;
IFN-GAMMA; TNF-ALPHA; UVEITIS; PROTEINS
AB PURPOSE. Suppressors of cytokine signaling (SOCS) proteins regulate the intensity and duration of cytokine signals and defective expression of SOCS1 and SOCS3 has been reported in a number of human diseases. The purpose of this study was to investigate the role of SOCS1 in intraocular inflammatory diseases (uveitis) and whether SOCS1 expression is defective in patients with ocular inflammatory diseases.
METHODS. Blood from patients with scleritis or healthy human volunteers was analyzed for SOCS expression by RNase protection assay and RT-PCR. The authors generated SOCS1 transgenic rats and mice (SOCS1-Tg), induced experimental autoimmune uveoretinitis (EAU) by active immunization with interphotoreceptor retinal binding protein or adoptive transfer of uveitogenic T cells, and investigated effects of SOCS1 overexpression on EAU. SOCS1-mediated protection of retinal cells from apoptosis was assessed by annexin V staining.
RESULTS. Induction of cytokine-induced SH2 protein was comparable between patients and volunteers, whereas 80% of lymphocytes from patients with scleritis failed to induce SOCS1 in response to IL-2. Compared with wild-type littermates, SOCS1-Tg rats/mice developed less severe EAU. Constitutive overexpression of SOCS1 in retina inhibited expression of chemokines (CCL17, CCL20, CXCL9, CXCL10), reduced Th17/Th1 expansion, and inhibited recruitment of inflammatory cells into the retina. The authors also show that SOCS1 protected retinal cells from staurosporine as well as H(2)O(2)-induced apoptosis.
CONCLUSIONS. Defective expression of SOCS1 in patients with scleritis, taken together with SOCS1-mediated protection of neuroretinal cells from apoptosis, suggest that SOCS1 has neuroprotective function in the retina, implying that administration of SOCS1 mimetic peptides may be useful in treating uveitis or scleritis. (Invest Ophthalmol Vis Sci. 2011;52:6978-6986) DOI:10.1167/iovs.11-7688
C1 [Yu, Cheng-Rong; Mahdi, Rashid R.; Oh, Hyun-Mee; Amadi-Obi, Ahjoku; Burton, Jenna; Lee, YongJun; Egwuagu, Charles E.] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Levy-Clarke, Grace] NEI, Clin Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Eseonu, Amarachi] Harvard Univ, Dept Biomed Engn, Harvard Coll, Cambridge, MA 02138 USA.
RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, Immunol Lab, NIH, Bldg 10,Room 10N116,10 Ctr Dr, Bethesda, MD 20892 USA.
EM egwuaguc@nei.nih.gov
FU National Eye Institute; National Institutes of Health
FX Supported in part by the National Eye Institute and National Institutes
of Health Intramural Research Programs.
NR 49
TC 20
Z9 20
U1 0
U2 2
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 AUG
PY 2011
VL 52
IS 9
BP 6978
EP 6986
DI 10.1167/iovs.11-7688
PG 9
WC Ophthalmology
SC Ophthalmology
GA 815SI
UT WOS:000294548300079
PM 21778271
ER
PT J
AU Perez-Edgar, K
Reeb-Sutherland, BC
McDermott, JM
White, LK
Henderson, HA
Degnan, KA
Hane, AA
Pine, DS
Fox, NA
AF Perez-Edgar, Koraly
Reeb-Sutherland, Bethany C.
McDermott, Jennifer Martin
White, Lauren K.
Henderson, Heather A.
Degnan, Kathryn A.
Hane, Amie A.
Pine, Daniel S.
Fox, Nathan A.
TI Attention Biases to Threat Link Behavioral Inhibition to Social
Withdrawal over Time in Very Young Children
SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY
LA English
DT Article
DE Temperament; Behavioral inhibition; Social withdrawal; Attention biases;
Early childhood
ID GENERALIZED ANXIETY DISORDER; PREFRONTAL CORTEX ACTIVATION; SEROTONIN
TRANSPORTER GENE; EARLY-CHILDHOOD; SELECTIVE ATTENTION; MIDDLE
CHILDHOOD; EMOTIONAL FACES; SHY CHILDREN; ANGRY FACES; FACIAL
EXPRESSIONS
AB Behaviorally inhibited children display a temperamental profile characterized by social withdrawal and anxious behaviors. Previous research, focused largely on adolescents, suggests that attention biases to threat may sustain high levels of behavioral inhibition (BI) over time, helping link early temperament to social outcomes. However, no prior studies examine the association between attention bias and BI before adolescence. The current study examined the interrelations among BI, attention biases to threat, and social withdrawal already manifest in early childhood. Children (N=187, 83 Male, M(age)=61.96 months) were characterized for BI in toddlerhood (24 & 36 months). At 5 years, they completed an attention bias task and concurrent social withdrawal was measured. As expected, BI in toddlerhood predicted high levels of social withdrawal in early childhood. However, this relation was moderated by attention bias. The BI-withdrawal association was only evident for children who displayed an attention bias toward threat. The data provide further support for models associating attention with socioemotional development and the later emergence of clinical anxiety.
C1 [Perez-Edgar, Koraly] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[Reeb-Sutherland, Bethany C.; White, Lauren K.; Degnan, Kathryn A.; Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
[McDermott, Jennifer Martin] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA.
[Henderson, Heather A.] Univ Miami, Dept Psychol, Miami, FL 33124 USA.
[Hane, Amie A.] Williams Coll, Dept Psychol, Williamstown, MA 01267 USA.
[Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20895 USA.
RP Perez-Edgar, K (reprint author), George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
EM kperezed@gmu.edu
OI Perez-Edgar, Koraly/0000-0003-4051-9563
FU NICHD NIH HHS [R37 HD017899]; NIMH NIH HHS [K01 MH073569]
NR 92
TC 77
Z9 77
U1 10
U2 40
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0091-0627
J9 J ABNORM CHILD PSYCH
JI J. Abnorm. Child Psychol.
PD AUG
PY 2011
VL 39
IS 6
BP 885
EP 895
DI 10.1007/s10802-011-9495-5
PG 11
WC Psychology, Clinical; Psychology, Developmental
SC Psychology
GA 812CH
UT WOS:000294264800011
PM 21318555
ER
PT J
AU Timpano, KR
Schmidt, NB
Wheaton, MG
Wendland, JR
Murphy, DL
AF Timpano, Kiara R.
Schmidt, Norman B.
Wheaton, Michael G.
Wendland, Jens R.
Murphy, Dennis L.
TI Consideration of the BDNF Gene in Relation to Two Phenotypes: Hoarding
and Obesity
SO JOURNAL OF ABNORMAL PSYCHOLOGY
LA English
DT Article
DE brain derived neurotrophic factor gene; Val66Met SNP; hoarding; OCD;
body mass index
ID OBSESSIVE-COMPULSIVE DISORDER; NEUROTROPHIC FACTOR BDNF; OCD
COLLABORATIVE GENETICS; BODY-MASS INDEX; VAL66MET POLYMORPHISM; EUROPEAN
POPULATIONS; HIPPOCAMPAL FUNCTION; EMOTION REGULATION; ANOREXIA-NERVOSA;
EATING BEHAVIOR
AB The gene coding for the brain derived neurotrophic factor (BDNF) has emerged as an interesting candidate for multiple brain and brain disorder-related phenomena. The primary aim of the present investigation was to consider the relationship between the BDNF Val66Met variant and two phenotypes: compulsive hoarding as a symptom dimension of obsessive-compulsive disorder (OCD), and body mass index (BMI). We examined the BDNF gene in a large (N = 301) clinical sample of probands with OCD. Participants were classified as hoarding or nonhoarding using a strict, multimeasure grouping approach. Results revealed that the Val/Val genotype was linked with hoarding classification and more severe hoarding behaviors, as well as greater BMI levels. Hoarding status was also associated with greater BMI scores, with individuals in the hoarding group being far more likely to be classified as obese compared with the nonhoarding group. Our findings may provide a distinct avenue through which hoarding and BMI could be linked. These findings are suggestive of a complex gene, body weight, and psychopathology relationship wherein a primitive, survival "thrifty gene" strategy may be conserved and represented in a subgroup of humans manifesting severe hoarding symptoms.
C1 [Timpano, Kiara R.] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA.
[Schmidt, Norman B.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA.
[Wheaton, Michael G.; Wendland, Jens R.; Murphy, Dennis L.] NIMH, Clin Sci Lab, Intramural Res Program, Bethesda, MD 20892 USA.
RP Timpano, KR (reprint author), Univ Miami, Dept Psychol, 5665 Ponce de Leon Blvd, Coral Gables, FL 33146 USA.
EM kiaratimpano@gmail.com
RI Wendland, Jens/A-1809-2012; Timpano, Kiara/C-8760-2012;
OI Timpano, Kiara/0000-0002-0665-8722; Wheaton, Michael/0000-0002-7465-7879
FU Intramural NIH HHS [ZIA MH000336-31]
NR 84
TC 9
Z9 9
U1 3
U2 9
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0021-843X
J9 J ABNORM PSYCHOL
JI J. Abnorm. Psychol.
PD AUG
PY 2011
VL 120
IS 3
BP 700
EP 707
DI 10.1037/a0024159
PG 8
WC Psychology, Clinical; Psychology, Multidisciplinary
SC Psychology
GA 813LZ
UT WOS:000294369800017
PM 21668081
ER
PT J
AU Jiang, H
Haltli, B
Feng, XD
Cai, P
Summers, M
Lotvin, J
He, M
AF Jiang, Hao
Haltli, Bradley
Feng, Xidong
Cai, Ping
Summers, Mia
Lotvin, Jason
He, Min
TI Investigation of the biosynthesis of the pipecolate moiety of
neuroprotective polyketide meridamycin
SO JOURNAL OF ANTIBIOTICS
LA English
DT Article
DE FTMS; isotope feeding; meridamycin; pipecolate
ID RESONANCE MASS-SPECTROMETRY; COMPLETE GENOME SEQUENCE; GENE-CLUSTER;
LYSINE 6-AMINOTRANSFERASE; IMMUNOSUPPRESSANT FK506; ACID; RAPAMYCIN;
CYCLODEAMINASE; MICROBES; RAPL
AB Biogenesis of the pipecolate moiety of neuroprotective agent meridamycin in Streptomyces sp. NRRL30748 was investigated in feeding studies using lysine specifically labeled with (15)N at the a-amino or the e-amino nitrogen position. Fourier transform mass spectrometry analysis with ultra-high mass resolving power and accurate mass measurement capability was employed to resolve the (15)N peak of labeled meridamycin from the (13)C peak of unlabeled meridamycin, allowing the precise calculation of labeling contents under each condition. The relative enrichment of (15)N-labeled meridamycin was similar to 43% with L-[alpha-(15)N]-lysine feeding and similar to 14% with L-[epsilon-(15)N]-lysine feeding, suggesting two distinguishable pathways, with concomitant loss of either the epsilon-amino group or the alpha-amino group of lysine, were involved in the generation of the pipecolate moiety of meridamycin in this bacterium. PCR cloning using degenerate primers identified a proC gene encoding a putative pyrroline-5-carboxylate reductase, which was expected to catalyze the conversion of piperideine-6-carboxylate to pipecolate. However, inactivation of this locus did not significantly affect the incorporation of alpha-(15)N- or epsilon-(15)N-labeled lysine into meridamycin, indicating the existence of an alternative route for the last step of the lysine epsilon-transamination pathway. This work revealed the diversity and complexity of the biosynthetic pathways for pipecolate synthesis in the meridamycin producing bacterium Streptomyces sp. NRRL30748. The Journal of Antibiotics (2011) 64, 533-538; doi:10.1038/ja.2011.45; published online 25 May 2011
C1 [Jiang, Hao; Cai, Ping; Lotvin, Jason] Pfizer, Dept Bioproc Dev, Pearl River, NY USA.
[Haltli, Bradley; Feng, Xidong; Summers, Mia; He, Min] Pfizer, Dept Chem Sci, Pearl River, NY USA.
RP He, M (reprint author), NCI, Div Canc Treatment & Diag, Dev Therapeut Program, NIH, 6130 Execut Blvd,MSC7458,EPN RM 8024, Bethesda, MD 20892 USA.
EM hem3@mail.nih.gov
NR 23
TC 0
Z9 0
U1 0
U2 5
PU JAPAN ANTIBIOTICS RESEARCH ASSOC
PI TOKYO
PA 2 20 8 KAMIOSAKI SHINAGAWA KU, TOKYO, 141, JAPAN
SN 0021-8820
J9 J ANTIBIOT
JI J. Antibiot.
PD AUG
PY 2011
VL 64
IS 8
BP 533
EP 538
DI 10.1038/ja.2011.45
PG 6
WC Biotechnology & Applied Microbiology; Immunology; Microbiology;
Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Immunology; Microbiology;
Pharmacology & Pharmacy
GA 812YC
UT WOS:000294329300002
PM 21610714
ER
PT J
AU Berezhkovskii, AM
Tofoleanu, F
Buchete, NV
AF Berezhkovskii, Alexander M.
Tofoleanu, Florentina
Buchete, Nicolae-Viorel
TI Are Peptides Good Two-State Folders?
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID PROTEIN-FOLDING KINETICS; HELIX-COIL TRANSITION; COARSE-GRAINED
POTENTIALS; SPEED LIMIT; MOLECULAR-DYNAMICS; EXPLICIT SOLVENT;
SIMPLE-MODEL; TIME SCALES; FORCE-FIELD; ALANINE
AB The folding kinetics of proteins is frequently single-exponential, as basins of folded and unfolded conformations are well separated by a high barrier. However, for relatively short peptides, a two-state character of folding is rather the exception than the rule. In this work, we use a Zwanzig-type model of protein conformational dynamics to study the dependence of folding kinetics on the protein chain length, M. The analysis is focused on the gap in the eigenvalue spectrum of the rate matrix that describes the protein's conformational dynamics. When there is a large gap between the two smallest in magnitude nonzero eigenvalues, the corresponding relaxation times have qualitatively different physical interpretations. The longest of these two times characterizes the interbasin equilibration (i.e., folding), whereas the second time characterizes the intrabasin relaxation. We derive approximate analytical solutions for the two eigenvalues that show how they depend on M. From these solutions, we infer that there is a large gap between the two, and thus, the kinetics is essentially single-exponential when M is large enough such that 2(M+1) is much larger than M-2.
C1 [Tofoleanu, Florentina; Buchete, Nicolae-Viorel] Univ Coll Dublin, Sch Phys, Dublin 4, Ireland.
[Tofoleanu, Florentina; Buchete, Nicolae-Viorel] Univ Coll Dublin, Complex & Adapt Syst Lab, Dublin 4, Ireland.
[Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Buchete, NV (reprint author), Univ Coll Dublin, Sch Phys, Dublin 4, Ireland.
EM buchete@ucd.ie
RI Buchete, Nicolae-Viorel/C-6200-2015
OI Buchete, Nicolae-Viorel/0000-0001-9861-1157
FU National Institutes of Health (NIH), Center for Information Technology;
Irish Research Council for Science, Engineering & Technology (IRCSET)
FX We thank Gerhard Hummer and Attila Szabo for many helpful and
stimulating discussions. This study was supported by the Intramural
Research Program of the National Institutes of Health (NIH), Center for
Information Technology, and it used the computational resources of the
Irish Centre for High-End Computing (ICHEC). F.T. and N.V.B gratefully
acknowledge financial support from the Irish Research Council for
Science, Engineering & Technology (IRCSET).
NR 52
TC 11
Z9 11
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD AUG
PY 2011
VL 7
IS 8
BP 2370
EP 2375
DI 10.1021/ct200281d
PG 6
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 804OF
UT WOS:000293662500006
PM 26606612
ER
PT J
AU Send, R
Kaila, VRI
Sundholm, D
AF Send, Robert
Kaila, Ville R. I.
Sundholm, Dage
TI Benchmarking the Approximate Second-Order Coupled-Cluster Method on
Biochromophores
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID PHOTOACTIVE YELLOW PROTEIN; GREEN FLUORESCENT PROTEIN; GAUSSIAN-BASIS
SETS; MULTICONFIGURATIONAL PERTURBATION-THEORY; GAS-PHASE ABSORPTION;
ZETA-VALENCE QUALITY; EXCITED-STATES; IDENTITY APPROXIMATION; ELECTRONIC
EXCITATIONS; VISUAL EXCITATION
AB Extensive benchmarking calculations are presented to assess the accuracy of commonly used quantum chemical methods in studying excited state properties of biochromophores. The first few excited states of 12 common model chromophores of photoactive yellow protein, green fluorescent protein, and rhodopsin have been studied using approximate second-order coupled-cluster (CC2) and linear-response time-dependent density functional theory (TDDFT) calculations. The study comprises investigations of basis-set dependences on CC2 excitation energies as well as comparisons of the CC2 results with excitation energies obtained at other computational levels and with experimental data. The basis-set study shows that the accuracy of the two lowest excitation energies is generally sufficient when triple-zeta basis sets augmented with polarization functions are employed, whereas the third and higher excited states were found to require diffuse basis functions in the basis set. Augmenting the basis set with diffuse functions contributes less than 0.15 eV to the excitation energies of low-lying excited states, except for some of the studied anionic states and for Rydberg states. Calculations at the TDDFT level using the B3LYP functional show the necessity of stabilizing anions with point charges or counterions when aiming at reliable electronic excitation spectra. The two lowest excitation energies of the green fluorescent protein and rhodopsin chromophores calculated at the CC2 level agree within 0.15 eV with experimental excitation energies, whereas the B3LYP values are somewhat less accurate, with a maximum deviation of 0.27 eV. The computed excitation energies for the photoactive yellow protein chromophore models deviate from available experimental values by 0.3-0.4 eV and 0.1-0.5 eV, at the CC2 and B3LYP levels of theory, respectively.
C1 [Kaila, Ville R. I.; Sundholm, Dage] Univ Helsinki, Dept Chem, FIN-00014 Helsinki, Finland.
[Send, Robert] Karlsruher Inst Technol, Inst Phys Chem, D-76131 Karlsruhe, Germany.
[Kaila, Ville R. I.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Kaila, Ville R. I.] Univ Helsinki, Inst Biotechnol, Helsinki Bioenerget Grp, Programme Struct Biol & Biophys, FI-00014 Helsinki, Finland.
RP Sundholm, D (reprint author), Univ Helsinki, Dept Chem, POB 55,AI Virtanens Pl 1, FIN-00014 Helsinki, Finland.
EM sundholm@chem.helsinki.fi
OI Sundholm, Dage Matts Borje/0000-0002-2367-9277
FU Academy of Finland through its Centers of Excellence; Center for
Functional Nanostructures (CFN) of the Deutsche Forschungsgemeinschaft
(DFG) [C3.9]; Sigrid Juselius Foundation; European Commission-Capacities
Area-Research Infrastructures [228398]; European Molecular Biology
Organization; National Institutes of Health, National Institute of
Diabetes and Digestive and Kidney Diseases
FX We thank Claudia Filippi for helpful comments on the manuscript. This
research has been supported by the Academy of Finland through its
Centers of Excellence Programme 2006-2011. This work was also supported
by the Center for Functional Nanostructures (CFN) of the Deutsche
Forschungsgemeinschaft (DFG) within project C3.9, by the Sigrid Juselius
Foundation, and the HPC-EUROPA2 project (project number: 228398) with
the support of the European Commission-Capacities Area-Research
Infrastructures. CSC-the Finnish IT Center for Science is acknowledged
for computer time and hosting this HPC-EUROPA2 project. V.R.I.K.
acknowledges the European Molecular Biology Organization for Long-Term
Fellowship, and the Intramural Research Program of the National
Institutes of Health, National Institute of Diabetes and Digestive and
Kidney Diseases for support.
NR 71
TC 30
Z9 30
U1 2
U2 20
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD AUG
PY 2011
VL 7
IS 8
BP 2473
EP 2484
DI 10.1021/ct200215d
PG 12
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 804OF
UT WOS:000293662500016
PM 26606621
ER
PT J
AU Albrecht, S
Roux, AD
Gallo, L
Kandula, N
Osypuk, T
Ni, H
Shrager, S
AF Albrecht, S.
Roux, A. Diez
Gallo, L.
Kandula, N.
Osypuk, T.
Ni, H.
Shrager, S.
TI INFLUENCE OF THE NEIGHBOURHOOD ENVIRONMENT ON WAIST SIZE OVER TIME AMONG
IMMIGRANTS TO THE USA: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
LA English
DT Meeting Abstract
C1 [Albrecht, S.; Roux, A. Diez] Univ Michigan, Ann Arbor, MI 48109 USA.
[Gallo, L.] San Diego State Univ, San Diego, CA 92182 USA.
[Kandula, N.] Northwestern Univ, Chicago, IL 60611 USA.
[Osypuk, T.] Northeastern Univ, Boston, MA 02115 USA.
[Ni, H.] NIH, Bethesda, MD 20892 USA.
[Shrager, S.] Univ Washington, Seattle, WA 98195 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0143-005X
J9 J EPIDEMIOL COMMUN H
JI J. Epidemiol. Community Health
PD AUG
PY 2011
VL 65
SU 1
BP A221
EP A221
DI 10.1136/jech.2011.142976h.43
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 807MG
UT WOS:000293901801107
ER
PT J
AU Murray, ET
Ben-Shlomo, Y
Southall, H
Aucott, P
Tilling, K
Guralnik, J
Kuh, D
Hardy, R
AF Murray, E. T.
Ben-Shlomo, Y.
Southall, H.
Aucott, P.
Tilling, K.
Guralnik, J.
Kuh, D.
Hardy, R.
TI ASSOCIATIONS OF AREA DEPRIVATION OVER THE LIFECOURSE AND PHYSICAL
CAPABILITY IN MID-LIFE: FINDINGS FROM THE 1946 BRITISH BIRTH COHORT
SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
LA English
DT Meeting Abstract
C1 [Murray, E. T.; Kuh, D.; Hardy, R.] MRC Unit Lifelong Hlth & Ageing, London, England.
[Murray, E. T.; Guralnik, J.] NIA, NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Ben-Shlomo, Y.; Tilling, K.] Univ Bristol, Dept Social Med, Bristol, Avon, England.
[Southall, H.; Aucott, P.] Univ Portsmouth, Dept Geog, Great Britain Hist GIS Project, Portsmouth, Hants, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0143-005X
J9 J EPIDEMIOL COMMUN H
JI J. Epidemiol. Community Health
PD AUG
PY 2011
VL 65
SU 1
BP A78
EP A78
DI 10.1136/jech.2011.142976c.35
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 807MG
UT WOS:000293901800183
ER
PT J
AU O'Doherty, M
Freedman, N
Hollenbeck, A
Abnet, C
AF O'Doherty, M.
Freedman, N.
Hollenbeck, A.
Abnet, C.
TI A PROSPECTIVE STUDY OF OBESITY AND RISK OF OESOPHAGEAL AND GASTRIC
ADENOCARCINOMA
SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
LA English
DT Meeting Abstract
C1 [O'Doherty, M.] Queens Univ Belfast, Belfast, Antrim, North Ireland.
[Freedman, N.; Abnet, C.] NCI, Rockville, MD USA.
[Hollenbeck, A.] AARP, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0143-005X
J9 J EPIDEMIOL COMMUN H
JI J. Epidemiol. Community Health
PD AUG
PY 2011
VL 65
SU 1
BP A139
EP A139
DI 10.1136/jech.2011.142976e.55
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 807MG
UT WOS:000293901800401
ER
PT J
AU Pearce, M
Salotti, J
McHugh, K
Kim, KP
Craft, A
Lubin, J
Ron, E
Parker, L
AF Pearce, M.
Salotti, J.
McHugh, K.
Kim, K. P.
Craft, A.
Lubin, J.
Ron, E.
Parker, L.
TI SOCIO-ECONOMIC VARIATION IN THE USE OF CT SCANS IN YOUNG PEOPLE IN THE
NORTH OF ENGLAND, 1990-2002
SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
LA English
DT Meeting Abstract
C1 [Pearce, M.; Salotti, J.; Craft, A.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[McHugh, K.] Great Ormond St Hosp Sick Children, London, England.
[Kim, K. P.] Kyung Hee Univ, Gyeongi Do, South Korea.
[Lubin, J.; Ron, E.] NCI, Bethesda, MD 20892 USA.
[Parker, L.] Dalhousie Univ, Halifax, NS, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0143-005X
J9 J EPIDEMIOL COMMUN H
JI J. Epidemiol. Community Health
PD AUG
PY 2011
VL 65
SU 1
BP A202
EP A203
DI 10.1136/jech.2011.142976g.79
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 807MG
UT WOS:000293901801043
ER
PT J
AU Tejada, R
Alarcon, J
Zunt, J
Montano, S
AF Tejada, R.
Alarcon, J.
Zunt, J.
Montano, S.
TI TRENDS AND CHARACTERISTICS OF SELF-REPORTED HIV TESTING IN WOMEN OF
CHILDBEARING AGE, IN PERU 2000, 2004-2008
SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
LA English
DT Meeting Abstract
C1 [Tejada, R.; Alarcon, J.] Univ Nacl Mayor San Marcos, Lima 14, Peru.
[Tejada, R.] Fogarty Int Ctr, Bethesda, MD USA.
[Zunt, J.] Univ Washington, Seattle, WA 98195 USA.
[Montano, S.] USN, Med Search Ctr Detachment, Lima, Peru.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0143-005X
J9 J EPIDEMIOL COMMUN H
JI J. Epidemiol. Community Health
PD AUG
PY 2011
VL 65
SU 1
BP A420
EP A420
DI 10.1136/jech.2011.142976o.42
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 807MG
UT WOS:000293901802192
ER
PT J
AU Thurston, GD
Lall, R
Shao, Y
Ahn, J
Park, Y
Hayes, RB
AF Thurston, G. D.
Lall, R.
Shao, Y.
Ahn, JiY
Park, Y.
Hayes, R. B.
TI LONG-TERM PM2.5 AIR POLLUTION EXPOSURE AND MORTALITY AMONG CALIFORNIA
RESIDENTS IN THE NIH-AARP COHORT
SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
LA English
DT Meeting Abstract
C1 [Thurston, G. D.; Lall, R.; Shao, Y.; Ahn, JiY; Hayes, R. B.] NYU, Sch Med, New York, NY USA.
[Park, Y.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0143-005X
J9 J EPIDEMIOL COMMUN H
JI J. Epidemiol. Community Health
PD AUG
PY 2011
VL 65
SU 1
BP A165
EP A165
DI 10.1136/jech.2011.142976f.47
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 807MG
UT WOS:000293901800493
ER
PT J
AU Wilson, JC
Murray, L
Hughes, C
Black, A
Anderson, L
AF Wilson, J. C.
Murray, L.
Hughes, C.
Black, A.
Anderson, L.
TI NON-STEROIDAL ANTI-INFLAMMATORY DRUG AND ASPIRIN USE AND THE RISK OF
HEAD AND NECK CANCER
SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
LA English
DT Meeting Abstract
C1 [Wilson, J. C.; Murray, L.; Hughes, C.; Anderson, L.] Queens Univ Belfast, Belfast, Antrim, North Ireland.
[Black, A.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0143-005X
J9 J EPIDEMIOL COMMUN H
JI J. Epidemiol. Community Health
PD AUG
PY 2011
VL 65
SU 1
BP A44
EP A44
DI 10.1136/jech.2011.142976b.24
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 807MG
UT WOS:000293901800124
ER
PT J
AU Thorgeirsson, SS
AF Thorgeirsson, Snorri S.
TI The almighty MYC: Orchestrating the micro-RNA universe to generate
aggressive liver cancer
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
ID EXPRESSION; CATENIN
AB Myc activation has been implicated in the pathogenesis of hepatoblastoma (HB), a rare embryonal neoplasm derived from liver progenitor cells. Here, microRNA (miR) expression profiling of 65 HBs evidenced differential patterns related to developmental stage and Myc activity. Undifferentiated aggressive HBs overexpressed the miR-371-3 cluster with concomitant down-regulation of the miR-100/let-7a-2/miR125b-1 cluster, evoking an ES cell expression profile. ChIP and Myc inhibition assays in hepatoma cells demonstrated that both miR clusters are regulated by Myc in an opposite manner. We show that the two miR clusters exert antagonistic effects on cell proliferation and tumorigenicity. Moreover, their combined deregulation cooperated in modulating the hepatic tumor phenotype, implicating stem cell-like regulation of Myc dependent miRs in poorly differentiated HBs. Importantly, a four-miR signature representative of these clusters efficiently stratified HB patients, and when applied to 241 hepatocellular carcinomas (HCCs), it identified invasive tumors with a poor prognosis. Our data argue that Myc-driven reprograming of miR expression patterns contributes to the aggressive phenotype of liver tumors originating from hepatic progenitor cells. (C) 2011 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
FU NIH Institutes of Health
FX The underlying research reported in the study was funded by the NIH
Institutes of Health
NR 13
TC 6
Z9 6
U1 1
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD AUG
PY 2011
VL 55
IS 2
BP 486
EP 487
DI 10.1016/j.jhep.2011.01.042
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 801HL
UT WOS:000293429100034
PM 21349304
ER
PT J
AU Swinburn, BA
Sacks, G
Hall, KD
McPherson, K
Finegood, DT
Moodie, ML
Gortmaker, SL
AF Swinburn, Boyd A.
Sacks, Gary
Hall, Kevin D.
McPherson, Klim
Finegood, Diane T.
Moodie, Marjory L.
Gortmaker, Steven L.
TI Obesity 1 The global obesity pandemic: shaped by global drivers and
local environments
SO LANCET
LA English
DT Article
ID CHILDHOOD OBESITY; PHYSICAL-ACTIVITY; WEIGHT-GAIN; BODY-SIZE; MISSING
HERITABILITY; DEVELOPING-COUNTRIES; LIFE EXPECTANCY; MARKET FAILURE;
FOOD-INDUSTRY; UNITED-STATES
AB The simultaneous increases in obesity in almost all countries seem to be driven mainly by changes in the global food system, which is producing more processed, affordable, and effectively marketed food than ever before. This passive overconsumption of energy leading to obesity is a predictable outcome of market economies predicated on consumption-based growth. The global food system drivers interact with local environmental factors to create a wide variation in obesity prevalence between populations. Within populations, the interactions between environmental and individual factors, including genetic makeup, explain variability in body size between individuals. However, even with this individual variation, the epidemic has predictable patterns in subpopulations. In low-income countries, obesity mostly affects middle-aged adults (especially women) from wealthy, urban environments; whereas in high-income countries it affects both sexes and all ages, but is disproportionately greater in disadvantaged groups. Unlike other major causes of preventable death and disability, such as tobacco use, injuries, and infectious diseases, there are no exemplar populations in which the obesity epidemic has been reversed by public health measures. This absence increases the urgency for evidence-creating policy action, with a priority on reduction of the supply-side drivers.
C1 [Swinburn, Boyd A.; Sacks, Gary] Deakin Univ, WHO Collaborating Ctr Obes Prevent, Melbourne, Vic 3125, Australia.
[Hall, Kevin D.] NIDDKD, NIH, Washington, DC USA.
[McPherson, Klim] Univ Oxford, New Coll, Oxford, England.
[Finegood, Diane T.] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Vancouver, BC, Canada.
[Gortmaker, Steven L.] Harvard Univ, Dept Soc Human Dev & Hlth, Harvard Sch Publ Hlth, Boston, MA 02115 USA.
RP Swinburn, BA (reprint author), Deakin Univ, WHO Collaborating Ctr Obes Prevent, Melbourne, Vic 3125, Australia.
EM boyd.swinburn@deakin.edu.au
OI Sacks, Gary/0000-0001-9736-1539
FU National Collaborative on Childhood Obesity Research; RWJF [260639,
61468, 66284]; CDC [U48/DP00064-00S1, 1U48DP001946]
FX This work was done under auspices of the Collaborative Obesity Modeling
Network as part of the Envision Project, supported by the National
Collaborative on Childhood Obesity Research, which coordinates childhood
obesity research across the National Institutes of Health (NIH), Centers
for Disease Control and Prevention (CDC), Department of Agriculture, and
the Robert Wood Johnson Foundation (RWJF). This work was supported in
part by grants from RWJF (grant numbers 260639, 61468 and 66284), CDC
(U48/DP00064-00S1 and 1U48DP001946), including the Nutrition and Obesity
Policy, Research and Evaluation Network, and the Office of Behavioral
and Social Sciences Research of NIH. This work is solely the
responsibility of the authors and does not represent official views of
the Centers for Disease Control and Prevention or any of the other
funders.
NR 119
TC 802
Z9 834
U1 29
U2 273
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD AUG-SEP
PY 2011
VL 378
IS 9793
BP 804
EP 814
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 816FY
UT WOS:000294585300036
PM 21872749
ER
PT J
AU Hall, KD
Sacks, G
Chandramohan, D
Chow, CC
Wang, YC
Gortmaker, SL
Swinburn, BA
AF Hall, Kevin D.
Sacks, Gary
Chandramohan, Dhruva
Chow, Carson C.
Wang, Y. Claire
Gortmaker, Steven L.
Swinburn, Boyd A.
TI Obesity 3 Quantification of the effect of energy imbalance on bodyweight
SO LANCET
LA English
DT Article
ID LOW-FAT DIET; WEIGHT-LOSS MAINTENANCE; VERY-LOW-CARBOHYDRATE; RANDOMIZED
CONTROLLED-TRIAL; DOUBLY LABELED WATER; LOW-CALORIE DIET; BODY-WEIGHT;
METABOLIC ADAPTATION; PHYSICAL-ACTIVITY; RISK-FACTORS
AB Obesity interventions can result in weight loss, but accurate prediction of the bodyweight time course requires properly accounting for dynamic energy imbalances. In this report, we describe a mathematical modelling approach to adult human metabolism that simulates energy expenditure adaptations during weight loss. We also present a web-based simulator for prediction of weight change dynamics. We show that the bodyweight response to a change of energy intake is slow, with half times of about 1 year. Furthermore, adults with greater adiposity have a larger expected weight loss for the same change of energy intake, and to reach their steady-state weight will take longer than it would for those with less initial body fat. Using a population-averaged model, we calculated the energy-balance dynamics corresponding to the development of the US adult obesity epidemic. A small persistent average daily energy imbalance gap between intake and expenditure of about 30 kJ per day underlies the observed average weight gain. However, energy intake must have risen to keep pace with increased expenditure associated with increased weight. The average increase of energy intake needed to sustain the increased weight (the maintenance energy gap) has amounted to about 09 MJ per day and quantifies the public health challenge to reverse the obesity epidemic.
C1 [Hall, Kevin D.; Chandramohan, Dhruva; Chow, Carson C.] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Sacks, Gary; Swinburn, Boyd A.] Deakin Univ, WHO Collaborating Ctr Obes Prevent, Melbourne, Vic, Australia.
[Wang, Y. Claire] Columbia Univ, Sch Publ Hlth, New York, NY USA.
[Gortmaker, Steven L.] Harvard Univ, Dept Soc Human Dev & Hlth, Harvard Sch Publ Hlth, Boston, MA 02115 USA.
RP Hall, KD (reprint author), NIDDKD, Lab Biol Modeling, NIH, 12A S Dr,Room 4007, Bethesda, MD 20892 USA.
EM kevinh@niddk.nih.gov
RI Chow, Carson/A-7970-2009;
OI Sacks, Gary/0000-0001-9736-1539
FU National Institutes of Health, NIDDK; Robert Wood Johnson Foundation
[260639, 61468, 66284]; US Centers for Disease Control and Prevention
[U48/DP00064-00S1, 1U48DP001946]; Office of Behavioral and Social
Sciences Research of the National Institutes for Health
[HHSN276200700356P]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, NIDDK, and grants from the Robert
Wood Johnson Foundation (#260639, #61468, and #66284), the US Centers
for Disease Control and Prevention (U48/DP00064-00S1 and 1U48DP001946)
and the Office of Behavioral and Social Sciences Research of the
National Institutes for Health (#HHSN276200700356P). The funders had no
role in the formulation of the major concepts, data analysis, data
interpretation, or writing of the report. The authors received no
payment for writing the report.
NR 118
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U2 77
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD AUG-SEP
PY 2011
VL 378
IS 9793
BP 826
EP 837
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 816FY
UT WOS:000294585300038
PM 21872751
ER
PT J
AU Gortmaker, SL
Swinburn, BA
Levy, D
Carter, R
Mabry, PL
Finegood, DT
Huang, T
Marsh, T
Moodie, ML
AF Gortmaker, Steven L.
Swinburn, Boyd A.
Levy, David
Carter, Rob
Mabry, Patricia L.
Finegood, Diane T.
Huang, Terry
Marsh, Tim
Moodie, Marjory L.
TI Obesity 4 Changing the future of obesity: science, policy, and action
SO LANCET
LA English
DT Article
ID SUGAR-SWEETENED BEVERAGES; PHYSICAL-ACTIVITY INTERVENTIONS; ASSESSING
COST-EFFECTIVENESS; PUBLIC-HEALTH; CHRONIC DISEASES; CHILDHOOD
OVERWEIGHT; WEIGHT MANAGEMENT; PREVENT OBESITY; LIFE EXPECTANCY; US
CHILDREN
AB The global obesity epidemic has been escalating for four decades, yet sustained prevention efforts have barely begun. An emerging science that uses quantitative models has provided key insights into the dynamics of this epidemic, and enabled researchers to combine evidence and to calculate the effect of behaviours, interventions, and policies at several levels from individual to population. Forecasts suggest that high rates of obesity will affect future population health and economics. Energy gap models have quantified the association of changes in energy intake and expenditure with weight change, and have documented the effect of higher intake on obesity prevalence. Empirical evidence that shows interventions are effective is limited but expanding. We identify several cost-effective policies that governments should prioritise for implementation. Systems science provides a framework for organising the complexity of forces driving the obesity epidemic and has important implications for policy makers. Many parties (such as governments, international organisations, the private sector, and civil society) need to contribute complementary actions in a coordinated approach. Priority actions include policies to improve the food and built environments, cross-cutting actions (such as leadership, healthy public policies, and monitoring), and much greater funding for prevention programmes. Increased investment in population obesity monitoring would improve the accuracy of forecasts and evaluations. The integration of actions within existing systems into both health and non-health sectors (trade, agriculture, transport, urban planning, and development) can greatly increase the influence and sustainability of policies. We call for a sustained worldwide effort to monitor, prevent, and control obesity.
C1 [Gortmaker, Steven L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Swinburn, Boyd A.] Deakin Univ, WHO Collaborating Ctr Obes Prevent, Melbourne, Vic, Australia.
[Carter, Rob; Moodie, Marjory L.] Deakin Univ, Deakin Hlth Econ, Deakin Populat Hlth, Melbourne, Vic, Australia.
[Levy, David] Univ Baltimore, Pacific Inst Res & Evaluat, Baltimore, MD 21201 USA.
[Levy, David] Univ Baltimore, Dept Econ, Baltimore, MD 21201 USA.
[Mabry, Patricia L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Finegood, Diane T.] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Vancouver, BC, Canada.
[Huang, Terry] Univ Nebraska, Dept Hlth Promot Social & Behav Hlth, Med Ctr, Omaha, NE 68182 USA.
[Marsh, Tim] Natl Heart Forum, London, England.
RP Gortmaker, SL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM sgortmak@hsph.harvard.edu
FU National Collaborative on Childhood Obesity Research; RWJF [260639,
61468, 66284]; CDC [U48/DP00064-00S1, 1U48DP001946]; Office of
Behavioral and Social Sciences Research of NIH [HHSN276200700356P]
FX We thank William Dietz and Angie Cradock for comments and suggestions.
This work was done under the auspices of the Collaborative Obesity
Modeling Network as part of the Envision Project, supported by the
National Collaborative on Childhood Obesity Research, which coordinates
childhood obesity research across the National Institutes of Health
(NIH), Centers for Disease Control and Prevention (CDC), Department of
Agriculture, and the Robert Wood Johnson Foundation (RWJF). This work
was supported in part by grants from RWJF (#260639, #61468 and #66284),
CDC (U48/DP00064-00S1 and 1U48DP001946), including the Nutrition and
Obesity Policy, Research and Evaluation Network, and the Office of
Behavioral and Social Sciences Research of NIH (#HHSN276200700356P).
This work is solely the responsibility of the authors and does not
represent official views of the CDC or any of the other funders.
NR 115
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U1 9
U2 136
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD AUG-SEP
PY 2011
VL 378
IS 9793
BP 838
EP 847
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 816FY
UT WOS:000294585300039
PM 21872752
ER
PT J
AU Duffy, PE
Fried, M
AF Duffy, Patrick Emmet
Fried, Michal
TI Pregnancy malaria: cryptic disease, apparent solution
SO MEMORIAS DO INSTITUTO OSWALDO CRUZ
LA English
DT Article
DE Plasmodium falciparum; pregnancy malaria; placenta; chondroitin sulphate
A; vaccine
ID CHONDROITIN-SULFATE-A; PLASMODIUM-FALCIPARUM MALARIA; BIRTH-WEIGHT;
INFECTED ERYTHROCYTES; PREVENTIVE TREATMENT; PLACENTAL MALARIA; VAR2CSA;
CHEMOPROPHYLAXIS; PARASITES; IDENTIFICATION
AB Malaria during pregnancy can be severe in non-immune women, but in areas of stable transmission, where women are semi-immune and often asymptomatic during infection, malaria is an insidious cause of disease and death for mothers and their offspring. Sequelae, such as severe anaemia and hypertension in the mother and low birth weight and infant mortality in the offspring, are often not recognised as consequences of infection. Pregnancy malaria, caused by Plasmodium falciparum, is mediated by infected erythrocytes (IEs) that bind to chondroitin sulphate A and are sequestered in the placenta. These parasites have a unique adhesion phenotype and distinct antigenicity, which indicates that novel targets may be required for development of an effective vaccine. Women become resistant to malaria as they acquire antibodies against placental IE, which leads to higher haemoglobin levels and heavier babies. Proteins exported from the placental parasites have been identified, including both variant and conserved antigens, and some of these are in preclinical development for vaccines. A vaccine that prevents P. falciparum malaria in pregnant mothers is feasible and would potentially save hundreds of thousands of lives each year.
C1 [Duffy, Patrick Emmet; Fried, Michal] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
RP Duffy, PE (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
EM patrick.duffy@nih.gov
FU Bill & Melinda Gates Foundation [47029]; Grand Challenges in Global
Health/Foundation for NIH, DIR, NIAID, NIH
FX Bill & Melinda Gates Foundation (47029), Grand Challenges in Global
Health/Foundation for NIH, DIR, NIAID, NIH (to PED)
NR 27
TC 4
Z9 4
U1 0
U2 2
PU FUNDACO OSWALDO CRUZ
PI RIO DE JANEIRO, RJ
PA AV BRASIL 4365, 21045-900 RIO DE JANEIRO, RJ, BRAZIL
SN 0074-0276
J9 MEM I OSWALDO CRUZ
JI Mem. Inst. Oswaldo Cruz
PD AUG
PY 2011
VL 106
SU 1
BP 64
EP 69
PG 6
WC Parasitology; Tropical Medicine
SC Parasitology; Tropical Medicine
GA 814IA
UT WOS:000294440600008
PM 21881758
ER
PT J
AU Andrade, BB
Barral-Netto, M
AF Andrade, Bruno Bezerril
Barral-Netto, Manoel
TI Biomarkers for susceptibility to infection and disease severity in human
malaria
SO MEMORIAS DO INSTITUTO OSWALDO CRUZ
LA English
DT Article
DE malaria; Plasmodium; biomarker; inflammation
ID PLASMODIUM-VIVAX MALARIA; SICKLE-CELL TRAIT; SEVERE FALCIPARUM-MALARIA;
BRAZILIAN AMAZON REGION; SALIVARY-GLAND PROTEINS; TUMOR-NECROSIS-FACTOR;
ANTIBODY-RESPONSE; UNCOMPLICATED MALARIA; EPIDEMIOLOGIC MARKER;
ANOPHELES-GAMBIAE
AB Malaria remains a major infectious disease that affects millions of people. Once infected with Plasmodium parasites, a host can develop a broad range of clinical presentations, which result from complex interactions between factors derived from the host, the parasite and the environment. Intense research has focused on the identification of reliable predictors for exposure, susceptibility to infection and the development of severe complications during malaria. Although most promising markers are based on the current understanding of malaria immunopathogenesis, some are also focused more broadly on mechanisms of tissue damage and inflammation. Taken together, these markers can help optimise therapeutic strategies and reduce disease burden. Here, we review the recent advances in the identification of malarial biomarkers, focusing on those related to parasite exposure and disease susceptibility. We also discuss priorities for research in biomarkers for severe malaria.
C1 [Barral-Netto, Manoel] Univ Fed Bahia, Fac Med, Salvador, BA, Brazil.
[Barral-Netto, Manoel] Ctr Pesquisas Goncalo Moniz Fiocruz, Salvador, BA, Brazil.
[Barral-Netto, Manoel] Inst Nacl Ciencia & Tecnol Invest Imunol, Salvador, BA, Brazil.
[Andrade, Bruno Bezerril] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Barral-Netto, M (reprint author), Univ Fed Bahia, Fac Med, Salvador, BA, Brazil.
EM mbarral@bahia.fiocruz.br
RI Barral Netto, Manoel/B-3904-2009; Andrade, Bruno/J-9111-2012
OI Barral Netto, Manoel/0000-0002-5823-7903; Andrade,
Bruno/0000-0001-6833-3811
FU FINEP [010409605]
FX FINEP (010409605)/FNDCT-CT Amazonia
NR 92
TC 16
Z9 16
U1 0
U2 4
PU FUNDACO OSWALDO CRUZ
PI RIO DE JANEIRO, RJ
PA AV BRASIL 4365, 21045-900 RIO DE JANEIRO, RJ, BRAZIL
SN 0074-0276
J9 MEM I OSWALDO CRUZ
JI Mem. Inst. Oswaldo Cruz
PD AUG
PY 2011
VL 106
SU 1
BP 70
EP 78
PG 9
WC Parasitology; Tropical Medicine
SC Parasitology; Tropical Medicine
GA 814IA
UT WOS:000294440600009
PM 21881759
ER
PT J
AU Batchelor, E
Lahav, G
AF Batchelor, Eric
Lahav, Galit
TI Suppressing variation in synthetic circuits
SO MOLECULAR SYSTEMS BIOLOGY
LA English
DT Editorial Material
ID INCOHERENT FEEDFORWARD LOOP; NETWORKS
C1 [Lahav, Galit] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Batchelor, Eric] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Lahav, G (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA.
EM galit@hms.harvard.edu
NR 9
TC 1
Z9 1
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1744-4292
J9 MOL SYST BIOL
JI Mol. Syst. Biol.
PD AUG
PY 2011
VL 7
AR 520
DI 10.1038/msb.2011.53
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 815PP
UT WOS:000294537800009
PM 21811231
ER
PT J
AU Jett, DA
AF Jett, David A.
TI Neurotoxic Pesticides and Neurologic Effects
SO NEUROLOGIC CLINICS
LA English
DT Article
DE Pesticides; Neurologic effects; Neurologic diseases
ID AMYOTROPHIC-LATERAL-SCLEROSIS; PARKINSONS-DISEASE; ORGANOCHLORINE
INSECTICIDES; RISK-FACTORS; EXPOSURE; ALS; SUSCEPTIBILITY; INGESTION;
SARIN
AB Pesticides represent one of the largest classes of toxic chemicals produced, stored, and used in the United States and abroad. These chemicals are designed to be toxic and many, besides being toxic to the pests they are intended to control, are also toxic to nontarget species including humans. The article gives a brief review of their toxicity to humans with emphasis on their effects on the nervous system. Examples of case studies are included to illustrate their toxicity. A discussion of the possible contribution of occupational and other pesticide exposures to neurologic diseases and disorders is also included.
C1 Natl Inst Neurol Disorders & Stroke, Off Translat Res, NIH, NSC, Bethesda, MD 20892 USA.
RP Jett, DA (reprint author), Natl Inst Neurol Disorders & Stroke, Off Translat Res, NIH, NSC, 6001 Execut Blvd,Room 2177,MSC 9527, Bethesda, MD 20892 USA.
EM jettd@ninds.nih.gov
NR 36
TC 8
Z9 8
U1 0
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 0733-8619
J9 NEUROL CLIN
JI Neurol. Clin.
PD AUG
PY 2011
VL 29
IS 3
BP 667
EP +
DI 10.1016/j.ncl.2011.06.002
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 813NI
UT WOS:000294373800010
PM 21803217
ER
PT J
AU Olive, M
Odgerel, Z
Martinez, A
Poza, JJ
Bragado, FG
Zabalza, RJ
Jerico, I
Gonzalez-Mera, L
Shatunov, A
Lee, HS
Armstrong, J
Maravi, E
Arroyo, MR
Pascual-Calvet, J
Navarro, C
Paradas, C
Huerta, M
Marquez, F
Gutierrez-Rivas, E
Pou, A
Ferrer, I
Goldfarb, LG
AF Olive, Montse
Odgerel, Zagaa
Martinez, Amaia
Jose Poza, Juan
Garcia Bragado, Federico
Zabalza, Ramon J.
Jerico, Ivonne
Gonzalez-Mera, Laura
Shatunov, Alexey
Lee, Hee Suk
Armstrong, Judith
Maravi, Elias
Ramos Arroyo, Maria
Pascual-Calvet, Jordi
Navarro, Carmen
Paradas, Carmen
Huerta, Mariano
Marquez, Fabian
Gutierrez-Rivas, Eduardo
Pou, Adolf
Ferrer, Isidre
Goldfarb, Lev G.
TI Clinical and myopathological evaluation of early- and late-onset
subtypes of myofibrillar myopathy
SO NEUROMUSCULAR DISORDERS
LA English
DT Article
DE Myofibrillar myopathy; Desmin; Myotilin; Zasp
ID GIRDLE MUSCULAR-DYSTROPHY; ELECTRON-MICROSCOPY; SKELETAL MYOPATHY;
DISTAL MYOPATHY; DESMIN GENE; MYOTILIN; MUTATIONS; PROTEIN; FILAMIN;
PATTERNS
AB Myofibrillar myopathies (MFM) are a group of disorders associated with mutations in DES, CRY A B, M YOT, ZASP, FLNC, or BAG3 genes and characterized by disintegration of myofibrils and accumulation of degradation products into intracellular inclusions. We retrospectively evaluated 53 M FM patients from 35 Spanish families. Studies included neurologic exam, muscle imaging, light and electron microscopic analysis of muscle biopsy, respiratory function testing and cardiologic work-up. Search for pathogenic mutations was accomplished by sequencing of coding regions of the six genes known to cause MFM. Mutations in M YOT were the predominant cause of MFM in Spain affecting 18 of 35 families, followed by DES in 11 and ZASP in 3; in 3 families the cause of MFM remains undetermined. Comparative analysis of DES, MYOT and ZASP associated phenotypes demonstrates substantial phenotypic distinctions that should be considered in studies of disease pathogenesis, for optimization of subtype-specific treatments and management, and directing molecular analysis. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Olive, Montse; Martinez, Amaia; Gonzalez-Mera, Laura; Armstrong, Judith; Ferrer, Isidre] IDIBELL Hosp Bellvitge, Dept Pathol, Inst Neuropathol, Barcelona 08907, Spain.
[Olive, Montse; Jose Poza, Juan; Shatunov, Alexey; Lee, Hee Suk; Paradas, Carmen; Ferrer, Isidre] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain.
[Odgerel, Zagaa; Goldfarb, Lev G.] NINDS, NIH, Bethesda, MD 20892 USA.
[Jose Poza, Juan; Zabalza, Ramon J.] Hosp Donostia, Dept Neurol, San Sebastian, Spain.
[Garcia Bragado, Federico] Hosp Virgen Camino, Dept Pathol, Pamplona, Spain.
[Jerico, Ivonne; Maravi, Elias] Hosp Virgen Camino, Dept Neurol, Pamplona, Spain.
[Ramos Arroyo, Maria] Hosp Virgen Camino, Dept Med Genet, Pamplona, Spain.
[Pascual-Calvet, Jordi; Pou, Adolf] Hosp Mar, Dept Neurol, Barcelona, Spain.
[Navarro, Carmen] Univ Hosp Vigo Meixoeiro, Ctr Invest Biomad Red Enfermedades Raras CIBERER, Dept Pathol, Vigo, Spain.
[Paradas, Carmen] Hosp Virgen Rocio, Dept Neurol, Seville, Spain.
[Huerta, Mariano] Hosp Viladecans, Dept Neurol, Barcelona, Spain.
[Marquez, Fabian] Hosp Josep Trueta, Dept Neurol, Girona, Spain.
[Gutierrez-Rivas, Eduardo] Hosp 12 Octubre, Dept Neurol, E-28041 Madrid, Spain.
RP Olive, M (reprint author), IDIBELL Hosp Bellvitge, Dept Pathol, Inst Neuropathol, Feixa Llarga S-N, Barcelona 08907, Spain.
EM 25169mop@comb.cat
RI Navarro, Carmen/A-9210-2012; Shatunov, Aleksey/E-6946-2011; IBIS,
FISIOLOGIA/O-9485-2015;
OI Olive, Montse/0000-0001-5727-0165; Gonzalez-Mera,
Laura/0000-0001-5691-0343
FU FIS [PI08-574]; National Institute of Neurological Disorders and Stroke,
National Institutes of Health
FX We would like to thank the patients and families for collaboration. We
also wish to thank D. Moreno, C. Gimenez, and S. Arnedo for their
excellent technical assistance. This work was supported in part by a FIS
grant PI08-574 and the Intramural Research Program of the National
Institute of Neurological Disorders and Stroke, National Institutes of
Health.
NR 36
TC 28
Z9 28
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD AUG
PY 2011
VL 21
IS 8
BP 533
EP 542
DI 10.1016/j.nmd.2011.05.002
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 815LQ
UT WOS:000294527500001
PM 21676617
ER
PT J
AU Bhattacharjee, AK
Lang, LX
Jacobson, O
Shinkre, B
Ma, Y
Niu, G
Trenkle, WC
Jacobson, KA
Chen, XY
Kiesewetter, DO
AF Bhattacharjee, Abesh Kumar
Lang, Lixin
Jacobson, Orit
Shinkre, Bidhan
Ma, Ying
Niu, Gang
Trenkle, William C.
Jacobson, Kenneth A.
Chen, Xiaoyuan
Kiesewetter, Dale O.
TI Striatal adenosine A(2A) receptor-mediated positron emission tomographic
imaging in 6-hydroxydopamine-lesioned rats using [(18)F]-MRS5425
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE SCH442416; MRS5425; Parkinson's disease; Adenosine A(2A); 6-OHDA; rat
ID PARKINSONS-DISEASE; ARACHIDONIC-ACID; MESSENGER-RNA; TIME-COURSE;
L-DOPA; DOPAMINE-D-2 RECEPTORS; CIRCLING BEHAVIOR; D-2 RECEPTORS; BRAIN;
MODEL
AB Introduction: A(2A) receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an (18)F-labeled A(2A) analog radiotracer ([(18)F]-MRS5425) for A(2A) receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A(2A) receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra.
Methods: [(18)F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D(2) agonist quinpirole (1.0 mg/kg) or IN antagonist raclopricle (6.0 mg/kg).
Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raelopride did not produce any change in uptake compared to baseline or between the hemispheres.
Conclusion: Thus, increase of A(2A) receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging. Published by Elsevier Inc.
C1 [Bhattacharjee, Abesh Kumar; Lang, Lixin; Jacobson, Orit; Ma, Ying; Niu, Gang; Chen, Xiaoyuan; Kiesewetter, Dale O.] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Shinkre, Bidhan; Trenkle, William C.] NIDDK, Chem Biol Unit, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
[Niu, Gang] NIH, Dept Radiol & Imaging Sci, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Kiesewetter, DO (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM dk7k@nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU National Institute of Biomedical Imaging and Bioengineering; National
Institute of Diabetes and Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
National Institute of Biomedical Imaging and Bioengineering and the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 47
TC 10
Z9 10
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD AUG
PY 2011
VL 38
IS 6
BP 897
EP 906
DI 10.1016/j.nucmedbio.2011.01.009
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 813QF
UT WOS:000294381300015
PM 21843786
ER
PT J
AU Blanke, CD
Goldberg, RM
Grothey, A
Mooney, M
Roach, N
Saltz, LB
Welch, JJ
Wood, WA
Meropol, NJ
AF Blanke, Charles D.
Goldberg, Richard M.
Grothey, Axel
Mooney, Margaret
Roach, Nancy
Saltz, Leonard B.
Welch, John J.
Wood, William A.
Meropol, Neal J.
CA NCI GI Steering Comm Colon Canc
TI KRAS and Colorectal Cancer: Ethical and Pragmatic Issues in Effecting
Real-Time Change in Oncology Clinical Trials and Practice
SO ONCOLOGIST
LA English
DT Editorial Material
DE Ethics; KRAS; Clinical trials; Colorectal neoplasms
ID CETUXIMAB; CHEMOTHERAPY; PANITUMUMAB; OXALIPLATIN; COMBINATION;
MUTATIONS; THERAPY
AB Systemic therapy has led to a median survival time for patients with advanced colorectal cancer (CRC) almost fourfold longer than that expected with best supportive care, an outcome achieved through combining chemotherapeutic and targeted biologic agents. Although the latter can include anti-epidermal growth factor receptor antibodies, such as cetuximab and panitumumab, we now have strong evidence that patients whose tumors harbor mutated KRAS will not benefit from this class of agent. Acceptance of the reliability and importance of the KRAS data took several years to evolve, however, for a variety of reasons. The timeline from the presentation and publication of small, retrospective phase II studies to widespread acceptance of the KRAS predictive value and changes in behavior-specifically, modifications of ongoing national trials in advanced/metastatic CRC, changes in national guidelines and practice patterns, and adjustments to the labeled indications for the monoclonal antibodies-was lengthy. In this commentary, we discuss whether or not the process of data disclosure regarding KRAS status and treatment of advanced CRC patients was effective in permitting timely decisions regarding ongoing publicly funded clinical trials and whether or not such decisions were rational and ethical. The overall goals are to highlight lessons learned regarding early disclosure of clinical trial results, as well as vetting and adoption of new scientific data, and to propose modifications for handling similar situations in the future. The Oncologist 2011; 16: 1061-1068
C1 [Blanke, Charles D.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Blanke, Charles D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Goldberg, Richard M.; Wood, William A.] Univ N Carolina, Chapel Hill, NC USA.
[Grothey, Axel] Mayo Clin, Rochester, MN USA.
[Mooney, Margaret; Welch, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Roach, Nancy] Colorectal Canc Coalit, Alexandria, VA USA.
[Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Meropol, Neal J.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
RP Blanke, CD (reprint author), 600 W 10th Ave,4211-C, Vancouver, BC V5Y 2E7, Canada.
EM cblanke@bccancer.bc.ca
RI Inov Farmaceutica, Inct/K-2313-2013; Goldberg , Richard/M-1311-2013;
OI Saltz, Leonard/0000-0001-8353-4670
NR 24
TC 14
Z9 14
U1 0
U2 2
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PD AUG
PY 2011
VL 16
IS 8
BP 1061
EP 1068
DI 10.1634/theoncologist.2011-0011
PG 8
WC Oncology
SC Oncology
GA 812KH
UT WOS:000294291800001
PM 21737577
ER
PT J
AU Zjawiony, JK
Polepally, PR
Roth, BL
Setola, V
Vardy, E
AF Zjawiony, J. K.
Polepally, P. R.
Roth, B. L.
Setola, V
Vardy, E.
TI Design and synthesis of natural product-based ligands with high affinity
to the kappa-opioid receptor
SO PLANTA MEDICA
LA English
DT Meeting Abstract
CT 59th International Congress and Annual Meeting of the
Society-for-Medicinal-Plant-and-Natural-Product-Research
CY SEP 04-09, 2011
CL Antalya, TURKEY
SP Soc Med Plant & Nat Prod Res
DE Salvia divinorum; salvinorin A; kappa-opioid receptor; synthesis of new
ligands; affinity; ligand-receptor interactions
ID SALVINORIN-A; AGONIST
C1 [Zjawiony, J. K.; Polepally, P. R.] Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA.
[Zjawiony, J. K.; Polepally, P. R.] Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, University, MS 38677 USA.
[Roth, B. L.; Setola, V; Vardy, E.] Univ N Carolina, NIMH Psychoact Drug Screening Program, Sch Pharm, Dept Pharmacol, Chapel Hill, NC 27599 USA.
RI Roth, Bryan/F-3928-2010
NR 5
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
J9 PLANTA MED
JI Planta Med.
PD AUG
PY 2011
VL 77
IS 12
BP 1243
EP 1243
PG 1
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 810PT
UT WOS:000294139000050
ER
PT J
AU Koonin, EV
AF Koonin, Eugene V.
TI Are There Laws of Genome Evolution?
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Review
ID UNIVERSAL DISTRIBUTION; STATISTICAL PHYSICS; PROTEIN EVOLUTION; BIOLOGY;
COMPLEXITY; CONSTRAINT; NETWORKS; ORIGINS; GENES; RATES
AB Research in quantitative evolutionary genomics and systems biology led to the discovery of several universal regularities connecting genomic and molecular phenomic variables. These universals include the log-normal distribution of the evolutionary rates of orthologous genes; the power law-like distributions of paralogous family size and node degree in various biological networks; the negative correlation between a gene's sequence evolution rate and expression level; and differential scaling of functional classes of genes with genome size. The universals of genome evolution can be accounted for by simple mathematical models similar to those used in statistical physics, such as the birth-death-innovation model. These models do not explicitly incorporate selection; therefore, the observed universal regularities do not appear to be shaped by selection but rather are emergent properties of gene ensembles. Although a complete physical theory of evolutionary biology is inconceivable, the universals of genome evolution might qualify as "laws of evolutionary genomics" in the same sense "law" is understood in modern physics.
C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM koonin@ncbi.nlm.nih.gov
FU US Department of Health and Human Services
FX The author's research is supported by intramural funds of the US
Department of Health and Human Services (to National Library of
Medicine, NIH). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 37
TC 36
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U1 2
U2 42
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-734X
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD AUG
PY 2011
VL 7
IS 8
AR e1002173
DI 10.1371/journal.pcbi.1002173
PG 6
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 812NH
UT WOS:000294299700025
PM 21901087
ER
PT J
AU Rasmussen, DA
Ratmann, O
Koelle, K
AF Rasmussen, David A.
Ratmann, Oliver
Koelle, Katia
TI Inference for Nonlinear Epidemiological Models Using Genealogies and
Time Series
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID MONTE-CARLO METHODS; BAYESIAN-INFERENCE; POPULATION-DYNAMICS; CHILDHOOD
DISEASES; COALESCENT; SEQUENCES; HISTORY; VIRUS; TRANSMISSION; EPIDEMICS
AB Phylodynamics - the field aiming to quantitatively integrate the ecological and evolutionary dynamics of rapidly evolving populations like those of RNA viruses - increasingly relies upon coalescent approaches to infer past population dynamics from reconstructed genealogies. As sequence data have become more abundant, these approaches are beginning to be used on populations undergoing rapid and rather complex dynamics. In such cases, the simple demographic models that current phylodynamic methods employ can be limiting. First, these models are not ideal for yielding biological insight into the processes that drive the dynamics of the populations of interest. Second, these models differ in form from mechanistic and often stochastic population dynamic models that are currently widely used when fitting models to time series data. As such, their use does not allow for both genealogical data and time series data to be considered in tandem when conducting inference. Here, we present a flexible statistical framework for phylodynamic inference that goes beyond these current limitations. The framework we present employs a recently developed method known as particle MCMC to fit stochastic, nonlinear mechanistic models for complex population dynamics to gene genealogies and time series data in a Bayesian framework. We demonstrate our approach using a nonlinear Susceptible-Infected-Recovered (SIR) model for the transmission dynamics of an infectious disease and show through simulations that it provides accurate estimates of past disease dynamics and key epidemiological parameters from genealogies with or without accompanying time series data.
C1 [Rasmussen, David A.; Ratmann, Oliver; Koelle, Katia] Duke Univ, Dept Biol, Durham, NC 27706 USA.
[Ratmann, Oliver] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London, England.
[Koelle, Katia] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Rasmussen, DA (reprint author), Duke Univ, Dept Biol, Durham, NC 27706 USA.
EM dar24@duke.edu; katia.koelle@duke.edu
OI Ratmann, Oliver/0000-0001-8667-4118
FU NSF; Sir Henry Wellcome fellowship [WR092311MF]; Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health; [NSF-EF-08-27416]
FX This work was supported by a NSF graduate research fellowship to DAR
(www.nsf.gov), by Sir Henry Wellcome fellowship WR092311MF to OR
(www.wellcome.ac.uk), by grant NSF-EF-08-27416 to KK, and by the RAPIDD
program of the Science & Technology Directorate, Department of Homeland
Security, and the Fogarty International Center, National Institutes of
Health (www.fic.nih.gov/about/dieps.htm#rapidd). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 45
TC 46
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U1 0
U2 23
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-734X
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD AUG
PY 2011
VL 7
IS 8
AR e1002136
DI 10.1371/journal.pcbi.1002136
PG 11
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 812NH
UT WOS:000294299700017
PM 21901082
ER
PT J
AU Shrestha, S
King, AA
Rohani, P
AF Shrestha, Sourya
King, Aaron A.
Rohani, Pejman
TI Statistical Inference for Multi-Pathogen Systems
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID DENGUE HEMORRHAGIC-FEVER; ANTIBODY-DEPENDENT ENHANCEMENT; TRANSMISSION
DYNAMICS; RURAL MALAWI; INFECTION; MALARIA; DISEASE; INTERFERENCE;
POPULATION; INFLUENZA
AB There is growing interest in understanding the nature and consequences of interactions among infectious agents. Pathogen interactions can be operational at different scales, either within a co-infected host or in host populations where they co-circulate, and can be either cooperative or competitive. The detection of interactions among pathogens has typically involved the study of synchrony in the oscillations of the protagonists, but as we show here, phase association provides an unreliable dynamical fingerprint for this task. We assess the capacity of a likelihood-based inference framework to accurately detect and quantify the presence and nature of pathogen interactions on the basis of realistic amounts and kinds of simulated data. We show that when epidemiological and demographic processes are well understood, noisy time series data can contain sufficient information to allow correct inference of interactions in multi-pathogen systems. The inference power is dependent on the strength and time-course of the underlying mechanism: stronger and longer-lasting interactions are more easily and more precisely quantified. We examine the limitations of our approach to stochastic temporal variation, under-reporting, and over-aggregation of data. We propose that likelihood shows promise as a basis for detection and quantification of the effects of pathogen interactions and the determination of their (competitive or cooperative) nature on the basis of population-level time-series data.
C1 [Shrestha, Sourya; King, Aaron A.; Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Shrestha, Sourya; Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[King, Aaron A.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA.
[King, Aaron A.; Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Shrestha, S (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
EM sourya@umich.edu
OI Shrestha, Sourya/0000-0002-6106-6834; King, Aaron/0000-0001-6159-3207
FU National Oceanic and Atmospheric Administration [NA08NOS4730321];
Science & Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; Vaccine
Modeling Initiative of the Bill & Melinda Gates Foundation; NSF
[DEB-0553768]
FX SS & AAK acknowledge the support of the National Oceanic and Atmospheric
Administration (grant #NA08NOS4730321). AAK and PR acknowledge the
support of the RAPIDD program of the Science & Technology Directorate,
Department of Homeland Security and the Fogarty International Center,
National Institutes of Health. PR received support from the Vaccine
Modeling Initiative of the Bill & Melinda Gates Foundation. This work
was facilitated by the Inference for Mechanistic Models Working Group
supported by the National Center for Ecological Analysis and Synthesis,
a Center funded by NSF (grant #DEB-0553768), the University of
California, Santa Barbara, and the State of California. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 48
TC 20
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U1 0
U2 17
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-734X
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD AUG
PY 2011
VL 7
IS 8
AR e1002135
DI 10.1371/journal.pcbi.1002135
PG 14
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 812NH
UT WOS:000294299700016
PM 21876665
ER
PT J
AU Gething, PW
Tatem, AJ
AF Gething, Peter W.
Tatem, Andrew J.
TI Can Mobile Phone Data Improve Emergency Response to Natural Disasters?
SO PLOS MEDICINE
LA English
DT Editorial Material
ID PATTERNS
C1 [Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
[Tatem, Andrew J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Tatem, Andrew J.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Gething, PW (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, S Parks Rd, Oxford OX1 3PS, England.
EM peter.gething@zoo.ox.ac.uk
OI Gething, Peter/0000-0001-6759-5449
FU Wellcome Trust [079091]
NR 6
TC 7
Z9 7
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1549-1277
J9 PLOS MED
JI PLos Med.
PD AUG
PY 2011
VL 8
IS 8
AR e1001085
DI 10.1371/journal.pmed.1001085
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 814SK
UT WOS:000294477300019
PM 21918644
ER
PT J
AU Durbin, AP
Whitehead, SS
Shaffer, D
Elwood, D
Wanionek, K
Thumar, B
Blaney, JE
Murphy, BR
Schmidt, AC
AF Durbin, Anna P.
Whitehead, Stephen S.
Shaffer, Donna
Elwood, Dan
Wanionek, Kimberli
Thumar, Bhavin
Blaney, Joseph E.
Murphy, Brian R.
Schmidt, Alexander C.
TI A Single Dose of the DENV-1 Candidate Vaccine rDEN1 Delta 30 Is Strongly
Immunogenic and Induces Resistance to a Second Dose in a Randomized
Trial
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID ATTENUATED DENGUE VACCINE; FLAVIVIRUS-NAIVE ADULTS; HEMORRHAGIC-FEVER;
3'-UNTRANSLATED REGION; ANTIBODY-RESPONSE; HUMAN VOLUNTEERS;
CLINICAL-TRIAL; VIRUS-VACCINE; 4 SEROTYPES; LIVE
AB Dengue is an emerging infectious disease that has become the most important arboviral infection worldwide. There are four serotypes of dengue virus, DENV-1, DENV-2, DENV-3, and DENV-4, each capable of causing the full spectrum of disease. rDEN1 Delta 30 is a live attenuated investigational vaccine for the prevention of DENV-1 illness and is also a component of an investigational tetravalent DENV vaccine currently in Phase I evaluation. A single subcutaneous dose of rDEN1 Delta 30 was previously shown to be safe and immunogenic in healthy adults. In the current randomized placebo-controlled trial, 60 healthy flavivirus-naive adults were randomized to receive 2 doses of rDEN1 Delta 30 (N = 50) or placebo (N = 10), either on study days 0 and 120 (cohort 1) or 0 and 180 (cohort 2). We sought to evaluate the safety and immunogenicity of this candidate vaccine in 50 additional vaccinees and to test whether the humoral immune response could be boosted by a second dose administered 4 or 6 months after the first dose. The first dose of vaccine was well tolerated, infected 47/50 vaccinees and induced seroconversion in 46/50 vaccinees. Irrespective of dosing interval, the second dose of vaccine was also well tolerated but did not induce any detectable viremia or >= 4-fold rise in serum neutralizing antibody titer. Only five subjects had an anamnestic antibody response detectable by ELISA following a second dose of vaccine, demonstrating that the vaccine induced sterilizing humoral immunity in most vaccinees for at least six months following primary vaccination. The promising safety and immunogenicity profile of this vaccine confirms its suitability for inclusion in a tetravalent dengue vaccine.
C1 [Durbin, Anna P.; Shaffer, Donna; Elwood, Dan; Wanionek, Kimberli; Thumar, Bhavin] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, Baltimore, MD USA.
[Whitehead, Stephen S.; Blaney, Joseph E.; Murphy, Brian R.; Schmidt, Alexander C.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Durbin, AP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, Baltimore, MD USA.
EM adurbin@jhsph.edu
RI Mavoa, Suzanne/B-5372-2010
FU National Institutes of Allergy and Infectious Diseases, National
Institutes of Health; NIAID [N01-A1-15444]; Johns Hopkins Bloomberg
School of Public Health
FX This study was funded and sponsored by the Intramural Research Program
of the National Institutes of Allergy and Infectious Diseases, National
Institutes of Health. The clinical trial was conducted as part of a
research contract between NIAID and the Johns Hopkins Bloomberg School
of Public Health. (NIAID Contract No. N01-A1-15444
NR 41
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U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD AUG
PY 2011
VL 5
IS 8
AR e1267
DI 10.1371/journal.pntd.0001267
PG 10
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 814TJ
UT WOS:000294479800022
PM 21829748
ER
PT J
AU Fink, DL
Kamgno, J
Nutman, TB
AF Fink, Doran L.
Kamgno, Joseph
Nutman, Thomas B.
TI Rapid Molecular Assays for Specific Detection and Quantitation of Loa
loa Microfilaremia
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID POLYMERASE-CHAIN-REACTION; REVERSE-TRANSCRIPTASE-PCR; REAL-TIME PCR;
HUMAN OCCULT LOIASIS; WUCHERERIA-BANCROFTI; DNA; INFECTION; MOSQUITOS;
SEQUENCE; LARVAE
AB Background: Accurate diagnosis of Loa loa infection is essential to the success of mass drug administration efforts to eliminate onchocerciasis and lymphatic filariasis, due to the risk of fatal encephalopathic reactions to ivermectin occurring among highly microfilaremic Loa-infected individuals living in areas co-endemic for multiple filarial species.
Methodology/Principal Findings: From a pool of over 1,800 L. loa microfilaria (mf) expressed sequence tags, 18 candidate L. loa mf-specific PCR targets were identified. Real-time PCR (qPCR) assays were developed for two targets (LLMF72 and LLMF269). The qPCR assays were highly specific for L. loa compared with related filariae and also highly sensitive, with detection limits of 0.1 pg genomic DNA, or 1% of DNA extracted from normal blood spiked with a single L. loa microfilaria. Using various DNA extraction methods with dried blood spots obtained from Cameroonian subjects with parasitologically proven loiasis, the LLMF72 qPCR assay successfully estimated mf burden in 65 of 68 samples (50-96,000 mf/mL by microscopy), including all 12 samples subjected to a simple 10-minute boiling extraction. Additionally, the assay detected low-level microfilaremia among 5 of 16 samples from patients thought to be amicrofilaremic by microscopy.
Conclusions/Significance: This novel, rapid, highly sensitive and specific qPCR assay is an important step forward in the laboratory diagnosis of L. loa infection.
C1 [Fink, Doran L.; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Kamgno, Joseph] Univ Yaounde 1, Filariasis Res Ctr, Yaounde, Cameroon.
[Kamgno, Joseph] Univ Yaounde 1, Fac Med & Biomed Sci, Yaounde, Cameroon.
RP Fink, DL (reprint author), US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
EM tnutman@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Mectizan Donation
Program
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. Fieldwork in
Cameroon was funded by the Mectizan Donation Program as part of their
support to the Filariasis Research Center in Cameroon. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 29
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U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1935-2727
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD AUG
PY 2011
VL 5
IS 8
AR e1299
DI 10.1371/journal.pntd.0001299
PG 8
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 814TJ
UT WOS:000294479800045
PM 21912716
ER
PT J
AU Stamper, LW
Patrick, RL
Fay, MP
Lawyer, PG
Elnaiem, DEA
Secundino, N
Debrabant, A
Sacks, DL
Peters, NC
AF Stamper, Lisa W.
Patrick, Rachel L.
Fay, Michael P.
Lawyer, Phillip G.
Elnaiem, Dia-Eldin A.
Secundino, Nagila
Debrabant, Alain
Sacks, David L.
Peters, Nathan C.
TI Infection Parameters in the Sand Fly Vector That Predict Transmission of
Leishmania major
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID LUTZOMYIA-LONGIPALPIS; CUTANEOUS LEISHMANIASIS; FLIES; BITE; SKIN
AB To identify parameters of Leishmania infection within a population of infected sand flies that reliably predict subsequent transmission to the mammalian host, we sampled groups of infected flies and compared infection intensity and degree of metacyclogenesis with the frequency of transmission. The percentage of parasites within the midgut that were metacyclic promastigotes had the highest correlation with the frequency of transmission. Meta-analysis of multiple transmission experiments allowed us to establish a percent-metacyclic "cutoff" value that predicted transmission competence. Sand fly infections initiated with variable doses of parasites resulted in correspondingly altered percentages of metacyclic promastigotes, resulting in altered transmission frequency and disease severity. Lastly, alteration of sand fly oviposition status and environmental conditions at the time of transmission also influenced transmission frequency. These observations have implications for transmission of Leishmania by the sand fly vector in both the laboratory and in nature, including how the number of organisms acquired by the sand fly from an infection reservoir may influence the clinical outcome of infection following transmission by bite.
C1 [Stamper, Lisa W.; Patrick, Rachel L.; Lawyer, Phillip G.; Elnaiem, Dia-Eldin A.; Secundino, Nagila; Sacks, David L.; Peters, Nathan C.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Elnaiem, Dia-Eldin A.] Univ Maryland Eastern Shore, Princess Anne, MD USA.
[Debrabant, Alain] US FDA, Div Emerging & Transfus Transmitted Dis, OBRR, CBER, Bethesda, MD 20014 USA.
RP Stamper, LW (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM NPeters@niaid.nih.gov
OI Fay, Michael P./0000-0002-8643-9625
FU National Institutes of Health, National Institute of Allergy and
Infectious Disease
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Disease. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 21
TC 11
Z9 11
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1935-2727
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD AUG
PY 2011
VL 5
IS 8
AR e1288
DI 10.1371/journal.pntd.0001288
PG 9
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 814TJ
UT WOS:000294479800038
PM 21886852
ER
PT J
AU Tsuda, Y
Caposio, P
Parkins, CJ
Botto, S
Messaoudi, I
Cicin-Sain, L
Feldmann, H
Jarvis, MA
AF Tsuda, Yoshimi
Caposio, Patrizia
Parkins, Christopher J.
Botto, Sara
Messaoudi, Ilhem
Cicin-Sain, Luka
Feldmann, Heinz
Jarvis, Michael A.
TI A Replicating Cytomegalovirus-Based Vaccine Encoding a Single Ebola
Virus Nucleoprotein CTL Epitope Confers Protection against Ebola Virus
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID T-CELL RESPONSES; BACTERIAL ARTIFICIAL CHROMOSOME; MURINE
CYTOMEGALOVIRUS; NONHUMAN-PRIMATES; HEMORRHAGIC-FEVER; HERPESVIRUS
GENOME; FILOVIRUS VACCINE; VIRAL-INFECTION; MOUSE MODEL; EFFECTOR
AB Background: Human outbreaks of Ebola virus (EBOV) are a serious human health concern in Central Africa. Great apes (gorillas/chimpanzees) are an important source of EBOV transmission to humans due to increased hunting of wildlife including the 'bush-meat' trade. Cytomegalovirus (CMV) is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential to re-infect and disseminate through target populations regardless of prior CMV immunity, which may be ideal for achieving high vaccine coverage in inaccessible populations such as great apes.
Methodology/Principal Findings: We hypothesize that a vaccine strategy using CMV-based vectors expressing EBOV antigens may be ideally suited for use in inaccessible wildlife populations. To establish a 'proof-of-concept' for CMV-based vaccines against EBOV, we constructed a mouse CMV (MCMV) vector expressing a CD8(+) T cell epitope from the nucleoprotein (NP) of Zaire ebolavirus (ZEBOV) (MCMV/ZEBOV-NP(CTL)). MCMV/ZEBOV-NP(CTL) induced high levels of long-lasting (> 8 months) CD8(+) T cells against ZEBOV NP in mice. Importantly, all vaccinated animals were protected against lethal ZEBOV challenge. Low levels of anti-ZEBOV antibodies were only sporadically detected in vaccinated animals prior to ZEBOV challenge suggesting a role, at least in part, for T cells in protection.
Conclusions/Significance: This study demonstrates the ability of a CMV-based vaccine approach to protect against an highly virulent human pathogen, and supports the potential for 'disseminating' CMV-based EBOV vaccines to prevent EBOV transmission in wildlife populations.
C1 [Tsuda, Yoshimi; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Caposio, Patrizia; Parkins, Christopher J.; Botto, Sara; Messaoudi, Ilhem; Jarvis, Michael A.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97201 USA.
[Cicin-Sain, Luka] Helmholtz Ctr Infect Res, Dept Vaccinol & Appl Microbiol, Braunschweig, Germany.
[Jarvis, Michael A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA.
RP Tsuda, Y (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
EM jarvismi@ohsu.edu
OI Cicin-Sain, Luka/0000-0003-3978-778X
FU R21 [AI088442]; National Institutes of Health
FX This study was supported by R21 (AI088442), and intramural research
programs of the National Institutes of Health. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 73
TC 35
Z9 37
U1 0
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1935-2727
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD AUG
PY 2011
VL 5
IS 8
AR e1275
DI 10.1371/journal.pntd.0001275
PG 10
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 814TJ
UT WOS:000294479800029
PM 21858240
ER
PT J
AU Schmidt, AC
AF Schmidt, Alexander C.
TI Progress in Respiratory Virus Vaccine Development
SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Review
DE Vaccine; parainfluenza virus; metapneumovirus; respiratory syncytial
virus; clinical trial; clinical development
ID AFRICAN-GREEN MONKEYS; HUMANIZED MONOCLONAL-ANTIBODY;
CELL-MEDIATED-IMMUNITY; L-POLYMERASE PROTEIN; ATTENUATION IN-VIVO; OPEN
READING FRAME; HIGH-RISK ADULTS; SYNCYTIAL-VIRUS; REVERSE GENETICS;
NEUTRALIZING ANTIBODIES
AB Viral respiratory infections cause significant morbidity and mortality in infants and young children as well as in at-risk adults and the elderly. Although many viral pathogens are capable of causing respiratory disease, vaccine development has to focus on a limited number of pathogens, such as those that commonly cause serious lower respiratory illness (LRI). Whereas influenza virus vaccines have been available for some time (see the review by Clark and Lynch in this issue), vaccines against other medically important viruses such as respiratory syncytial virus (RSV), the parainfluenza viruses (PIVs), and metapneumovirus (MPVs) are not available. This review aims to provide a brief update on investigational vaccines against RSV, the PIVs, and MPV that have been evaluated in clinical trials or are currently in clinical development.
C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Schmidt, AC (reprint author), NIAID, Infect Dis Lab, NIH, 50 South Dr,Rm 6511, Bethesda, MD 20892 USA.
EM schmidta@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. The helpful comments of Peter Coffins, Ph.D. are
greatly appreciated.
NR 118
TC 14
Z9 16
U1 0
U2 2
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1069-3424
EI 1098-9048
J9 SEMIN RESP CRIT CARE
JI Semin. Respir. Crit. Care Med.
PD AUG
PY 2011
VL 32
IS 4
BP 527
EP 540
DI 10.1055/s-0031-1283289
PG 14
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 804VB
UT WOS:000293681000013
PM 21858754
ER
PT J
AU Vines, AI
Thu, TXN
Ta, M
Esserman, D
Baird, DD
AF Vines, Anissa I.
Thu Thi Xuan Nguyen
Ta, Myduc
Esserman, Denise
Baird, Donna D.
TI Self-Reported Daily Stress, Squelching of Anger and the Management of
Daily Stress and the Prevalence of Uterine Leiomyomata: The Ultrasound
Screening Study
SO STRESS AND HEALTH
LA English
DT Article
DE anger; stress; coping; leiomyoma; disparities
ID BLOOD-PRESSURE; PREMENOPAUSAL WOMEN; EXPRESSION; HEALTH; BLACK; RISK;
DETERMINANTS; SECRETION; FIBROIDS; RACE
AB Self-reported daily stress, ways of managing stress and squelching anger were examined in association with uterine leiomyomata (aka fibroids). These stress factors were obtained from 560 Black and 375 White women enrolled in the National Institute of Environmental Health Sciences Uterine Fibroid Study. Race-specific prevalence differences (PD) and 95% confidence intervals (95% CI) were calculated. Black women with severe stress had a prevalence of fibroids that was 11% higher (95% CI: 0%, 21%) than those in the no or mild stress group (referent). White women with severe stress, compared to the referent, had a non-significantly (NS) higher prevalence of fibroids [PD = 7%; 95% CI: (-10%, 21%)]. For both groups, moderate daily stress was associated with a weak elevation (NS) in fibroid prevalence. Black women who reported squelching their anger had an elevated prevalence of fibroids (8%) compared to non-squelchers [95% CI: (-0%, 15%)] while there was no association for White women. Women with symptomatic fibroids had higher stress than those without, but exclusion of symptomatic women only slightly attenuated the associations. Consistent with a previous report, symptomatic fibroids may cause stress. However, further research is warranted to prospectively investigate a possible aetiologic role for stress in the development of fibroids. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Vines, Anissa I.; Thu Thi Xuan Nguyen; Ta, Myduc] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Esserman, Denise] Univ N Carolina, Dept Med, Sch Med, Chapel Hill, NC 27599 USA.
[Baird, Donna D.] NIEHS, Epidemiol Branch, Womens Hlth Grp, Res Triangle Pk, NC 27709 USA.
RP Vines, AI (reprint author), Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, 266 Rosenau Hall,CB 7435, Chapel Hill, NC 27599 USA.
EM avines@email.unc.edu
OI Baird, Donna/0000-0002-5544-2653
NR 27
TC 4
Z9 4
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1532-3005
EI 1532-2998
J9 STRESS HEALTH
JI Stress Health
PD AUG
PY 2011
VL 27
IS 3
BP E188
EP E194
DI 10.1002/smi.1360
PG 7
WC Psychology, Applied; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 814LK
UT WOS:000294454600010
ER
PT J
AU Rosenberg, PS
Tamary, H
Alter, BP
AF Rosenberg, Philip S.
Tamary, Hannah
Alter, Blanche P.
TI How High Are Carrier Frequencies of Rare Recessive Syndromes?
Contemporary Estimates for Fanconi Anemia in the United States and
Israel
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE epidemiologic methods; Fanconi anemia; gene frequency; prevalence
ID SOUTH-AFRICA; CANCER INCIDENCE; APLASTIC-ANEMIA; HIGH PREVALENCE;
BLOOM-SYNDROME; ETHNIC-ORIGIN; GROUP-A; MUTATION; POPULATION; DISEASE
AB For many recessive genetic syndromes, carrier frequencies have been assessed through screening studies in founder populations but remain unclear in heterogeneous populations. One such syndrome is Fanconi Anemia (FA). FA is a model disease in cancer research, yet there are no contemporary data on carrier frequency or prevalence in the general United States (US) population or elsewhere. We inferred carrier frequency from birth incidence using the Hardy-Weinberg law. We estimated prevalence using birth incidence and survival data. We defined "plausible ranges" to incorporate uncertainty about completeness of case ascertainment. We made estimates for the US and Israel using demographic data from the Fanconi Anemia Research Fund and Israeli Fanconi Anemia Registry. In the US, a plausible range for the carrier frequency is 1:156-1:209 [midpoint 1:181[; we estimate that 550-975 persons were living with FA in 2010. For Israel, a plausible range for the carrier frequency is 1:66-1:128 [midpoint 1:931 in line with founder screening studies; we estimate that 40-135 Israelis were living with FA in 2008. The estimated US FA carrier frequency of 1:181 is significantly higher than the historical estimate of 1:300; hence, the gap may be narrower than previously recognized between the US carrier frequency and higher carrier frequencies of around 1:100 in several founder groups including Ashkenazi Jews. Assessment of cancer risks in heterozygous carriers merits further study. Clinical trials in FA will require co-ordination and innovative design because the number of living US patients is probably less than 1,000. Published 2011 Wiley-Liss, Inc.
C1 [Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Tamary, Hannah] Schneider Childrens Med Ctr Israel, Dept Pediat Hematol Oncol, Petah Tiqwa, Israel.
[Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
RP Rosenberg, PS (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Execut Plaza S,Room 8022, Rockville, MD 20852 USA.
EM rosenbep@mail.nih.gov
FU Intramural NIH HHS [Z01 CP010181-05]
NR 46
TC 20
Z9 21
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD AUG
PY 2011
VL 155A
IS 8
BP 1877
EP 1883
DI 10.1002/ajmg.a.34087
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 809WT
UT WOS:000294088100014
PM 21739583
ER
PT J
AU Solomon, BD
Raam, MS
Pineda-Alvarez, DE
Cummings, DAT
AF Solomon, Benjamin D.
Raam, Manu S.
Pineda-Alvarez, Daniel E.
Cummings, Derek A. T.
TI Patients With VACTERL Association Deserve Careful Scrutiny: Response to
Jenetzky et al.
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Letter
ID MALFORMATIONS
C1 [Solomon, Benjamin D.; Raam, Manu S.; Pineda-Alvarez, Daniel E.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Cummings, Derek A. T.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
RP Solomon, BD (reprint author), NHGRI, Med Genet Branch, NIH, MSC 3717,Bldg 35,Room 1B-207, Bethesda, MD 20892 USA.
EM solomonb@mail.nih.gov
NR 8
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD AUG
PY 2011
VL 155A
IS 8
BP 2042
EP 2043
DI 10.1002/ajmg.a.33982
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA 809WT
UT WOS:000294088100043
ER
PT J
AU Donsante, A
Johnson, P
Jansen, LA
Kaler, SG
AF Donsante, Anthony
Johnson, Paul
Jansen, Laura A.
Kaler, Stephen G.
TI Somatic Mosaicism in Menkes Disease Suggests Choroid Plexus-Mediated
Copper Transport to the Developing Brain (vol 152A, pg 2529, 2010)
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Correction
C1 [Donsante, Anthony; Johnson, Paul; Kaler, Stephen G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD USA.
[Jansen, Laura A.] Univ Washington, Div Pediat Neurol, Seattle Childrens Hosp, Res Inst, Seattle, WA 98195 USA.
RP Kaler, SG (reprint author), NICHD, NIH, Program Mol Med, 10 Ctr Dr,Rm 5-2571, Bethesda, MD 20814 USA.
EM kalers@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD AUG
PY 2011
VL 155A
IS 8
BP 2044
EP 2044
DI 10.1002/ajmg.a.34065
PG 1
WC Genetics & Heredity
SC Genetics & Heredity
GA 809WT
UT WOS:000294088100044
ER
PT J
AU Tomic, M
Kucka, M
Kretschmannova, K
Li, S
Nesterova, M
Stratakis, CA
Stojilkovic, SS
AF Tomic, Melanija
Kucka, Marek
Kretschmannova, Karla
Li, Shuo
Nesterova, Maria
Stratakis, Constantine A.
Stojilkovic, Stanko S.
TI Role of nonselective cation channels in spontaneous and protein kinase
A-stimulated calcium signaling in pituitary cells
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE adenylyl cyclase; adenosine 3 ',5 '-cyclic monophosphate; calcium
transients; transient receptor potential channels; gonadotrophs;
lactotrophs; somatotrophs
ID BACKGROUND SODIUM CONDUCTANCE; HORMONE-RELEASING-HORMONE; VOLTAGE-GATED
NA+; SUBUNIT TYPE 1A; ANTERIOR-PITUITARY; REGULATORY SUBUNIT; CA2+
CHANNELS; CARNEY COMPLEX; RAT; MECHANISM
AB Tomic M, Kucka M, Kretschmannova K, Li S, Nesterova M, Stratakis CA, Stojilkovic SS. Role of nonselective cation channels in spontaneous and protein kinase A-stimulated calcium signaling in pituitary cells. Am J Physiol Endocrinol Metab 301: E370-E379, 2011. First published May 17, 2011; doi:10.1152/ajpendo.00130.2011.-Several receptors linked to the adenylyl cyclase signaling pathway stimulate electrical activity and calcium influx in endocrine pituitary cells, and a role for an unidentified sodium-conducting channel in this process has been proposed. Here we show that forskolin dose-dependently increases cAMP production and facilitates calcium influx in about 30% of rat and mouse pituitary cells at its maximal concentration. The stimulatory effect of forskolin on calcium influx was lost in cells with inhibited PKA (cAMP-dependent protein kinase) and in cells that were haploinsufficient for the main PKA regulatory subunit but was preserved in cells that were also haploinsufficient for the main PKA catalytic subunit. Spontaneous and forskolin-stimulated calcium influx was present in cells with inhibited voltage-gated sodium and hyperpolarization-activated cation channels but not in cells bathed in medium, in which sodium was replaced with organic cations. Consistent with the role of sodium-conducting nonselective cation channels in PKA-stimulated Ca(2+) influx, cAMP induced a slowly developing current with a reversal potential of about 0 mV. Two TRP (transient receptor potential) channel blockers, SKF96365 and 2-APB, as well as flufenamic acid, an inhibitor of nonselective cation channels, also inhibited spontaneous and forskolin-stimulated electrical activity and calcium influx. Quantitative RT-PCR analysis indicated the expression of mRNA transcripts for TRPC1 >> TRPC6 > TRPC4 > TRPC5 > TRPC3 in rat pituitary cells. These experiments suggest that in pituitary cells constitutively active cation channels are stimulated further by PKA and contribute to calcium signaling indirectly by controlling the pacemaking depolarization in a sodium-dependent manner and directly by conducting calcium.
C1 [Tomic, Melanija; Kucka, Marek; Kretschmannova, Karla; Li, Shuo; Stojilkovic, Stanko S.] Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, Sect Cellular Signaling, Programs Dev Neurosci, NIH, Bethesda, MD USA.
[Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, Sect Endocrinol & Genet, Programs Dev Neurosci, NIH, Bethesda, MD USA.
[Tomic, Melanija; Kucka, Marek; Kretschmannova, Karla; Li, Shuo; Stojilkovic, Stanko S.] Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, Sect Cellular Signaling, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
[Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Stojilkovic, SS (reprint author), NICHD, Bldg 49,Rm 6A-36,49 Convent Dr, Bethesda, MD 20892 USA.
EM stojilks@mail.nih.gov
RI Tomic, Melanija/C-3371-2016
FU National Institute of Child Health and Human Development
FX This work was supported by the Intramural Research Program of the
National Institute of Child Health and Human Development.
NR 44
TC 13
Z9 13
U1 0
U2 7
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 AUG
PY 2011
VL 301
IS 2
BP E370
EP E379
DI 10.1152/ajpendo.00130.2011
PG 10
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 811KZ
UT WOS:000294210200017
PM 21586701
ER
PT J
AU Yang, IV
Alper, S
Lackford, B
Rutledge, H
Warg, LA
Burch, LH
Schwartz, DA
AF Yang, Ivana V.
Alper, Scott
Lackford, Brad
Rutledge, Holly
Warg, Laura A.
Burch, Lauranell H.
Schwartz, David A.
TI Novel Regulators of the Systemic Response to Lipopolysaccharide
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE endotoxic shock; gram-negative sepsis; inbred murine strains; gene
expression; microarray; transcription factor
ID NF-KAPPA-B; LUNG NEUTROPHIL RECRUITMENT; GENE-EXPRESSION PROFILES;
TOLL-LIKE RECEPTORS; TRANSCRIPTION FACTORS; SONIC HEDGEHOG; SIGNALING
PATHWAY; INNATE IMMUNITY; HUMAN-DISEASE; SEPSIS
AB Our understanding of the role that host genetic factors play in the initiation and severity of infections caused by gram-negative bacteria is incomplete. To identify novel regulators of the host response to lipopolysaccharide (LPS), 11 inbred murine strains were challenged with LPS systemically. In addition to two strains lacking functional TLR4 (C3H/HeJ and C57BL/6J(TLR4-/-)), three murine strains with functional TLR4 (C57BL/6J, 129/SvImJ, and NZW/LacJ) were found to be relatively resistant to systemic LPS challenge; the other six strains were classified as sensitive. RNA from lung, liver, and spleen tissue was profiled on oligonucleotide microarrays to determine if unique transcripts differentiate susceptible and resistant strains. Gene expression analysis identified the Hedgehog signaling pathway and a number of transcription factors (TFs) involved in the response to LPS. RNA interference-mediated inhibition of six TFs (C/EBP, Cdx-2, E2F1, Hoxa4, Nhlh1, and Tead2) was found to diminish IL-6 and TNF-alpha production by murine macrophages. Mouse lines with targeted mutations were used to verify the involvement of two novel genes in innate immunity. Compared with wild-type control mice, mice deficient in the E2F1 transcription factor were found to have a reduced inflammatory response to systemic LPS, and mice heterozygote for Ptch, a gene involved in Hedgehog signaling, were found to be more responsive to systemic LPS. Our analysis of gene expression data identified novel pathways and transcription factors that regulate the host response to systemic LPS. Our results provide potential sepsis biomarkers and therapeutic targets that should be further investigated in human populations.
C1 [Yang, Ivana V.; Alper, Scott; Warg, Laura A.; Schwartz, David A.] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO 80206 USA.
[Yang, Ivana V.; Alper, Scott; Warg, Laura A.; Schwartz, David A.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA.
[Yang, Ivana V.; Schwartz, David A.] Univ Colorado Denver, Dept Med, Aurora, CO USA.
[Alper, Scott; Schwartz, David A.] Univ Colorado, Integrated Dept Immunol, Denver, CO 80202 USA.
[Lackford, Brad; Rutledge, Holly; Burch, Lauranell H.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA.
RP Yang, IV (reprint author), Natl Jewish Hlth, Ctr Genes Environm & Hlth, 1400 Jackson St,Smith Bldg A651, Denver, CO 80206 USA.
EM yangi@njhealth.org
FU Department of Veterans' Affairs; National Institute of Environmental
Health Sciences [ES11375, ES011961]; NIH, National Institute of the
Environmental Health Sciences; National Heart Lung and Blood Institute
FX This study was supported by the Department of Veterans' Affairs (Merit
Review), the National Institute of Environmental Health Sciences grants
ES11375 and ES011961 and by the Intramural Research Program of the NIH,
National Institute of the Environmental Health Sciences and National
Heart Lung and Blood Institute.
NR 52
TC 18
Z9 18
U1 0
U2 4
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 AUG
PY 2011
VL 45
IS 2
BP 393
EP 402
DI 10.1165/rcmb.2010-0342OC
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 808BQ
UT WOS:000293948900023
PM 21131441
ER
PT J
AU Kim, TH
Youn, YS
Jiang, HH
Lee, S
Chen, XY
Lee, KC
AF Kim, Tae Hyung
Youn, Yu Seok
Jiang, Hai Hua
Lee, Seulki
Chen, Xiaoyuan
Lee, Kang Choon
TI PEGylated TNF-Related Apoptosis-Inducing Ligand (TRAIL) Analogues:
Pharmacokinetics and Antitumor Effects
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID IN-VIVO; TUMOR; STABILITY; SITE; INTERFERON; RECEPTORS; MOLECULE;
EFFICACY; DELIVERY; SAFETY
AB The low stability and fast clearance of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) are the main obstacles to its implementation as an antitumor agent. Here, we attempted to improve its pharmacokinetic and pharmacodynamic profiles by using PEGylation. N-terminal PEGylated TRAIL (PEG-TRAIL) was synthesized using 2, 5, 10, 20, and 30 kDa PEG. Antitumor effect assessments in HCT116 tumor bearing nude mice showed that all PEG-TRAIL analogues efficiently suppressed mean tumor growth, with mean tumor growth inhibition (TGI) values (5K-, 20K-, 30K-PEG-TRAIL) of 43.5, 61.7, and 72.3%, respectively. In particular, 30K-PEG-TRAIL was found to have antitumor efficacy for five days after a single administration (1 mg/mouse, ip). The different antitumor effects of these PEG-TRAIL analogues were attributed to augmented pharmacokinetics and metabolic resistance. All analogues were found to have higher metabolic stabilities in rat plasma, extended pharmacokinetic profiles, and greater circulating half-lives (3.9, 5.3, 6.2, 12.3, and 17.7 h for 2, 5, 10, 20, and 30K-PEG-TRAIL, respectively, versus 1.1 h for TRAIL, ip) in ICR mice. Our findings suggest that TRAIL derivatized with PEG of an appropriate M(w) might be useful antitumor agent with protracted activity.
C1 [Kim, Tae Hyung; Youn, Yu Seok; Jiang, Hai Hua; Lee, Kang Choon] Sungkyunkwan Univ, Coll Pharm, Jangan Ku, Suwon 440746, South Korea.
[Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Lee, KC (reprint author), Sungkyunkwan Univ, Coll Pharm, Jangan Ku, 300 Chonchon Dong, Suwon 440746, South Korea.
EM kclee@skku.edu
FU Korean Ministry of Education, Science, and Technology [2010K001256]
FX This work was supported by a grant from the Korean Ministry of
Education, Science, and Technology (grant no. 2010K001256).
NR 25
TC 26
Z9 26
U1 1
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD AUG
PY 2011
VL 22
IS 8
BP 1631
EP 1637
DI 10.1021/bc200187k
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 809SC
UT WOS:000294076000021
PM 21751817
ER
PT J
AU Nakajima, T
Mitsunaga, M
Bander, NH
Heston, WD
Choyke, PL
Kobayashi, H
AF Nakajima, Takahito
Mitsunaga, Makoto
Bander, Neil H.
Heston, Warren D.
Choyke, Peter L.
Kobayashi, Hisataka
TI Targeted, Activatable, In Vivo Fluorescence Imaging of Prostate-Specific
Membrane Antigen (PSMA) Positive Tumors Using the Quenched Humanized
J591 Antibody-Indocyanine Green (ICG) Conjugate
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID RADIOLABELED MONOCLONAL-ANTIBODIES; EXTRACELLULAR DOMAIN; CANCER;
EXPRESSION; THERAPY
AB In patients with prostate cancer, a positive surgical margin is associated with an increased risk of cancer recurrence and poorer outcome, yet margin status cannot be determined during the surgery. An in vivo optical imaging probe that could identify the tumor margins during surgery could result in improved outcomes. The design of such a probe focuses on a highly specific targeting moiety and a near-infrared (NIR) fluorophore that is activated only when bound to the tumor. In this study, we successfully synthesized an activatable monoclonal antibody-fluorophore conjugate consisting of a humanized anti-Prostate-Specific Membrane Antigen (PSMA) antibody 0591) linked to an indocyanine green (ICG) derivative. Prior to binding to PSMA and cellular internalization, the conjugate yielded little light; however, after binding an 18-fold activation was observed permitting the specific detection of PSMA+ tumors up to 10 days after injection of a low dose (0.25 mg/kg) of the reagent. This agent demonstrates promise as a method to image the extent of prostate cancer in vivo and could assist with real-time resection of extracapsular extension of tumor and positive lymph nodes.
C1 [Nakajima, Takahito; Mitsunaga, Makoto; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Bander, Neil H.] Cornell Univ, Dept Urol, Weill Med Coll, New York, NY 10065 USA.
[Heston, Warren D.] Cleveland Clin, Dept Canc Biol, Cleveland, OH 44195 USA.
[Heston, Warren D.] Cleveland Clin, Inst Urol, Cleveland, OH 44195 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM Kobayash@mail.nih.gov
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. N.H.B. is a paid consultant to and owns stock in BZL
Biologics, Inc., the company to which the patents were licensed by
Cornell Research Foundation for further research and development for the
J591 antibody utilized in this article.
NR 23
TC 44
Z9 47
U1 1
U2 29
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD AUG
PY 2011
VL 22
IS 8
BP 1700
EP 1705
DI 10.1021/bc2002715
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 809SC
UT WOS:000294076000029
PM 21740058
ER
PT J
AU Budde, MD
Janes, L
Gold, E
Turtzo, LC
Frank, JA
AF Budde, Matthew D.
Janes, Lindsay
Gold, Eric
Turtzo, Lisa Christine
Frank, Joseph A.
TI The contribution of gliosis to diffusion tensor anisotropy and
tractography following traumatic brain injury: validation in the rat
using Fourier analysis of stained tissue sections
SO BRAIN
LA English
DT Article
DE anisotropy; traumatic brain injury; gliosis; axonal degeneration;
diffusion tensor imaging
ID CONTROLLED CORTICAL IMPACT; WHITE-MATTER; REACTIVE ASTROCYTES;
NERVOUS-SYSTEM; AXONAL INJURY; ORIENTATION DISTRIBUTIONS; COGNITIVE
FUNCTION; WATER DIFFUSION; IMAGING DETECTS; WEIGHTED MRI
AB Diffusion tensor imaging is highly sensitive to the microstructural integrity of the brain and has uncovered significant abnormalities following traumatic brain injury not appreciated through other methods. It is hoped that this increased sensitivity will aid in the detection and prognostication in patients with traumatic injury. However, the pathological substrates of such changes are poorly understood. Specifically, decreases in fractional anisotropy derived from diffusion tensor imaging are consistent with axonal injury, myelin injury or both in white matter fibres. In contrast, in both humans and animal models, increases in fractional anisotropy have been suggested to reflect axonal regeneration and plasticity, but the direct histological evidence for such changes remains tenuous. We developed a method to quantify the anisotropy of stained histological sections using Fourier analysis, and applied the method to a rat controlled cortical impact model to identify the specific pathological features that give rise to the diffusion tensor imaging changes in subacute to chronic traumatic brain injury. A multiple linear regression was performed to relate the histological measurements to the measured diffusion tensor changes. The results show that anisotropy was significantly increased (P < 0.001) in the perilesioned cortex following injury. Cortical anisotropy was independently associated (standardized beta = 0.62, P = 0.04) with the coherent organization of reactive astrocytes (i.e. gliosis) and was not attributed to axons. By comparison, a decrease in white matter anisotropy (P < 0.001) was significantly related to demyelination (beta = 0.75, P = 0.0015) and to a lesser extent, axonal degeneration (beta = -0.48, P = 0.043). Gliosis within the lesioned cortex also influenced diffusion tensor tractography, highlighting the fact that spurious tracts in the injured brain may not necessarily reflect continuous axons and may instead depict glial scarring. The current study demonstrates a novel method to relate pathology to diffusion tensor imaging findings, elucidates the underlying mechanisms of anisotropy changes following traumatic brain injury and significantly impacts the clinical interpretation of diffusion tensor imaging findings in the injured brain.
C1 [Budde, Matthew D.; Frank, Joseph A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Budde, Matthew D.; Janes, Lindsay; Gold, Eric; Turtzo, Lisa Christine; Frank, Joseph A.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Budde, Matthew D.] Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA.
[Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
RP Budde, MD (reprint author), C1890 Neurosci Res Ctr, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM mdbudde@mcw.edu
FU Centre for Neuroscience and Regenerative Medicine [300604-8.01-60855];
National Institutes of Health Clinical Centre
FX The work was supported by the Intramural Research Programme at the
National Institutes of Health Clinical Centre and the Centre for
Neuroscience and Regenerative Medicine (300604-8.01-60855 to J.A.F.).
NR 67
TC 116
Z9 117
U1 0
U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD AUG
PY 2011
VL 134
BP 2248
EP 2260
DI 10.1093/brain/awr161
PN 8
PG 13
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 809OX
UT WOS:000294067700012
PM 21764818
ER
PT J
AU Palos, GR
Hare, M
AF Palos, Guadalupe R.
Hare, Martha
TI Patients, Family Caregivers, and Patient Navigators A Partnership
Approach
SO CANCER
LA English
DT Article
DE patient navigation; cancer; vulnerable population; caregiver; survivors
ID AFRICAN-AMERICAN WOMEN; SOCIAL SUPPORT; DEPRESSIVE SYMPTOMS; ADVANCED
CANCER; VALIDATION; NETWORKS; HEALTH; CARE; RELIABILITY; INSTRUMENT
AB BACKGROUND: Navigation services may be strengthened by establishing a partnership between the patient, family/caregiver, and the navigator. Involvement of a patient's familial or social network in the navigation process would allow patient navigators to spend more time and resources with the subset of patients who do not have support from family and friends. The Partnership Approach evolves from combining the strength of a patient's existing social support and network with the delivery of navigation services. METHODS: To develop this novel approach, the Family and Caregiver Workgroup was convened at the American Cancer Society's National Leadership Summit. Individuals were asked to serve in this group due to their interest, research, or experience in family and caregiver issues. RESULTS: By the end of the Summit, the workgroup had achieved 3 major outcomes: 1) enhancement of current patient navigation services by building a partnership between the patient, family or primary caregivers, and navigators; 2) identification of a set of core functions that a family/caregiver could perform in a partnership; and 3) consensus on a set of metrics to use with caregivers and patients. Five major domains were selected to measure patient and/or caregiver outcomes: quality of life, satisfaction with care, social support, distress, and caregiver burden. Metrics appropriate for each domain were recommended. CONCLUSIONS: Integration of these domains and scales in current navigation services is needed to develop future research. Evidence from such research would help determine whether the Partnership Approach contributes to improved patient and caregiver outcomes. Cancer 2011;117(15 suppl):3592-602. (C) 2011 American Cancer Society.
C1 [Palos, Guadalupe R.] Univ Texas MD Anderson Canc Ctr, Canc Survivorship Program, Houston, TX 77030 USA.
[Hare, Martha] NCI, Ctr Reduce Canc Hlth Dispar, NIH, Rockville, MD USA.
RP Palos, GR (reprint author), Univ Texas MD Anderson Canc Ctr, Canc Survivorship Program, 1515 Holcombe Blvd,Box 1455, Houston, TX 77030 USA.
EM gpalos@mdanderson.org
FU Pfizer Oncology; Livestrong (Lance Armstrong Foundation); Susan G. Komen
for the Cure; Oncology Nursing Society (ONS); American College of
Surgeons Commission on Cancer; American Cancer Society; AstraZeneca
FX This conference and supplement were cosponsored by Pfizer Oncology,
Livestrong (Lance Armstrong Foundation), Susan G. Komen for the Cure,
the Oncology Nursing Society (ONS), the American College of Surgeons
Commission on Cancer, the American Cancer Society, and AstraZeneca.
NR 51
TC 9
Z9 9
U1 4
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD AUG 1
PY 2011
VL 117
IS 15
SU S
BP 3592
EP 3602
DI 10.1002/cncr.26263
PG 11
WC Oncology
SC Oncology
GA 797DF
UT WOS:000293104000008
PM 21780094
ER
PT J
AU Bernhard, EJ
AF Bernhard, E. J.
TI Interventions that induce modifications in the tumor microenvironment
SO CANCER RADIOTHERAPIE
LA English
DT Review
DE Hypoxia; Angiogenesis; Vasculogenesis; Cell signaling; Stem cells; Tumor
stroma
ID VASCULAR NORMALIZATION; IONIZING-RADIATION; NECK-CANCER;
PANCREATIC-CANCER; ENDOTHELIAL-CELLS; PHASE-II; VASCULOGENIC MIMICRY;
STROMAL SENSITIVITY; ANTITUMOR-ACTIVITY; CYCLIC HYPOXIA
AB Non-surgical cancer therapeutic strategies have focused primarily on direct killing of cancer cells by chemotherapy and/or radiation therapy. However, it is becoming increasingly clear that the efficacy of these therapies can be significantly influenced by the tumor microenvironment. The microenvironment poses both obstacles and opportunities for new therapeutic interventions. New developments in this area are the topic of this review. Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.
C1 NCI, Radiotherapy Dev Branch, RRP, DCTD,NIH, Rockville, MD 20892 USA.
RP Bernhard, EJ (reprint author), NCI, Radiotherapy Dev Branch, RRP, DCTD,NIH, 6130 Execut Blvd,Rm 6010,MSC 7440, Rockville, MD 20892 USA.
EM bernhardej@mail.nih.gov
NR 101
TC 8
Z9 12
U1 0
U2 4
PU ELSEVIER
PI BRIDGEWATER
PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA
SN 1278-3218
J9 CANCER RADIOTHER
JI Cancer Radiother.
PD AUG
PY 2011
VL 15
IS 5
BP 376
EP 382
DI 10.1016/j.canrad.2011.01.007
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 810BA
UT WOS:000294099200005
PM 21571567
ER
PT J
AU Francis, SP
Kramarenko, II
Brandon, CS
Lee, FS
Baker, TG
Cunningham, LL
AF Francis, S. P.
Kramarenko, I. I.
Brandon, C. S.
Lee, F-S
Baker, T. G.
Cunningham, L. L.
TI Celastrol inhibits aminoglycoside-induced ototoxicity via heat shock
protein 32
SO CELL DEATH & DISEASE
LA English
DT Article
DE ototoxicity; hair cell; celastrol; heat shock protein; utricle; cochlea;
hearing loss
ID HAIR CELL-DEATH; N-TERMINAL KINASE; WILFORDII HOOK-F; HEME OXYGENASE-1;
IN-VITRO; TRIPTERYGIUM-WILFORDII; RHEUMATOID-ARTHRITIS; PROTEASOME
INHIBITOR; MOUSE UTRICLE; HEARING-LOSS
AB Hearing loss is often caused by death of the mechanosensory hair cells of the inner ear. Hair cells are susceptible to death caused by aging, noise trauma, and ototoxic drugs, including the aminoglycoside antibiotics and the antineoplastic agent cisplatin. Ototoxic drugs result in permanent hearing loss for over 500 000 Americans annually. We showed previously that induction of heat shock proteins (HSPs) inhibits both aminoglycoside-and cisplatin-induced hair cell death in whole-organ cultures of utricles from adult mice. In order to begin to translate these findings into a clinical therapy aimed at inhibiting ototoxic drug-induced hearing loss, we have now examined a pharmacological HSP inducer, celastrol. Celastrol induced upregulation of HSPs in utricles, and it provided significant protection against aminoglycoside-induced hair cell death in vitro and in vivo. Moreover, celastrol inhibited hearing loss in mice receiving systemic aminoglycoside treatment. Our data indicate that the major heat shock transcription factor HSF-1 is not required for celastrol-mediated protection. HSP32 (also called heme oxygenase-1, HO-1) is the primary mediator of the protective effect of celastrol. HSP32/HO-1 inhibits pro-apoptotic c-Jun N-terminal kinase (JNK) activation and hair cell death. Taken together, our data indicate that celastrol inhibits aminoglycoside ototoxicity via HSP32/HO-1 induction. Cell Death and Disease (2011) 2, e195; doi: 10.1038/cddis.2011.76; published online 25 August 2011
C1 [Cunningham, L. L.] Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA.
[Francis, S. P.; Kramarenko, I. I.; Brandon, C. S.; Baker, T. G.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA.
[Lee, F-S] Med Univ S Carolina, Dept Otolaryngol HNS, Charleston, SC 29425 USA.
RP Cunningham, LL (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Court, Rockville, MD 20850 USA.
EM lisa.cunningham@nih.gov
FU National Institutes of Health [NIDCD 5R01 DC007613, DC007613-SI, 5F31
DC010559]; Division of Intramural Research at the National Institute on
Deafness and Other Communication Disorders; National Center for Research
Resources [C06 RR015455, C06 RR14516]; MUSC
FX This work was supported by the National Institutes of Health (NIDCD 5R01
DC007613, DC007613-SI, and 5F31 DC010559). Additional support was
provided by the Division of Intramural Research at the National
Institute on Deafness and Other Communication Disorders, NIH/NCRR
extramural research facilities construction (C06) Grants C06 RR015455
and C06 RR14516 from the National Center for Research Resources, and the
MUSC Initiative for Maximizing Student Diversity (IMSD) Program. We
thank Dr. Margaret Lomax for providing us with Hsf-1-/- mice.
We also thank Dr. Thomas Friedman, Dr. Olivia Bermingham-McDonogh and
Dr. Christina Voelkel-Johnson for helpful comments on the manuscript,
and Lisa M. Fennessy for assistance in the development of the diagram of
the mechanism of celastrol's protective effect.
NR 43
TC 13
Z9 14
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD AUG
PY 2011
VL 2
AR e195
DI 10.1038/cddis.2011.76
PG 11
WC Cell Biology
SC Cell Biology
GA 811VQ
UT WOS:000294244700009
PM 21866174
ER
PT J
AU Bahta, M
Burke, TR
AF Bahta, Medhanit
Burke, Terrence R., Jr.
TI Oxime-Based Click Chemistry in the Development of 3-Isoxazolecarboxylic
Acid Containing Inhibitors of Yersinia pestis Protein Tyrosine
Phosphatase, YopH
SO CHEMMEDCHEM
LA English
DT Article
DE aminooxy platform; docking studies; inhibitors; oxime-based click
chemistry; substrate screening
ID PROMISCUOUS INHIBITORS; BIDENTATE INHIBITORS; PURIFICATION;
PHOSPHOTYROSINE; IDENTIFICATION; OVERPRODUCTION; MECHANISM; MIMETICS;
LIGATION; DESIGN
AB The pathogenicity of Yersinia pestis relies on several effector proteins including YopH, a protein tyrosine phosphatase (PTP). We previously screened a library of analogues based on the ubiquitous PTP substrate para-nitrophenylphosphate (pNPP) and found that incorporation of a 3-phenyl substituent to give 6-nitro-[1,1'-biphenyl]-3-yldihydrogen phosphate (1) enhanced affinity. Herein we report the conversion of 1 from a substrate into an inhibitor by replacing the hydrolysable phosphoryl group with a 3-isoxazolecarboxylic acid moiety and by introduction of an aminooxy group and subsequent diversification using oxime-based click chemistry. This approach led to the identification of non-promiscuous bidentate YopH inhibitors with affinity in the low micromolar range.
C1 [Bahta, Medhanit; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Bahta, M (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, POB,Bldg 376,Boyles St, Frederick, MD 21702 USA.
EM tburke@helix.nih.gov
RI Burke, Terrence/N-2601-2014
FU National Institutes of Health (NIH), Center for Cancer Research,
NCI-Frederick; National Cancer Institute, NIH
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health (NIH), Center for Cancer Research,
NCI-Frederick and the National Cancer Institute, NIH. The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does the mention of
trade names, commercial products, or organizations imply endorsement by
the U.S. Government.
NR 37
TC 12
Z9 12
U1 0
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1860-7179
J9 CHEMMEDCHEM
JI ChemMedChem
PD AUG 1
PY 2011
VL 6
IS 8
BP 1363
EP 1370
DI 10.1002/cmdc.201100200
PG 8
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 810GE
UT WOS:000294112900006
PM 21671403
ER
PT J
AU Costanzi, S
Vilar, S
Micozzi, D
Carpi, FM
Ferino, G
Vita, A
Vincenzetti, S
AF Costanzi, Stefano
Vilar, Santiago
Micozzi, Daniela
Carpi, Francesco M.
Ferino, Giulio
Vita, Alberto
Vincenzetti, Silvia
TI Delineation of the Molecular Mechanisms of Nucleoside Recognition by
Cytidine Deaminase through Virtual Screening
SO CHEMMEDCHEM
LA English
DT Article
DE cancer; enzymes; hydrolases; inhibitors; virtual screening
ID DRUG-LIKE MOLECULES; CRYSTAL-STRUCTURE; PSEUDOISOCYTIDINE; PURIFICATION;
INHIBITION; PREDICTION
AB Cytidine deaminase (EC 3.5.4.5, CDA), an enzyme of the pyrimidine salvage pathways, is responsible for the degradation and inactivation of several cytidine-based antitumor drugs such as cytarabine, gemcitabine, decitabine, and azacytidine. Thus, CDA inhibitors are highly sought after as compounds to be co-administered with said drugs to improve their effectiveness. Alternatively, the design of antitumor drugs not susceptible to the action of CDA is also regarded as an attractive solution. Herein we describe a virtual screen for CDA ligands based on chemical similarity and molecular docking. The campaign led to the identification of three novel inhibitors and one novel substrate, with a 19% hit rate, and allowed a significant extension of the structure-activity relationships, also in light of the compounds that resulted inactive. The most active compound identified through the screen is the inhibitor pseudoisocytidine, which has the potential to serve as a lead for highly stable compounds. The study also delineated the detrimental effect of 5-aza and 6-aza substitutions, the incompatibility of the presence of an amino group at the 3'-position, as well as the presence of very strict steric requirements around the 2'-arabino position and, even more, the N4-position. Importantly, these features can be exploited for the design of novel antineoplastic agents resistant to the action of CDA.
C1 [Costanzi, Stefano; Vilar, Santiago; Ferino, Giulio] NIDDKD, Lab Biol Modeling, NIH, DHHS, Bethesda, MD 20892 USA.
[Vita, Alberto; Vincenzetti, Silvia] Univ Camerino, Sch Vet Med Sci, I-62024 Matelica, MC, Italy.
[Micozzi, Daniela; Carpi, Francesco M.] Sch Biosci & Biotechnol, I-62032 Camerino, MC, Italy.
RP Costanzi, S (reprint author), NIDDKD, Lab Biol Modeling, NIH, DHHS, 12A South Dr, Bethesda, MD 20892 USA.
EM stefanoc@mail.nih.gov; silvia.vincenzetti@unicam.it
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 in part by the intramural research program
of the NIH, NIDDK. We thank the NCI/DTP for providing the compounds.
NR 18
TC 6
Z9 6
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1860-7179
J9 CHEMMEDCHEM
JI ChemMedChem
PD AUG 1
PY 2011
VL 6
IS 8
BP 1452
EP 1458
DI 10.1002/cmdc.201100139
PG 7
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 810GE
UT WOS:000294112900013
PM 21598398
ER
PT J
AU Adeva, MM
Souto, G
AF Adeva, Maria M.
Souto, Gema
TI Diet-induced metabolic acidosis
SO CLINICAL NUTRITION
LA English
DT Review
DE Metabolic acidosis; Ammonium ions; Citrate; Insulin resistance
ID NUTRITION EXAMINATION SURVEY; RANDOMIZED CLINICAL-TRIAL; SERUM ANION
GAP; INSULIN-RESISTANCE; AMMONIUM-CHLORIDE; BLOOD-PRESSURE;
PROTEIN-INTAKE; POSTMENOPAUSAL WOMEN; HORMONAL RESPONSES;
CALCIUM-METABOLISM
AB The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. (C) 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
C1 [Adeva, Maria M.] Hosp Gen Juan Cardona, La Coruna 15406, Spain.
[Souto, Gema] NIH, Ctr Clin, Washington, DC USA.
RP Adeva, MM (reprint author), Hosp Gen Juan Cardona, C Pardo Bazan S-N, La Coruna 15406, Spain.
EM madevaa@yahoo.com
NR 62
TC 46
Z9 46
U1 2
U2 37
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0261-5614
EI 1532-1983
J9 CLIN NUTR
JI Clin. Nutr.
PD AUG
PY 2011
VL 30
IS 4
BP 416
EP 421
DI 10.1016/j.clnu.2011.03.008
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 809DT
UT WOS:000294032700003
PM 21481501
ER
PT J
AU Yamamoto, KN
Hirota, K
Kono, K
Takeda, S
Sakamuru, S
Xia, MH
Huang, RL
Austin, CP
Witt, KL
Tice, RR
AF Yamamoto, Kimiyo N.
Hirota, Kouji
Kono, Koichi
Takeda, Shunichi
Sakamuru, Srilatha
Xia, Menghang
Huang, Ruili
Austin, Christopher P.
Witt, Kristine L.
Tice, Raymond R.
TI Characterization of Environmental Chemicals With Potential for DNA
Damage Using Isogenic DNA Repair-Deficient Chicken DT40 Cell Lines
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE DT40 DNA repair-deficient cell lines; quantitative high throughput
screens; cytotoxicity; genotoxicity; chromosomal aberrations; gamma H2AX
positive foci
ID HOMOLOGOUS RECOMBINATION; VERTEBRATE CELLS; EXCISION-REPAIR; CHROMOSOMAL
BREAKS; TOPOISOMERASE-II; POLYMERASE-ZETA; RAD51 PARALOGS; PATHWAYS;
ASSAY; TOXICOLOGY
AB Included among the quantitative high throughput screens (qHTS) conducted in support of the US Tox21 program are those being evaluated for the detection of genotoxic compounds. One such screen is based on the induction of increased cytotoxicity in seven isogenic chicken DT40 cell lines deficient in DNA repair pathways compared to the parental DNA repair-proficient cell line. To characterize the utility of this approach for detecting genotoxic compounds and identifying the type(s) of DNA damage induced, we evaluated nine of 42 compounds identified as positive for differential cytotoxicity in qHTS (actinomycin D, adriamycin, alachlor, benzotrichloride, diglycidyl resorcinol ether, lovastatin, melphalan, trans-1,4-dichloro-2-butene, tris(2,3-epoxypropyl)isocyanurate) and one non-cytotoxic genotoxic compound (2-aminothiamine) for (1) clastogenicity in mutant and wild-type cells; (2) the comparative induction of gamma H2AX positive foci by melphalan; (3) the extent to which a 72-hr exposure duration increased assay sensitivity or specificity; (4) the use of 10 additional DT40 DNA repair-deficient cell lines to better analyze the type(s) of DNA damage induced; and (5) the involvement of reactive oxygen species in the induction of DNA damage. All compounds but lovastatin and 2-aminothiamine were more clastogenic in at least one DNA repair-deficient cell line than the wild-type cells. The differential responses across the various DNA repair-deficient cell lines provided information on the type(s) of DNA damage induced. The results demonstrate the utility of this DT40 screen for detecting genotoxic compounds, for characterizing the nature of the DNA damage, and potentially for analyzing mechanisms of mutagenesis. Environ. Mol. Mutagen. 52:547-561, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Yamamoto, Kimiyo N.; Hirota, Kouji; Takeda, Shunichi] Kyoto Univ, Grad Sch Med, Sakyo Ku, Kyoto, Japan.
[Yamamoto, Kimiyo N.; Kono, Koichi] Osaka Med Coll, Grad Sch Med, Osaka, Japan.
[Sakamuru, Srilatha; Xia, Menghang; Huang, Ruili; Austin, Christopher P.] NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA.
[Witt, Kristine L.; Tice, Raymond R.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, NIH, Res Triangle Pk, NC USA.
RP Yamamoto, KN (reprint author), Kyoto Univ, Grad Sch Med, Sakyo Ku, Kyoto, Japan.
EM kimiyonomaisinn520@ybb.ne.jp
FU National Institute of Environmental Health Sciences [Y2-ES-7020-01]
FX Grant sponsor: National Toxicology Program, National Institute of
Environmental Health Sciences; Grant Number Y2-ES-7020-01.
NR 49
TC 24
Z9 24
U1 0
U2 12
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD AUG
PY 2011
VL 52
IS 7
BP 547
EP 561
DI 10.1002/em.20656
PG 15
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 811DL
UT WOS:000294182300005
PM 21538559
ER
PT J
AU Orsburn, BC
Stockwin, LH
Newton, DL
AF Orsburn, Benjamin C.
Stockwin, Luke H.
Newton, Dianne L.
TI Challenges in plasma membrane phosphoproteomics
SO EXPERT REVIEW OF PROTEOMICS
LA English
DT Review
DE CID; enrichment; ETD; HCD; neutral loss; phosphopeptide;
phosphoproteomics; plasma membrane
ID TANDEM MASS-SPECTROMETRY; HYDROPHILIC INTERACTION CHROMATOGRAPHY; SCALE
PHOSPHORYLATION ANALYSIS; METAL AFFINITY-CHROMATOGRAPHY; PROTEOMIC
ANALYSIS; SACCHAROMYCES-CEREVISIAE; PROTEIN IDENTIFICATION; SELECTIVE
ENRICHMENT; SUBCELLULAR FRACTIONATION; PHOSPHOPEPTIDE ENRICHMENT
AB The response to extracellular stimuli often alters the phosphorylation state of plasma membrane-associated proteins. In this regard, generation of a comprehensive membrane phosphoproteome can significantly enhance signal transduction and drug mechanism studies. However, analysis of this subproteome is regarded as technically challenging, given the low abundance and insolubility of integral membrane proteins, combined with difficulties in isolating, ionizing and fragmenting phosphopeptides. In this article, we highlight recent advances in membrane and phosphoprotein enrichment techniques resulting in improved identification of these elusive peptides. We also describe the use of alternative fragmentation techniques, and assess their current and future value to the field of membrane phosphoproteomics.
C1 [Orsburn, Benjamin C.; Stockwin, Luke H.; Newton, Dianne L.] NCI, Drug Mech Grp, Dev Therapeut Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Newton, DL (reprint author), NCI, Drug Mech Grp, Dev Therapeut Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM newtondianne@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Division of Cancer Treatment and Diagnosis of the
National Cancer Institute
FX This project has been funded in whole or in part with federal fiends
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 Developmental Therapeutics Program in the
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute. The authors have no other relevant affiliations or financial
involvement with any organization or entity with a financial interest in
or financial conflict with the subject matter or materials discussed in
the manuscript apart from those disclosed.
NR 95
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U1 0
U2 8
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1478-9450
J9 EXPERT REV PROTEOMIC
JI Expert Rev. Proteomics
PD AUG
PY 2011
VL 8
IS 4
BP 483
EP 494
DI 10.1586/EPR.11.40
PG 12
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 810PX
UT WOS:000294139500012
PM 21819303
ER
PT J
AU Devalaraja, S
Jain, S
Yadav, H
AF Devalaraja, Samir
Jain, Shalini
Yadav, Hariom
TI Exotic fruits as therapeutic complements for diabetes, obesity and
metabolic syndrome
SO FOOD RESEARCH INTERNATIONAL
LA English
DT Article
DE Exotic fruits; Diabetes; Obesity; Metabolic syndrome; Antioxidant
ID EUTERPE-OLERACEA MART.; LYCIUM-BARBARUM POLYSACCHARIDE; LITCHI-CHINENSIS
SONN; FATTY LIVER-DISEASE; POMEGRANATE SEED OIL; AMAZONIAN PALM BERRY;
OXIDATIVE STRESS; ANTIOXIDANT ACTIVITY; INSULIN-RESISTANCE;
PSIDIUM-GUAJAVA
AB The prevalence and severity of obesity, type 2-diabetes, and the resultant metabolic syndrome are rapidly increasing. As successful preventive and therapeutic strategies for these life-threatening health ailments often come with adverse side effects, nutritional elements are widely used in many countries as preventive therapies to prevent or manage metabolic syndrome. Fruits are important dietary components, and contain various bioactive constituents. Many of these constituents have been proven to be useful to manage and treat various chronic diseases such as diabetes, obesity, cancer and cardiovascular diseases. Although exotic fruits are understudied throughout the world due to their limited regional presence, many studies reveal their potent ability to ameliorate metabolic derangements and the resultant conditions i.e. diabetes and obesity. The aim of this article is to review the role of exotic fruits and their constituents in the regulation of metabolic functions, which can beneficially alter diabetes and obesity pathophysiology. Published by Elsevier Ltd.
C1 [Yadav, Hariom] NIDDK, Endocrinol & Obes Branch, Clin Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Yadav, H (reprint author), NIDDK, Endocrinol & Obes Branch, Clin Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM yadavh@mail.nih.gov
OI Yadav, Hariom/0000-0003-4504-1597
FU Intramural NIH HHS [Z99 DK999999]
NR 98
TC 39
Z9 43
U1 5
U2 72
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0963-9969
J9 FOOD RES INT
JI Food Res. Int.
PD AUG
PY 2011
VL 44
IS 7
SI SI
BP 1856
EP 1865
DI 10.1016/j.foodres.2011.04.008
PG 10
WC Food Science & Technology
SC Food Science & Technology
GA 805WJ
UT WOS:000293759400019
PM 21857774
ER
PT J
AU Buckley, AW
Sassower, K
Rodriguez, AJ
Jennison, K
Wingert, K
Buckley, J
Thurm, A
Sato, S
Swedo, S
AF Buckley, Ashura Williams
Sassower, Kenneth
Rodriguez, Alcibiades J.
Jennison, Kaitlin
Wingert, Katherine
Buckley, Jack
Thurm, Audrey
Sato, Susumu
Swedo, Susan
TI An Open Label Trial of Donepezil for Enhancement of Rapid Eye Movement
Sleep in Young Children with Autism Spectrum Disorders
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID LONG-TERM POTENTIATION; REM-SLEEP; HEALTHY-PERSONS; MEMORY
AB Background: Rapid eye movement (REM) sleep is greatest in the developing brain, is driven by acetylcholine, and may represent a protected time for neuroplasticity. Recently published data from our lab observed that children with autism spent significantly less time in this state during a single night recording than did typically developing children and those with developmental delay without autism. The objective of this study was to determine whether or not donepezil can increase the REM % in children with diagnosed autism spectrum disorder (ASD) found to have REM % values of at least two standard deviations below expected for age.
Methods: Five subjects found to have an ASD (ages 2.5-6.9 years) and demonstrated deficits in REM sleep compared with within-lab controls were enrolled in a dose finding study of donepezil. Each subject was examined by polysomnography for REM sleep augmentation after drug administration.
Results: REM sleep as a percentage of Total Sleep Time was increased significantly and REM latency was decreased significantly after drug administration in all subjects. No other observed sleep parameter was changed significantly.
Conclusions: Donepezil can increase the amount of time that children with an ASD spend in the REM sleep state. A double-blind, placebo-controlled trial is needed to assess the association between REM sleep augmentation and learning, cognition, and behavior in such children.
C1 [Buckley, Ashura Williams; Jennison, Kaitlin; Wingert, Katherine; Thurm, Audrey; Swedo, Susan] NIMH, Dept Pediat & Dev Neurosci, Bethesda, MD 20892 USA.
[Sassower, Kenneth] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Rodriguez, Alcibiades J.] NYU, Dept Neurol, New York, NY 10016 USA.
[Sato, Susumu] Natl Inst Neurol Disorders & Stroke, Dept Electrophysiol, Bethesda, MD USA.
RP Buckley, AW (reprint author), NIMH, Dept Pediat & Dev Neurosci, Bethesda, MD 20892 USA.
EM shu.buckley@nih.gov
FU NIH; National Institute of Mental Health [T32MH067763]
FX All research was funded by intramural NIH and by Award Number
T32MH067763 from the National Institute of Mental Health. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institute of Mental Health
or the National Institutes of Health.
NR 26
TC 19
Z9 19
U1 0
U2 8
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD AUG
PY 2011
VL 21
IS 4
BP 353
EP 357
DI 10.1089/cap.2010.0121
PG 5
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA 809MH
UT WOS:000294060000007
PM 21851192
ER
PT J
AU Popplewell, WL
Ratnayake, R
Wilson, JA
Beutler, JA
Colburn, NH
Henrich, CJ
McMahon, JB
McKee, TC
AF Popplewell, Wendy L.
Ratnayake, Ranjala
Wilson, Jennifer A.
Beutler, John A.
Colburn, Nancy H.
Henrich, Curtis J.
McMahon, James B.
McKee, Tawnya C.
TI Grassypeptolides F and G, Cyanobacterial Peptides from Lyngbya majuscula
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID CHEMICAL-SHIFTS; AP-1; MARINE; PROMOTION; CELLS
AB Grassypeptolides F (1) and G (2), bis-thiazoline-containing cyclic depsipeptides with a rare beta-amino acid, extensive N-methylation, and a large number of D-amino acids, are reported from an extract of the Palauan cyanobacterium Lyngbya majuscula. Both 1 and 2 were found to have moderate inhibitory activity against the transcription factor AP-1 (IC(50) = 5.2 and 6.0 mu M, respectively).
C1 [Popplewell, Wendy L.; Ratnayake, Ranjala; Wilson, Jennifer A.; Beutler, John A.; Henrich, Curtis J.; McMahon, James B.; McKee, Tawnya C.] NCI Frederick, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Colburn, Nancy H.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
[Henrich, Curtis J.] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP McKee, TC (reprint author), NCI Frederick, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM mckeeta@mail.nih.gov
RI Beutler, John/B-1141-2009
OI Beutler, John/0000-0002-4646-1924
FU National Institutes of Health, National Cancer Institute, Center of
Cancer Research; National Cancer Institute, National Institutes of
Health [HHSN2612008-00001E]
FX This project has been funded in part by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute, Center
of Cancer Research, and in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
HHSN2612008-00001E. 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. We would like to
thank D. Newman (NPB) for coordinating collections, P. Colin (CRRF) for
sample collections, G. C. Trono Jr. (University of the Philippines) for
identification, T. McCloud (SAIC-Frederick, retired) for sample
extractions, S. Tarasov and M. Dyba (Biophysics Resource) for providing
technical assistance with QTOF LC/MS/MS experiments, C. Hixson (ACVP)
for assistance with sample hydrolysis, and H. Luesch (University of
Florida) and E. Juaristi (Centro de Investigacion y de Estudios
Avanzados del IPN, Mexico) for kindly providing standards for the Maba
analysis.
NR 18
TC 10
Z9 10
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD AUG
PY 2011
VL 74
IS 8
BP 1686
EP 1691
DI 10.1021/np2005083
PG 6
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 811UY
UT WOS:000294242800002
PM 21806011
ER
PT J
AU Vlad, SC
Neogi, T
Aliabadi, P
Fontes, JDT
Felson, DT
AF Vlad, Steven C.
Neogi, Tuhina
Aliabadi, Piran
Fontes, Joao D. T.
Felson, David T.
TI No Association Between Markers of Inflammation and Osteoarthritis of the
Hands and Knees
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Article
DE OSTEOARTHRITIS; BIOLOGICAL MARKERS; INFLAMMATION
ID C-REACTIVE PROTEIN; BODY-MASS INDEX; BIOCHEMICAL MARKERS; HIP
OSTEOARTHRITIS; MOLECULAR MARKERS; DISEASE; SEVERITY; CRP; PROGRESSION;
JOINT
AB Objective. Local inflammation plays a prominent role in osteoarthritis (OA). This could be reflected in the presence of elevated soluble inflammatory markers. We conducted analyses to assess the association of inflammatory markers with radiographic OA of the hands and knees in a large community-based cohort.
Methods. The Framingham Offspring cohort consists of the adult children of the original cohort and their spouses. In 1998-2001 these subjects provided blood specimens that were tested for 17 markers of systemic inflammation. In 2002-2005 these subjects had radiographs of both knees and hands. Each hand and knee joint was assigned a Kellgren and Lawrence (KL) score (0-4). We used logistic regression with generalized estimating equations and adjustment for age, sex, and body mass index to examine the association between each inflammatory marker and the presence of radiographic OA (ROA = KL grade >= 2) in any joint. We also constructed models for hand joints and knee joints alone.
Results. Radiographs and measures of inflammation were done for 1235 subjects (56% women, mean age 65 yrs). Of that group, 729 subjects (59%) had ROA in >= 1 hand or knee joint: 179 (14.3%) had knee OA, and 694 (56.2%) had hand OA. There were no significant associations between any marker of inflammation and ROA.
Conclusion. In this large sample, in which OA was carefully assessed and multiple markers measured, we found no evidence of an association between any inflammatory marker and the presence of radiographic OA. (First Release May 152011; J Rheumatol 2011;38:1665-70; doi:10.3899/jrheum.100971)
C1 [Vlad, Steven C.; Neogi, Tuhina; Felson, David T.] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA.
[Vlad, Steven C.; Neogi, Tuhina; Felson, David T.] Boston Univ, Sch Med, Div Rheumatol, Boston, MA 02118 USA.
[Aliabadi, Piran] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Fontes, Joao D. T.] Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA.
[Fontes, Joao D. T.] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Vlad, SC (reprint author), Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, 650 Albany St,Suite X200, Boston, MA 02118 USA.
EM svlad@bu.edu
OI Felson, David/0000-0002-2668-2447; Neogi, Tuhina/0000-0002-9515-1711
FU NIH [T32 007598, K23 AR056301, K23 AR055127, R01 HL076784, R01 AG028321,
R01 HL064753, R01 AG018393, P60 AR047785, N01 HC025195]
FX Supported by NIH grants T32 007598, K23 AR056301, K23 AR055127, R01
HL076784, R01 AG028321, R01 HL064753, R01 AG018393, P60 AR047785, and
N01 HC025195.
NR 29
TC 20
Z9 24
U1 0
U2 4
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA
SN 0315-162X
J9 J RHEUMATOL
JI J. Rheumatol.
PD AUG
PY 2011
VL 38
IS 8
BP 1665
EP 1670
DI 10.3899/jrheum.100971
PG 6
WC Rheumatology
SC Rheumatology
GA 799VU
UT WOS:000293315000023
PM 21572158
ER
PT J
AU Tugwell, PS
Petersson, IF
Boers, M
Gossec, L
Kirwan, JR
Rader, T
Sanderson, TC
van de Laar, MA
Ueffing, E
Witter, JP
AF Tugwell, Peter S.
Petersson, Ingemar F.
Boers, Maarten
Gossec, Laure
Kirwan, John R.
Rader, Tamara
Sanderson, Tessa C.
van de Laar, Mart A.
Ueffing, Erin
Witter, James P.
TI Domains Selection for Patient-Reported Outcomes: Current Activities and
Options for Future Methods
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Article
DE OUTCOME MEASURES; RHEUMATOID ARTHRITIS; PATIENT REPORTED OUTCOMES
ID RHEUMATOID-ARTHRITIS; CORE SET; FATIGUE; PERSPECTIVE; DISEASE;
RECOMMENDATIONS
AB Introduction. Over the years, Outcome Measures in Rheumatology Clinical Trials (OMERACT) has worked toward consensus on core sets for outcome measurement in specific rheumatologic diseases. OMERACT core sets refer to the minimum number of domains and instruments essential to address the desired outcomes in trials. "Domains" are the attributes of an activity or function. This article discusses the need for an open process for selecting domains, existing frameworks for choosing domains, and the importance of describing the methods for selecting domains.
Methods. We reviewed the domains selection process of 3 OMERACT groups working on patient-reported outcomes (PRO). We categorized these methods in a hierarchy of comprehensiveness and examined the extent to which they address related issues.
Results. There was agreement that a gold standard for domain selection would include 3 important aspects: following a framework, remaining true to the clinical question, and including the clinically relevant outcomes for both benefits and harms.
Discussion. OMERACT participants agreed that a guide for the options for developing domains that meet the OMERACT Filter would be useful. More discussion and explanation is needed to outline outcomes related to the patient perspective that are not covered by the current version of the International Classification of Functioning, Disability and Health (ICF) and to explain the usefulness of the population/intervention/comparison/outcome (PICO) structure in domain selection. Future OMERACT work includes addressing these issues and developing a framework based on the ICF to support comprehensive outcome measurements. (J Rheumatol 2011;38:1702-10; doi:10.3899/jrheum.110389)
C1 [Tugwell, Peter S.] Univ Ottawa, Fac Med, Ottawa, ON, Canada.
[Tugwell, Peter S.] Ottawa Hosp, Dept Med, Ottawa, ON, Canada.
[Tugwell, Peter S.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
[Tugwell, Peter S.] Univ Ottawa, Inst Populat Hlth, Ottawa, ON, Canada.
[Petersson, Ingemar F.] Lund Univ, Dept Clin Sci, Lund, Sweden.
[Boers, Maarten] Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands.
[Gossec, Laure] Paris Descartes Univ, Cochin Hosp, AP HP, Rheumatol Dept B, Paris, France.
[Kirwan, John R.] Univ Bristol, Bristol Royal Infirm, Acad Rheumatol Unit, Bristol, Avon, England.
[Sanderson, Tessa C.] Univ W England, Fac Life Sci, Bristol BS16 1QY, Avon, England.
[van de Laar, Mart A.] Univ Twente, Dept Psychol & Commun Hlth & Risk, Arthrit Ctr Twente, NL-7500 AE Enschede, Netherlands.
[Witter, James P.] NIAMSD, Rheumat Dis Clin Program, Div Skin & Rheumat Dis, NIH,DHHS, Bethesda, MD 20892 USA.
RP Rader, T (reprint author), Univ Ottawa, Cochrane Musculoskeletal Grp, Ottawa, ON K1N 6N5, Canada.
EM trader@uottawa.ca
RI Rader, Tamara/H-9469-2013;
OI Tugwell, Peter/0000-0001-5062-0556; Kirwan, John/0000-0002-6617-3217
FU Canadian Institutes of Health Research
FX P. Tugwell is supported in part by the Canadian Institutes of Health
Research.
NR 35
TC 7
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U1 0
U2 1
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA
SN 0315-162X
J9 J RHEUMATOL
JI J. Rheumatol.
PD AUG
PY 2011
VL 38
IS 8
BP 1702
EP 1710
DI 10.3899/jrheum.110389
PG 9
WC Rheumatology
SC Rheumatology
GA 799VU
UT WOS:000293315000030
PM 21807789
ER
PT J
AU Fries, J
Rose, M
Krishnan, E
AF Fries, James
Rose, Matthias
Krishnan, Eswar
TI The PROMIS of Better Outcome Assessment: Responsiveness, Floor and
Ceiling Effects, and Internet Administration
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Article
DE ITEM RESPONSE THEORY; PROMIS; PHYSICAL FUNCTION; DISABILITY;
COMPUTERIZED ADAPTIVE TESTING; SAMPLE SIZES
ID PATIENT-REPORTED OUTCOMES; HEALTH-ASSESSMENT QUESTIONNAIRE;
INFORMATION-SYSTEM PROMIS; ITEM RESPONSE THEORY; RHEUMATOID-ARTHRITIS;
PAPER; RELIABILITY; TELEPHONE; MAIL; COLLECTION
AB Objective. Use of item response theory (IRT) and; Subsequently, computerized adaptive testing (CAT); under the umbrella of the NIH-PROMIS initiative (National Institutes of Health Patient-Reported Outcomes Measurement Information System), to bring strong new assets to the development of more sensitive, more widely applicable, and more efficiently administered patient-reported outcome (PRO) instruments. We present data on current progress in 3 crucial areas: floor and ceiling effects, responsiveness to change, and interactive computer-based administration over the Internet.
Methods. We examined nearly 1000 patient's with rheumatoid arthritis and related diseases in a series of studies including a one-year longitudinal examination of detection of change; compared responsiveness of the Legacy SF-36 and HAQ-DI instruments with 1RT-baSed instruments; performed a randomized head-to-head trial of 4 modes of item administration; and simulated the effect of lack of floor and ceiling items upon statistical power and sample sizes.
Results. IRT-based PROMIS instruments are more sensitive to change, resulting in the potential to reduce sample size requirements substantially by Lip to a factor of 4. The modes of administration tested did not differ from each other in any instance by more than one-tenth of a standard deviation. Floor and ceiling effects greatly reduce the number of available subjects, particularly at the ceiling.
Conclusion. Failure to adequately address floor and ceiling effects, which determine the range of an instrument; can result in suboptimal assessment of many patients. Improved items, improved instruments, and computer-based administration improve PRO assessment and represent a fundamental advance in clinical outcomes research. (J Rheumatol 2011;38:1759-64; doi:10.3899/jrheum.110402)
C1 [Fries, James; Krishnan, Eswar] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA.
NIAMSD, NIH, Bethesda, MD 20892 USA.
[Rose, Matthias] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA.
RP Fries, J (reprint author), Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA.
EM jff@stanford.edu
RI KRISHNAN, ESWAR/A-1072-2009; Rose, Matthias/A-8920-2015; Fries,
James/F-6271-2011
FU Statistical Coordinating Center [U01 AR52177]; Duke University
[U01AR52186]; University of North Carolina [U01AR52181]; University of
Pittsburgh; Stanford University [U01AR52158]; Stony Brook University
[U01 AR52170]; University of Washington [U01AR52171]
FX The Patient-Reported Outcomes Measurement Information System (PROMIS) is
a National Institutes of Health (NIH) Roadmap initiative to develop a
computerized system measuring patient-reported outcomes in respondents
with a wide range of chronic diseases and demographic characteristics.
PROMIS was funded by cooperative agreements to a Statistical
Coordinating Center [Evanston Northwestern Healthcare, Principal
Investigator (PI): David Cella, PhD, U01 AR52177] and 6 Primary Research
Sites (Duke University, PI: Kevin Weinfurt, PhD, U01AR52186; University
of North Carolina, PI: Darren De Walt, MD, MPH, U01AR52181; University
of Pittsburgh; PI: Paul A. Pilkonis, PhD, U01AR52155; Stanford
University, PI: James Fries, MD, U01AR52158; Stony Brook University, PI:
Arthur Stone, PhD, U01 AR52170; and University of Washington, PI: Dagmar
Amtmann, PhD, U01AR52171). NIH Science Officers on this project have
included Deborah Ader, PhD, Susan Czajkowski, PhD, Lawrence Fine, MD,
DrPH, Laura Lee Johnson, PhD, Louis Quatrano, PhD, Bryce Reeve, PhD,
William Riley, PhD, Susana Serrate-Sztein, MD, and James Witter, MD,
PhD. This report was reviewed by the PROMIS Publications Subcommittee
before external peer review.
NR 32
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U1 1
U2 12
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA
SN 0315-162X
J9 J RHEUMATOL
JI J. Rheumatol.
PD AUG
PY 2011
VL 38
IS 8
BP 1759
EP 1764
DI 10.3899/jrheum.110402
PG 6
WC Rheumatology
SC Rheumatology
GA 799VU
UT WOS:000293315000039
PM 21807798
ER
PT J
AU Tobian, AAR
Kong, XR
Wawer, MJ
Kigozi, G
Gravitt, PE
Serwadda, D
Eaton, KP
Nalugoda, F
Quinn, TC
Gray, RH
AF Tobian, Aaron A. R.
Kong, Xiangrong
Wawer, Maria J.
Kigozi, Godfrey
Gravitt, Patti E.
Serwadda, David
Eaton, Kevin P.
Nalugoda, Fred
Quinn, Thomas C.
Gray, Ronald H.
TI Circumcision of HIV-infected men and transmission of human
papillomavirus to female partners: analyses of data from a randomised
trial in Rakai, Uganda
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID RISK HUMAN-PAPILLOMAVIRUS; COLLECTED VAGINAL SWABS; CERVICAL-CANCER;
NEGATIVE MEN; INCIDENT HIV; YOUNG MEN; WOMEN; PREVENTION; METAANALYSIS;
ACQUISITION
AB Background Male circumcision reduces the transmission of high-risk human papillomavirus (HPV) in HIV-uninfected men and their female partners. We assessed whether circumcision of HIV-infected men would reduce the transmission of high-risk HPV to their female partners.
Methods Female partners of HIV-infected men (aged 15-49 years) in Rakai, Uganda, with CD4 counts of greater than 350 cells per mL who were randomly assigned to undergo circumcision immediately (intervention group) and after 24 months (control group) were assessed for infection with high-risk HPV. Randomisation was done in blocks of 20, stratified by community, with computer-generated random numbers. Laboratory technicians and female fieldworkers were masked to the circumcision status of male participants. The main outcome assessed in this study was the effects of circumcision of HIV-infected men on transmission of HPV to their female partners. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00124878.
Findings 474 men were assigned to the intervention group, 448 to the control group. 211 women were in consensual relationships with 193 men in the intervention group, and 171 women were in consensual unions with 155 men in the control group. High-risk HPV at the 2-year follow-up was prevalent in 88 female partners (55%) of 159 men in the intervention group and 68 (52%) of 131 female partners of men in the control group (prevalence risk ratio 1.07, 95% CI 0.86-1.32, p=0.64). Incidence of high-risk HPV over 2 years was 32.0 per 100 person-years in the female partners of men in the intervention group and 30.6 per 100 person-years in the female partners of men in the control group (incidence rate ratio 1.05, 0 77-1.43, p=0.78). No difference was noted in the clearance of genotype-specific high-risk HPV between the intervention group (196 [46%] of 424) and control group (167 [48%] of 347; rate ratio 0.96, 0.83-1.12; p=0.61).
Interpretation Because circumcision of HIV-infected men did not affect transmission of high-risk HPV to their female partners, promotion of consistent safe sexual practices for HIV-infected men remains important.
C1 [Tobian, Aaron A. R.] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21287 USA.
[Eaton, Kevin P.; Quinn, Thomas C.] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21287 USA.
[Tobian, Aaron A. R.; Kong, Xiangrong; Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD 21287 USA.
[Kong, Xiangrong] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21287 USA.
[Gravitt, Patti E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA.
[Wawer, Maria J.; Kigozi, Godfrey; Serwadda, David; Nalugoda, Fred; Gray, Ronald H.] Rakai Hlth Sci Program, Entebbe, Uganda.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Tobian, AAR (reprint author), Johns Hopkins Univ, Dept Pathol, Sch Med, Carnegie 667,600 N Wolfe St, Baltimore, MD 21287 USA.
EM atobian1@jhmi.edu
FU Bill & Melinda Gates Foundation [22006.02]; National Institutes of
Health; Roche Molecular Diagnostics; The Fogarty International Center
[5D43TW001508, 2D43TW000010-19-AITRP]; National Institute of Allergy and
Infectious Diseases (NIAID), NIH [U01-AI-068613, 3U01-A1075115-03S1];
Johns Hopkins University
FX Bill & Melinda Gates Foundation and National Institutes of Health.; PEG
received research funding from Roche Molecular Diagnostics who
manufacture the HPV genotyping test used in this study, and is a member
of Qiagen Women's Health Scientific Advisory Board. The other authors
declare that they have no other potential conflicts of interest relevant
to this report.; The trial was funded by the Bill & Melinda Gates
Foundation (grant number 22006.02). The Fogarty International Center
(5D43TW001508 and 2D43TW000010-19-AITRP) contributed to training.
National Institute of Allergy and Infectious Diseases (NIAID), NIH
(U01-AI-068613 and 3U01-A1075115-03S1) and the NIAID Intramural Program
provided laboratory support. AART was supported by the Johns Hopkins
University Clinician Scientist Award. We are most grateful to the study
participants and the Rakai Community Advisory Board whose commitment and
cooperation made this study possible. We thank Edward M'bidde, Uganda
Virus Research Institute, for his ongoing support, and Renee Ridzon of
the Bill & Melinda Gates Foundation for her assistance with the trial.
NR 30
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U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD AUG
PY 2011
VL 11
IS 8
BP 604
EP 612
DI 10.1016/S1473-3099(11)70038-X
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA 810BU
UT WOS:000294101200017
PM 21489882
ER
PT J
AU Introne, WJ
Perry, MB
Troendle, J
Tsilou, E
Kayser, MA
Suwannarat, P
O'Brien, KE
Bryant, J
Sachdev, V
Reynolds, JC
Moylan, E
Bernardini, I
Gahl, WA
AF Introne, Wendy J.
Perry, Monique B.
Troendle, James
Tsilou, Ekaterini
Kayser, Michael A.
Suwannarat, Pim
O'Brien, Kevin E.
Bryant, Joy
Sachdev, Vandana
Reynolds, James C.
Moylan, Elizabeth
Bernardini, Isa
Gahl, William A.
TI A 3-year randomized therapeutic trial of nitisinone in alkaptonuria
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Alkaptonuria; Ochronosis; Nitisinone; Homogentisic acid
ID TYROSINEMIA TYPE-I; HOMOGENTISIC ACID; CONNECTIVE TISSUE; 6-MINUTE WALK;
ALCAPTONURIA; OCHRONOSIS; NTBC; METABOLISM; MOBILITY; GO
AB Alkaptonuria is a rare, autosomal recessive disorder of tyrosine degradation due to deficiency of the third enzyme in the catabolic pathway. As a result, homogentisic acid (HGA) accumulates and is excreted in gram quantities in the urine, which turns dark upon alkalization. The first symptoms, occurring in early adulthood, involve a painful, progressively debilitating arthritis of the spine and large joints. Cardiac valvular disease and renal and prostate stones occur later. Previously suggested therapies have failed to show benefit, and management remains symptomatic. Nitisinone, a potent inhibitor of the second enzyme in the tyrosine catabolic pathway, is considered a potential therapy; proof-of-principle studies showed 95% reduction in urinary HGA. Based on those findings, a prospective, randomized clinical trial was initiated in 2005 to evaluate 40 patients over a 36-month period. The primary outcome parameter was hip total range of motion with measures of musculoskeletal function serving as secondary parameters. Biochemically, this study consistently demonstrated 95% reduction of HGA in urine and plasma over the course of 3 years. Clinically, primary and secondary parameters did not prove benefit from the medication. Side effects were infrequent. This trial illustrates the remarkable tolerability of nitisinone, its biochemical efficacy, and the need to investigate its use in younger individuals prior to development of debilitating arthritis. Published by Elsevier Inc.
C1 [Introne, Wendy J.; O'Brien, Kevin E.; Bryant, Joy; Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Reynolds, James C.] NIH, Ctr Clin, Div Nucl Med, Radiol & Imaging Sci Dept, Bethesda, MD 20892 USA.
[Troendle, James] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Tsilou, Ekaterini] NEI, NIH, Bethesda, MD 20892 USA.
[Kayser, Michael A.; Suwannarat, Pim; Bernardini, Isa; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[O'Brien, Kevin E.] NIH, Off Rare Dis Res, Off Director, Bethesda, MD 20892 USA.
RP Introne, WJ (reprint author), 10 Ctr Dr,Bldg 10 CRC,Room 3-2551, Bethesda, MD 20892 USA.
EM wintrone@mail.nih.gov
FU National Human Genome Research Institute
FX This study was funded by the intramural program of the National Human
Genome Research Institute.
NR 29
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U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD AUG
PY 2011
VL 103
IS 4
BP 307
EP 314
DI 10.1016/j.ymgme.2011.04.016
PG 8
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 809ZY
UT WOS:000294096400001
PM 21620748
ER
PT J
AU Shin, EJ
Jeong, JH
Chung, YH
Kim, WK
Ko, KH
Bach, JH
Hong, JS
Yoneda, Y
Kim, HC
AF Shin, Eun-Joo
Jeong, Ji Hoon
Chung, Yoon Hee
Kim, Won-Ki
Ko, Kwang-Ho
Bach, Jae-Hyung
Hong, Jau-Shyong
Yoneda, Yukio
Kim, Hyoung-Chun
TI Role of oxidative stress in epileptic seizures
SO NEUROCHEMISTRY INTERNATIONAL
LA English
DT Review
DE Epileptic seizures; Oxidative stress; Antioxidant strategies; Animal
models
ID PILOCARPINE-INDUCED SEIZURES; PENTYLENETETRAZOL-INDUCED SEIZURES;
KAINATE-INDUCED NEUROTOXICITY; PLACEBO-CONTROLLED TRIAL;
GLUTATHIONE-S-TRANSFERASE; TEMPORAL-LOBE EPILEPSY; ACID-INDUCED
SEIZURES; THIOL REDOX STATE; ADD-ON THERAPY; SENESCENCE-ACCELERATED
MOUSE
AB Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of epilepsy. Therefore, antioxidant therapies aimed at reducing oxidative stress have received considerable attention in epilepsy treatment. However, much evidence suggests that oxidative stress does not always have the same pattern in all seizures models. Thus, this review provides an overview aimed at achieving a better understanding of this issue. We summarize work regarding seizure models (i.e., genetic rat models, kainic acid, pilocarpine, pentylenetetrazol, and trimethyltin), oxidative stress as an etiologic factor in epileptic seizures (i.e.. impairment of antioxidant systems, mitochondrial dysfunction, involvement of redox-active metals, arachidonic acid pathway activation, and aging), and antioxidant strategies for seizure treatment. Combined, this review highlights pharmacological mechanisms associated with oxidative stress in epileptic seizures and the potential for neuroprotection in epilepsy that targets oxidative stress and is supported by effective antioxidant treatment. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Shin, Eun-Joo; Bach, Jae-Hyung; Kim, Hyoung-Chun] Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 200701, South Korea.
[Jeong, Ji Hoon] Chung Ang Univ, Dept Pharmacol, Coll Med, Seoul 156756, South Korea.
[Chung, Yoon Hee] Chung Ang Univ, Dept Anat, Coll Med, Seoul 156756, South Korea.
[Kim, Won-Ki] Korea Univ, Dept Neurosci, Coll Med, Seoul 136705, South Korea.
[Ko, Kwang-Ho] Cha Univ, Coll Pharm, Pochon 487801, South Korea.
[Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
[Yoneda, Yukio] Kanazawa Univ, Mol Pharmacol Lab, Div Pharmaceut Sci, Grad Sch Nat Sci & Technol, Kanazawa, Ishikawa 9201192, Japan.
RP Kim, HC (reprint author), Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 200701, South Korea.
EM kimhc@kangwon.ac.kr
FU Ministry of Science and Technology, Republic of Korea [2011K000271]; BK
21 program
FX This study was supported by a grant #2011K000271 from the Brain Research
Center from 21st Century Frontier Research Program funded by the
Ministry of Science and Technology, Republic of Korea. Jae-Hyung Bach
was supported by BK 21 program.
NR 243
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U2 26
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0197-0186
J9 NEUROCHEM INT
JI Neurochem. Int.
PD AUG
PY 2011
VL 59
IS 2
BP 122
EP 137
DI 10.1016/j.neuint.2011.03.025
PG 16
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 809YC
UT WOS:000294091600006
PM 21672578
ER
PT J
AU Kapustin, Y
Chan, E
Sarkar, R
Wong, F
Vorechovsky, I
Winston, RM
Tatusova, T
Dibb, NJ
AF Kapustin, Yuri
Chan, Elcie
Sarkar, Rupa
Wong, Frederick
Vorechovsky, Igor
Winston, Robert M.
Tatusova, Tatiana
Dibb, Nick J.
TI Cryptic splice sites and split genes
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PRE-MESSENGER-RNA; PROCESSING ENHANCER; INTRONLESS GENES; EXON;
TRANSCRIPTS; EVOLUTION; SEQUENCE; DISEASE; ORIGIN; DISRUPTION
AB We describe a new program called cryptic splice finder (CSF) that can reliably identify cryptic splice sites (css), so providing a useful tool to help investigate splicing mutations in genetic disease. We report that many css are not entirely dormant and are often already active at low levels in normal genes prior to their enhancement in genetic disease. We also report a fascinating correlation between the positions of css and introns, whereby css within the exons of one species frequently match the exact position of introns in equivalent genes from another species. These results strongly indicate that many introns were inserted into css during evolution and they also imply that the splicing information that lies outside some introns can be independently recognized by the splicing machinery and was in place prior to intron insertion. This indicates that non-intronic splicing information had a key role in shaping the split structure of eukaryote genes.
C1 [Kapustin, Yuri; Tatusova, Tatiana] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20814 USA.
[Chan, Elcie; Sarkar, Rupa; Wong, Frederick; Winston, Robert M.; Dibb, Nick J.] Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London W12 ONN, England.
[Vorechovsky, Igor] Univ Southampton, Sch Med, Div Human Genet, Southampton SO16 6YD, Hants, England.
RP Kapustin, Y (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20814 USA.
EM yurikapustin@gmail.com; n.dibb@imperial.ac.uk
OI Sarkar, Rupa/0000-0003-0014-2239
FU Biotechnology and Biosciences Research Council; Atazoa; Genesis Trust
FX Reserch grants from Biotechnology and Biosciences Research Council and
Atazoa. Funding for open access charge: Genesis Trust.
NR 53
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U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD AUG
PY 2011
VL 39
IS 14
BP 5837
EP 5844
DI 10.1093/nar/gkr203
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 807SI
UT WOS:000293919600010
PM 21470962
ER
PT J
AU Iben, JR
Mazeika, JK
Hasson, S
Rijal, K
Arimbasseri, AG
Russo, AN
Maraia, RJ
AF Iben, James R.
Mazeika, Julie K.
Hasson, Sam
Rijal, Keshab
Arimbasseri, Aneeshkumar G.
Russo, Amy N.
Maraia, Richard J.
TI Point mutations in the Rpb9-homologous domain of Rpc11 that impair
transcription termination by RNA polymerase III
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID HUMAN LA ANTIGEN; FISSION YEAST; SACCHAROMYCES-CEREVISIAE; 2ND-LARGEST
SUBUNIT; ELONGATION COMPLEX; SIGNAL RECOGNITION; CLEAVAGE ACTIVITY;
STRUCTURAL BASIS; SERINE 366; IN-VITRO
AB RNA polymerase III recognizes and pauses at its terminator, an oligo(dT) tract in non-template DNA, terminates 3' oligo(rU) synthesis within this sequence, and releases the RNA. The pol III subunit Rpc11p (C11) mediates RNA 3'-5' cleavage in the catalytic center of pol III during pausing. The amino and carboxyl regions of C11 are homologous to domains of the pol II subunit Rpb9p, and the pol II elongation and RNA cleavage factor, TFIIS, respectively. We isolated C11 mutants from Schizosaccharomyces pombe that cause pol III to readthrough terminators in vivo. Mutant RNA confirmed the presence of terminator readthrough transcripts. A predominant mutation site, F32, resides in the C11 Rpb9-like domain. Another mutagenic approach confirmed the F32 mutation and also isolated I34 and Y30 mutants. Modeling Y30, F32 and I34 of C11 in available cryoEM pol III structures predicts a hydrophobic patch that may interface with C53/37. Another termination mutant, Rpc2-T455I, appears to reside internally, near the RNA-DNA hybrid. We show that the Rpb9 and TFIIS homologous mutants of C11 reflect distinct activities, that differentially affect terminator recognition and RNA 3' cleavage. We propose that these C11 domains integrate action at the upper jaw and center of pol III during termination.
C1 [Iben, James R.; Mazeika, Julie K.; Hasson, Sam; Rijal, Keshab; Arimbasseri, Aneeshkumar G.; Russo, Amy N.; Maraia, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, NIH, Commissioned Corps,US PHS Bethesda, Bethesda, MD USA.
RP Maraia, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, NIH, Commissioned Corps,US PHS Bethesda, Bethesda, MD USA.
EM maraiar@mail.nih.gov
RI Rijal, Keshab/B-9031-2012;
OI Arimbasseri, Gopalakrishnan Aneeshkumar/0000-0001-5266-2688
FU NICHD, NIH
FX Funding for open access charge: Intramural Research Program of the
NICHD, NIH.
NR 52
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U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD AUG
PY 2011
VL 39
IS 14
BP 6100
EP 6113
DI 10.1093/nar/gkr182
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 807SI
UT WOS:000293919600030
PM 21450810
ER
PT J
AU Tsao, D
Shabalina, SA
Gauthier, J
Dokholyan, NV
Diatchenko, L
AF Tsao, Douglas
Shabalina, Svetlana A.
Gauthier, Josee
Dokholyan, Nikolay V.
Diatchenko, Luda
TI Disruptive mRNA folding increases translational efficiency of
catechol-O-methyltransferase variant
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID MENTAL-RETARDATION PROTEIN; DISCRETE MOLECULAR-DYNAMICS; SECONDARY
STRUCTURE; ESCHERICHIA-COLI; GENE-EXPRESSION; BIOPSYCHOSOCIAL INFLUENCE;
STRUCTURE PREDICTION; INITIATION CODON; SHOULDER PAIN; HAPLOTYPES
AB Catechol-O-methyltransferase (COMT) is a major enzyme controlling catecholamine levels that plays a central role in cognition, affective mood and pain perception. There are three common COMT haplotypes in the human population reported to have functional effects, divergent in two synonymous and one nonsynonymous position. We demonstrate that one of the haplotypes, carrying the non-synonymous variation known to code for a less stable protein, exhibits increased protein expression in vitro. This increased protein expression, which would compensate for lower protein stability, is solely produced by a synonymous variation ((CT)-T-166) situated within the haplotype and located in the 5' region of the RNA transcript. Based on mRNA secondary structure predictions, we suggest that structural destabilization near the start codon caused by the T allele could be related to the observed increase in COMT expression. Our folding simulations of the tertiary mRNA structures demonstrate that destabilization by the T allele lowers the folding transition barrier, thus decreasing the probability of occupying its native state. These data suggest a novel structural mechanism whereby functional synonymous variations near the translation initiation codon affect the translation efficiency via entropy-driven changes in mRNA dynamics and present another example of stable compensatory genetic variations in the human population.
C1 [Tsao, Douglas; Gauthier, Josee; Dokholyan, Nikolay V.; Diatchenko, Luda] Univ N Carolina, Sch Dent, Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA.
[Tsao, Douglas] Univ N Carolina, Sch Dent, Dept Chem, Chapel Hill, NC 27599 USA.
[Shabalina, Svetlana A.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Dokholyan, Nikolay V.] Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
RP Dokholyan, NV (reprint author), Univ N Carolina, Sch Dent, Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA.
EM dokh@med.unc.edu; lbdiatch@email.unc.edu
RI Shabalina, Svetlana/N-8939-2013;
OI Shabalina, Svetlana/0000-0003-2272-7473; Dokholyan,
Nikolay/0000-0002-8225-4025
FU The US National Institutes of Health [R01GM080742]; American Recovery
and Reinvestment Act supplements [GM080742-03S1, GM066940-06S1];
National Institute of Dental and Craniofacial Research and National
Institute of Neurological Disorders and Stroke [RO1-DE16558,
UO1-DE017018, PO1 NS045685, 5-U01-DE017018-04-06, 2-P01-NS045685-06A1];
National Center Biotechnology Information a National Library of Medicine
FX The US National Institutes of Health grant (R01GM080742 to N.V.D.);
American Recovery and Reinvestment Act supplements (GM080742-03S1,
GM066940-06S1 to N.V.D.); National Institute of Dental and Craniofacial
Research and National Institute of Neurological Disorders and Stroke
grants (RO1-DE16558, UO1-DE017018, PO1 NS045685 to L.D.); and Intramural
Research Programs of National Center Biotechnology Information a
National Library of Medicine (to SA. S.). Funding for open access
charge: National Institutes of Dental and Craniofacial Research and
National Institute of Neurological Disorders and Stroke grants
(5-U01-DE017018-04-06 and 2-P01-NS045685-06A1 to L.D.).
NR 55
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U1 0
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD AUG
PY 2011
VL 39
IS 14
BP 6201
EP 6212
DI 10.1093/nar/gkr165
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 807SI
UT WOS:000293919600038
PM 21486747
ER
PT J
AU Brzezinski, K
Brzuszkiewicz, A
Dauter, M
Kubicki, M
Jaskolski, M
Dauter, Z
AF Brzezinski, Krzysztof
Brzuszkiewicz, Anna
Dauter, Miroslawa
Kubicki, Maciej
Jaskolski, Mariusz
Dauter, Zbigniew
TI High regularity of Z-DNA revealed by ultra high-resolution crystal
structure at 0.55 A(dagger)
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID HANDED Z-DNA; PURE-SPERMINE FORM; ATOMIC-RESOLUTION; NUCLEIC-ACIDS;
MINOR-GROOVE; ANGSTROM RESOLUTION; MOLECULAR-STRUCTURE; PROTEINS;
COMPLEX; POLYAMINE
AB The crystal structure of a Z-DNA hexamer duplex d(CGCGCG)(2) determined at ultra high resolution of 0.55 A and refined without restraints, displays a high degree of regularity and rigidity in its stereochemistry, in contrast to the more flexible B-DNA duplexes. The estimations of standard uncertainties of all individually refined parameters, obtained by full-matrix least-squares optimization, are comparable with values that are typical for small-molecule crystallography. The Z-DNA model generated with ultra high-resolution diffraction data can be used to revise the stereochemical restraints applied in lower resolution refinements. Detailed comparisons of the stereochemical library values with the present accurate Z-DNA parameters, shows in general a good agreement, but also reveals significant discrepancies in the description of guanine-sugar valence angles and in the geometry of the phosphate groups.
C1 [Brzezinski, Krzysztof; Brzuszkiewicz, Anna; Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA.
[Brzezinski, Krzysztof; Jaskolski, Mariusz] Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, Poznan, Poland.
[Dauter, Miroslawa] SAIC Frederick Inc, Basic Res Program, Argonne Natl Lab, Argonne, IL 60439 USA.
[Kubicki, Maciej; Jaskolski, Mariusz] Adam Mickiewicz Univ Poznan, Fac Chem, Dept Crystallog, PL-60780 Poznan, Poland.
RP Dauter, Z (reprint author), NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA.
EM dauter@anl.gov
FU NIH, National Cancer Institute, Center for Cancer Research; National
Cancer Institute, National Institutes of Health [HHSN2612008000001E];
Polish Ministry of Science and Higher Education [N N204 005136];
National Center for Research Resources at the National Institutes of
Health, NE-CAT beam line [RR-15301]; U.S. Department of Energy, Office
of Basic Energy Sciences, Advanced Photon Source [W-31-109-Eng-38];
Budget of the National Cancer Institute
FX Intramural Research Program of NIH, National Cancer Institute, Center
for Cancer Research, and with Federal funds from the National Cancer
Institute, National Institutes of Health (Contract HHSN2612008000001E,
partial). Polish Ministry of Science and Higher Education (grant no. N
N204 005136 to M.K.); National Center for Research Resources at the
National Institutes of Health, NE-CAT beam line (award RR-15301); U.S.
Department of Energy, Office of Basic Energy Sciences, Advanced Photon
Source (Contract No. W-31-109-Eng-38). Funding for open access charge:
Budget of the National Cancer Institute.
NR 44
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U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD AUG
PY 2011
VL 39
IS 14
BP 6238
EP 6248
DI 10.1093/nar/gkr202
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 807SI
UT WOS:000293919600042
PM 21459852
ER
PT J
AU Ahmadi, N
Brewer, CC
Zalewski, C
King, KA
Butman, JA
Plass, N
Henderson, C
Goldbach-Mansky, R
Kim, HJ
AF Ahmadi, Neda
Brewer, Carmen C.
Zalewski, Christopher
King, Kelly A.
Butman, John A.
Plass, Nicole
Henderson, Cailin
Goldbach-Mansky, Raphaela
Kim, H. Jeffrey
TI Cryopyrin-Associated Periodic Syndromes: Otolaryngologic and Audiologic
Manifestations
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
DE cryopyrin-associated periodic syndromes; familial cold auto-inflammatory
syndrome; Muckle-Wells syndrome; neonatalonset multisystem inflammatory
disease; chronic infantile neurological cutaneous and articular syndrome
ID COLD AUTOINFLAMMATORY SYNDROME; MUCKLE-WELLS-SYNDROME; CIAS1 MUTATIONS;
DISEASES; INFLAMMATION; PATHOGENESIS; INHIBITION; ANAKINRA; SPECTRUM;
FEATURES
AB Objective. Cryopyrin-associated periodic syndromes (CAPS) represent a spectrum of CIAS1 gene-mediated autoinflammatory diseases characterized by recurrent systemic inflammation. The clinical spectrum of CAPS varies from mild to severe and includes the syndromes historically described as familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID). This article presents the largest cohort of patients with CAPS. The objective is to describe the pathogenesis, otolaryngologic, and audiologic manifestations of CAPS.
Study Design. Prospective (2003-2009).
Setting. National Institutes of Health.
Subjects and Methods. Fifty-seven patients with a diagnosis of CAPS were identified (31 NOMID, 11 NOMID/MWS, 9 MWS, and 6 FCAS). Comprehensive data regarding clinical manifestations, audiologic phenotype, and fluid attenuation inversion recovery MRI (FLAIR-MRI) of the brain and inner ear were obtained.
Results. Complete audiologic data obtained on 70% of ears revealed conductive hearing loss in 4 (11%) NOMID ears and mixed hearing loss in 5 (13%) NOMID and 2 (14%) NOMID/MWS ears. Sensorineural hearing loss (SNHL), worse in higher frequencies, was the most common type of hearing loss and was present in 23 (61%) NOMID, 10 (71%) NOMID/MWS, and 4 (33%) MWS ears. All of the patients with FCAS had normal hearing except 2, who had SNHL from 4 to 8 kHz. On FLAIR-MRI sequence, cochlear enhancement was noted in 26 of 29 (90%) NOMID, 6 of 11 (55%) NOMID/MWS, 3 of 9 (33%) MWS, and 1 of 6 (17%) FCAS patients and was significantly associated with the presence of hearing loss. Maxillary sinus hypoplasia and mucosal thickening were found in 39% and 86% of the cohort, respectively.
Conclusion. CIAS1 pathway-mediated CAPS is associated with unregulated autoinflammation mediated by interleukin-1 in the cochlea and hearing loss. Timely diagnosis is crucial to initiate early treatment with interleukin-1 receptor antagonists.
C1 [Kim, H. Jeffrey] Georgetown Univ Hosp, Dept Otolaryngol HNS, Washington, DC 20007 USA.
[Brewer, Carmen C.; Zalewski, Christopher; King, Kelly A.; Kim, H. Jeffrey] Natl Inst Deafness & Other Communicat Disorders, NIH, Bethesda, MD USA.
[Butman, John A.] NIH, NIH Clin Ctr, Bethesda, MD 20892 USA.
[Plass, Nicole; Henderson, Cailin; Goldbach-Mansky, Raphaela] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Kim, HJ (reprint author), Georgetown Univ Hosp, Dept Otolaryngol HNS, Gorman 1,3800 Reservoir Rd NW, Washington, DC 20007 USA.
EM hk7@gunet.georgetown.edu
RI Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases;
National Institute on Deafness and Other Communication Disorders at the
NIH
FX This work was sponsored by the intramural research programs of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
and the National Institute on Deafness and Other Communication Disorders
at the NIH.
NR 29
TC 20
Z9 25
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD AUG
PY 2011
VL 145
IS 2
BP 295
EP 302
DI 10.1177/0194599811402296
PG 8
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 809QG
UT WOS:000294071200021
PM 21493283
ER
PT J
AU Pickens, CL
Airavaara, M
Theberge, F
Fanous, S
Hope, BT
Shaham, Y
AF Pickens, Charles L.
Airavaara, Mikko
Theberge, Florence
Fanous, Sanya
Hope, Bruce T.
Shaham, Yavin
TI Neurobiology of the incubation of drug craving
SO TRENDS IN NEUROSCIENCES
LA English
DT Review
ID COCAINE-SEEKING BEHAVIOR; MEDIAL PREFRONTAL CORTEX; MESOLIMBIC DOPAMINE
SYSTEM; CUE-INDUCED REINSTATEMENT; TIME-DEPENDENT INCREASES; VENTRAL
TEGMENTAL AREA; SELF-ADMINISTRATION ENVIRONMENT; CENTRAL AMYGDALA
INJECTIONS; AGONIST LY379268 ATTENUATE; AMPA RECEPTOR TRAFFICKING
AB It was suggested in 1986 that cue-induced drug craving in cocaine addicts progressively increases over the first several weeks of abstinence and remains high for extended periods. During the past decade, investigators have identified an analogous incubation phenomenon in rodents, in which time-dependent increases in cue-induced drug seeking are observed after withdrawal from intravenous cocaine self-administration. Such an incubation of drug craving is not specific to cocaine, as similar findings have been observed after self-administration of heroin, nicotine, methamphetamine and alcohol in rats. In this review, we discuss recent results that have identified important brain regions involved in the incubation of drug craving, as well as evidence for the underlying cellular mechanisms. Understanding the neurobiology of the incubation of drug craving in rodents is likely to have significant implications for furthering understanding of brain mechanisms and circuits that underlie craving and relapse in human addicts.
C1 [Pickens, Charles L.; Airavaara, Mikko; Theberge, Florence; Fanous, Sanya; Hope, Bruce T.; Shaham, Yavin] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Shaham, Y (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM yshaham@intra.nida.nih.gov
RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014;
OI Hope, Bruce/0000-0001-5804-7061; Airavaara, Mikko/0000-0002-2026-1609
FU NIH, NIDA
FX The writing of this review was supported (in part) by the Intramural
Research Program of the NIH, NIDA. We thank Marina Wolf and Kuei Tseng
for helpful comments, and Aldo Badiani for providing the template for
Figure 2.
NR 118
TC 176
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U1 3
U2 25
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD AUG
PY 2011
VL 34
IS 8
BP 411
EP 420
DI 10.1016/j.tins.2011.06.001
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 811SX
UT WOS:000294237500003
PM 21764143
ER
PT J
AU Dusing, RW
Drisko, JA
Grado, GG
Levine, M
Holzbeierlein, JM
Van Veldhuizen, P
AF Dusing, Reginald W.
Drisko, Jeanne A.
Grado, Gordon G.
Levine, Mark
Holzbeierlein, Jeffrey M.
Van Veldhuizen, Peter
TI Prostate Imaging Modalities that Can Be Used for Complementary and
Alternative Medicine Clinical Studies
SO UROLOGIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Prostate cancer; Bone scan; TRUS; PET; ProstaScint; SPECT; C-11 acetate;
Vitamin C
ID PLANAR BONE-SCINTIGRAPHY; C-11-ACETATE PET; RADICAL PROSTATECTOMY;
HIGH-RISK; CANCER; ANTIGEN; DISEASE; RECURRENCE; METASTASES; SCAN
AB This article provides an overview of imaging modalities that aid in diagnosing, staging, and assessing therapeutic response in prostate cancer. Prostate cancer is the second most common type of cancer in American men and the second leading cause of cancer death among men. Prostate cancer is difficult to diagnose in early stages, and advanced disease often recurs after treatment. To localize sites of recurrence many imaging modalities have been used with varying success. This article presents case studies of PET scanning using carbon 11 acetate and discusses intravenously infused ascorbate, a complementary and alternative medicine therapy for prostate cancer.
C1 [Dusing, Reginald W.] Univ Kansas, Med Ctr, Dept Radiol, Div Nucl Med, Kansas City, KS 66160 USA.
[Drisko, Jeanne A.] Univ Kansas, Med Ctr, Program Integrat Med, Kansas City, KS 66160 USA.
[Grado, Gordon G.] SW Oncol Ctr, Scottsdale, AZ 85251 USA.
[Grado, Gordon G.] Univ Minnesota, Dept Radiat Oncol, Minneapolis, MN USA.
[Levine, Mark] NIH, Mol & Clin Nutr Sect, Bethesda, MD 20892 USA.
[Holzbeierlein, Jeffrey M.] Univ Kansas, Med Ctr, Dept Urol Surg, Prostate Canc Prevent Program, Kansas City, KS 66160 USA.
[Van Veldhuizen, Peter] Univ Kansas, Med Ctr, Dept Internal Med, Div Hematol & Oncol, Kansas City, KS 66160 USA.
RP Dusing, RW (reprint author), Univ Kansas, Med Ctr, Dept Radiol, Div Nucl Med, MS 4032,3901 Rainbow Blvd, Kansas City, KS 66160 USA.
EM rdusing@kumc.edu
FU Clinical Radiology Foundation; KU Endowment foundation of the University
of Kansas; National Institute of Diabetes, Digestive, and Kidney
Diseases, National Institutes of Health
FX Dr Reginald Dusing's work was supported by The Clinical Radiology
Foundation and the Molecular Imaging Research Fund of the KU Endowment
foundation of the University of Kansas. Dr Mark Levine was supported by
the intramural research program, National Institute of Diabetes,
Digestive, and Kidney Diseases, National Institutes of Health.
NR 34
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Z9 3
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 0094-0143
J9 UROL CLIN N AM
JI Urol. Clin. N. Am.
PD AUG
PY 2011
VL 38
IS 3
BP 343
EP +
DI 10.1016/j.ucl.2011.04.003
PG 16
WC Urology & Nephrology
SC Urology & Nephrology
GA 811FE
UT WOS:000294188700012
PM 21798397
ER
PT J
AU Tosh, DK
Phan, K
Deflorian, F
Wei, Q
Gao, ZG
Jacobson, KA
AF Tosh, Dilip K.
Phan, Khai
Deflorian, Francesca
Wei, Qiang
Gao, Zhan-Guo
Jacobson, Kenneth A.
TI Truncated (N)-Methanocarba Nucleosides as A(1) Adenosine Receptor
Agonists and Partial Agonists: Overcoming Lack of a Recognition Element
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE G protein-coupled receptor; purines; molecular modeling; radioligand
binding; adenylate cyclase
ID DERIVATIVES; LIGANDS; ANTAGONISTS; ACTIVATION; EFFICACY
AB A(1) adenosine receptor (AR) agonists are neuroprotective, cardioprotective, and anxiolytic. (N)-Methanocarba adenine nucleosides designed to bind to human A(1)AR were truncated to eliminate 5'-CH2OH. This modification previously converted A(3)AR agonists into antagonists, but the comparable effect at A(1)AR is unknown. In comparison to ribosides, affinity at the A(1)AR was less well preserved than that at the A(3)AR, although a few derivatives were moderately A(1)AR selective, notably full agonist 21 (N-6-dicyclopropyl-methyl, K-i 47.9 nM). Thus, at the A(1)AR, recognition elements for nucleoside binding depend more on 5' region interactions, and in their absence, A(3)AR selectivity predominates. Based on the recently reported agonist-bound AR structure, this difference between subtypes likely correlates with an essential His residue in transmembrane domain 6 of A(1) but not A(3)AR The derivatives ranged from partial to full agonists in A(1)AR-mediated adenylate cyclase inhibition. Truncated derivatives have more druglike physical properties than other A(1)AR agonists; this approach is appealing for preclinical development.
C1 [Tosh, Dilip K.; Phan, Khai; Deflorian, Francesca; Wei, Qiang; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, LBC, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@-helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIH, NIDDK
FX The authors thank the Intramural Research Program of the NIH, NIDDK, for
support.
NR 18
TC 8
Z9 8
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD AUG
PY 2011
VL 2
IS 8
BP 626
EP 631
DI 10.1021/ml200114q
PG 6
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 809SB
UT WOS:000294075900013
PM 21858244
ER
PT J
AU Delvolve, AM
Colsch, B
Woods, AS
AF Delvolve, Alice M.
Colsch, Benoit
Woods, Amina S.
TI Highlighting anatomical sub-structures in rat brain tissue using lipid
imaging
SO ANALYTICAL METHODS
LA English
DT Article
ID ION MASS-SPECTROMETRY; BIOLOGICAL SAMPLES; MOBILITY-TOFMS; MALDI-MS/MS;
MEMBRANE; PHOSPHATIDYLCHOLINES; PHOSPHOLIPIDS; LOCALIZATION; DISEASE; MS
AB Cell membranes are made up of a mixture of glycerolipids, sphingolipids, gangliosides and cholesterol. Lipids play important roles in a cell's life. However many of their functions have still to be discovered. In the present work, we describe an efficient, easy and rapid methodology to accurately localize phosphatidylcholines and sphingomyelins from a single coronal rat brain section in the cerebrum area. Matrix assisted laser desorption/ionization (MALDI) mass spectrometry was used to profile and image lipids. The best resolved structure was 25-50 mu m in the hippocampus.
C1 [Delvolve, Alice M.; Colsch, Benoit; Woods, Amina S.] NIDA IRP, NIH, Baltimore, MD 21224 USA.
RP Woods, AS (reprint author), NIDA IRP, NIH, 333 Cassell Dr,Room 1120, Baltimore, MD 21224 USA.
EM awoods@mail.nih.gov
FU National Institute on Drug Abuse, NIH; Office of National Drug Control
Policy (ONDCP)
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, NIH. We thank the Office of National
Drug Control Policy (ONDCP) for instrumentation funding, without which
this and other projects could not have been accomplished. We also would
like to thank Elsevier publishing for allowing us to use a plate from
their Atlas The Rat Brain in Stereotaxic Coordinates. The authors
acknowledge Cristina Backman and YaJun Zhang of Cellular Neurobiology
Research Branch, NIDA-IRP, NIH, for tissue staining training.
NR 56
TC 18
Z9 19
U1 2
U2 35
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1759-9660
J9 ANAL METHODS-UK
JI Anal. Methods
PD AUG
PY 2011
VL 3
IS 8
BP 1729
EP 1736
DI 10.1039/c1ay05107e
PG 8
WC Chemistry, Analytical; Food Science & Technology; Spectroscopy
SC Chemistry; Food Science & Technology; Spectroscopy
GA 802MG
UT WOS:000293515000003
PM 21961026
ER
PT J
AU Bertuccio, P
La Vecchia, C
Silverman, DT
Petersen, GM
Bracci, PM
Negri, E
Li, D
Risch, HA
Olson, SH
Gallinger, S
Miller, AB
Bueno-De-Mesquita, HB
Talamini, R
Polesel, J
Ghadirian, P
Baghurst, PA
Zatonski, W
Fontham, E
Bamlet, WR
Holly, EA
Lucenteforte, E
Hassan, M
Yu, H
Kurtz, RC
Cotterchio, M
Su, J
Maisonneuve, P
Duell, EJ
Bosetti, C
Boffetta, P
AF Bertuccio, P.
La Vecchia, C.
Silverman, D. T.
Petersen, G. M.
Bracci, P. M.
Negri, E.
Li, D.
Risch, H. A.
Olson, S. H.
Gallinger, S.
Miller, A. B.
Bueno-de-Mesquita, H. B.
Talamini, R.
Polesel, J.
Ghadirian, P.
Baghurst, P. A.
Zatonski, W.
Fontham, E.
Bamlet, W. R.
Holly, E. A.
Lucenteforte, E.
Hassan, M.
Yu, H.
Kurtz, R. C.
Cotterchio, M.
Su, J.
Maisonneuve, P.
Duell, E. J.
Bosetti, C.
Boffetta, P.
TI Reply to Are cohort data on smokeless tobacco use and pancreatic cancer
confounded by alcohol use?
SO ANNALS OF ONCOLOGY
LA English
DT Letter
ID RISK
C1 [Bertuccio, P.; La Vecchia, C.; Negri, E.; Lucenteforte, E.; Bosetti, C.] Ist Ric Farmacol Mario Negri, Dept Epidemiol, Milan, Italy.
[La Vecchia, C.; Lucenteforte, E.] Univ Milan, Sect Med Stat, Dept Occupat Hlth, Milan, Italy.
[Silverman, D. T.; Su, J.] NCI, Bethesda, MD 20892 USA.
[Petersen, G. M.; Bamlet, W. R.] Mayo Clin, Rochester, MN USA.
[Bracci, P. M.; Holly, E. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Li, D.; Hassan, M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Risch, H. A.; Yu, H.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Olson, S. H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Gallinger, S.] Toronto Gen Hosp, Toronto, ON, Canada.
[Miller, A. B.; Cotterchio, M.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Bueno-de-Mesquita, H. B.] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. B.] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Talamini, R.; Polesel, J.] Ctr Riferimento Oncol, Unit Epidemiol & Biostat, I-33081 Aviano, PN, Italy.
[Ghadirian, P.] Res Ctr CRCHUM, Epidemiol Res Unit, Montreal, PQ, Canada.
[Baghurst, P. A.] Womens & Childrens Hosp, Adelaide, SA, Australia.
[Zatonski, W.] Ctr Canc, Warsaw, Poland.
[Zatonski, W.] Inst Oncol, Warsaw, Poland.
[Fontham, E.] Louisiana State Univ, New Orleans, LA USA.
[Kurtz, R. C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Cotterchio, M.] Canc Care Ontario, Toronto, ON, Canada.
[Maisonneuve, P.] European Inst Oncol, Milan, Italy.
[Duell, E. J.] Catalan Inst Oncol, Barcelona, Spain.
[Boffetta, P.] Int Prevent Res Inst, Lyon, France.
[Boffetta, P.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
RP Bertuccio, P (reprint author), Ist Ric Farmacol Mario Negri, Dept Epidemiol, Milan, Italy.
EM paolo.boffetta@mssm.edu
RI Negri, Eva/B-7244-2013; Gallinger, Steven/E-4575-2013;
OI Negri, Eva/0000-0001-9712-8526; La Vecchia, Carlo/0000-0003-1441-897X;
Lucenteforte, Ersilia/0000-0001-5608-5902; Maisonneuve,
Patrick/0000-0002-5309-4704
NR 6
TC 0
Z9 0
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD AUG
PY 2011
VL 22
IS 8
BP 1931
EP 1932
DI 10.1093/annonc/mdr305
PG 2
WC Oncology
SC Oncology
GA 799QH
UT WOS:000293300700038
ER
PT J
AU Katz, SI
AF Katz, Stephen I.
TI Gluten-Free Diet in Patients With Dermatitis Herpetiformis: Not Only a
Matter of Skin reply
SO ARCHIVES OF DERMATOLOGY
LA English
DT Letter
ID CELIAC-DISEASE
C1 NCI, Dept Dermatol, NIH, Bethesda, MD 20892 USA.
RP Katz, SI (reprint author), NCI, Dept Dermatol, NIH, Bldg 31-4C32, Bethesda, MD 20892 USA.
EM katzs@od.niams.nih.gov
NR 4
TC 0
Z9 0
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 AUG
PY 2011
VL 147
IS 8
BP 989
EP 989
PG 1
WC Dermatology
SC Dermatology
GA 806ZG
UT WOS:000293856400031
ER
PT J
AU O'Dell, JR
Mikuls, TR
Colbert, RA
Weinblatt, ME
AF O'Dell, J. R.
Mikuls, T. R.
Colbert, R. A.
Weinblatt, M. E.
CA Amer Coll Rheumatology Rheumatoid
TI American College of Rheumatology Clinical Trial Priorities and Design
Conference, July 22-23, 2010
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; PHASE-III; RECEPTOR INHIBITION;
INADEQUATE RESPONSE; RANDOMIZED-TRIAL; ARTHRITIS; METHOTREXATE;
MULTICENTER; THERAPY
C1 [O'Dell, J. R.] Univ Nebraska, Med Ctr, Sect Rheumatol & Immunol, Omaha, NE 68198 USA.
[Colbert, R. A.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Weinblatt, M. E.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP O'Dell, JR (reprint author), Univ Nebraska, Med Ctr, Sect Rheumatol & Immunol, 983025 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM jrodell@unmc.edu
FU Abbott; Amgen; Astellas; Astra-Zeneca; Biogen Idec; Bristol-Myers
Squibb; Centocor; Crescendo; Lilly; Pfizer; Roche
FX Dr. Weinblatt has received consulting fees from Abbott, Amgen, Astellas,
Astra-Zeneca, Biogen Idec, Bristol-Myers Squibb, Centocor, Crescendo,
Lilly, Pfizer, and Roche (less than $10,000 each).
NR 24
TC 5
Z9 5
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD AUG
PY 2011
VL 63
IS 8
BP 2151
EP 2156
DI 10.1002/art.30402
PG 6
WC Rheumatology
SC Rheumatology
GA 806US
UT WOS:000293840200001
ER
PT J
AU Dvir-Ginzberg, M
Gagarina, V
Lee, EJ
Booth, R
Gabay, O
Hall, DJ
AF Dvir-Ginzberg, Mona
Gagarina, Viktoria
Lee, Eun Jin
Booth, Richard
Gabay, Odile
Hall, David J.
TI Tumor Necrosis Factor alpha-Mediated Cleavage and Inactivation of SirT1
in Human Osteoarthritic Chondrocytes
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID NF-KAPPA-B; FEMORAL-HEAD CARTILAGE; MESENCHYMAL STEM-CELLS; CATHEPSIN-B;
DEACETYLASE ACTIVITY; EXPRESSION; SURVIVAL; PROTEIN; INFLAMMATION;
FAMILY
AB Objective. The protein deacetylase SirT1 positively regulates cartilage-specific gene expression, while the proinflammatory cytokine tumor necrosis factor alpha (TNF alpha) negatively regulates these same genes. This study was undertaken to test the hypothesis that SirT1 is adversely affected by TNF alpha, resulting in altered gene expression.
Methods. Cartilage-specific gene expression, SirT1 activity, and results of chromatin immunoprecipitation analysis at the alpha 2(I) collagen enhancer site were determined in RNA, protein extracts, and nuclei of human osteoarthritic chondrocytes left untreated or treated with TNF alpha. Protein extracts from human chondrocytes transfected with epitope-tagged SirT1 that had been left untreated or had been treated with TNF alpha were analyzed by immunoblotting with SirT1 and epitope-specific antibodies. The 75-kd SirT1-reactive protein present in TNF alpha-treated extracts was identified by mass spectroscopy, and its amino-terminal cleavage site was identified via Edman sequencing. SirT1 activity was assayed following an in vitro cathepsin B cleavage reaction. Cathepsin B small interfering RNA (siRNA) was transfected into chondrocytes left untreated or treated with TNF alpha.
Results. TNF alpha-treated chondrocytes had impaired SirT1 enzymatic activity and displayed 2 forms of the enzyme: a full-length 110-kd protein and a smaller 75-kd fragment. The 75-kd SirT1 fragment was found to lack the carboxy-terminus. Cathepsin B was identified as the TNF alpha-responsive protease that cleaves SirT1 at residue 533. Reducing cathepsin B levels via siRNA following TNF alpha exposure blocked the generation of the 75-kd SirT1 fragment.
Conclusion. These data indicate that TNF alpha, a cytokine that mediates joint inflammation in arthritis, induces cathepsin B-mediated cleavage of SirT1, resulting in reduced SirT1 activity. This reduced SirT1 activity correlates with the reduced cartilage-specific gene expression evident in these TNF alpha-treated cells.
C1 [Gagarina, Viktoria; Lee, Eun Jin; Booth, Richard; Gabay, Odile; Hall, David J.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Dvir-Ginzberg, M (reprint author), Hebrew Univ Jerusalem, Fac Med Dent, Inst Dent Sci, Lab Cartilage Biol, POB 12272, IL-91120 Jerusalem, Israel.
EM monad@ekmd.huji.ac.il
FU NIH (National Institute of Arthritis and Musculoskeletal and Skin
Diseases)
FX Supported by the NIH (Intramural Research Program of the National
Institute of Arthritis and Musculoskeletal and Skin Diseases).
NR 43
TC 49
Z9 51
U1 2
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD AUG
PY 2011
VL 63
IS 8
BP 2363
EP 2373
DI 10.1002/art.30279
PG 11
WC Rheumatology
SC Rheumatology
GA 806US
UT WOS:000293840200026
PM 21305533
ER
PT J
AU Du, YH
Nikolovska-Coleska, Z
Qui, M
Li, L
Lewis, I
Dingledine, R
Stuckey, JA
Krajewski, K
Roller, PP
Wang, SM
Fu, HA
AF Du, Yuhong
Nikolovska-Coleska, Zaneta
Qui, Min
Li, Lian
Lewis, Iestyn
Dingledine, Raymond
Stuckey, Jeanne A.
Krajewski, Krzysztof
Roller, Peter P.
Wang, Shaomeng
Fu, Haian
TI A Dual-Readout F-2 Assay That Combines Fluorescence Resonance Energy
Transfer and Fluorescence Polarization for Monitoring Bimolecular
Interactions
SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
LA English
DT Article
ID SMALL-MOLECULE INHIBITORS; ANTIAPOPTOTIC BCL-2 PROTEINS; THROUGHPUT
SCREENING ASSAYS; STRUCTURE-BASED DESIGN; CELL-DEATH; POTENT; MCL-1;
FAMILY; IDENTIFICATION; TECHNOLOGIES
AB Forster (fluorescence) resonance energy transfer (FRET) and fluorescence polarization (FP) are widely used technologies for monitoring bimolecular interactions and have been extensively used in high-throughput screening (HTS) for probe and drug discovery. Despite their popularity in HTS, it has been recognized that different assay technologies may generate different hit lists for the same biochemical interaction. Due to the high cost of large-scale HTS campaigns, one has to make a critical choice to employee one assay platform for a particular HTS. Here we report the design and development of a dual-readout HTS assay that combines two assay technologies into one system using the Mcl-1 and Noxa BH3 peptide interaction as a model system. In this system, both FP and FRET signals were simultaneously monitored from one reaction, which is termed "Dual-Readout F-2 assay'' with F-2 for FP and FRET. This dual-readout technology has been optimized in a 1,536-well ultra-HTS format for the discovery of Mcl-1 protein inhibitors and achieved a robust performance. This F-2 assay was further validated by screening a library of 102,255 compounds. As two assay platforms are utilized for the same target simultaneously, hit information is enriched without increasing the screening cost. This strategy can be generally extended to other FP-based assays and is expected to enrich primary HTS information and enhance the hit quality of HTS campaigns.
C1 [Du, Yuhong; Qui, Min; Li, Lian; Lewis, Iestyn; Dingledine, Raymond; Fu, Haian] Emory Univ, Dept Pharmacol, Sch Med, Atlanta, GA 30322 USA.
[Du, Yuhong; Qui, Min; Li, Lian; Lewis, Iestyn; Dingledine, Raymond; Fu, Haian] Emory Univ, Emory Chem Biol Discovery Ctr, Atlanta, GA 30322 USA.
[Nikolovska-Coleska, Zaneta] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Stuckey, Jeanne A.] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA.
[Stuckey, Jeanne A.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
[Wang, Shaomeng] Univ Michigan, Dept Internal Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Wang, Shaomeng] Univ Michigan, Dept Med Chem, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Krajewski, Krzysztof; Roller, Peter P.] NCI, Med Chem Lab, NIH, Frederick, MD 21701 USA.
[Fu, Haian] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
RP Fu, HA (reprint author), Emory Univ, Dept Pharmacol, Sch Med, Atlanta, GA 30322 USA.
EM zanetan@med.umich.edu; hfu@emory.edu
RI dingledine, Ray/F-5173-2011
FU National Institutes of Health [PHS 5U54 HG003918, NS056915-01, P01
CA116676]; Emory University [P50 CA128613]; Emory Faculty Distinction
Fund; Georgia Cancer Coalition and Georgia Research Alliance
FX This work was supported in part by the grants from the National
Institutes of Health PHS 5U54 HG003918 (to R. D. and H. F.), NS056915-01
(to Z.N.-C.), P01 CA116676 (to H. F.), Emory University's SPORE in Head
and Neck Cancer Career Development award (P50 CA128613; to Y.D.), Emory
Faculty Distinction Fund, and Georgia Cancer Coalition and Georgia
Research Alliance (to H. F.).
NR 35
TC 5
Z9 5
U1 0
U2 6
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-658X
J9 ASSAY DRUG DEV TECHN
JI ASSAY DRUG DEV. TECHNOL.
PD AUG
PY 2011
VL 9
IS 4
BP 382
EP 393
DI 10.1089/adt.2010.0292
PG 12
WC Biochemical Research Methods; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 802IW
UT WOS:000293504300006
PM 21395401
ER
PT J
AU Mathew, A
Daniel, CR
Ferrucci, LM
Seth, T
Devesa, SS
George, PS
Shetty, H
Devasenapathy, N
Yurgalevitch, S
Rastogi, T
Prabhakaran, D
Gupta, PC
Chatterjee, N
Sinha, R
AF Mathew, Aleyamma
Daniel, Carrie R.
Ferrucci, Leah M.
Seth, Tulika
Devesa, Susan S.
George, Preethi S.
Shetty, Hemali
Devasenapathy, Niveditha
Yurgalevitch, Susan
Rastogi, Tanuja
Prabhakaran, Dorairaj
Gupta, Prakash C.
Chatterjee, Nilanjan
Sinha, Rashmi
TI Assessment of follow-up, and the completeness and accuracy of cancer
case ascertainment in three areas of India
SO CANCER EPIDEMIOLOGY
LA English
DT Article
DE Cancer; End-point; Follow-up; Registry; Prospective cohort; India
ID LONGITUDINAL-STUDY HEALS; LATE-STAGE PRESENTATION; HEART-DISEASE RISK;
CENTRAL OBESITY; INSULIN-RESISTANCE; HIGH PREVALENCE; MUMBAI BOMBAY;
EPIC-GERMANY; SOUTH-INDIA; NORTH-INDIA
AB Background: A prospective study of diet and cancer has not been conducted in India; consequently, little is known regarding follow-up rates or the completeness and accuracy of cancer case ascertainment. Methods: We assessed follow-up in the India Health Study (IHS; 4671 participants aged 35-69 residing in New Delhi, Mumbai, or Trivandrum). We evaluated the impact of medical care access and relocation, recontacted the IHS participants to estimate follow-up rates, and conducted separate studies of cancer cases to evaluate registry coverage (604 cases in Trivandrum) and the accuracy of self- and proxy-reporting (1600 cases in New Delhi and Trivandrum). Results: Over 97% of people reported seeing a doctor and 85% had lived in their current residence for over six years. The 2-year follow-up rate was 91% for Trivandrum and 53% for New Delhi. No cancer cases were missed among public institutions participating in the surveillance program in Trivandrum during 2003-2004; but there are likely to be unmatched cases (ranging from 5 to 13% of total cases) from private hospitals in the Trivandrum registry, as there are no mandatory reporting requirements. Vital status was obtained for 36% of cancer cases in New Delhi as compared to 78% in Trivandrum after a period of 4 years. Conclusions: A prospective cohort study of cancer may be feasible in some centers in India with active follow-up to supplement registry data. Inclusion of cancers diagnosed at private institutions, unique identifiers for individuals, and computerized medical information would likely improve cancer registries. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Mathew, Aleyamma; George, Preethi S.] Reg Canc Ctr, Trivandrum 695011, Kerala, India.
[Daniel, Carrie R.; Ferrucci, Leah M.; Devesa, Susan S.; Chatterjee, Nilanjan; Sinha, Rashmi] NCI, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
[Seth, Tulika] All India Inst Med Sci, New Delhi, India.
[Shetty, Hemali; Gupta, Prakash C.] Healis Sekhsaria Inst Publ Hlth, Navi Mumbai, India.
[Devasenapathy, Niveditha; Prabhakaran, Dorairaj] Ctr Chron Dis Control, New Delhi, India.
[Yurgalevitch, Susan] WESTAT Corp, Rockville, MD USA.
[Rastogi, Tanuja] United Nations World Food Program, Rome, Italy.
RP Mathew, A (reprint author), Reg Canc Ctr, Trivandrum 695011, Kerala, India.
EM amathew@rcctvm.org
RI Sinha, Rashmi/G-7446-2015;
OI Sinha, Rashmi/0000-0002-2466-7462; Prabhakaran,
Dorairaj/0000-0002-3172-834X
FU Intramural NIH HHS [ZIA CP010194-03]
NR 40
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1877-7821
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD AUG
PY 2011
VL 35
IS 4
BP 334
EP 341
DI 10.1016/j.canep.2011.03.006
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 809FU
UT WOS:000294038000004
PM 21621499
ER
PT J
AU Li, JX
Cho, YY
Langfald, A
Carper, A
Lubet, RA
Grubbs, CJ
Ericson, ME
Bode, AM
AF Li, Jixia
Cho, Yeon-Yong
Langfald, Alyssa
Carper, Andria
Lubet, Ronald A.
Grubbs, Clinton J.
Ericson, Marna E.
Bode, Ann M.
TI Lapatinib, a Preventive/Therapeutic Agent against Mammary Cancer,
Suppresses RTK-Mediated Signaling through Multiple Signaling Pathways
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; METASTATIC BREAST-CANCER; EGF RECEPTOR;
GEFITINIB IRESSA; CELL-GROWTH; P53; PROMOTES; AKT; ACTIVATION; INHIBITOR
AB Activation of receptor tyrosine kinases (RTK) plays a key role in the prognosis of mammary cancer. Lapatinib is a small molecule dual RTK inhibitor that targets epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Identifying the protein targets involved in the effects of lapatinib and other RTK inhibitors might help determine why preventive efficacy varies. In this study, female Sprague-Dawley rats were given methylnitrosourea (MNU) by intravenous injection resulting in the development of multiple estrogen receptor-positive tumors. Treatment with lapatinib beginning 5 days after MNU was highly effective in preventing cancer development. In addition, we treated rats with palpable mammary tumors with lapatinib daily. In these tumor-bearing animals, treatment continued for 42 days and therapeutic results were obtained. Some rats bearing cancers were treated for 5 days, and the resulting lesions were examined for biomarker modulation. Lapatinib effectively suppressed the abundance of HER2, phosphorylated HER2 (Tyr1221/1222), and phosphorylated EGFR (Tyr1173, Tyr1110) compared with tumors from untreated rats. Protein array analyses allowed parallel determination of the effect of lapatinib on the relative levels of protein phosphorylation and proteins associated with apoptosis. These results combined with immunoreactivity data indicated that, in addition to EGFR and HER2, lapatinib treatment was associated with changes in a number of other signaling molecules, including IGF-1R, Akt, and downstream targets such as GSK3, p27, p53, and cyclin D1 presumably leading to impaired proliferation, apoptosis, or cell-cycle arrest. Cancer Prev Res; 4(8); 1190-7. (C) 2011 AACR.
C1 [Li, Jixia; Cho, Yeon-Yong; Langfald, Alyssa; Carper, Andria; Bode, Ann M.] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA.
[Lubet, Ronald A.] NCI, Bethesda, MD 20892 USA.
[Grubbs, Clinton J.] Univ Alabama, Birmingham, AL USA.
[Ericson, Marna E.] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA.
[Ericson, Marna E.] Univ Minnesota, Ctr Drug Design, Minneapolis, MN USA.
RP Bode, AM (reprint author), Univ Minnesota, Hormel Inst, 801 16th Ave NE, Austin, MN 55912 USA.
EM ambode@hi.umn.edu
FU NIH [HHSN-261200433009C, NO1-CN-55006-72]
FX This work was supported by NIH contract HHSN-261200433009C and
NO1-CN-55006-72.
NR 48
TC 11
Z9 11
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD AUG
PY 2011
VL 4
IS 8
BP 1190
EP 1197
DI 10.1158/1940-6207.CAPR-10-0330
PG 8
WC Oncology
SC Oncology
GA 802JJ
UT WOS:000293505700006
PM 21791570
ER
PT J
AU Sharma, S
Lee, J
Zhou, JL
Steele, VE
AF Sharma, Sheela
Lee, Jin
Zhou, Jianliang
Steele, Vernon E.
TI Chemopreventive Efficacy and Mechanism of Licofelone in a Mouse Lung
Tumor Model via Aspiration
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID <2,2-DIMETHYL-6-(4-CHLOROPHENYL)-7-PHENYL-2,3-DIHYDRO-1H-PYRROLIZINE-5-Y
L>-ACET ACID; CANCER CHEMOPREVENTION; DUAL INHIBITION; 5-LIPOXYGENASE;
CYCLOOXYGENASE; BUDESONIDE; PREVENTION; CELECOXIB; ML-3000; COX-2
AB Our previous study comparing inhalation and aspiration to administer agents directly to lung indicated that aspiration route is as effective as inhalation while reducing costs for equipment and chemopreventive agent. This study evaluated the chemopreventive efficacy and mechanism of licofelone, a dual inhibitor of COX-2 and 5-lipoxygenase (5-Lox), via oropharyngeal aspiration against mouse lung adenoma. Eight-week-old female A/J mice were given three doses of benzo[a] pyrene (B[a] P; 2 mg/dose, gavage) to induce lung adenomas. After dysplasia developed, the mice were given licofelone (0, 0.03, 0.1, or 0.3 mg/kg) for 16 weeks, and tumor incidence and multiplicity in lung were measured. In addition, the expression of a series of biomarkers in lung cancer progression was evaluated at 2 and 16 weeks. Licofelone showed dose-related inhibition of B[a] P-induced tumor incidence and multiplicity at 0.03 and 0.1 mg/kg following 16-week treatment. Licofelone also showed dose-dependent inhibition of COX-2 (25%-41%) and 5-Lox (35%-61%) at 2 and 16 weeks and proliferating cell nuclear antigen (PCNA; 41%-61%) at 16 weeks. A dose-dependent increase in apoptosis (1.5- to 2.4-fold) was also observed in licofelone groups. A marginal inhibition of survivin was observed at one dose. In conclusion, this study showed that licofelone via aspiration showed chemopreventive efficacy against mouse lung adenoma with good correlation to early and late biomarkers of lung cancer progression. This is the first study to show that the aspiration route can be an excellent inexpensive alternative to inhalation for direct delivery of drugs to rodent lungs for efficacy testing of potential chemopreventive agents. Cancer Prev Res; 4(8); 1233-42. (C) 2011 AACR.
C1 [Sharma, Sheela; Lee, Jin; Zhou, Jianliang] Hamner Inst Hlth Sci, Ctr Preclin Safety & Efficacy, Res Triangle Pk, NC 27709 USA.
[Steele, Vernon E.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Sharma, S (reprint author), Hamner Inst Hlth Sci, Ctr Preclin Safety & Efficacy, 6 Davis Dr, Res Triangle Pk, NC 27709 USA.
EM ssharma@thehamner.org
FU Division of Cancer Prevention, NCI [N01-CN-53301]
FX This work was supported by research contract N01-CN-53301, Division of
Cancer Prevention, NCI (S. Sharma).
NR 41
TC 9
Z9 10
U1 0
U2 3
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 AUG
PY 2011
VL 4
IS 8
BP 1233
EP 1242
DI 10.1158/1940-6207.CAPR-10-0117
PG 10
WC Oncology
SC Oncology
GA 802JJ
UT WOS:000293505700010
PM 21562034
ER
PT J
AU Moss, J
AF Moss, Joel
TI Ahead of the Curve
SO CHEST
LA English
DT Editorial Material
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
RP Moss, J (reprint author), NHLBI, NIH, Bldg 10,Room 6DO5,MSC 1590 NHLBI,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mossj@nhlbi.nih.gov
FU Intramural NIH HHS [ZIA HL002541-15]
NR 3
TC 2
Z9 2
U1 0
U2 3
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD AUG
PY 2011
VL 140
IS 2
BP 275
EP 276
DI 10.1378/chest.11-1353
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 808QS
UT WOS:000293994100001
PM 21813519
ER
PT J
AU Dibble, CT
Lima, JAC
Bluemke, DA
Chirinos, JA
Chahal, H
Bristow, MR
Kronmal, RA
Barr, RG
Ferrari, VA
Propert, KJ
Kawut, SM
AF Dibble, Christopher T.
Lima, Joao A. C.
Bluemke, David A.
Chirinos, Julio A.
Chahal, Harjit
Bristow, Michael R.
Kronmal, Richard A.
Barr, R. Graham
Ferrari, Victor A.
Propert, Kathleen J.
Kawut, Steven. M.
TI Regional Left Ventricular Systolic Function and the Right Ventricle The
Multi-Ethnic Study of Atherosclerosis Right Ventricle Study
SO CHEST
LA English
DT Article
ID MAGNETIC-RESONANCE; ASYMPTOMATIC INDIVIDUALS; PULMONARY-HYPERTENSION;
CONSCIOUS DOGS; ISOLATED HEART; WORK OUTPUT; STRAIN; MASS; AFTERLOAD;
PRESSURE
AB Background: Dysfunction of the interventricular septum has been implicated in right ventricular (RV) failure. However, little is known about the relationship between ventricular septal and RV function in patients without clinical cardiovascular disease. We hypothesized that better septal function would be associated with higher RV ejection fraction and lower RV mass and volume by cardiac MRI.
Methods: In the Multi-Ethnic Study of Atherosclerosis (MESA), cardiac MRI was performed on community-based participants without clinical cardiovascular disease. Images were analyzed by the harmonic phase method to measure peak circumferential systolic midventricular strain for each wall (anterior, lateral, inferior, and septal). Multivariable linear regression and generalized additive models were used to assess the relationship between septal strain and RV morphology.
Results: There were 917 participants (45.7% women) with a mean age of 65.7 years. Better septal function was associated with higher RV ejection fraction in a nonlinear fashion after adjustment for all covariates (P =.03). There appeared to be a threshold effect for the contribution of septal strain to RV systolic function, with an almost linear decrement in RV ejection fraction with septal strain from - 18% to - 10%. Septal function was not related to RV mass or volume.
Conclusions: Interventricular septal function was linked to RV systolic function independent of other left ventricular regions, even in individuals without clinical cardiovascular disease. This finding confirms animal and human research suggesting the importance of septal function to the right ventricle and implies that changes in septal function could herald RV dysfunction. Trial registry: ClinicalTrials.gov; No.: NCT00005487; URL: www.clinicaltrials.gov CHEST 2011; 140(2):310-316
C1 [Dibble, Christopher T.; Chirinos, Julio A.; Ferrari, Victor A.; Kawut, Steven. M.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Dibble, Christopher T.; Propert, Kathleen J.; Kawut, Steven. M.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Chirinos, Julio A.; Ferrari, Victor A.; Kawut, Steven. M.] Univ Penn, Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Lima, Joao A. C.; Chahal, Harjit] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
[Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Bristow, Michael R.] Univ Colorado Denver, Anschutz Med Ctr, Dept Med, Aurora, CO USA.
[Kronmal, Richard A.] Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
[Barr, R. Graham] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA.
RP Kawut, SM (reprint author), Univ Penn, Sch Med, Dept Med, 718 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM kawut@mail.med.upenn.edu
RI bristow, michael/G-7850-2011;
OI Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health [R01-H L066075, R01-HL086719, N01-HC95159,
HC95165, T32-HL-007891]
FX This work was supported by the National Institutes of Health [R01-H
L066075, R01-HL086719, N01-HC95159 through HC95165, and T32-HL-007891].
NR 37
TC 10
Z9 10
U1 0
U2 2
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD AUG
PY 2011
VL 140
IS 2
BP 310
EP 316
DI 10.1378/chest.10-1750
PG 7
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 808QS
UT WOS:000293994100013
PM 21330384
ER
PT J
AU Kiley, JP
AF Kiley, James P.
TI Advancing Respiratory Research
SO CHEST
LA English
DT Article
ID IDIOPATHIC PULMONARY-FIBROSIS; STEM-CELLS; AIRWAY EPITHELIUM;
GENE-EXPRESSION; LUNG; ASTHMA; IDENTIFICATION; EXACERBATIONS;
INFLAMMATION; PROGRAM
AB Respiratory diseases remain a major public health problem in the United States and worldwide, with increasing morbidity and mortality. Substantial progress has been made to advance understanding of the basic mechanisms of lung disease and to optimize clinical management of patients with a range of respiratory diseases. Despite this progress, our knowledge of how to predict disease prior to symptoms, improve disease definition and subclassification, and target novel and new treatments in a more personalized manner still remains inadequate. This article highlights several future opportunities and challenges related to genomics and molecular characterization of lung disease, lung injury and repair, translational lung research, the microbiome, and sleep and circadian biology as potential frontiers to advance progress in respiratory biology in health and disease. CHEST 2011; 140(2):497-501
C1 NHLBI, Div Lung Dis, NIH, Rockledge Ctr 2,US Dept HHS, Bethesda, MD 20892 USA.
RP Kiley, JP (reprint author), NHLBI, Div Lung Dis, NIH, Rockledge Ctr 2,US Dept HHS, 6701 Rockledge Dr,Ste 10042,MSC 7952, Bethesda, MD 20892 USA.
EM kileyj@nhlbi.nih.gov
NR 28
TC 12
Z9 14
U1 0
U2 6
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD AUG
PY 2011
VL 140
IS 2
BP 497
EP 501
DI 10.1378/chest.11-e774
PG 5
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 808QS
UT WOS:000293994100037
PM 21813528
ER
PT J
AU Santos, FPS
Kantarjian, H
McConkey, D
O'Brien, S
Faderl, S
Borthakur, G
Ferrajoli, A
Wright, J
Cortes, J
AF Santos, Fabio P. S.
Kantarjian, Hagop
McConkey, David
O'Brien, Susan
Faderl, Stefan
Borthakur, Gautam
Ferrajoli, Alessandra
Wright, John
Cortes, Jorge
TI Pilot Study of Bortezomib for Patients With Imatinib-Refractory Chronic
Myeloid Leukemia in Chronic or Accelerated Phase
SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
LA English
DT Article
DE Bortezomib; Chronic myelogenous leukemia; Proteasome inhibitors
ID CHRONIC MYELOGENOUS LEUKEMIA; UBIQUITIN-PROTEASOME PATHWAY; NF-KAPPA-B;
NILOTINIB FORMERLY AMN107; TYROSINE KINASE INHIBITOR; MULTIPLE-MYELOMA;
DEPENDENT DEGRADATION; PERIPHERAL NEUROPATHY; CELL-LINES; ABL
AB Background: Proteasome inhibitors are anticancer compounds that disrupt the proteolytic activity of the proteasome and lead to tumor cell growth arrest and apoptosis. Bortezomib is a proteasome inhibitor that is currently approved for use in multiple myeloma (MM) and mantle-cell lymphoma. It induces apoptosis of chronic myeloid leukemia (CML) cells in vitro, but the activity of bortezomib in patients with imatinib-resistant CML is unknown. Methods: We conducted a pilot trial to evaluate the activity of single-agent bortezomib in CML. Seven patients with imatinib-refractory CML were treated with bortezomib at a dose of 1.5 mg/m(2) on days 1, 4, 8, and 11 every 3 weeks. Results: The median number of cycles received was 2. No patient had a hematologic or cytogenetic response. Three patients had a temporary decrease in basophil counts associated with therapy with bortezomib. Six patients experienced grade 3/4 nonhematologic toxicities. Conclusion: Bortezomib had minimal efficacy and considerable toxicity in patients with imatinib-refractory CML. Further studies should focus on alternative approaches to using proteasome inhibitors in the treatment of CML, such as in combination with tyrosine kinase inhibitors (TKIs) or as a strategy to eradicate leukemic stem cells.
C1 [Santos, Fabio P. S.; Kantarjian, Hagop; O'Brien, Susan; Faderl, Stefan; Borthakur, Gautam; Ferrajoli, Alessandra; Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
[McConkey, David] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Wright, John] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Cortes, J (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Leukemia, 1515 Holcombe Blvd,Unit 0428, Houston, TX 77030 USA.
EM jcortes@mdanderson.org
FU NCI NIH HHS [P30 CA016672, P01 CA049639]
NR 43
TC 10
Z9 11
U1 0
U2 1
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 2152-2650
J9 CL LYMPH MYELOM LEUK
JI Clin. Lymphoma Myeloma Leuk.
PD AUG
PY 2011
VL 11
IS 4
BP 355
EP 360
DI 10.1016/j.clml.2011.06.004
PG 6
WC Oncology; Hematology
SC Oncology; Hematology
GA 805BA
UT WOS:000293699900008
PM 21816374
ER
PT J
AU Al-Riyami, A
Jaju, D
Jaju, S
Silverman, HJ
AF Al-Riyami, Asya
Jaju, Deepali
Jaju, Sanjay
Silverman, Henry J.
TI THE ADEQUACY OF INFORMED CONSENT FORMS IN GENETIC RESEARCH IN OMAN: A
PILOT STUDY
SO DEVELOPING WORLD BIOETHICS
LA English
DT Article
DE Oman; genetic research; research ethics; informed consent
ID POPULATION; COMPREHENSION; STATEMENT; MEDICINE; STORAGE; SAMPLES; ETHICS
AB Genetic research presents ethical challenges to the achievement of valid informed consent, especially in developing countries with areas of low literacy. During the last several years, a number of genetic research proposals involving Omani nationals were submitted to the Department of Research and Studies, Ministry of Health, Oman.
The objective of this paper is to report on the results of an internal quality assurance initiative to determine the extent of the information being provided in genetic research informed consent forms. In order to achieve this, we developed checklists to assess the inclusion of basic elements of informed consent as well as elements related to the collection and future storage of biological samples. Three of the authors independently evaluated and reached consensus on seven informed consent forms that were available for review.
Of the seven consent forms, four had less than half of the basic elements of informed consent. None contained any information regarding whether genetic information relevant to health would be disclosed, whether participants may share in commercial products, the extent of confidentiality protections, and the inclusion of additional consent forms for future storage and use of tissue samples. Information regarding genetic risks and withdrawal of samples were rarely mentioned (1/7), whereas limits on future use of samples were mentioned in 3 of 7 consent forms.
Ultimately, consent forms are not likely to address key issues regarding genetic research that have been recommended by research ethics guidelines. We recommend enhanced educational efforts to increase awareness, on the part of researchers, of information that should be included in consent forms.
C1 [Al-Riyami, Asya] Minist Hlth Res & Studies, Muscat 100, Oman.
[Silverman, Henry J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Silverman, Henry J.] NIH, Fogarty Int Ctr, Middle E Res Eth Training Initiat, Bethesda, MD USA.
RP Al-Riyami, A (reprint author), Minist Hlth Res & Studies, POB 393, Muscat 100, Oman.
EM asyariyami@gmail.com
NR 33
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1471-8731
J9 DEV WORLD BIOETH
JI Dev. World Bioeth.
PD AUG
PY 2011
VL 11
IS 2
BP 57
EP 62
DI 10.1111/j.1471-8847.2010.00293.x
PG 6
WC Ethics; Medical Ethics
SC Social Sciences - Other Topics; Medical Ethics
GA 801PI
UT WOS:000293452100002
PM 21266001
ER
PT J
AU Vassy, JL
Shrader, P
Jonsson, A
Fox, CS
Lyssenko, V
Isomaa, B
Groop, L
Meigs, JB
Franks, PW
AF Vassy, Jason L.
Shrader, Peter
Jonsson, Anna
Fox, Caroline S.
Lyssenko, Valeriya
Isomaa, Bo
Groop, Leif
Meigs, James B.
Franks, Paul W.
TI Association between parental history of diabetes and type 2 diabetes
genetic risk scores in the PPP-Botnia and Framingham Offspring Studies
SO DIABETES RESEARCH AND CLINICAL PRACTICE
LA English
DT Article
DE Type 2 diabetes mellitus; Genetic risk score; Family history
ID SUSCEPTIBILITY LOCI; HEART-DISEASE; MELLITUS; PREDICTION
AB Objective: Parental history of diabetes and specific gene variants are risk factors for type 2 diabetes, but the extent to which these factors are associated is unknown. Methods: We examined the association between parental history of diabetes and a type 2 diabetes genetic risk score (GRS) in two cohort studies from Finland (population-based PPP-Botnia study) and the US (family-based Framingham Offspring Study). Results: Mean (95% CI) GRS increased from 16.8 (16.8-16.9) to 16.9 (16.8-17.1) to 17.1 (16.8-17.4) among PPP-Botnia participants with 0, 1, and 2 parents with diabetes, respectively (p(trend) = 0.03). The trend was similar among Framingham Offspring but was not statistically significant (p = 0.07). The meta-analyzed p value for trend from the two studies was 0.005. Conclusions: The very modest associations reported above suggest that the increased risk of diabetes in offspring of parents with diabetes is largely the result of shared environmental/lifestyle factors and/or hitherto unknown genetic factors. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Vassy, Jason L.; Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Vassy, Jason L.; Fox, Caroline S.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA.
[Vassy, Jason L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Jonsson, Anna; Lyssenko, Valeriya; Groop, Leif] Lund Univ, Diabet & Endocrinol Unit, Dept Clin Sci, S-20502 Malmo, Sweden.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[Isomaa, Bo] Folkhalsan Res Ctr, Pietarsaari 68660, Finland.
[Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari 68601, Finland.
[Groop, Leif] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Franks, Paul W.] Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, S-20502 Malmo, Sweden.
[Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
RP Franks, PW (reprint author), Lund Univ, Skane Univ Hosp UMAS, Dept Clin Sci, Genet & Mol Epidemiol Unit,Clin Res Ctr, Bldg 60,Entrance 72,Level 12, S-20502 Malmo, Sweden.
EM Paul.Franks@med.lu.se
OI Franks, Paul/0000-0002-0520-7604
FU Swedish Diabetes Association; Swedish Heart Lung-Foundation; Novo
Nordisk; Knut and Alice Wallenberg Foundation; Pahlsson Foundation;
Sigrid Juselius Foundation; Folkhalsan Research Foundation; Nordic
Center of Excellence in Disease Genetics; EU; Signe and Ane Gyllenberg
Foundation; Swedish Cultural Foundation in Finland; Finnish Diabetes
Research Foundation; Foundation for Life and Health in Finland; Finnish
Medical Society; Paavo Nurmi Foundation; Helsinki University Central
Hospital Research Foundation; Perklen Foundation; Ollqvist Foundation;
Narpes Health Care Foundation; Swedish Research Council; National Heart,
Lung and Blood Institute's Framingham Heart Study [N01 HC 25195];
Affymetrix, Inc. [N02 HL 6 4278]; Robert Dawson Evans Endowment of the
Department of Medicine at Boston University School of Medicine and
Boston Medical Center; National Institute for Diabetes and Digestive and
Kidney Diseases (NIDDK) [R01 DK078616, NIDDK K24 DK080140]; National
Research Service [T32 HP12706]
FX The PPP-Botnia study: we thank the study participants and the Botnia
Study Group. We are also grateful for the technical assistance of the
staff of the CRC in Malmo. This work was funded in part by grants from
the Swedish Diabetes Association, Swedish Heart Lung-Foundation, Novo
Nordisk, the Knut and Alice Wallenberg Foundation, the Pahlsson
Foundation, the Sigrid Juselius Foundation, the Folkhalsan Research
Foundation, the Nordic Center of Excellence in Disease Genetics, an EU
grant (EXGENESIS), the Signe and Ane Gyllenberg Foundation, the Swedish
Cultural Foundation in Finland, the Finnish Diabetes Research
Foundation, the Foundation for Life and Health in Finland, the Finnish
Medical Society, the Paavo Nurmi Foundation, Helsinki University Central
Hospital Research Foundation, the Perklen Foundation, the Ollqvist
Foundation and the Narpes Health Care Foundation. P.W.F. was supported
in part by grants from the Swedish Research Council, Swedish Heart
Lung-Foundation, Novo Nordisk, and the Swedish Diabetes Association.;
Framingham Offspring Study: This research was conducted in part using
data and resources from the Framingham Heart Study of the National Heart
Lung and Blood Institute of the National Institutes of Health and Boston
University School of Medicine. The analyses reflect intellectual input
and resource development from the Framingham Heart Study investigators
participating in the SNP Health Association Resource (SHARe) project.
This work was partially supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (Contract no. N01 HC 25195) and its
contract with Affymetrix, Inc. for genotyping services (Contract no. N02
HL 6 4278). A portion of this research utilized the Linux Cluster for
Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment
of the Department of Medicine at Boston University School of Medicine
and Boston Medical Center. Also supported by National Institute for
Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK078616, NIDDK
K24 DK080140 (J.B.M.) and a National Research Service Award grant T32
HP12706 (J.L.V.).
NR 14
TC 8
Z9 8
U1 1
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0168-8227
J9 DIABETES RES CLIN PR
JI Diabetes Res. Clin. Pract.
PD AUG
PY 2011
VL 93
IS 2
BP E76
EP E79
DI 10.1016/j.diabres.2011.04.013
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 806QQ
UT WOS:000293825400007
PM 21570145
ER
PT J
AU Rudel, RA
Fenton, SE
Ackerman, JM
Euling, SY
Makris, SL
AF Rudel, Ruthann A.
Fenton, Suzanne E.
Ackerman, Janet M.
Euling, Susan Y.
Makris, Susan L.
TI Environmental Exposures and Mammary Gland Development: State of the
Science, Public Health Implications, and Research Recommendations
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Review
DE breast cancer; carcinogen susceptibility; development; endocrine
disruptors; human health; lactation; mammary gland; risk assessment;
rodent model; whole mount
ID BREAST-CANCER RISK; SPRAGUE-DAWLEY RATS; PERINATAL EXPOSURE; NEONATAL
EXPOSURE; DIETHYLSTILBESTROL DES; HUMAN-MILK; IN-UTERO;
PERFLUOROOCTANOIC ACID; ENDOCRINE DISRUPTORS; LACTATIONAL EXPOSURE
AB OBJECTIVES: Perturbations in mammary gland (MG) development may increase risk for later adverse effects, including lactation impairment, gynecomastia (in males), and breast cancer. Animal studies indicate that exposure to hormonally active agents leads to this type of develop mental effect and related later life susceptibilities. In this review we describe current science, public health issues, and research recommendations for evaluating MG development.
DATA SOURCES: The Mammary Gland Evaluation and Risk Assessment Workshop was convened in Oakland, California, USA, 16-17 November 2009, to integrate the expertise and perspectives of scientists, risk assessors, and public health advocates. Interviews were conducted with 18 experts, and seven laboratories conducted an MG slide evaluation exercise. Workshop participants discussed effects of gestational and early life exposures to hormonally active agents on MG development, the relationship of these develop mental effects to lactation and cancer, the relative sensitivity of MG and other develop mental end points, the relevance of animal models to humans, and methods for evaluating MG effects.
SYNTHESIS: Normal MG development and MG carcinogenesis demonstrate temporal, morphological, and mechanistic similarities among test animal species and humans. Diverse chemicals, including many not considered primarily estrogenic, alter MG development in rodents. Inconsistent reporting methods hinder comparison across studies, and relationships between altered development and effects on lactation or carcinogenesis are still being defined. In some studies, altered MG development is the most sensitive endocrine end point.
CONCLUSIONS: Early life environmental exposures can alter MG development, disrupt lactation, and increase susceptibility to breast cancer. Assessment of MG development should be incorporated in chemical test guidelines and risk assessment.
C1 [Rudel, Ruthann A.; Ackerman, Janet M.] Silent Spring Inst, Newton, MA 02458 USA.
[Fenton, Suzanne E.] NIEHS, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Euling, Susan Y.; Makris, Susan L.] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA.
RP Rudel, RA (reprint author), Silent Spring Inst, 29 Crafts St, Newton, MA 02458 USA.
EM rudel@silentspring.org
FU U.S. Environmental Protection Agency (U.S. EPA); National Institute of
Environmental Health Sciences (NIEHS); National Toxicology Program
(NTP); Silent Spring Institute
FX This workshop was supported by the California Breast Cancer Research
Program, U.S. Environmental Protection Agency (U.S. EPA), National
Institute of Environmental Health Sciences (NIEHS), National Toxicology
Program (NTP), and Silent Spring Institute.
NR 112
TC 59
Z9 60
U1 3
U2 21
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD AUG
PY 2011
VL 119
IS 8
BP 1053
EP 1061
DI 10.1289/ehp.1002864
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 801MU
UT WOS:000293444300020
PM 21697028
ER
PT J
AU White, SS
Stanko, JP
Kato, K
Calafat, AM
Hines, EP
Fenton, SE
AF White, Sally S.
Stanko, Jason P.
Kato, Kayoko
Calafat, Antonia M.
Hines, Erin P.
Fenton, Suzanne E.
TI Gestational and Chronic Low-Dose PFOA Exposures and Mammary Gland Growth
and Differentiation in Three Generations of CD-1 Mice
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE delayed development; fetal origins of adult disease; lactation; mammary
gland; multigenerational; perfluorooctanoic acid (PFOA)
ID PERFLUOROOCTANOIC ACID; DEVELOPMENTAL TOXICITY; CROSS-FOSTER; MOUSE;
PREGNANCY; C57BL/6; SERUM
AB BACKGROUND: Prenatal exposure to perfluorooctanoic acid (PFOA), a ubiquitous industrial surfactant, has been reported to delay mammary gland development in female mouse offspring (F(1)) and the treated lactating dam (P(0)) after gestational treatments at 3 and 5 mg PFOA/kg/day.
OBJECTIVE: We investigated the consequences of gestational and chronic PFOA exposure on F(1) lactational function and subsequent development of F(2) offspring.
METHODS: We treated P(0) dams with 0, 1, or 5 mg PFOA/kg/day on gestation days 1-17. In addition, a second group of P(0) dams treated with 0 or 1 mg/kg/day during gestation and their F(1) and F(2) offspring received continuous PFOA exposure (5 ppb) in drinking water. Resulting adult F(1) females were bred to generate F(2) offspring, whose development was monitored over post natal days (PNDs) 1-63. F(1) gland function was assessed on PND10 by timed-lactation experiments. Mammary tissue was isolated from P(0), F(1), and F(2) females throughout the study and histologically assessed for age-appropriate development.
RESULTS: PFOA-exposed F(1) dams exhibited diminished lactational morphology, although F(1) maternal behavior and F(2) offspring body weights were not significantly affected by P(0) treatment. In addition to reduced gland development in F(1) females under all exposures, F(2) females with chronic low-dose drinking-water exposures exhibited visibly slowed mammary gland differentiation from weaning onward. F(2) females derived from 5 mg/kg PFOA-treated P(0) dams displayed gland morphology similar to F(2) chronic water exposure groups on PNDs 22-63.
CONCLUSIONS: Gestational PFOA exposure induced delays in mammary gland development and/or lactational differentiation across three generations. Chronic, low-dose PFOA exposure in drinking water was also sufficient to alter mammary morphological development in mice, at concentrations approximating those found in contaminated human water supplies.
C1 [White, Sally S.; Stanko, Jason P.; Fenton, Suzanne E.] NIEHS, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Kato, Kayoko; Calafat, Antonia M.] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA.
[Hines, Erin P.] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
RP Fenton, SE (reprint author), POB 12233,Mail Drop E1-08, Res Triangle Pk, NC 27709 USA.
EM fentonse@niehs.nih.gov
OI Hines, Erin Pias/0000-0002-2458-6267
FU U.S. EPA; National Health and Environmental Effects Research
Laboratory-University of North Carolina with the University of North
Carolina-Chapel Hill [T829472, CR833237]; NTP [HHSN27300239]
FX S.S.W. was supported by U.S. EPA, National Health and Environmental
Effects Research Laboratory-University of North Carolina Toxicology
Curriculum Cooperative Training Agreements (T829472 and CR833237) with
the University of North Carolina-Chapel Hill, and NTP contract
HHSN27300239.
NR 19
TC 33
Z9 33
U1 2
U2 12
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD AUG
PY 2011
VL 119
IS 8
BP 1070
EP 1076
DI 10.1289/ehp.1002741
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 801MU
UT WOS:000293444300022
PM 21501981
ER
PT J
AU Bauer, AK
Rondini, EA
Hummel, KA
Degraff, LM
Walker, C
Jedlicka, AE
Kleeberger, SR
AF Bauer, Alison K.
Rondini, Elizabeth A.
Hummel, Kristin A.
Degraff, Laura M.
Walker, Christopher
Jedlicka, Anne E.
Kleeberger, Steven R.
TI Identification of Candidate Genes Downstream of TLR4 Signaling after
Ozone Exposure in Mice: A Role for Heat-Shock Protein 70
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE heat-shock protein 70; inflammation; ozone; pulmonary; toll-like
receptor 4; transcriptomics
ID ACUTE LUNG INJURY; LOW-LEVEL OZONE; INDUCED INFLAMMATION; IN-VIVO;
RESPIRATORY SYMPTOMS; INNATE IMMUNITY; AIR-POLLUTION; RECEPTOR 4;
SUSCEPTIBILITY; STRESS
AB BACKGROUND: Toll-like receptor 4 (TLR4) is involved in ozone (O(3))-induced pulmonary hyperpermeability and inflammation, although the downstream signaling events are unknown.
OBJECTIVES: The aims of our study were to determine the mechanism through which TLR4 modulates O(3)-induced pulmonary responses and to use transcriptomics to determine potential TLR4 effector molecules.
METHODS: C3H/HeJ (HeJ; Tlr4 mutant) and C3H/HeOuJ (OuJ; Tlr4 normal) mice were exposed continuously to 0.3 ppm O(3) or filtered air for 6, 24, 48, or 72 hr. We assessed inflammation using bronchoalveolar lavage and molecular analysis by mRNA micro array, quantitative RT-PCR (real-time polymerase chain reaction), immuno blots, immunostaining, and ELISAs (enzyme-linked immunosorbent assays). B6-Hspa1a/Hspa1btm1Dix/NIEHS (Hsp70-/-) and C57BL/6 (B6; Hsp70+/+ wild-type control) mice were used for candidate gene validation studies.
RESULTS: O(3)-induced TLR4 signaling occurred through myeloid differentiation protein 88 (MyD88)-dependent and -independent pathways in OuJ mice and involved multiple downstream pathways. Genomewide transcript analyses of lungs from air-and O(3)-exposed HeJ and OuJ mice identified a cluster of genes that were significantly up-regulated in O(3)-exposed OuJ mice compared with O(3)-exposed HeJ mice or air-exposed controls of both strains; this cluster included genes for heat-shock proteins (e.g., Hspa1b, Hsp70). Moreover, O(3)-induced inflammation, MyD88 up-regulation, extracellular-signal-related kinase-1/2 (ERK1/2) and activator protein-1 (AP-1) activation, and kerotinocyte-derived chemokine (KC) protein content were significantly reduced in Hspa1a/Hspa1b(tm1Dix) (Hsp70(-/-)) compared with Hsp70(+/+) mice (p < 0.05).
CONCLUSIONS: These studies suggest that HSP70 is an effector molecule downstream of TLR4 and is involved in the regulation of O(3)-induced lung inflammation by triggering similar pathways to TLR4. These novel findings may have therapeutic and preventive implications for inflammatory diseases resulting from environmental exposures.
C1 [Bauer, Alison K.; Rondini, Elizabeth A.; Hummel, Kristin A.] Michigan State Univ, Dept Pathobiol & Diagnost Invest, E Lansing, MI 48824 USA.
[Degraff, Laura M.; Walker, Christopher; Kleeberger, Steven R.] NIEHS, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Jedlicka, Anne E.] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
RP Bauer, AK (reprint author), Univ Colorado, Dept Environm & Occupat Hlth, Mail Stop B119-V20,Rm V20-3125,Anschutz Med Campu, Aurora, CO 80045 USA.
EM alison.bauer@ucdenver.edu
FU National Institute of Environmental Health Sciences (NIEHS) [ES014731];
Michigan State University; Division of Intramural Research, NIEHS,
National Institutes of Health
FX This work was supported by National Institute of Environmental Health
Sciences (NIEHS) grant ES014731 (to A.K.B.), Michigan State University
internal funds (A.K.B., E.A.R., K.A.H.), and the Division of Intramural
Research, NIEHS, National Institutes of Health (S.R.K., L.M.D., C.W.).
NR 56
TC 17
Z9 17
U1 0
U2 5
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 AUG
PY 2011
VL 119
IS 8
BP 1091
EP 1097
DI 10.1289/ehp.1003326
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 801MU
UT WOS:000293444300025
PM 21543283
ER
PT J
AU Huang, RL
Xia, MH
Cho, MH
Sakamuru, S
Shinn, P
Houck, KA
Dix, DJ
Judson, RS
Witt, KL
Kavlock, RJ
Tice, RR
Austin, CP
AF Huang, Ruili
Xia, Menghang
Cho, Ming-Hsuang
Sakamuru, Srilatha
Shinn, Paul
Houck, Keith A.
Dix, David J.
Judson, Richard S.
Witt, Kristine L.
Kavlock, Robert J.
Tice, Raymond R.
Austin, Christopher P.
TI Chemical Genomics Profiling of Environmental Chemical Modulation of
Human Nuclear Receptors
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE assay performance; chemical genomics; cytotoxicity; nuclear receptors;
qHTS; Tox21
ID IN-VITRO; ESTROGEN-RECEPTOR; TOXICITY; IDENTIFICATION; DISEASE; HEALTH;
ASSAYS; SUPERFAMILY; ANTAGONISM; EVOLUTION
AB BACKGROUND: The large and increasing number of chemicals released into the environment demands more efficient and cost-effective approaches for assessing environmental chemical toxicity. The U.S. Tox21 program has responded to this challenge by proposing alternative strategies for toxicity testing, among which the quantitative high-throughput screening (qHTS) paradigm has been adopted as the primary tool for generating data from screening large chemical libraries using a wide spectrum of assays.
OBJECTIVES: The goal of this study was to develop methods to evaluate the data generated from these assays to guide future assay selection and prioritization for the Tox21 program.
METHODS: We examined the data from the Tox21 pilot-phase collection of approximately 3,000 environmental chemicals profiled in qHTS format against a panel of 10 human nuclear receptors (AR, ER alpha, FXR, GR, LXR beta, PPAR gamma, PPAR delta, RXR alpha, TR beta, and VDR) for reproducibility, concordance of biological activity profiles with sequence homology of the receptor ligand binding domains, and structure-activity relationships.
RESULTS: We determined the assays to be appropriate in terms of biological relevance. We found better concordance for replicate compounds for the agonist-mode than for the antagonist-mode assays, likely due to interference of cytotoxicity in the latter assays. This exercise also enabled us to formulate data-driven strategies for discriminating true signals from artifacts, and to prioritize assays based on data quality.
CONCLUSIONS: The results demonstrate the feasibility of qHTS to identify the potential for environmentally relevant chemicals to interact with key toxicity pathways related to human disease induction.
C1 [Huang, Ruili; Xia, Menghang; Cho, Ming-Hsuang; Sakamuru, Srilatha; Shinn, Paul; Austin, Christopher P.] NIH, Chem Genom Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Houck, Keith A.; Dix, David J.; Judson, Richard S.; Kavlock, Robert J.] US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
[Witt, Kristine L.; Tice, Raymond R.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
RP Huang, RL (reprint author), NIH, Chem Genom Ctr, Dept Hlth & Human Serv, 9800 Med Ctr Dr, Bethesda, MD 20892 USA.
EM huangru@mail.nih.gov
OI Judson, Richard/0000-0002-2348-9633
FU Intramural Research Programs of the National Toxicology Program;
National Institute of Environmental Health Sciences; U.S. Environmental
Protection Agency; National Human Genome Research Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Programs of the
National Toxicology Program, the National Institute of Environmental
Health Sciences, the U.S. Environmental Protection Agency, and the
National Human Genome Research Institute, National Institutes of Health.
NR 41
TC 69
Z9 70
U1 2
U2 31
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 AUG
PY 2011
VL 119
IS 8
BP 1142
EP 1148
DI 10.1289/ehp.1002952
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 801MU
UT WOS:000293444300033
PM 21543282
ER
PT J
AU Levesque, S
Taetzsch, T
Lull, ME
Kodavanti, U
Stadler, K
Wagner, A
Johnson, JA
Duke, L
Kodavanti, P
Surace, MJ
Block, ML
AF Levesque, Shannon
Taetzsch, Thomas
Lull, Melinda E.
Kodavanti, Urmila
Stadler, Krisztian
Wagner, Alison
Johnson, Jo Anne
Duke, Laura
Kodavanti, Prasada
Surace, Michael J.
Block, Michelle L.
TI Diesel Exhaust Activates and Primes Microglia: Air Pollution,
Neuroinflammation, and Regulation of Dopaminergic Neurotoxicity
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE air pollution; brain; microglia; neuroinflammation; oxidative stress;
Parkinson's disease
ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; BLOOD-BRAIN-BARRIER;
PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; OXIDATIVE STRESS;
GENE-EXPRESSION; NADPH OXIDASE; NEURON LOSS; RAT-BRAIN; PARTICLES
AB BACKGROUND: Air pollution is linked to central nervous system disease, but the mechanisms responsible are poorly understood.
OBJECTIVES: Here, we sought to address the brain-region-specific effects of diesel exhaust (DE) and key cellular mechanisms underlying DE-induced microglia activation, neuroinflammation, and dopaminergic (DA) neurotoxicity.
METHODS: Rats were exposed to DE (2.0, 0.5, and 0 mg/m(3)) by inhalation over 4 weeks or as a single intratracheal administration of DE particles (DEP; 20 mg/kg). Primary neuron-glia cultures and the HAPI (highly aggressively proliferating immortalized) microglial cell line were used to explore cellular mechanisms.
RESULTS: Rats exposed to DE by inhalation demonstrated elevated levels of whole-brain IL-6 (interleukin-6) protein, nitrated proteins, and IBA-1 (ionized calcium-binding adaptor molecule 1) protein (microglial marker), indicating generalized neuro inflammation. Analysis by brain region revealed that DE increased TNF alpha (tumor necrosis factor-alpha), IL-1 beta, IL-6, MIP-1 alpha (macrophage inflammatory protein-1 alpha) RAGE (receptor for advanced glycation end products), fractalkine, and the IBA-1 microglial marker in most regions tested, with the midbrain showing the greatest DE response. Intratracheal administration of DEP increased microglial IBA-1 staining in the substantia nigra and elevated both serum and whole-brain TNF alpha at 6 hr post treatment. Although DEP alone failed to cause the production of cytokines and chemokines, DEP (5 mu g/mL) pretreatment followed by lipopolysaccharide (2.5 ng/mL) in vitro synergistically amplified nitric oxide production, TNF alpha release, and DA neurotoxicity. Pretreatment with fractalkine (50 pg/mL) in vitro ameliorated DEP (50 mu g/mL)-induced microglial hydrogen peroxide production and DA neurotoxicity.
CONCLUSIONS: Together, these findings reveal complex, interacting mechanisms responsible for how air pollution may cause neuroinflammation and DA neurotoxicity.
C1 [Levesque, Shannon; Taetzsch, Thomas; Lull, Melinda E.; Wagner, Alison; Duke, Laura; Surace, Michael J.; Block, Michelle L.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA.
[Kodavanti, Urmila] US EPA, Environm Publ Hlth Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA.
[Stadler, Krisztian] Louisiana State Univ Syst, Oxidat Stress & Dis Lab, Pennington Biomed Res Ctr, Baton Rouge, LA USA.
[Johnson, Jo Anne] Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Kodavanti, Prasada] US EPA, Neurotoxicol Branch, Toxic Assessment Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, Res Triangle Pk, NC 27711 USA.
RP Block, ML (reprint author), Virginia Commonwealth Univ, Dept Anat & Neurobiol, Box 980709, Richmond, VA 23298 USA.
EM MBlock@vcu.edu
FU National Institute of Environmental Health Sciences/National Institutes
of Health [R01ES016591]
FX This research was supported by the National Institute of Environmental
Health Sciences/National Institutes of Health (R01ES016591).
NR 45
TC 75
Z9 75
U1 1
U2 16
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 AUG
PY 2011
VL 119
IS 8
BP 1149
EP 1155
DI 10.1289/ehp.1002986
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 801MU
UT WOS:000293444300034
PM 21561831
ER
PT J
AU Pollack, AZ
Schisterman, EF
Goldman, LR
Mumford, SL
Albert, PS
Jones, RL
Wactawski-Wende, J
AF Pollack, Anna Z.
Schisterman, Enrique F.
Goldman, Lynn R.
Mumford, Sunni L.
Albert, Paul S.
Jones, Robert L.
Wactawski-Wende, Jean
TI Cadmium, Lead, and Mercury in Relation to Reproductive Hormones and
Anovulation in Premenopausal Women
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE anovulation; cadmium; lead; menstrual cycle; mercury; reproductive
hormones
ID MARGINAL STRUCTURAL MODELS; HEAVY-METALS; MENSTRUAL CYCLES;
NATIONAL-HEALTH; BREAST-CANCER; IN-VITRO; ASSOCIATION; EXPOSURE;
ESTROGENICITY; EPIDEMIOLOGY
AB BACKGROUND: Metals can interfere with hormonal functioning by binding at the receptor site and through indirect mechanisms; thus, they may be associated with hormonal changes in premenopausal women.
OBJECTIVES: We examined the associations between cadmium, lead, and mercury, and anovulation and patterns of reproductive hormones [estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone] among 252 premenopausal women 18-44 years of age who were enrolled in the BioCycle Study in Buffalo, New York.
METHODS: Women were followed for up to two menstrual cycles, with serum samples collected up to eight times per cycle. Metal concentrations were determined at baseline in whole blood by inductively coupled mass spectroscopy. Marginal structural models with stabilized inverse probability weights and nonlinear mixed models with harmonic terms were used to estimate the effects of cadmium, lead, and mercury on reproductive hormone levels during the menstrual cycle and anovulation.
RESULTS: Geometric mean (interquartile range) cadmium, lead, and mercury levels were 0.29 (0.19-0.43) mu g/L, 0.93 (0.68-1.20) mu g/dL, and 1.03 (0.58-2.10) mu g/L, respectively. We observed decreases in mean FSH with increasing cadmium [second vs. first tertile: -10.0%; 95% confidence interval (CI), -17.3% to -2.5%; third vs. first tertile: -8.3%; 95% CI, -16.0% to 0.1%] and increases in mean progesterone with increasing lead level (second vs. first tertile: 7.5%; 95% CI, 0.1-15.4%; third vs. first tertile: 6.8%; 95% CI, -0.8% to 14.9%). Metals were not significantly associated with anovulation.
CONCLUSIONS: Our findings support the hypothesis that environmentally relevant levels of metals are associated with modest changes in reproductive hormone levels in healthy, premenopausal women.
C1 [Pollack, Anna Z.; Goldman, Lynn R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD USA.
[Jones, Robert L.] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Pollack, Anna Z.; Schisterman, Enrique F.; Mumford, Sunni L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Rockville, MD USA.
RP Schisterman, EF (reprint author), 6100 Execut Blvd 7B03, Rockville, MD 20852 USA.
EM schistee@mail.nih.gov
RI Pollack, Anna/F-2021-2011; Goldman, Lynn/D-5372-2012;
OI Pollack, Anna/0000-0002-4313-3298; Schisterman,
Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health; Long-Range Research
Initiative of the American Chemistry Council
FX This research was supported partially by the Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, National Institutes of Health, and by the Long-Range
Research Initiative of the American Chemistry Council.
NR 53
TC 26
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U1 0
U2 17
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD AUG
PY 2011
VL 119
IS 8
BP 1156
EP 1161
DI 10.1289/ehp.1003284
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 801MU
UT WOS:000293444300035
PM 21543284
ER
PT J
AU Gray, K
Lawler, CP
AF Gray, Kimberly
Lawler, Cindy P.
TI Strength in Numbers: Three Separate Studies Link in Utero
Organophosphate Pesticide Exposure and Cognitive Development
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
ID PRENATAL EXPOSURE; CHLORPYRIFOS; CHILDREN
C1 [Lawler, Cindy P.] NIEHS, Cellular Organs & Syst Pathobiol Branch, Div Extramural Res & Training, NIH,Dept Hlth Human Serv, Res Triangle Pk, NC 27709 USA.
RP Gray, K (reprint author), NIEHS, Susceptibil Populat Hlth Branch, Div Extramural Res & Training, NIH,Dept Hlth Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM Gray6@niehs.nih.gov
NR 8
TC 5
Z9 5
U1 0
U2 4
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 AUG
PY 2011
VL 119
IS 8
BP A328
EP A329
DI 10.1289/ehp.1104137
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 801MU
UT WOS:000293444300002
PM 21807587
ER
PT J
AU Balla, T
AF Balla, Tamas
TI Detection and rapid manipulation of phosphoinositides with engineered
molecular tools
SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
LA English
DT Meeting Abstract
CT 8th EBSA European Biophysics Congress
CY AUG 23-27, 2011
CL Budapest, HUNGARY
SP Hungarian Biophys Soc, European Biophys Soc Assoc
C1 [Balla, Tamas] NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0175-7571
J9 EUR BIOPHYS J BIOPHY
JI Eur. Biophys. J. Biophys. Lett.
PD AUG
PY 2011
VL 40
SU 1
BP 36
EP 36
PG 1
WC Biophysics
SC Biophysics
GA 804EO
UT WOS:000293637300005
ER
PT J
AU Nizsaloczki, E
Csomos, I
Mocsar, G
Szaloki, N
Waldmann, TA
Damjanovich, S
Vamosi, G
Bodnar, A
AF Nizsaloczki, E.
Csomos, I.
Mocsar, G.
Szaloki, N.
Waldmann, T. A.
Damjanovich, S.
Vamosi, G.
Bodnar, A.
TI Biophysical investigation of IL-9R assembly and function in human
T-lymphoma cells
SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
LA English
DT Meeting Abstract
CT 8th EBSA European Biophysics Congress
CY AUG 23-27, 2011
CL Budapest, HUNGARY
SP Hungarian Biophys Soc, European Biophys Soc Assoc
C1 [Nizsaloczki, E.; Csomos, I.; Mocsar, G.; Szaloki, N.; Damjanovich, S.; Vamosi, G.; Bodnar, A.] Univ Debrecen, HAS UD Cell Biol & Signaling Res Grp, Dept Biophys & Cell Biol, H-4012 Debrecen, Hungary.
[Waldmann, T. A.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0175-7571
EI 1432-1017
J9 EUR BIOPHYS J BIOPHY
JI Eur. Biophys. J. Biophys. Lett.
PD AUG
PY 2011
VL 40
SU 1
BP 73
EP 73
PG 1
WC Biophysics
SC Biophysics
GA 804EO
UT WOS:000293637300127
ER
PT J
AU Sebestyen, V
Nagy, E
Mocsar, G
Papp, F
Hajdu, P
Panyi, G
Toth, K
Waldmann, TA
Damjanovich, S
Bodnar, A
Vamosi, G
AF Sebestyen, V.
Nagy, E.
Mocsar, G.
Papp, F.
Hajdu, P.
Panyi, G.
Toth, K.
Waldmann, T. A.
Damjanovich, S.
Bodnar, A.
Vamosi, G.
TI Membrane potential influences mobility, interactions and signaling of
interleukin-2 and-15 receptors in T cells
SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
LA English
DT Meeting Abstract
CT 8th EBSA European Biophysics Congress
CY AUG 23-27, 2011
CL Budapest, HUNGARY
SP Hungarian Biophys Soc, European Biophys Soc Assoc
C1 [Sebestyen, V.; Nagy, E.; Mocsar, G.; Papp, F.; Damjanovich, S.; Bodnar, A.; Vamosi, G.] Hungarian Acad Sci, Cell Biol & Signaling Res Grp, Budapest, Hungary.
[Hajdu, P.; Panyi, G.] Univ Debrecen, Med & Hlth Sci Ctr, Dept Biophys & Cell Biol, Debrecen, Hungary.
[Toth, K.] German Canc Res Ctr, Div Biophys Macromol, D-6900 Heidelberg, Germany.
[Waldmann, T. A.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM even@mailbox.hu
NR 0
TC 0
Z9 0
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0175-7571
J9 EUR BIOPHYS J BIOPHY
JI Eur. Biophys. J. Biophys. Lett.
PD AUG
PY 2011
VL 40
SU 1
BP 86
EP 86
PG 1
WC Biophysics
SC Biophysics
GA 804EO
UT WOS:000293637300171
ER
PT J
AU Volko, J
Mocsar, G
Menczel, E
Nagy, P
Toth, K
Waldmann, TA
Damjanovich, S
Bodnar, A
Vamosi, G
AF Volko, J.
Mocsar, G.
Menczel, E.
Nagy, P.
Toth, K.
Waldmann, T. A.
Damjanovich, S.
Bodnar, A.
Vamosi, G.
TI MHC I organizes protein clusters and inhibits IL-2/IL-15 signaling in
human T cells
SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
LA English
DT Meeting Abstract
CT 8th EBSA European Biophysics Congress
CY AUG 23-27, 2011
CL Budapest, HUNGARY
SP Hungarian Biophys Soc, European Biophys Soc Assoc
C1 [Volko, J.; Mocsar, G.; Menczel, E.; Damjanovich, S.; Bodnar, A.; Vamosi, G.] Hung Acad Sci, Cell Biol & Signaling Res Grp, Budapest, Hungary.
[Nagy, P.] Univ Debrecen, Med & Hlth Sci Ctr, Dept Biophys & Cell Biol, Debrecen, Hungary.
[Toth, K.] DKFZ, Div Biophys Macromol, Heidelberg, Germany.
[Waldmann, T. A.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0175-7571
J9 EUR BIOPHYS J BIOPHY
JI Eur. Biophys. J. Biophys. Lett.
PD AUG
PY 2011
VL 40
SU 1
BP 86
EP 86
PG 1
WC Biophysics
SC Biophysics
GA 804EO
UT WOS:000293637300172
ER
PT J
AU Konig, G
Wu, XW
Brooks, B
AF Koenig, Gerhard
Wu, Xiongwu
Brooks, Bernard
TI Crossing energy barriers with self-guided Langevin dynamics
SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
LA English
DT Meeting Abstract
CT 8th EBSA European Biophysics Congress
CY AUG 23-27, 2011
CL Budapest, HUNGARY
SP Hungarian Biophys Soc, European Biophys Soc Assoc
C1 [Koenig, Gerhard; Wu, Xiongwu; Brooks, Bernard] NHLBI, NIH, Lab Computat Biol, Rockville, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0175-7571
J9 EUR BIOPHYS J BIOPHY
JI Eur. Biophys. J. Biophys. Lett.
PD AUG
PY 2011
VL 40
SU 1
BP 108
EP 109
PG 2
WC Biophysics
SC Biophysics
GA 804EO
UT WOS:000293637300245
ER
PT J
AU Milac, AL
Anishkin, A
Fatakia, SN
Chow, CC
Sukharev, S
Guy, HR
AF Milac, Adina L.
Anishkin, Andriy
Fatakia, Sarosh N.
Chow, Carson C.
Sukharev, Sergei
Guy, H. Robert
TI Symmetry constraints improve accuracy of ion channels models.
Application to two-pore-domain channels
SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
LA English
DT Meeting Abstract
CT 8th EBSA European Biophysics Congress
CY AUG 23-27, 2011
CL Budapest, HUNGARY
SP Hungarian Biophys Soc, European Biophys Soc Assoc
C1 [Milac, Adina L.] Acad Romana, Inst Biochem, Bucharest 060031 17, Romania.
[Milac, Adina L.; Guy, H. Robert] NCI, NIH, Bethesda, MD 20892 USA.
[Anishkin, Andriy; Sukharev, Sergei] Univ Maryland, College Pk, MD 20742 USA.
[Fatakia, Sarosh N.; Chow, Carson C.] NIDDK, NIH, Bethesda, MD 20892 USA.
RI Chow, Carson/A-7970-2009; Milac, Adina/C-1070-2011
OI Milac, Adina/0000-0003-1845-4281
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0175-7571
J9 EUR BIOPHYS J BIOPHY
JI Eur. Biophys. J. Biophys. Lett.
PD AUG
PY 2011
VL 40
SU 1
BP 113
EP 113
PG 1
WC Biophysics
SC Biophysics
GA 804EO
UT WOS:000293637300260
ER
PT J
AU Cortini, R
Kornyshev, AA
Lee, DJ
Leikin, S
AF Cortini, R.
Kornyshev, A. A.
Lee, D. J.
Leikin, S.
TI Helix specific electrostatic effects in DNA braiding and supercoiling
SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
LA English
DT Meeting Abstract
CT 8th EBSA European Biophysics Congress
CY AUG 23-27, 2011
CL Budapest, HUNGARY
SP Hungarian Biophys Soc, European Biophys Soc Assoc
C1 [Cortini, R.; Kornyshev, A. A.; Lee, D. J.] Univ London Imperial Coll Sci Technol & Med, Dept Chem, London SW7 2AZ, England.
[Leikin, S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0175-7571
J9 EUR BIOPHYS J BIOPHY
JI Eur. Biophys. J. Biophys. Lett.
PD AUG
PY 2011
VL 40
SU 1
BP 219
EP 219
PG 1
WC Biophysics
SC Biophysics
GA 804EO
UT WOS:000293637300618
ER
PT J
AU Huang, SW
Kiang, D
Smith, DJ
Wang, JR
AF Huang, Sheng-Wen
Kiang, David
Smith, Derek J.
Wang, Jen-Ren
TI Evolution of re-emergent virus and its impact on enterovirus 71
epidemics
SO EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Review
DE enterovirus 71; epidemiology; phylogenetic analysis; evolution;
recombination; antigenicity
ID POLIOMYELITIS-LIKE DISEASE; CENTRAL-NERVOUS-SYSTEM; MOUTH-DISEASE;
MOLECULAR EPIDEMIOLOGY; GENETIC-ANALYSIS; VIRAL REPLICATION;
WESTERN-AUSTRALIA; NATURAL-SELECTION; PACIFIC REGION; VP1 REGION
AB Enterovirus 71 (EV71), a member of the Enterovirus genus in the Picornaviridae family, has become an emergent infectious disease worldwide, most notably in Asia. As a neurotropic virus, EV71 infection occasionally causes neurological diseases with pulmonary edema, which is fatal for children. In this review, we examine the epidemiology of EV71, with three waves of increased EV71 activity since the 1970s and discuss the genotypic changes in phylogeny between the outbreaks or epidemics. Genetic changes including mutations and recombinations as well as the diversity of antigenic properties among EV71 strains in various outbreaks are described. Furthermore, the impact of genetic changes on viral pathogenesis and vaccine candidate selection are addressed. In conclusion, these genetic and antigenic investigations of EV71 evolution have provided us with new insight into the trend of EV71 epidemiology, which may contribute to a better understanding of the viral pathogenesis and vaccine development.
C1 [Wang, Jen-Ren] Natl Cheng Kung Univ, Dept Med Lab Sci & Biotechnol, Tainan 701, Taiwan.
[Huang, Sheng-Wen; Wang, Jen-Ren] Natl Cheng Kung Univ, Inst Basic Med Sci, Tainan 701, Taiwan.
[Kiang, David] Calif Dept Publ Hlth, Microbiol Sect, Food & Drug Lab Branch, Richmond, CA 94804 USA.
[Smith, Derek J.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
[Smith, Derek J.] Erasmus MC, Dept Virol, NL-3015 GE Rotterdam, Netherlands.
[Smith, Derek J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Wang, Jen-Ren] Natl Hlth Res Inst, Div Infect Dis, Tainan 701, Taiwan.
RP Wang, JR (reprint author), Natl Cheng Kung Univ, Dept Med Lab Sci & Biotechnol, 1 Univ Rd, Tainan 701, Taiwan.
EM jrwang@mail.ncku.edu.tw
RI Wang, Ren-Jen/F-5254-2011; Huang, Sheng Wen/H-6338-2013;
OI Wang, Jen-Ren/0000-0002-4127-4046
FU National Health Research Institutes, Taiwan [NHRI-ID-099-PP-13,
NHRI-ID-100-PP-12]; National Science Council, Taiwan [NSC
97-3112-B-006-006, NSC 98-3112-B-006-006, NSC 99-3112-B-006-006];
Department of Health, Taiwan Centers for Disease Control [CB097135]
FX The authors thank Dr Bruce Thorley for his comments about the
manuscript. The authors also acknowledge financial support from National
Health Research Institutes, Taiwan (NHRI-ID-099-PP-13 and
NHRI-ID-100-PP-12); National Science Council, Taiwan (NSC
97-3112-B-006-006, NSC 98-3112-B-006-006 and NSC 99-3112-B-006-006); and
the Department of Health, Taiwan Centers for Disease Control (CB097135).
NR 79
TC 27
Z9 32
U1 2
U2 8
PU SOC EXPERIMENTAL BIOLOGY MEDICINE
PI MAYWOOD
PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA
SN 1535-3702
J9 EXP BIOL MED
JI Exp. Biol. Med.
PD AUG
PY 2011
VL 236
IS 8
BP 899
EP 908
DI 10.1258/ebm.2010.010233
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 807EK
UT WOS:000293877200002
PM 21715436
ER
PT J
AU Houzet, L
Jeang, KT
AF Houzet, Laurent
Jeang, Kuan-Teh
TI Genome-wide screening using RNA interference to study host factors in
viral replication and pathogenesis
SO EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Review
DE siRNA; shRNA; HIV; genome-wide screening; virus replication
ID IMMUNODEFICIENCY-VIRUS TYPE-1; DOUBLE-STRANDED-RNA; INFLUENZA-A VIRUS;
WEST-NILE-VIRUS; JURKAT T-CELLS; HIV-1 REPLICATION; CELLULAR MICRORNA;
CAENORHABDITIS-ELEGANS; SILENCING SUPPRESSOR; MAMMALIAN-CELLS
AB With the recent development of short interfering RNA and short hairpin RNA expression libraries, RNA interference (RNAi) technology has been extensively employed to identify genes involved in diverse cellular processes, such as signal transduction, cell cycle, cancer biology and host-pathogen interactions. In the field of viral infection, this approach has already identified hundreds of new genes not previously known to be important for various virus lifecycles. In this brief review, we focus on recent studies performed using genome-wide RNAi-based screens in mammalian cells for the identification of essential host factors for viral infection and pathogenesis.
C1 [Houzet, Laurent; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kj7e@nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU National Institute of Allergy and Infectious Diseases; office of the
Director, NIH
FX Work in K-TJ's laboratory is supported by intramural funds from the
National Institute of Allergy and Infectious Diseases and by funds from
the Intramural AIDS Targeted Antiviral Program (IATAP) from the office
of the Director, NIH.
NR 50
TC 17
Z9 17
U1 0
U2 10
PU SOC EXPERIMENTAL BIOLOGY MEDICINE
PI MAYWOOD
PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA
SN 1535-3702
J9 EXP BIOL MED
JI Exp. Biol. Med.
PD AUG
PY 2011
VL 236
IS 8
BP 962
EP 967
DI 10.1258/ebm.2010.010272
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 807EK
UT WOS:000293877200009
PM 21727185
ER
PT J
AU Laiyemo, AO
Doubeni, C
Sanderson, AK
Pinsky, PF
Badurdeen, DS
Doria-Rose, VP
Marcus, PM
Schoen, RE
Lanza, E
Schatzkin, A
Cross, AJ
AF Laiyemo, Adeyinka O.
Doubeni, Chyke
Sanderson, Andrew K., II
Pinsky, Paul F.
Badurdeen, Dilhana S.
Doria-Rose, V. Paul
Marcus, Pamela M.
Schoen, Robert E.
Lanza, Elaine
Schatzkin, Arthur
Cross, Amanda J.
TI Likelihood of missed and recurrent adenomas in the proximal versus the
distal colon
SO GASTROINTESTINAL ENDOSCOPY
LA English
DT Article
ID METACHRONOUS COLORECTAL ADENOMAS; SCREENING SIGMOIDOSCOPY; NEGATIVE
COLONOSCOPY; CANCER PREVENTION; MORTALITY; RISK; TRIAL; ASSOCIATION;
POLYPECTOMY; MULTICENTER
AB Background: Colonoscopy may be less efficacious in reducing colorectal cancer mortality in the proximal compared with the distal colon. A greater likelihood for missed and recurrent adenomas in the proximal colon may contribute to this phenomenon.
Objective: To examine whether a proximal adenoma is associated with the risk and location of missed and recurrent adenomas.
Design: Prospective.
Setting: Polyp Prevention Trial.
Participants: A total of 1864 patients with an adenoma at baseline underwent a follow-up colonoscopy 4 years later (adenoma recurrence). Of these, 1731 underwent a clearing colonoscopy 1 year after the baseline examination (missed adenoma).
Main Outcome Measurements: Association of baseline adenoma location with the risk and location of adenomas found at colonoscopy performed 1 year and 4 years later.
Results: At the year 1 colonoscopy, 598 patients (34.6%) had an adenoma (missed adenoma). Compared with those with a distal-only adenoma at baseline, patients with a proximal-only adenoma at baseline were more likely to have any missed adenomas (relative risk [RR] 1.28; 95% CI, 1.09-1.49) and a proximal-only missed adenoma (RR 2.05; 95% CI, 1.49-2.80). At the year 4 colonoscopy, 733 patients (39.3%) had adenoma recurrence. Patients with a baseline proximal-only adenoma were more likely to have any adenoma recurrence (RR 1.14; 95% CI, 1.00-1.31) and a proximal-only adenoma recurrence (RR 1.52; 95% CI, 1.15-2.02). Sensitivity analyses involving missed adenomas did not materially affect the risk or location of recurrent adenomas at year 4 colonoscopy.
Limitation: Lesions may still be missed on repeated colonoscopies.
Conclusions: Missed and recurrent adenomas are more likely to be in the proximal colon. (Gastrointest Endosc 2011;74:253-61.)
C1 [Laiyemo, Adeyinka O.] Howard Univ, Coll Med, Div Gastroenterol, Dept Med, Washington, DC 20060 USA.
[Laiyemo, Adeyinka O.; Marcus, Pamela M.] NCI, Biometry Res Grp, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Pinsky, Paul F.] NCI, Early Detect Res Grp, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Doria-Rose, V. Paul] NCI, Canc Prevent Div, Hlth Serv & Econ Branch, Div Canc Epidemiol & Genet,NIH, Bethesda, MD 20892 USA.
[Lanza, Elaine] NCI, Div Canc Control & Populat Sci, Lab Canc Prevent, Div Canc Epidemiol & Genet,NIH, Bethesda, MD 20892 USA.
[Schatzkin, Arthur; Cross, Amanda J.] NCI, Ctr Canc Res, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet,NIH, Bethesda, MD 20892 USA.
[Doubeni, Chyke] Univ Massachusetts, Dept Family Med, Worcester, MA 01605 USA.
[Schoen, Robert E.] Univ Pittsburgh, Dept Med & Epidemiol, Pittsburgh, PA USA.
RP Laiyemo, AO (reprint author), Howard Univ, Coll Med, Div Gastroenterol, Dept Med, 2041 Georgia Ave NW, Washington, DC 20060 USA.
EM adeyinka.laiyemo@howard.edu
OI Doria-Rose, Vincent/0000-0002-8802-5143; Doubeni,
Chyke/0000-0001-7495-0285
FU National Cancer Institute [5U54CA091431-09 S1, 5K01CA127118-03];
National Cancer Institute, National Institutes of Health
FX The following authors disclosed financial relationships relevant to this
publication: Dr. Laiyemo is supported by the National Cancer Institute's
new faculty recruitment supplement to the Comprehensive Minority
Institution/Cancer Center Partnership between Howard University Cancer
Center and Sidney Kimmel Comprehensive Cancer Center of Johns Hopkins
University (5U54CA091431-09 S1). Dr. Doubeni is supported by a mentored
career development award (5K01CA127118-03) from the National Cancer
Institute. This research was funded by the Intramural Research Program
of the National Cancer Institute, National Institutes of Health. The
other authors disclosed no financial relationships relevant to this
publication.
NR 34
TC 20
Z9 21
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0016-5107
J9 GASTROINTEST ENDOSC
JI Gastrointest. Endosc.
PD AUG
PY 2011
VL 74
IS 2
BP 253
EP 261
DI 10.1016/j.gie.2011.02.023
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 808DB
UT WOS:000293954600003
PM 21549375
ER
PT J
AU Cecchini, S
Virag, T
Kotin, RM
AF Cecchini, Sylvain
Virag, Tamas
Kotin, Robert M.
TI Reproducible High Yields of Recombinant Adeno-Associated Virus Produced
Using Invertebrate Cells in 0.02-to 200-Liter Cultures
SO HUMAN GENE THERAPY
LA English
DT Article
ID LARGE-SCALE PRODUCTION; GENE-TRANSFER; INSECT CELLS; CONGENITAL
AMAUROSIS; BACULOVIRUS; VECTORS; STABILITY; SYSTEM; STOCKS; RAAV
AB The large amounts of recombinant adeno-associated virus (rAAV) vector needed for clinical trials and eventual commercialization require robust, economical, reproducible, and scalable production processes compatible with current good manufacturing practice. rAAV produced using baculovirus and insect cells satisfies these conditions; however, recovering rAAV particles from 200-liter bioreactors is more complicated than bench-scale vector preparations. Using a variety of processing media, we developed a reliable and routine downstream procedure for rAAV production that is scalable from 0.02- to 200-liter cultures. To facilitate the upstream process, we adapted the titerless infected-cell preservation and scale-up process for rAAV production. Single-use aliquots of cryopreserved baculovirus-infected insect cells (BIIC) are thawed and added to the suspension culture to achieve the desired ratio of BIIC to rAAV-producer cells. By using conditions established with small-scale cultures, rAAV was produced in larger volume cultures. Strikingly consistent rAAV yields were attained in cultures ranging from 10 liters to 200 liters. Based on the final yield, each cell produced 18,000 +/- 6,800 particles of purified rAAV in 10-, 20-, 100-, and 200-liter cultures. Thus, with an average cell density of 4.32 +/- 10(6) cells/ml, >= 10(16) purified rAAV particles are produced from 100 to 200 liters. The downstream process resulted in about 20% recovery estimated from comparing the quantities of capsid protein antigen in the crude bioreactor material and in the final, purified product. The ease and reproducibility of rAAV production in 200-liter bioreactors suggest that the limit has not been reached, and 500-liter productions are planned.
C1 [Cecchini, Sylvain; Virag, Tamas; Kotin, Robert M.] NHLBI, Lab Mol Virol & Gene Therapy, NIH, Bethesda, MD 20892 USA.
RP Kotin, RM (reprint author), NHLBI, Lab Mol Virol & Gene Therapy, NIH, Bldg 10,Room 7D05, Bethesda, MD 20892 USA.
EM kotinr@nhlbi.nih.gov
FU Division of Intramural Research of the National Heart, Lung, and Blood
Institute [National Institutes of Health (NIH)]; International
Collaborative Effort (ICE) for Duchenne Muscular Dystrophy; Association
Monogasque contre les Myopathies
FX Funding was provided by the Division of Intramural Research of the
National Heart, Lung, and Blood Institute [National Institutes of Health
(NIH)]. Additional funding was provided by the International
Collaborative Effort (ICE) for Duchenne Muscular Dystrophy comprised of
the French Duchenne Parent Project and the Association Monogasque contre
les Myopathies. This research was conducted under a cooperative research
and development agreement (CRADA) with Amsterdam Molecular Therapy. The
authors are grateful to Richard H. Smith, Alejandro Negrete, and Lina Li
for their assistance and insights related to this work. Thomas Wallach
performed preliminary TIPS experiments, and Linda Yang and Yu Yang
provided important technical support.
NR 15
TC 27
Z9 27
U1 1
U2 5
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD AUG
PY 2011
VL 22
IS 8
BP 1021
EP 1030
DI 10.1089/hum.2010.250
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 810GZ
UT WOS:000294115100013
PM 21381980
ER
PT J
AU Shah, MR
Califf, RM
Nohria, A
Bhapkar, M
Bowers, M
Mancini, DM
Fluzat, M
Stevenson, LW
O'Connor, CM
AF Shah, Monica R.
Califf, Robert M.
Nohria, Anju
Bhapkar, Manju
Bowers, Margaret
Mancini, Donna M.
Fluzat, Mona
Stevenson, Lynne W.
O'Connor, Christopher M.
TI The STARBRITE Trial: A Randomized, Pilot Study of B-Type Natriuretic
Peptide-Guided Therapy in Patients With Advanced Heart Failure
SO JOURNAL OF CARDIAC FAILURE
LA English
DT Article
DE BNP-guided therapy; diuretics; heart failure disease management; heart
failure
ID QUALITY-OF-CARE; EMERGENCY-DEPARTMENT; ESCAPE TRIAL; MORTALITY;
MANAGEMENT; DIURETICS; POPULATION; MORBIDITY; DIAGNOSIS; OUTCOMES
AB Background: STARBRITE, a multicenter randomized pilot trial, tested whether outpatient diuretic management guided by B-type natriuretic peptide (BNP) and clinical assessment resulted in more days alive and not hospitalized over 90 days compared with clinical assessment alone.
Methods and Results: A total of 130 patients from 3 sites with left ventricular ejection fraction <= 35% were enrolled during hospitalization for heart failure (HF) and randomly assigned to therapy guided by BNP and clinical assessment (BNP strategy) or clinical assessment alone. The clinical goal was resolution of congestion without hypotension or renal dysfunction. In the BNP arm, therapy was adjusted to achieve optimal fluid status, defined as the BNP level and congestion score obtained at the time of discharge. In the clinical assessment arm, therapy was titrated to achieve optimal fluid status, represented by the patient's signs and symptoms at the time of discharge. Exclusion criteria were serum creatinine >3.5 mg/dL and acute coronary syndrome. Follow-up was done in HF clinics. BNP was measured with the use of a rapid assay test. There was no significant difference in number of days alive and not hospitalized (hazard ratio 0.72, 95% confidence interval 0.41-1.27; P = .25), change in serum creatinine, or change in systolic blood pressure (SBP). BNP strategy was associated with a trend toward a lower blood urea nitrogen (24 mg/dL vs 29 mg/dL; P = .07); BNP strategy patients received significantly more angiotensin converting enzyme (ACE) inhibitors, beta-blockers, and the combination of ACE inhibitor or angiotensin receptor blocker plus beta-blockers.
Conclusions: BNP strategy was not associated with more days alive and not hospitalized, but the strategy appeared to be safe and was associated with increased use of evidence-based medications. (J Cardiac Fail 2011;17:613-621)
C1 [Califf, Robert M.; Bhapkar, Manju; Bowers, Margaret; Fluzat, Mona; O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA.
[Shah, Monica R.] NHLBI, Bethesda, MD USA.
[Nohria, Anju; Stevenson, Lynne W.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Mancini, Donna M.] Columbia Univ, Med Ctr, New York, NY USA.
RP O'Connor, CM (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, DUMC Box 3356, Durham, NC 27710 USA.
EM oconn002@mc.duke.edu
FU American Heart Association; ACC/Merck Foundation; Duke Clinical Research
Institute; Roche Diagnostics
FX Funding: American Heart Association National Scientist Development
Award, ACC/Merck Foundation Career Development Award, and the Duke
Clinical Research Institute Faculty Development Award. Biosite
Diagnostics provided BNP meters and assays.; Dr. Mancini: consulting
fees for Celladon Corporation and Acorn. Dr. O'Connor and Fiuzat:
research funding from Roche Diagnostics.
NR 33
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U1 1
U2 4
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 1071-9164
J9 J CARD FAIL
JI J. Card. Fail.
PD AUG
PY 2011
VL 17
IS 8
BP 613
EP 621
DI 10.1016/j.cardfail.2011.04.012
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 807YJ
UT WOS:000293938600001
PM 21807321
ER
PT J
AU Ahmet, I
Lakatta, EG
Talan, MI
AF Ahmet, Ismayil
Lakatta, Edward G.
Talan, Mark I.
TI Therapeutic Window for Cardioprotection by Recombinant Human
Erythropoietin (rhEPO) in the Rat Model of Ischemia-Reperfusion:
Implications for Clinical Trial Design
SO JOURNAL OF CARDIAC FAILURE
LA English
DT Meeting Abstract
C1 [Ahmet, Ismayil; Lakatta, Edward G.; Talan, Mark I.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
NR 0
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U1 0
U2 4
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 1071-9164
J9 J CARD FAIL
JI J. Card. Fail.
PD AUG
PY 2011
VL 17
IS 8
SU 1
BP S63
EP S63
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 807YK
UT WOS:000293938700201
ER
PT J
AU Bhasin, S
Pencina, M
Jasuja, GK
Travison, TG
Coviello, A
Orwoll, E
Wang, PY
Nielson, C
Wu, F
Tajar, A
Labrie, F
Vesper, H
Zhang, AQ
Ulloor, J
Singh, R
D'Agostino, R
Vasan, RS
AF Bhasin, Shalender
Pencina, Michael
Jasuja, Guneet Kaur
Travison, Thomas G.
Coviello, Andrea
Orwoll, Eric
Wang, Patty Y.
Nielson, Carrie
Wu, Frederick
Tajar, Abdelouahid
Labrie, Fernand
Vesper, Hubert
Zhang, Anqi
Ulloor, Jagadish
Singh, Ravinder
D'Agostino, Ralph
Vasan, Ramachandran S.
TI Reference Ranges for Testosterone in Men Generated Using Liquid
Chromatography Tandem Mass Spectrometry in a Community-Based Sample of
Healthy Nonobese Young Men in the Framingham Heart Study and Applied to
Three Geographically Distinct Cohorts
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID HORMONE-BINDING GLOBULIN; SYMPTOMATIC ANDROGEN DEFICIENCY; ENDOGENOUS
SEX-HORMONES; MIDDLE-AGED MEN; OLDER MEN; SERUM TESTOSTERONE; PHYSICAL
PERFORMANCE; ADULT MEN; STANDARDIZATION PROGRAM; REFERENCE INTERVALS
AB Context: Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men.
Methods: TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study.
Results: In a reference sample of 456 men, mean (SD), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes.
Conclusion: Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials. (J Clin Endocrinol Metab 96: 2430-2439, 2011)
C1 [Bhasin, Shalender; Travison, Thomas G.; Coviello, Andrea; Zhang, Anqi; Ulloor, Jagadish] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Preventat Med & Cardiol, Boston, MA 02118 USA.
[Pencina, Michael; Travison, Thomas G.; D'Agostino, Ralph] Boston Univ, Dept Biostat, Boston, MA 02118 USA.
[Pencina, Michael; Jasuja, Guneet Kaur] Boston Univ, Dept Math, Stat & Consulting Unit, Boston, MA 02215 USA.
[Pencina, Michael; Jasuja, Guneet Kaur; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01701 USA.
[Orwoll, Eric; Wang, Patty Y.; Nielson, Carrie] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
[Wu, Frederick] Univ Manchester, Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Androl Res Unit,Dev & Regenerat Biomed Res Grp, Manchester M13 9WL, Lancs, England.
[Tajar, Abdelouahid] Univ Manchester, Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Arthrit Res UK,Epidemiol Unit, Manchester M13 9WL, Lancs, England.
[Labrie, Fernand] Univ Laval, Quebec City, PQ G1K 7P4, Canada.
[Vesper, Hubert] Ctr Dis Control & Prevent, Atlanta, GA 30329 USA.
[Singh, Ravinder] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA.
RP Bhasin, S (reprint author), Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, 650 Albany St, Boston, MA 02118 USA.
EM bhasin@bu.edu
OI Orwoll, Eric/0000-0002-8520-7355; Ramachandran,
Vasan/0000-0001-7357-5970
FU National Institutes of Health (NIH) [1RO1AG31206]; National Institute on
Aging (NIA) [5P30AG031679]; CDC Foundation; National Heart, Lung, and
Blood Institute's Framingham Heart Study [N01-HC-25195]; Commission of
the European Community [QLK6-CT-2001-00258]; National Institute of
Arthritis and Musculoskeletal and Skin Diseases; National Center for
Research Resources; NIH Roadmap for Medical Research [U01 AR45580, U01
AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01
AG18197, U01-AG027810, UL1 RR024140]
FX This work was supported by primarily by National Institutes of Health
(NIH) Grant 1RO1AG31206 to S.B. and R.S.V. Additional support was
provided by the Boston Claude D. Pepper Older Americans Independence
Center Grant 5P30AG031679 from the National Institute on Aging (NIA) and
by a grant from the CDC Foundation. The Framingham Heart Study is
supported by the National Heart, Lung, and Blood Institute's Framingham
Heart Study contract N01-HC-25195. The EMAS is funded by the Commission
of the European Communities Fifth Framework Program "Quality of Life and
Management of Living Resources" Grant QLK6-CT-2001-00258. The
Osteoporotic Fractures in Men (MrOS) Study is supported by the National
Institute of Arthritis and Musculoskeletal and Skin Diseases, the NIA,
the National Center for Research Resources, and NIH Roadmap for Medical
Research under the following grant numbers: U01 AR45580, U01 AR45614,
U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197,
U01-AG027810, and UL1 RR024140.
NR 51
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U1 5
U2 16
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 AUG
PY 2011
VL 96
IS 8
BP 2430
EP 2439
DI 10.1210/jc.2010-3012
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 802MT
UT WOS:000293516400043
PM 21697255
ER
PT J
AU Chow, CC
Periwal, V
Csako, G
Ricks, M
Courville, AB
Miller, BV
Vega, GL
Sumner, AE
AF Chow, Carson C.
Periwal, Vipul
Csako, Gyorgy
Ricks, Madia
Courville, Amber B.
Miller, Bernard V., III
Vega, Gloria L.
Sumner, Anne E.
TI Higher Acute Insulin Response to Glucose May Determine Greater Free
Fatty Acid Clearance in African-American Women
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID VISCERAL ADIPOSE-TISSUE; BETA-CELL FUNCTION; LIPOPROTEIN-LIPASE;
ETHNIC-DIFFERENCES; TRIGLYCERIDE LEVELS; US POPULATION; IN-VIVO;
RESISTANCE; PLASMA; LIPOLYSIS
AB Context: Obesity and diabetes are more common in African-Americans than whites. Because free fatty acids (FFA) participate in the development of these conditions, studying race differences in the regulation of FFA and glucose by insulin is essential.
Objective: The objective of the study was to determine whether race differences exist in glucose and FFA response to insulin.
Design: This was a cross-sectional study.
Setting: The study was conducted at a clinical research center.
Participants: Thirty-four premenopausal women (17 African-Americans, 17 whites) matched for age [36 +/- 10 yr (mean +/- SD)] and body mass index (30.0 +/- 6.7 kg/m(2)).
Interventions: Insulin-modified frequently sampled iv glucose tolerance tests were performed with data analyzed by separate minimal models for glucose and FFA.
Main Outcome Measures: Glucose measures were insulin sensitivity index (S-I) and acute insulin response to glucose (AIRg). FFA measures were FFA clearance rate (c(f)).
Results: Body mass index was similar but fat mass was higher in African-Americans than whites (P < 0.01). Compared with whites, African-Americans had lower S-I (3.71 +/- 1.55 vs. 5.23 +/- 2.74 [x 10(-4) min(-1)/(microunits per milliliter)] (P = 0.05) and higher AIRg (642 +/- 379 vs. 263 +/- 206 mU/liter(-1).min, P < 0.01). Adjusting for fat mass, African-Americans had higher FFA clearance, c(f) (0.13 +/- 0.06 vs. 0.08 +/- 0.05 min(-1), P < 0.01). After adjusting for AIRg, the race difference in c(f) was no longer present (P = 0.51). For all women, the relationship between cf and AIRg was significant (r = 0.64, P < 0.01), but the relationship between c(f) and S-I was not (r = -0.07, P = 0.71). The same pattern persisted when the two groups were studied separately.
Conclusion: African-American women were more insulin resistant than white women, yet they had greater FFA clearance. Acutely higher insulin concentrations in African-American women accounted for higher FFA clearance. (J Clin Endocrinol Metab 96: 2456-2463, 2011)
C1 [Ricks, Madia; Miller, Bernard V., III; Sumner, Anne E.] Natl Inst Diabet & Digest & Kidney Dis, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
[Chow, Carson C.; Periwal, Vipul] Natl Inst Diabet & Digest & Kidney Dis, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Csako, Gyorgy] Natl Inst Diabet & Digest & Kidney Dis, Dept Lab Med, NIH, Bethesda, MD 20892 USA.
[Courville, Amber B.] Natl Inst Diabet & Digest & Kidney Dis, Dept Nutr, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Vega, Gloria L.] Univ Texas SW Med Ctr Dallas, Ctr Human Nutr, Dallas, TX 75235 USA.
RP Sumner, AE (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Clin Endocrinol Branch, NIH, Bldg 10-CRC,Room 6-5940,MSC 1612, Bethesda, MD 20892 USA.
EM annes@intra.niddk.nih.gov
RI Chow, Carson/A-7970-2009; Periwal, Vipul/I-1728-2012
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institutes of Health Clinical Center; Moss Heart Foundation;
D.W. Reynolds Foundation; Veterans Administration
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases (to
C.C.C., V.P., M.R., B.V.M., and A.E.S.) and the National Institutes of
Health Clinical Center (to G.C.). The Moss Heart Foundation, D.W.
Reynolds Foundation, and Veterans Administration provided support ( to
G.L V.).
NR 35
TC 14
Z9 16
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD AUG
PY 2011
VL 96
IS 8
BP 2456
EP 2463
DI 10.1210/jc.2011-0532
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 802MT
UT WOS:000293516400046
PM 21593106
ER
PT J
AU Heiss, JD
Taha, S
Oldfield, EH
Ram, Z
AF Heiss, John D.
Taha, Sara
Oldfield, Edward H.
Ram, Zvi
TI Intrathecal gene therapy for treatment of leptomeningeal carcinomatosis
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Injections; Intraventricular; Meningeal carcinomatosis; Gene therapy;
Genetic vector; Thymidine kinase; Ganciclovir
ID THYMIDINE KINASE; BREAST-CANCER; MALIGNANT GLIOMAS; METASTASES; BRAIN;
GANCICLOVIR; ADJUVANT; TUMORS; CELLS
AB Leptomeningeal carcinomatosis occurs occasionally in patients with solid malignancies and carries a poor prognosis despite treatment with systemic chemotherapy and/or radiotherapy. We describe the case of a 43 year old man who presented with leptomeningeal carcinomatosis secondary to malignant melanoma. The patient received intraventricular delivery of NIH3T3 producer cells expressing the thymidine kinase (HSV-Tk1) gene via a retroviral vector followed by intravenous ganciclovir. He experienced abrupt and severe meningeal irritation and hyperpyrexia immediately after injection of the producer cells into the ventricular CSF. Vector producer cells (VPC) survived and were detected by NeoR marker gene expression in the CSF for a week, until a single dose of ganciclovir (GCV) was followed by a decline in the copy number of the NeoR marker gene to undetectable levels over 24 h. This decline upon introduction of ganciclovir suggests effective distribution of ganciclovir to producer cells bearing the HSV-Tk gene. The patient survived 9 months after treatment. Side-effects from the treatment included acute hyperpyrexia which was short-lived and medically manageable.
C1 [Heiss, John D.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20889 USA.
[Taha, Sara] UCL, Sch Med, London W1N 8AA, England.
[Oldfield, Edward H.] Univ Virginia, Dept Neurosurg, Charlottesville, VA USA.
[Ram, Zvi] Tel Aviv Med Ctr & Sch Med, Dana Childrens Hosp, Dept Neurosurg, IL-64239 Tel Aviv, Israel.
RP Heiss, JD (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, 10 Ctr Dr,10-3D20,MSC-1414, Bethesda, MD 20889 USA.
EM heissj@ninds.nih.gov
OI Heiss, John/0000-0002-3890-0165
FU Intramural NIH HHS [Z01 NS002850-06]
NR 24
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U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD AUG
PY 2011
VL 104
IS 1
BP 365
EP 369
DI 10.1007/s11060-010-0458-4
PG 5
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 804IS
UT WOS:000293648100039
PM 21110219
ER
PT J
AU Hart, TL
McClain, JJ
Tudor-Locke, C
AF Hart, Teresa L.
McClain, James J.
Tudor-Locke, Catrine
TI Controlled and Free-Living Evaluation of Objective Measures of Sedentary
and Active Behaviors
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE sitting time; walking; accelerometer; adult
ID PHYSICAL-ACTIVITY; ACTIVITY MONITOR; COMPUTER-SCIENCE; UNITED-STATES;
LIFE-STYLE; ACCELEROMETER; OBESITY; TIME; VALIDITY; RELIABILITY
AB Background: Emerging interest in the health impacts of sedentary behaviors has driven the exploration of objective instrumentation capable of capturing these behaviors. The purpose was to compare (under laboratory conditions) outputs from ActiGraph (AG), Intelligent Device for Energy Expenditure and Physical Activity (IDEEA), and activPAL Professional (AP) against direct observation (DO) in sedentary, standing, and active behaviors; and assess convergent validity of instrument outputs under free-living conditions. Methods: Participants (13 males/16 females; 28.9 +/- 6.2 years) wore instruments concurrently during laboratory and free-living studies. AG cutpoints of <= 50, <100, and <= 259 counts/minute were used to determine time in sedentary behaviors. Laboratory data were evaluated using mean percent error. Free-living data were analyzed using dependent t tests and RM ANOVA. Results: AP precisely measured all identified DO behaviors under laboratory conditions; IDEEA precisely identified sitting and standing. For the free-living study, there was no difference in sedentary time detected by AP and IDEEA but a significant difference was observed in standing time. No difference was apparent between AP and AG259 in sit/lie/stand or ambulatory activity time. Conclusions: In a laboratory setting, the utility of all instruments to classify activities into behavioral categories was confirmed. This may enhance research on sedentary behaviors and health-related outcomes.
C1 [Hart, Teresa L.] Univ Wisconsin Milwaukee, Dept Human Movement Sci, Milwaukee, WI USA.
[McClain, James J.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Tudor-Locke, Catrine] Pennington Biomed Res Ctr, Walking Behav Lab, Baton Rouge, LA USA.
RP Hart, TL (reprint author), Univ Wisconsin Milwaukee, Dept Human Movement Sci, Milwaukee, WI USA.
NR 24
TC 16
Z9 16
U1 2
U2 11
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD AUG
PY 2011
VL 8
IS 6
BP 848
EP 857
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 808NS
UT WOS:000293986300014
PM 21832301
ER
PT J
AU Inaba, M
White, L
Bell, C
Chen, RD
Petrovitch, H
Launer, L
Abbott, RD
Ross, GW
Masaki, K
AF Inaba, Michiko
White, Lon
Bell, Christina
Chen, Randi
Petrovitch, Helen
Launer, Lenore
Abbott, Robert D.
Ross, G. Webster
Masaki, Kamal
TI White Matter Lesions on Brain Magnetic Resonance Imaging Scan and 5-Year
Cognitive Decline: The Honolulu-Asia Aging Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article; Proceedings Paper
CT Annual Scientific Meeting on the American-Geriatrics-Society
CY MAY 13, 2010
CL Orlando, FL
SP Amer Geriatr Soc
DE white matter lesions; brain magnetic resonance imaging; cognitive
decline; aged; Japanese-American men
ID MIDLIFE BLOOD-PRESSURE; CORONARY HEART-DISEASE; CARDIOVASCULAR HEALTH;
PHYSICAL-ACTIVITY; RISK-FACTORS; MEN; HYPERINTENSITIES; ABNORMALITIES;
DEMENTIA; LEUKOARAIOSIS
AB OBJECTIVES: To study white matter lesions (WMLs) and 5-year cognitive decline in elderly Japanese-American men. DESIGN: Longitudinal cohort study.
SETTING: Population-based study in Honolulu, Hawaii.
PARTICIPANTS: Japanese-American men aged 74 to 95 from the Honolulu-Asia Aging Study (HAAS) who were free of prevalent dementia, underwent a protocol brain MRI scan at the fifth HAAS examination (1994-1996), and returned for cognitive testing 5 years later (N = 267).
MEASUREMENTS: WMLs were dichotomized as present (grade 3-9, 38.2%) or absent (grade 1-2, 61.8%). Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI), and 5-year cognitive decline was defined as a drop in CASI score of 12 points or more (1 standard deviation).
RESULTS: Men with WMLs on MRI at baseline were significantly more likely to experience cognitive decline at 5 years than those without (22.4% vs 34.4%, P = .03). Using multiple logistic regression, adjusting for age, education, apolipoprotein (Apo) E4 allele, large or small infarcts on MRI, baseline CASI score, and hypertension, those with WMLs were significantly more likely to develop 5-year cognitive decline (odds ratio = 2.00, 95% confidence interval = 1.10-3.65, P = .02). This association was stronger in men who were cognitively intact and free of the ApoE4 genotype and clinical stroke at baseline.
CONCLUSION: Presence of WMLs on MRI was significantly associated with higher odds of 5-year cognitive decline in older Japanese-American men. Presence of WMLs may help identify people at risk for developing dementia, who may benefit from early intervention. J Am Geriatr Soc 59:1484-1489, 2011.
C1 [Inaba, Michiko; White, Lon; Bell, Christina; Petrovitch, Helen; Abbott, Robert D.; Ross, G. Webster; Masaki, Kamal] Univ Hawaii, John A Burns Sch Med, John A Hartford Ctr Excellence Geriatr, Dept Geriatr Med, Honolulu, HI 96817 USA.
[White, Lon; Chen, Randi; Petrovitch, Helen; Masaki, Kamal] Kuakini Med Ctr, Honolulu, HI USA.
[Bell, Christina; Petrovitch, Helen; Ross, G. Webster] Pacific Hlth Res & Educ Inst, Honolulu, HI USA.
[Petrovitch, Helen; Ross, G. Webster] Vet Affairs Pacific Islands Hlth Care Syst, Honolulu, HI USA.
[Launer, Lenore] NIA, Bethesda, MD 20892 USA.
[Abbott, Robert D.] Radiat Effects Res Fdn, Hiroshima, Japan.
RP Inaba, M (reprint author), Univ Hawaii, John A Burns Sch Med, John A Hartford Ctr Excellence Geriatr, Dept Geriatr Med, 347 N Kuakini St,HPM 9, Honolulu, HI 96817 USA.
EM mckinaba@hotmail.com
FU Intramural NIH HHS [Z01 AG007270-08]; NHLBI NIH HHS [N01-HC-05102]; NIA
NIH HHS [N01-AG-4-2149, 5 U01 AG019349-05]
NR 31
TC 19
Z9 20
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD AUG
PY 2011
VL 59
IS 8
BP 1484
EP 1489
DI 10.1111/j.1532-5415.2011.03490.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 808MA
UT WOS:000293980600016
PM 21718274
ER
PT J
AU Humphrey, RW
Brockway-Lunardi, LM
Bonk, DT
Dohoney, KM
Doroshow, JH
Meech, SJ
Ratain, MJ
Topalian, SL
Pardoll, DM
AF Humphrey, Rachel W.
Brockway-Lunardi, Laura M.
Bonk, David T.
Dohoney, Kathleen M.
Doroshow, James H.
Meech, Sandra J.
Ratain, Mark J.
Topalian, Suzanne L.
Pardoll, Drew M.
TI Opportunities and Challenges in the Development of Experimental Drug
Combinations for Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID PHASE-I TRIALS; MOUSE MODEL; INHIBITION; AGENTS; IMMUNOTHERAPY;
RESISTANCE; MELANOMA; BRAF; MEK
AB It is becoming increasingly evident that cancers are dependent on a number of altered molecular pathways and can develop diverse mechanisms of resistance to therapy with single agents. Therefore, combination regimens may provide the best hope for effective therapies with durable effects. Despite preclinical data to support this notion, there are many challenges to the development of targeted combinations including scientific, economic, legal, and regulatory barriers. A discussion of these challenges and identification of models and best practices are presented with intent of aiding the research community in addressing real and perceived barriers to the development of combination therapies for cancer.
C1 [Brockway-Lunardi, Laura M.; Topalian, Suzanne L.] Melanoma Res Alliance, Washington, DC 20005 USA.
[Humphrey, Rachel W.] Bristol Myers Squibb Co, Global Dev, Princeton, NJ USA.
[Bonk, David T.] Bristol Myers Squibb Co, Dept Law, Princeton, NJ USA.
[Dohoney, Kathleen M.] Novartis Inst Biomed Res Inc, Oncol Translat Med, Cambridge, MA USA.
[Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Meech, Sandra J.] Pfizer Inc, Pfizer Oncol, New London, CT USA.
[Ratain, Mark J.] Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA.
[Ratain, Mark J.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Pardoll, Drew M.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Baltimore, MD 21218 USA.
RP Brockway-Lunardi, LM (reprint author), Melanoma Res Alliance, 1101 New York Ave NW,Ste 620, Washington, DC 20005 USA.
EM lbl@curemelanoma.org
FU NCI NIH HHS [P30 CA021765]
NR 29
TC 31
Z9 31
U1 0
U2 4
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 AUG
PY 2011
VL 103
IS 16
BP 1222
EP 1226
DI 10.1093/jnci/djr246
PG 5
WC Oncology
SC Oncology
GA 809RN
UT WOS:000294074500007
PM 21765011
ER
PT J
AU Campa, D
Kaaks, R
Le Marchand, L
Haiman, CA
Travis, RC
Berg, CD
Buring, JE
Chanock, SJ
Diver, WR
Dostal, L
Fournier, A
Hankinson, SE
Henderson, BE
Hoover, RN
Isaacs, C
Johansson, M
Kolonel, LN
Kraft, P
Lee, IM
McCarty, CA
Overvad, K
Panico, S
Peeters, PHM
Riboli, E
Sanchez, MJ
Schumacher, FR
Skeie, G
Stram, DO
Thun, MJ
Trichopoulos, D
Zhang, SM
Ziegler, RG
Hunter, DJ
Lindstrom, S
Canzian, F
AF Campa, Daniele
Kaaks, Rudolf
Le Marchand, Loic
Haiman, Christopher A.
Travis, Ruth C.
Berg, Christine D.
Buring, Julie E.
Chanock, Stephen J.
Diver, W. Ryan
Dostal, Lucie
Fournier, Agnes
Hankinson, Susan E.
Henderson, Brian E.
Hoover, Robert N.
Isaacs, Claudine
Johansson, Mattias
Kolonel, Laurence N.
Kraft, Peter
Lee, I-Min
McCarty, Catherine A.
Overvad, Kim
Panico, Salvatore
Peeters, Petra H. M.
Riboli, Elio
Jose Sanchez, Maria
Schumacher, Fredrick R.
Skeie, Guri
Stram, Daniel O.
Thun, Michael J.
Trichopoulos, Dimitrios
Zhang, Shumin
Ziegler, Regina G.
Hunter, David J.
Lindstroem, Sara
Canzian, Federico
TI Interactions Between Genetic Variants and Breast Cancer Risk Factors in
the Breast and Prostate Cancer Cohort Consortium
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BASE-LINE CHARACTERISTICS; SUSCEPTIBILITY LOCI;
CONFER SUSCEPTIBILITY; COMMON VARIANTS; FGFR2 GENE; WOMEN; AMERICAN;
VALIDITY; ALLELES
AB Background Recently, several genome-wide association studies have identified various genetic susceptibility loci for breast cancer. Relatively little is known about the possible interactions between these loci and the established risk factors for breast cancer.
Methods To assess interactions between single-nucleotide polymorphisms (SNPs) and established risk factors, we prospectively collected DNA samples and questionnaire data from 8576 breast cancer case subjects and 11 892 control subjects nested within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). We genotyped 17 germline SNPs (FGFR2-rs2981582, FGFR2-rs3750817, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, CASP8-rs1045485, LSP1-rs3817198, COL1A1-rs2075555, COX11-rs6504950, RNF146-rs2180341, 6q25-rs2046210, SLC4A7-rs4973768, NOTCH2-rs11249433, 5p12-rs4415084, 5p12-rs10941679, RAD51L1-rs999737), and odds ratios were estimated by logistic regression to confirm previously reported associations with breast cancer risk. We performed likelihood ratio test to assess interactions between 17 SNPs and nine established risk factors (age at menarche, parity, age at menopause, use of hormone replacement therapy, family history, height, body mass index, smoking status, and alcohol consumption), and a correction for multiple testing of 153 tests (adjusted P value threshold = .05/153 = 3 x 10(-4)) was done. Casecase comparisons were performed for possible differential associations of polymorphisms by subgroups of tumor stage, estrogen and progesterone receptor status, and age at diagnosis. All statistical tests were two-sided.
Results We confirmed the association of 14 SNPs with breast cancer risk (P(trend) = 2.57 x 10(-3) -3.96 x 10(-19)). Three SNPs (LSP1-rs3817198, COL1A1-rs2075555, and RNF146-rs2180341) did not show association with breast cancer risk. After accounting for multiple testing, no statistically significant interactions were detected between the 17 SNPs and the nine risk factors. We also confirmed that SNPs in FGFR2 and TNRC9 were associated with greater risk of estrogen receptor-positive than estrogen receptor-negative breast cancer (P(heterogeneity) = .0016 for FGFR2-rs2981582 and P(heterogeneity) = .0053 for TNRC9-rs3803662). SNP 5p12-rs10941679 was statistically significantly associated with greater risk of progesterone receptor-positive than progesterone receptor-negative breast cancer (P(heterogeneity) = .0028).
Conclusion This study does not support the hypothesis that known common breast cancer susceptibility loci strongly modify the associations between established risk factors and breast cancer.
C1 [Campa, Daniele; Canzian, Federico] Deutsch Krebsforschungszentrum, Genom Epidemiol Grp, German Canc Res Ctr, D-69120 Heidelberg, Germany.
[Kaaks, Rudolf; Dostal, Lucie] Deutsch Krebsforschungszentrum, Div Canc Epidemiol, German Canc Res Ctr, D-69120 Heidelberg, Germany.
[Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA.
[Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick R.; Stram, Daniel O.] Univ So Calif, Los Angeles, CA USA.
[Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Berg, Christine D.; Chanock, Stephen J.; Hoover, Robert N.; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Buring, Julie E.; Kraft, Peter; Trichopoulos, Dimitrios; Hunter, David J.; Lindstroem, Sara] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Buring, Julie E.; Hankinson, Susan E.; Lee, I-Min; Zhang, Shumin] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Buring, Julie E.; Hankinson, Susan E.; Lee, I-Min; Zhang, Shumin] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Diver, W. Ryan; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Fournier, Agnes] Ctr Res Epidemiol & Populat Hlth, INSERM, Nutr Hormones & Womens Hlth Team, U1018, Villejuif, France.
[Fournier, Agnes] Paris S Univ, UMRS 1018, Villejuif, France.
[Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Johansson, Mattias] Int Agcy Res Canc, F-69372 Lyon, France.
[Johansson, Mattias] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
[McCarty, Catherine A.] Marshfield Clin Fdn Med Res & Educ, Ctr Human Genet, Marshfield, WI 54449 USA.
[Overvad, Kim] Aarhus Univ Hosp, Dept Clin Epidemiol, Aalborg, Denmark.
[Panico, Salvatore] Univ Naples Federico 2, Dept Clin & Expt Med, Naples, Italy.
[Peeters, Petra H. M.] Univ Med Ctr, Julius Ctr, Utrecht, Netherlands.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, London, England.
[Jose Sanchez, Maria] Andalusian Sch Publ Hlth, Granada, Spain.
[Jose Sanchez, Maria] Consorcio Invest Biomed Red Epidemiol & Salud Pub, Granada, Spain.
[Skeie, Guri] Univ Tromso, Dept Community Med, Tromso, Norway.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
RP Canzian, F (reprint author), Deutsch Krebsforschungszentrum, Genom Epidemiol Grp, German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
EM f.canzian@dkfz.de
RI Berg , Christine/K-1047-2014; SANCHEZ-PEREZ, MARIA JOSE/D-1087-2011;
Campa, Daniele/K-1617-2016; Panico, Salvatore/K-6506-2016;
OI SANCHEZ-PEREZ, MARIA JOSE/0000-0003-4817-0757; Campa,
Daniele/0000-0003-3220-9944; Panico, Salvatore/0000-0002-5498-8312;
Skeie, Guri/0000-0003-2476-4251
FU US National Institutes of Health, National Cancer Institute
[U01-CA98233-07, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07];
National Institutes of Health and National Cancer Institute, Division of
Cancer Epidemiology and Genetics
FX Funding; US National Institutes of Health, National Cancer Institute
(cooperative agreements U01-CA98233-07 to D.J.H.; U01-CA98710-06 to
M.J.T.; U01-CA98216-06 to E. R. and R. K.; and U01-CA98758-07 to B. E.
H.) and Intramural Research Program of National Institutes of Health and
National Cancer Institute, Division of Cancer Epidemiology and Genetics.
NR 37
TC 104
Z9 106
U1 1
U2 21
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 AUG
PY 2011
VL 103
IS 16
BP 1252
EP 1263
DI 10.1093/jnci/djr265
PG 12
WC Oncology
SC Oncology
GA 809RN
UT WOS:000294074500010
PM 21791674
ER
PT J
AU Chang, R
Horne, MK
Shawker, TH
Kam, AW
Chen, EA
Joe, GO
Ching, WL
Mao, E
Wyrick, DA
Lozier, JN
AF Chang, Richard
Horne, McDonald K., III
Shawker, Thomas H.
Kam, Anthony W.
Chen, Enn Alexandria
Joe, Galen O.
Ching, Willie L.
Mao, Edie
Wyrick, David A., Jr.
Lozier, Jay N.
TI Low-Dose, Once-Daily, Intraclot Injections of Alteplase for Treatment of
Acute Deep Venous Thrombosis
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID TISSUE-PLASMINOGEN-ACTIVATOR; CATHETER-DIRECTED THROMBOLYSIS; VEIN
THROMBOSIS; LOWER-EXTREMITY; HEMODIALYSIS-PATIENTS; T-PA; THERAPY;
UROKINASE; STREPTOKINASE; INSUFFICIENCY
AB Purpose: To evaluate the safety and efficacy of once-daily intraclot injections of low doses (<= 10 mg) of tissue plasminogen activator (tPA) for thrombolysis of venous thrombosis.
Materials and Methods: In prospective studies, 33 patients with subclavian, jugular, and central venous thrombosis (SJ-CVT) (all but two cases associated with central catheters) were treated once a day with <= 4 mg/day of tPA, and 30 patients with acute deep vein thrombosis of the lower extremity (DVT-LE) < 14 days old were treated once a day with <= 10 mg/leg/day of tPA by intraclot "lacing" of thrombus without continuous infusions of tPA.
Results: Patency was restored in 26 (79%) of 33 patients with SJ-CVT using an average total dose of 7.1 mg of tPA/per patient and average of 2.1 treatments or days of therapy. Five patients received thrombolytic therapy for SJ-CVT as outpatients. Initial patency was restored in 29 (97%) of 30 patients with acute DVT-LE using an average total dose of 20 mg of tPA per patient over an average of 2.7 treatments/or days per patient. Follow-up imaging examinations at 6 months showed continued patency in 27 (96%)/of 28 patients. There were no major bleeding complications, and no patient required a blood transfusion.
Conclusions: Intraclot injection of low doses of alteplase is effective for acute venous thrombosis, and pharmacokinetic data suggest potentially greater safety.
C1 [Chang, Richard; Shawker, Thomas H.; Mao, Edie; Wyrick, David A., Jr.] NIH, Radiol & Imaging Sci Dept, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Horne, McDonald K., III; Lozier, Jay N.] NIH, Hematol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Kam, Anthony W.] Johns Hopkins Bayview Med Ctr, Dept Imaging, Baltimore, MD USA.
[Chen, Enn Alexandria] Excela Hlth Westmoreland Hosp, Dept Radiol, Greensburg, PA USA.
[Joe, Galen O.; Ching, Willie L.] NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
RP Chang, R (reprint author), NIH, Radiol & Imaging Sci Dept, Warren G Magnuson Clin Ctr, 9000 Rockville Pike,Bldg 10,Room 1C-338, Bethesda, MD 20892 USA.
EM rchang@cc.nih.gov
FU National Institutes of Health
FX These studies were supported by intramural research grants of the
National Institutes of Health and preformed under supervision of
Institutional Review Boards of the National Cancer Institute and
National Heart Lung Blood Institute.
NR 25
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD AUG
PY 2011
VL 22
IS 8
BP 1107
EP 1116
DI 10.1016/j.jvir.2011.03.023
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 802AW
UT WOS:000293482700006
PM 21664144
ER
PT J
AU Ungvari, Z
Bailey-Downs, L
Gautam, T
Sosnowska, D
Wang, MY
Monticone, RE
Telljohann, R
Pinto, JT
de Cabo, R
Sonntag, WE
Lakatta, EG
Csiszar, A
AF Ungvari, Zoltan
Bailey-Downs, Lora
Gautam, Tripti
Sosnowska, Danuta
Wang, Mingyi
Monticone, Robert E.
Telljohann, Richard
Pinto, John T.
de Cabo, Raphael
Sonntag, William E.
Lakatta, Edward G.
Csiszar, Anna
TI Age-Associated Vascular Oxidative Stress, Nrf2 Dysfunction, and NF-kappa
B Activation in the Nonhuman Primate Macaca mulatta
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Artery; Inflammation; Oxidative stress; Smooth muscle; Vascular aging
ID MITOCHONDRIAL SUPEROXIDE-PRODUCTION; ENDOTHELIUM-DEPENDENT DILATION;
TRANSCRIPTION FACTOR NRF2; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE-CELLS;
LIFE-SPAN; ANTIOXIDANT GENES; PROINFLAMMATORY PHENOTYPE; NF-E2-RELATED
FACTOR-2; OXIDIZED PHOSPHOLIPIDS
AB Aging promotes oxidative stress in vascular endothelial and smooth muscle cells, which contribute to the development of cardiovascular diseases. NF-E2-related factor 2 (Nrf2) is a transcription factor, which is activated by reactive oxygen species in the vasculature of young animals, leading to adaptive upregulation of numerous reactive oxygen species detoxifying and antioxidant genes. The present study was designed to elucidate age-associated changes in the homeostatic role of Nrf2-driven free radical detoxification mechanisms in the vasculature of nonhuman primates. We found that carotid arteries of aged rhesus macaques (Macaca mulatta, age: >= 20 years) exhibit significant oxidative stress (as indicated by the increased 8-iso-PGF2 alpha and 4-HNE content and decreased glutathione and ascorbate levels) as compared with vessels of young macaques (age: similar to 10 years) that is associated with activation of the redox-sensitive proinflammatory transcription factor, nuclear factor-kappaB. However, age-related oxidative stress does not activate Nrf2 and does not induce Nrf2 target genes (NQO1, GCLC, and HMOX1). In cultured vascular smooth muscle cells (VSMCs) derived from young M mulatta, treatment with H(2)O(2) and high glucose significantly increases transcriptional activity of Nrf2 and upregulates the expression of Nrf2 target genes. In contrast, in cultured vascular smooth muscle cells cells derived from aged macaques, H(2)O(2)- and high glucose-induced Nrf2 activity and Nrf2-driven gene expression are blunted. High glucose-induced H(2)O(2) production was significantly increased in aged vascular smooth muscle cells compared with that in vascular smooth muscle cells from young M mulatta. Taken together, aging is associated with Nrf2 dysfunction in M mulatta arteries, which likely exacerbates age-related cellular oxidative stress, promoting nuclear factor-kappaB activation and vascular inflammation in aging.
C1 [Ungvari, Zoltan; Bailey-Downs, Lora; Gautam, Tripti; Sosnowska, Danuta; Sonntag, William E.; Csiszar, Anna] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK 73104 USA.
[Ungvari, Zoltan; Bailey-Downs, Lora; Gautam, Tripti; Sosnowska, Danuta; Sonntag, William E.; Csiszar, Anna] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK 73104 USA.
[Wang, Mingyi; Monticone, Robert E.; Telljohann, Richard; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
[Pinto, John T.] New York Med Coll, Dept Biochem, Valhalla, NY 10595 USA.
[de Cabo, Raphael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
RP Csiszar, A (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, 975 NE 10th St,BRC 1303, Oklahoma City, OK 73104 USA.
EM anna-csiszar@ouhsc.edu
RI de Cabo, Rafael/J-5230-2016
OI de Cabo, Rafael/0000-0002-3354-2442
FU American Diabetes Association; American Federation for Aging Research;
University of Oklahoma College of Medicine Alumni Association; National
Institutes of Health [AG031085, AT006526, HL077256, P01 AG11370];
National Institute on Aging
FX This work was supported by grants from the American Diabetes Association
(to Z. Ungvari), American Federation for Aging Research (to A. Csiszar),
the University of Oklahoma College of Medicine Alumni Association (to A.
Csiszar), the National Institutes of Health (AG031085 to A. Csiszar;
AT006526 and HL077256 to Z. Ungvari; P01 AG11370 to W. E. Sonntag), and
the Intramural Research Program of the National Institute on Aging (M.
Wang, E. Lakatta, R. de Cabo).
NR 65
TC 67
Z9 68
U1 2
U2 14
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD AUG
PY 2011
VL 66
IS 8
BP 866
EP 875
DI 10.1093/gerona/glr092
PG 10
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 808EA
UT WOS:000293958300005
PM 21622983
ER
PT J
AU Koster, A
Ding, JZ
Stenholm, S
Caserotti, P
Houston, DK
Nicklas, BJ
You, TJ
Lee, JS
Visser, M
Newman, AB
Schwartz, AV
Cauley, JA
Tylavsky, FA
Goodpaster, BH
Kritchevsky, SB
Harris, TB
AF Koster, Annemarie
Ding, Jingzhong
Stenholm, Sari
Caserotti, Paolo
Houston, Denise K.
Nicklas, Barbara J.
You, Tongjian
Lee, Jung Sun
Visser, Marjolein
Newman, Anne B.
Schwartz, Ann V.
Cauley, Jane A.
Tylavsky, Frances A.
Goodpaster, Bret H.
Kritchevsky, Stephen B.
Harris, Tamara B.
CA Hlth ABC Study
TI Does the Amount of Fat Mass Predict Age-Related Loss of Lean Mass,
Muscle Strength, and Muscle Quality in Older Adults?
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Adipose tissue; Muscle mass; Muscle strength; Obesity; Aging
ID HOMEOSTASIS MODEL ASSESSMENT; BODY-COMPOSITION; PHYSICAL-ACTIVITY;
SKELETAL-MUSCLE; ELDERLY-MEN; INSULIN-RESISTANCE; ADIPOSE-TISSUE;
SARCOPENIA; OBESITY; HEALTH
AB Background. An excessive amount of adipose tissue may contribute to sarcopenia and may be one mechanism underlying accelerated loss of muscle mass and strength with aging. We therefore examined the association of baseline total body fat with changes in leg lean mass, muscle strength, and muscle quality over 7 years of follow-up and whether this link was explained by adipocytokines and insulin resistance.
Methods. Data were from 2,307 men and women, aged 70-79 years, participating in the Health, Aging, and Body Composition study. Total fat mass was acquired from dual energy X-ray absorptiometry. Leg lean mass was assessed by dual energy X-ray absorptiometry in Years 1, 2, 3, 4, 5, 6, and 8. Knee extension strength was measured by isokinetic dynamometer in Years 1, 2, 4, 6, and 8. Muscle quality was calculated as muscle strength divided by leg lean mass.
Results. Every SD greater fat mass was related to 1.3 kg more leg lean mass at baseline in men and 1.5 kg in women (p < .01). Greater fat mass was also associated with a greater decline in leg lean mass in both men and women (0.02 kg/year, p < .01), which was not explained by higher levels of adipocytokines and insulin resistance. Larger fat mass was related to significantly greater muscle strength but significantly lower muscle quality at baseline (p < .01). No significant differences in decline of muscle strength and quality were found.
Conclusions. High fatness was associated with lower muscle quality, and it predicts accelerated loss of lean mass. Prevention of greater fatness in old age may decrease the loss of lean mass and maintain muscle quality and thereby reducing disability and mobility impairments.
C1 [Koster, Annemarie; Caserotti, Paolo; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Koster, Annemarie] Maastricht Univ, Med Ctr, Sch Publ Hlth & Primary Care CAPHRI, Dept Internal Med, Maastricht, Netherlands.
[Ding, Jingzhong; Houston, Denise K.; Nicklas, Barbara J.; Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med,Sticht Ctr Aging, Winston Salem, NC 27103 USA.
[Stenholm, Sari] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Stenholm, Sari] Natl Inst Hlth & Welf, Dept Hlth Funct Capacity & Welf, Turku, Finland.
[Caserotti, Paolo] Univ So Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark.
[You, Tongjian] SUNY Buffalo, Dept Exercise & Nutr Sci, Buffalo, NY 14260 USA.
[Lee, Jung Sun] Univ Georgia, Dept Food & Nutr, Athens, GA 30602 USA.
[Visser, Marjolein] Vrije Univ Amsterdam, Fac Earth & Life Sci, Dept Hlth Sci, Amsterdam, Netherlands.
[Visser, Marjolein] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Dept Epidemiol & Biostat, Amsterdam, Netherlands.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Tylavsky, Frances A.] Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA.
[Goodpaster, Bret H.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15260 USA.
RP Koster, A (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,3C309, Bethesda, MD 20892 USA.
EM a.koster@maastrichtuniversity.nl
RI Stenholm, Sari/G-6940-2011; Koster, Annemarie/E-7438-2010; Newman,
Anne/C-6408-2013
OI Kritchevsky, Stephen/0000-0003-3336-6781; Cauley, Jane
A/0000-0003-0752-4408; Newman, Anne/0000-0002-0106-1150
FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; National Institutes of Health
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 the National
Institutes of Health, National Institute on Aging.
NR 41
TC 56
Z9 56
U1 3
U2 21
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD AUG
PY 2011
VL 66
IS 8
BP 888
EP 895
DI 10.1093/gerona/glr070
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 808EA
UT WOS:000293958300007
PM 21572082
ER
PT J
AU Papaleo, F
Silverman, JL
Aney, J
Tian, QJ
Barkan, CL
Chadman, KK
Crawley, JN
AF Papaleo, Francesco
Silverman, Jill L.
Aney, Jordan
Tian, Qingjun
Barkan, Charlotte L.
Chadman, Kathryn K.
Crawley, Jacqueline N.
TI Working memory deficits, increased anxiety-like traits, and seizure
susceptibility in BDNF overexpressing mice
SO LEARNING & MEMORY
LA English
DT Article
ID NEUROTROPHIC FACTOR VAL66MET; MESSENGER-RNA EXPRESSION; ELEVATED
PLUS-MAZE; RADIAL-ARM MAZE; PREFRONTAL CORTEX; SPATIAL MEMORY; MUTANT
MICE; HIPPOCAMPAL FUNCTION; PREPULSE INHIBITION; GENDER-DIFFERENCES
AB BDNF regulates components of cognitive processes and has been implicated in psychiatric disorders. Here we report that genetic overexpression of the BDNF mature isoform (BDNF-tg) in female mice impaired working memory functions while sparing components of fear conditioning. BDNF-tg mice also displayed reduced breeding efficiency, higher anxiety-like scores, high self-grooming, impaired prepulse inhibition, and higher susceptibility to seizures when placed in a new empty cage, as compared with wild-type (WT) littermate controls. Control measures of general health, locomotor activity, motor coordination, depression-related behaviors, and sociability did not differ between genotypes. The present findings, indicating detrimental effects of life-long increased BDNF in mice, may inform human studies evaluating the role of BDNF functional genetic variations on cognitive abilities and vulnerability to psychiatric disorders.
C1 [Papaleo, Francesco] Ist Italiano Tecnol, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy.
[Papaleo, Francesco; Aney, Jordan; Tian, Qingjun] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program, Bethesda, MD 20812 USA.
[Silverman, Jill L.; Barkan, Charlotte L.; Chadman, Kathryn K.; Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20812 USA.
RP Papaleo, F (reprint author), Ist Italiano Tecnol, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy.
EM francesco.papaleo@iit.it
OI Papaleo, Francesco/0000-0002-6326-0657
FU National Institute of Mental Health; Italian Institute of Technology;
Marie Curie FP7-Reintegration grant [268247]
FX We thank Dr. J. Chen, S. Garcia, S. Turner, A. Bebensee, and K. Jenkins
for excellent technical assistance. We thank Drs. D. R. Weinberger and
M. Canossa for critical reading of the manuscript. This research was
supported by the Intramural Research Program of the National Institute
of Mental Health. F. P. was also supported by The Italian Institute of
Technology and by the Marie Curie FP7-Reintegration grant no. 268247.
NR 88
TC 51
Z9 54
U1 1
U2 5
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1072-0502
J9 LEARN MEMORY
JI Learn. Mem.
PD AUG
PY 2011
VL 18
IS 8
BP 534
EP 544
DI 10.1101/lm.2213711
PG 11
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 806ZT
UT WOS:000293858000006
PM 21791566
ER
PT J
AU Banga, A
Handratta, V
Ibrahim, L
Connor, DF
AF Banga, Alok
Handratta, Venkatesh
Ibrahim, Lobna
Connor, Daniel F.
TI SSRIs and placental dysfunction
SO MEDICAL HYPOTHESES
LA English
DT Letter
ID SEROTONIN-REUPTAKE INHIBITORS; INDOLEAMINE 2,3-DIOXYGENASE;
TRYPTOPHAN-METABOLISM; PREGNANCY; MALFORMATIONS; LOCALIZATION;
PAROXETINE; RISK
C1 [Banga, Alok; Handratta, Venkatesh; Connor, Daniel F.] Univ Connecticut, Dept Psychiat, Sch Med & Hlth Care, Div Child & Adolescent Psychiat, Farmington, CT 06030 USA.
[Ibrahim, Lobna] NIMH, Bethesda, MD 20892 USA.
RP Banga, A (reprint author), Univ Connecticut, Dept Psychiat, Sch Med & Hlth Care, Div Child & Adolescent Psychiat, 263 Farmington Ave, Farmington, CT 06030 USA.
OI Connor, Daniel/0000-0002-7867-4094
NR 13
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0306-9877
J9 MED HYPOTHESES
JI Med. Hypotheses
PD AUG
PY 2011
VL 77
IS 2
BP 311
EP 312
DI 10.1016/j.mehy.2011.05.023
PG 2
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 809GF
UT WOS:000294039100045
PM 21664765
ER
PT J
AU De Luca, P
Vazquez, ES
Moiola, CP
Zalazar, F
Cotignola, J
Gueron, G
Gardner, K
De Siervi, A
AF De Luca, Paola
Vazquez, Elba S.
Moiola, Cristian P.
Zalazar, Florencia
Cotignola, Javier
Gueron, Geraldine
Gardner, Kevin
De Siervi, Adriana
TI BRCA1 Loss Induces GADD153-Mediated Doxorubicin Resistance in Prostate
Cancer
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; SUSCEPTIBILITY GENE BRCA1; BREAST-CANCER;
MAMMARY-TUMORS; CELL-CYCLE; INDUCED APOPTOSIS; DNA-DAMAGE;
TRANSCRIPTIONAL REGULATION; ANTITUMOR-ACTIVITY; SECONDARY BRCA1
AB BRCA1 plays numerous roles in the regulation of genome integrity and chemoresistance. Although BRCA1 interaction with key proteins involved in DNA repair is well known, its role as a coregulator in the transcriptional response to DNA damage remains poorly understood. In this study, we show that BRCA1 plays a central role in the transcriptional response to genotoxic stress in prostate cancer. BRCA1 expression mediates apoptosis, cell-cycle arrest, and decreased viability in response to doxorubicin treatment. Xenograft studies using human prostate carcinoma PC3 cells show that BRCA1 depletion results in increased tumor growth. A focused survey of BRCA1-regulated genes in prostate carcinoma reveals that multiple regulators of genome stability and cell-cycle control, including BLM, FEN1, DDB2, H3F3B, BRCA2, CCNB2, MAD2L1, and GADD153, are direct transcriptional targets of BRCA1. Furthermore, we show that BRCA1 targets GADD153 promoter to increase its transcription in response to DNA damage. Finally, GADD153 depletion significantly abrogates BRCA1 influence on cell-cycle progression and cell death in response to doxorubicin treatment. These findings define a novel transcriptional pathway through which BRCA1 orchestrates cell fate decisions in response to genotoxic insults, and suggest that BRCA1 status should be considered for new chemotherapeutic treatment strategies in prostate cancer. Mol Cancer Res; 9(8); 1078-90. (C)2011 AACR.
C1 [De Siervi, Adriana] Univ Buenos Aires, FCEN, Lab Canc & Apoptosis, Dept Quim Biol,Sch Sci,CONICET, Buenos Aires, DF, Argentina.
[Gardner, Kevin] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP De Siervi, A (reprint author), Univ Buenos Aires, FCEN, Lab Canc & Apoptosis, Dept Quim Biol,Sch Sci,CONICET, Intendente Guiraldes 2160 Pab 2,2Do Piso,CM1,Ciud, Buenos Aires, DF, Argentina.
EM adesiervi@qb.fcen.uba.ar
RI Mendez, Pedro /J-8955-2016;
OI Mendez, Pedro /0000-0001-6713-7907; Cotignola,
Javier/0000-0003-4473-9854
FU CONICET; Argentinean Agency of Science and Technology (ANPCyT) [PICT
2006-00228, PICT 2006-00367]
FX We thank Dr. Monica Kotler for her kind help with the caspase 3
measurement technique. E. Vazquez, J. Cotignola and A. De Siervi are
members of the career of scientific researcher at the National Research
Council (CONICET). G. Gueron holds postdoctoral fellowship from CONICET.
P. De Luca, C. Moiola and F. Zalazar hold PhD scholarships from CONICET.
K. Gardner is a principal investigator at the NCI-NIH. These results are
part of Paola De Luca's PhD thesis.; This research was supported by the
Argentinean Agency of Science and Technology (ANPCyT, PICT 2006-00228
and PICT 2006-00367).
NR 53
TC 19
Z9 19
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD AUG
PY 2011
VL 9
IS 8
BP 1078
EP 1090
DI 10.1158/1541-7786.MCR-11-0155
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 807GX
UT WOS:000293885600010
PM 21700680
ER
PT J
AU Burton, ER
Gaffar, A
Lee, SJ
Adeshuko, F
Whitney, KD
Chung, JY
Hewitt, SM
Huang, GS
Goldberg, GL
Libutti, SK
Kwon, M
AF Burton, Elizabeth R.
Gaffar, Aneesa
Lee, Soo Jin
Adeshuko, Folashade
Whitney, Kathleen D.
Chung, Joon-Yong
Hewitt, Stephen M.
Huang, Gloria S.
Goldberg, Gary L.
Libutti, Steven K.
Kwon, Mijung
TI Downregulation of Filamin A Interacting Protein 1-Like is Associated
with Promoter Methylation and Induces an Invasive Phenotype in Ovarian
Cancer
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID GENE-EXPRESSION CHANGES; DNA METHYLATION; ENDOTHELIAL-CELLS; CREB
BINDING; EPITHELIAL-CELLS; CPG METHYLATION; PROSTATE-CANCER; CANDIDATE
GENES; BREAST-CANCER; MASS ARRAY
AB Ovarian cancer is the most lethal gynecologic malignancy with a five-year survival rate below 25% for patients with stages III and IV disease. Identifying key mediators of ovarian cancer invasion and metastasis is critical to the development of more effective therapeutic interventions. We previously identified Filamin A interacting protein 1-like (FILIP1L) as an important mediator of cell proliferation and migration. In addition, targeted expression of FILIP1L in tumors inhibited tumor growth in vivo. In our present study, we confirmed that both mRNA and protein expression of FILIP1L were downregulated in ovarian cancer cells compared with normal ovarian epithelial cells. FILIP1L expression was inversely correlated with the invasive potential of ovarian cancer cell lines and clinical ovarian cancer specimens. We also provide evidence that DNA methylation is a mechanism by which FILIP1L is downregulated in ovarian cancer. The CpG island in the FILIP1L promoter was heavily methylated in ovarian cancer cells. Methylation status of the FILIP1L promoter was inversely correlated with FILIP1L expression in ovarian cell lines and clinical ovarian specimens. Reduced methylation in the FILIP1L promoter following treatment with a DNA demethylating agent was associated with restoration of FILIP1L expression in ovarian cancer cells. A transcription activator, cAMP-responsive element binding protein (CREB) was shown to bind to the CREB/ATF site in the CpG island of the FILIP1L promoter. Overall, these findings suggest that downregulation of FILIP1L associated with DNA methylation is related with the invasive phenotype in ovarian cancer and that modulation of FILIP1L expression has the potential to be a target for ovarian cancer therapy. Mol Cancer Res; 9(8); 1126-38. (C)2011 AACR.
C1 [Burton, Elizabeth R.; Gaffar, Aneesa; Lee, Soo Jin; Adeshuko, Folashade; Libutti, Steven K.; Kwon, Mijung] Yeshiva Univ Albert Einstein Coll Med, Dept Surg, Bronx, NY 10461 USA.
[Whitney, Kathleen D.] Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA.
[Burton, Elizabeth R.; Huang, Gloria S.; Goldberg, Gary L.] Yeshiva Univ Albert Einstein Coll Med, Montefiore Med Ctr, Dept Obstet & Gynecol & Womens Hlth, Div Gynecol Oncol, Bronx, NY 10461 USA.
[Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Pathol Lab, Appl Mol Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Kwon, M (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Surg, Ullmann 1219,1250 Morris Pk Ave, Bronx, NY 10461 USA.
EM mijung.kwon@einstein.yu.edu
OI Huang, Gloria/0000-0002-0001-888X; Hewitt, Stephen/0000-0001-8283-1788;
Chung, Joon-Yong/0000-0001-5041-5982
FU Linda and Earle Altman; Albert Einstein College of Medicine; NCI
Intramural Program
FX This research was supported in part by a generous gift from Linda and
Earle Altman, the Albert Einstein College of Medicine, and the NCI
Intramural Program.
NR 40
TC 16
Z9 17
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD AUG
PY 2011
VL 9
IS 8
BP 1126
EP 1138
DI 10.1158/1541-7786.MCR-11-0162
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 807GX
UT WOS:000293885600014
PM 21693594
ER
PT J
AU Aksentijevich, I
Kastner, DL
AF Aksentijevich, Ivona
Kastner, Daniel L.
TI Genetics of monogenic autoinflammatory diseases: past successes, future
challenges
SO NATURE REVIEWS RHEUMATOLOGY
LA English
DT Review
ID FAMILIAL MEDITERRANEAN FEVER; MULTISYSTEM INFLAMMATORY DISEASE; ENCODING
MEVALONATE KINASE; GENOME-WIDE ASSOCIATION; MUCKLE-WELLS-SYNDROME;
PERIODIC FEVER; HYPERIMMUNOGLOBULINEMIA-D; TNF RECEPTOR; HYPER-IGD;
CIAS1 MUTATIONS
AB The term autoinflammation was initially coined to distinguish disorders characterized by recurrent episodes of inflammation in the absence of high-titer autoantibodies and antigen-specific T cells from the more common autoimmune diseases. Although this concept originally applied to monogenic hereditary recurrent fevers, it has expanded over time to include polygenic (complex) autoinflammatory diseases. Understanding of the pathogenesis of autoinflammatory diseases has grown rapidly in the past decade owing to advances in genome research and technology. Genome-wide linkage analysis, positional cloning, homozygosity mapping and candidate gene screening have led to the identification of mutations in 12 genes that are associated with monogenic diseases. Genome-wide association studies have begun to elucidate the molecular basis of complex autoinflammatory diseases. The discovery of disease-causing genetic variants has defined autoinflammation as disorder within the innate immune system, implicating IL-1 as a master cytokine, and has led to a breakthrough in therapy, with IL-1 inhibitors producing rapid and sustained amelioration of symptoms. Despite major advances, however, a substantial number of patients have no mutations in the known autoinflammatory genes. The challenge now is to find the undiscovered genes, considering that most cases are sporadic or occur within small families. New approaches and tools such as next-generation sequencing are discussed.
C1 [Aksentijevich, Ivona; Kastner, Daniel L.] NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA.
RP Aksentijevich, I (reprint author), NHGRI, Inflammatory Dis Sect, Bldg 10,Room 10C101B,10 Ctr Dr,MSC 1849, Bethesda, MD 20892 USA.
EM aksentii@exchange.nih.gov
NR 66
TC 52
Z9 52
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4790
EI 1759-4804
J9 NAT REV RHEUMATOL
JI Nat. Rev. Rheumatol.
PD AUG
PY 2011
VL 7
IS 8
BP 468
EP 477
DI 10.1038/nrrheum.2011.94
PG 10
WC Rheumatology
SC Rheumatology
GA 801VM
UT WOS:000293468700007
PM 21727933
ER
PT J
AU Shin, EJ
Duong, CX
Nguyen, XKT
Bing, G
Bach, JH
Park, DH
Nakayama, K
Ali, SF
Kanthasamy, AG
Cadet, JL
Nabeshima, T
Kim, HC
AF Shin, Eun-Joo
Duong, Chu Xuan
Xuan-Khanh Thi Nguyen
Bing, Guoying
Bach, Jae-Hyung
Park, Dae Hun
Nakayama, Keiichi
Ali, Syed F.
Kanthasamy, Anumantha G.
Cadet, Jean L.
Nabeshima, Toshitaka
Kim, Hyoung-Chun
TI PKC delta inhibition enhances tyrosine hydroxylase phosphorylation in
mice after methamphetamine treatment
SO NEUROCHEMISTRY INTERNATIONAL
LA English
DT Article
DE Methamphetamine; Dopaminergic toxicity; Hyperthermia; PKC delta gene;
Phospho-TH at ser-40; Striatum
ID PROTEIN-KINASE-C; DOPAMINERGIC NEURONAL CELLS; PANCREATIC ACINAR-CELLS;
OXIDATIVE STRESS; PROTEOLYTIC ACTIVATION; PARKINSONS-DISEASE; INDUCED
APOPTOSIS; SH-SY5Y CELLS; ANIMAL-MODELS; PC12 CELLS
AB The present study was designed to evaluate the specific role of protein kinase C (PKC) delta in methamphetamine (MA)-induced dopaminergic toxicity. A multiple-dose administration regimen of MA significantly increases PKC delta expression, while rottlerin, a PKC delta inhibitor, significantly attenuates MA-induced hyperthermia and behavioral deficits. These behavioral effects were not significantly observed in PKC delta antisense oligonucleotide (ASO)-treated- or PKC delta knockout (-/-)-mice. There were no MA-induced significant decreases of dopamine (DA) content or tyrosine hydroxylase (TH) expression in the striatum in rottlerin-treated-, ASO-treated- or PKC delta (-/-)-mice. The administration of MA also results in a significant decrease of TH phosphorylation at set 40, but not ser 31, while the inhibition of PKC delta consistently and significantly attenuates MA-induced reduction in the phosphorylation of TH at ser 40. Therefore, these results suggest that the MA-induced enhancement of PKC delta expression is a critical factor in the impairment of TH phosphorylation at ser 40 and that pharmacological or genetic inhibition of PKC delta may be protective against MA-induced dopaminergic neurotoxicity in vivo. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Shin, Eun-Joo; Duong, Chu Xuan; Xuan-Khanh Thi Nguyen; Bach, Jae-Hyung; Park, Dae Hun; Kim, Hyoung-Chun] Kangwon Natl Univ, Neuropsychopharmacol & Toxicol Program, Coll Pharm, Chunchon 200701, South Korea.
[Bing, Guoying] Univ Kentucky, Dept Anat & Neurobiol, Coll Med, Lexington, KY 40536 USA.
[Nakayama, Keiichi] Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Fukuoka 8128582, Japan.
[Ali, Syed F.] Natl Ctr Toxicol Res, FDA, Div Neurotoxicol, Jefferson, AR 72079 USA.
[Kanthasamy, Anumantha G.] Iowa State Univ, Dept Biomed Sci, Iowa Ctr Adv Neurotoxicol, Parkinsons Disorder Res Lab, Ames, IA 50011 USA.
[Cadet, Jean L.] NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD 21224 USA.
[Nabeshima, Toshitaka] Meijo Univ, Grad Sch Pharmaceut Sci, Dept Chem Pharmacol, Nagoya, Aichi 4688503, Japan.
RP Kim, HC (reprint author), Kangwon Natl Univ, Neuropsychopharmacol & Toxicol Program, Coll Pharm, Chunchon 200701, South Korea.
EM kimhc@kangwon.ac.kr
FU Ministry of Science and Technology, Republic of Korea [2011K000271];
National Research Foundation of Korea, Republic of Korea [E00025];
Ministry of Health Labour and Welfare (MHLW); Ministry of Education,
Culture, Sports, Science and Technology (MEXT); BK 21 Program
FX This study was supported by a Grant (#2011K000271) from the Brain
Research Center from 21st Century Frontier Research Program funded by
the Ministry of Science and Technology, Republic of Korea, and by a
Grant (#E00025) of the Korea-Japan Joint Research Program, National
Research Foundation of Korea, Republic of Korea. This work was, in part,
supported by grants from Ministry of Health Labour and Welfare (MHLW):
Research on Risk of Chemical Substances, and Ministry of Education,
Culture, Sports, Science and Technology (MEXT): Academic Frontier
Project. Xuan-Khanh Thi Nguyen and Jae-Hyung Bach were supported by BK
21 Program.
NR 78
TC 13
Z9 13
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0197-0186
J9 NEUROCHEM INT
JI Neurochem. Int.
PD AUG
PY 2011
VL 59
IS 1
BP 39
EP 50
DI 10.1016/j.neuint.2011.03.022
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 802FA
UT WOS:000293493500006
PM 21672585
ER
PT J
AU Fyfe, JC
Al-Tamimi, RA
Liu, JL
Schaffer, AA
Agarwala, R
Henthorn, PS
AF Fyfe, John C.
Al-Tamimi, Raba A.
Liu, Junlong
Schaeffer, Alejandro A.
Agarwala, Richa
Henthorn, Paula S.
TI A novel mitofusin 2 mutation causes canine fetal-onset neuroaxonal
dystrophy
SO NEUROGENETICS
LA English
DT Article
DE Neuroaxonal dystrophy; Mitofusin 2; Linkage analysis; Animal model;
Disease gene
ID HUMAN GENETIC-DISEASE; MITOCHONDRIAL FUSION; PHOSPHOLIPASE A(2); PLA2G6
MUTATION; MOUSE MODEL; SEQUENCE; NEURODEGENERATION; PROTEIN; DOGS;
PAPILLON
AB We recently reported autosomal recessive fetal-onset neuroaxonal dystrophy (FNAD) in a large family of dogs that is not caused by mutation in the PLA2G6 locus (Fyfe et al., J Comp Neurol 518:3771-3784, 2010). Here, we report a genome-wide linkage analysis using 333 microsatellite markers to map canine FNAD to the telomeric end of chromosome 2. The interval of zero recombination was refined by single-nucleotide polymorphism (SNP) haplotype analysis to similar to 200 kb, and the included genes were sequenced. We found a homozygous 3-nucleotide deletion in exon 14 of mitofusin 2 (MFN2), predicting loss of a glutamate residue at position 539 in the protein of affected dogs. RT-PCR demonstrated near normal expression of the mutant mRNA, but MFN2 expression was undetectable to very low on western blots of affected dog brainstem, cerebrum, kidney, and cultured fibroblasts and by immunohistochemistry on brainstem sections. MFN2 is a multifunctional, membrane-bound GTPase of mitochondria and endoplasmic reticulum most commonly associated with human Charcot-Marie-Tooth disease type 2A2. The canine disorder extends the range of MFN2-associated phenotypes and suggests MFN2 as a candidate gene for rare cases of human FNAD.
C1 [Fyfe, John C.; Al-Tamimi, Raba A.] Michigan State Univ, Coll Vet Med, Lab Comparat Med Genet, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
[Liu, Junlong; Henthorn, Paula S.] Univ Penn, Sch Vet Med, Med Genet Sect, Philadelphia, PA 19104 USA.
[Schaeffer, Alejandro A.; Agarwala, Richa] NIH, Natl Ctr Biotechnol Informat, US Dept HHS, Bethesda, MD 20894 USA.
RP Fyfe, JC (reprint author), Michigan State Univ, Coll Vet Med, Lab Comparat Med Genet, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
EM fyfe@cvm.msu.edu
RI Schaffer, Alejandro/F-2902-2012
FU National Institutes of Health [NS41989, RR02512, HV48141]; Purebred Dog
Endowment Fund; College of Veterinary Medicine; Michigan State
University; NIH, NLM; Department of Pathology from the Kuwait University
Faculty of Medicine [KU-984]
FX This work was supported by the National Institutes of Health (NS41989,
RR02512, and contract HV48141), the Purebred Dog Endowment Fund, College
of Veterinary Medicine, Michigan State University, and in part by the
Intramural Research Program of the NIH, NLM. Author RAA was supported by
a Department of Pathology Scholarship for Basic Medical Sciences
(KU-984) from the Kuwait University Faculty of Medicine.
NR 56
TC 9
Z9 9
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1364-6745
J9 NEUROGENETICS
JI Neurogenetics
PD AUG
PY 2011
VL 12
IS 3
BP 223
EP 232
DI 10.1007/s10048-011-0285-6
PG 10
WC Genetics & Heredity; Clinical Neurology
SC Genetics & Heredity; Neurosciences & Neurology
GA 809ME
UT WOS:000294059600007
PM 21643798
ER
PT J
AU Jinnah, HA
Hallett, M
AF Jinnah, H. A.
Hallett, Mark
TI In the wink of an eye Nature and nurture in blepharospasm
SO NEUROLOGY
LA English
DT Editorial Material
ID DYSTONIAS
C1 [Jinnah, H. A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
[Jinnah, H. A.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA.
[Jinnah, H. A.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Jinnah, HA (reprint author), Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
EM hjinnah@emory.edu
FU Intramural NIH HHS; NCATS NIH HHS [U54 TR001456]; NINDS NIH HHS
[NS067501, NS040470]
NR 5
TC 2
Z9 2
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 AUG
PY 2011
VL 77
IS 7
BP 616
EP 617
DI 10.1212/WNL.0b013e3182299f84
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 807FL
UT WOS:000293881600006
PM 21775742
ER
PT J
AU Cheung, HH
Davis, AJ
Lee, TL
Pang, AL
Nagrani, S
Rennert, OM
Chan, WY
AF Cheung, H-H
Davis, A. J.
Lee, T-L
Pang, A. L.
Nagrani, S.
Rennert, O. M.
Chan, W-Y
TI Methylation of an intronic region regulates miR-199a in testicular tumor
malignancy
SO ONCOGENE
LA English
DT Article
DE intronic methylation; miR-199a; testicular tumor; PODXL; malignancy
ID GERM-CELL TUMORS; OVARIAN-CANCER CELLS; DNA METHYLATION; MICRORNA
EXPRESSION; PROSTATE-CANCER; BLADDER-CANCER; IDENTIFICATION;
PODOCALYXIN; METASTASIS; CARCINOMA
AB In the testicular cancer cell line, NT2, we previously demonstrated that differentially methylated regions were located in introns or intergenic regions, and postulated these might regulate non-coding RNAs. Three microRNAs and three small nucleolar RNAs were differentially methylated; one, miR-199a, was associated with the progression and prognosis of gastric and ovarian cancers. In this report we document, by epigenomic profiling of testicular tissue, that miR-199a is transcribed as antisense of dynamin 3 (chromosome 1q24.3), and hypermethylation of this region is correlated with miR-199a-5p/3p repression and tumor malignancy. Re-expression of miR-199a in testicular cancer cells led to suppression of cell growth, cancer migration, invasion and metastasis. The miR-199a-5p, one of two mature miRNA species derived from miR-199a, is associated with tumor malignancy. We further identified the embryonal carcinoma antigen podocalyxin-like protein 1 (PODXL), an anti-adhesive protein expressed in aggressive tumors, as a target of miR-199a-5p. We demonstrated PODXL is overexpressed in malignant testicular tumor, and cellular depletion of PODXL resulted in suppression of cancer invasion. The inverse relationship between PODXL and miR-199a-5p expression suggests PODXL is a downstream effector mediating the action of miR199a-5p. This report identifies DNA methylation, miR-199a dysregulation and PODXL as critical factors in tumor malignancy. Oncogene (2011) 30, 3404-3415; doi:10.1038/onc.2011.60; published online 7 March 2011
C1 [Cheung, H-H; Chan, W-Y] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Shatin, Hong Kong, Peoples R China.
[Cheung, H-H; Davis, A. J.; Lee, T-L; Pang, A. L.; Nagrani, S.; Rennert, O. M.; Chan, W-Y] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Clin & Dev Genom, NIH, Bethesda, MD USA.
RP Chan, WY (reprint author), Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Room 518B,Choh Ming Li Basic Med Sci Bldg, Shatin, Hong Kong, Peoples R China.
EM chanwy@cuhk.edu.hk
RI Cheung, Hoi-Hung/G-7605-2011; Lee, Tin-Lap/A-7853-2009;
OI Lee, Tin-Lap/0000-0002-6654-0988; Davis, Andrew/0000-0001-9556-4498
FU National Institutes of Health (NIH); Eunice Kennedy Shriver National
Institute of Child Health and Human Development; Chinese University of
Hong Kong
FX We thank Dr Yun-Fai Chris Lau for providing the 833K cell line. This
research was supported in part by the Intramural Research Program of the
National Institutes of Health (NIH), Eunice Kennedy Shriver National
Institute of Child Health and Human Development and the Chinese
University of Hong Kong.
NR 45
TC 69
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U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD AUG
PY 2011
VL 30
IS 31
BP 3404
EP 3415
DI 10.1038/onc.2011.60
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 802KA
UT WOS:000293508100002
PM 21383689
ER
PT J
AU Watkins-Chow, D
Leeds, K
Mullen, R
Incao, A
Rivas, C
Pavan, W
AF Watkins-Chow, D.
Leeds, K.
Mullen, R.
Incao, A.
Rivas, C.
Pavan, W.
TI Sox10 modifier loci identified in a sensitized ENU mutagenesis screen
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Meeting Abstract
C1 [Watkins-Chow, D.; Leeds, K.; Mullen, R.; Incao, A.; Rivas, C.; Pavan, W.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD AUG
PY 2011
VL 24
IS 4
BP 765
EP 765
PG 1
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 808YZ
UT WOS:000294019200048
ER
PT J
AU Coelho, SG
Ito, S
Wakamatsu, K
Miller, SA
Beer, JZ
Hearing, VJ
AF Coelho, S. G.
Ito, S.
Wakamatsu, K.
Miller, S. A.
Beer, J. Z.
Hearing, V. J.
TI Distribution patterns of eumelanin and pheomelanin in human skin
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Meeting Abstract
C1 [Coelho, S. G.; Ito, S.; Wakamatsu, K.; Miller, S. A.; Beer, J. Z.; Hearing, V. J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD AUG
PY 2011
VL 24
IS 4
BP 786
EP 786
PG 1
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 808YZ
UT WOS:000294019200115
ER
PT J
AU Valencia, JC
Coelho, SG
Yin, L
Vieira, WD
Hearing, VJ
AF Valencia, J. C.
Coelho, S. G.
Yin, L.
Vieira, W. D.
Hearing, V. J.
TI Fighting Proliferation with Differentiation: How Pmel17/gp100 binding to
FHL2 leads the charge in melanoma
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Meeting Abstract
C1 [Valencia, J. C.; Coelho, S. G.; Yin, L.; Vieira, W. D.; Hearing, V. J.] NCI, PCBS, LCB, CCR, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD AUG
PY 2011
VL 24
IS 4
BP 802
EP 802
PG 1
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 808YZ
UT WOS:000294019200165
ER
PT J
AU Choi, W
Kolbe, L
Hearing, VJ
AF Choi, W.
Kolbe, L.
Hearing, V. J.
TI Characterization of the bioactive motif of neuregulin-1, a
fibroblast-derived paracrine factor that regulates constitutive color
and melanocyte function in human skin
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Meeting Abstract
C1 [Choi, W.; Kolbe, L.; Hearing, V. J.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD AUG
PY 2011
VL 24
IS 4
BP 813
EP 813
PG 1
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 808YZ
UT WOS:000294019200201
ER
PT J
AU Debbache, J
Pickel, J
Arnheiter, H
AF Debbache, J.
Pickel, J.
Arnheiter, H.
TI In vivo role of serine-73 phosphorylation of the transcription factor
MITF: effects on coat color in mice with targeted mutations
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Meeting Abstract
C1 [Debbache, J.; Pickel, J.; Arnheiter, H.] NINDS, Mammalian Dev Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD AUG
PY 2011
VL 24
IS 4
BP 825
EP 825
PG 1
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 808YZ
UT WOS:000294019200240
ER
PT J
AU Kondo, T
Hearing, VJ
AF Kondo, T.
Hearing, V. J.
TI Subcellular localization of the P protein in human melanocytes
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Meeting Abstract
C1 [Kondo, T.; Hearing, V. J.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD AUG
PY 2011
VL 24
IS 4
BP 826
EP 826
PG 1
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 808YZ
UT WOS:000294019200245
ER
PT J
AU Shafighi, M
Olariu, R
Fathi, AR
Djafarzadeh, S
Jakob, SM
Banic, A
Constantinescu, MA
AF Shafighi, Maziar
Olariu, Radu
Fathi, Ali R.
Djafarzadeh, Siamak
Jakob, Stephan M.
Banic, Andrej
Constantinescu, Mihai A.
TI Dimethyloxalylglycine Stabilizes HIF-1 alpha in Cultured Human
Endothelial Cells and Increases Random-Pattern Skin Flap Survival In
Vivo
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTOR-1; GROWTH-FACTOR; GENE-THERAPY; HIF-ALPHA; RAT
MODEL; ANGIOGENESIS; VEGF; ANGIOPOIETIN-1; ISCHEMIA; VASCULARIZATION
AB Background: The goal of this study was to evaluate in vitro and in vivo the effects of up-regulation of the proangiogenic hypoxia inducible factor (HIF)-1 alpha induced by dimethyloxalylglycine on endothelial cell cultures and on skin flap survival.
Methods: Human umbilical vein endothelial cell cultures were exposed to hypoxic conditions, to dimethyloxalylglycine, and to cobalt chloride for up to 24 hours. Expression of HIF-1 alpha and vascular endothelial growth factor (VEGF) in cell culture media was analyzed. In vivo, 20 male Wistar rats were assigned randomly to either the treatment group (dimethyloxalylglycine intraperitoneal injection, n = 10) or the control group (saline intraperitoneal injection, n = 10). A dorsal skin flap was raised in all animals and sutured back into place. Flap survival was evaluated on postoperative day 7 by laser Doppler and digital planimetry.
Results: In vitro treatment of human umbilical vein endothelial cells during a 24-hour period showed a significant elevation of VEGF expression with dimethyloxalylglycine exposure (92 +/- 35 pg/mg total cellular protein) or hypoxia exposure (88 +/- 21 pg/mg total cellular protein) compared with controls (23 +/- 10 pg/mg total cellular protein) (p < 0.05 for both). In vivo experiments showed a significant decrease of flap necrosis in the treatment group animals versus controls (35.95 +/- 5.03 percent versus 44.42 +/- 5.18 percent, p < 0.05). The laser Doppler evaluation revealed significantly increased blood flow in the proximal two-thirds of the flap in the treatment group compared with the control group (p < 0.05).
Conclusion: Dimethyloxalylglycine treatment significantly increases VEGF and HIF-1 alpha expression in endothelial cell cultures and enhances skin flap survival in vivo in a rat model. (Plast. Reconstr. Surg. 128: 415, 2011.)
C1 Univ Hosp Bern, Dept Plast Reconstruct & Hand Surg, Inselspital, CH-3010 Bern, Switzerland.
Univ Hosp Bern, Dept Intens Care Med, Inselspital, CH-3010 Bern, Switzerland.
Univ Bern, Bern, Switzerland.
NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Shafighi, M (reprint author), Univ Hosp Bern, Univ Clin Plast & Hand Surg, Inselspital, CH-3010 Bern, Switzerland.
EM maziar_shafighi@yahoo.com
NR 39
TC 6
Z9 8
U1 2
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0032-1052
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD AUG
PY 2011
VL 128
IS 2
BP 415
EP 422
DI 10.1097/PRS.0b013e31821e6e69
PG 8
WC Surgery
SC Surgery
GA 801TV
UT WOS:000293464400036
PM 21788833
ER
PT J
AU Stetson, B
Schlundt, D
Peyrot, M
Ciechanowski, P
Austin, MM
Young-Hyman, D
McKoy, J
Hall, M
Dorsey, R
Fitzner, K
Quintana, M
Narva, A
Urbanski, P
Homko, C
Sherr, D
AF Stetson, Barbara
Schlundt, David
Peyrot, Mark
Ciechanowski, Paul
Austin, Mary M.
Young-Hyman, Deborah
McKoy, June
Hall, Micki
Dorsey, Rashida
Fitzner, Karen
Quintana, Martha
Narva, Andrew
Urbanski, Patricia
Homko, Carol
Sherr, Dawn
TI Monitoring in Diabetes Self-Management: Issues and Recommendations for
Improvement
SO POPULATION HEALTH MANAGEMENT
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; BLOOD-GLUCOSE; GLYCEMIC CONTROL;
CARDIOVASCULAR-DISEASE; AMERICAN-ASSOCIATION; EDUCATION; CARE; OUTCOMES;
ADULTS; DEPRESSION
AB The American Association of Diabetes Educators hosted a Monitoring Symposium during which 18 invited participants considered pre-set questions regarding how diabetes education can more effectively address barriers to monitoring for people with diabetes and related conditions. This report provides a summary of the moderated discussion and highlights the key points that apply to diabetes educators and other providers involved with diabetes care.
The participating thought leaders reviewed findings from published literature and participated in a moderated discussion with the aim of providing practical advice for health care practitioners regarding monitoring for people with diabetes so that the overall health of this population can be enhanced. The discussants also defined monitoring for diabetes as including that done by the clinician or laboratory, as well as self-monitoring. The discussion was distilled into key points that apply to diabetes educators and other providers involved with diabetes care. Participants developed specific recommendations for a self-monitoring behavior and monitoring framework.
People with diabetes benefit from instruction and guidance about self-monitoring and decision making that is based on monitored results and informed interactions with providers. Importantly, collaboration among the entire diabetes care community is needed to ensure that monitoring is performed and utilized to its fullest advantage. Going forward, it will be critical to mitigate barriers to diabetes self-management and training and to identify linkages and partnerships to address barriers to self-monitoring. (Population Health Management 2011; 14: 189-197)
C1 [Stetson, Barbara] Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40208 USA.
[Schlundt, David] Vanderbilt Univ, Nashville, TN USA.
[Peyrot, Mark] Loyola Univ Maryland, Dept Sociol, Baltimore, MD USA.
[Ciechanowski, Paul] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Austin, Mary M.] Austin Grp LLC, Houston, TX USA.
[Young-Hyman, Deborah] Med Coll Georgia, Georgia Prevent Inst, Augusta, GA 30912 USA.
[McKoy, June] Northwestern Univ, Evanston, IL USA.
[Hall, Micki] Univ Oklahoma, Tulsa, OK USA.
[Dorsey, Rashida] US Dept HHS, Washington, DC 20201 USA.
[Fitzner, Karen; Sherr, Dawn] Amer Assoc Diabet Educators, Chicago, IL USA.
[Quintana, Martha] DiabetesHealthCtr, Watsonville, CA USA.
[Narva, Andrew] NIDDKD, Natl Kidney Dis Educ Program, Bethesda, MD 20892 USA.
[Urbanski, Patricia] Duluth Family Practice Ctr, Duluth, MN USA.
[Homko, Carol] Temple Univ, Sch Med, Philadelphia, PA 19122 USA.
RP Stetson, B (reprint author), Univ Louisville, Dept Psychol & Brain Sci, 2301 S 3rd St, Louisville, KY 40208 USA.
EM Bastet01@louisville.edu
NR 67
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U1 1
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1942-7891
J9 POPUL HEALTH MANAG
JI Popul. Health Manag.
PD AUG
PY 2011
VL 14
IS 4
BP 189
EP 197
DI 10.1089/pop.2010.0030
PG 9
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 806QO
UT WOS:000293825200006
PM 21323462
ER
PT J
AU Pages, N
Maurois, P
Delplanque, B
Bac, P
Martin, JC
Du, Q
Rapoport, SI
Vamecq, J
AF Pages, Nicole
Maurois, Pierre
Delplanque, Bernadette
Bac, Pierre
Martin, Jean-Charles
Du, Qin
Rapoport, Stanley I.
Vamecq, Joseph
TI Brain protection by rapeseed oil in magnesium-deficient mice
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE Polyunsaturated fatty acids; Alpha-linolenic acid (ALA);
Eicosapentaenoic acid (EPA); Rapeseed oil; Brain protection; Magnesium
deficiency; Hyperexcitability; Chemical seizures; Electrical seizures;
Audiogenic seizures; Anticonvulsant; Anti-inflammatory
ID POLYUNSATURATED FATTY-ACIDS; ALPHA-LINOLENIC ACID; ASPARTATE-INDUCED
SEIZURES; DOCOSAHEXAENOIC ACID; CALCIUM-CHANNELS; INHIBITION;
GLUTATHIONE; NEURONS; DRUGS; RATS
AB Diets given for 30 days with various mono-(MUFA) and poly-(PUFA) unsaturated fatty acid contents were evaluated for brain protection in magnesium-deficient mice: a commercial and three synthetic diets (n-6PUFA, n-3PUFA and MUFA-based chows enriched with 5% corn/sunflower oils 1:3, with 5% rapeseed oil and with 5% high oleic acid sunflower oil/sunflower oil 7:3, respectively). Unlike magnesium deprivation, they induced significant differences in brain and erythrocyte membrane phospholipid fatty acid compositions. n-3PUFA but not other diets protected magnesium-deficient mice against hyperactivity and moderately towards maximal electroshock- and NMDA-induced seizures. This diet also inhibited audiogenic seizures by 50%, preventing animal deaths. Because, like n-6PUFA diet, matched control MUFA diet failed to induce brain protections, alpha-linolenate (ALA) rather than reduced n-6 PUFA diet content is concluded to cause n-3PUFA neuroprotection. Present in vivo data also corroborate literature in vitro inhibition of T type calcium channels by n-3 PUFA, adding basis to ALA supplementation in human anti-epileptic/neuroprotective strategies. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Vamecq, Joseph] CHRU Lille, INSERM, Ctr Biol & Pathol Pierre Marie Degand, Dept Prof Nicole Porchet, Lille, France.
[Pages, Nicole; Delplanque, Bernadette] Univ Paris 11, NMPA, CNPS, Orsay, France.
[Pages, Nicole] Strasbourg Univ, Illkirch Graffenstaden, France.
[Maurois, Pierre; Bac, Pierre] Ctr Chirurg Marie Lannelongue, INSERM, IFR 141, U999, F-92350 Le Plessis Robinson, France.
[Maurois, Pierre; Bac, Pierre] Univ Paris 11, Fac Pharm, Neuropharmacol Lab, F-92290 Chatenay Malabry, France.
[Martin, Jean-Charles; Du, Qin] Inst Natl Rech Agron, UMR1260, Marseille, France.
[Rapoport, Stanley I.] NIH, Bethesda, MD 20892 USA.
RP Vamecq, J (reprint author), CHRU Lille, INSERM, Ctr Biol & Pathol Pierre Marie Degand, Dept Prof Nicole Porchet, Lille, France.
EM joseph.vamecq@inserm.fr
FU French Inserm; National Institute of Aging, Bethesda, Maryland, USA
FX This work was supported by the French Inserm (BD, PM and JV). The
research conducted by S.I. Rapoport was supported entirely by the
Intramural Program of the National Institute of Aging, Bethesda,
Maryland, USA.
NR 56
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U1 2
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
EI 1532-2823
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD AUG
PY 2011
VL 85
IS 2
BP 53
EP 60
DI 10.1016/j.plefa.2011.05.001
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 797HD
UT WOS:000293114200001
PM 21664114
ER
PT J
AU Okuda, M
Olfson, M
Hasin, D
Grant, BF
Lin, KH
Blanco, C
AF Okuda, Mayumi
Olfson, Mark
Hasin, Deborah
Grant, Bridget F.
Lin, Keng-Han
Blanco, Carlos
TI Mental Health of Victims of Intimate Partner Violence: Results From a
National Epidemiologic Survey
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID DISORDERS; COMORBIDITY
AB Objective: This study assessed the national incidence and mental health correlates of recent intimate partner violence among adults interviewed by the wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. Methods: Data were collected about minor and severe forms of intimate partner violence among adults who reported being married, recently married, or in a romantic relationship in the past 12 months (N=25,626). Results: A total of 1,608 individuals reported being victims of intimate partner violence, including 5.8% of men and 5.6% of women. New onset of axis I disorders was significantly more common among victims of intimate partner violence than among nonvictims (22.5% and 9.7%, respectively; OR=2.6) and was related to frequency of violent acts. Conclusions: Intimate partner violence is common, and victimization, especially if recurrent, markedly increases the risk for developing several psychiatric disorders. (Psychiatric Services 62:959-962, 2011)
C1 [Okuda, Mayumi; Olfson, Mark; Hasin, Deborah; Grant, Bridget F.; Lin, Keng-Han; Blanco, Carlos] Columbia Univ, Coll Surg, Dept Psychiat, New York, NY 10032 USA.
[Okuda, Mayumi; Olfson, Mark; Hasin, Deborah; Grant, Bridget F.; Lin, Keng-Han; Blanco, Carlos] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Hasin, Deborah] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA.
RP Blanco, C (reprint author), Columbia Univ, Coll Surg, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA.
EM cb255@columbia.edu
RI Blanco, Carlos/I-4906-2013; Okuda, Mayumi/L-6210-2013
OI Blanco, Carlos/0000-0001-6187-3057; Okuda, Mayumi/0000-0002-3479-5599
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National
Institutes of Health (NIH) [DA019606, DA020783, DA023200, DA023973,
MH076051, P60 MD000206, R01 AA08159, K05 AA00161, U01 AA01 8111];
American Foundation for Suicide Prevention
FX NESARC was sponsored by the National Institute on Alcohol Abuse and
Alcoholism (NIAAA) and funded, in part, by the Intramural Program,
NIAAA, and the National Institutes of Health (NIH). This study is
supported by NIH grants DA019606, DA020783, DA023200, DA023973 and
MH076051, P60 MD000206, R01 AA08159, K05 AA00161, and U01 AA01 8111 and
the American Foundation for Suicide Prevention. The views and opinions
expressed in this report are those of the authors and should not be
construed to represent the views of any of the sponsoring organizations
or agencies or the U.S. government.
NR 12
TC 18
Z9 18
U1 1
U2 4
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD AUG
PY 2011
VL 62
IS 8
BP 959
EP 962
PG 4
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 800CP
UT WOS:000293336900020
PM 21807838
ER
PT J
AU Kolobow, T
Cressoni, M
Epp, M
Corti, I
Cadringher, P
Zanella, A
AF Kolobow, Theodor
Cressoni, Massimo
Epp, Myra
Corti, Ivan
Cadringher, Paolo
Zanella, Alberto
TI Comparison of a Novel Lycra Endotracheal Tube Cuff to Standard Polyvinyl
Chloride Cuff and Polyurethane Cuff for Fluid Leak Prevention
SO RESPIRATORY CARE
LA English
DT Article
DE endotracheal tube; cuff; ventilator; mechanical ventilation;
ventilator-associated pneumonia
ID MECHANICAL VENTILATION; PULMONARY ASPIRATION; SUBGLOTTIC SECRETION;
TRACHEAL TUBES; PRESSURE; PNEUMONIA; SEAL
AB BACKGROUND: A high-volume low-pressure endotracheal tube (ETT) cuff forms folds along its contact with the trachea, allowing mucus leakage into the lungs. We developed a thin-walled ETT cuff made of Lycra polyurethane. METHODS: In vitro, we tested 6 of each of the new prototype Lycra cuff, the Mallinkrodt Hi-Lo ETT (polyvinyl chloride cuff), and the Kimberly-Clark Microcuff ETT (polyurethane cull), for leakage, in an acrylic mock trachea (inner diameter 20-mm), with a cuff inflation pressure of 20 cm H(2)O. We poured 15 mL of methylene-blue colored water into the acrylic tube above the cuff and observed for leakage for 24 hours. RESULTS: The Lycra cuffs had no folds upon inflation in the mock trachea and completely prevented fluid leakage for 24 hours (P < .001 vs the Hi-Lo and the Microcuff). The average leakage past the Hi-Lo was 1,182 +/- 1,321 mL/h. The average leakage past the Microcuff was 1.2 +/- 0.4 mL/h (P < .001 vs the Hi-Lo). CONCLUSIONS: Our Lycra cuff provided complete tracheal sealing in vitro.
C1 [Kolobow, Theodor; Epp, Myra; Corti, Ivan] NHLBI, Sect Pulm & Cardiac Assist Devices, Pulm & Crit Care Med Branch, NIH, Bethesda, MD 20892 USA.
[Cressoni, Massimo; Cadringher, Paolo] Osped Maggiore Policlin Mangiagalli Regina Elena, Ist Anestesiol & Rianimaz, Fdn Ist Ricovero & Cura Carattere Sci, Milan, Italy.
[Zanella, Alberto] Univ Milano Bicocca, Dept Expt Med, Monza, Italy.
RP Cressoni, M (reprint author), Osped Maggiore Policlin, Ist Anestesiol & Rianimaz, Fdn Ist Ricovero & Cura Carattere Sci, Via Francesco Sforza 35, I-20122 Milan, Italy.
EM mcressoni@hotmail.com
RI Cressoni, Massimo/B-7315-2017;
OI Cressoni, Massimo/0000-0002-0089-2905; zanella,
Alberto/0000-0002-2967-2527
NR 18
TC 18
Z9 19
U1 0
U2 2
PU DAEDALUS ENTERPRISES INC
PI IRVING
PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA
SN 0020-1324
J9 RESP CARE
JI Respir. Care
PD AUG
PY 2011
VL 56
IS 8
BP 1095
EP 1099
DI 10.4187/respcare.01099
PG 5
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 807BO
UT WOS:000293868500003
PM 21496368
ER
PT J
AU Shin, IS
Jang, BS
Paik, CH
Maeng, JS
AF Shin, In Soo
Jang, Beom-Su
Paik, Chang H.
Maeng, Jin-Soo
TI Synthesis, Optimization and Imaging Study of Avidin-Conjugated
Petidomimetic Antagonist to Pre-Target an Angiogenic Marker, Integrin
alpha(v)beta(3)
SO TISSUE ENGINEERING AND REGENERATIVE MEDICINE
LA Korean
DT Article
DE neovasculature imaging; matrigel-scaffolded melanoma; angiogenic
biomarker; integrin alpha(v)beta(3); avidin-conjugated integrin
antagonist
ID TUMOR; NEOVASCULATURE; ANTIBODY; THERAPY; CELLS
AB Determination of angiogenesis has been used for the verification of new tissue generation or tumor cell growth. In this study, we developed a pre-targeting method with non-invasive imaging technique, which can detect angiogenic stage of neovasculature in tumor xenografted mouse model. The angiogenesis was induced by transplanting M21 melanoma with continuous proliferation activity and the aid of biomaterial scaffold, Matrigel, as a tissue engineering drug preparations from basement membrane matrix. Angiogenic biomarker, integrin alpha(v)beta(3) receptor molecule was selected as the target of this pre-targeting study and one of the RGD peptide mimics or integrin alpha(v)beta(3) receptor antagonist (IA), 4-[2-(3,4,5,6-tetrahydro-pyrimidine-2-ylamino)ethyloxy]benzoyl-2-(S)-amino-ethylsulfonyl-amino-beta-alanine with specific binding ability to integrin alpha(v)beta(3) was chosen as a potent bio-nano probe for imaging. IA was conjugated to avidin (Av) to increase its receptor-binding avidity and to optimize parameters to pre-target alpha(v)beta(3)-expressing tumor. Parameters including conjugation levels, amount of conjugates injected, and injection time intervals between Av-(IA)(n) and In-111-DOTA-biotin were investigated to optimize tumor-to-blood (T/B) and tumor-to-liver (T/L) ratios in nude mice with s.c. receptor-expressing M21 human melanoma. Mice were imaged 2 hours after In-111-DOTA-biotin injection with a gamma camera. Comparing the level (n) of Av-(IA)(n) (200 mu g) injected, the case of n=10 to 15 produced higher T/B (8.11 +/- 4.23) and T/L (1.55 +/- 1.42) ratios than the case of n=5. This neovasculature pre-targeting approach using the avidin-biotin system resulted in high tumor-to-background (angiogenic-to-normal) ratios and warrants further studies for assessing the alpha(v)beta(3) receptor expression in angiogenesis induced by the combined xenografts of implanted tumor and basement membrane matrix scaffold.
C1 [Maeng, Jin-Soo] Korea Food Res Inst, Bionanotechnol Res Ctr, Songnam 463746, Gyeonggi Do, South Korea.
[Shin, In Soo] Korea Food & Drug Adm, Blood Prod Teams, Natl Inst Food & Drug Safety Evaluat, Chungwon Kun 369951, Chungbuk, South Korea.
[Jang, Beom-Su] Korea Atom Energy Res Inst, Adv Radiat Technol Inst, Radiat Biotechnol Res Div, Jeongeup Si 580185, Jeonbuk, South Korea.
[Paik, Chang H.] NIH, Radiopharmacueitcal Lab, Radiol & Imaging Sci Dept, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Maeng, JS (reprint author), Korea Food Res Inst, Bionanotechnol Res Ctr, 516 Baekhyun Dong, Songnam 463746, Gyeonggi Do, South Korea.
EM maengjs@kfri.re.kr
NR 17
TC 0
Z9 0
U1 0
U2 4
PU KOREAN TISSUE ENGINEERING REGENERATIVE MEDICINE SOC
PI JONGRO-GU
PA 199-1, DONGSUNG-DONG,, JONGRO-GU, SEOUL 110-810, SOUTH KOREA
SN 1738-2696
J9 TISSUE ENG REGEN MED
JI Tissue Eng. Regen. Med.
PD AUG
PY 2011
VL 8
IS 4
BP 99
EP 107
PG 9
WC Cell & Tissue Engineering; Engineering, Biomedical
SC Cell Biology; Engineering
GA 802DV
UT WOS:000293490400017
ER
PT J
AU Favoni, RE
Florio, T
AF Favoni, Roberto E.
Florio, Tullio
TI Combined chemotherapy with cytotoxic and targeted compounds for the
management of human malignant pleural mesothelioma
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID PHASE-II TRIAL; SOUTHWEST-ONCOLOGY-GROUP; CANCER STEM-CELLS; LEUKEMIA
GROUP-B; SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR;
PREVIOUSLY TREATED PATIENTS; ENDOTHELIAL GROWTH-FACTOR; HIGH-DOSE
CISPLATIN; LUNG-CANCER
AB Human malignant pleural mesothelioma (hMPM) is an aggressive asbestos-associated cancer, the incidence of which is increasing and which, despite progress in diagnosis and therapy, continues to have a poor prognosis. Asbestos fibers induce aberrant cell signaling, leading to proto-oncogene activation and chemoresistance. In this review, we discuss the evolution of pharmacological management of hMPM up to the most recent advances. Monotherapy with single cytotoxic drugs achieves modest objective response rates, seldom reaching 30%. However, combination regimens using novel drugs and standard molecules are showing gradually improving responses and clinical benefits. Phase II/III studies have identified pemetrexed, a multitarget folate pathway inhibitor in combination with platinum derivatives, and the cisplatin/gemcitabine association as front-line chemotherapy for hMPM. Detailed knowledge of molecular mechanisms of signal transduction and neoangiogenesis in hMPM should aid in the design and screening of other promising compounds such as more efficacious receptor tyrosine kinase inhibitors.
C1 [Favoni, Roberto E.] Natl Canc Inst, Gene Transfer Lab, Dept Translat Oncol Res, I-16132 Genoa, Italy.
[Favoni, Roberto E.; Florio, Tullio] Univ Genoa, Dept Oncol Biol & Genet, Pharmacol Sect, I-16132 Genoa, Italy.
[Florio, Tullio] Univ Genoa, Ctr Excellence Biomed Res, I-16132 Genoa, Italy.
RP Favoni, RE (reprint author), Natl Canc Inst, Gene Transfer Lab, Dept Translat Oncol Res, Largo Rosanna Benzi 10, I-16132 Genoa, Italy.
EM roberto.favoni@istge.it
RI Florio, Tullio/A-2211-2012
OI Florio, Tullio/0000-0002-2394-996X
NR 151
TC 13
Z9 13
U1 0
U2 0
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD AUG
PY 2011
VL 32
IS 8
BP 463
EP 479
DI 10.1016/j.tips.2011.03.011
PG 17
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 807WA
UT WOS:000293932500003
PM 21620489
ER
PT J
AU Crea, F
Duhagon, MA
Farrar, WL
Danesi, R
AF Crea, Francesco
Ana Duhagon, Maria
Farrar, William L.
Danesi, Romano
TI Pharmacogenomics and cancer stem cells: a changing landscape?
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID METASTATIC BREAST-CANCER; DISSEMINATED TUMOR-CELLS; LUNG-CANCER;
SELF-RENEWAL; SIDE POPULATION; COLON-CANCER; IN-VIVO; BIOLOGICAL
FUNCTIONS; COLORECTAL-CANCER; DRUG-RESISTANCE
AB Pharmacogenomics in oncology holds the promise to personalize cancer therapy. However, its clinical application is still limited to a few genes, and, in the large majority of cancers, the correlation between genotype and clinical outcome has been disappointing. One possible explanation is that current pharmacogenomic studies do not take into account the emerging role of cancer stem cells (CSCs) in drug sensitivity and resistance. CSCs are a subpopulation of cells driven by specific signal-transduction pathways, but genetic variants affecting their activity are generally neglected in current pharmacogenomic studies. Moreover, in several malignancies, CSCs represent a rare sub-population; therefore, whole tumor profiling might mask CSC gene expression patterns. This article reviews current evidence on CSC chemoresistance and shows how common genetic variations in CSC-related genes may predict individual response to anti-cancer agents. Furthermore, we provide insights into the design of pharmacogenomic studies to address the clinical usefulness of CSC genetic profiling.
C1 [Crea, Francesco; Danesi, Romano] Univ Pisa, Dept Internal Med, Div Pharmacol, Pisa, Italy.
[Ana Duhagon, Maria] Univ Republica, Fac Med, Dept Genet, Lab Interacc Mol, Montevideo, Uruguay.
[Farrar, William L.] NCI, Lab Canc Prevent, Canc Stem Cell Sect, Frederick, MD 21701 USA.
RP Danesi, R (reprint author), Univ Pisa, Dept Internal Med, Div Pharmacol, Pisa, Italy.
EM r.danesi@med.unipi.it
RI Crea, Francesco /I-8383-2015;
OI Crea, Francesco/0000-0002-4903-2973
FU Intramural NIH HHS [ZIA BC010794-04]
NR 79
TC 10
Z9 10
U1 0
U2 5
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD AUG
PY 2011
VL 32
IS 8
BP 487
EP 494
DI 10.1016/j.tips.2011.03.010
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 807WA
UT WOS:000293932500005
PM 21529973
ER
PT J
AU Deb, G
Boeshanes, K
Idler, WK
Ahvazi, B
AF Deb, Gouri
Boeshanes, Karen
Idler, William K.
Ahvazi, Bijan
TI Cloning, expression, purification, crystallization and preliminary X-ray
diffraction studies of a 12R-LOX-chaperone complex
SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION
COMMUNICATIONS
LA English
DT Article
ID ESCHERICHIA-COLI; PROTEINS; ACID; OVEREXPRESSION; AGGREGATION; SUBSTRATE
AB Lipoxygenases are a family of nonheme iron-containing dioxygenases. An Escherichia coli expression system producing the bacterial chaperones GroES and GroEL was engineered and successfully used to produce large quantities of recombinant human 12R-LOX (LOXR; MW 80.34 kDa; 701 amino-acid residues). The co-overproduction of the two chaperones with 12R-LOX resulted in increased solubility of 12R-LOX and allowed the purification of milligram amounts of active enzyme for structural studies by X-ray diffraction. The lipoxygenase protein was purified on an affinity column and a gel-filtration column with chaperone protein (MW 57.16 kDa). The LOXR-chaperone complex was crystallized with ligand by the hanging-drop vapor-diffusion method using 1.5 M ammonium hydrogen phosphate as precipitant. The crystals belonged to the monoclinic system, space group P2(1), with unit-cell parameters a = 138.97, b = 266.11, c = 152.26 angstrom, beta = 101.07 degrees. Based on the calculated Matthews coefficient (3.1 angstrom(3) Da(-1)), it is estimated that one molecule of LOXR complexed with two molecules of chaperone is present in the asymmetric unit of the crystal lattice. X-ray diffraction data were collected to 4 A resolution using synchrotron radiation.
C1 [Deb, Gouri; Boeshanes, Karen; Idler, William K.; Ahvazi, Bijan] NIAMSD, Xray Crystallog Facil, NIH, Bethesda, MD 20892 USA.
RP Deb, G (reprint author), NIAMSD, Xray Crystallog Facil, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gou5skm2001@yahoo.com
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health
FX The 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. The authors gratefully acknowledge
Brookhaven National Laboratory for the provision of beamline and other
facilities.
NR 25
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1744-3091
J9 ACTA CRYSTALLOGR F
JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun.
PD AUG
PY 2011
VL 67
BP 903
EP 906
DI 10.1107/S1744309111021361
PN 8
PG 4
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 805AM
UT WOS:000293698400014
PM 21821891
ER
PT J
AU Simone, O
Bejarano, MT
Pierce, SK
Antonaci, S
Wahlgren, M
Troye-Blomberg, M
Donati, D
AF Simone, Olivia
Bejarano, Maria Teresa
Pierce, Susan K.
Antonaci, Salvatore
Wahlgren, Mats
Troye-Blomberg, Marita
Donati, Dania
TI TLRs innate immunereceptors and Plasmodium falciparum erythrocyte
membrane protein 1 (PfEMP1) CIDR1 alpha-driven human polyclonal B-cell
activation
SO ACTA TROPICA
LA English
DT Article
DE B cells; Toll-like receptors (TLRs); Malaria; Signal transduction
ID TOLL-LIKE RECEPTORS; PLASMACYTOID DENDRITIC CELLS; HUMAN MALARIA;
ANTIGEN-RECEPTOR; EXPRESSION; RNA; IDENTIFICATION; STIMULATION;
ASSOCIATION; LYMPHOCYTES
AB Chronic malaria severely affects the immune system and causes polyclonal B-cell activation, as evidenced by the presence of hypergammaglobulinemia, elevated levels of autoantibodies, loss of B-cell memory and the frequent occurrence of Burkitt's lymphomas (BL) in children living in malaria endemic areas.
Previous studies have shown that the cysteine-rich interdomain region 1 alpha (CIDR1 alpha) of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) of the FCR3S1.2 strain, subsequently named CIDR1a, interacts with B cells partially through the binding to the B-cell receptor (BCR). This interaction leads to an activated phenotype, increased survival, and a low degree of proliferation. CIDR1 alpha preferentially activates the memory B-cell compartment, therefore PfEMP1 is considered to act as a polyclonal B-cell activator and its role in memory maintenance has been suggested.
In this report, we extend the analysis of the PfEMP1-CIDR1 alpha B-cell interaction and demonstrate that PfEMP1-CIDR1 alpha increases the expression of TLR7 and TLR10 mRNA transcripts and sensitizes B cells to TLR9 signalling via the MyD88 adaptor molecule. Furthermore, despite its ability to bind to surface Igs, PfEMP1-CIDR1 alpha-induced B-cell activation does not seem to proceed through the BCR, since it does not induce Lyn and/or phospho-tyrosine mediated signalling pathways. Rather PfEMP1-CIDR1 alpha induces the phosphorylation of downstream kinases, such as ERK1/2, p38 and IKB alpha, in human B cells. These findings indicate that PfEMP1-CIDR1 alpha induces a persistent activation of B cells, which in turn can contribute to the exhaustion and impairment of B-cell functions during chronic malaria infection. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Simone, Olivia; Antonaci, Salvatore] Univ Bari, Policlin Bari, Dept Internal Med Immunol & Infect Dis, Sch Med, I-70124 Bari, Italy.
[Bejarano, Maria Teresa; Donati, Dania] Karolinska Univ Sjukh Tumor & Uset Huddinge, Karolinska Inst, SE-14186 Stockholm, Sweden.
[Bejarano, Maria Teresa; Wahlgren, Mats] Karolinska Inst, Dept Microbiol, SE-17177 Stockholm, Sweden.
[Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Simone, Olivia; Troye-Blomberg, Marita] Stockholm Univ, Dept Immunol, SE-10691 Stockholm, Sweden.
[Bejarano, Maria Teresa; Donati, Dania] Ctr Infect Med, Dept Med, Huddinge, Sweden.
RP Simone, O (reprint author), Univ Bari, Policlin Bari, Dept Internal Med Immunol & Infect Dis, Sch Med, Pzza G Cesare 11, I-70124 Bari, Italy.
EM olivia.simone@intmed.uniba.it
RI Troye-Blomberg, Marita/B-9210-2016
OI Troye-Blomberg, Marita/0000-0002-2804-0325
FU Swedish Agency for Research Development; Swedish Research Council (VR);
EviMalaR Network of Excellence; BioMalPar European Network of Excellence
[LSMP-CT-2004-503578]; Priority 1 "Life Sciences, Genomics and
Biotechnology for Health" in the 6th Framework Programme
FX This work was supported by grants to from the Swedish Agency for
Research Development with Developing Countries (SIDA, SAREC), the
Swedish Research Council (VR) as well as grants within the EviMalaR and
BioMalPar European Networks of Excellence (LSMP-CT-2004-503578) and from
the Priority 1 "Life Sciences, Genomics and Biotechnology for Health" in
the 6th Framework Programme.
NR 39
TC 19
Z9 20
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0001-706X
J9 ACTA TROP
JI Acta Trop.
PD AUG
PY 2011
VL 119
IS 2-3
BP 144
EP 150
DI 10.1016/j.actatropica.2011.05.005
PG 7
WC Parasitology; Tropical Medicine
SC Parasitology; Tropical Medicine
GA 805HJ
UT WOS:000293717200013
PM 21620790
ER
PT J
AU Hasler, WL
Wilson, LA
Parkman, HP
Nguyen, L
Abell, TL
Koch, KL
Pasricha, PJ
Snape, WJ
Farrugia, G
Lee, L
Tonascia, J
Unalp-Arida, A
Hamilton, F
AF Hasler, William L.
Wilson, Laura A.
Parkman, Henry P.
Linda Nguyen
Abell, Thomas L.
Koch, Kenneth L.
Pasricha, Pankaj J.
Snape, William J.
Farrugia, Gianrico
Lee, Linda
Tonascia, James
Unalp-Arida, Aynur
Hamilton, Frank
CA NIDDK Gastroparesis Clinical Res C
TI Bloating in Gastroparesis: Severity, Impact, and Associated Factors
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID IRRITABLE-BOWEL-SYNDROME; MEAL-RELATED SYMPTOMS; FUNCTIONAL DYSPEPSIA;
VISCERAL SENSATION; DIABETES-MELLITUS; RISK-FACTORS; PREVALENCE;
PREDICTORS; DISTENSION; DISORDERS
AB OBJECTIVES: Bloating is commonly reported in gastroparesis, but its prevalence, impact, and associated factors are uninvestigated. We aimed to quantify the prevalence of bloating in gastroparesis and relate its severity to clinical factors and quality of life.
METHODS: Survey, examination, and scintigraphy data were compared in 335 gastroparesis patients from 6 centers of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Gastroparesis Clinical Research Consortium. Bloating severity was stratified using Gastroparesis Cardinal Symptom Index (GCSI) bloating subscale scores.
RESULTS: Bloating severity of at least mild (GCSI >= 2) and severe (GCSI >= 4) grades were reported by 76 and 41% of patients, respectively. Bloating severity related to female gender (P < 0.0001) and overweight status (P = 0.04) on regression analysis and correlated with intensity of nausea, postprandial fullness, visible distention, abdominal pain, and altered bowel function (P < 0.05). Disease etiology, smoking status, and gastric emptying did not relate to bloating subset (P > 0.05). Disease-specific quality of life and general measures of well-being were progressively impaired with increasing bloating severity (P = 0.01). Probiotic use (P = 0.03) and use of antidepressants with significant norepinephrine reuptake inhibitor activity (P = 0.045) use related to bloating severity; antiemetic use trended higher with worsening bloating (P = 0.06).
CONCLUSIONS: Bloating is prevalent in gastroparesis and is severe in many individuals. Bloating severity relates to female gender, body weight, and intensity of other symptoms. The symptom impairs quality of life but is not influenced by gastric emptying rates. Antiemetics, probiotics, and antidepressants with significant norepinephrine reuptake inhibitor activity may affect reports of bloating. These findings provide insight into this underappreciated symptom of gastroparesis.
C1 [Wilson, Laura A.; Lee, Linda; Tonascia, James; Unalp-Arida, Aynur] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Parkman, Henry P.] Temple Univ, Gastroenterol Sect, Philadelphia, PA 19122 USA.
[Linda Nguyen; Pasricha, Pankaj J.] Stanford Univ, Div Gastroenterol & Hepatol, Palo Alto, CA 94304 USA.
[Abell, Thomas L.] Univ Mississippi, Div Digest Dis, Jackson, MS 39216 USA.
[Koch, Kenneth L.] Wake Forest Univ, Dept Internal Med, Winston Salem, NC 27109 USA.
[Snape, William J.] Calif Pacific Med Ctr, Div Gastroenterol, San Francisco, CA USA.
[Farrugia, Gianrico] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Hamilton, Frank] NIDDK, Digest Dis Branch, Bethesda, MD USA.
[Hasler, William L.] Univ Michigan, Taubman Ctr 3912, Dept Internal Med, Ann Arbor, MI 48109 USA.
RP Hasler, WL (reprint author), Univ Michigan, Taubman Ctr 3912, Dept Internal Med, Ann Arbor, MI 48109 USA.
EM whasler@umich.edu
RI Vaughn, Ivana/B-6138-2016
OI Vaughn, Ivana/0000-0002-7201-0289
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
as part of the Gastroparesis Clinical Research Consortium (GpCRC)
[U01DK073983, U01DK073975, U01DK073985, U01DK074007, U01DK073974,
U01DK074008]
FX This project received support from the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK) (grants U01DK073983,
U01DK073975, U01DK073985, U01DK074007, U01DK073974, and U01DK074008) as
part of its funding of the Gastroparesis Clinical Research Consortium
(GpCRC).
NR 36
TC 17
Z9 18
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD AUG
PY 2011
VL 106
IS 8
BP 1492
EP 1502
DI 10.1038/ajg.2011.81
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 801PS
UT WOS:000293453200012
PM 21483459
ER
PT J
AU Ungvari, Z
Bailey-Downs, L
Sosnowska, D
Gautam, T
Koncz, P
Losonczy, G
Ballabh, P
de Cabo, R
Sonntag, WE
Csiszar, A
AF Ungvari, Zoltan
Bailey-Downs, Lora
Sosnowska, Danuta
Gautam, Tripti
Koncz, Peter
Losonczy, Gyorgy
Ballabh, Praveen
de Cabo, Rafael
Sonntag, William E.
Csiszar, Anna
TI Vascular oxidative stress in aging: a homeostatic failure due to
dysregulation of NRF2-mediated antioxidant response
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE senescence; apoptosis; oxidative stress resistance; vascular injury
ID ARTERIAL ENDOTHELIAL-CELLS; TRANSCRIPTION FACTOR NRF2; MN
SUPEROXIDE-DISMUTASE; LONGEST-LIVING RODENT; NECROSIS-FACTOR-ALPHA;
KAPPA-B ACTIVATION; NAKED MOLE-RAT; LIFE-SPAN; NF-E2-RELATED FACTOR-2;
OXIDIZED PHOSPHOLIPIDS
AB Ungvari Z, Bailey-Downs L, Sosnowska D, Gautam T, Koncz P, Losonczy G, Ballabh P, de Cabo R, Sonntag WE, Csiszar A. Vascular oxidative stress in aging: a homeostatic failure due to dysregulation of NRF2-mediated antioxidant response. Am J Physiol Heart Circ Physiol 301: H363-H372, 2011. First published May 20, 2011; doi:10.1152/ajpheart.01134.2010.-There is strong evidence showing that aging is associated with vascular oxidative stress, which has been causally linked to the development of cardiovascular diseases. NF-E2-related factor-2 (Nrf2) is a transcription factor, which is activated by reactive oxygen species in the vasculature of young animals leading to the upregulation of various antioxidant genes. The present study was designed to elucidate age-related changes in the homeostatic role of Nrf2-driven free radical detoxification mechanisms in the vasculature. We found that in the aorta of Fischer 344 x Brown Norway rats, aging results in a progressive increase in O(2)(-) production, and downregulates protein and mRNA expression of Nrf2, which is associated with a decreased nuclear Nrf2 activity and a decrease in the Nrf2 target genes NAD(P) H: quinone oxidoreductase 1, gamma-glutamylcysteine synthetase, and heme oxygenase-1. There was an inverse relationship between vascular expression of Nrf2 target genes and age-related increases in the expression of the NF-kappa B target genes ICAM-1 and IL-6, which was significant by regression analysis. In cultured aorta segments of young (3 mo old) rats treatment with H(2)O(2) and high glucose significantly increases nuclear translocation of Nrf2 and upregulates the expression of Nrf2 target genes. In contrast, in cultured aorta segments of aged (24 mo old) rats, the induction of Nrf2-dependent responses by H(2)O(2) and high glucose are blunted. High glucose-induced vascular oxidative stress was more severe in aortas of aged rats, as shown by the significantly increased H(2)O(2) production in these vessels, compared with responses obtained in aortas from young rats. Moreover, we found that aging progressively increases vascular sensitivity to the proapoptotic effects of H(2)O(2) and high glucose treatments. Taken together, aging is associated with Nrf2 dysfunction in the vasculature, which likely exacerbates age-related cellular oxidative stress and increases sensitivity of aged vessels to oxidative stress-induced cellular damage.
C1 [Ungvari, Zoltan; Bailey-Downs, Lora; Sosnowska, Danuta; Gautam, Tripti; Koncz, Peter; Sonntag, William E.; Csiszar, Anna] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK 73104 USA.
[Losonczy, Gyorgy] Semmelweis Univ, Dept Pulmonol, Budapest, Hungary.
[Ballabh, Praveen] New York Med Coll, Dept Pediat, Westchester Med Ctr, Valhalla, NY 10595 USA.
[Ballabh, Praveen] New York Med Coll, Westchester Med Ctr, Dept Anat, Valhalla, NY 10595 USA.
[Ballabh, Praveen] New York Med Coll, Westchester Med Ctr, Dept Cell Biol, Valhalla, NY 10595 USA.
[de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
RP Csiszar, A (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, 975 NE 10th St,BRC 1303, Oklahoma City, OK 73104 USA.
EM zoltan-ungvari@ouhsc.edu; anna-csiszar@ouhsc.edu
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU American Diabetes Association; American Federation for Aging Research;
American Heart Association; University of Oklahoma College of Medicine
Alumni Association; The Oklahoma Center for the Advancement of Science
and Technology; National Institutes of Health (NIH) [AG-031085,
AT-006526, HL-077256, 1R01-AG-038747, 5R01-NS-056218, P01 AG-11370]
FX This work was supported by grants from the American Diabetes Association
(to Z. Ungvari), American Federation for Aging Research (to A. Csiszar),
the American Heart Association (to A. Csiszar), the University of
Oklahoma College of Medicine Alumni Association (to A. Csiszar), The
Oklahoma Center for the Advancement of Science and Technology (to A.
Csiszar and Z. Ungvari), the National Institutes of Health (NIH;
AG-031085 to A. Csiszar; AT-006526 and HL-077256 to Z. Ungvari;
1R01-AG-038747, 5R01-NS-056218, and P01 AG-11370 to W. E. Sonntag), and
the Intramural Research Program of NIH (to R. D. Cabo).
NR 65
TC 72
Z9 75
U1 0
U2 12
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD AUG
PY 2011
VL 301
IS 2
BP H363
EP H372
DI 10.1152/ajpheart.01134.2010
PG 10
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 801MQ
UT WOS:000293443800011
PM 21602469
ER
PT J
AU Wadley, VG
Unverzagt, FW
McGuire, LC
Moy, CS
Go, R
Kissela, B
McClure, LA
Crowe, M
Howard, VJ
Howard, G
AF Wadley, Virginia G.
Unverzagt, Frederick W.
McGuire, Lisa C.
Moy, Claudia S.
Go, Rodney
Kissela, Brett
McClure, Leslie A.
Crowe, Michael
Howard, Virginia J.
Howard, George
TI Incident Cognitive Impairment is Elevated in the Stroke Belt: The
REGARDS Study
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID CARDIOVASCULAR RISK-FACTORS; TRANSIENT ISCHEMIC ATTACK; SILENT BRAIN
INFARCTS; MINI-MENTAL-STATE; RACIAL-DIFFERENCES; AFRICAN-AMERICANS;
OLDER-ADULTS; POPULATION; DECLINE; MORTALITY
AB Objective: To determine whether incidence of impaired cognitive screening status is higher in the southern Stroke Belt region of the United States than in the remaining United States.
Methods: A national cohort of adults age >= 45 years was recruited by the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from 2003 to 2007. Participants' global cognitive status was assessed annually by telephone with the Six-Item Screener (SIS) and every 2 years with fluency and recall tasks. Participants who reported no stroke history and who were cognitively intact at enrollment (SIS >4 of 6) were included (N = 23,913, including 56% women; 38% African Americans and 62% European Americans; 56% Stroke Belt residents and 44% from the remaining contiguous United States and the District of Columbia). Regional differences in incident cognitive impairment (SIS score <= 4) were adjusted for age, sex, race, education, and time between first and last assessments.
Results: A total of 1,937 participants (8.1%) declined to an SIS score <= 4 at their most recent assessment, over a mean of 4.1 (+/- 1.6) years. Residents of the Stroke Belt had greater adjusted odds of incident cognitive impairment than non-Belt residents (odds ratio, 1.18; 95% confidence interval, 1.07-1.30). All demographic factors and time independently predicted impairment.
Interpretation: Regional disparities in cognitive decline mirror regional disparities in stroke mortality, suggesting shared risk factors for these adverse outcomes. Efforts to promote cerebrovascular and cognitive health should be directed to the Stroke Belt. ANN NEUROL 2011;70:229-236
C1 [Wadley, Virginia G.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Unverzagt, Frederick W.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA.
[McGuire, Lisa C.] Ctr Dis Control & Prevent, Healthy Aging Program, Atlanta, GA USA.
[Moy, Claudia S.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Go, Rodney; Howard, Virginia J.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA.
[Kissela, Brett] Univ Cincinnati, Dept Neurol, Cincinnati, OH USA.
[McClure, Leslie A.; Howard, George] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA.
[Crowe, Michael] Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA.
RP Wadley, VG (reprint author), Univ Alabama, Dept Med, CH19 218T, Birmingham, AL 35294 USA.
EM vwadley@uab.edu
RI McClure, Leslie/P-2929-2015;
OI Kissela, Brett/0000-0002-9773-4013
FU National Institute of Neurological Disorders and Stroke, NIH, Department
of Health and Human Services [U01 NS041588]; Centers for Disease Control
and Prevention
FX This research project is supported by a cooperative agreement U01
NS041588 from the National Institute of Neurological Disorders and
Stroke, NIH, Department of Health and Human Services. Additional funding
was provided by the Centers for Disease Control and Prevention's Healthy
Aging Program. The content is solely the responsibility of the authors
and does not necessarily represent the official views and positions of
the National Institute of Neurological Disorders and Stroke, the NIH, or
the Centers for Disease Control and Prevention. Representatives of the
funding agencies were involved in the review of the manuscript prior to
submission for publication.
NR 37
TC 25
Z9 25
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD AUG
PY 2011
VL 70
IS 2
BP 229
EP 236
DI 10.1002/ana.22432
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 806NP
UT WOS:000293815200009
PM 21618586
ER
PT J
AU Kipfer, S
Stephan, MA
Schupbach, WMM
Ballinari, P
Kaelin-Lang, A
AF Kipfer, Stefan
Stephan, Marianne A.
Schuepbach, W. M. Michael
Ballinari, Pietro
Kaelin-Lang, Alain
TI Resting Tremor in Parkinson Disease A Negative Predictor of
Levodopa-Induced Dyskinesia
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID SUBTHALAMIC NUCLEUS STIMULATION; PROGRESSION
AB Background: It is unclear whether patients with different clinical subtypes of Parkinson disease (PD) differ in their risk of developing levodopa-induced dyskinesia (LID) and whether resting tremor is negatively correlated with this risk.
Objectives: To determine whether resting tremor as an initial manifestation of PD negatively correlated with subsequent occurrence and severity of LID and to study the correlations between LID and other epidemiological factors (eg, age at onset of PD and duration of PD).
Design: Logistic regression analysis was used to determine predictive factors of LID. Spearman rank correlations between LID and epidemiological factors and motor signs (including tremor) were calculated.
Setting: Institutional tertiary referral center for movement disorders.
Patients: Cohort of 85 patients with PD.
Main Outcome Measure: Occurrence of LID according to the Unified Parkinson Disease Rating Scale part IV.
Results: Resting tremor as an initial manifestation of PD was associated with reduced risk of developing LID independent of other predictors of LID (duration of PD, axial signs, and levodopa dose).
Conclusion: Resting tremor as an initial manifestation of PD predicts lower probability of developing LID under levodopa treatment.
C1 [Kipfer, Stefan; Stephan, Marianne A.; Schuepbach, W. M. Michael; Kaelin-Lang, Alain] Univ Bern, Inselspital, Berne Univ Hosp, Movement Disorders Ctr,Dept Neurol, CH-3010 Bern, Switzerland.
[Ballinari, Pietro] Univ Bern, Inselspital, Berne Univ Hosp, Dept Psychiat Neurophysiol, CH-3010 Bern, Switzerland.
[Ballinari, Pietro] Univ Bern, Inselspital, Berne Univ Hosp, Dept Psychiat, CH-3010 Bern, Switzerland.
RP Stephan, MA (reprint author), Natl Inst Neurol Disorders & Stroke, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bldg 10,Room 7D50-52, Bethesda, MD 20892 USA.
EM marianne.stephan@alumni.ethz.ch
FU Swiss National Science Foundation; Parkinson Switzerland; Mach-Gaensslen
Stiftung Switzerland; Swiss Parkinson Association
FX Dr Stephan received a fellowship from the Swiss National Science
Foundation to perform scientific studies at the National Institutes of
Health, Bethesda, Maryland. Dr Schupbach received speaker's honoraria
and travel reimbursement from Medtronic and UCB Pharma; he received
research grants from Parkinson Switzerland and Mach-Gaensslen Stiftung
Switzerland. Dr Kaelin-Lang received speaker's and advisory board
honoraria and travel reimbursement from UCB Pharma, Boehringer
Ingelheim, Novartis, and Allergan Inc; he received research grants from
Parkinson Switzerland.; This work was supported by a grant from Swiss
Parkinson Association (Dr Kaelin-Lang).
NR 18
TC 6
Z9 6
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD AUG
PY 2011
VL 68
IS 8
BP 1037
EP 1039
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 804IM
UT WOS:000293647500011
PM 21825240
ER
PT J
AU Fuchtbauer, A
Lassen, LB
Jensen, AB
Howard, J
Quiroga, AD
Warming, S
Sorensen, AB
Pedersen, FS
Fuchtbauer, EM
AF Fuchtbauer, Annette
Lassen, Louise B.
Jensen, Astrid B.
Howard, Jennifer
Quiroga, Adan de Salas
Warming, Soren
Sorensen, Annette B.
Pedersen, Finn S.
Fuchtbauer, Ernst-Martin
TI Septin9 is involved in septin filament formation and cellular stability
SO BIOLOGICAL CHEMISTRY
LA English
DT Article
DE cell migration; cytokinesis; mice; Sept9 knockout; septin
ID ACUTE MYELOID-LEUKEMIA; MAMMALIAN SEPTIN; PUTATIVE PROTOONCOGENE;
OVARIAN-TUMORS; GENE; EXPRESSION; FAMILY; MSF; REGION; CELLS
AB Septin9 (Sept9) is a member of the filament-forming septin family of structural proteins and is associated with a variety of cancers and with hereditary neuralgic amyotrophy. We have generated mice with constitutive and conditional Sept9 knockout alleles. Homozygous deletion of Sept9 results in embryonic lethality around day 10 of gestation whereas mice homozygous for the conditional allele develop normally. Here we report the consequences of homozygous loss of Sept9 in immortalized murine embryonic fibroblasts. Proliferation rate was not changed but cells without Sept9 had an altered morphology compared to normal cells, particularly under low serum stress. Abnormal, fragmented, and multiple nuclei were more frequent in cells without Sept9. Cell migration, as measured by gap-filling and filter-invasion assays, was impaired, but individual cells did not move less than wild-type cells. Sept9 knockout cells showed a reduced resistance to hypo-osmotic stress. Stress fiber and vinculin staining at focal adhesion points was less prominent. Long septin filaments stained for Sept7 disappeared. Instead, staining was found in short, often curved filaments and rings. Furthermore, Sept7 was no longer localized to the mitotic spindle. Together, these data reveal the importance of Sept9 for septin filament formation and general cell stability.
C1 [Fuchtbauer, Annette; Lassen, Louise B.; Jensen, Astrid B.; Howard, Jennifer; Quiroga, Adan de Salas; Sorensen, Annette B.; Pedersen, Finn S.; Fuchtbauer, Ernst-Martin] Univ Aarhus, DK-8000 Aarhus, Denmark.
[Warming, Soren] NCI, Ctr Canc Res, Frederick, MD 21702 USA.
RP Fuchtbauer, EM (reprint author), Univ Aarhus, CF Mollers Alle 3, DK-8000 Aarhus, Denmark.
EM emf@mb.au.dk
RI Sorensen, Annette/B-6955-2008
OI Sorensen, Annette/0000-0002-2462-6281
FU National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research; Danish Cancer Society; Danish Center for Transgenic
Mice (now DAGMAR); Danish Research Council for Health and Disease;
Novo-Nordic Foundation; Fru Astrid Thaysens Legat for Laegevidenskabelig
Grundforskning; Karen Elise Jensens Fond
FX We thank Dr. Peter Hjorth for the blastocyst injection, Dr. Koh-ichi
Nagata for the anti-SEPT9 antibodies, Dr. Anders Lund for the
Cre-encoding retroviral vector, Dr. Hauke Werner and Dr. Julia Patzig
for their help, Tine Birch, Lone Hojgaard, and Astrid Kuhle for their
technical assistance, Joana Dias for her help with the PCR and Dr. Anna
Jurkiewicz for her help with the confocal microscope. The construct for
the Sept9 conditional allele was generated in the laboratory of Drs.
Neal G. Copeland and Nancy A. Jenkins at NCI-Frederick, MD, USA, and we
thank them both for their support. The research carried out by the
Copeland/Jenkins laboratory was supported by the Intramural Research
Program of the National Institutes of Health (NIH), National Cancer
Institute, Center for Cancer Research.; The work was supported by grants
from the Danish Cancer Society to E. M. F. and F. S. P., by the Danish
Center for Transgenic Mice (now DAGMAR), and by grants from the Danish
Research Council for Health and Disease, The Novo-Nordic Foundation, Fru
Astrid Thaysens Legat for Laegevidenskabelig Grundforskning, and Karen
Elise Jensens Fond to F.S.P.
NR 29
TC 15
Z9 15
U1 0
U2 9
PU WALTER DE GRUYTER & CO
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 1431-6730
J9 BIOL CHEM
JI Biol. Chem.
PD AUG-SEP
PY 2011
VL 392
IS 8-9
BP 769
EP 777
DI 10.1515/BC.2011.088
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 805OA
UT WOS:000293736800010
PM 21824004
ER
PT J
AU Klabunde, CN
Cronin, KA
Breen, N
Waldron, WR
Ambs, AH
Nadel, MR
AF Klabunde, Carrie N.
Cronin, Kathleen A.
Breen, Nancy
Waldron, William R.
Ambs, Anita H.
Nadel, Marion R.
TI Trends in Colorectal Cancer Test Use among Vulnerable Populations in the
United States
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HEALTH INTERVIEW SURVEY; MEDICARE ENROLLEES; GUIDELINES; PATTERNS;
QUALITY
AB Background: Evaluating trends in colorectal cancer (CRC) screening use is critical for understanding screening implementation, and whether population groups targeted for screening are receiving it, consistent with guidelines. This study examines recent national trends in CRC test use, including among vulnerable populations.
Methods: We used the 2000, 2003, 2005, and 2008 National Health Interview Survey to examine national trends in CRC screening use overall and for fecal occult blood test (FOBT), sigmoidoscopy, and colonoscopy. We also assessed trends by race/ethnicity, educational attainment, income, time in the United States, and access to health care.
Results: During 2000 to 2008, significant declines in FOBT and sigmoidoscopy use and significant increases in colonoscopy use and in the percentages of adults up-to-date with CRC screening occurred overall and for most population subgroups. Subgroups with consistently lower rates of colonoscopy use and being up-to-date included Hispanics; people with minimal education, low income, or no health insurance; recent immigrants; and those with no usual source of care or physician visits in the past year. Among up-to-date adults, there were few subgroup differences in the type of test by which they were up-to-date (i.e., FOBT, sigmoidoscopy, or colonoscopy).
Conclusions: Although use of CRC screening and colonoscopy increased among U.S. adults, including those from vulnerable populations, 45% of adults aged 50 to 75-or nearly 35 million people-were not up-to-date with screening in 2008.
Impact: Continued monitoring of CRC screening rates among population subgroups with consistently low utilization is imperative. Improvement in CRC screening rates among all population groups in the United States is still needed. Cancer Epidemiol Biomarkers Prev; 20(8); 1611-21. (C)2011 AACR.
C1 [Klabunde, Carrie N.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Bethesda, MD 20892 USA.
[Cronin, Kathleen A.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Waldron, William R.] Informat Management Serv Inc, Silver Spring, MD USA.
[Nadel, Marion R.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA.
RP Klabunde, CN (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, 6130 Execut Blvd,Room 4005, Bethesda, MD 20892 USA.
EM klabundC@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 28
TC 106
Z9 107
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 AUG
PY 2011
VL 20
IS 8
BP 1611
EP 1621
DI 10.1158/1055-9965.EPI-11-0220
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 804AK
UT WOS:000293625600005
PM 21653643
ER
PT J
AU Cook, MB
McGlynn, KA
Devesa, SS
Freedman, ND
Anderson, WF
AF Cook, Michael B.
McGlynn, Katherine A.
Devesa, Susan S.
Freedman, Neal D.
Anderson, William F.
TI Sex Disparities in Cancer Mortality and Survival
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS INFECTION; CELL LUNG-CANCER;
ESTROGEN-RECEPTOR-BETA; BLADDER-CANCER; GENDER-DIFFERENCES; CARCINOMA
PATIENTS; GENE-EXPRESSION; POPULATION; AGE; COMORBIDITY
AB Background: Previous research has noted higher cancer mortality rates and lower survival among males than females. However, systematic comparisons of these two metrics by sex have been limited.
Methods: We extracted U.S. vital rates and survival data from the Surveillance, Epidemiology and End Results Database for 36 cancers by sex and age for the period 1977 to 2006. We compared sex-specific mortality rates and examined male-to-female mortality rate ratios (MRR). We also extracted case data which included age and date of diagnosis, sex, primary cancer site, tumor stage and grade, survival time, vital status, and cause of death. Relative cancer-specific HRs for death in the 5-year period following diagnosis were estimated with Cox proportional hazards models, adjusted for covariates.
Results: For the vast majority of cancers, age-adjusted mortality rates were higher among males than females with the highest male-to-female MRR for lip (5.51), larynx (5.37), hypopharynx (4.47), esophagus (4.08), and urinary bladder (3.36). Cancer-specific survival was, for most cancers, worse for males than females, but such disparities were drastically less than corresponding MRRs [e.g., lip (HR = 0.93), larynx (HR = 1.09), hypopharynx (HR = 0.98), esophagus (HR = 1.05), and urinary bladder (HR = 0.83)].
Conclusions: Male-to-female MRRs differed markedly while cancer survival disparities were much less pronounced. This suggests that sex-related cancer disparities are more strongly related to etiology than prognosis.
Impact: Future analytic studies should attempt to understand causes of observed sex disparities in cancer. Cancer Epidemiol Biomarkers Prev; 20(8); 1629-37. (C)2011 AACR.
C1 [Cook, Michael B.; McGlynn, Katherine A.; Devesa, Susan S.; Freedman, Neal D.; Anderson, William F.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20852 USA.
RP Cook, MB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS Suite 550,Room 5014, Bethesda, MD 20852 USA.
EM michael.cook@nih.gov
RI Cook, Michael/A-5641-2009; Freedman, Neal/B-9741-2015
OI Cook, Michael/0000-0002-0533-7302; Freedman, Neal/0000-0003-0074-1098
FU National Cancer Institute, NIH, Department of Health and Human Services
FX This work was supported by grants from the Intramural Program of the
National Cancer Institute, NIH, Department of Health and Human Services.
NR 66
TC 54
Z9 56
U1 2
U2 12
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 AUG
PY 2011
VL 20
IS 8
BP 1629
EP 1637
DI 10.1158/1055-9965.EPI-11-0246
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 804AK
UT WOS:000293625600007
PM 21750167
ER
PT J
AU Anfinsen, KP
Devesa, SS
Bray, F
Troisi, R
Jonasdottir, TJ
Bruland, OS
Grotmol, T
AF Anfinsen, Kristin P.
Devesa, Susan S.
Bray, Freddie
Troisi, Rebecca
Jonasdottir, Thora J.
Bruland, Oyvind S.
Grotmol, Tom
TI Age-Period-Cohort Analysis of Primary Bone Cancer Incidence Rates in the
United States (1976-2005)
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID NEOADJUVANT CHEMOTHERAPY; OSTEOSARCOMA INCIDENCE; SEER DATABASE;
SARCOMA; CHONDROSARCOMA; TUMORS; RISK; GROWTH; EXPRESSION; MANAGEMENT
AB Background: Primary bone cancer comprises three major histologic types: osteosarcoma (OS), Ewing sarcoma (ES), and chondrosarcoma (CS). Given the limited knowledge about the etiology of primary bone cancer, we undertook an age-period-cohort (APC) analysis to determine whether incidence varied by birth cohort or calendar period. The purpose was to examine the temporal development of each bone cancer type and generate etiologic hypotheses via the observed birth cohort-related changes.
Methods: An APC model was fitted to incidence data for U. S. whites for OS, ES, and CS obtained from nine registries of the Surveillance, Epidemiology, and End Results program, which covers about 10% of the U. S. population, 1976-2005.
Results: The incidence of OS decreased between 1976 and 2005 among those aged over 60 years, a decline that occurred among patients with OS as their primary malignancy only. From 1986-1995 to 1996-2005, the incidence rate of CS among females of 20 to 69 years rose by about 50%, with rates increasing among consecutive cohorts born during 1935-1975. CS rates among males were stable, as were rates of ES.
Conclusion: The risk reduction in OS as a primary malignancy at older ages could possibly be related to diminished exposure over time to bone-seeking radionuclides. The CS increase among females corresponds to birth cohorts with rising exposures to oral contraceptives and menopausal hormonal therapy.
Impact: As the estrogen signaling pathway has been shown to stimulate proliferation of normal and malignant chondrocytes, estrogen exposure may increase the risk for CS. Further studies are warranted to clarify its possible etiological significance. Cancer Epidemiol Biomarkers Prev; 20(8); 1770-7. (C)2011 AACR.
C1 [Grotmol, Tom] Canc Registry Norway, Dept Etiol Res, NO-0304 Oslo, Norway.
[Anfinsen, Kristin P.; Jonasdottir, Thora J.; Grotmol, Tom] Norwegian Sch Vet Sci, Small Anim Sect, Dept Compan Anim Clin Sci, Oslo, Norway.
[Bruland, Oyvind S.] Norwegian Radium Hosp, Dept Oncol, Oslo, Norway.
[Bruland, Oyvind S.] Univ Oslo, Fac Med, Oslo, Norway.
[Bray, Freddie] Canc Registry Norway, Dept Clin & Registry Based Res, NO-0304 Oslo, Norway.
[Devesa, Susan S.; Troisi, Rebecca] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Bray, Freddie] Int Agcy Res Canc, Canc Informat Sect, F-69372 Lyon, France.
RP Grotmol, T (reprint author), Canc Registry Norway, Dept Etiol Res, POB 5313 Majorstuen, NO-0304 Oslo, Norway.
EM tom.grotmol@kreftregisteret.no
NR 40
TC 14
Z9 15
U1 0
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD AUG
PY 2011
VL 20
IS 8
BP 1770
EP 1777
DI 10.1158/1055-9965.EPI-11-0136
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 804AK
UT WOS:000293625600023
PM 21724855
ER
PT J
AU Permuth-Wey, J
Chen, ZH
Tsai, YY
Lin, HY
Chen, YA
Barnholtz-Sloan, J
Birrer, MJ
Chanock, SJ
Cramer, DW
Cunningham, JM
Fenstermacher, D
Fridley, BL
Garcia-Closas, M
Gayther, SA
Gentry-Maharaj, A
Gonzalez-Bosquet, J
Iversen, E
Jim, H
McLaughlin, J
Menon, U
Narod, SA
Phelan, CM
Ramus, SJ
Risch, H
Song, HL
Sutphen, R
Terry, KL
Tyrer, J
Vierkant, RA
Wentzensen, N
Lancaster, JM
Cheng, JQ
Berchuck, A
Pharoah, PDP
Schildkraut, JM
Goode, EL
Sellers, TA
AF Permuth-Wey, Jennifer
Chen, Zhihua
Tsai, Ya-Yu
Lin, Hui-Yi
Chen, Y. Ann
Barnholtz-Sloan, Jill
Birrer, Michael J.
Chanock, Stephen J.
Cramer, Daniel W.
Cunningham, Julie M.
Fenstermacher, David
Fridley, Brooke L.
Garcia-Closas, Montserrat
Gayther, Simon A.
Gentry-Maharaj, Aleksandra
Gonzalez-Bosquet, Jesus
Iversen, Edwin
Jim, Heather
McLaughlin, John
Menon, Usha
Narod, Steven A.
Phelan, Catherine M.
Ramus, Susan J.
Risch, Harvey
Song, Honglin
Sutphen, Rebecca
Terry, Kathryn L.
Tyrer, Jonathan
Vierkant, Robert A.
Wentzensen, Nicolas
Lancaster, Johnathan M.
Cheng, Jin Q.
Berchuck, Andrew
Pharoah, Paul D. P.
Schildkraut, Joellen M.
Goode, Ellen L.
Sellers, Thomas A.
CA OCAC
TI MicroRNA Processing and Binding Site Polymorphisms Are Not Replicated in
the Ovarian Cancer Association Consortium
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY; RISK
AB Background: Single nucleotide polymorphisms (SNP) in microRNA-related genes have been associated with epithelial ovarian cancer (EOC) risk in two reports, yet associated alleles may be inconsistent across studies.
Methods: We conducted a pooled analysis of previously identified SNPs by combining genotype data from 3,973 invasive EOC cases and 3,276 controls from the Ovarian Cancer Association Consortium. We also conducted imputation to obtain dense coverage of genes and comparable genotype data for all studies. In total, 226 SNPs within 15 kb of 4 miRNA biogenesis genes (DDX20, DROSHA, GEMIN4, and XPO5) and 23 SNPs located within putative miRNA binding sites of 6 genes (CAV1, COL18A1, E2F2, IL1R1, KRAS, and UGT2A3) were genotyped or imputed and analyzed in the entire dataset.
Results: After adjustment for European ancestry, no overall association was observed between any of the analyzed SNPs and EOC risk.
Conclusions: Common variants in these evaluated genes do not seem to be strongly associated with EOC risk.
Impact: This analysis suggests earlier associations between EOC risk and SNPs in these genes may have been chance findings, possibly confounded by population admixture. To more adequately evaluate the relationship between genetic variants and cancer risk, large sample sizes are needed, adjustment for population stratification should be carried out, and use of imputed SNP data should be considered. Cancer Epidemiol Biomarkers Prev; 20(8); 1793-7. (C)2011 AACR.
C1 [Permuth-Wey, Jennifer; Tsai, Ya-Yu] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA.
[Chen, Zhihua; Fenstermacher, David] H Lee Moffitt Canc Ctr & Res Inst, Dept Biomed Informat, Tampa, FL 33612 USA.
[Lin, Hui-Yi; Chen, Y. Ann] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat, Tampa, FL 33612 USA.
[Gonzalez-Bosquet, Jesus; Lancaster, Johnathan M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Womens Oncol, Tampa, FL 33612 USA.
[Jim, Heather] H Lee Moffitt Canc Ctr & Res Inst, Dept Hlth Outcomes & Behav, Tampa, FL 33612 USA.
[Phelan, Catherine M.; Cheng, Jin Q.] H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL 33612 USA.
[Sutphen, Rebecca] Univ S Florida, Coll Med, Pediat Epidemiol Ctr, Tampa, FL USA.
[Barnholtz-Sloan, Jill] Case Sch Med, Case Comprehens Canc Ctr, Cleveland, OH USA.
[Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Cramer, Daniel W.; Terry, Kathryn L.] Brigham Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02114 USA.
[Chanock, Stephen J.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Cunningham, Julie M.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA.
[Fridley, Brooke L.; Vierkant, Robert A.; Goode, Ellen L.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA.
[Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
[Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA.
[Iversen, Edwin] Duke Univ, Dept Stat Sci, Durham, NC USA.
[Risch, Harvey] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Gayther, Simon A.; Ramus, Susan J.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[McLaughlin, John] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Narod, Steven A.] Ctr Res Womens Hlth, Toronto, ON, Canada.
[Song, Honglin; Tyrer, Jonathan; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England.
[Garcia-Closas, Montserrat] Inst Canc Res, Epidemiol Sect, London SW3 6JB, England.
[Garcia-Closas, Montserrat] Inst Canc Res, Genet Sect, London SW3 6JB, England.
[Garcia-Closas, Montserrat] Breakthrough Breast Canc Res Ctr, London, England.
[Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, EGA Inst Womens Hlth, Dept Gynaecol Oncol, London, England.
RP Sellers, TA (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Epidemiol, MRC CANCONT, 12902 Magnolia Dr, Tampa, FL 33612 USA.
EM Thomas.Sellers@Moffitt.org
RI McLaughlin, John/E-4577-2013; Fridley, Brooke/D-8315-2015;
Garcia-Closas, Montserrat /F-3871-2015;
OI Fridley, Brooke/0000-0001-7739-7956; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Vierkant, Robert/0000-0001-6242-5221; Ramus,
Susan/0000-0003-0005-7798
FU Mayo Foundation; American Cancer Society [CRTG-00-196-01-CCE]; Advanced
Cancer Detection Center; Department of Defense [DAMD-17-98-1-8659];
Canadian Cancer Society; NIH [R01-CA-63682, R01-CA-63678]; National
Cancer Institute [P30-CA-15083]; NIH, National Cancer Institute,
Division of Cancer Epidemiology and Genetics; Center for Cancer
Research; Cancer Research UK; Eve Appeal; OAK Foundation; Department of
Health; [R01-CA-114343]; [R01-CA114343-S1]; [R01-CA-122443];
[P50-CA-136393]; [R01-CA-76016]; [R01-CA-106414]; [CA-54419]; [P50
CA105009]
FX The genotyping, bioinformatic, and biostatistical data analysis for MAY,
NCO, and TOR was supported by R01-CA-114343 and R01-CA114343-S1. The MAY
study is supported by R01-CA-122443 and P50-CA-136393 and funding from
the Mayo Foundation. The NCO study is supported by R01-CA-76016. The TBO
study is supported by R01-CA-106414, the American Cancer Society
(CRTG-00-196-01-CCE), and the Advanced Cancer Detection Center Grant,
Department of Defense (DAMD-17-98-1-8659). The TOR study is supported by
grants from the Canadian Cancer Society and the NIH (R01-CA-63682 and
R01-CA-63678). The Mayo Clinic Genotyping Shared Resource is supported
by the National Cancer Institute (P30-CA-15083). The NEC study is
supported by grants CA-54419 and P50 CA105009. The POL study was
supported by the Intramural Research Program of the NIH, National Cancer
Institute, Division of Cancer Epidemiology and Genetics, and the Center
for Cancer Research. The SEA study is funded by a program grant from
Cancer Research UK. The UKO study is supported by funding from Cancer
Research UK, the Eve Appeal, and the OAK Foundation; some of this work
was undertaken at UCLH/UCL who received some funding from the Department
of Health's NIHR Biomedical Research Centre funding scheme. UK
genotyping and data analysis were supported by a project grant from
Cancer Research UK. UK studies also make use of data generated by the
Wellcome Trust Case-Control consortium. A list of investigators who
contributed to the generation of data is available at www.wtccc.org.uk.
NR 12
TC 14
Z9 14
U1 0
U2 11
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 AUG
PY 2011
VL 20
IS 8
BP 1793
EP 1797
DI 10.1158/1055-9965.EPI-11-0397
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 804AK
UT WOS:000293625600026
PM 21636674
ER
PT J
AU Sprague, BL
Thompson, CL
Ganz, PA
Kanetsky, PA
Kushi, LH
Nebeling, L
AF Sprague, Brian L.
Thompson, Cheryl L.
Ganz, Patricia A.
Kanetsky, Peter A.
Kushi, Lawrence H.
Nebeling, Linda
TI The Business of Research: Budgets, Personnel, Planning, and Pitfalls-a
Report from the American Society of Preventive Oncology's Junior Members
Interest Group
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
C1 [Sprague, Brian L.] Univ Vermont, Dept Surg, Burlington, VT 05405 USA.
[Thompson, Cheryl L.] Case Western Reserve Univ, Dept Family Med, Cleveland, OH 44106 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA.
[Kanetsky, Peter A.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Kushi, Lawrence H.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Nebeling, Linda] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Sprague, BL (reprint author), Off Hlth Promot Res, 1 S Prospect St,Rm 4428B, Burlington, VT 05401 USA.
EM bsprague@uvm.edu
OI Kushi, Lawrence/0000-0001-9136-1175
NR 1
TC 0
Z9 0
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD AUG
PY 2011
VL 20
IS 8
BP 1802
EP 1804
DI 10.1158/1055-9965.EPI-11-0580
PG 3
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 804AK
UT WOS:000293625600028
PM 21784957
ER
PT J
AU Wallace, TA
Martin, DN
Ambs, S
AF Wallace, Tiffany A.
Martin, Damali N.
Ambs, Stefan
TI Interactions among genes, tumor biology and the environment in cancer
health disparities: examining the evidence on a national and global
scale
SO CARCINOGENESIS
LA English
DT Review
ID AFRICAN-AMERICAN WOMEN; PROSTATE-SPECIFIC ANTIGEN; GENOME-WIDE
ASSOCIATION; NEGATIVE BREAST-CANCER; ESTROGEN-RECEPTOR STATUS;
BLACK-WHITE DIFFERENCES; RACIAL-DIFFERENCES; LUNG-CANCER; UNITED-STATES;
SOCIOECONOMIC-STATUS
AB Cancer incidence and mortality rates show great variations across nations and between population groups. These variations are largely explained by differences in age distribution, diet and lifestyle, access to health care, cultural barriers and exposure to carcinogens and pathogens. Cancers caused by infections are significantly more common in developing than developed countries, and they overproportionally affect immigrant populations in the USA and other countries. The global pattern of cancer is not stagnant. Instead, it is dynamic because of fluctuations in the age distribution of populations, improvements in cancer prevention and early detection in affluent countries and rapid changes in diet and lifestyle in parts of the world. For example, increased smoking rates have caused tobacco-induced cancers to rise in various Asian countries, whereas reduced smoking rates have caused these cancers to plateau or even begin to decline in Western Europe and North America. Some population groups experience a disproportionally high cancer burden. In the USA and the Caribbean, cancer incidence and mortality rates are excessively high in populations of African ancestry when compared with other population groups. The causes of this disparity are multifaceted and may include tumor biological and genetic factors and their interaction with the environment. In this review, we will discuss the magnitude and causes of global cancer health disparities and will, with a focus on African-Americans and selected cancer sites, evaluate the evidence that genetic and tumor biological factors contribute to existing cancer incidence and outcome differences among population groups in the USA.
C1 [Wallace, Tiffany A.; Ambs, Stefan] Natl Canc Inst, Ctr Canc Res, Human Carcinogenesis Lab, Bethesda, MD 20892 USA.
[Martin, Damali N.] Natl Canc Inst, Ctr Canc Res, Div Canc Control & Populat Sci, Epidemiol & Genet Res Program, Bethesda, MD 20892 USA.
RP Ambs, S (reprint author), Natl Canc Inst, Ctr Canc Res, Human Carcinogenesis Lab, Bldg 37,Room 3050B, Bethesda, MD 20892 USA.
EM ambss@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research, USA
FX Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research, USA.
NR 310
TC 30
Z9 30
U1 1
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
EI 1460-2180
J9 CARCINOGENESIS
JI Carcinogenesis
PD AUG
PY 2011
VL 32
IS 8
BP 1107
EP 1121
DI 10.1093/carcin/bgr066
PG 15
WC Oncology
SC Oncology
GA 804EI
UT WOS:000293636700001
PM 21464040
ER
PT J
AU Neta, G
Brenner, AV
Sturgis, EM
Pfeiffer, RM
Hutchinson, AA
Aschebrook-Kilfoy, B
Yeager, M
Xu, L
Wheeler, W
Abend, M
Ron, E
Tucker, MA
Chanock, SJ
Sigurdson, AJ
AF Neta, Gila
Brenner, Alina V.
Sturgis, Erich M.
Pfeiffer, Ruth M.
Hutchinson, Amy A.
Aschebrook-Kilfoy, Briseis
Yeager, Meredith
Xu, Li
Wheeler, William
Abend, Michael
Ron, Elaine
Tucker, Margaret A.
Chanock, Stephen J.
Sigurdson, Alice J.
TI Common genetic variants related to genomic integrity and risk of
papillary thyroid cancer
SO CARCINOGENESIS
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITORS; US RADIOLOGIC TECHNOLOGISTS;
FIRST-DEGREE RELATIVES; DNA-REPAIR; CARCINOMA CELLS; ADULT GLIOMA;
NECK-CANCER; POLYMORPHISMS; ASSOCIATION; EXPRESSION
AB DNA damage is an important mechanism in carcinogenesis, so genes related to maintaining genomic integrity may influence papillary thyroid cancer (PTC) risk. Candidate gene studies targeting some of these genes have identified only a few polymorphisms associated with risk of PTC. Here, we expanded the scope of previous candidate studies by increasing the number and coverage of genes related to maintenance of genomic integrity. We evaluated 5077 tag single-nucleotide polymorphisms (SNPs) from 340 candidate gene regions hypothesized to be involved in DNA repair, epigenetics, tumor suppression, apoptosis, telomere function and cell cycle control and signaling pathways in a case-control study of 344 PTC cases and 452 matched controls. We estimated odds ratios for associations of single SNPs with PTC risk and combined P values for SNPs in the same gene region or pathway to obtain gene region-specific or pathway-specific P values using adaptive rank-truncated product methods. Nine SNPs had P values < 0.0005, three of which were in HDAC4 and were inversely related to PTC risk. After multiple comparisons adjustment, no SNPs remained associated with PTC risk. Seven gene regions were associated with PTC risk at P < 0.01, including HUS1, ALKBH3, HDAC4, BAK1, FAF1_CDKN2C, DACT3 and FZD6. Our results suggest a possible role of genes involved in maintenance of genomic integrity in relation to risk of PTC.
C1 [Neta, Gila] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv,EPS, Rockville, MD 20852 USA.
[Sturgis, Erich M.; Xu, Li] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Hutchinson, Amy A.; Yeager, Meredith] NCI, SAIC Frederick Inc, Core Genotyping Facil, Frederick, MD 21701 USA.
[Aschebrook-Kilfoy, Briseis] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Wheeler, William] Informat Management Serv Inc, Silver Spring, MD USA.
[Abend, Michael] Bundeswehr Inst Radiobiol, Munich, Germany.
[Tucker, Margaret A.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Gaithersburg, MD USA.
RP Neta, G (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv,EPS, Room 7049,6120 Execut Blvd, Rockville, MD 20852 USA.
EM netagil@mail.nih.gov
RI Aschebrook-Kilfoy, Briseis/A-2537-2012; Xu, Li/B-9535-2012; Tucker,
Margaret/B-4297-2015
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health; American Thyroid Association; National
Cancer Institute, National Institutes of Health [HHSN261200800001E]
FX This research was supported in part by the Intramural Research Program
of the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health and by a grant from the
American Thyroid Association (Principal Investigator: E. M. S.). 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.
NR 67
TC 24
Z9 24
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD AUG
PY 2011
VL 32
IS 8
BP 1231
EP 1237
DI 10.1093/carcin/bgr100
PG 7
WC Oncology
SC Oncology
GA 804EI
UT WOS:000293636700016
PM 21642358
ER
PT J
AU Hollander, MC
Zhou, X
Maier, CR
Patterson, AD
Ding, XX
Dennis, PA
AF Hollander, M. Christine
Zhou, Xin
Maier, Colleen R.
Patterson, Andrew D.
Ding, Xinxin
Dennis, Phillip A.
TI A Cyp2a polymorphism predicts susceptibility to NNK-induced lung
tumorigenesis in mice
SO CARCINOGENESIS
LA English
DT Article
ID TOBACCO-SPECIFIC CARCINOGEN; K-RAS; METABOLIC-ACTIVATION; MOUSE LUNG;
4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; CYTOCHROME-P450; CANCER;
8-METHOXYPSORALEN; ADENOCARCINOMA; IDENTIFICATION
AB Lung tumors from smokers as well as lung tumors from mice exposed to tobacco carcinogens such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), often carry mutations in K-ras, which activates downstream-signaling pathways such as PI3K/AKT/mTOR pathway. Mice with genetic deletion of one of three isoforms of AKT were used to investigate the role of AKT in mutant K-ras-induced lung tumorigenesis in mice. Although deletion of Akt1 or Akt2 decreased NNK-induced lung tumor formation by 90%, deletion of Akt2 failed to decrease lung tumorigenesis in two other mouse models driven by mutant K-ras. Genetic mapping showed that Akt2 was tightly linked to the cytochrome P450 Cyp2a locus on chromosome 7. Consequently, targeted deletion of Akt2 created linkage to a strain-specific Cyp2a5 polymorphism that decreased activation of NNK in vitro. Mice with this Cyp2a5 polymorphism had decreased NNK-induced DNA adduct formation in vivo and decreased NNK-induced lung tumorigenesis. These studies support human epidemiological studies linking CYP2A polymorphisms with lung cancer risk in humans and highlight the need to confirm phenotypes of genetically engineered mice in multiple mouse strains.
C1 [Hollander, M. Christine; Maier, Colleen R.; Dennis, Phillip A.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Patterson, Andrew D.] NCI, Lab Metab, Bethesda, MD 20892 USA.
[Zhou, Xin; Ding, Xinxin] SUNY Albany, Wadsworth Ctr, New York State Dept Hlth, Albany, NY 12201 USA.
[Zhou, Xin; Ding, Xinxin] SUNY Albany, Sch Publ Hlth, Albany, NY 12201 USA.
RP Dennis, PA (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM DennisP@mail.nih.gov
RI Patterson, Andrew/G-3852-2012
OI Patterson, Andrew/0000-0003-2073-0070
FU NIH; National Cancer Institute, NIH [CA092596]
FX This work was funded in part through the NIH intramural research program
(P.A.D.) and supported in part by a grant (CA092596) from the National
Cancer Institute, NIH (to X.D.).
NR 31
TC 7
Z9 8
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD AUG
PY 2011
VL 32
IS 8
BP 1279
EP 1284
DI 10.1093/carcin/bgr097
PG 6
WC Oncology
SC Oncology
GA 804EI
UT WOS:000293636700022
PM 21625009
ER
PT J
AU Berger, VW
AF Berger, Vance W.
TI Minimization: not all it's cracked up to be
SO CLINICAL TRIALS
LA English
DT Letter
ID RANDOMIZATION
C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
RP Berger, VW (reprint author), NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
EM vb78c@nih.gov
NR 5
TC 3
Z9 3
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
J9 CLIN TRIALS
JI Clin. Trials
PD AUG
PY 2011
VL 8
IS 4
BP 443
EP 443
DI 10.1177/1740774511409769
PG 1
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 806HN
UT WOS:000293797000014
PM 21835864
ER
PT J
AU Semple, RK
Savage, DB
Cochran, EK
Gorden, P
O'Rahilly, S
AF Semple, Robert K.
Savage, David B.
Cochran, Elaine K.
Gorden, Phillip
O'Rahilly, Stephen
TI Genetic Syndromes of Severe Insulin Resistance
SO ENDOCRINE REVIEWS
LA English
DT Review
ID FAMILIAL PARTIAL LIPODYSTROPHY; SEIP CONGENITAL LIPODYSTROPHY;
GROWTH-FACTOR-I; RABSON-MENDENHALL-SYNDROME; FATTY LIVER-DISEASE;
EARLY-ONSET OBESITY; LEPTIN-REPLACEMENT THERAPY;
POLYCYSTIC-OVARY-SYNDROME; ACTIVATED-RECEPTOR-GAMMA; BARDET-BIEDL
SYNDROME
AB Insulin resistance is among the most prevalent endocrine derangements in the world, and it is closely associated with major diseases of global reach including diabetes mellitus, atherosclerosis, nonalcoholic fatty liver disease, and ovulatory dysfunction. It is most commonly found in those with obesity but may also occur in an unusually severe form in rare patients with monogenic defects. Such patients may loosely be grouped into those with primary disorders of insulin signaling and those with defects in adipose tissue development or function (lipodystrophy). The severe insulin resistance of both subgroups puts patients at risk of accelerated complications and poses severe challenges in clinical management. However, the clinical disorders produced by different genetic defects are often biochemically and clinically distinct and are associated with distinct risks of complications. This means that optimal management of affected patients should take into account the specific natural history of each condition. In clinical practice, they are often underdiagnosed, however, with low rates of identification of the underlying genetic defect, a problem compounded by confusing and overlapping nomenclature and classification. We now review recent developments in understanding of genetic forms of severe insulin resistance and/or lipodystrophy and suggest a revised classification based on growing knowledge of the underlying pathophysiology. (Endocrine Reviews 32: 498-514, 2011)
C1 [Semple, Robert K.; Savage, David B.; O'Rahilly, Stephen] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 0QQ, England.
[Cochran, Elaine K.; Gorden, Phillip] Natl Inst Diabet Digest & Kidney Dis, Clin Endocrinol Branch, Bethesda, MD 20892 USA.
RP Semple, RK (reprint author), Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Hills Rd, Cambridge CB2 0QQ, England.
EM rks16@cam.ac.uk; dbs23@medschl.cam.ac.uk
OI Semple, Robert/0000-0001-6539-3069
FU Wellcome Trust [080952/Z/06/Z, 078986/Z/06/Z]; GlaxoSmithKline; UK
National Institute for Health Research Cambridge Biomedical Research
Centre; UK Medical Research Council Centre for Obesity and Related
Metabolic Disease
FX This work was supported by research grants from the Wellcome Trust
(Intermediate Clinical Fellowship 080952/Z/06/Z, to R.K.S.; Programme
Grant 078986/Z/06/Z, to S.O.), GlaxoSmithKline (to D.B.S.), the UK
National Institute for Health Research Cambridge Biomedical Research
Centre, and the UK Medical Research Council Centre for Obesity and
Related Metabolic Disease.
NR 182
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U1 0
U2 14
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD AUG
PY 2011
VL 32
IS 4
BP 498
EP 514
DI 10.1210/er.2010-0020
PG 17
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 803II
UT WOS:000293574600003
PM 21536711
ER
PT J
AU Machha, A
Schechter, AN
AF Machha, Ajay
Schechter, Alan N.
TI Dietary nitrite and nitrate: a review of potential mechanisms of
cardiovascular benefits
SO EUROPEAN JOURNAL OF NUTRITION
LA English
DT Review
DE Cardiovascular disease; Diet; Endothelial dysfunction; Nitric oxide;
Nitrite; Nitrate
ID ISCHEMIA-REPERFUSION INJURY; SYNTHASE REDUCES NITRITE;
CORONARY-HEART-DISEASE; N-NITROSO COMPOUNDS; SODIUM-NITRITE; INORGANIC
NITRATE; OXIDE SYNTHASE; ENDOTHELIAL DYSFUNCTION; MYOCARDIAL-ISCHEMIA;
BLOOD-PRESSURE
AB In the last decade, a growing scientific and medical interest has emerged toward cardiovascular effects of dietary nitrite and nitrate; however, many questions concerning their mode of action(s) remain unanswered. In this review, we focus on multiple mechanisms that might account for potential cardiovascular beneficial effects of dietary nitrite and nitrate.
Beneficial changes to cardiovascular health from dietary nitrite and nitrate might result from several mechanism(s) including their reduction into nitric oxide, improvement in endothelial function, vascular relaxation, and/or inhibition of the platelet aggregation. From recently obtained evidence, it appears that the longstanding concerns about the toxicity of oral nitrite or nitrate are overstated.
Dietary nitrite and nitrate may have cardiovascular protective effects in both healthy individuals and also those with cardiovascular disease conditions. A role for nitrite and nitrate in nitric oxide biosynthesis and/or in improving nitric oxide bioavailability may eventually provide a rationale for using dietary nitrite and nitrate supplementation in the treatment and prevention of cardiovascular diseases.
C1 [Machha, Ajay; Schechter, Alan N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
RP Schechter, AN (reprint author), NIDDK, Mol Med Branch, NIH, Bldg 10,Room 9N314B,10 Ctr Dr, Bethesda, MD 20892 USA.
EM alans@intra.niddk.nih.gov
OI Schechter, Alan N/0000-0002-5235-9408
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
at National Institutes of Health (NIH), Bethesda, Maryland, USA
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
at National Institutes of Health (NIH), Bethesda, Maryland, USA. We
thank Dr Barbora Piknova (Molecular Medicine Branch, NIDDK) for her
valuable inputs.
NR 109
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U1 5
U2 21
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1436-6207
J9 EUR J NUTR
JI Eur. J. Nutr.
PD AUG
PY 2011
VL 50
IS 5
BP 293
EP 303
DI 10.1007/s00394-011-0192-5
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 804EY
UT WOS:000293638300002
PM 21626413
ER
PT J
AU Erie, AJ
Samsel, L
Takaku, T
Desierto, MJ
Keyvanfar, K
McCoy, JP
Young, NS
Chen, JC
AF Erie, Andrew J.
Samsel, Leigh
Takaku, Tomoiku
Desierto, Marie J.
Keyvanfar, Keyvan
McCoy, J. Philip
Young, Neal S.
Chen, Jichun
TI MHC class II upregulation and colocalization with Fas in experimental
models of immune-mediated bone marrow failure
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID CD4(+) T-CELLS; HEMATOPOIETIC STEM-CELLS; APLASTIC-ANEMIA PATIENTS;
COMPLEX CLASS-II; MOUSE MODEL; IFN-GAMMA; EXPRESSION; LYMPHOCYTES;
IMMUNOSUPPRESSION; CYTOTOXICITY
AB Objective. To test the hypothesis that gamma-interferon (IFN-gamma) promotes major histocompatibility complex (MHC) class II expression on bone marrow (BM) cell targets that facilitate T-cell-mediated BM destruction in immune-mediated BM failure.
Materials and Methods. Allogeneic lymph node (LN) cells were infused into MHC- or minor histocompatibility antigen-mismatched hosts to induce BM failure. MHC class II and Fas expression and cell apoptosis were analyzed by flow cytometry. MHC class II-Fas colocalization was detected by ImageStream Imaging Flow Cytometry and other cell-to-cell associations were visualized by confocal microscopy. T-cell mediated BM cell apoptosis and effects of IFN-gamma on MHC class II-Fas colocalization on normal BM cells were studied using cell culture in vitro followed by conventional and imaging flow cytometry.
Results. BM failure animals had significantly upregulated MHC class II expression on CD4(-)CD8(-)CD11b(-)CD415R(-) residual BM cells and significantly increased MHC class II-Fas colocalization on BM CD150(+) and CD34(+) hematopoietic cells. MHC class II(+)Fas(+) BM cells were closely associated with CD4(+) T cells in the BM of affected animals, and they were significantly more responsive to T-cell-mediated cell apoptosis relative to MHC class II(-)Fas(-) BM cells. Infusion of IFN-gamma-deficient LN cells into minor histocompatibility antigen-mismatched recipients resulted in no MHC class II-Fas upregulation and no clinically overt BM failure. Treatment with recombinant IFN-gamma significantly increased both MHC class II-Fas coexpression and colocalization on normal BM cells.
Conclusions. Elevation of the inflammatory cytokine IFN-gamma stimulated MHC class H expression and MHC class H-Fas colocalization, which may facilitate T-cell mediated cell destruction. Published by Elsevier Inc. on behalf of the ISEH - Society for Hematology and Stem Cells.
C1 [Erie, Andrew J.; Takaku, Tomoiku; Desierto, Marie J.; Keyvanfar, Keyvan; Young, Neal S.; Chen, Jichun] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Samsel, Leigh; McCoy, J. Philip] NHLBI, Flow Cytometty Core Facil, NIH, Bethesda, MD 20892 USA.
RP Chen, JC (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC Room 3E-5140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chenji@nhlbi.nih.gov
FU NHLBI intramural research
FX We thank Dr. Jan Joseph Melenhorst from Hematology Branch, National
Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health,
for helpful scientific discussions, and NHLBI Light Microscopy Core
Facility for Confocal microscopy image acquisition and analyses. This
research was supported by funds for NHLBI intramural research.
NR 38
TC 3
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD AUG
PY 2011
VL 39
IS 8
BP 837
EP 849
DI 10.1016/j.exphem.2011.05.005
PG 13
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 806IR
UT WOS:000293801600004
PM 21635935
ER
PT J
AU Staudt, L
AF Staudt, L.
TI TARGETING THE ACHILLES HEEL OF CANCER THERAPEUTICALLY
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Staudt, L.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD AUG
PY 2011
VL 39
IS 8
SU 1
BP S9
EP S9
PG 1
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 806IS
UT WOS:000293801700023
ER
PT J
AU Parkman, HP
Yates, KP
Hasler, WL
Nguyan, L
Pasricha, PJ
Snape, WJ
Farrugia, G
Calles, J
Koch, KL
Abell, TL
McCallum, RW
Petito, D
Parrish, CR
Duffy, F
Lee, L
Unalp-Arida, A
Tonascia, J
Hamilton, F
AF Parkman, Henry P.
Yates, Katherine P.
Hasler, William L.
Nguyan, Linda
Pasricha, Pankaj J.
Snape, William J.
Farrugia, Gianrico
Calles, Jorge
Koch, Kenneth L.
Abell, Thomas L.
McCallum, Richard W.
Petito, Dorothy
Parrish, Carol Rees
Duffy, Frank
Lee, Linda
Unalp-Arida, Aynur
Tonascia, James
Hamilton, Frank
CA NIDDK Gastroparesis Clinical Res
TI Dietary Intake and Nutritional Deficiencies in Patients With Diabetic or
Idiopathic Gastroparesis
SO GASTROENTEROLOGY
LA English
DT Article
DE FFQ; Stomach; Vomiting; Clinical Trial; Motility Disorder
ID CARDINAL SYMPTOM INDEX; SEVERITY; RISK; RECOMMENDATIONS; VALIDATION;
MEDICINE; OBESITY
AB BACKGROUND & AIMS: Gastroparesis can lead to food aversion, poor oral intake, and subsequent malnutrition. We characterized dietary intake and nutritional deficiencies in patients with diabetic and idiopathic gastroparesis. METHODS: Patients with gastroparesis on oral intake (N = 305) were enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry and completed diet questionnaires at 7 centers. Medical history, gastroparesis symptoms, answers to the Block Food Frequency Questionnaire, and gastric emptying scintigraphy results were analyzed. RESULTS: Caloric intake averaged 1168 +/- 801 kcal/day, amounting to 58% +/- 39% of daily total energy requirements (TER). A total of 194 patients (64%) reported caloric-deficient diets, defined as <60% of estimated TER. Only 5 patients (2%) followed a diet suggested for patients with gastroparesis. Deficiencies were present in several vitamins and minerals; patients with idiopathic disorders were more likely to have diets with estimated deficiencies in vitamins A, B(6), C, K, iron, potassium, and zinc than diabetic patients. Only one-third of patients were taking multivitamin supplements. More severe symptoms (bloating and constipation) were characteristic of patients who reported an energy-deficient diet. Overall, 32% of patients had nutritional consultation after the onset of gastroparesis; consultation was more likely among patients with longer duration of symptoms and more hospitalizations and patients with diabetes. Multivariable logistic regression analysis indicated that nutritional consultation increased the chances that daily TER were met (odds ratio, 1.51; P = .08). CONCLUSIONS: Many patients with gastroparesis have diets deficient in calories, vitamins, and minerals. Nutritional consultation is obtained infrequently but is suggested for dietary therapy and to address nutritional deficiencies.
C1 [Parkman, Henry P.] Temple Univ, Gastroenterol Sect, Sch Med, Dept Med, Philadelphia, PA 19140 USA.
[Yates, Katherine P.; Unalp-Arida, Aynur; Tonascia, James] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
[Hasler, William L.] Univ Michigan, Dept Med, Gastroenterol Sect, Ann Arbor, MI 48109 USA.
[Nguyan, Linda; Pasricha, Pankaj J.] Stanford Univ, Gastroenterol Sect, Dept Med, Palo Alto, CA 94304 USA.
[Snape, William J.] Calif Pacific Med Ctr, Gastroenterol Sect, Dept Med, San Francisco, CA USA.
[Farrugia, Gianrico] Mayo Clin, Gastroenterol Sect, Dept Med, Rochester, MN USA.
[Calles, Jorge; Koch, Kenneth L.] Wake Forest Univ, Endocrinol Sect, Dept Med, Winston Salem, NC 27109 USA.
[Abell, Thomas L.] Univ Mississippi, Gastroenterol Sect, Dept Med, Jackson, MS 39216 USA.
[McCallum, Richard W.] Texas Tech Univ, Dept Med, El Paso, TX USA.
[Parrish, Carol Rees] Univ Virginia, Dept Nutr, Charlottesville, VA USA.
[Duffy, Frank] Temple Univ Hosp & Med Sch, Dept Nutr, Philadelphia, PA 19140 USA.
[Lee, Linda] Johns Hopkins Univ, Dept Med, Gastroenterol Sect, Baltimore, MD USA.
[Hamilton, Frank] NIDDK, Bethesda, MD USA.
RP Parkman, HP (reprint author), Temple Univ, Gastroenterol Sect, Sch Med, Dept Med, 8th Floor,3401 N Broad St, Philadelphia, PA 19140 USA.
EM henry.parkman@temple.edu
RI Vaughn, Ivana/B-6138-2016
OI Vaughn, Ivana/0000-0002-7201-0289
FU National Institute of Diabetes and Digestive and Kidney Diseases
[U01DK073983, U01DK073975, U01DK073985, U01DK074007, U01DK073974,
U01DK074008]
FX The Gastroparesis Clinical Research Consortium is supported by the
National Institute of Diabetes and Digestive and Kidney Diseases (grants
U01DK073983, U01DK073975, U01DK073985, U01DK074007, U01DK073974,
U01DK074008).
NR 32
TC 37
Z9 37
U1 1
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD AUG
PY 2011
VL 141
IS 2
BP 486
EP U571
DI 10.1053/j.gastro.2011.04.045
PG 20
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 802PK
UT WOS:000293523300028
PM 21684286
ER
PT J
AU Shin, EC
Park, SH
Demino, M
Nascimbeni, M
Mihalik, K
Major, M
Veerapu, NS
Heller, T
Feinstone, SM
Rice, CM
Rehermann, B
AF Shin, Eui-Cheol
Park, Su-Hyung
Demino, Mary
Nascimbeni, Michelina
Mihalik, Kathleen
Major, Marian
Veerapu, Naga S.
Heller, Theo
Feinstone, Stephen M.
Rice, Charles M.
Rehermann, Barbara
TI Delayed Induction, Not Impaired Recruitment, of Specific CD8(+) T Cells
Causes the Late Onset of Acute Hepatitis C
SO GASTROENTEROLOGY
LA English
DT Article
DE Liver Disease; Virology; Immune Response; Monkey
ID VIRUS-INFECTION; GENOMIC ANALYSIS; HOST RESPONSE; B-VIRUS; LIVER;
CHEMOKINE; LYMPHOCYTES; KINETICS; IMMUNITY; DISEASE
AB BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is characterized by lack of immune-mediated liver injury despite a high level of HCV replication during the incubation phase, which lasts about 8 weeks. We investigated whether this results from delayed recruitment of HCV-specific T cells and whether it facilitates HCV persistence. METHODS: Six chimpanzees were infected with HCV; blood and liver samples were collected for 28 weeks and analyzed for immune cells and chemokines. RESULTS: Two chimpanzees developed self-limited infections, whereas the remaining 4 developed chronic infections. Levels of the chemokines CXCL10, CXCL11, CCL4, and CCL5 increased in blood and liver samples from all chimpanzees within 1 month of HCV infection. Chemokine induction correlated with intrahepatic type I interferon (IFN) responses in vivo and was blocked by neutralizing antibodies against IFN-beta in vitro. Despite the early-stage induction of chemokines, the intrahepatic lymphocytic infiltrate started to increase no earlier than 8 weeks after HCV infection, when HCV-specific, tetramer-positive CD8(+) T cells appeared in the circulation. The HCV-specific CD8(+) T cells expressed chemokine receptors when they were initially detected in blood samples, so they could be recruited to the liver as soon as they entered the circulation. CONCLUSIONS: Chemokines are induced during early stages of HCV infection, which requires a type I IFN-mediated response. The delayed onset of acute hepatitis does not result from delayed recruitment of HCV-specific T cells, but could instead be related to a primary delay in the induction of HCV-specific T cells. Divergent outcomes occur without evident differences in chemokine induction and T-cell recruitment.
C1 [Shin, Eui-Cheol; Park, Su-Hyung; Nascimbeni, Michelina; Veerapu, Naga S.; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Mihalik, Kathleen; Major, Marian; Feinstone, Stephen M.] US FDA, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA.
RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA.
EM rehermann@nih.gov
RI Veerapu, Naga Suresh/F-4338-2011; Park, Su-Hyung/N-3514-2014
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health; Center for Biologics Evaluation and
Research, Food and Drug Administration; US Public Health Service
[CA85883-01]
FX Supported by the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health intramural research program; the
Center for Biologics Evaluation and Research, Food and Drug
Administration intramural research program; and the US Public Health
Service grant CA85883-01 (to C.M.R.).
NR 29
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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 AUG
PY 2011
VL 141
IS 2
BP 686
EP U804
DI 10.1053/j.gastro.2011.05.006
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 802PK
UT WOS:000293523300047
PM 21699897
ER
PT J
AU Cao, X
Yang, M
Wei, RC
Zeng, Y
Gu, JF
Huang, WD
Yang, DQ
Li, HL
Ding, M
Wei, N
Zhang, KJ
Xu, B
Liu, XR
Qian, QJ
Liu, XY
AF Cao, X.
Yang, M.
Wei, R-C
Zeng, Y.
Gu, J-F
Huang, W-D
Yang, D-Q
Li, H-L
Ding, M.
Wei, N.
Zhang, K-J
Xu, B.
Liu, X-R
Qian, Q-J
Liu, X-Y
TI Cancer targeting Gene-Viro-Therapy of liver carcinoma by dual-regulated
oncolytic adenovirus armed with TRAIL gene
SO GENE THERAPY
LA English
DT Article
DE cancer targeting Gene-Viro-Therapy; dual-regulated oncolytic adenovirus;
tumor necrosis factor-related apoptosis-inducing ligand; autophagy;
apoptosis
ID HUMAN HEPATOCELLULAR-CARCINOMA; PROGRAMMED CELL-DEATH;
ANTITUMOR-ACTIVITY; ALPHA-FETOPROTEIN; TUMOR-CELLS; COLORECTAL-CANCER;
SURVIVIN PROMOTER; MALIGNANT GLIOMA; HUMAN HEPATOMA; SV40 ENHANCER
AB Liver cancer is a common and aggressive malignancy, but available treatment approaches remain suboptimal. Cancer targeting Gene-Viro-Therapy (CTGVT) has shown excellent anti-tumor effects in a preclinical study. CTGVT takes advantage of both gene therapy and virotherapy by incorporating an anti-tumor gene into an oncolytic virus vector. Potent anti-tumor activity is achieved by virus replication and exogenous expression of the anti-tumor gene. A dual-regulated oncolytic adenoviral vector designated Ad.AFP.E1A.E1B (Delta 55) (Ad.AFP.D55 for short thereafter) was constructed by replacing the native viral E1A promoter with the simian virus 40 enhancer/alpha-fetoprotein (AFP) composite promoter (AFPep) based on an E1B-55K-deleted construct, ZD55. Ad.AFP.D55 showed specific replication and cytotoxicity in AFP-positive hepatoma cells. It also showed enhanced safety in normal cells when compared with the mono-regulated vector ZD55. To improve the anti-hepatoma activities of the virus, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene was introduced into Ad.AFP.D55. Ad.AFP.D55-TRAIL exhibited remarkable anti-tumor activities in vitro and in vivo. Treatment with Ad.AFP.D55-TRAIL can induce both autophagy owing to the Ad.AFP.D55 vector and caspase-dependent apoptosis owing to the TRAIL protein. Therefore, Ad.AFP.D55-TRAIL could be a potential anti-hepatoma agent with anti-tumor activities due to AFP-specific replication and TRAIL-induced apoptosis. Gene Therapy (2011) 18, 765-777; doi:10.1038/gt.2011.16; published online 17 March 2011
C1 [Cao, X.; Gu, J-F; Huang, W-D; Yang, D-Q; Li, H-L; Ding, M.; Wei, N.; Zhang, K-J; Liu, X-R; Liu, X-Y] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China.
[Yang, M.] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wei, R-C] Guangxi Normal Univ, Sch Life Sci, Guilin, Peoples R China.
[Zeng, Y.] Chinese Acad Sci, Inst Pasteur Shanghai, Mol Virol Lab, Shanghai 200031, Peoples R China.
[Li, H-L] Southwestern Univ, Chongqing Engn Res Ctr Floriculture, Dept Hort & Garden, Chongqing, Peoples R China.
[Xu, B.] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Gen Surg, Shanghai 200092, Peoples R China.
[Qian, Q-J; Liu, X-Y] Zhejiang Sci Tech Univ, Xinyuan Inst Med & Biotechnol, Hangzhou, Zhejiang, Peoples R China.
[Qian, Q-J] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Lab Gene & Virus Therapy, Shanghai, Peoples R China.
RP Liu, XY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
EM xyliu@sibs.ac.cn
FU National Nature Science Foundation of China [30623003]; Science and
Technology Commission of Shanghai Municipality [06DZ22032]; National
Basic Research Program of China (973 Program) [2004 CB51804]; Hi-Tech
Research Development Program of China (863 Program) [2007AA 021006];
Chinese Academy of Science [KSCX2-YW-R -09, R-04]; Zhejiang Sci-Tech
University [0616033]
FX We are grateful to Professor Mu-Jun Zhao for providing the EGFP-LC3
plasmid, Professor Hong-Bin Ji for providing the BEAS-2B cell line,
Professor You-Cheng Xu for critical reading the manuscript, Dr Han Di
for help with the molecular cloning and Ms Lan-Ying Sun for help with
the cell culture. This study was supported by grants from the National
Nature Science Foundation of China (No. 30623003), the Science and
Technology Commission of Shanghai Municipality (No. 06DZ22032), the
National Basic Research Program of China (973 Program) (No. 2004
CB51804), the Hi-Tech Research Development Program of China (863
Program) (No. 2007AA 021006), the Key Project of the Chinese Academy of
Science (No. KSCX2-YW-R -09, R-04) and the Zhejiang Sci-Tech University
Grant 0616033.
NR 47
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U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
EI 1476-5462
J9 GENE THER
JI Gene Ther.
PD AUG
PY 2011
VL 18
IS 8
BP 765
EP 777
DI 10.1038/gt.2011.16
PG 13
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Research & Experimental Medicine
GA 806CE
UT WOS:000293779500003
PM 21412282
ER
PT J
AU Liu, DF
Martina, JA
Wu, XS
Hammer, JA
Long, EO
AF Liu, Dongfang
Martina, Jose A.
Wu, Xufeng S.
Hammer, John A., III
Long, Eric O.
TI Two modes of lytic granule fusion during degranulation by natural killer
cells
SO IMMUNOLOGY AND CELL BIOLOGY
LA English
DT Article
DE degranulation; fusion; human; lytic granules; natural killer cells
ID KISS-AND-RUN; FROG NEUROMUSCULAR JUNCTION; CYTOTOXIC T-LYMPHOCYTES;
PROTEIN-KINASE-C; MEDIATED CYTOTOXICITY; IMMUNOLOGICAL SYNAPSE; FAS
LIGAND; NK CELLS; SECRETORY LYSOSOMES; MYOSIN-IIA
AB Lytic granules in cytotoxic lymphocytes, which include T cells and natural killer (NK) cells, are secretory lysosomes that release their content upon fusion with the plasma membrane (PM), a process known as degranulation. Although vesicle exocytosis has been extensively studied in endocrine and neuronal cells, much less is known about the fusion of lytic granules in cytotoxic lymphocytes. Here, we used total internal reflection fluorescence microscopy to examine lytic granules labeled with fluorescently tagged Fas ligand (FasL) in the NK cell line NKL stimulated with phorbol ester and ionomycin and in primary NK cells activated by physiological receptor-ligand interactions. Two fusion modes were observed: complete fusion, characterized by loss of granule content and rapid diffusion of FasL at the PM; and incomplete fusion, characterized by transient fusion pore opening and retention of FasL at the fusion site. The pH-sensitive green fluorescence protein (pHluorin) fused to the lumenal domain of FasL was used to visualize fusion pore opening with a time resolution of 30 ms. Upon incomplete fusion, pHluorin emission lasted several seconds in the absence of noticeable diffusion. Thus, we conclude that lytic granules in NK cells undergo both complete and incomplete fusion with the PM, and propose that incomplete fusion may promote efficient recycling of lytic granule membrane after the release of cytotoxic effector molecules. Immunology and Cell Biology (2011) 89, 728-738; doi:10.1038/icb.2010.167; published online 12 April 2011
C1 [Liu, Dongfang; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Martina, Jose A.; Wu, Xufeng S.; Hammer, John A., III] NHLBI, Sect Mol Cell Biol, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Liu, DF (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA.
EM donfangliu@gmail.com; eLong@nih.gov
RI Long, Eric/G-5475-2011
OI Long, Eric/0000-0002-7793-3728
FU National Institutes of Health, National Institute of Allergy and
Infectious Disease; National Heart, Lung, and Blood Institute
FX We thank G Griffiths (University of Cambridge) for the GFP-FasL plasmid,
G Miesenbock (Yale University) for the vesicle-associated membrane
protein 2-pHluorin plasmid, and J Brzostowski and P Tolar (NIAID-NIH,
USA) for advice with imaging. We also thank the NIH Fellows Editorial
Board for editorial assistance. This work has been supported by the
Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Disease, and National
Heart, Lung, and Blood Institute.
NR 59
TC 19
Z9 20
U1 0
U2 3
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 AUG-SEP
PY 2011
VL 89
IS 6
BP 728
EP 738
DI 10.1038/icb.2010.167
PG 11
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 806CV
UT WOS:000293783300010
PM 21483445
ER
PT J
AU Cizza, G
Rother, KI
AF Cizza, Giovanni
Rother, Kristina I.
TI Was Feuerbach right: are we what we eat?
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID GHRELIN; SLEEP; STRESS; APPETITE; OBESITY
AB Food and stress are powerful modulators of the body-mind connection, which is Unbalanced in obese individuals. Why do we choose chocolate over an apple when overworked and stressed, and why does comfort food make us feel better? Two independent studies in the JCI, one in this issue, home in on the role of stress on gut hormones and food choices and, conversely, on the effect of the intestinal system on modulation of brain activity by sadness. These studies broaden our understanding of the ties between food and mood and underscore promising targets for obesity treatments.
C1 [Cizza, Giovanni] NIDDK, Sect Neuroendocrinol Obes, NIH, Bethesda, MD USA.
[Rother, Kristina I.] NIDDK, Sect Pediat Diabet & Metab, NIH, Bethesda, MD USA.
RP Cizza, G (reprint author), Bldg 10,CRC,Rm 6-3940, Bethesda, MD 20892 USA.
EM cizzag@intra.niddk.nih.gov
FU Intramural NIH HHS
NR 20
TC 5
Z9 5
U1 0
U2 6
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD AUG
PY 2011
VL 121
IS 8
BP 2969
EP 2971
DI 10.1172/JCI58595
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 802FU
UT WOS:000293495500005
PM 21785214
ER
PT J
AU Goldstein, DS
Holmes, C
Kopin, IJ
Sharabi, Y
AF Goldstein, David S.
Holmes, Courtney
Kopin, Irwin J.
Sharabi, Yehonatan
TI Intra-neuronal vesicular uptake of catecholamines is decreased in
patients with Lewy body diseases
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID PURE AUTONOMIC FAILURE; NEUROGENIC ORTHOSTATIC HYPOTENSION; MULTIPLE
SYSTEM ATROPHY; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; MONOAMINE
TRANSPORTER-2; SYMPATHETIC DENERVATION; OXIDATIVE STRESS; PC12 CELLS;
REACTIVE INTERMEDIATE
AB Several neuro&generative disorders, including Parkinson disease (PD), are characterized by the presence of Lewy bodies cytoplasmic inclusions containing a-synuclein protein aggregates in the affected neurons. A poorly understood feature of Lewy body diseases is loss of sympathetic nerves in the heart and other organs, manifesting as orthostatic hypotension (OH; also known as postural hypotension). We asked whether sympathetic denervation is associated with decreased uptake of catecholamines, such as dopamine and norepinephrine, into storage vesicles within sympathetic neurons. We used 6-[(18)F]-dopamine ((18)F-DA) to track myocardial uptake and retention of catecholamines. Concurrently, the fate of intra-neuronal (18)F-DA was followed by assessment of arterial plasma levels of the (18)F-DA metabolite (18)F-dihydroxyphenylacetic acid ((18)F-DOPAC). The ratio of myocardial (18)F-DA to arterial (18)F-DOPAC provided an index of vesicular uptake. Tracer concentrations were measured in patients with PD with or without orthostatic hypotension (PD+OH, PD-No-OH); in patients with pure autonomic failure (PAF, a Lewy body disease without parkinsonism); in patients with multiple system atrophy (MSA, a non-Lewy body synucleinopathy); and in normal controls. Patients with PD+OH or PAF had decreased vesicular (18)F-DA uptake and accelerated (18)F-DA loss, compared with MSA and control subjects. PD-No-OH patients could be subtyped into one of these categories based on their initial (18)F-DA uptake. We conclude that sympathetic denervation in Lewy body diseases is associated with decreased vesicular uptake of neuronal catecholamines, suggesting that vesicular monoamine transport is impaired. Vesicular uptake may constitute a novel target for diagnosis, treatment, and prevention.
C1 [Goldstein, David S.; Holmes, Courtney; Kopin, Irwin J.; Sharabi, Yehonatan] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC-1620,Bldg 10,Room 5N220, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU NIH, NINDS
FX This research was supported by the Intramural Research Program of the
NIH, NINDS. Tereza Jenkins coordinated patient travel. Sandra Pechnik
assisted with clinical procedures and scheduling. Basil Eldadah and
Richard Imrich served as postdoctoral fellows when the work was
performed.
NR 57
TC 25
Z9 26
U1 0
U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD AUG
PY 2011
VL 121
IS 8
BP 3320
EP 3330
DI 10.1172/JCI45803
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 802FU
UT WOS:000293495500038
PM 21785221
ER
PT J
AU Tiano, JP
Delghingaro-Augusto, V
Le May, C
Liu, SH
Kaw, MK
Khuder, SS
Latour, MG
Bhatt, SA
Korach, KS
Najjar, SM
Prentki, M
Mauvais-Jarvis, F
AF Tiano, Joseph P.
Delghingaro-Augusto, Viviane
Le May, Cedric
Liu, Suhuan
Kaw, Meenakshi K.
Khuder, Saja S.
Latour, Martin G.
Bhatt, Surabhi A.
Korach, Kenneth S.
Najjar, Sonia M.
Prentki, Marc
Mauvais-Jarvis, Franck
TI Estrogen receptor activation reduces lipid synthesis in pancreatic
islets and prevents beta cell failure in rodent models of type 2
diabetes
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID IMPROVES INSULIN SENSITIVITY; FATTY-ACID SYNTHASE; OB/OB MICE; IN-VIVO;
RESISTANCE; ALPHA; STAT3; RAT; MECHANISMS; EXPRESSION
AB The failure of pancreatic beta cells to adapt to an increasing demand for insulin is the major mechanism by which patients progress from insulin resistance to type 2 diabetes (T2D) and is thought to be related to dysfunctional lipid homeostasis within those cells. In multiple animal models of diabetes, females demonstrate relative protection from beta cell failure. We previously found that the hormone 17 beta-estradiol (E2) in part mediates this benefit. Here, we show that treating male Zucker diabetic fatty (ZDF) rats with E2 suppressed synthesis and accumulation of fatty acids and glycerolipids in islets and protected against beta cell failure. The antilipogenic actions of E2 were recapitulated by pharmacological activation of estrogen receptor alpha (ERa alpha) or ER beta in a rat beta cell line and in cultured ZDF rat, mouse, and human islets. Pancreas-specific null deletion of ER alpha in mice (PER alpha(-/-)) prevented reduction of lipid synthesis by E2 via a direct action in islets, and PER alpha(-/-) mice were predisposed to islet lipid accumulation and beta cell dysfunction in response to feeding with a high-fat diet. ER activation inhibited beta cell lipid synthesis by suppressing the expression (and activity) of fatty acid synthase via a nonclassical pathway dependent on activated Stat3. Accordingly, pancreas-specific deletion of Stat3 in mice curtailed ER-mediated suppression of lipid synthesis. These data suggest that extranuclear ERs may be promising therapeutic targets to prevent beta cell failure in T2D.
C1 [Tiano, Joseph P.; Le May, Cedric; Liu, Suhuan; Bhatt, Surabhi A.; Mauvais-Jarvis, Franck] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60611 USA.
[Delghingaro-Augusto, Viviane; Latour, Martin G.; Prentki, Marc] CRCHUM, Mol Nutr Unit, Montreal Diabet Res Ctr, Montreal, PQ, Canada.
[Delghingaro-Augusto, Viviane; Latour, Martin G.; Prentki, Marc] Univ Montreal, Dept Nutr, Montreal, PQ H3C 3J7, Canada.
[Kaw, Meenakshi K.; Khuder, Saja S.; Najjar, Sonia M.] Univ Toledo, Ctr Diabet & Endocrine Res CeDER, Coll Med, Toledo, OH 43606 USA.
[Korach, Kenneth S.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA.
[Mauvais-Jarvis, Franck] Northwestern Univ, Feinberg Sch Med, Comprehens Ctr Obes, Chicago, IL 60611 USA.
RP Mauvais-Jarvis, F (reprint author), Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, 303 E Chicago Ave,Tarry 15-761, Chicago, IL 60611 USA.
EM f-mauvais-jarvis@northwestern.edu
RI Le May, cedric/D-2691-2009;
OI Korach, Kenneth/0000-0002-7765-418X
FU National Cancer Institute Cancer Center [P30 CA060553]; National
Institutes of Diabetes and Digestive and Kidney Disease, Juvenile
Diabetes Research Foundation; NIH [R01DK074970-01, P50HD044405, T32
DK007169, R01DK054254, R01DK083850]; Juvenile Diabetes Research
Foundation [1-2006-837, 6-FY07-678]; NIH/NIEHS [Z01ES70065]; Canadian
Diabetes Association; Canadian Institute of Health Research; United
States Department of Agriculture (USDA) [38903-19826]
FX We are grateful to Winifred P.S. Wong for technical assistance in
generating and characterizing the ER alphalox/lox and PER
alpha-/- male mice. Imaging work was performed at the
Northwestern University Cell Imaging Facility, supported by National
Cancer Institute Cancer Center Support Grant P30 CA060553. We are
thankful to the Integrated Islet Distribution Program, funded by the
National Institutes of Diabetes and Digestive and Kidney Disease with
support from the Juvenile Diabetes Research Foundation International,
for providing human islets. This research was supported by grants from
the NIH (R01DK074970-01 and P50HD044405), the Juvenile Diabetes Research
Foundation (1-2006-837), and the March of Dimes (6-FY07-678) to F.
Mauvais-Jarvis. J.P. Tiano was supported in part by NIH Training Grant
T32 DK007169, and C. Le May was the recipient of a Juvenile Diabetes
Research Foundation Post-Doctoral Fellowship. ER alphalox/lox
mouse generation was funded by NIH/NIEHS division of intramural research
grant Z01ES70065 to K.S. Korach. Experiments of lipid cycling in Figure
3 were partially funded by grants from the Canadian Diabetes Association
and the Canadian Institute of Health Research to M. Prentki. FAS
activity assays were funded by grants from the NIH (R01DK054254 and
R01DK083850) and the United States Department of Agriculture (USDA
38903-19826) to S.M. Najjar.
NR 45
TC 64
Z9 65
U1 1
U2 10
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD AUG
PY 2011
VL 121
IS 8
BP 3331
EP 3342
DI 10.1172/JCI44564
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 802FU
UT WOS:000293495500039
PM 21747171
ER
PT J
AU Schambra, HM
Abe, M
Luckenbaugh, DA
Reis, J
Krakauer, JW
Cohen, LG
AF Schambra, Heidi M.
Abe, Mitsunari
Luckenbaugh, David A.
Reis, Janine
Krakauer, John W.
Cohen, Leonardo G.
TI Probing for hemispheric specialization for motor skill learning: a
transcranial direct current stimulation study
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE motor cortex; neurorehabilitation; neuromodulation; brain stimulation
ID DORSAL INTEROSSEOUS MUSCLE; TOOL-USE PANTOMIMES; EVENT-RELATED FMRI;
MAGNETIC STIMULATION; CORTEX EXCITABILITY; FINGER MOVEMENTS; NEURAL
REPRESENTATIONS; VOLUNTARY CONTRACTION; CORTICAL ACTIVATION;
BRAIN-STIMULATION
AB Schambra HM, Abe M, Luckenbaugh DA, Reis J, Krakauer JW, Cohen LG. Probing for hemispheric specialization for motor skill learning: a transcranial direct current stimulation study. J Neurophysiol 106: 652-661, 2011. First published May 25, 2011; doi:10.1152/jn.00210.2011.-Convergent findings point to a left-sided specialization for the representation of learned actions in right-handed humans, but it is unknown whether analogous hemispheric specialization exists for motor skill learning. In the present study, we explored this question by comparing the effects of anodal transcranial direct current stimulation (tDCS) over either left or right motor cortex (M1) on motor skill learning in either hand, using a tDCS montage to better isolate stimulation to one hemisphere. Results were compared with those previously found with a montage more commonly used in the field. Six groups trained for three sessions on a visually guided sequential pinch force modulation task with their right or left hand and received right M1, left M1, or sham tDCS. A linear mixed-model analysis for motor skill showed a significant main effect for stimulation group (left M1, right M1, sham) but not for hand (right, left) or their interaction. Left M1 tDCS induced significantly greater skill learning than sham when hand data were combined, a result consistent not only with the hypothesized left hemisphere specialization for motor skill learning but also with possible increased left M1 responsiveness to tDCS. The unihemispheric montage effect size was one-half that of the more common montage, and subsequent power analysis indicated that 75 subjects per group would be needed to detect differences seen with only 12 subjects with the customary bihemispheric montage.
C1 [Schambra, Heidi M.; Abe, Mitsunari; Reis, Janine; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabilitat Sect, NIH, Bethesda, MD 20892 USA.
[Schambra, Heidi M.] Columbia Univ, Motor Performance Lab, Neurol Inst, New York, NY USA.
[Luckenbaugh, David A.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Reis, Janine] Univ Freiburg, Dept Neurol, D-7800 Freiburg, Germany.
[Krakauer, John W.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Krakauer, John W.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21218 USA.
RP Cohen, LG (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabilitat Sect, NIH, 9000 Rockville Pike,Bldg 10,7D54, Bethesda, MD 20892 USA.
EM cohenl@ninds.nih.gov
RI Abe, Mitsunari/F-1373-2014
OI Abe, Mitsunari/0000-0002-3913-2292
FU National Institute of Neurological Disorders and Stroke (NINDS)
[R01-052804]
FX This work was supported by the National Institute of Neurological
Disorders and Stroke (NINDS) Intramural Research Program (H. M.
Schambra, M. Abe, J. Reis, L. G. Cohen), NINDS Competitive Postdoctoral
Fellowship (H. M. Schambra), and NINDS Grant R01-052804 (J. W.
Krakauer).
NR 107
TC 54
Z9 56
U1 0
U2 13
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD AUG
PY 2011
VL 106
IS 2
BP 652
EP 661
DI 10.1152/jn.00210.2011
PG 10
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 805NR
UT WOS:000293735300015
PM 21613597
ER
PT J
AU Moore, HM
Kelly, AB
Jewell, SD
McShane, LM
Clark, DP
Greenspan, R
Hayes, DF
Hainaut, P
Kim, P
Mansfield, E
Potapova, O
Riegman, P
Rubinstein, Y
Seijo, E
Somiari, S
Watson, P
Weier, HU
Zhu, C
Vaught, J
AF Moore, Helen M.
Kelly, Andrea B.
Jewell, Scott D.
McShane, Lisa M.
Clark, Douglas P.
Greenspan, Renata
Hayes, Daniel F.
Hainaut, Pierre
Kim, Paula
Mansfield, Elizabeth
Potapova, Olga
Riegman, Peter
Rubinstein, Yaffa
Seijo, Edward
Somiari, Stella
Watson, Peter
Weier, Heinz-Ulrich
Zhu, Claire
Vaught, Jim
TI Biospecimen Reporting for Improved Study Quality (BRISQ)
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE biospecimen; specimen; sample; collection; processing; handling;
storage; preanalytical; reporting; BRISQ
ID FLIGHT-MASS-SPECTROMETRY; PATHOLOGISTS GUIDELINE RECOMMENDATIONS;
APPROACHING CLINICAL PROTEOMICS; GENE-EXPRESSION PROFILES;
NEEDLE-ASPIRATION BIOPSY; PARAFFIN-EMBEDDED TISSUE; HUMAN POSTMORTEM
TISSUES; MICROARRAY ANALYSIS; BREAST-CANCER; HUMAN BRAIN
AB Human biospecimens are subjected to a number of different collection, processing, and storage factors that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research utilizing human tissues, it is crucial that information the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen-related research and help reassure patient contributors and the advocacy community that their contributions are valued and respected. Copyright (C) 2011 American Cancer Society.
C1 [Moore, Helen M.; Vaught, Jim] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA.
[McShane, Lisa M.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
[Zhu, Claire] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Kelly, Andrea B.] Rose Li & Associates Inc, Bethesda, MD USA.
[Jewell, Scott D.] Program Biospecimen Sci, Grand Rapids, MI USA.
[Jewell, Scott D.] Van Andel Res Inst, Grand Rapids, MI USA.
[Clark, Douglas P.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Greenspan, Renata] US Mil Canc Inst, Washington, DC USA.
[Hayes, Daniel F.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Hainaut, Pierre] WHO, Int Agcy Res Canc, Lyon, France.
[Mansfield, Elizabeth] US FDA, Silver Spring, MD USA.
[Potapova, Olga] Cureline Inc, San Francisco, CA USA.
[Riegman, Peter] Erasmus MC Tissue Bank, Rotterdam, Netherlands.
[Rubinstein, Yaffa] NIH, Off Rare Dis Res, Rockville, MD USA.
[Seijo, Edward] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Somiari, Stella] Windber Res Inst, Windber, PA USA.
[Watson, Peter] British Columbia Canc Agcy, Vancouver Isl Ctr, Victoria, BC, Canada.
[Weier, Heinz-Ulrich] Lawrence Berkeley Natl Lab, Berkeley, CA USA.
RP Vaught, J (reprint author), NCI, Off Biorepositories & Biospecimen Res, 11400 Rockville Pike,Rm 700,MSC 9160, Bethesda, MD 20892 USA.
EM kellya2@mail.nih.gov
RI Hainaut, Pierre /B-6018-2012
OI Hainaut, Pierre /0000-0002-1303-1610
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH [CA 136685, DE-AC02-05CH11231]
FX This project has been funded in whole or in part with Federal Funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This work was supported in part by NIH grant CA 136685 (HUW) carried out
at the Lawrence Berkeley National Laboratory under contract
DE-AC02-05CH11231.
NR 85
TC 61
Z9 62
U1 1
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
J9 J PROTEOME RES
JI J. Proteome Res.
PD AUG
PY 2011
VL 10
IS 8
BP 3429
EP 3438
DI 10.1021/pr200021n
PG 10
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 802CW
UT WOS:000293487900011
PM 21574648
ER
PT J
AU Fenton, JJ
Abraham, L
Taplin, SH
Geller, BM
Carney, PA
D'Orsi, C
Elmore, JG
Barlow, WE
AF Fenton, Joshua J.
Abraham, Linn
Taplin, Stephen H.
Geller, Berta M.
Carney, Patricia A.
D'Orsi, Carl
Elmore, Joann G.
Barlow, William E.
CA Breast Canc Surveillance Consortiu
TI Effectiveness of Computer-Aided Detection in Community Mammography
Practice
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID POSTMENOPAUSAL HORMONE-THERAPY; ESTROGEN PLUS PROGESTIN; BREAST-CANCER
DETECTION; SCREENING MAMMOGRAPHY; DIGITAL MAMMOGRAPHY; DETECTION SYSTEM;
UNITED-STATES; IN-SITU; PERFORMANCE; POPULATION
AB Background Computer-aided detection (CAD) is applied during screening mammography for millions of US women annually, although it is uncertain whether CAD improves breast cancer detection when used by community radiologists.
Methods We investigated the association between CAD use during film-screen screening mammography and specificity, sensitivity, positive predictive value, cancer detection rates, and prognostic characteristics of breast cancers (stage, size, and node involvement). Records from 684 956 women who received more than 1.6 million film-screen mammograms at Breast Cancer Surveillance Consortium facilities in seven states in the United States from 1998 to 2006 were analyzed. We used random-effects logistic regression to estimate associations between CAD and specificity (true-negative examinations among women without breast cancer), sensitivity (true-positive examinations among women with breast cancer diagnosed within 1 year of mammography), and positive predictive value (breast cancer diagnosed after positive mammograms) while adjusting for mammography registry, patient age, time since previous mammography, breast density, use of hormone replacement therapy, and year of examination (1998-2002 vs 2003-2006). All statistical tests were two-sided.
Results Of 90 total facilities, 25 (27.8%) adopted CAD and used it for an average of 27.5 study months. In adjusted analyses, CAD use was associated with statistically significantly lower specificity (OR = 0.87, 95% confidence interval [CI] = 0.85 to 0.89, P < .001) and positive predictive value (OR = 0.89, 95% CI = 0.80 to 0.99, P = .03). A non-statistically significant increase in overall sensitivity with CAD (OR = 1.06, 95% CI = 0.84 to 1.33, P = .62) was attributed to increased sensitivity for ductal carcinoma in situ (OR = 1.55, 95% CI = 0.83 to 2.91; P = .17), although sensitivity for invasive cancer was similar with or without CAD (OR = 0.96, 95% CI = 0.75 to 1.24; P = .77). CAD was not associated with higher breast cancer detection rates or more favorable stage, size, or lymph node status of invasive breast cancer.
Conclusion CAD use during film-screen screening mammography in the United States is associated with decreased specificity but not with improvement in the detection rate or prognostic characteristics of invasive breast cancer. J Natl Cancer Inst 2011; 103: 1152-1161
C1 [Fenton, Joshua J.] Univ Calif Davis, Dept Family & Community Med, Sacramento, CA 95817 USA.
[Fenton, Joshua J.] Univ Calif Davis, Ctr Healthcare Policy & Res, Sacramento, CA 95817 USA.
[Abraham, Linn] Grp Hlth Res Inst, Seattle, WA USA.
[Taplin, Stephen H.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Geller, Berta M.] Univ Vermont, Dept Family Med, Off Hlth Promot Res, Burlington, VT USA.
[Carney, Patricia A.] Oregon Hlth & Sci Univ, Dept Family Med & Publ Hlth & Prevent Med, Portland, OR 97201 USA.
[D'Orsi, Carl] Emory Univ, Dept Radiol, Atlanta, GA 30322 USA.
[Elmore, Joann G.] Univ Washington, Dept Med, Seattle, WA USA.
[Elmore, Joann G.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Barlow, William E.] Canc Res & Biostat, Seattle, WA USA.
RP Fenton, JJ (reprint author), Univ Calif Davis, Dept Family & Community Med, 4860 Y St,Ste 2300, Sacramento, CA 95817 USA.
EM joshua.fenton@ucdmc.ucdavis.edu
OI Fenton, Joshua/0000-0002-0581-835X
FU National Cancer Institute-funded Breast Cancer Surveillance Consortium
[U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976,
U01CA63731, U01CA70040]; National Cancer Institute [CA104699]; American
Cancer Society [MRSGT-05-214-01-CPPB]
FX This work was supported by the National Cancer Institute-funded Breast
Cancer Surveillance Consortium co-operative agreement (grants
U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976,
U01CA63731, and U01CA70040), the National Cancer Institute (grant
CA104699 to J.G.E.), and the American Cancer Society (grant
MRSGT-05-214-01-CPPB to J.J.F.). The collection of cancer data used in
this study was supported in part by several state public health
departments and cancer registries throughout the U.S. For a full
description of these sources, please see:
http://breastscreening.cancer.gov/work/acknowledgement.html.
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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 AUG
PY 2011
VL 103
IS 15
BP 1152
EP 1161
DI 10.1093/jnci/djr206
PG 10
WC Oncology
SC Oncology
GA 804BH
UT WOS:000293628200007
PM 21795668
ER
PT J
AU Edwards, LA
Woolard, K
Son, MJ
Li, AG
Lee, JW
Ene, C
Mantey, SA
Maric, D
Song, H
Belova, G
Jensen, RT
Zhang, W
Fine, HA
AF Edwards, Lincoln A.
Woolard, Kevin
Son, Myung Jin
Li, Aiguo
Lee, Jeongwu
Ene, Chibawanye
Mantey, Samuel A.
Maric, Dragan
Song, Hua
Belova, Galina
Jensen, Robert T.
Zhang, Wei
Fine, Howard A.
TI Effect of Brain- and Tumor-Derived Connective Tissue Growth Factor on
Glioma Invasion
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID BREAST-CANCER CELLS; NF-KAPPA-B; E-CADHERIN; MESENCHYMAL TRANSITION;
HUMAN GLIOBLASTOMA; NERVOUS-SYSTEM; STEM-CELLS; METASTASIS; RECEPTOR;
KINASE
AB Background Tumor cell invasion is the principal cause of treatment failure and death among patients with malignant gliomas. Connective tissue growth factor (CTGF) has been previously implicated in cancer metastasis and invasion in various tumors. We explored the mechanism of CTGF-mediated glioma cell infiltration and examined potential therapeutic targets.
Methods Highly infiltrative patient-derived glioma tumor-initiating or tumor stem cells (TIC/TSCs) were harvested and used to explore a CTGF-induced signal transduction pathway via luciferase reporter assays, chromatin immuno-precipitation (ChIP), real-time polymerase chain reaction, and immunoblotting. Treatment of TIC/TSCs with small-molecule inhibitors targeting integrin beta 1 (ITGB1) and the tyrosine kinase receptor type A (TrkA), and short hairpin RNAs targeting CTGF directly were used to reduce the levels of key protein components of CTGF-induced cancer infiltration. TIC/TSC infiltration was examined in real-time cell migration and invasion assays in vitro and by immunohistochemistry and in situ hybridization in TIC/TSC orthotopic xenograft mouse models (n = 30; six mice per group). All statistical tests were two-sided.
Results Treatment of TIC/TSCs with CTGF resulted in CTGF binding to ITGB1-TrkA receptor complexes and nuclear factor kappa B (NF-kappa B) transcriptional activation as measured by luciferase reporter assays (mean relative luciferase activity, untreated vs CTGF(200 ng/mL): 0.53 vs 1.87, difference = 1.34, 95% confidence interval [ CI] = 0.69 to 2, P < .001). NF-kappa B activation resulted in binding of ZEB-1 to the E-cadherin promoter as demonstrated by ChIP analysis with subsequent E-cadherin suppression (fold increase in ZEB-1 binding to the E-cadherin promoter region: untreated + ZEB-1 antibody vs CTGF(200 ng/mL) + ZEB-1 antibody: 1.5 vs 6.4, difference = 4.9, 95% CI = 4.8 to 5.0, P < .001). Immunohistochemistry and in situ hybridization revealed that TrkA is selectively expressed in the most infiltrative glioma cells in situ and that the surrounding reactive astrocytes secrete CTGF.
Conclusion A CTGF-rich microenvironment facilitates CTGF-ITGB1-TrkA complex activation in TIC/TSCs, thereby increasing the invasiveness of malignant gliomas. J Natl Cancer Inst 2011; 103: 1162-1178
C1 [Edwards, Lincoln A.; Woolard, Kevin; Son, Myung Jin; Li, Aiguo; Lee, Jeongwu; Ene, Chibawanye; Song, Hua; Belova, Galina; Zhang, Wei; Fine, Howard A.] Natl Inst Neurol Disorders & Stroke, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA.
[Mantey, Samuel A.; Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA.
RP Fine, HA (reprint author), Natl Inst Neurol Disorders & Stroke, Neurooncol Branch, NCI, NIH, 10 Ctr Dr,Bloch Bldg,82,9030 Old Georgetown Rd, Bethesda, MD 20892 USA.
EM hfine@mail.nih.gov
FU National Cancer Institute; National Institute of Neurological Disorders
and Stroke of the National Institutes of Health
FX This work was supported by the intramural programs of National Cancer
Institute and the National Institute of Neurological Disorders and
Stroke of the National Institutes of Health.
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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 AUG
PY 2011
VL 103
IS 15
BP 1162
EP 1178
DI 10.1093/jnci/djr224
PG 17
WC Oncology
SC Oncology
GA 804BH
UT WOS:000293628200008
PM 21771732
ER
PT J
AU Barr, RA
AF Barr, Robin A.
TI NIA funding for Alzheimer's research
SO LANCET NEUROLOGY
LA English
DT Letter
C1 NIA, Div Extramural Act, NIH, Bethesda, MD 20892 USA.
RP Barr, RA (reprint author), NIA, Div Extramural Act, NIH, Bethesda, MD 20892 USA.
EM rb42h@nih.gov
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD AUG
PY 2011
VL 10
IS 8
BP 683
EP 683
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA 803WJ
UT WOS:000293612600010
PM 21777823
ER
PT J
AU Nutt, JG
Bloem, BR
Giladi, N
Hallett, M
Horak, FB
Nieuwboer, A
AF Nutt, John G.
Bloem, Bastiaan R.
Giladi, Nir
Hallett, Mark
Horak, Fay B.
Nieuwboer, Alice
TI Freezing of gait: moving forward on a mysterious clinical phenomenon
SO LANCET NEUROLOGY
LA English
DT Review
ID ANTICIPATORY POSTURAL ADJUSTMENTS; SUBTHALAMIC NUCLEUS STIMULATION;
PARKINSONS-DISEASE PATIENTS; QUALITY-OF-LIFE; PEDUNCULOPONTINE NUCLEUS;
AUDITORY CUES; BILATERAL COORDINATION; BASAL GANGLIA; OLDER-ADULTS;
BRAIN-STEM
AB Freezing of gait (FoG) is a unique and disabling clinical phenomenon characterised by brief episodes of inability to step or by extremely short steps that typically occur on initiating gait or on turning while walking. Patients with FoG, which is a feature of parldnsonian syndromes, show variability in gait metrics between FoG episodes and a substantial reduction in step length with frequent trembling of the legs during FoG episodes. Physiological, functional imaging, and clinical pathological studies point to disturbances in frontal cortical regions, the basal ganglia, and the midbrain locomotor region as the probable origins of FoG. Medications, deep brain stimulation, and rehabilitation techniques can alleviate symptoms of FoG in some patients, but these treatments lack efficacy in patients with advanced FoG. A better understanding of the phenomenon is needed to aid the development of effective therapeutic strategies.
C1 [Nutt, John G.; Horak, Fay B.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
[Bloem, Bastiaan R.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands.
[Giladi, Nir] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
[Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[Nieuwboer, Alice] Katholieke Univ Leuven, Dept Rehabil Sci, Tervuursevest, Belgium.
RP Nutt, JG (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
EM nuttj@ohsu.edu
RI Bloem, Bastiaan/E-3812-2010; Nieuwboer, Alice/F-5643-2013; Bloem,
B.R./H-8013-2014
OI Nieuwboer, Alice/0000-0003-1193-6229;
FU Teva Pharmaceutical; Ipsen; Xenoport; Impax Laboratories; Neurogen;
Synosia; Neuroderm; Merck; Lilly/Medtronics; Elan; Addex; Lurnbeck; Merz
Pharmaceuticals; SynAgile; National Institutes of Health (NIH); Veterans
Administration; National Parkinson Foundation; Michael J Fox Foundation;
RJG Foundation; Boehringer Ingelheim; Teva; GlaxoSmithKline; Novartis;
European Federation of Neurological Societies; Tijdschrift voor
Neurolgie en Neurochiugie; Netherlands Organisation for Scientific
Research; Prinses Beatrix Fonds; Stichting Internationaal Parkinson
Fonds; van Alkemade-Keuls Foundation; UCB; Schwarz Pharma; Lundbeck;
Eisai; Intec Pharma; Solvay; Merz; Biogen; Israel Science Foundation;
Hong Kong Polytechnical University; APDM Inc OHSU Hospital; Movement
Disorder Society, National Institutes of Health (NIH) [1R13NS67914-1];
Movement Disorder Society
FX This Review is partly the product of presentations and discussions at an
international workshop, held on Feb 24-25,2010, in Washington DC, USA,
to review the phenomenonology of freezing of gait (FoG), the physiology
of locomotion and sites of dysfunction that could conceivably produce
FoG, hypotheses for causes of FoG, and future directions. The invited
participants were chosen for their basic or clinical research experience
in locomotion and FoG. The workshop was organised and undertaken by the
authors of the report. The meeting was supported by the Movement
Disorder Society, National Institutes of Health (NIH) Grant
1R13NS67914-1, and unrestricted educational grants from Teva
Pharmaceutical and Ipsen. We thank A Achterman and D Potts of Oregon
Health & Science University, OR, USA, for their assistance in arranging
the workshop and preparing the report.; In the past 3 years, JGN and the
Oregon Health & Sciences University (OHS U) have received consulting
fees from Xenoport, Impax Laboratories, Neurogen, Synosia, Neuroderm,
Merck, Lilly/Medtronics, Elan, Addex, Lurnbeck, Merz Pharmaceuticals,
and SynAgile, and grants from the National Institutes of Health (NIH),
the Veterans Administration, the National Parkinson Foundation, the
Michael J Fox Foundation, the RJG Foundation, and Merck. In the past 3
years, BRB and the Radboud University Nijmegen Medical Centre have
received consulting fees, travel funds, board membership fees, and
grants from Boehringer Ingelheim, Teva, GlaxoSmithKline, Novartis, the
Movement Disorder Society, the European Federation of Neurological
Societies, Tijdschrift voor Neurolgie en Neurochiugie, the Netherlands
Organisation for Scientific Research, the Michael J Fox Foundation,
Prinses Beatrix Fonds, Stichting Internationaal Parkinson Fonds, and the
van Alkemade-Keuls Foundation. In the past 3 years, NG and the Sadder
School of Medicine, Tel Aviv University, have received board membership
fees, consulting fees, speaking fees, travel fees, and grants from the
Movement Disorder Society, Teva, UCB, Schwarz Pharma, Lundbeck, Eisai,
Intec Pharma, GlaxoSmithKline, Solvay, Merz, Biogen, Neuroderm, the
Michael J Fox Foundation, the National Parkinson Foundation, and the
Israel Science Foundation. In the past 3 years, FBH and the OHSU have
received speaker fees, board membership fees, and grants from the Hong
Kong Polytechnical University, the APDM Inc OHSU Hospital Innovation
Fund, and NIH. MH and AN declare that they have no conflicts of
interest.
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PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD AUG
PY 2011
VL 10
IS 8
BP 734
EP 744
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA 803WJ
UT WOS:000293612600015
PM 21777828
ER
PT J
AU Kappos, L
Bates, D
Edan, G
Eraksoy, M
Garcia-Merino, A
Grigoriadis, N
Hartung, HP
Havrdova, E
Hillert, J
Hohlfeld, R
Kremenchutzky, M
Lyon-Caen, O
Miller, A
Pozzilli, C
Ravnborg, M
Saida, T
Sindic, C
Vass, K
Clifford, DB
Hauser, S
Major, EO
O'Connor, PW
Weiner, HL
Clanet, M
Gold, R
Hirsch, HH
Radu, EW
Sorensen, PS
King, J
AF Kappos, Ludwig
Bates, David
Edan, Gilles
Eraksoy, Mefkure
Garcia-Merino, Antonio
Grigoriadis, Nikolaos
Hartung, Hans-Peter
Havrdova, Eva
Hillert, Jan
Hohlfeld, Reinhard
Kremenchutzky, Marcelo
Lyon-Caen, Olivier
Miller, Ariel
Pozzilli, Carlo
Ravnborg, Mads
Saida, Takahiko
Sindic, Christian
Vass, Karl
Clifford, David B.
Hauser, Stephen
Major, Eugene O.
O'Connor, Paul W.
Weiner, Howard L.
Clanet, Michel
Gold, Ralf
Hirsch, Hans H.
Radue, Ernst-Wilhelm
Sorensen, Per Soelberg
King, John
TI Natalizumab treatment for multiple sclerosis: updated recommendations
for patient selection and monitoring
SO LANCET NEUROLOGY
LA English
DT Review
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; POTENT ANTIRETROVIRAL
THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; PLACEBO-CONTROLLED TRIAL;
NERVOUS-SYSTEM LYMPHOMA; JC VIRUS; RHEUMATIC-DISEASES; ALPHA-INTERFERON;
COMPLICATING TREATMENT; TREATED PATIENTS
AB Natalizumab, a highly specific alpha 4-integrin antagonist, is approved for treatment of patients with active relapsing-remitting multiple sclerosis (RRMS). It is generally recommended for individuals who have not responded to a currently available first-line disease-modifying therapy or who have very active disease. The expected benefits of natalizumab treatment have to be weighed against risks, especially the rare but serious adverse event of progressive multifocal leukoencephalopathy. In this Review, we revisit and update previous recommendations on natalizumab for treatment of patients with RRMS, based on additional long-term follow-up of clinical studies and post-marketing observations, including appropriate patient selection and management recommendations.
C1 [Kappos, Ludwig; Hirsch, Hans H.; Radue, Ernst-Wilhelm] Univ Basel Hosp, CH-4031 Basel, Switzerland.
[Bates, David] Royal Victoria Hosp, Newcastle Upon Tyne, Tyne & Wear, England.
[Edan, Gilles] CHU Rennes, INSERM, Serv Neurol, CIC P 0203, Rennes, France.
[Eraksoy, Mefkure] Istanbul Univ, Istanbul, Turkey.
[Garcia-Merino, Antonio] Puerta de Hierro Univ Hosp, Madrid, Spain.
[Grigoriadis, Nikolaos] Aristotle Univ Thessaloniki, AHEPA Univ Hosp, GR-54006 Thessaloniki, Greece.
[Hartung, Hans-Peter] Univ Dusseldorf, Dept Neurol, D-4000 Dusseldorf, Germany.
[Havrdova, Eva] Charles Univ Prague, Prague, Czech Republic.
[Hillert, Jan] Karolinska Univ Hosp, Huddinge, Sweden.
[Hohlfeld, Reinhard] Univ Munich, Munich, Germany.
[Kremenchutzky, Marcelo] Univ Western Ontario, Univ Hosp, London, ON N6A 5A5, Canada.
[Lyon-Caen, Olivier] Hop La Pitie Salpetriere, Paris, France.
[Miller, Ariel] Carmel Hosp, Haifa, Israel.
[Pozzilli, Carlo] Univ Roma La Sapienza, Rome, Italy.
[Ravnborg, Mads] Odense Univ Hosp, DK-5000 Odense, Denmark.
[Saida, Takahiko] Natl Utano Hosp, Kyoto, Japan.
[Sindic, Christian] Univ Louvain, Brussels, Belgium.
[Vass, Karl] Univ Vienna, Vienna, Austria.
[Clifford, David B.] Washington Univ, St Louis, MO USA.
[Hauser, Stephen] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Major, Eugene O.] Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, Bethesda, MD USA.
[O'Connor, Paul W.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[Weiner, Howard L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Clanet, Michel] Univ Hop Purpan, Toulouse, France.
[Gold, Ralf] Univ Bochum, Bochum, Germany.
[Sorensen, Per Soelberg] Univ Copenhagen Hosp, DK-2100 Copenhagen, Denmark.
[King, John] Univ Melbourne, Royal Melbourne Hosp, Melbourne, Vic 3050, Australia.
RP Kappos, L (reprint author), Univ Basel Hosp, Petersgraben 4, CH-4031 Basel, Switzerland.
EM lkappos@uhbs.ch
RI Kremenchutzky, Marcelo/B-6413-2015
FU Biogen Idec; Actelion; Advancell; Allozyne; BaroFold; Bayer Health Care
Pharmaceuticals; Bayer Schering Pharma; Bayhill; BioMarin; CLC Behring;
Elan; Genmab; Genmark; GeNeuro SA; GlaxoSmithKline; Lilly; Merck Serono;
MediciNova; Novartis; Novonordisk; Peptimmune; Sanofi-Aventis; Santhera;
Roche; Teva; UCB; Wyeth; Biogen Idec, Serono; Schering; Teva
Pharmaceuticals; Bayer; Biogen Idec, Schering; Serono; Genesis Pharma;
Bayer Healthcare; Genzyme; Bayer Schering, University of Dusseldorf;
Novartis Pharmaceuticals; Octapharma; Merck; EMD Serono; Bayer Schering;
Bristol-Myers Squibb; Genentech; Millennium; Pfizer; Wyeth-Pfizer;
Receptos; BioMS; Cognosci; Daiichi Sankyo; Autoimmune; Pepgen; Vascular
Biogenics; Biogen
FX This Review is based on meetings between several independent committees,
consisting of lead investigators of clinical studies of natalizumab in
multiple sclerosis and experts in the area of multiple sclerosis, PML,
and natalizumab from Europe, the USA, Canada, and Australia. We thank
the members of these committees for their valuable input, especially
participants of the International Multiple Sclerosis Expert Forum
(IMSEF), a group of experts established by Biogen Idec to provide
guidance on the indication and necessary precautions for treatment with
natalizumab in multiple sclerosis. Meetings of the IMSEF and other
expert committees were supported by Biogen Idec. We thank Frauke Treppke
for assistance with preparation and submission of this Review.
Jacqueline Cannon and Joan Ryan (Infusion Communications, Haddam, CT,
USA) helped with language and formal editing of this Review but had no
influence on content; their work was funded by Biogen Idec.; LK
discloses that the University Hospital, Basel, has received research
support from Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care
Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, BioMarin,
CLC Behring, Elan, Genmab, Genmark, GeNeuro SA, GlaxoSmithKline, Lilly,
Merck Serono, MediciNova, Novartis, Novonordisk, Peptimmune,
Sanofi-Aventis, Santhera, Roche, Teva, UCB, and Wyeth. LK has been
principal investigator, member, or chair of steering committees or
advisory boards on multiple sclerosis clinical trials sponsored by these
companies, and has received lecture fees from one or more of these
companies. Payments and consultancy fees have been used exclusively for
support of research activities. DB has received honoraria and research
support from Biogen Idec, Serono, Schering, and Teva Pharmaceuticals. GE
has received honoraria for advisory board participation from Bayer,
Biogen Idec, and LFB, and his institution has received grant support
from Bayer, Merck Serono, and Teva. AG-M has received honoraria for
consultancy and research support from Biogen Idec, Schering, Serono, and
Teva Pharmaceuticals. NG has received honoraria and travel support from
Biogen Idec, consultancy fees from Biogen Idec and Novartis, lecture
fees from Biogen Idec and Merck Serono, and grants from Biogen Idec,
Merck Serono, Sanofi-Aventis, and Genesis Pharma. H-PH has received
honoraria and consultancy fees from Bayer Healthcare, Biogen Idec, Merck
Serono, Novartis, and Genzyme and travel costs from Biogen Idec,
Novartis, Merck Serono, and Bayer Schering with the approval of the
Rector of the University of Dusseldorf. EH has received research funding
from Biogen Idec, Novartis Pharmaceuticals, Octapharma, Schering,
Serono, and Teva Pharmaceuticals and honoraria for lecturing from Biogen
Idec, Pfizer, Schering, and Teva Pharmaceuticals. JH has received
honoraria for consultancy from Biogen Idec and for lecturing from Bayer,
Merck, and Teva, and grant support to his institution from Bayer, Biogen
Idec, Merck, and Sanofi-Aventis. RH has received consultancy honoraria
from Biogen Idec, Schering, Novartis, Teva, Sanofi-Aventis, and Merck
Serono. MK has received payment for consultancy from Biogen Idec, Bayer,
EMD Serono, Teva, and Novartis and clinical trial support from Biogen
Idec, Sanofi-Aventis, Genzyme, CellGene, Teva, Bayer, EMD Serono, and
Novartis. OL-C has received payments as advisory board member and for
development of educational programmes by Biogen Idec. CP has received
honoraria for consultancy, board membership, and lectures, including
service of speakers' bureaus, from Bayer Schering, Merck Serono,
Novartis, and Sanofi-Aventis, and research grants from Bayer Schering,
Merck Serono, and Sanofi-Aventis. MR has received honoraria for
consultancy from Novartis and Sanofi-Aventis, for lecturing from
Novartis, and for grant support and travel expenses from Biogen Idec. CS
has received payments to his institution for consultancy from Bayer
Schering, GSK Biologicals Vaccines, Merck Serono, Novartis, and
Sanofi-Aventis and for lecturing from Bayer Schering, Merck Serono, and
Sanofi-Aventis, and has received research grants from Merck Serono and
Novartis. KV has received honoraria for lectures and board memberships
from Biogen Idec, Bayer Schering, Merck Serono, Sanofi-Aventis, and
Novartis.; DBC has received honoraria and consultancy fees from Biogen
Idec, Bristol-Myers Squibb, Genentech, Genzyme, Millennium, and Pfizer,
fees for expert testimony from Biogen Idec, lecture fees from
GlaxoSmithKline, Millenium, and Biogen Idec, and travel osts from Biogen
Idec. SH has received travel support from Roche, and his institution has
received consulting and advisory board membership fees from
Wyeth-Pfizer, Novartis, Receptos, and BioMarin. SH and his institution
own stock in Receptos. PWO'C has received consulting fees, research
support for MS trials, or both from Actelion, Bayer, Biogen Idec, BioMS,
Cognosci, Daiichi Sankyo, EMD Serono, Genentech, and Genmab. H LW has
received consultancy fees from Autoimmune, Biogen Idec, Pepgen, Pfizer,
Serono, Teva Pharmaceuticals, and Vascular Biogenics. MC has received
consultancy honoraria from Biogen and Novartis and grant support from
Biogen, Novartis, Teva, Sanofi-Aventis, and Merck Serono. RG has
received payments for consultancy from Biogen and Teva. E-WR has
received payments to his institution for membership of advisory boards
of Biogen Idec and Novartis, honoraria for consultancy from Biogen Idec,
Bayer Schering, Merck, and Novartis, and for lecturing from Bayer
Schering, Biogen Idec, and Novartis. PSS has received grant support,
honoraria, and support for travel from Biogen Idec, consultancy fees
from Merck Serono, Teva, Elan, Genmab, Novartis, and Sanofi-Aventis, and
payments for lectures from Merck Serono, Novartis, Bayer Schering, Teva,
and Sanofi-Aventis. JK has received honoraria and consultancy fees from
Biogen Idec, Sanofi-Aventis, Schering, and Serono. ME, AM, TS, EOM, and
HHH declare that they have no conflicts of interest.
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PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
EI 1474-4465
J9 LANCET NEUROL
JI Lancet Neurol.
PD AUG
PY 2011
VL 10
IS 8
BP 745
EP 758
PG 14
WC Clinical Neurology
SC Neurosciences & Neurology
GA 803WJ
UT WOS:000293612600016
PM 21777829
ER
PT J
AU Dar, A
Schajnovitz, A
Lapid, K
Kalinkovich, A
Itkin, T
Ludin, A
Kao, WM
Battista, M
Tesio, M
Kollet, O
Cohen, NN
Margalit, R
Buss, EC
Baleux, F
Oishi, S
Fujii, N
Larochelle, A
Dunbar, CE
Broxmeyer, HE
Frenette, PS
Lapidot, T
AF Dar, A.
Schajnovitz, A.
Lapid, K.
Kalinkovich, A.
Itkin, T.
Ludin, A.
Kao, W-M
Battista, M.
Tesio, M.
Kollet, O.
Cohen, N. N.
Margalit, R.
Buss, E. C.
Baleux, F.
Oishi, S.
Fujii, N.
Larochelle, A.
Dunbar, C. E.
Broxmeyer, H. E.
Frenette, P. S.
Lapidot, T.
TI Rapid mobilization of hematopoietic progenitors by AMD3100 and
catecholamines is mediated by CXCR4-dependent SDF-1 release from bone
marrow stromal cells
SO LEUKEMIA
LA English
DT Article
DE rapid mobilization; AMD3100; catecholamines; uPA; SDF-1/CXCR4;
hematopoietic progenitor cells
ID COLONY-STIMULATING FACTOR; PLASMINOGEN-ACTIVATOR RECEPTOR; G-CSF;
PERIPHERAL-BLOOD; STEM-CELLS; CXCR4 ANTAGONIST; CHEMOKINE SDF-1; CD34(+)
CELLS; MICE; MIGRATION
AB Steady-state egress of hematopoietic progenitor cells can be rapidly amplified by mobilizing agents such as AMD3100, the mechanism, however, is poorly understood. We report that AMD3100 increased the homeostatic release of the chemokine stromal cell derived factor-1 (SDF-1) to the circulation in mice and non-human primates. Neutralizing antibodies against CXCR4 or SDF-1 inhibited both steady state and AMD3100-induced SDF-1 release and reduced egress of murine progenitor cells over mature leukocytes. Intra-bone injection of biotinylated SDF-1 also enhanced release of this chemokine and murine progenitor cell mobilization. AMD3100 directly induced SDF-1 release from CXCR4(+) human bone marrow osteoblasts and endothelial cells and activated uPA in a CXCR4/JNK-dependent manner. Additionally, ROS inhibition reduced AMD3100-induced SDF-1 release, activation of circulating uPA and mobilization of progenitor cells. Norepinephrine treatment, mimicking acute stress, rapidly increased SDF-1 release and progenitor cell mobilization, whereas beta 2-adrenergic antagonist inhibited both steady state and AMD3100-induced SDF-1 release and progenitor cell mobilization in mice. In conclusion, this study reveals that SDF-1 release from bone marrow stromal cells to the circulation emerges as a pivotal mechanism essential for steady-state egress and rapid mobilization of hematopoietic progenitor cells, but not mature leukocytes. Leukemia (2011) 25, 1286-1296; doi:10.1038/leu.2011.62; published online 15 April 2011
C1 [Dar, A.; Schajnovitz, A.; Lapid, K.; Kalinkovich, A.; Itkin, T.; Ludin, A.; Tesio, M.; Kollet, O.; Cohen, N. N.; Margalit, R.; Buss, E. C.; Lapidot, T.] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
[Kao, W-M; Battista, M.; Frenette, P. S.] Mt Sinai Sch Med, Dept Med, Inst Immunol, New York, NY USA.
[Kao, W-M; Battista, M.; Frenette, P. S.] Mt Sinai Sch Med, Black Family Stem Cell Inst, New York, NY USA.
[Oishi, S.; Fujii, N.] Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto, Japan.
[Baleux, F.] Inst Pasteur, Paris, France.
[Larochelle, A.; Dunbar, C. E.] NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Broxmeyer, H. E.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN USA.
RP Lapidot, T (reprint author), Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
EM Tsvee.Lapidot@weizmann.ac.il
RI Frenette, Paul/J-8272-2012; Lapidot, Tsvee/A-1812-2010; Kollet,
Orit/A-6861-2008; Oishi, Shinya/C-1350-2011;
OI Oishi, Shinya/0000-0002-2833-2539; Lapid, Kfir/0000-0002-8898-8695
FU Helen and Martin Kimmel Institute for Stem Cell Research at the Weizmann
Institute; Israeli Science Foundation [544/09]; European Union (Advance
Cell-based Therapies for the Treatment of Primary Immunodeficiency)
[HEALTH-F5-2010-261387]; Legacy Heritage Fund; National Institutes of
Health; Ministry of Education, Culture, Sports, Science, and Technology
of Japan
FX This study was partially supported by the Helen and Martin Kimmel
Institute for Stem Cell Research at the Weizmann Institute, Israeli
Science Foundation grant 544/09, the European Union (Advance Cell-based
Therapies for the Treatment of Primary Immunodeficiency
HEALTH-F5-2010-261387) and the Legacy Heritage Fund (TL). PSF is an
established investigator of the American Heart Association supported by
the National Institutes of Health. This work was also partially
supported by Grant-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science, and Technology of Japan (SO and
NF). TL holds The Edith Arnoff Stein Professorial Chair in Stem Cell
Research. We would like to thank Dr Abraham Avigdor for supplying us
with human BM aspirations from healthy donors and to Dr Scott Cooper for
performing experiments with Anormed-derived AMD3100. Our special thanks
to Drs Sara Rankin, Isabelle Petit, Shoham Shivtiel and Jonathan Canaani
for fruitful discussions and for critically reviewing the manuscript.
NR 66
TC 91
Z9 95
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD AUG
PY 2011
VL 25
IS 8
BP 1286
EP 1296
DI 10.1038/leu.2011.62
PG 11
WC Oncology; Hematology
SC Oncology; Hematology
GA 806CA
UT WOS:000293778900008
PM 21494253
ER
PT J
AU Chen, XJ
Bagci, U
AF Chen, Xinjian
Bagci, Ulas
TI 3D automatic anatomy segmentation based on iterative graph-cut-ASM
SO MEDICAL PHYSICS
LA English
DT Article
DE statistical models; object recognition; image segmentation; active shape
models; graph cut
ID ACTIVE SHAPE MODELS; IMAGE SEGMENTATION; ENERGY MINIMIZATION; FUZZY
CONNECTEDNESS; OBJECT DEFINITION; ALGORITHMS
AB Purpose: This paper studies the feasibility of developing an automatic anatomy segmentation (AAS) system in clinical radiology and demonstrates its operation on clinical 3D images.
Methods: The AAS system, the authors are developing consists of two main parts: object recognition and object delineation. As for recognition, a hierarchical 3D scale-based multiobject method is used for the multiobject recognition task, which incorporates intensity weighted ball-scale (b-scale) information into the active shape model (ASM). For object delineation, an iterative graph-cut-ASM (IGCASM) algorithm is proposed, which effectively combines the rich statistical shape information embodied in ASM with the globally optimal delineation capability of the GC method. The presented IGCASM algorithm is a 3D generalization of the 2D GC-ASM method that they proposed previously in Chen et al. [Proc. SPIE, 7259, 72590C1-72590C-8 (2009)]. The proposed methods are tested on two datasets comprised of images obtained from 20 patients (10 male and 10 female) of clinical abdominal CT scans, and 11 foot magnetic resonance imaging (MRI) scans. The test is for four organs (liver, left and right kidneys, and spleen) segmentation, five foot bones (calcaneus, tibia, cuboid, talus, and navicular). The recognition and delineation accuracies were evaluated separately. The recognition accuracy was evaluated in terms of translation, rotation, and scale (size) error. The delineation accuracy was evaluated in terms of true and false positive volume fractions (TPVF, FPVF). The efficiency of the delineation method was also evaluated on an Intel Pentium IV PC with a 3.4 GHZ CPU machine.
Results: The recognition accuracies in terms of translation, rotation, and scale error over all organs are about 8 mm, 10 degrees and 0.03, and over all foot bones are about 3.5709 mm, 0.35 degrees and 0.025, respectively. The accuracy of delineation over all organs for all subjects as expressed in TPVF and FPVF is 93.01% and 0.22%, and all foot bones for all subjects are 93.75% and 0.28%, respectively. While the delineations for the four organs can be accomplished quite rapidly with average of 78 s, the delineations for the five foot bones can be accomplished with average of 70 s.
Conclusions: The experimental results showed the feasibility and efficacy of the proposed automatic anatomy segmentation system: (a) the incorporation of shape priors into the GC framework is feasible in 3D as demonstrated previously for 2D images; (b) our results in 3D confirm the accuracy behavior observed in 2D. The hybrid strategy IGCASM seems to be more robust and accurate than ASM and GC individually; and (c) delineations within body regions and foot bones of clinical importance can be accomplished quite rapidly within 1.5 min. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3602070]
C1 [Chen, Xinjian; Bagci, Ulas] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Chen, Xinjian] Xidian Univ, Life Sci Res Ctr, Sch Life Sci & Technol, Xian 710071, Peoples R China.
RP Chen, XJ (reprint author), NIH, Ctr Clin, Bldg 10,Room 1C515, Bethesda, MD 20892 USA.
EM chenx6@mail.nih.gov
RI Bagci, Ulas/A-4225-2012; Chen, Xinjian/E-8592-2016; zhang,
feng/L-7009-2016;
OI Chen, Xinjian/0000-0001-9627-6009; Bagci, Ulas/0000-0001-7379-6829
NR 40
TC 21
Z9 21
U1 1
U2 10
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD AUG
PY 2011
VL 38
IS 8
BP 4610
EP 4622
DI 10.1118/1.3602070
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 801DV
UT WOS:000293417500022
PM 21928634
ER
PT J
AU Prasad, R
Beard, WA
Batra, VK
Liu, Y
Shock, DD
Wilson, SH
AF Prasad, R.
Beard, W. A.
Batra, V. K.
Liu, Y.
Shock, D. D.
Wilson, S. H.
TI A review of recent experiments on step-to-step "hand-off" of the DNA
intermediates in mammalian base excision repair pathways
SO MOLECULAR BIOLOGY
LA English
DT Review
DE DNA repair; DNA polymerase beta; single-nucleotide base excision repair
(SN BER); long patch base excision repair (LP BER); flap endonuclease 1
(FEN1); AP endonuclease 1 (APE1); uracil-DNA glycosylase (UDG); 5
'-deoxyribose phosphate (5 '-dRP)
ID APURINIC-APYRIMIDINIC SITES; DEOXYRIBOSE PHOSPHATE LYASE;
POLYMERASE-BETA; MASS-SPECTROMETRY; BOVINE TESTIS; LIGASE-I; MECHANISM;
CELLS; IDENTIFICATION; RECONSTITUTION
AB The current "working model" for mammalian base excision repair involves two sub-pathways termed single-nucleotide base excision repair and long patch base excision repair that are distinguished by their repair patch sizes and the enzymes/co-factors involved. These base excision repair sub-pathways are designed to sequester the various DNA intermediates, passing them along from one step to the next without allowing these toxic molecules to trigger cell cycle arrest, necrotic cell death, or apoptosis. Although a variety of DNA-protein and protein-protein interactions are known for the base excision repair intermediates and enzymes/co-factors, the molecular mechanisms accounting for step-to-step coordination are not well understood. In this review, we explore the question of whether there is an actual step-to-step "hand-off" of the DNA intermediates during base excision repair in vitro. The results show that when base excision repair enzymes are pre-bound to the initial single-nucleotide base excision repair intermediate, the DNA is channeled from apurinic/apyrimidinic endonuclease 1 to DNA polymerase beta and then to DNA ligase. In the long patch base excision repair sub-pathway, where the 5'-end of the incised strand is blocked, the intermediate after polymerase beta gap filling is not channeled from polymerase beta to the subsequent enzyme, flap endonuclease 1. Instead, flap endonuclease 1 must recognize and bind to the intermediate in competition with other molecules.
C1 [Prasad, R.; Beard, W. A.; Batra, V. K.; Liu, Y.; Shock, D. D.; Wilson, S. H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Liu, Y.] Florida Int Univ, Miami, FL 33174 USA.
RP Prasad, R (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr,POB 12233,MD F1-12, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU National Institutes of Health, National Institute of Environmental
Health Sciences [Z01-ES050158, Z01-ES050159]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences (Research Projects Z01-ES050158 and Z01-ES050159).
NR 48
TC 4
Z9 4
U1 0
U2 18
PU MAIK NAUKA/INTERPERIODICA/SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA
SN 0026-8933
J9 MOL BIOL+
JI Mol. Biol.
PD AUG
PY 2011
VL 45
IS 4
BP 536
EP 550
DI 10.1134/S0026893311040091
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 804EJ
UT WOS:000293636800002
PM 21954590
ER
PT J
AU Kanakkanthara, A
Wilmes, A
O'Brate, A
Escuin, D
Chan, A
Gjyrezi, A
Crawford, J
Rawson, P
Kivell, B
Northcote, PT
Hamel, E
Giannakakou, P
Miller, JH
AF Kanakkanthara, Arun
Wilmes, Anja
O'Brate, Aurora
Escuin, Daniel
Chan, Ariane
Gjyrezi, Ada
Crawford, Janet
Rawson, Pisana
Kivell, Bronwyn
Northcote, Peter T.
Hamel, Ernest
Giannakakou, Paraskevi
Miller, John H.
TI Peloruside- and Laulimalide-Resistant Human Ovarian Carcinoma Cells Have
beta I-Tubulin Mutations and Altered Expression of beta II- and beta
III-Tubulin Isotypes
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID MICROTUBULE-STABILIZING AGENTS; ALPHA-TUBULIN; CANCER CELLS;
LUNG-CANCER; TAXOID SITE; BREAST-CANCER; PACLITAXEL; DRUGS;
BETA(III)-TUBULIN; PHOSPHORYLATION
AB Peloruside A and laulimalide are potent microtubule-stabilizing natural products with a mechanism of action similar to that of paclitaxel. However, the binding site of peloruside A and laulimalide on tubulin remains poorly understood. Drug resistance in anticancer treatment is a serious problem. We developed peloruside A- and laulimalide-resistant cell lines by selecting 1A9 human ovarian carcinoma cells that were able to grow in the presence of one of these agents. The 1A9-laulimalide resistant cells (L4) were 39-fold resistant to the selecting agent and 39-fold cross-resistant to peloruside A, whereas the 1A9-peloruside A resistant cells (R1) were 6-fold resistant to the selecting agent while they remained sensitive to laulimalide. Neither cell line showed resistance to paclitaxel or other drugs that bind to the taxoid site on beta-tubulin nor was there resistance to microtubule-destabilizing drugs. The resistant cells exhibited impaired peloruside A/laulimalide-induced tubulin polymerization and impaired mitotic arrest. Tubulin mutations were found in the beta I-tubulin isotype, R306H or R306C for L4 and A296T for R1 cells. This is the first cell-based evidence to support a beta-tubulin-binding site for peloruside A and laulimalide. To determine whether the different resistance phenotypes of the cells were attributable to any other tubulin alterations, the beta-tubulin isotype composition of the cells was examined. Increased expression of beta II- and beta III-tubulin was observed in L4 cells only. These results provide insight into how alterations in tubulin lead to unique resistance profiles for two drugs, peloruside A and laulimalide, that have a similar mode of action. Mol Cancer Ther; 10(8); 1419-29. (C) 2011 AACR.
C1 [Kanakkanthara, Arun; Wilmes, Anja; Chan, Ariane; Crawford, Janet; Rawson, Pisana; Kivell, Bronwyn; Giannakakou, Paraskevi; Miller, John H.] Victoria Univ Wellington, Sch Biol Sci, Wellington 6140, New Zealand.
[Northcote, Peter T.] Victoria Univ Wellington, Sch Chem & Phys Sci, Wellington 6140, New Zealand.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21701 USA.
[O'Brate, Aurora; Escuin, Daniel; Gjyrezi, Ada; Giannakakou, Paraskevi] Weill Cornell Med Coll, Dept Med, Div Hematol Clin Oncol, New York, NY USA.
RP Miller, JH (reprint author), Victoria Univ Wellington, Sch Biol Sci, POB 600, Wellington 6140, New Zealand.
EM john.h.miller@vuw.ac.nz
RI Kivell, Bronwyn/P-3140-2014; Pitman, Janet/B-1558-2012;
OI Kivell, Bronwyn/0000-0001-9699-553X; Wilmes, Anja/0000-0001-9485-4565
FU New Zealand Foundation of Research, Science, and Technology; Cancer
Society of NZ; Wellington Medical Research Foundation; Victoria
University of Wellington; NIH [CA100202, RO1 CA114335]
FX This work was supported in part by grants to J.H. Miller from the New
Zealand Foundation of Research, Science, and Technology, the Cancer
Society of NZ, the Wellington Medical Research Foundation, and Victoria
University of Wellington. This work was also supported in part by NIH
RO1 grants CA100202 and RO1 CA114335 to P. Giannakakou.
NR 41
TC 24
Z9 24
U1 0
U2 13
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD AUG
PY 2011
VL 10
IS 8
BP 1419
EP 1429
DI 10.1158/1535-7163.MCT-10-1057
PG 11
WC Oncology
SC Oncology
GA 804YR
UT WOS:000293692500012
PM 21653684
ER
PT J
AU Sooryakumar, D
Dexheimer, TS
Teicher, BA
Pommier, Y
AF Sooryakumar, Dhriti
Dexheimer, Thomas S.
Teicher, Beverly A.
Pommier, Yves
TI Molecular and Cellular Pharmacology of the Novel Noncamptothecin
Topoisomerase I Inhibitor Genz-644282
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID DOUBLE-STRAND BREAKS; DNA COVALENT COMPLEX; MULTIDRUG-RESISTANCE;
CLEAVAGE COMPLEXES; MAMMALIAN-CELLS; CAMPTOTHECIN; CANCER; H2AX;
MECHANISM; DAMAGE
AB Camptothecin derivatives are powerful anticancer drugs because of their ability to trap topoisomerase I (Top1)-DNA cleavage complexes. However, they exhibit clinical limitations due to the instability of their alpha-hydroxylactone six-membered E-ring structure. In addition, they exhibit bone marrow and intestinal toxicity, especially in adults, and are drug efflux substrates. Here, we report a novel Top1 inhibitor, Genz-644282. We show that Genz-644282 and its metabolites induce Top1 cleavage at similar, as well as unique genomic positions, compared with camptothecin. The compound also induces protein-linked DNA breaks and Top1-DNA cleavage complexes that persist longer after compound removal than camptothecin. Concentration-dependent and persistent gamma H2AX formation was readily observed in cells treated with Genz-644282, and was present in greater than 50% of the cell population following 24 hours compound exposure. The compound shows partial cross-resistance in cell lines resistant to camptothecin. These cell lines include the human prostate DU145RC0.1 and the leukemic CEM/C2 cells. Limited cross-resistance to Genz-644282 was also found in the Top1 knockdown colon cancer (HCT116) and breast cancer (MCF7) cell lines and in human adenocarcinoma cells (KB31/KBV1) that overexpress (P-glycoprotein, ABCB1), a member of the ATP-binding cassette family of cell surface transport proteins known to confer MDR. Together, our results provide the first molecular and cellular characterization of Genz-644282 and its clinically relevant metabolites. Mol Cancer Ther; 10(8); 1490-9. (C) 2011 AACR.
C1 [Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Teicher, Beverly A.] Genzyme Corp, Framingham, MA 01701 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU NCI; Center for Cancer Research; Genzyme Corporation
FX This work was supported by the NCI intramural program, Center for Cancer
Research, and by Genzyme Corporation.
NR 42
TC 9
Z9 10
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD AUG
PY 2011
VL 10
IS 8
BP 1490
EP 1499
DI 10.1158/1535-7163.MCT-10-1043
PG 10
WC Oncology
SC Oncology
GA 804YR
UT WOS:000293692500019
PM 21636699
ER
PT J
AU Hipp, SJ
Steffen-Smith, E
Hammoud, D
Shih, JH
Bent, R
Warren, KE
AF Hipp, Sean J.
Steffen-Smith, Emilie
Hammoud, Dima
Shih, Joanna H.
Bent, Robyn
Warren, Katherine E.
TI Predicting outcome of children with diffuse intrinsic pontine gliomas
using multiparametric imaging
SO NEURO-ONCOLOGY
LA English
DT Article
DE diffuse intrinsic pontine glioma; MR spectroscopy; pediatric; prognosis;
susceptibility perfusion
ID PEDIATRIC BRAIN-TUMORS; STEM GLIOMAS; ADULTS; MRI
AB Noninvasive evaluation using MRI is the primary means to routinely assess children with diffuse intrinsic pontine gliomas (DIPGs). However, no standard MR sequence has correlated with outcome in these patients. In this study, patients with DIPGs were assessed to determine the combined prognostic value via dynamic susceptibility contrast (DSC) MRI, single-voxel spectroscopy (SVS), multivoxel MR spectroscopy (MRS), and T1-weighted post-gadolinium imaging. Eligible patients had clinical and radiographic findings consistent with a DIPG. Imaging studies were acquired on a 1.5T MRI at various time points during each patient's course. Data were evaluated using a Cox proportional hazard model, a time-dependent covariant Cox model, a Wald test, and a Kaplan-Meier analysis. Ninety-eight studies were performed on 34 patients of median age 5.5 years. Median survival from diagnosis was 468 days. At baseline imaging only, increased ratio of choline to N-acetylaspartate (Cho:NAA) on SVS and increased perfusion on DSC-MRI each predicted shorter survival (relative risk [RR] = 1.48, P = .015 and RR = 4.91, P = .0012, respectively). When analyzing all subsequent time points, increased maximum Cho:NAA on MRS (RR = 1.45, P = .042), increased Cho:NAA on SVS (RR = 1.69, P = .003), increased perfusion (RR = 4.68, P = .0016), and the presence of enhancement (RR = 5.69, P = .022) each predicted shorter survival. Kaplan-Meier analysis showed shorter survival associated with increased perfusion at baseline (P = .0004). Increased perfusion at any time point predicts a significantly shorter survival in children with DIPG. In addition, enhancement, increased Cho:NAA on SVS, and increased maximum Cho:NAA on chemical shift imaging are predictive of shorter survival over time. Routine baseline and subsequent imaging for children with DIPG should, at minimum, incorporate DSC-MRI and SVS.
C1 [Hipp, Sean J.; Steffen-Smith, Emilie; Bent, Robyn; Warren, Katherine E.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hipp, Sean J.] Walter Reed Army Med Ctr, Dept Pediat, Washington, DC 20307 USA.
[Hipp, Sean J.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA.
[Hammoud, Dima] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Shih, Joanna H.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Hipp, SJ (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 1-5750,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sean.hipp@us.army.mil
RI Hammoud, Dima/C-2286-2015
FU National Institutes of Health, National Cancer Institute, and Center for
Cancer Research
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute, and
Center for Cancer Research.
NR 18
TC 28
Z9 30
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD AUG
PY 2011
VL 13
IS 8
BP 904
EP 909
DI 10.1093/neuonc/nor076
PG 6
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 806PU
UT WOS:000293820900011
PM 21757444
ER
PT J
AU Zimon, M
Baets, J
Fabrizi, GM
Jaakkola, E
Kabzinska, D
Pilch, J
Schindler, AB
Cornblath, DR
Fischbeck, KH
Auer-Grumbach, M
Guelly, C
Huber, N
De Vriendt, E
Timmerman, V
Suter, U
Hausmanowa-Petrusewicz, I
Niemann, A
Kochanski, A
De Jonghe, P
Jordanova, A
AF Zimon, M.
Baets, J.
Fabrizi, G. M.
Jaakkola, E.
Kabzinska, D.
Pilch, J.
Schindler, A. B.
Cornblath, D. R.
Fischbeck, K. H.
Auer-Grumbach, M.
Guelly, C.
Huber, N.
De Vriendt, E.
Timmerman, V.
Suter, U.
Hausmanowa-Petrusewicz, I.
Niemann, A.
Kochanski, A.
De Jonghe, P.
Jordanova, A.
TI Dominant GDAP1 mutations cause predominantly mild CMT phenotypes
SO NEUROLOGY
LA English
DT Article
ID MARIE-TOOTH-DISEASE; DIFFERENTIATION-ASSOCIATED PROTEIN-1;
NEUROFILAMENT-LIGHT GENE; GLUTATHIONE TRANSFERASE; VOCAL CORD;
NEUROPATHY; MYELINOPATHIES; DYNACTIN; MUTANT; 4A
AB Objective: Ganglioside-induced differentiation associated-protein 1 (GDAP1) mutations are commonly associated with autosomal recessive Charcot-Marie-Tooth (ARCMT) neuropathy; however, in rare instances, they also lead to autosomal dominant Charcot-Marie-Tooth (ADCMT). We aimed to investigate the frequency of disease-causing heterozygous GDAP1 mutations in ADCMT and their associated phenotype.
Methods: We performed mutation analysis in a large cohort of ADCMT patients by means of bidirectional sequencing of coding regions and exon-intron boundaries of GDAP1. Intragenic GDAP1 deletions were excluded using an allele quantification assay. We confirmed the pathogenic character of one sequence variant by in vitro experiments assaying mitochondrial morphology and function.
Results: In 8 Charcot-Marie-Tooth disease (CMT) families we identified 4 pathogenic heterozygous GDAP1 mutations, 3 of which are novel. Three of the mutations displayed reduced disease penetrance. Disease onset in the affected individuals was variable, ranging from early childhood to adulthood. Disease progression was slow in most patients and overall severity milder than typically seen in autosomal recessive GDAP1 mutations. Electrophysiologic changes are heterogeneous but compatible with axonal neuropathy in the majority of patients.
Conclusions: With this study, we broaden the phenotypic and genetic spectrum of autosomal dominant GDAP1-associated neuropathies. We show that patients with dominant GDAP1 mutations may display clear axonal CMT, but may also have only minimal clinical and electrophysiologic abnormalities. We demonstrate that cell-based functional assays can be reliably used to test the pathogenicity of unknown variants. We discuss the implications of phenotypic variability and the reduced penetrance of autosomal dominant GDAP1 mutations for CMT diagnostic testing and counseling. Neurology (R) 2011;77:540-548
C1 [Zimon, M.; Baets, J.; De Vriendt, E.; De Jonghe, P.; Jordanova, A.] Univ Antwerp VIB, Dept Mol Genet, Neurogenet Grp, B-2610 Antwerp, Belgium.
[Timmerman, V.] Univ Antwerp VIB, Dept Mol Genet, Peripheral Neuropathy Grp, B-2610 Antwerp, Belgium.
[Zimon, M.; Baets, J.; De Vriendt, E.; Timmerman, V.; De Jonghe, P.; Jordanova, A.] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, Antwerp, Belgium.
[Baets, J.; De Jonghe, P.] Univ Antwerp Hosp, Div Neurol, Antwerp, Belgium.
[Fabrizi, G. M.] Univ Verona, Dept Neurol Neuropsychol Morphol & Motor Sci, I-37100 Verona, Italy.
[Jaakkola, E.] Oulu Univ Hosp, Dept Clin Genet, Oulu, Finland.
[Kabzinska, D.; Hausmanowa-Petrusewicz, I.; Kochanski, A.] Polish Acad Sci, Mossakowski Med Res Ctr, Neuromuscular Unit, Warsaw, Poland.
[Pilch, J.] Med Univ Silesia, Dept Child Neurol, Katowice, Poland.
[Schindler, A. B.; Fischbeck, K. H.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Cornblath, D. R.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Auer-Grumbach, M.] Med Univ Graz, Dept Internal Med, Div Endocrinol & Metab, Graz, Austria.
[Guelly, C.] Med Univ Graz, Med Res Ctr, Graz, Austria.
[Huber, N.; Suter, U.; Niemann, A.] ETH, Dept Biol, Inst Cell Biol, Zurich, Switzerland.
RP Jordanova, A (reprint author), Univ Antwerp VIB, Dept Mol Genet, Mol Neurogenom Grp, Univ Pl 1, B-2610 Antwerp, Belgium.
EM albena.jordanova@molgen.vib-ua.be
RI Suter, Ueli/A-1624-2010; Niemann, Axel/A-6245-2012; Niemann,
Axel/J-5245-2013; Jordanova, Albena/H-8323-2015;
OI Niemann, Axel/0000-0002-2930-0950; Jordanova,
Albena/0000-0002-3833-3754; Zimon, Magdalena/0000-0001-7255-6639
FU University of Antwerp; Fund for Scientific Research (FWO-Flanders)
[G017209N]; "Association Belge contre les Maladies Neuromusculaires"
(ABMM); Medical Foundation Queen Elisabeth (GSKE); Belgian Federal
Science Policy Office (BELSPO); Flemish Government; Austrian Science
Fond (FWF) [P19455-B05]; Polish Ministry of Science and Higher Education
[NN 402 27 63 36]; Swiss National Science Foundation; NCCR Neural
Plasticity and Repair; NIH/NINDS; FWO-Flanders
FX This study was supported by the University of Antwerp, the Fund for
Scientific Research (FWO-Flanders, grant G017209N), the "Association
Belge contre les Maladies Neuromusculaires" (ABMM), the Medical
Foundation Queen Elisabeth (GSKE), the Interuniversity Attraction Poles
P6/43 program of the Belgian Federal Science Policy Office (BELSPO), the
"Methusalem excellence grant" of the Flemish Government, and the
Austrian Science Fond (FWF, P19455-B05). M.Z. and J.B. are supported by
PhD fellowships of the FWO-Flanders. This study was also supported by
the Polish Ministry of Science and Higher Education (grant No. NN 402 27
63 36) to A.K. Work in the laboratory of U.S. is supported by the Swiss
National Science Foundation and the NCCR Neural Plasticity and Repair.;
M. Zimon, Dr. Baets, Dr. Fabrizi, Dr. Jaakkola, Dr. Kabzinska, Dr.
Pilch, and A.B. Schindler report no disclosures. Dr. Cornblath
serves/has served on scientific advisory boards for Ardea Biosciences,
Inc., Avigen, Inc., Pfizer Inc, Johnson & Johnson, GlaxoSmithKline,
Abbott, Acorda Therapeutics Inc., Alexion Pharmaceuticals, Inc.,
Astellas Pharma Inc., Baxter International Inc., Bionevia
Pharmaceuticals Inc., Bristol-Myers Squibb, Cebix, CSL Behring, Eisai
Inc., Exelixis Inc., FoldRx, Genzyme Corporation, Keryx
Biopharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation,
Octapharma AG, Sangamo BioSciences, Inc., sanofi-aventis, and Talecris
Biotherapeutics; holds and has received license fee payments for patents
re: Total neuropathy score (nurse, clinical), Methods to assess
neuropathy. Dr. Fischbeck receives intramural research support from the
NIH/NINDS. Dr. Auer-Grumbach, Dr. Guelly, N. Huber, E. De Vriendt, and
Dr. Timmerman report no disclosures. Dr. Suter receives research support
from the Swiss National Science Foundation and the NCCR Neural
Plasticity and Repair. Dr. Hausmanowa-Petrusewicz, Dr. Niemann, Dr.
Kochanski, Dr. De Jonghe, and Dr. Jordanova report no disclosures.
NR 34
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U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD AUG
PY 2011
VL 77
IS 6
BP 540
EP 548
DI 10.1212/WNL.0b013e318228fc70
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 804MW
UT WOS:000293658900009
PM 21753178
ER
PT J
AU Mancini, M
Horak, FB
Zampieri, C
Carlson-Kuhta, P
Nutt, JG
Chiari, L
AF Mancini, Martina
Horak, Fay B.
Zampieri, Cris
Carlson-Kuhta, Patricia
Nutt, John G.
Chiari, Lorenzo
TI Trunk accelerometry reveals postural instability in untreated
Parkinson's disease
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Untreated Parkinson's disease; Posture; Accelerometry
ID SWAY; LEVODOPA; COORDINATION; PARAMETERS; STABILITY; STANCE; ARM
AB While several studies have shown that subjects with advanced Parkinson's disease (PD) exhibit abnormalities in sway parameters during quiet standing, abnormalities of postural sway associated with untreated PD have not been reported. Although not clinically apparent, we hypothesized that spontaneous sway in quiet stance is abnormal in people with untreated PD.
We examined 13 subjects, recently diagnosed with PD, who were not yet taking any anti-parkinsonian medications and 12 healthy, age-matched control subjects. Postural sway was measured with a linear accelerometer on the posterior trunk (L5 level) and compared with traditional force plate measures of sway. Subjects stood for 2 min under two conditions: eyes open (EO) and eyes closed (EC).
One of the most discriminative measures of postural changes in subjects with untreated PD was the increased 'JERK' of lower trunk in the EO condition, measured with the accelerometer. Root mean square and the frequency dispersion of postural sway in the EO condition also discriminated sway in untreated PD subjects compared to control subjects.
We conclude that accelerometer-based sway metrics could be used as objective measures of postural instability in untreated PD. Accelerometer-based analysis of spontaneous sway may provide a powerful tool for early clinical trials and for monitoring the effects of treatment of balance disorders in subjects with PD. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Mancini, Martina; Horak, Fay B.; Carlson-Kuhta, Patricia; Nutt, John G.] Oregon Hlth & Sci Univ, Dept Neurol, Sch Med, Balance Disorders Lab, Beaverton, OR 97006 USA.
[Mancini, Martina; Chiari, Lorenzo] Alma Mater Studiorum Univ Bologna, Dept Elect Comp Sci & Syst, Biomed Engn Unit, I-40136 Bologna, Italy.
[Zampieri, Cris] NIH, Funct & Appl Biomech Lab, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Mancini, M (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Sch Med, Balance Disorders Lab, 505 NW 185th Ave, Beaverton, OR 97006 USA.
EM mancinim@ohsu.edu
OI Chiari, Lorenzo/0000-0002-2318-4370
FU Kinetics Foundation; National Institute on Aging (NIA) [006457]; NIH
FX We thank all the participants, Triana Nagel for recruiting subjects and
data collection assistance, and Edward King for technical assistance.
This research was supported by grants from the Kinetics Foundation and
the National Institute on Aging (NIA, 006457). This research was also
supported in part by the Intramural Research Program of the NIH. Dr.
Horak was a consultant for Kinetics Foundation. This potential conflict
of interest has been reviewed and managed by OHSU.
NR 30
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U1 2
U2 17
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD AUG
PY 2011
VL 17
IS 7
BP 557
EP 562
DI 10.1016/j.parkreldis.2011.05.010
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 805LQ
UT WOS:000293728300011
PM 21641263
ER
PT J
AU Balasubramaniam, M
Freed, EO
AF Balasubramaniam, Muthukumar
Freed, Eric O.
TI New Insights into HIV Assembly and Trafficking
SO PHYSIOLOGY
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCYTE-DERIVED MACROPHAGES; ACTIVE
ANTIRETROVIRAL THERAPY; VIROLOGICAL SYNAPSE FORMATION; ADAPTER PROTEIN
COMPLEXES; NUCLEAR EXPORT ELEMENTS; HOST-CELL CYTOSKELETON; MURINE
LEUKEMIA-VIRUS; TRANS-GOLGI NETWORK; PLASMA-MEMBRANE
AB Assembly and release of human immunodeficiency virus type 1 (HIV-1) particles is mediated by the viral Gag polyprotein precursor. Gag is synthesized in the cytosol and rapidly translocates to membrane to orchestrate particle production. The cell biology of HIV-1 Gag trafficking is currently one of the least understood aspects of HIV-1 replication. In this review, we highlight the current understanding of the cellular machinery involved in Gag trafficking and virus assembly.
C1 [Balasubramaniam, Muthukumar; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
RP Balasubramaniam, M (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
EM efreed@nih.gov
FU Intramural NIH HHS [Z01 BC010775-01]
NR 248
TC 48
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U1 0
U2 17
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1548-9213
EI 1548-9221
J9 PHYSIOLOGY
JI Physiology
PD AUG
PY 2011
VL 26
IS 4
BP 236
EP 251
DI 10.1152/physiol.00051.2010
PG 16
WC Physiology
SC Physiology
GA 806SA
UT WOS:000293829900004
PM 21841072
ER
PT J
AU Jokinen, MP
Lieuallen, WG
Boyle, MC
Johnson, CL
Malarkey, DE
Nyska, A
AF Jokinen, Micheal P.
Lieuallen, Warren G.
Boyle, Michael C.
Johnson, Crystal L.
Malarkey, David E.
Nyska, Abraham
TI Morphologic Aspects of Rodent Cardiotoxicity in a Retrospective
Evaluation of National Toxicology Program Studies
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE heart; cardiotoxicity; rat; mouse; pathology
ID ADVERSE CARDIOVASCULAR EVENTS; SPRAGUE-DAWLEY RATS; DAMAGE;
MITOCHONDRIAL; RESTRICTION; EPHEDRINE; LESIONS; HEALTH; HEART
AB The heart is increasingly recognized as a target for toxicity. As studies in laboratory rodents are commonly used to investigate the potential toxicity of various agents, the identification and characterization of lesions of cardiotoxicity is of utmost importance. Although morphologic criteria have been established for degenerative myocardial lesions in rats and mice, differentiation of spontaneously occurring lesions from toxin-induced or toxin-related lesions remains difficult. A retrospective light microscopic evaluation was performed on the hearts of F344 rats and B6C3F(1) mice from National Toxicology Program (NTP) studies of six chemicals identified in the NTP database in which treatment-induced myocardial toxicity was present. Two previously defined myocardial lesions were observed: "cardiomyopathy" that occurred spontaneously or as a treatment-related effect and "myocardial degeneration" that occurred as a treatment-related effect. Both lesions consisted of the same basic elements, beginning with myofiber degeneration and necrosis, with varying amounts of inflammation, interstitial cell proliferation, and eventual fibrosis. This observation is indicative of the heart's limited repertoire of responses to myocardial injury, regardless of the nature of the inciting agent. A prominent differentiating factor between spontaneous and treatment-induced lesions was distribution and lesion onset. Once the respective lesions had undergone fibrosis, however, they generally appeared morphologically indistinguishable.
C1 [Jokinen, Micheal P.; Lieuallen, Warren G.; Johnson, Crystal L.] Charles River Labs Pathol Associates, Durham, NC USA.
[Boyle, Michael C.; Malarkey, David E.; Nyska, Abraham] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Nyska, A (reprint author), Haharuv 18,POB 184, IL-36576 Timrat, Israel.
EM anyska@bezeqint.net
NR 33
TC 9
Z9 9
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD AUG
PY 2011
VL 39
IS 5
BP 850
EP 860
DI 10.1177/0192623311413788
PG 11
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 800RF
UT WOS:000293381400009
PM 21747121
ER
PT J
AU Tsao, CW
Gona, P
Salton, C
Murabito, JM
Oyama, N
Danias, PG
O'Donnell, CJ
Manning, WJ
Yeon, SB
AF Tsao, Connie W.
Gona, Philimon
Salton, Carol
Murabito, Joanne M.
Oyama, Noriko
Danias, Peter G.
O'Donnell, Christopher J.
Manning, Warren J.
Yeon, Susan B.
TI Relationship between central and peripheral atherosclerosis and left
ventricular dysfunction in a community population
SO VASCULAR MEDICINE
LA English
DT Article
DE aortic atherosclerosis; epidemiology; left ventricular wall motion
abnormality; MRI; peripheral artery disease
ID ANKLE-BRACHIAL INDEX; CORONARY-ARTERY-DISEASE; CARDIOVASCULAR
MAGNETIC-RESONANCE; WALL-MOTION ABNORMALITIES; HEART-DISEASE; ARM INDEX;
PROGNOSTIC-SIGNIFICANCE; MYOCARDIAL-INFARCTION; MORTALITY; RISK
AB We aimed to determine the relationships between resting left ventricular (LV) wall motion abnormalities (WMAs), aortic plaque, and peripheral artery disease (PAD) in a community cohort. A total of 1726 Framingham Heart Study Offspring Cohort participants (806 males, 65 +/- 9 years) underwent cardiovascular magnetic resonance with quantification of aortic plaque volume and assessment of regional left ventricular systolic function. Claudication, lower extremity revascularization, and ankle-brachial index (ABI) were recorded at the most contemporaneous examination visit. WMAs were associated with greater aortic plaque burden, decreased ABI, and claudication in age-and sex-adjusted analyses (all p < 0.001), which were not significant after adjustment for cardiovascular risk factors. In age-and sex-adjusted analyses, both the presence (p < 0.001) and volume of aortic plaque were associated with decreased ABI (p < 0.001). After multivariable adjustment, an ABI <= 0.9 or prior revascularization was associated with a threefold odds of aortic plaque (p = 0.0083). Plaque volume significantly increased with decreasing ABI in multivariable-adjusted analyses (p < 0.0001). In this free-living population, associations of WMAs with aortic plaque burden and clinical measures of PAD were attenuated after adjustment for coronary heart disease risk factors. Aortic plaque volume and ABI remained strongly negatively correlated after multivariable adjustment. Our findings suggest that the association between coronary heart disease and non-coronary atherosclerosis is explained by cardiovascular risk factors. Aortic atherosclerosis and PAD remain strongly associated after multivariable adjustment, suggesting shared mechanisms beyond those captured by traditional risk factors.
C1 [Yeon, Susan B.] Beth Israel Deaconess Med Ctr, Div Cardiol, Harvard Thorndike Lab, Boston, MA 02215 USA.
[Tsao, Connie W.; Salton, Carol; Oyama, Noriko; Danias, Peter G.; Manning, Warren J.; Yeon, Susan B.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA.
[O'Donnell, Christopher J.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Div, Boston, MA USA.
[Gona, Philimon] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Gona, Philimon; Murabito, Joanne M.; O'Donnell, Christopher J.] NHLBI, NIH, Framingham Heart Study, Framingham, MA USA.
[Murabito, Joanne M.] Boston Univ, Dept Med, Gen Internal Med Sect, Boston, MA 02215 USA.
[Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA.
RP Yeon, SB (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiol, Harvard Thorndike Lab, 330 Brookline Ave, Boston, MA 02215 USA.
EM syeon@bidmc.harvard.edu
RI Oyama-Manabe, Noriko/A-5212-2012;
OI Murabito, Joanne/0000-0002-0192-7516
FU National Heart, Lung and Blood Institute, Bethesda, Maryland, USA
[N01-HC-25195]; National Institutes of Health [RO1 HL70279, T32 HL07374]
FX The Framingham Heart Study is supported by Grant N01-HC-25195 from the
National Heart, Lung and Blood Institute, Bethesda, Maryland, USA. This
work is also partially supported by a grant from the National Institutes
of Health (RO1 HL70279) and a National Institutes of Health training
grant (T32 HL07374 to CWT).
NR 35
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U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
J9 VASC MED
JI Vasc. Med.
PD AUG
PY 2011
VL 16
IS 4
BP 253
EP 259
DI 10.1177/1358863X11408640
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 805AW
UT WOS:000293699400003
PM 21708875
ER
PT J
AU Kapetanovic, S
Wiegand, RE
Dominguez, K
Blumberg, D
Bohannon, B
Wheeling, J
Rutstein, R
AF Kapetanovic, Suad
Wiegand, Ryan E.
Dominguez, Ken
Blumberg, Dean
Bohannon, Beverly
Wheeling, John
Rutstein, Richard
CA LEGACY Consortium
TI Associations of Medically Documented Psychiatric Diagnoses and Risky
Health Behaviors in Highly Active Antiretroviral Therapy-Experienced
Perinatally HIV-Infected Youth
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID LOGISTIC-REGRESSION ANALYSIS; PATIENT-RELATED RISKS; UNITED-STATES;
ADOLESCENTS; PREVALENCE; CHILDREN; NONADHERENCE; DISORDERS; ADHERENCE;
RATES
AB The Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY) study is a prospective, multisite, longitudinal cohort of U. S. HIV-infected youth. This analysis was limited to perinatally HIV-infected youth (n = 197), 13 years and older, with selected variables completely abstracted from HIV diagnosis through 2006. We evaluated relationships between ever having one or more nonsubstance related medically documented psychiatric diagnoses and three risky health behaviors (substance abuse, preadult sexual activity, and treatment adherence problems) recorded between 2001 and 2006. Logistic regression was used for all binary outcomes and participant age was included as a covariate when possible. All 197 participants included in the analysis were prescribed antiretroviral therapy during the study period; 110 (56%) were female, 100 (51%) were black non-Hispanic, and 86 (44%) were Hispanic; mean age at the last visit was 16.8 years, ranging from 13 to 24 years. One hundred forty-six (74%) participants had a history of at least one risky health behavior. There were 108 (55%) participants with at least one medically documented psychiatric diagnosis, 17 (9%) with at least one record of substance abuse, 12 (6%) with documented preadult sexual activity, and 142 (72%) participants with reported adherence problems. In the final model, a history of at least one psychiatric diagnosis was associated with having at least one of the three risky behaviors (odds ratio [OR] = 2.33, p = 0.015). There is a need for a continued close partnership between HIV specialty care providers and mental health services treating perinatally HIV-infected youth with an added focus on improving treatment adherence.
C1 [Kapetanovic, Suad] NIMH, NIH, Off Clin Director, Bethesda, MD 20892 USA.
[Wiegand, Ryan E.; Dominguez, Ken; Bohannon, Beverly] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA.
[Blumberg, Dean] Univ Calif Davis, Childrens Hosp, Sacramento, CA 95817 USA.
[Wheeling, John] Northrop Grumman Inc, Atlanta, GA USA.
[Rutstein, Richard] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
RP Kapetanovic, S (reprint author), NIMH, NIH, Off Clin Director, Bldg 10-CRC,Room 6-5340,10 Ctr Dr, Bethesda, MD 20892 USA.
EM suad.kapetanovic@nih.gov
FU Westat Inc. [2004-N-01211, 200-2004-09976]
FX Funded through CDC Solicitation No. 2004-N-01211 and prime contract
#200-2004-09976 with Westat Inc.
NR 24
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U1 2
U2 4
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 AUG
PY 2011
VL 25
IS 8
BP 493
EP 501
DI 10.1089/apc.2011.0107
PG 9
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 799ED
UT WOS:000293265500007
PM 21745118
ER
PT J
AU Chakrabarti, BK
Pancera, M
Phogat, S
O'Dell, S
McKee, K
Guenaga, J
Robinson, J
Mascola, J
Wyatt, RT
AF Chakrabarti, Bimal K.
Pancera, Marie
Phogat, Sanjay
O'Dell, Sijy
McKee, Krisha
Guenaga, Javier
Robinson, James
Mascola, John
Wyatt, Richard T.
TI HIV Type 1 Env Precursor Cleavage State Affects Recognition by Both
Neutralizing and Nonneutralizing gp41 Antibodies
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN TRIMERS; HUMAN
MONOCLONAL-ANTIBODIES; B-CELL RESPONSES; SOLUBLE CD4;
CONFORMATIONAL-CHANGES; INFECTION; GP120; SENSITIVITY; EXPRESSION
AB HIV-1 is relatively resistant to antibody-mediated neutralization; however, rare antibodies to the exterior envelope glycoprotein, gp120, and the transmembrane glycoprotein, gp41, can neutralize a broad array of isolates. Two antibodies, 2F5 and 4E10, are directed against the gp41 membrane proximal external region (MPER); however, the kinetic neutralization signature of these antibodies remains unresolved. Previously, we reported that the fully cleaved, cell surface envelope glycoproteins (Env) derived from the primary isolate, JR-FL, are well recognized exclusively by gp120-directed neutralizing ligands and not by nonneutralizing gp120 antibodies. However, the gp120 nonneutralizing antibodies can recognize HIV spikes that are rendered fully cleavage defective by site-directed mutagenesis. Here, we extended such analysis to gp41 neutralizing and nonneutralizing antibodies and, relative to the rules of gp120-specific antibody recognition, we observed marked contrasts. Similar to gp120 recognition, the nonneutralizing gp41 cluster 1 or cluster 2 antibodies bound much more efficiently to cleavage-defective spikes when compared to their recognition of cleaved spikes. In contrast to gp120 neutralizing antibody recognition, the broadly neutralizing gp41 antibodies 2F5 and 4E10, like the nonneutralizing gp41 antibodies, did not efficiently recognize the predominantly cleaved, primary isolate JR-FL spikes. However, if the spikes were rendered cleavage defective, recognition by both the neutralizing and nonneutralizing ligand markedly increased. CD4 interaction with the cleaved spikes markedly increased recognition by most nonneutralizing gp41 antibodies, whereas such treatment had a minimal increase of 2F5 and 4E10 recognition. These data indicate again the profound influence that cleavage imposes on the quaternary packing of primary isolate spikes and have important implications for soluble trimer candidate immunogens.
C1 [Chakrabarti, Bimal K.; Pancera, Marie; Phogat, Sanjay; O'Dell, Sijy; McKee, Krisha; Guenaga, Javier; Mascola, John; Wyatt, Richard T.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Robinson, James] Tulane Med Sch, New Orleans, LA USA.
RP Wyatt, RT (reprint author), Scripps Res Inst, IAVI Neutralizing Antibody Ctr TSRI, 10550 N Torrey Pines Rd,IMM 28, La Jolla, CA 92037 USA.
EM wyatt@scripps.edu
FU NIH; International AIDS Vaccine Initiative; Bill and Melinda Gates
Foundation; NYU CFAR [AI27742]
FX We thank Brenda Hartman for help with the figures and Dennis Burton,
Hermann Katinger, and Marshal Posner for the monoclonal antibodies b12,
2G12, 2F5, 4E10, and F105. We thank Mirek Gorny and Susan Zolla-Pazner
for the antibodies 50-69, 98-6D, 126-D, and 240-D provided by funding
from the NYU CFAR (AI27742). This study was funded by the NIH intramural
research program and funding was also provided by the International AIDS
Vaccine Initiative and the Bill and Melinda Gates Foundation.
NR 74
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U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD AUG
PY 2011
VL 27
IS 8
BP 877
EP 887
DI 10.1089/aid.2010.0281
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 803IV
UT WOS:000293575900009
PM 21158699
ER
PT J
AU Minniti, CP
Taylor, JG
Hildesheim, M
O'Neal, P
Wilson, J
Castro, O
Gordeuk, VR
Kato, GJ
AF Minniti, Caterina P.
Taylor, James G.
Hildesheim, Mariana
O'Neal, Patricia
Wilson, Jonathan
Castro, Oswaldo
Gordeuk, Victor R.
Kato, Gregory J.
TI Laboratory and echocardiography markers in sickle cell patients with leg
ulcers
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID PULMONARY-HYPERTENSION; RISK-FACTOR; DISEASE; HEMOLYSIS; ULCERATION;
ANEMIA; DEATH; DESATURATION; CHILDREN; BIOMARKER
C1 [Minniti, Caterina P.; Taylor, James G.; Hildesheim, Mariana; Wilson, Jonathan; Kato, Gregory J.] NHLBI, Cardiovasc & Pulm Branch, Sickle Cell Vasc Dis Sect, NIH, Bethesda, MD 20892 USA.
[O'Neal, Patricia; Castro, Oswaldo; Gordeuk, Victor R.] Howard Univ, Dept Med, Ctr Sickle Cell Dis, Washington, DC 20059 USA.
RP Minniti, CP (reprint author), NHLBI, NIH, Pulm & Vasc Med Branch, Bldg 10CRC,Room 5-5140, Bethesda, MD 20892 USA.
EM minnitic@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 HL006012-01, ZIA HL006012-02]
NR 30
TC 13
Z9 13
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD AUG
PY 2011
VL 86
IS 8
BP 705
EP 708
DI 10.1002/ajh.22065
PG 4
WC Hematology
SC Hematology
GA 802KE
UT WOS:000293508600018
PM 21630312
ER
PT J
AU Bem, RA
Domachowske, JB
Rosenberg, HF
AF Bem, Reinout A.
Domachowske, Joseph B.
Rosenberg, Helene F.
TI Animal models of human respiratory syncytial virus disease
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Review
DE respiratory virus; pneumovirus; rodent; inflammation
ID ACUTE PNEUMOVIRUS INFECTION; AGE-DEPENDENT DIFFERENCES; RAT
SIGMODON-HISPIDUS; ACUTE LUNG INJURY; PNEUMONIA VIRUS; VIRAL LOAD;
INFLAMMATORY RESPONSES; INFLUENZA-VIRUS; COTTON RATS; IN-VIVO
AB Bem RA, Domachowske JB, Rosenberg HF. Animal models of human respiratory syncytial virus disease. Am J Physiol Lung Cell Mol Physiol 301: L148-L156, 2011. First published May 13, 2011; doi:10.1152/ajplung.00065.2011.-Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for novel therapies and preventative strategies. Present animal models include several target species for hRSV, including chimpanzees, cattle, sheep, cotton rats, and mice, as well as alternative animal pneumovirus models, such as bovine RSV and pneumonia virus of mice. These diverse animal models reproduce different features of hRSV disease, and their utilization should therefore be based on the scientific hypothesis under investigation. The purpose of this review is to summarize the strengths and limitations of each of these animal models. Our intent is to provide a resource for investigators and an impetus for future research.
C1 [Bem, Reinout A.] Emma Childrens Hosp, Acad Med Ctr, Dept Pediat, Pediat Intens Care Unit, NL-1105 AZ Amsterdam, Netherlands.
[Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY USA.
[Rosenberg, Helene F.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Bem, RA (reprint author), Emma Childrens Hosp, Acad Med Ctr, Dept Pediat, Pediat Intens Care Unit, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM r.a.bem@amc.uva.nl
FU NIAID Division of Intramural Research [AI000943]
FX H. F. Rosenberg is funded by NIAID Division of Intramural Research no.
AI000943.
NR 120
TC 74
Z9 75
U1 3
U2 17
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD AUG
PY 2011
VL 301
IS 2
BP L148
EP L156
DI 10.1152/ajplung.00065.2011
PG 9
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 800HI
UT WOS:000293350000002
PM 21571908
ER
PT J
AU Gwinn, WM
Kapita, MC
Wang, PM
Cesta, MF
Martin, WJ
AF Gwinn, William M.
Kapita, Mayanga C.
Wang, Ping M.
Cesta, Mark F.
Martin, William J., II
TI Synthetic liposomes are protective from bleomycin-induced lung toxicity
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE lung injury; pulmonary fibrosis
ID RESPIRATORY-DISTRESS-SYNDROME; INDUCED PULMONARY-FIBROSIS; EXOGENOUS
SURFACTANT INSTILLATION; ALVEOLAR MACROPHAGES; AEROSOLIZED SURFACTANT;
REPLACEMENT THERAPY; IMMUNE-RESPONSES; INJURY; PHOSPHOLIPIDS; MODEL
AB Gwinn WM, Kapita MC, Wang PM, Cesta MF, Martin WJ 2nd. Synthetic liposomes are protective from bleomycin-induced lung toxicity. Am J Physiol Lung Cell Mol Physiol 301: L207-L217, 2011. First published May 20, 2011; doi:10.1152/ajplung.00149.2010.-Idiopathic pulmonary fibrosis is a devastating disease characterized by a progressive, irreversible, and ultimately lethal form of lung fibrosis. Except for lung transplantation, no effective treatment options currently exist. The bleomycin animal model is one of the best studied models of lung injury and fibrosis. A previous study using mouse tumor models observed that liposome-encapsulated bleomycin exhibited reduced lung toxicity. Therefore, we hypothesized that airway delivery of synthetic phosphatidylcholine-containing liposomes alone would protect mice from bleomycin-induced lung toxicity. C57BL/6 mice were administered uncharged multilamellar liposomes (100 mu l) or PBS vehicle on day 0 by airway delivery. Bleomycin (3.33 U/kg) or saline vehicle was then given intratracheally on day 1 followed by four additional separate doses of liposomes on days 4, 8, 12, and 16. Fluorescent images of liposomes labeled with 1,1'-dioctadecyl-3,3,3', 3' tetramethylindocarbocyanine perchlorate confirmed effective and widespread delivery of liposomes to the lower respiratory tract as well as uptake primarily by alveolar macrophages and to a lesser extent by type II alveolar epithelial cells. Results at day 22, 3 wk after bleomycin treatment, showed that airway delivery of liposomes before and after intratracheal administration of bleomycin significantly reduced bleomycin-induced lung toxicity as evidenced by less body weight loss, chronic lung inflammation, and fibrosis as well as improved lung compliance compared with controls. These data indicate that airway-delivered synthetic liposomes represent a novel treatment strategy to reduce the lung toxicity associated with bleomycin in a mouse model.
C1 [Gwinn, William M.; Kapita, Mayanga C.; Wang, Ping M.; Martin, William J., II] Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC USA.
[Cesta, Mark F.] Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, Res Triangle Pk, NC USA.
RP Martin, WJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd,Rm 2A01, Rockville, MD 20852 USA.
EM wjmartin@mail.nih.gov
FU NIEHS, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
NIEHS, National Institutes of Health.
NR 44
TC 2
Z9 2
U1 0
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD AUG
PY 2011
VL 301
IS 2
BP L207
EP L217
DI 10.1152/ajplung.00149.2010
PG 11
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 800HI
UT WOS:000293350000009
PM 21602446
ER
PT J
AU Addington, J
Cornblatt, BA
Cadenhead, KS
Cannon, TD
McGlashan, TH
Perkins, DO
Seidman, LJ
Tsuang, MT
Walker, EF
Woods, SW
Heinssen, R
AF Addington, Jean
Cornblatt, Barbara A.
Cadenhead, Kristin S.
Cannon, Tyrone D.
McGlashan, Thomas H.
Perkins, Diana O.
Seidman, Larry J.
Tsuang, Ming T.
Walker, Elaine F.
Woods, Scott W.
Heinssen, Robert
TI At Clinical High Risk for Psychosis: Outcome for Nonconverters
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID ULTRA-HIGH RISK; INTERRATER RELIABILITY; PREDICTIVE-VALIDITY; PRODROMAL
SYNDROMES; INITIAL PRODROME; FOLLOW-UP; SCHIZOPHRENIA; INTERVIEW
AB Objective: A major focus of early intervention research is determining the risk of conversion to psychosis and developing optimal algorithms of prediction. Although reported rates of nonconversion vary in the literature, the nonconversion rate always encompasses a majority (50%-85%) of the sample participants. Less is known about the outcome among this group, referred to as false positive individuals.
Method: A longitudinal study was conducted of more than 300 prospectively identified treatment-seeking individuals meeting criteria for a psychosis-risk syndrome. Participants were recruited and evaluated across eight clinical research centers as part of the North American Prodrome Longitudinal Study. Over a 2.5-year follow-up assessment period, 214 (71%) participants had not made the transition to psychosis.
Results: The sample examined included 111 individuals who had at least 1 year of follow-up data available and did not transition to psychosis within the study duration. In year 1, there was significant improvement in ratings for attenuated positive and negative symptoms. However, at least one attenuated positive symptom was still present for 43% of the sample at 1 year and for 41% at 2 years. At the follow-up timepoints, social and role functioning were significantly poorer in the clinical sample relative to nonpsychiatric comparison subjects.
Conclusions: Help-seeking individuals who meet prodromal criteria appear to represent those who are truly at risk for psychosis and are showing the first signs of illness, those who remit in terms of the symptoms used to index clinical high-risk status, and those who continue to have attenuated positive symptoms.
C1 [Addington, Jean] Univ Calgary, Ctr Mental Hlth Res & Educ, Dept Psychiat, Calgary, AB T2N 4Z6, Canada.
Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA.
Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Psychiat, Sch Med, Boston, MA 02215 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Emory Univ, Dept Psychiat & Psychol, Atlanta, GA 30322 USA.
NIMH, Schizophrenia Spectrum Res Program, Div Adult Translat Res, Bethesda, MD 20892 USA.
RP Addington, J (reprint author), Univ Calgary, Ctr Mental Hlth Res & Educ, Dept Psychiat, 3280 Hosp Dr NW, Calgary, AB T2N 4Z6, Canada.
EM jmadding@ucalgary.ca
FU National Institute of Mental Health [U01 MH-066160, U01 MH0-66134, R01
MH-60720, K24 MH-76191, R01 MH-065079, R01 MH-061523, R01 MH-066069, K23
MH-01905, R18 MH-43518, R01 MH-065562, P50 MH-080272, R21MH-075027,
RO1MH-062066, K05MH01654]; Donaghue Foundation; Eli Lilly
FX Supported by the National Institute of Mental Health (grants U01
MH-066160 [Dr. Woods], U01 MH0-66134 [Dr. Addington], R01 MH-60720 and
K24 MH-76191 [Dr. Cadenhead], R01 MH-065079 [Dr. Cannon], R01 MH-061523
[Dr. Cornblatt], R01 MH-066069 and K23 MH-01905 [Dr. Perkins], R18
MH-43518 [Drs. Tsuang and Seidman], R01 MH-065562 and P50 MH-080272 [Dr.
Seidman], R21MH-075027 [Dr. Tsuang], RO1MH-062066 [Dr. Walker], and
K05MH01654 [Dr. McGlashan]); the Donaghue Foundation (Dr. Woods); and
Eli Lilly (Drs. McGlashan, Addington, and Perkins).
NR 17
TC 170
Z9 173
U1 3
U2 18
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD AUG
PY 2011
VL 168
IS 8
BP 800
EP 805
DI 10.1176/appi.ajp.2011.10081191
PG 6
WC Psychiatry
SC Psychiatry
GA 800SQ
UT WOS:000293387600010
PM 21498462
ER
PT J
AU Folio, LR
Fischer, T
Shogan, P
Frew, M
Dwyer, A
Provenzale, JM
AF Folio, Les R.
Fischer, Tatjana
Shogan, Paul
Frew, Michael
Dwyer, Andrew
Provenzale, James M.
TI Blast and Ballistic Trajectories in Combat Casualties: A Preliminary
Analysis Using a Cartesian Positioning System With MDCT
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE ballistic injuries; blast injuries; trajectory; wound path
ID GUIDED VIRTUAL AUTOPSY; BULLET; RADIOLOGY; INJURIES; HEAD
AB OBJECTIVE. The purpose of this study is to determine the agreement with which radiologists identify wound paths in vivo on MDCT and calculate missile trajectories on the basis of Cartesian coordinates using a Cartesian positioning system (CPS).
MATERIALS AND METHODS. Three radiologists retrospectively identified 25 trajectories on MDCT in 19 casualties who sustained penetrating trauma in Iraq. Trajectories were described qualitatively in terms of directional path descriptors and quantitatively as trajectory vectors. Directional descriptors, trajectory angles, and angles between trajectories were calculated based on Cartesian coordinates of entrance and terminus or exit recorded in x, y image and table space (z) using a Trajectory Calculator created using spreadsheet software. The consistency of qualitative descriptor determinations was assessed in terms of frequency of observer agreement and multirater kappa statistics. Consistency of trajectory vectors was evaluated in terms of distribution of magnitude of the angles between vectors and the differences between their paraaxial and parasagittal angles.
RESULTS. In 68% of trajectories, the observers' visual assessment of qualitative descriptors was congruent. Calculated descriptors agreed across observers in 60% of the trajectories. Estimated kappa also showed good agreement (0.65-0.79, p < 0.001); 70% of calculated paraaxial and parasagittal angles were within 20 degrees across observers, and 61.3% of angles between trajectory vectors were within 20 degrees across observers.
CONCLUSION. Results show agreement of visually assessed and calculated qualitative descriptors and trajectory angles among observers. The Trajectory Calculator describes trajectories qualitatively similar to radiologists' visual assessment, showing the potential feasibility of automated trajectory analysis.
C1 [Folio, Les R.; Dwyer, Andrew] NIH, Dept Radiol, Bethesda, MD 20892 USA.
[Fischer, Tatjana] Univ Munich, Munich, Germany.
[Shogan, Paul; Frew, Michael] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA.
[Provenzale, James M.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA.
[Provenzale, James M.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA.
[Provenzale, James M.] Emory Univ, Sch Med, Dept Oncol, Atlanta, GA USA.
[Provenzale, James M.] Emory Univ, Sch Med, Dept Biomed Engn, Atlanta, GA USA.
RP Folio, LR (reprint author), NIH, Dept Radiol, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Les.folio@nih.gov
NR 20
TC 5
Z9 5
U1 0
U2 3
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD AUG
PY 2011
VL 197
IS 2
BP W233
EP W240
DI 10.2214/AJR.10.5959
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 796OY
UT WOS:000293062600004
PM 21785047
ER
PT J
AU Moss, DM
Priest, JW
Boyd, A
Weinkopff, T
Kucerova, Z
Beach, MJ
Lammie, PJ
AF Moss, Delynn M.
Priest, Jeffrey W.
Boyd, Alexis
Weinkopff, Tiffany
Kucerova, Zuzana
Beach, Michael J.
Lammie, Patrick J.
TI Multiplex Bead Assay for Serum Samples from Children in Haiti Enrolled
in a Drug Study for the Treatment of Lymphatic Filariasis
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID PEPSIN INHIBITOR HOMOLOG; BANCROFTIAN FILARIASIS; DIROFILARIA-IMMITIS;
ANTIBODY-RESPONSES; WUCHERERIA-BANCROFTI; ALBENDAZOLE THERAPY;
FOLLOW-UP; DIETHYLCARBAMAZINE; INFECTION; CYTOKINES
AB A multiplex bead assay (MBA) was used to analyze serum samples collected longitudinally from children enrolled in a drug trial for treatment of filariasis in Leogane, Haiti. Recombinant antigens Bm14 and Bm33 from Brugia malayi, third polar tube protein (PTP3) from Encephalitozoon cuniculi, and merozoite surface protein-1(19) (MSP-1(19)) from Plasmodium falciparum were coupled to carboxylated polystyrene microspheres. IgG responses to PTP3 and MSP-1(19) were not affected by albendazole (ALB), diethylcarbamazine (DEC), or combination of diethylcarbamazine and albendazole (DEC/ALB). However, IgG and IgG4 responses to Bm14 and Bm33 were significantly decreased (P <0.001) by DEC and DEC/ALB treatment. Antibody responses to Bm14 and Bm33 decreased after DEC treatment (but not placebo) among children who were negative for microfilaremia and antigenemia at baseline, suggesting that these children harbored early stages of infection. The MBA is an excellent serologic technique for multiple antigens that offers substantial advantages over single-antigen based enzyme-linked immunosorbent assay in mass drug administration studies for monitoring changes in antibody levels.
C1 [Moss, Delynn M.] Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA 30329 USA.
[Moss, Delynn M.; Priest, Jeffrey W.] Ctr Dis Control & Prevent, Waterborne Dis Prevent Branch, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30329 USA.
[Boyd, Alexis] NIH, Off Intramural Training & Educ, Bethesda, MD 20892 USA.
[Beach, Michael J.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30329 USA.
RP Moss, DM (reprint author), Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Zoonot Vector Borne & Enter Dis, 1600 Clifton Rd NE, Atlanta, GA 30329 USA.
EM dmm3@cdc.gov; jip8@cdc.gov; boyda2@od.nih.gov;
tiffany.weinkopff@unil.ch; zik0@cdc.gov; mjb3@cdc.gov; pjl1@cdc.gov
NR 45
TC 24
Z9 24
U1 0
U2 8
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD AUG
PY 2011
VL 85
IS 2
BP 229
EP 237
DI 10.4269/ajtmh.2011.11-0029
PG 9
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 803WN
UT WOS:000293613000009
PM 21813840
ER
PT J
AU Facchinelli, L
Valerio, L
Bond, JG
de Valdez, MRW
Harrington, LC
Ramsey, JM
Casas-Martinez, M
Scott, TW
AF Facchinelli, Luca
Valerio, Laura
Bond, J. Guillermo
de Valdez, Megan R. Wise
Harrington, Laura C.
Ramsey, Janine M.
Casas-Martinez, M.
Scott, Thomas W.
TI Development of a Semi-Field System for Contained Field Trials with Aedes
aegypti in Southern Mexico
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID RELEASE-RECAPTURE; PUERTO-RICO; CULICIDAE; DIPTERA; MOSQUITOS; SURVIVAL;
DISPERSAL; EPIDEMIOLOGY; OVIPOSITION; AUSTRALIA
AB Development of new genetic approaches to either interfere with the ability of mosquitoes to transmit dengue virus or to reduce vector population density requires progressive evaluation from the laboratory to contained field trials, before open field release. Trials in contained outdoor facilities are an important part of this process because they can be used to evaluate the effectiveness and reliability of modified strains in settings that include natural environmental variations without releasing mosquitoes into the open field. We describe a simple and cost-effective semi-field system designed to study Aedes aegypti carrying a dominant lethal gene (fsRIDL) in semi-field conditions. We provide a protocol for establishing, maintaining, and monitoring stable Ae. aegypti population densities inside field cages.
C1 [Facchinelli, Luca; Valerio, Laura; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
Univ Roma La Sapienza, Ist Pasteur Fdn Cenci Bolognetti, Rome, Italy.
[Bond, J. Guillermo; Ramsey, Janine M.; Casas-Martinez, M.] INSP, CRISP, Tapachula, Chiapas, Mexico.
[de Valdez, Megan R. Wise] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[Harrington, Laura C.] Cornell Univ, Dept Entomol, Ithaca, NY 14853 USA.
[Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Facchinelli, L (reprint author), Univ Calif Davis, Dept Entomol, 1 Shields Ave, Davis, CA 95616 USA.
EM lfacchinelli@ucdavis.edu; lvalerio@ucdavis.edu; gbond@insp.mx;
megwise@lamar.colostate.edu; lch27@cornell.edu; jramsey@insp.mx;
mcasas@insp.mx; twscott@ucdavis.edu
OI Facchinelli, Luca/0000-0002-8987-1472
FU Regents of the University of California from the Foundation for the
National Institutes of Health through the Grand Challenges in Global
Health Initiative [316]; Pasteur Institute-Cenci Bolognetti Foundation
FX This research was supported by funds from the Regents of the University
of California from the Foundation for the National Institutes of Health
through the Grand Challenges in Global Health Initiative (GC7 #316) and
by a Pasteur Institute-Cenci Bolognetti Foundation grant to Laura
Valerio.
NR 23
TC 13
Z9 13
U1 1
U2 9
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD AUG
PY 2011
VL 85
IS 2
BP 248
EP 256
DI 10.4269/ajtmh.2011.10-0426
PG 9
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 803WN
UT WOS:000293613000012
PM 21813843
ER
PT J
AU Ellis, AM
Garcia, AJ
Focks, DA
Morrison, AC
Scott, TW
AF Ellis, Alicia M.
Garcia, Andres J.
Focks, Dana A.
Morrison, Amy C.
Scott, Thomas W.
TI Parameterization and Sensitivity Analysis of a Complex Simulation Model
for Mosquito Population Dynamics, Dengue Transmission, and Their Control
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID AEDES-AEGYPTI DIPTERA; MALARIA TRANSMISSION; DENSITY-DEPENDENCE;
RELEASE-RECAPTURE; BITING ACTIVITY; HUMAN BLOOD; CULICIDAE; RISK;
PATTERNS; SURVIVAL
AB Models can be useful tools for understanding the dynamics and control of mosquito-borne disease. More detailed models may be more realistic and better suited for understanding local disease dynamics; however, evaluating model suitability, accuracy, and performance becomes increasingly difficult with greater model complexity. Sensitivity analysis is a technique that permits exploration of complex models by evaluating the sensitivity of the model to changes in parameters. Here, we present results of sensitivity analyses of two interrelated complex simulation models of mosquito population dynamics and dengue transmission. We found that dengue transmission may be influenced most by survival in each life stage of the mosquito, mosquito biting behavior, and duration of the infectious period in humans. The importance of these biological processes for vector-borne disease models and the overwhelming lack of knowledge about them make acquisition of relevant field data on these biological processes a top research priority.
C1 [Ellis, Alicia M.; Morrison, Amy C.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95618 USA.
[Ellis, Alicia M.; Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Focks, Dana A.] Univ Florida, Emerging Pathogens Inst, Dept Environm & Global Hlth, Gainesville, FL USA.
[Garcia, Andres J.] Univ Florida, Dept Geog, Emerging Pathogens Inst, Gainesville, FL 32611 USA.
[Morrison, Amy C.] USN, Med Res Ctr Detachment, Washington, DC USA.
RP Ellis, AM (reprint author), Univ Calif Davis, Dept Entomol, 1 Shields Ave, Davis, CA 95618 USA.
EM alicia.m.ellis@gmail.com; andygarcia@gmail.com; DAFocks@id-analysis.com;
amy.aegypti@gmail.com; twscott@caes.ucdavis.edu
RI Barley, Kamal/F-9579-2011
OI Barley, Kamal/0000-0003-1874-9813
FU Innovative Vector Control Consortium; Department of Homeland Security,
and Fogarty International Center, National Institutes of Health
FX This research was supported by the Innovative Vector Control Consortium
(http://www.ivcc.com/) and the Research and Policy for Infectious
Disease Dynamics (RAPIDD) program of the Science and Technology
Directory, Department of Homeland Security, and Fogarty International
Center, National Institutes of Health. Initial support for the
improvement of the dengue models came from the Jean and Julius Tahija
Family Foundation, Jakarta, Indonesia. Many thanks to Dr. Steven
Stoddard for help in obtaining and interpreting epidemiological and
entomological data from the Iquitos surveys, Bborie Park (University of
California Davis) for help with computer setup and data organization,
and Dr. Chonggang Xu for valuable input on sensitivity analysis
procedures.
NR 48
TC 20
Z9 20
U1 2
U2 14
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD AUG
PY 2011
VL 85
IS 2
BP 257
EP 264
DI 10.4269/ajtmh.2011.10-0516
PG 8
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 803WN
UT WOS:000293613000013
PM 21813844
ER
PT J
AU Lynch, SK
Pai, V
Auxier, J
Stein, AF
Bennett, EE
Kemble, CK
Xiao, XH
Lee, WK
Morgan, NY
Wen, HH
AF Lynch, Susanna K.
Pai, Vinay
Auxier, Julie
Stein, Ashley F.
Bennett, Eric E.
Kemble, Camille K.
Xiao, Xianghui
Lee, Wah-Keat
Morgan, Nicole Y.
Wen, Han Harold
TI Interpretation of dark-field contrast and particle-size selectivity in
grating interferometers
SO APPLIED OPTICS
LA English
DT Article
ID X-RAY-SCATTERING; PHASE-CONTRAST; SHEARING INTERFEROMETER; TALBOT
INTERFEROMETRY; RADIOGRAPHY
AB In grating-based x-ray phase sensitive imaging, dark-field contrast refers to the extinction of the interference fringes due to small-angle scattering. For configurations where the sample is placed before the beamsplitter grating, the dark-field contrast has been quantified with theoretical wave propagation models. Yet when the grating is placed before the sample, the dark-field contrast has only been modeled in the geometric optics regime. Here we attempt to quantify the dark-field effect in the grating-before-sample geometry with first-principle wave calculations and understand the associated particle-size selectivity. We obtain an expression for the dark-field effect in terms of the sample material's complex refractive index, which can be verified experimentally without fitting parameters. A dark-field computed tomography experiment shows that the particle-size selectivity can be used to differentiate materials of identical x-ray absorption.
C1 [Lynch, Susanna K.; Pai, Vinay; Bennett, Eric E.; Kemble, Camille K.; Morgan, Nicole Y.; Wen, Han Harold] NHLBI, Lab Imaging Phys, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Auxier, Julie] Oregon State Univ, Sch Chem Biol & Environm Engn, Corvallis, OR 97331 USA.
[Stein, Ashley F.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Xiao, Xianghui; Lee, Wah-Keat] Argonne Natl Lab, Adv Photon Source, Xray Sci Div, Argonne, IL 60439 USA.
RP Wen, HH (reprint author), NHLBI, Lab Imaging Phys, Translat Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM wenh@nhlbi.nih.gov
RI Bennett, Eric/A-2551-2013; Wen, Han/G-3081-2010
OI Wen, Han/0000-0001-6844-2997
FU Intramural NIH HHS [ZIA HL004606-15]
NR 25
TC 54
Z9 54
U1 2
U2 24
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1559-128X
EI 2155-3165
J9 APPL OPTICS
JI Appl. Optics
PD AUG 1
PY 2011
VL 50
IS 22
BP 4310
EP 4319
DI 10.1364/AO.50.004310
PG 10
WC Optics
SC Optics
GA 800CE
UT WOS:000293335300015
PM 21833104
ER
PT J
AU Russo, I
Amornphimoltham, P
Weigert, R
Barlati, S
Bosetti, F
AF Russo, Isabella
Amornphimoltham, Panomwat
Weigert, Roberto
Barlati, Sergio
Bosetti, Francesca
TI Cyclooxygenase-1 is involved in the inhibition of hippocampal
neurogenesis after lipopolysaccharide-induced neuroinflammation
SO CELL CYCLE
LA English
DT Article
DE neurogenesis; cyclooxygenase-1; lipopolysaccharide; inflammation; brain
ID NEURAL STEM-CELLS; ADULT NEUROGENESIS; DENTATE GYRUS; NEURONS BORN;
INFLAMMATORY RESPONSE; GLIAL-CELLS; BRAIN; MICE; ACTIVATION; EXPRESSION
AB Growing evidence indicates that neuroinflammation can alter adult neurogenesis by mechanisms as yet unclear. We have previously demonstrated that the neuroinflammatory response and neuronal damage after lipopolysaccharide (LPS) injection is reduced in cyclooxygenase-1 deficient (COX-1(-/-)) mice. In this study, we investigated the role of COX-1 on hippocampal neurogenesis during LPS-induced neuroinflammation, using COX-1(-/-) and wild type (WT) mice. We found that LPS-induced neuroinflammation resulted in the decrease of proliferation, survival and differentiation of hippocampal progenitor cells in WT but not in COX-1(-/-) mice. Thus, we demonstrate for the first time that COX-1 is involved in the inhibition of BrdU progenitor cells in proliferation and hippocampal neurogenesis after LPS. These results suggest that COX-1 may represent a viable therapeutic target to reduce neuroinflammation and promote neurogenesis in neurodegenerative diseases with a strong inflammatory component.
C1 [Russo, Isabella; Bosetti, Francesca] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Russo, Isabella; Barlati, Sergio] Univ Brescia, Div Biol & Genet, Dept Biomed Sci & Biotechnol, Brescia, Italy.
[Russo, Isabella; Barlati, Sergio] Univ Brescia, Natl Inst Neurosci, Brescia, Italy.
[Amornphimoltham, Panomwat; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RP Bosetti, F (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
EM frances@mail.nih.gov
OI Russo, Isabella/0000-0002-6151-2451
FU NIH; NIA
FX This research was supported by the Intramural Research Program of the
NIH, NIA. We would like to thank Henriette Van Praag for useful
discussion and technical advice, Yosuke Mukoyama for kindly providing
microscopy and Erik Runko for critically reading and editing this
manuscript.
NR 49
TC 15
Z9 16
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD AUG 1
PY 2011
VL 10
IS 15
BP 2568
EP 2573
DI 10.4161/cc.10.15.15946
PG 6
WC Cell Biology
SC Cell Biology
GA 800GD
UT WOS:000293346900031
PM 21694498
ER
PT J
AU Nelson, PG
AF Nelson, Phillip G.
TI Codes and Circuits
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Neurexin; Neuroligins; Synaptic circuits
ID EXCITATORY SYNAPSE FORMATION; BETA-NEUREXINS; CELL-ADHESION;
ADENYLATE-CYCLASE; RNA INTERFERENCE; HOMEOBOX GENES; HYBRID-CELLS;
NEUROLIGINS; ALPHA; PLASTICITY
AB Marshall Nirenberg will always be remembered for deciphering the genetic code by which DNA and RNA sequences specify the amino acid sequence in proteins. His switch to neurobiology in the 1960s was driven, in part, by an interest in the possibility of a neural code specifying the development and functioning of the neural circuits that underlie brain function. Neural cell adhesion or recognition molecules would probably be involved in such circuit formation, and this review briefly examines one set of such molecules. The specific binding between presynaptic neurexins and postsynaptic neuroligins could constitute one aspect of the code underlying the formation of specific synaptic circuits.
C1 NICHHD, NIH, Bethesda, MD 20892 USA.
RP Nelson, PG (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA.
EM nelsonp@mail.nih.gov
NR 44
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD AUG
PY 2011
VL 31
IS 6
SI SI
BP 809
EP 813
DI 10.1007/s10571-011-9677-2
PG 5
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 799ZF
UT WOS:000293325300003
PM 21448809
ER
PT J
AU Xia, MH
Guo, V
Huang, RL
Shahane, SA
Austin, CP
Nirenberg, M
Sharma, SK
AF Xia, Menghang
Guo, Vicky
Huang, Ruili
Shahane, Sampada A.
Austin, Christopher P.
Nirenberg, Marshall
Sharma, Shail K.
TI Inhibition of Morphine-Induced cAMP Overshoot: A Cell-Based Assay Model
in a High-Throughput Format
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Adenylyl cyclase (AC); Adenosine-3 ',5 '-monophosphate (cAMP);
Quantitative high-throughput screening (qHTS); mu Opioid receptor
(morphine receptor); Human embryonic kidney293-mu opioid receptor cell
line (HEK-MOR); Homogeneous time-resolved fluorescence (HTRF)
ID MU-OPIOID RECEPTOR; NEUROBLASTOMA SH-SY5Y CELLS; ADENYLYL-CYCLASE
ACTIVITY; CYCLIC-AMP FORMATION; MOLECULAR-MECHANISMS; DEPENDENCE;
SENSITIZATION; TOLERANCE; TERM
AB Opiates are not only potent analgesics but also drugs of abuse mainly because they produce euphoria. Chronic use of opiates results in the development of tolerance and dependence. Dr Marshall Nirenberg's group at the National Institutes of Health (NIH) was the first to use a cellular model system of Neuroblastoma 9 Glioma hybrid cells (NG108-15) to study morphine addiction. They showed that opiates affect adenylyl cyclase (AC) by two opposing mechanisms mediated by the opiate receptor. Although the cellular mechanisms that cause addiction are not yet completely understood, the most observed correlative biochemical adaptation is the upregulation of AC. This model also provides the opportunity to look for compounds which could dissociate the acute effect of opiates from the delayed response, upregulation of AC, and thus lead to the discovery of non-addictive drugs. To identify small molecule compounds that can inhibit morphine-induced cAMP overshoot, we have validated and optimized a cell-based assay in a high throughput format that measures cellular cAMP production after morphine withdrawal. The assay performed well in the 1536-well plate format. The LOPAC library of 1,280 compounds was screened in this assay on a quantitative high-throughput screening (qHTS) platform. A group of compounds that can inhibit morphine-induced cAMP overshoot were identified. The most potent compounds are eight naloxone-related compounds, including levallorphan tartrate, naloxonazine dihydrochloride, naloxone hydrochloride, naltrexone hydrochloride, and naltriben methanesulfonate. The qHTS approach we used in this study will be useful in identifying novel inhibitors of morphine induced addiction from a larger scale screening.
C1 [Xia, Menghang; Huang, Ruili; Shahane, Sampada A.; Austin, Christopher P.] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Guo, Vicky; Nirenberg, Marshall; Sharma, Shail K.] NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA.
RP Xia, MH (reprint author), NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
EM mxia@mail.nih.gov; sharmshail@gmail.com
FU Laboratory of Biochemical Genetics (LBG), the National Heart Lung and
Blood Institute, the National Institutes of Health; Molecular Libraries
Initiative of the NIH Roadmap for Medical Research; National Human
Genome Research Institute
FX This research was supported by the Laboratory of Biochemical Genetics
(LBG), the National Heart Lung and Blood Institute, the National
Institutes of Health, and the Molecular Libraries Initiative of the NIH
Roadmap for Medical Research, and the Intramural Research Program of the
National Human Genome Research Institute. The authors wish to thank Dr
R. Balaban, Scientific Director, at NHLBI for providing the support for
this study. SKS was a visiting senior scientist in LBG.
NR 28
TC 11
Z9 12
U1 0
U2 9
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD AUG
PY 2011
VL 31
IS 6
SI SI
BP 901
EP 907
DI 10.1007/s10571-011-9689-y
PG 7
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 799ZF
UT WOS:000293325300012
PM 21598037
ER
PT J
AU Seeds, N
Mikesell, S
Vest, R
Bugge, T
Schaller, K
Minor, K
AF Seeds, Nicholas
Mikesell, Steve
Vest, Rebekah
Bugge, Thomas
Schaller, Kristin
Minor, Kenneth
TI Plasminogen Activator Promotes Recovery Following Spinal Cord Injury
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Plasminogen activator; uPA; uPAR; Crossed phrenic phenomenon; Spinal
cord plasticity
ID HEPATOCYTE GROWTH-FACTOR; SCIATIC-NERVE CRUSH; CROSSED PHRENIC
PHENOMENON; FACTOR SCATTER FACTOR; MICE LACKING; GRANULE NEURONS;
DEVELOPING CEREBELLUM; EXTRACELLULAR-MATRIX; FUNCTIONAL RECOVERY;
SENSORY NEURONS
AB Plasminogen activators play an important role in synaptic plasticity associated with the crossed phrenic phenomenon (CPP) and recovery of respiratory function after spinal cord injury. A genetic approach using knockout mice lacking various genes in the plasminogen activator/plasmin system has shown that induction of urokinase plasminogen activator (uPA) is required during the first hour after a C2-hemisection for the acquisition of the CPP response. The uPA knockout mice do not show the structural remodeling of phrenic motor neuron synapses characteristic of the CPP response. As shown here uPA acts in a cell signaling manner via binding to its receptor uPAR rather than as a protease, since uPAR knockout mice or knock-in mice possessing a modified uPA that is unable to bind to uPAR both fail to generate a CPP and recover respiratory function. Microarray data and real-time PCR analysis of mRNAs induced in the phrenic motor nucleus after C2-hemisection in C57Bl/6 mice as compared to uPA knockout mice indicate a potential cell signaling cascade downstream possibly involving beta-integrin and Src, and other pathways. Identification of these uPA-mediated signaling pathways may provide the opportunity to pharmacologically upregulate the synaptic plasticity necessary for recovery of phrenic motoneuron activity following cervical spinal cord injury.
C1 [Seeds, Nicholas; Mikesell, Steve; Vest, Rebekah; Schaller, Kristin; Minor, Kenneth] Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA.
[Seeds, Nicholas; Mikesell, Steve; Vest, Rebekah; Schaller, Kristin; Minor, Kenneth] Univ Colorado, Sch Med, Neurosci Program, Aurora, CO 80045 USA.
[Bugge, Thomas] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
RP Seeds, N (reprint author), Univ Colorado, Sch Med, Dept Biochem & Mol Genet, MS 8315,POB 6511, Aurora, CO 80045 USA.
EM Nicholas.Seeds@ucdenver.edu
FU [NIH-NS044129]
FX The authors greatly appreciate the excellent assistance of Karin Layton.
These studies were supported in part by a grant from NIH-NS044129 to
NWS.
NR 42
TC 6
Z9 6
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD AUG
PY 2011
VL 31
IS 6
SI SI
BP 961
EP 967
DI 10.1007/s10571-011-9701-6
PG 7
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 799ZF
UT WOS:000293325300018
PM 21573723
ER
PT J
AU Tachibana, M
Wu, YM
Iriko, H
Muratova, O
MacDonald, NJ
Sattabongkot, J
Takeo, S
Otsuki, H
Torii, M
Tsuboi, T
AF Tachibana, Mayumi
Wu, Yimin
Iriko, Hideyuki
Muratova, Olga
MacDonald, Nicholas J.
Sattabongkot, Jetsumon
Takeo, Satoru
Otsuki, Hitoshi
Torii, Motomi
Tsuboi, Takafumi
TI N-Terminal Prodomain of Pfs230 Synthesized Using a Cell-Free System Is
Sufficient To Induce Complement-Dependent Malaria Transmission-Blocking
Activity
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID GAMETE-SURFACE PROTEIN; SEXUAL-STAGE ANTIGEN; PLASMODIUM-FALCIPARUM;
VACCINE CANDIDATES; TARGET ANTIGEN; ANTIBODIES; EXPRESSION; IMMUNITY;
VIVAX; PVS25
AB The aim of a malaria transmission-blocking vaccine is to block the development of malaria parasites in the mosquito and thus prevent subsequent infection of the human host. Previous studies have demonstrated that the gametocyte/gamete surface protein Pfs230 can induce transmission-blocking immunity and have evaluated Escherichia coli-produced Pfs230 as a transmission-blocking vaccine candidate. In this study, we used the wheat germ cell-free expression system to produce N-terminal fragments of Pfs230 and evaluated the transmission-blocking activity of antisera raised against the recombinant Pfs230 protein. The rabbit antisera reacted to the surface of cultured gametocytes and gametes of the Plasmodium falciparum NF54 line, recognized the 360-kDa form of parasite-produced Pfs230 by Western blot assay, and reduced the infectivity of NF54 parasites to Anopheles stefensi mosquitoes in the presence of complement in a standard membrane feeding assay. Thus, our data demonstrate that the N-terminal pro domain of Pfs230 is sufficient to induce complement-dependent transmission-blocking activity against P. falciparum.
C1 [Takeo, Satoru; Tsuboi, Takafumi] Ehime Univ, Cell Free Sci & Technol Res Ctr, Matsuyama, Ehime 7908577, Japan.
[Tsuboi, Takafumi] Ehime Univ, Venture Business Lab, Matsuyama, Ehime 7908577, Japan.
[Tachibana, Mayumi; Torii, Motomi] Ehime Univ, Grad Sch Med, Dept Mol Parasitol, Toon, Ehime 7910295, Japan.
[Wu, Yimin; Muratova, Olga; MacDonald, Nicholas J.] NIAID, Lab Malaria Immunol & Vaccinol, Rockville, MD 20852 USA.
[Iriko, Hideyuki; Otsuki, Hitoshi] Tottori Univ, Fac Med, Div Med Zool, Tottori 6838503, Japan.
[Sattabongkot, Jetsumon] Armed Forces Res Inst Med Sci, Dept Entomol, Bangkok 10400, Thailand.
[Torii, Motomi; Tsuboi, Takafumi] Ehime Univ, Ehime Proteomed Res Ctr, Toon, Ehime 7910295, Japan.
RP Tsuboi, T (reprint author), Ehime Univ, Cell Free Sci & Technol Res Ctr, Matsuyama, Ehime 7908577, Japan.
EM torii@m.ehime-u.ac.jp; tsuboi@ccr.ehime-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology
[21022034, 21249028, 21406010]; Ministry of Health, Labor, and Welfare,
Japan [H20-Shinkou-ippan-013, H21-Chikyukibo-ippan-005]; Bill and
Melinda Gates Foundation
FX This research was supported in part by the Ministry of Education,
Culture, Sports, Science and Technology (21022034, 21249028, 21406010)
and by the Ministry of Health, Labor, and Welfare, Japan
(H20-Shinkou-ippan-013, H21-Chikyukibo-ippan-005). This work was also
supported in part by a grant from The Bill and Melinda Gates Foundation.
NR 44
TC 26
Z9 26
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD AUG
PY 2011
VL 18
IS 8
BP 1343
EP 1350
DI 10.1128/CVI.05104-11
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 800ID
UT WOS:000293352100019
PM 21715579
ER
PT J
AU Farrance, CE
Rhee, A
Jones, RM
Musiychuk, K
Shamloul, M
Sharma, S
Mett, V
Chichester, JA
Streatfield, SJ
Roeffen, W
van de Vegte-Bolmer, M
Sauerwein, RW
Tsuboi, T
Muratova, OV
Wu, YM
Yusibov, V
AF Farrance, Christine E.
Rhee, Amy
Jones, R. Mark
Musiychuk, Konstantin
Shamloul, Moneim
Sharma, Satish
Mett, Vadim
Chichester, Jessica A.
Streatfield, Stephen J.
Roeffen, Will
van de Vegte-Bolmer, Marga
Sauerwein, Robert W.
Tsuboi, Takafumi
Muratova, Olga V.
Wu, Yimin
Yusibov, Vidadi
TI A Plant-Produced Pfs230 Vaccine Candidate Blocks Transmission of
Plasmodium falciparum
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID SURFACE PROTEIN PFS230; TARGET ANTIGENS; H5N1 INFLUENZA; SEXUAL STAGES;
MALARIA; ANTIBODIES; IMMUNITY; EXPRESSION; HEMAGGLUTININ; SERA
AB Plasmodium falciparum is transmitted to a new host after completing its sexual cycle within a mosquito. Developing vaccines against the parasite sexual stages is a critical component in the fight against malaria. We are targeting multiple proteins of P. falciparum which are found only on the surfaces of the sexual forms of the parasite and where antibodies against these proteins have been shown to block the progression of the parasite's life cycle in the mosquito and thus block transmission to the next human host. We have successfully produced a region of the Pfs230 antigen in our plant-based transient-expression system and evaluated this vaccine candidate in an animal model. This plant-produced protein, 230CMB, is expressed at approximately 800 mg/kg in fresh whole leaf tissue and is 100% soluble. Administration of 230CMB with >90% purity induces strong immune responses in rabbits with high titers of transmission-blocking antibodies, resulting in a greater than 99% reduction in oocyst counts in the presence of complement, as determined by a standard membrane feeding assay. Our data provide a clear perspective on the clinical development of a Pfs230-based transmission-blocking malaria vaccine.
C1 [Farrance, Christine E.; Rhee, Amy; Jones, R. Mark; Musiychuk, Konstantin; Shamloul, Moneim; Sharma, Satish; Mett, Vadim; Chichester, Jessica A.; Streatfield, Stephen J.; Yusibov, Vidadi] Fraunhofer USA Ctr Mol Biotechnol, Newark, DE 19711 USA.
[Roeffen, Will; van de Vegte-Bolmer, Marga; Sauerwein, Robert W.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Med Microbiol, NL-6500 HB Nijmegen, Netherlands.
[Tsuboi, Takafumi] Ehime Univ, Cell Free Sci & Technol Res Ctr, Matsuyama, Ehime 7908577, Japan.
[Tsuboi, Takafumi] Ehime Univ, Venture Business Lab, Matsuyama, Ehime 7908577, Japan.
[Tsuboi, Takafumi] Ehime Univ, Ehime Proteomed Res Ctr, Toon, Ehime 7910295, Japan.
[Muratova, Olga V.; Wu, Yimin] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
RP Yusibov, V (reprint author), Fraunhofer USA Ctr Mol Biotechnol, 9 Innovat Way,Suite 200, Newark, DE 19711 USA.
EM vyusibov@fraunhofer-cmb.org
RI Sauerwein, Robert/C-8519-2013; Roeffen, W.F.G./L-4607-2015
FU Bill and Melinda Gates Foundation, Seattle, WA
FX This work was funded by a grant from The Bill and Melinda Gates
Foundation, Seattle, WA.
NR 48
TC 32
Z9 33
U1 3
U2 12
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD AUG
PY 2011
VL 18
IS 8
BP 1351
EP 1357
DI 10.1128/CVI.05105-11
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 800ID
UT WOS:000293352100020
PM 21715576
ER
PT J
AU Shah, SR
Patel, K
Marcellin, P
Foster, GR
Manns, M
Kottilil, S
Healey, L
Pulkstenis, E
Subramanian, GM
McHutchison, JG
Sulkowski, MS
Zeuzem, S
Nelson, DR
AF Shah, Samir R.
Patel, Keyur
Marcellin, Patrick
Foster, Graham R.
Manns, Michael
Kottilil, Shyam
Healey, Letha
Pulkstenis, Erik
Subramanian, G. Mani
McHutchison, John G.
Sulkowski, Mark S.
Zeuzem, Stefan
Nelson, David R.
TI Steatosis Is an Independent Predictor of Relapse Following Rapid
Virologic Response in Patients With HCV Genotype 3
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Liver Disease; Response to Therapy; Prognosis; Recurrence
ID CHRONIC HEPATITIS-C; PEGYLATED INTERFERON-ALPHA; PEGINTERFERON ALPHA-2B;
PLUS RIBAVIRIN; INSULIN-RESISTANCE; ANTIVIRAL THERAPY; INFECTED
PATIENTS; VIRUS GENOTYPE-2; RANDOMIZED-TRIAL; LIVER
AB BACKGROUND & AIMS: It is recommended that patients with chronic hepatitis C virus (HCV) genotype 3 infections receive 24 weeks of treatment. A rapid virologic response (RVR; at week 4) predicts a sustained virologic response (SVR), although not all patients with an RVR achieve an SVR. We explored the relationships among hepatic steatosis, level of HCV RNA, relapse, and RVR in a phase 3 randomized controlled trial of 932 patients infected with HCV genotype 2 (n = 427) or 3 (n = 505) who received 24 weeks of therapy with interferon-alpha. METHODS: In patients with an RVR (HCV RNA <3 IU/mL), the presence of an SVR was modeled using multivariate logistic regression as a function of age, sex, weight, body mass index, insulin resistance, steatosis, and levels of gamma-glutamyl transpeptidase, alanine aminotransferase, liver fibrosis, and baseline HCV RNA. RESULTS: RVR, SVR, and relapse rates among patients with HCV genotype 3 were 79.6%, 79.2%, and 15.6%, respectively; corresponding rates among patients with HCV genotype 2 were 86.7%, 84.3%, and 10.1%. An RVR had high predictive value for an SVR in patients with HCV genotypes 2 (88.9%) and 3 (88.1%). The strongest independent predictors of relapse in patients with genotype 3 and an RVR were steatosis (odds ratio 3.0; P = .003) and HCV RNA >= 400,000 IU/mL (odds ratio 2.5; P = .04). Relapse rates in patients with steatosis were 17.4% and 20.9% for low and high baseline levels of HCV RNA, respectively; corresponding rates in those without steatosis were 2.5% and 8.8%. CONCLUSIONS: Steatosis was associated with significantly higher rates of relapse, irrespective of viral load, in patients infected with HCV genotype 3 who had an RVR. Further studies are needed to determine if longer treatment durations are effective in patients with an RVR and these risk factors.
C1 [Nelson, David R.] Univ Florida, Coll Med, Dept Med Hepatol & Liver Transplantat, Gainesville, FL 32610 USA.
[Shah, Samir R.] Jaslok Hosp, Dept Gastroenterol, Bombay, Maharashtra, India.
[Shah, Samir R.] Res Ctr, Bombay, Maharashtra, India.
[Shah, Samir R.] Breach Candy Hosp, Bombay, Maharashtra, India.
[Patel, Keyur; McHutchison, John G.] Duke Clin Res Inst, Durham, NC USA.
[Marcellin, Patrick] Hosp Beaujon, Serv Hepatol, Serv Hepatogastroenterol Rech Clin, Clichy, France.
[Foster, Graham R.] Queen Marys Univ London, Barts & London Sch Med, London, England.
[Manns, Michael] Hannover Med Sch, Dept Gastroenterol & Hepatol, Hannover, Germany.
[Kottilil, Shyam] NIAID, Bethesda, MD 20892 USA.
[Healey, Letha; Pulkstenis, Erik; Subramanian, G. Mani] Human Genome Sci Inc, Rockville, MD USA.
[Sulkowski, Mark S.] Johns Hopkins Ctr Viral Hepatitis, Baltimore, MD USA.
[Zeuzem, Stefan] JW Goethe Univ Hosp, Frankfurt, Germany.
RP Nelson, DR (reprint author), Univ Florida, Coll Med, Dept Med Hepatol & Liver Transplantat, Box 100214,Rm M-440, Gainesville, FL 32610 USA.
EM nelsodr@medicine.ufl.edu
FU Human Genome Sciences; Novartis; Hoffmann-La Roche, Inc, Nutley, New
Jersey; Roche; Human Genome Sciences, Inc, Rockville, Maryland; Novartis
Pharma AG, Basel, Switzerland; NIH/NCRR [UL1 RR029890]
FX Editorial support was provided by Geoff Marx of BioScience
Communications, New York, New York, and was funded by Human Genome
Sciences and Novartis.; These authors disclose the following: Graham R.
Foster has received funding from Hoffman-LaRoche Inc, Nutley, New
Jersey; and Novartis Pharma AG, Basel, Switzerland. Letha Healey, Erik
Pulkstenis, and G. Mani Subramanian are employees of and own stock in
Human Genome Sciences (HGS), Inc, Rockville, Maryland. John G.
McHutchison has received research support from and is a consultant for
HGS, Novartis, and Hoffmann-La Roche, Inc, Nutley, New Jersey. Mark S.
Sulkowski has received consulting fees and research support from HGS and
Roche. Stefan Zeuzem has received consulting fees from HGS and Novartis,
and lecture fees from Novartis. David R. Nelson has received research
grants from HGS and Novartis, and is a consultant for HGS. The remaining
authors disclose no conflicts.; Supported by Human Genome Sciences, Inc,
Rockville, Maryland, and Novartis Pharma AG, Basel, Switzerland. This
work supported in part by NIH/NCRR CTSA award to the University of
Florida UL1 RR029890.
NR 34
TC 36
Z9 36
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD AUG
PY 2011
VL 9
IS 8
BP 688
EP 693
DI 10.1016/j.cgh.2011.04.029
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 803OW
UT WOS:000293591600018
PM 21640198
ER
PT J
AU Roederer, M
AF Roederer, Mario
TI Multiple Stained Samples are Not Appropriate Compensation Controls
SO CYTOMETRY PART A
LA English
DT Editorial Material
C1 NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Roederer, M (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA.
EM Roederer@NIH.gov
FU Intramural NIH HHS
NR 1
TC 3
Z9 3
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD AUG
PY 2011
VL 79A
IS 8
BP 591
EP 593
DI 10.1002/cyto.a.21093
PG 3
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 801NF
UT WOS:000293445900002
PM 21674773
ER
PT J
AU Pollara, J
Hart, L
Brewer, F
Pickeral, J
Packard, BZ
Hoxie, JA
Komoriya, A
Ochsenbauer, C
Kappes, JC
Roederer, M
Huang, Y
Weinhold, KJ
Tomaras, GD
Haynes, BF
Montefiori, DC
Ferrari, G
AF Pollara, Justin
Hart, Lydia
Brewer, Faraha
Pickeral, Joy
Packard, Beverly Z.
Hoxie, James A.
Komoriya, Akira
Ochsenbauer, Christina
Kappes, John C.
Roederer, Mario
Huang, Ying
Weinhold, Kent J.
Tomaras, Georgia D.
Haynes, Barton F.
Montefiori, David C.
Ferrari, Guido
TI High-Throughput Quantitative Analysis of HIV-1 and SIV-Specific
ADCC-Mediating Antibody Responses
SO CYTOMETRY PART A
LA English
DT Article
DE ADCC; HIV; SIV; NK; Fc gamma receptors; Granzyme B; high throughput
ID DEPENDENT CELLULAR CYTOTOXICITY; MONOCLONAL-ANTIBODIES; NK CELLS;
INFECTION; VACCINE; IDENTIFICATION; LYMPHOCYTES; PROTECTION; BINDING;
GP41
AB We have developed a high-throughput platform to detect the presence of HIV-1 and SIV-specific ADCC-mediating antibody responses. The assay is based on the hydrolysis of a cell-permeable fluorogenic peptide substrate containing a sequence recognized by the serine protease, Granzyme B (GzB). GzB is delivered into target cells by cytotoxic effector cells as a result of antigen (Ag)-specific Ab-Fc gamma receptor interactions. Within the target cells, effector cell-derived GzB hydrolyzes the substrate, generating a fluorescent signal that allows individual target cells that have received a lethal hit to be identified by flow cytometry. Results are reported as the percentage of target cells with GzB activity (%GzB). Freshly isolated or cryopreserved PBMC and/or NK cells can be used as effector cells. CEM.NKR cells expressing the CCR5 co-receptor are used as a target cells following: (i) coating with recombinant envelope glycoprotein, (ii) infection with infectious molecular clones expressing the Env antigens of primary and lab adapted viruses, or (iii) chronic infection with a variant of HIV-1/IIIB, termed A1953. In addition, primary CD4(+) T cells infected with HIV-1 in vitro can also be used as targets. The assay is highly reproducible with a coefficient of variation of less than 25%. Target and effector cell populations, in the absence of serum/plasma, were used to calculate background (8.6 +/- 2.3%). We determined that an initial dilution of 1:50 and 1:100 is required for testing of human and non-human primate samples, respectively. This assay allows for rapid quantification of HIV-1 or SIV-specific ADCC-mediating antibodies that develop in response to vaccination, or in the natural course of infection, thus providing researchers with a new methodology for investigating the role of ADCC-mediating antibodies as correlates of control or prevention of HIV-1 and SIV infection. (C) 2011 International Society for Advancement of Cytometry
C1 [Pollara, Justin; Hart, Lydia; Brewer, Faraha; Pickeral, Joy; Weinhold, Kent J.; Tomaras, Georgia D.; Montefiori, David C.; Ferrari, Guido] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Packard, Beverly Z.; Komoriya, Akira] OncoImmunin, Gaithersburg, MD USA.
[Hoxie, James A.] Univ Penn, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA.
[Ochsenbauer, Christina; Kappes, John C.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Roederer, Mario] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Huang, Ying] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA.
[Weinhold, Kent J.; Tomaras, Georgia D.; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA.
[Tomaras, Georgia D.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
[Haynes, Barton F.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Haynes, Barton F.] Duke Univ, Med Ctr, Human Vaccine Inst, Durham, NC 27710 USA.
RP Ferrari, G (reprint author), Duke Univ, Med Ctr, Dept Surg, POB 2926, Durham, NC 27710 USA.
EM justin.pollara@duke.edu; gflmp@duke.edu
RI Ferrari, Guido/A-6088-2015; Tomaras, Georgia/J-5041-2016
FU Bill and Melinda Gates Foundation [38619, 5R01AI050483-09]; Center for
HIV/AIDS Vaccine Immunology [A1067854-03]; Duke University Center for
AIDS Research (CFAR); NIH [P30, AI 64518]; NIH/NIAID [AI07392]
FX Grant sponsors: Collaboration for AIDS Vaccine Discovery (CAVD), Bill
and Melinda Gates Foundation; Grant numbers: 38619 and 5R01AI050483-09;
Grant sponsor: Center for HIV/AIDS Vaccine Immunology; Grant number:
A1067854-03; Grant sponsor: Duke University Center for AIDS Research
(CFAR); Grant sponsor: NIH; Grant numbers: P30 and AI 64518 and
NIH/NIAID number AI07392 (to Justin Pollara).
NR 34
TC 76
Z9 77
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD AUG
PY 2011
VL 79A
IS 8
BP 603
EP 612
DI 10.1002/cyto.a.21084
PG 10
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 801NF
UT WOS:000293445900004
PM 21735545
ER
PT J
AU Deeb, KK
Luo, W
Karpf, AR
Omilian, AR
Bshara, W
Tian, LL
Tangrea, MA
Morrison, CD
Johnson, CS
Trump, DL
AF Deeb, Kristin K.
Luo, Wei
Karpf, Adam R.
Omilian, Angela R.
Bshara, Wiam
Tian, Lili
Tangrea, Michael A.
Morrison, Carl D.
Johnson, Candace S.
Trump, Donald L.
TI Differential vitamin D 24-hydroxylase/CYP24A1 gene promoter methylation
in endothelium from benign and malignant human prostate
SO EPIGENETICS
LA English
DT Article
DE CYP24A1; DNA methylation; human prostate cancer; tumor endothelium;
laser microdissection
ID LASER-CAPTURE MICRODISSECTION; EPIGENETIC REGULATION; HISTONE
MODIFICATIONS; CANDIDATE ONCOGENE; STROMAL CELLS; CANCER; EXPRESSION;
METABOLISM; CYP24; IDENTIFICATION
AB Epigenetic alterations occur in tumor-associated vessels in the tumor microenvironment. Methylation of the CYP24A1 gene promoter differs in endothelial cells isolated from tumors and non-tumor microenvironments in mice. The epigenetic makeup of endothelial cells of human tumor-associated vasculature is unknown due to difficulty of isolating endothelial cells populations from a heterogeneous tissue microenvironment. To ascertain CYP24A1 promoter methylation in tumor-associated endothelium, we utilized laser microdissection guided by CD31 immunohistochemistry to procure endothelial cells from human prostate tumor specimens. Prostate tissues were obtained following robotic radical prostatectomy from men with clinically localized prostate cancer. Adjacent histologically benign prostate tissues were used to compare endothelium from benign versus tumor microenvironments. Sodium bisulfite sequencing of CYP24A1 promoter region showed that the average CYP24A1 promoter methylation in the endothelium was 20% from the tumor microenvironment compared with 8.2% in the benign microenvironment (p < 0.05). A 2-fold to 17-fold increase in CYP24A1 promoter methylation was observed in the prostate tumor endothelium compared with the matched benign prostate endothelium in four patient samples, while CYP24A1 promoter methylation remained unchanged in two patient samples. In addition, there is no correlation of the level of CYP24A1 promoter methylation in prostate tumor-associated endothelium with that of epithelium/stroma. This study demonstrates that the CYP24A1 promoter is methylated in tumor-associated endothelium, indicating that epigenetic alterations in CYP24A1 may play a role in determining the phenotype of tumor-associated vasculature in the prostate tumor microenvironment.
C1 [Trump, Donald L.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA.
[Deeb, Kristin K.; Luo, Wei; Karpf, Adam R.; Johnson, Candace S.] Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA.
[Omilian, Angela R.; Bshara, Wiam; Morrison, Carl D.] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA.
[Tian, Lili] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA.
[Tangrea, Michael A.] NCI, Pathogenet Unit, Pathol Lab, Adv Technol Ctr,NIH, Gaithersburg, MD USA.
RP Trump, DL (reprint author), Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA.
EM donald.trump@roswellpark.org
FU NIH/NCI [CA067267, CA085142, CA095045]; American Cancer Society
[02-197-04]
FX This research was supported by NIH/NCI grants CA067267, CA085142 and
CA095045 (C.S.J., D. L. T.) and by the American Cancer Society
Institutional Research Grant 02-197-04 (K.K.D.).
NR 40
TC 21
Z9 21
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1559-2294
J9 EPIGENETICS-US
JI Epigenetics
PD AUG
PY 2011
VL 6
IS 8
BP 994
EP 1000
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 800FF
UT WOS:000293344500006
PM 21725204
ER
PT J
AU Murase, S
Poser, SW
Joseph, J
McKay, RD
AF Murase, Sachiko
Poser, Steve W.
Joseph, Joby
McKay, Ronald D.
TI p53 controls neuronal death in the CA3 region of the newborn mouse
hippocampus
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE Akt; apoptosis; Bax; integrin beta(1); neurotrophin
ID OCCURRING CELL-DEATH; SIGNALING PATHWAY; NERVOUS-SYSTEM; APOPTOSIS;
SURVIVAL; RECEPTORS; DISEASE; MICE; SIZE; RAT
AB It is important to determine the mechanisms controlling the number of neurons in the nervous system. Previously, we reported that neuronal activity plays a central role in controlling neuron number in the neonatal hippocampus of rodents. Neuronal survival requires sustained activation of the serine-threonine kinase Akt, which is initiated by neurotrophins and continued for several hours by neuronal activity and integrin signaling. Here, we focus on the CA3 region to show that neuronal apoptosis requires p53. As in wild-type animals, neuronal death occurs in the first postnatal week and ends by postnatal day (P) 10 in p53(-/-) mice. During this period, the CA3 region of p53(-/-) mice contains significantly lower numbers of apoptotic cells, and at the end of the death period, it contains more neurons than the wild type. At P10, the p53(-/-) CA3 region contains a novel subpopulation of neurons with small soma size. These neurons show normal levels of tropomyosin receptor kinase receptor activation, but lower levels of activated Akt than the neurons with somata of normal size. These results suggest that p53 is the key downstream regulator of the novel survival-signaling pathway that regulates the number of CA3 neurons in the first 10 days of postnatal life.
C1 [McKay, Ronald D.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
[Murase, Sachiko; Poser, Steve W.; McKay, Ronald D.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Joseph, Joby] NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA.
[Joseph, Joby] Univ Hyderabad, Ctr Neural & Cognit Sci, Hyderabad 500134, Andhra Pradesh, India.
RP McKay, RD (reprint author), Lieber Inst Brain Dev, 855 N Wolfe St, Baltimore, MD 21205 USA.
EM ronaldmckay@mac.com
FU NIH, NINDS
FX This research was supported by the Intramural Research Program of the
NIH, NINDS.
NR 24
TC 10
Z9 13
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD AUG
PY 2011
VL 34
IS 3
BP 374
EP 381
DI 10.1111/j.1460-9568.2011.07758.x
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 800HK
UT WOS:000293350200003
PM 21714817
ER
PT J
AU Meadows, KL
Andrews, DMK
Xu, ZL
Carswell, GK
Laughlin, SK
Baird, DD
Taylor, JA
AF Meadows, Kellen L.
Andrews, Danica M. K.
Xu, Zongli
Carswell, Gleta K.
Laughlin, Shannon K.
Baird, Donna D.
Taylor, Jack A.
TI Genome-wide analysis of loss of heterozygosity and copy number
amplification in uterine leiomyomas using the 100K single nucleotide
polymorphism array
SO EXPERIMENTAL AND MOLECULAR PATHOLOGY
LA English
DT Article
DE Uterine leiomyoma; Single nucleotide polymorphism array; LOH; Copy
number amplification
ID LOSS-OF-HETEROZYGOSITY; CYTOGENETIC ANALYSIS; SNP ARRAYS; FIBROIDS;
TUMORS; HYBRIDIZATION; ALLELOTYPE; GENETICS; GROWTH; SIZE
AB Purpose: Uterine leiomyomas (fibroids) are benign smooth muscle tumors commonly found among reproductive-aged women. Though benign, these tumors are the leading indication for hysterectomies in the United States and cause significant morbidity. Despite the importance of this tumor in women's health, relatively little is known about the molecular etiology.
Methods: In this study, we used the Affymetrix 100K single nucleotide polymorphism (SNP) chip to assess whether the pattern and frequency of genome-wide loss of heterozygosity (LOH) and copy number amplifications is associated with clinical heterogeneity.
Results: Thirty-seven tumors with varying sizes and histology from eleven patients were analyzed. LOH was observed in 4/37 tumors (10.8%) and significantly associated with large-sized tumors (p<0.0014). Two tumors revealed hemizygosity on chromosome 7q, a region that has been consistently reported to have LOH. Additionally, we detected one novel region of LOH, 16p13.11 in one tumor (2.7%). Copy number amplifications were observed on all chromosomes; however, most were low-level amplifications and only detected in a single tumor. One region of amplification at 3p26.3 was detected in four tumors.
Conclusions: Despite the use of a high-density SNP platform, our results suggest that genome-wide LOH and copy number amplifications are infrequent events and generally do not determine clinical and histologic characteristics of this disease. Published by Elsevier Inc.
C1 [Meadows, Kellen L.; Carswell, Gleta K.; Taylor, Jack A.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Andrews, Danica M. K.] Natl Inst Environm Hlth Sci, Microarray Grp, Res Triangle Pk, NC 27709 USA.
[Xu, Zongli; Laughlin, Shannon K.; Baird, Donna D.; Taylor, Jack A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Taylor, JA (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, PO 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM taylor@niehs.nih.gov
RI Baird, Donna/D-5214-2017;
OI Baird, Donna/0000-0002-5544-2653; xu, zongli/0000-0002-9034-8902;
taylor, jack/0000-0001-5303-6398
FU NIH, National Institute of Environmental Health Sciences; National
Center for Research on Minority Health and Health Disparities, NIH
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences. Financial
support for the parent study, The Fibroid Growth Study, was provided by
NIEHS, NIH intramural funding and the National Center for Research on
Minority Health and Health Disparities, NIH. Barbara Davis and Shyamal
Peddada provided design and oversight of the parentstudy. Ania Kowalik
was the clinical leader of the field study. Karen Haneke and Heather
Vahdat managed the field study and the study data. Martha Turvey was the
study nurse, Xiaoyu Ding conducted the pathological analyses of tumor
tissue, and Pamela Blackshear aided in tissue analyses. Anne Marie Jukic
and Lisa Chadwick provided comments on the manuscript.
NR 26
TC 3
Z9 3
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4800
J9 EXP MOL PATHOL
JI Exp. Mol. Pathol.
PD AUG
PY 2011
VL 91
IS 1
BP 434
EP 439
DI 10.1016/j.yexmp.2011.03.007
PG 6
WC Pathology
SC Pathology
GA 802ZE
UT WOS:000293548700016
PM 21497600
ER
PT J
AU Leng, SX
Li, HF
Xue, QL
Tian, J
Yang, X
Ferrucci, L
Fedarko, N
Fried, LP
Semba, RD
AF Leng, Sean X.
Li, Huifen
Xue, Qian-Li
Tian, Jing
Yang, Xi
Ferrucci, Luigi
Fedarko, Neal
Fried, Linda P.
Semba, Richard D.
TI Association of detectable cytomegalovirus (CMV) DNA in monocytes rather
than positive CMV IgG serology with elevated neopterin levels in
community-dwelling older adults
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article
DE Detectable CMV DNA in peripheral monocytes; Neopterin; Immune
activation; Older adults; Chronic CMV infection; CMV seropositivity; CMV
IgG titers
ID SWEDISH NONA IMMUNE; T-LYMPHOCYTE SUBPOPULATIONS; BLOOD
MONONUCLEAR-CELLS; HUMAN IMMUNOSENESCENCE; INFECTION; RISK; AGE;
INDIVIDUALS; ACTIVATION; MARKER
AB In immunocompetent persons, cytomegalovirus (CMV) is thought to persist primarily in monocytes and myeloid progenitor cells, establishing a chronic infection. In older adults, chronic CMV infection is typically diagnosed by a positive IgG serology. While many studies have shown CMV-specific T-cell expansion in CMV seropositive older individuals, significant heterogeneity has also been observed in this elderly population. In a study of 71 community-dwelling older adults, we assessed CMV viral DNA in peripheral monocytes by nested PCR and compared the relationships of detectable CMV DNA and IgG serology with serum levels of neopterin, a marker for monocyte/macrophage-mediated immune activation. The results showed that 52 (73.2%) participants were CMV seropositive, of whom 30 (57.5%) had detectable CMV DNA. CMV seropositive and seronegative participants did not differ in their neopterin levels, but individuals with detectable CMV DNA had higher neopterin than those without (10.6 +/- 4.4 vs 8.0 +/- 1.9 nM, respectively, p<.0001) adjusting for demographic and clinical covariates and interferon (IFN)-gamma levels. In addition, there was no association between IgG titers and neopterin. These findings suggest that detection of CMV viral DNA in monocytes may be an informative tool to evaluate chronic CMV infection and its potential role in monocyte/macrophage-mediated immune activation in the elderly. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Leng, Sean X.; Li, Huifen; Xue, Qian-Li; Tian, Jing; Yang, Xi; Fedarko, Neal] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Dept Med, Baltimore, MD 21224 USA.
[Semba, Richard D.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21224 USA.
[Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Fried, Linda P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
RP Leng, SX (reprint author), Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Dept Med, 5505 Hopkins Bayview Circle, Baltimore, MD 21224 USA.
EM sleng1@jhmi.edu
OI Fedarko, Neal/0000-0001-6055-6279
FU Paul Beeson Career Development Award in Aging Research [K23 AG028963];
Johns Hopkins Older American Independence Center [P30 AG021334];
National Institute on Aging; [R37 AG19905]
FX Dr. Sean Leng is a current recipient of the Paul Beeson Career
Development Award in Aging Research, K23 AG028963. This research was
also supported in part by R37 AG19905 (PI: Linda P. Fried) and by Johns
Hopkins Older American Independence Center, P30 AG021334, both funded by
National Institute on Aging.
NR 42
TC 16
Z9 16
U1 1
U2 2
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 AUG
PY 2011
VL 46
IS 8
BP 679
EP 684
DI 10.1016/j.exger.2011.04.002
PG 6
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 802CA
UT WOS:000293485700007
PM 21513787
ER
PT J
AU Boutte, AM
Friedman, DB
Bogyo, M
Min, YF
Yang, L
Lin, PC
AF Boutte, Angela M.
Friedman, David B.
Bogyo, Matthew
Min, Yongfen
Yang, Li
Lin, P. Charles
TI Identification of a myeloid-derived suppressor cell cystatin-like
protein that inhibits metastasis
SO FASEB JOURNAL
LA English
DT Article
DE cathepsin; angiogenesis; lymphanogenesis; NGP
ID CATHEPSIN-B; BREAST-CANCER; STEFIN-A; TUMOR; ANGIOGENESIS; ASSOCIATION;
DEGRADATION; PROGRESSION; MEMBRANE; MICE
AB Myeloid-derived suppressor cells (MDSCs) are significantly increased in cancer patients and tumor bearing-animals. MDSCs infiltrate into tumors and promote tumor invasion and metastasis. To identify the mediator responsible for the prometastatic property of MDSCs, we used proteomics. We found neutrophilic granule protein (NGP) was decreased > 2-fold in MDSCs from metastatic 4T1 tumor-bearing mice compared to nonmetastatic 67NR controls. NGP mRNA levels were decreased in bone marrow and in tumor-infiltrating MDSCs by 45 and 66%, respectively, in 4T1 tumor-bearing mice compared to 67NR controls. Interestingly, 4T1-conditioned medium reduced myeloid cell NGP expression by similar to 40%, suggesting that a secreted factor mediates gene reduction. Sequence analysis shows a putative cystatin domain in NGP, and biochemical analysis confirms NGP a novel cathepsin inhibitor. It inhibited cathepsin B activity by nearly 40% in vitro. NGP expression in 4T1 tumor cells suppressed cell invasion, delayed primary tumor growth, and greatly reduced lung metastasis in vivo. A 2.8-fold reduction of cathepsin activity was found in tumors expressing NGP compared to controls. NGP significantly reduced tumor angiogenesis to 12.6 from 19.6 and lymphangiogenesis to 4.6 from 9.1 vessels/field. Necrosis was detectable only in NGP-expressing tumors, and the number of apoptotic cells increased to 22.4 from 8.3 in controls. Taken together, this study identifies a negative regulator of tumor metastasis in MDSCs, NGP, which is down-regulated in metastatic conditions. The finding suggests that malignant tumors promote invasion/metastasis not only through up-regulation of proteases but also down-regulation of protease inhibitors.-Boutte, A. M., Friedman, D. B., Bogyo, M., Min, Y., Yang, L., Lin, P. C. Identification of a myeloid-derived suppressor cell cystatin-like protein that inhibits metastasis. FASEB J. 25, 2626-2637 (2011). www.fasebj.org
C1 [Min, Yongfen; Yang, Li; Lin, P. Charles] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Friedman, David B.] Vanderbilt Univ, Dept Biochem, Med Ctr, Nashville, TN 37232 USA.
[Boutte, Angela M.] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN USA.
[Bogyo, Matthew] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
RP Lin, PC (reprint author), NCI, 1050 Boyles St,Bldg 560,Rm 12-32, Frederick, MD 21702 USA.
EM p.lin@nih.edu
FU U.S. National Institutes of Health [1F32CA136118, UL1 RR 024975,
CA108856, NS45888, AR053718]
FX The authors thank Drs. Lynn Matrisian and Barbara Fingleton at
Vanderbilt University Medical Center for critical comments on the
manuscript. The authors thank Dr. Kelli Boyd for analysis of tumor
histology and Dr. Swati Biswas for her expertise in mouse models of
cancer at Vanderbilt University Medical Center. This work is supported
in part by U.S. National Institutes of Health grants to A.M.B.
(1F32CA136118 and UL1 RR 024975) and P.C.L. (CA108856, NS45888, and
AR053718).
NR 30
TC 7
Z9 9
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 AUG
PY 2011
VL 25
IS 8
BP 2626
EP 2637
DI 10.1096/fj.10-180604
PG 12
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 800CV
UT WOS:000293337800013
PM 21518852
ER
PT J
AU Ross, JR
Case, C
Confer, D
Weisdorf, DJ
Weinstock, D
Krawisz, R
Chute, J
Wilhauk, J
Navarro, W
Hartzman, R
Coleman, CN
Hatchett, R
Chao, N
AF Ross, Joel R.
Case, Cullen
Confer, Dennis
Weisdorf, Daniel J.
Weinstock, David
Krawisz, Robert
Chute, John
Wilhauk, Julie
Navarro, Willis
Hartzman, Robert
Coleman, C. Norman
Hatchett, Richard
Chao, Nelson
TI Radiation Injury Treatment Network (RITN): Healthcare professionals
preparing for a mass casualty radiological or nuclear incident
SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
LA English
DT Article
DE radiation accidents; cell therapy; haematology - radiation; radiation
injury; emergency response; emergency preparedness
ID MEDICAL-MANAGEMENT; BIODOSIMETRY; TERRORISM; TRIAGE
AB Purpose: To describe the history, composition, and activities of the Radiation Injury Treatment Network (RITN). The Radiation Injury Treatment Network (R) is a cooperative effort of the National Marrow Donor Program and the American Society for Blood and Marrow Transplantation. The goals of RITN are to educate hematologists, oncologists, and stem cell transplant practitioners about their potential involvement in the response to a radiation incident and provide treatment expertise. Injuries to the marrow system readily occur when a victim is exposed to ionising radiation. This focus therefore leverages the expertise of these specialists who are accustomed to providing the intensive supportive care required by patients with a suppressed marrow function. Following a radiological incident, RITN centres may be asked to: Accept patient transfers to their institutions; provide treatment expertise to practitioners caring for victims at other centres; travel to other centres to provide medical expertise; or provide data on victims treated at their centres. Moving forward, it is crucial that we develop a coordinated interdisciplinary approach in planning for and responding to radiological and nuclear incidents. The ongoing efforts of radiation biologists, radiation oncologists, and health physicists can and should complement the efforts of RITN and government agencies.
Conclusion: RITN serves as a vital partner in preparedness and response efforts for potential radiological and nuclear incidents.
C1 [Case, Cullen; Confer, Dennis; Krawisz, Robert; Navarro, Willis; Hartzman, Robert] Natl Marrow Donor Program, Minneapolis, MN USA.
[Weisdorf, Daniel J.] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA.
[Weinstock, David] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wilhauk, Julie] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Coleman, C. Norman] NCI, Bethesda, MD 20892 USA.
[Hatchett, Richard] NIAID, NIH, Bethesda, MD 20892 USA.
[Ross, Joel R.; Chute, John; Chao, Nelson] Duke Univ, Div Cellular Therapy, Durham, NC 27710 USA.
RP Chao, N (reprint author), Duke Univ, Div Cellular Therapy BMT, 2400 Pratt St,Suite 9011,Box 3961, Durham, NC 27710 USA.
EM chao0002@mc.duke.edu
FU NIH [U19 AI 067798]; Department of the Navy, Office of Naval Research
[N00014-10-1-0204]
FX This study was supported in part by NIH U19 AI 067798 and Department of
the Navy, Office of Naval Research Grant #N00014-10-1-0204 to the
National Marrow Donor Program.
NR 26
TC 9
Z9 9
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0955-3002
J9 INT J RADIAT BIOL
JI Int. J. Radiat. Biol.
PD AUG
PY 2011
VL 87
IS 8
SI SI
BP 748
EP 753
DI 10.3109/09553002.2011.556176
PG 6
WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Nuclear Science &
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 800HG
UT WOS:000293349800002
PM 21801106
ER
PT J
AU Lumley, T
Shaw, PA
Dai, JY
AF Lumley, Thomas
Shaw, Pamela A.
Dai, James Y.
TI Connections between Survey Calibration Estimators and Semiparametric
Models for Incomplete Data
SO INTERNATIONAL STATISTICAL REVIEW
LA English
DT Article
DE Regression; designed-based inference; causal inference
ID PROPORTIONAL HAZARDS MODELS; RANDOMIZED CLINICAL-TRIALS; CASE-COHORT;
MEASUREMENT-ERROR; STRATIFIED SAMPLES; REGRESSION; EFFICIENCY;
PARAMETERS; LIKELIHOOD; INFERENCE
AB Survey calibration (or generalized raking) estimators are a standard approach to the use of auxiliary information in survey sampling, improving on the simple Horvitz-Thompson estimator. In this paper we relate the survey calibration estimators to the semiparametric incomplete-data estimators of Robins and coworkers, and to adjustment for baseline variables in a randomized trial. The development based on calibration estimators explains the "estimated weights" paradox and provides useful heuristics for constructing practical estimators. We present some examples of using calibration to gain precision without making additional modelling assumptions in a variety of regression models.
C1 [Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Lumley, Thomas; Dai, James Y.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Shaw, Pamela A.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
RP Lumley, T (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
EM tlumley@uw.edu
FU Intramural NIH HHS [Z99 AI999999]
NR 50
TC 18
Z9 18
U1 1
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0306-7734
J9 INT STAT REV
JI Int. Stat. Rev.
PD AUG
PY 2011
VL 79
IS 2
BP 200
EP 220
DI 10.1111/j.1751-5823.2011.00138.x
PG 21
WC Statistics & Probability
SC Mathematics
GA 801AF
UT WOS:000293408100008
PM 23833390
ER
PT J
AU Kim, JY
Anderson, ED
Huynh, W
Dey, A
Ozato, K
AF Kim, Ji Young
Anderson, Eric D.
Huynh, Walter
Dey, Anup
Ozato, Keiko
TI Proteomic Survey of Ubiquitin-Linked Nuclear Proteins in
Interferon-Stimulated Macrophages
SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
LA English
DT Article
ID MASS-SPECTROMETRY; GENE-EXPRESSION; INNATE IMMUNITY; I INTERFERON;
LIGASE; UBIQUITYLATION; CELLS; ACTIN; IDENTIFICATION; APOPTOSIS
AB Ubiquitin modification plays a critical role in immune responses. Some cytoplasmic factors require ubiquitination to execute proper signaling upon pathogen and cytokine stimulation. However, ubiquitin modification and its functional significance have not been fully studied for many nuclear proteins. We report here that stimulation of RAW macrophages with interferon-gamma and toll-like receptor ligands that activates innate immune responses triggers a global increase in ubiquitinated proteins in the nucleus, pointing to the role for ubiquitin modification in regulating nuclear events during innate immune responses. By immunopurification and mass-spectrometry analyses, we found that more than 200 proteins are directly or indirectly associated with ubiquitin in stimulated RAW cells. These proteins included proteins in the ubiquitin pathways, those involved in DNA metabolism, chromatin and transcriptional regulation, and mRNA processing. The largest group of proteins found in our list was ribosomal proteins important for protein translation. Other proteins found here were heat shock proteins and stress-response factors, suggesting a link between macrophage activation and stress response. In conclusion, upon macrophage activation, a large number of nuclear proteins become associated with ubiquitin modification, presumably leading to a global shift in the genome activity, important for proper execution of innate immune responses.
C1 [Kim, Ji Young; Huynh, Walter; Dey, Anup; Ozato, Keiko] NICHHD, Program Genom Differentiat, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA.
[Anderson, Eric D.] NIDDK, Mass Spectrometry Facil, NIH, Bethesda, MD USA.
RP Ozato, K (reprint author), NICHHD, Program Genom Differentiat, Lab Mol Growth Regulat, NIH, Bldg 6,Room 2A01,6 Ctr Dr, Bethesda, MD 20892 USA.
EM ozatok@nih.gov
FU NIDHD; NIDDK; NIH-FDA; NIAID; National Institutes of Health
FX We thank Dr. M.K. Jang and Mr. D. Kim, and members of Ozato laboratory
for reagents, suggestions, and critical discussions on this work. This
work was supported by the Intramural Program of NIDHD, and NIDDK, as
well as the trans NIH-FDA Biodefense program of NIAID, National
Institutes of Health.
NR 42
TC 8
Z9 8
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1079-9907
J9 J INTERF CYTOK RES
JI J. Interferon Cytokine Res.
PD AUG
PY 2011
VL 31
IS 8
BP 619
EP 628
DI 10.1089/jir.2011.0006
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 804CC
UT WOS:000293630500004
PM 21428739
ER
PT J
AU Molleston, JP
Fontana, RJ
Lopez, MJ
Kleiner, DE
Gu, JZ
Chalasani, N
AF Molleston, Jean P.
Fontana, Robert J.
Lopez, M. James
Kleiner, David E.
Gu, Jiezhun
Chalasani, Naga
CA Drug-Induced Liver Injury Network
TI Characteristics of Idiosyncratic Drug-induced Liver Injury in Children:
Results From the DILIN Prospective Study
SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
LA English
DT Article
DE drug-induced liver injury; hepatotoxicity; liver biopsy; Roussel Uclaf
Causality Assessment Method
ID ADVERSE-REACTIONS; HEPATITIS; HEPATOTOXICITY; METABOLISM; DISEASE;
TOXICITY; THERAPY; FAILURE
AB Background: The spectrum and severity of idiosyncratic drug-induced liver injury (DILI) in children are not well established.
Patients and Methods: The DILIN (Drug-Induced Liver Injury Network) Prospective Study is a longitudinal multicenter study designed to determine the etiologies, risk factors, and outcomes of suspected DILI. Between September 2004 and September 2009, 30 children ages 2 to 18 years with suspected DILI who met eligibility criteria were enrolled and studied for at least 6 months.
Results: Mean age was 14 years; 70% were girls. Antimicrobial (50%) and central nervous system agents (40%) were the most commonly implicated drug classes, with minocycline (4), isoniazid (3), azithromycin (3), atomoxetine (3), and lamotrigine (3) the leading agents. Median time from drug initiation to symptom onset was 32 days. Peak (median) liver chemistries were aspartate aminotransferase 503 U/L, alanine aminotransferase 727 U/L, alkaline phosphatase 331 U/L, and total bilirubin 3.9 mg/dL. Autoantibodies were common (64%). Liver injury pattern was hepatocellular 78%, cholestatic 13%, and mixed 9%. The DILI episode was scored: mild 32%, moderate 44%, severe 20%, and fatal (within 6 months) 4%. Causality assessment was definite 36%, very likely 36%, probable 16%, possible 8%, and unlikely 4%. Seven percent had persistent liver test abnormalities at 6-month follow-up suggesting chronic DILI. Liver biopsies from 12 children most frequently demonstrated chronic hepatitis or bile duct injury.
Conclusions: Idiosyncratic DILI in children is most commonly caused by antimicrobial or central nervous system agents and usually presents with a hepatocellular injury pattern. The majority of patients recover, but morbidity and infrequent mortality are seen.
C1 [Molleston, Jean P.; Chalasani, Naga] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Fontana, Robert J.; Lopez, M. James] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Fontana, Robert J.; Lopez, M. James] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Kleiner, David E.] NCI, Bethesda, MD 20892 USA.
[Gu, Jiezhun] Duke Univ, Duke Clin Res Inst, Raleigh, NC USA.
RP Molleston, JP (reprint author), Indiana Univ Sch Med, James Whitcomb Riley Hosp Children, 702 Barnhill Dr,Room ROC 4210, Indianapolis, IN 46202 USA.
EM jpmolles@iupui.edu
OI Kleiner, David/0000-0003-3442-4453
FU National Institute of Diabetes and Digestive and Kidney Diseases
[1U01DK065021, 1U01DK065193, 1U01DK065201, 1U01DK065184, 1U01DK065211,
1U01DK065238, 1U01DK065176]; National Institutes of Health, National
Cancer Institute; Clinical and Translational Science Awards [UL1
RR025761, UL1 RR025747, UL1 RR024134, UL1 RR024986, UL1 RR024982, UL1
RR024150]; Teva Pharmaceuticals; Phenomix; Abbott; KaroBio; JJ; Salix
Pharmaceuticals; Gilead; Eli Lilly; Roche
FX The DILIN is supported by the National Institute of Diabetes and
Digestive and Kidney Diseases under the following cooperative
agreements: 1U01DK065021, 1U01DK065193, 1U01DK065201, 1U01DK065193,
1U01DK065184, 1U01DK065211, 1U01DK065238, and 1U01DK065176. This study
was supported in part by the intramural program of the National
Institutes of Health, National Cancer Institute. Additional funding was
provided by Clinical and Translational Science Awards grants: UL1
RR025761 (Indiana), UL1 RR025747 (UNC), UL1 RR024134 (UPenn), UL1
RR024986 (UMich), UL1 RR024982 (UTSW), and UL1 RR024150 (Mayo).; Dr
Chalasani has received consulting fees regarding drug-induced liver
injury in the past 12 months from the following companies: Teva
Pharmaceuticals, Phenomix, Abbott, KaroBio, J&J, Salix Pharmaceuticals,
and Gilead; he has received support from Eli Lilly for research on
drug-induced liver disease. Drs Lopez and Molleston receive research
support from Roche. Dr Fontana has provided expert consultation for
Abbott Laboratories, GlaxoSmithKline, and Vertex Pharmaceuticals. Dr
Kleiner and Dr Gu report no conflicts of interest.
NR 39
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U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-2116
J9 J PEDIATR GASTR NUTR
JI J. Pediatr. Gastroenterol. Nutr.
PD AUG
PY 2011
VL 53
IS 2
BP 182
EP 189
DI 10.1097/MPG.0b013e31821d6cfd
PG 8
WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
GA 797LK
UT WOS:000293129100012
PM 21788760
ER
PT J
AU Manier, ML
Reyzer, ML
Goh, A
Dartois, V
Via, LE
Barry, CE
Caprioli, RM
AF Manier, M. Lisa
Reyzer, Michelle L.
Goh, Anne
Dartois, Veronique
Via, Laura E.
Barry, Clifton E., III
Caprioli, Richard M.
TI Reagent Precoated Targets for Rapid In-Tissue Derivatization of the
Anti-Tuberculosis Drug Isoniazid Followed by MALDI Imaging Mass
Spectrometry
SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
LA English
DT Article
DE Matrix-assisted laser desorption/ionization; Imaging mass spectrometry;
Isoniazid; Tuberculosis; trans-cinnamaldehyde; Derivatization; Precoated
MALDI targets
ID ASSISTED-LASER-DESORPTION/IONIZATION; PERFORMANCE LIQUID-CHROMATOGRAPHY;
CONTINUOUS SAMPLE DEPOSITION; 6-AMINOQUINOLYL-N-HYDROXYSUCCINIMIDYL
CARBAMATE; SIALIC ACIDS; MS ANALYSIS; ION-TRAP; MATRIX; SECTIONS;
PROTEINS
AB Isoniazid (INH) is an important component of front-line anti-tuberculosis therapy with good serum pharmacokinetics but unknown ability to penetrate tuberculous lesions. However, endogenous background interferences hinder our ability to directly analyze INH in tissues. Chemical derivatization has been successfully used to measure isoniazid directly from tissue samples using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). MALDI targets were pretreated with trans-cinnamaldehyde (CA) prior to mounting tissue slices. Isoniazid present in the tissues was efficiently derivatized and the INH-CA product measured by MS/MS. Precoating of MALDI targets allows the tissues to be directly thaw-mounted and derivatized, thus simplifying the preparation. A time-course series of tissues from tuberculosis infected/INH dosed animals were assayed and the MALDI MS/MS response correlates well with the amount of INH determined to be in the tissues by high-performance liquid chromatography (HPLC)-MS/MS.
C1 [Manier, M. Lisa; Reyzer, Michelle L.; Caprioli, Richard M.] Vanderbilt Univ, Mass Spectrometry Res Ctr, Nashville, TN 37235 USA.
[Goh, Anne; Dartois, Veronique] Novartis Inst Trop Dis, Biopolis, Singapore.
[Via, Laura E.; Barry, Clifton E., III] NIAID, NIH, Bethesda, MD 20892 USA.
[Caprioli, Richard M.] Vanderbilt Univ, Sch Med, Dept Chem, Nashville, TN 37232 USA.
[Caprioli, Richard M.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA.
[Caprioli, Richard M.] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA.
RP Caprioli, RM (reprint author), Vanderbilt Univ, Mass Spectrometry Res Ctr, Nashville, TN 37235 USA.
EM r.caprioli@vanderbilt.edu
RI Barry, III, Clifton/H-3839-2012;
OI Via, Laura/0000-0001-6074-9521
FU Bill and Melinda Gates Foundation [N01 HD23342]; NIH/NIGMS [5R01
GM58008]; NIAID, NIH
FX The authors acknowledge support for this work (in part) by the Bill and
Melinda Gates Foundation Accelerator grant N01 HD23342, (in part) by
NIH/NIGMS grant 5R01 GM58008, and (in part) by the Intramural Research
Program of NIAID, NIH. The assistance of Dr. Joey C. Latham, Dr. Kenneth
E. Schriver, and Jamie Allen (Vanderbilt) and Danielle Weiner and
Jacqueline Gonzales (NIH) is gratefully acknowledged.
NR 53
TC 31
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U1 1
U2 22
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1044-0305
J9 J AM SOC MASS SPECTR
JI J. Am. Soc. Mass Spectrom.
PD AUG
PY 2011
VL 22
IS 8
BP 1409
EP 1419
DI 10.1007/s13361-011-0150-8
PG 11
WC Biochemical Research Methods; Chemistry, Analytical; Chemistry,
Physical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA 796DE
UT WOS:000293029600015
PM 21953196
ER
PT J
AU Brown, P
AF Brown, Patricia
TI A word from OLAW
SO LAB ANIMAL
LA English
DT Editorial Material
C1 NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD AUG
PY 2011
VL 40
IS 8
BP 241
EP 241
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 800LS
UT WOS:000293362100016
ER
PT J
AU Shen, M
Cawthon, R
Rothman, N
Weinstein, SJ
Virtamo, J
Hosgood, HD
Hu, W
Lim, U
Albanes, D
Lan, Q
AF Shen, Min
Cawthon, Richard
Rothman, Nathaniel
Weinstein, Stephanie J.
Virtamo, Jarmo
Hosgood, H. Dean, III
Hu, Wei
Lim, Unhee
Albanes, Demetrius
Lan, Qing
TI A prospective study of telomere length measured by monochrome multiplex
quantitative PCR and risk of lung cancer
SO LUNG CANCER
LA English
DT Article
DE Telomere length; Lung cancer; Cohort study
ID BLADDER-CANCER; INSTABILITY; CELLS; CHEMOTHERAPY; DYSFUNCTION; LYMPHOMA
AB Purpose: Telomere length plays an important role in chromosomal stability and tumorigenesis, and its measurement in peripheral white blood cell DNA may be a predictor of the development of lung cancer.
Experimental design: Using a new method - monochrome multiplex quantitative PCR - which reduces measurement variability, we compared telomere length relative to standard DNA in white blood cell DNA in 229 incident male lung cancer cases and 229 matched controls within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male smokers.
Results: Median (10th, 90th percentile) telomere length was 1.13 (0.86, 1.45) in cases and 1.08 (0.85, 1.38) in controls (P = 0.038). Telomere length was inversely associated with pack-years of smoking (Spearman's correlation r = -0.16, P = 0.02) among controls. Compared to subjects with shorter telomere length (median), subjects with greater telomere length (>median) had a 1.6-fold (95% CI, 1.06-2.36) increased risk of lung cancer. There was a significant linear relationship between quartiles of telomere length and risk of lung cancer (odds ratios (95% confidence intervals) by quartile: 1.00, 0.98(0.55-1.73). 1.62 (0.95-2.77), and 1.50(0.84-2.68): P(trend) = 0.05). In addition, subgroup analysis showed that greater telomere length was associated with an increased risk of lung cancer among longer-term smokers (>38 years) (OR, 1.90; 95% CI, 1.00-3.59) but not among shorter-term smokers (<= 38 years) (OR, 1.08; 95% CI, 0.56-2.11) (P(interaction) = 0.01).
Conclusions: Our results suggest that greater telomere length may be associated with higher risk of lung cancer among male smokers. (C) 2011 Published by Elsevier Ireland Ltd.
C1 [Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Cawthon, Richard] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Lim, Unhee] Canc Res Ctr Hawaii, Program Epidemiol, Honolulu, HI 96813 USA.
RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, MSC7240,6120 Execut Blvd,EPS8010, Bethesda, MD 20892 USA.
EM qingl@mail.nih.gov
RI Hu, Wei/M-3524-2013; Albanes, Demetrius/B-9749-2015
FU National Cancer Institute; U.S. Public Health Service from the National
Cancer Institute [N01-CN-45165, N01-RC-45035, N01-RC-37004]; National
Institutes of Health; Department of Health and Human Services
FX This work was supported by intramural funds from the National Cancer
Institute and extramural funds, including U.S. Public Health Service
contracts N01-CN-45165, N01-RC-45035, and N01-RC-37004 from the National
Cancer Institute, National Institutes of Health and Department of Health
and Human Services.
NR 25
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Z9 46
U1 1
U2 13
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
J9 LUNG CANCER
JI Lung Cancer
PD AUG
PY 2011
VL 73
IS 2
BP 133
EP 137
DI 10.1016/j.lungcan.2010.11.009
PG 5
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 801HT
UT WOS:000293429900003
PM 21507503
ER
PT J
AU Tigno, XT
Hansen, BC
Nawang, S
Shamekh, R
Albano, AM
AF Tigno, Xenia T.
Hansen, Barbara C.
Nawang, Salasa
Shamekh, Rania
Albano, Alfonso M.
TI Vasomotion Becomes Less Random as Diabetes Progresses in Monkeys
SO MICROCIRCULATION
LA English
DT Article
DE vasomotion; diabetes; monkey; complexity; randomness
ID AGE-RELATED-CHANGES; INSULIN ACTION; PHYSIOLOGICAL HYPERINSULINEMIA;
MICROVASCULAR VASOMOTION; CAPILLARY RECRUITMENT; AUTONOMIC DYSFUNCTION;
HEALTHY-VOLUNTEERS; NONHUMAN-PRIMATES; SKELETAL-MUSCLE; SKIN
AB Objective: Changes in vasomotion may precede other global indices of autonomic dysfunction that track the onset and progression of diabetes. Recently, we showed that baseline spectral properties of vasomotion can discriminate among N, PreDM, and T2DM nonhuman primates. In this study, our aims were to: (i) determine the time dependence and complexity of the spectral properties of vasomotion in three metabolic groups of monkeys; (ii) examine the effects of heat-provoked vasodilatation on the power spectrum; and (iii) compare the effects of exogenous insulin on the vasomotion.
Materials and Methods: Laser Doppler flow rates were measured from the foot in 9 N, 11 PreDM, and 7 T2DM monkeys. Baseline flow was measured at 34 degrees C, and under heat stimulation at 44 degrees C. Euglycemic-hyperinsulinemic clamps were performed to produce acute hyperinsulinemia. The Lempel-Ziv complexity, prediction error, and covariance complexity of five-dimensional embeddings were calculated as measures of randomness.
Results and Conclusions: With progression of diabetes, measures of randomness of the vasomotion progressively decreased, suggesting a progressive loss of the homeostatic capacity of the peripheral circulation to respond to environmental changes. Power spectral density among T2DM animals resided mostly in the 0-to 1.45-Hz range, which excluded the cardiac component, suggesting that with progression of the disease, regulation of flow shifts toward local rather than central (autonomic) mechanisms. Heating increased all components of the spectral power in all groups. In N, insulin increased the vasomotion contributed by endothelial, neurogenic, vascular myogenic, and respiratory processes, but diminished that due to heart rate. In contrast, in T2DM, insulin failed to stimulate the vascular myogenic and respiratory activities, but increased the neural/endothelial and heart rate components. Interestingly, acute hyperinsulinemia resulted in no significant vasomotion changes in the chronically hyperinsulinemic PreDM, suggesting yet another form of "insulin resistance" during this stage of the disease.
C1 [Tigno, Xenia T.] Univ S Florida, Coll Med, Dept Mol Pharmacol & Physiol, Tampa, FL USA.
[Hansen, Barbara C.; Shamekh, Rania] Univ S Florida, Coll Med, Dept Internal Med & Pediat, Tampa, FL USA.
[Nawang, Salasa] Mindanao State Univ, Iligan Inst Technol, Dept Phys, Iligan, Philippines.
[Albano, Alfonso M.] Bryn Mawr Coll, Dept Phys, Bryn Mawr, PA 19010 USA.
RP Tigno, XT (reprint author), NINR, Off Extramural Programs, NIH, Bethesda, MD 20892 USA.
EM xtigno@yahoo.com
RI Hansen, Barbara/J-8723-2012
OI Hansen, Barbara/0000-0001-9646-3525
FU [NIA N01AG31012]; [NIA HHSN2532008002C]
FX Dr. Tigno's work on this manuscript was performed during her tenure at
the University of South Florida and does not reflect the views of the
NIH or the United States government. This work was partially supported
by NIA N01AG31012 and NIA HHSN2532008002C (B C Hansen, PI).
NR 41
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U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1073-9688
EI 1549-8719
J9 MICROCIRCULATION
JI Microcirculation
PD AUG
PY 2011
VL 18
IS 6
BP 429
EP 439
DI 10.1111/j.1549-8719.2011.00103.x
PG 11
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 800GI
UT WOS:000293347400001
PM 21435082
ER
PT J
AU Miller, AC
Jamin, CT
Elamin, EM
AF Miller, A. C.
Jamin, C. T.
Elamin, E. M.
TI Continuous intravenous infusion of ketamine for maintenance sedation
SO MINERVA ANESTESIOLOGICA
LA English
DT Review
DE Infusions, intravenous; Ketamine; Deep sedation
ID ACUTE SEVERE ASTHMA; REFRACTORY ASTHMA; ANESTHESIA; CHILDREN; CARE;
EMERGENCY; PROPOFOL; EFFICACY; INJURY; HEMODYNAMICS
AB Ketamine HCl is a rapidly acting general anesthetic with sedative and analgesic properties that has been reported to have favorable effects on the cardiovascular and pulmonary systems. The goal of this review is to determine the hernodynamic and pulmonary effects of continuous intravenous (IV) ketamine infusion in mechanically ventilated patients, and to determine whether sufficient evidence exists to support its use as an agent for maintenance anesthesia. PubMed/Medline, EMBASE, and Index Medicus databases as well as relevant bibliographies were searched. Studies were independently evaluated for inclusion and exclusion criteria, as well as study parameters, by two evaluators. Any discrepancy was resolved by a third evaluator. Twenty studies (281 patients) met the inclusion criteria for this review including 11 prospective studies (250 patients). Data suggests that ketamine decreases airway resistance, improves dynamic compliance, and preserves functional residual capacity, minute ventilation and tidal volume, while retaining protective pharyngeal and laryngeal reflexes. In patients with refractory bronchospasm, continuous infusion of intravenous ketamine decreases audible wheeze, bronchodilator requirements, and hypercarbia. It also improves respiratory rate and oxygenation, and does not promote respiratory depression. Additionally, ketamine does not result in significant perturbations in blood pressure, heart rate, or vascular resistance. Ketamine may be a safe and effective tool for maintenance sedation of mechanically ventilated patients, however a large prospective clinical trial is warranted. (Minerva Anestesiol 2011;77:812-20)
C1 [Miller, A. C.] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA.
[Miller, A. C.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Jamin, C. T.] Stanford Univ, Med Ctr, Dept Crit Care Med, Palo Alto, CA 94304 USA.
[Elamin, E. M.] James A Haley Vet Hosp, Div Pulm Crit Care & Sleep Med, Tampa, FL 33612 USA.
[Elamin, E. M.] Univ S Florida, Tampa, FL USA.
RP Miller, AC (reprint author), Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, NW 628 MUH,3459 5th Ave, Pittsburgh, PA 15213 USA.
EM taqwa1@gmail.com
OI Miller, Andrew/0000-0001-8474-5090
FU American Lung Association
FX This project was funded in part by a grant from the American Lung
Association. The opinions expressed in this manuscript represent those
of the authors, and do not represent official policy of the National
Institutes of Health.
NR 54
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U1 0
U2 5
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 0375-9393
J9 MINERVA ANESTESIOL
JI Minerva Anestesiol.
PD AUG
PY 2011
VL 77
IS 8
BP 812
EP 820
PG 9
WC Anesthesiology; Critical Care Medicine
SC Anesthesiology; General & Internal Medicine
GA 797AV
UT WOS:000293095500009
PM 21730929
ER
PT J
AU Ho, L
Miller, EL
Ronan, JL
Ho, WQ
Jothi, R
Crabtree, GR
AF Ho, Lena
Miller, Erik L.
Ronan, Jehnna L.
Ho, Wen Qi
Jothi, Raja
Crabtree, Gerald R.
TI esBAF facilitates pluripotency by conditioning the genome for LIF/STAT3
signalling and by regulating polycomb function
SO NATURE CELL BIOLOGY
LA English
DT Article
ID EMBRYONIC STEM-CELLS; CHROMATIN REMODELING COMPLEX; SELF-RENEWAL;
TRANSCRIPTIONAL ACTIVATOR; DEVELOPMENTAL REGULATORS; SWI/SNF COMPLEXES;
STAT3 ACTIVATION; GROUND-STATE; IN-VIVO; GENE
AB Signalling by the cytokine LIF and its downstream transcription factor, STAT3, prevents differentiation of pluripotent embryonic stem cells (ESCs). This contrasts with most cell types where STAT3 signalling induces differentiation. We find that STAT3 binding across the pluripotent genome is dependent on Brg1, the ATPase subunit of a specialized chromatin remodelling complex (esBAF) found in ESCs. Brg1 is required to establish chromatin accessibility at STAT3 binding targets, preparing these sites to respond to LIF signalling. Brg1 deletion leads to rapid polycomb (PcG) binding and H3K27me3-mediated silencing of many Brg1-activated targets genome wide, including the target genes of the LIF signalling pathway. Hence, one crucial role of Brg1 in ESCs involves its ability to potentiate LIF signalling by opposing PcG. Contrary to expectations, Brg1 also facilitates PcG function at classical PcG targets, including all four Hox loci, reinforcing their repression in ESCs. Therefore, esBAF does not simply antagonize PcG. Rather, the two chromatin regulators act both antagonistically and synergistically with the common goal of supporting pluripotency.
C1 [Jothi, Raja] Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Ho, Lena; Ho, Wen Qi] Stanford Univ, Program Immunol, Sch Med, Stanford, CA 94305 USA.
[Miller, Erik L.] Stanford Univ, Genet Program, Sch Med, Stanford, CA 94305 USA.
[Ronan, Jehnna L.] Stanford Univ, Program Canc Biol, Sch Med, Stanford, CA 94305 USA.
[Crabtree, Gerald R.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Crabtree, Gerald R.] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA.
[Crabtree, Gerald R.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
RP Jothi, R (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM jothi@mail.nih.gov; crabtree@stanford.edu
RI Jothi, Raja/G-3780-2015
FU HHMI; NIH [R01NS46789, R01AI60037, R01HD55391]; NIH, National Institute
of Environmental Health Sciences [1ZIAES102625-02]; A*STAR (Singapore);
National Science Foundation
FX We thank G. Bejerano, A. Wenger, D. Bristor and C. McLean for their
computational expertise and assistance, NIEHS (NIH) core facility for
their advice and expertise in carrying out ChIP-seq, and P. Wade and G.
Hu for providing useful comments. We thank J. Wu and L. Chen for
assistance in the derivation of Brg1cond ESCs. This work was
financially supported by grants from the HHMI and NIH grants R01NS46789,
R01AI60037 and R01HD55391 to G.R.C., and the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences
(1ZIAES102625-02) to R.J. L.H. and W.Q.H. are financially supported by
A*STAR (Singapore); E.L.M. and J.L.R. are financially supported by the
National Science Foundation.
NR 48
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U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD AUG
PY 2011
VL 13
IS 8
BP 903
EP U334
DI 10.1038/ncb2285
PG 31
WC Cell Biology
SC Cell Biology
GA 800OW
UT WOS:000293373700008
PM 21785422
ER
PT J
AU Morton, LM
Chanock, SJ
AF Morton, Lindsay M.
Chanock, Stephen J.
TI A step toward slaying the hydra of second cancers
SO NATURE MEDICINE
LA English
DT Editorial Material
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHEMOTHERAPY; DISEASE; RISK; RADIOTHERAPY;
ASSOCIATION; PRDM1; GENE
AB Second cancers are a substantial clinical problem in survivorship. A genome-wide association study (GWAS) in survivors of Hodgkin's lymphoma treated with radiotherapy now identifies a region of susceptibility on chromosome 6q21 (pages 941-943), paving the way for further investigations of the complex interplay between genetic susceptibility and environmental exposures involved in the development of second cancers.
C1 [Morton, Lindsay M.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
RP Morton, LM (reprint author), NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
EM chanocks@mail.nih.gov
RI Morton, Lindsay/B-5234-2015
OI Morton, Lindsay/0000-0001-9767-2310
NR 14
TC 3
Z9 3
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD AUG
PY 2011
VL 17
IS 8
BP 924
EP 925
DI 10.1038/nm.2428
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 802JW
UT WOS:000293507400018
PM 21818085
ER
PT J
AU Zhou, Q
Xiao, JM
Jiang, DW
Wang, RW
Vembaiyan, K
Wang, AX
Smith, CD
Xie, CH
Chen, WQ
Zhang, JQ
Tian, XX
Jones, PP
Zhong, XW
Guo, A
Chen, HY
Zhang, L
Zhu, WZ
Yang, DM
Li, XD
Chen, J
Gillis, AM
Duff, HJ
Cheng, HP
Feldman, AM
Song, LS
Fill, M
Back, TG
Chen, SRW
AF Zhou, Qiang
Xiao, Jianmin
Jiang, Dawei
Wang, Ruiwu
Vembaiyan, Kannan
Wang, Aixia
Smith, Chris D.
Xie, Cuihong
Chen, Wenqian
Zhang, Jingqun
Tian, Xixi
Jones, Peter P.
Zhong, Xiaowei
Guo, Ang
Chen, Haiyan
Zhang, Lin
Zhu, Weizhong
Yang, Dongmei
Li, Xiaodong
Chen, Ju
Gillis, Anne M.
Duff, Henry J.
Cheng, Heping
Feldman, Arthur M.
Song, Long-Sheng
Fill, Michael
Back, Thomas G.
Chen, S. R. Wayne
TI Carvedilol and its new analogs suppress arrhythmogenic store
overload-induced Ca2+ release
SO NATURE MEDICINE
LA English
DT Article
ID POLYMORPHIC VENTRICULAR-TACHYCARDIA; CARDIAC RYANODINE RECEPTOR;
CONGESTIVE-HEART-FAILURE; BETA-BLOCKER THERAPY; IN MOUSE MODEL;
MYOCARDIAL-INFARCTION; INTRACELLULAR CALCIUM; PURKINJE-FIBERS;
SUDDEN-DEATH; MUSCLE
AB Carvedilol is one of the most effective beta blockers for preventing ventricular tachyarrhythmias in heart failure, but the mechanisms underlying its favorable antiarrhythmic benefits remain unclear. Spontaneous Ca2+ waves, also called store overload-induced Ca2+ release (SOICR), evoke ventricular tachyarrhythmias in individuals with heart failure. Here we show that carvedilol is the only beta blocker tested that effectively suppresses SOICR by directly reducing the open duration of the cardiac ryanodine receptor (RyR2). This unique anti-SOICR activity of carvedilol, combined with its beta-blocking activity, probably contributes to its favorable antiarrhythmic effect. To enable optimal titration of carvedilol's actions as a beta blocker and as a suppressor of SOICR separately, we developed a new SOICR-inhibiting, minimally beta-blocking carvedilol analog, VK-II-86. VK-II-86 prevented stress-induced ventricular tachyarrhythmias in RyR2-mutant mice and did so more effectively when combined with either of the selective beta blockers metoprolol or bisoprolol. Combining SOICR inhibition with optimal beta blockade has the potential to provide antiarrhythmic therapy that can be tailored to individual patients.
C1 [Zhou, Qiang; Xiao, Jianmin; Jiang, Dawei; Wang, Ruiwu; Xie, Cuihong; Chen, Wenqian; Tian, Xixi; Jones, Peter P.; Zhong, Xiaowei; Zhang, Lin; Gillis, Anne M.; Duff, Henry J.; Chen, S. R. Wayne] Univ Calgary, Dept Physiol & Pharmacol, Libin Cardiovasc Inst Alberta, Calgary, AB, Canada.
[Zhou, Qiang; Xie, Cuihong; Zhang, Jingqun; Chen, Haiyan; Fill, Michael; Chen, S. R. Wayne] Rush Univ, Med Ctr, Dept Physiol & Mol Biophys, Chicago, IL 60612 USA.
[Vembaiyan, Kannan; Wang, Aixia; Smith, Chris D.; Back, Thomas G.] Univ Calgary, Dept Chem, Calgary, AB T2N 1N4, Canada.
[Guo, Ang; Song, Long-Sheng] Univ Iowa, Dept Internal Med, Carver Coll Med, Div Cardiovasc Med, Iowa City, IA 52242 USA.
[Zhu, Weizhong; Feldman, Arthur M.] Thomas Jefferson Univ, Dept Med, Ctr Translat Med, Philadelphia, PA 19107 USA.
[Yang, Dongmei; Cheng, Heping] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Li, Xiaodong; Chen, Ju] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
RP Chen, SRW (reprint author), Univ Calgary, Dept Physiol & Pharmacol, Libin Cardiovasc Inst Alberta, Calgary, AB, Canada.
EM swchen@ucalgary.ca
RI cheng, heping/A-7299-2011; Song, Long-Sheng/D-5899-2012; Jones,
Peter/G-2618-2013; Guo, Ang/M-3549-2013; Chen, Ju/E-5579-2011;
OI Guo, Ang/0000-0002-5551-2279; Duff, Henry/0000-0001-9292-5411
FU Canadian Institutes of Health Research; US National Institutes of Health
(NIH); Heart and Stroke Foundation of Alberta; US National Institute on
Aging; Alberta Innovates-Health Solutions (AIHS); Heart and Stroke
Foundation; King family; Libin Cardiovascular Institute of Alberta
FX This work was supported by grants from the Canadian Institutes of Health
Research (S. R. W. C.), the US National Institutes of Health (NIH; S. R.
W. C., L.-S.S., M. F. and A. M. F.), the Heart and Stroke Foundation of
Alberta (A. M. G. and H.J.D.) and the Intramural Research Program of the
US National Institute on Aging (D.Y. and H. Cheng). D.J., W. C. and X.
T. were supported by Alberta Innovates-Health Solutions (AIHS)
studentship awards, C. D. S. by an AIHS fellowship award, P.P.J. by an
AIHS and Heart and Stroke Foundation fellowship award and H.J.D. and S.
R. W. C. by AIHS scientist awards. We thank the King family and the
Libin Cardiovascular Institute of Alberta for their donations and S.
Pogwizd and S. Priori for critical reading of the manuscript.
NR 53
TC 86
Z9 90
U1 4
U2 26
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD AUG
PY 2011
VL 17
IS 8
BP 1003
EP U126
DI 10.1038/nm.2406
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 802JW
UT WOS:000293507400035
PM 21743453
ER
PT J
AU Riddick, G
Fine, HA
AF Riddick, Gregory
Fine, Howard A.
TI Integration and analysis of genome-scale data from gliomas
SO NATURE REVIEWS NEUROLOGY
LA English
DT Article
ID GENE-EXPRESSION PROFILES; FREQUENT EPIGENETIC INACTIVATION; MOLECULAR
SUBTYPES; HUMAN GLIOBLASTOMA; ANALYSIS REVEALS; BREAST-CANCER;
HIGH-GRADE; TUMOR-SUPPRESSOR; DRUG DISCOVERY; CORE PATHWAYS
AB Primary brain tumors are a leading cause of cancer-related mortality among young adults and children. The most common primary malignant brain tumor, glioma, carries a median survival of only 14 months. Two major multi-institutional programs, the Glioma Molecular Diagnostic Initiative and The Cancer Genome Atlas, have pursued a comprehensive genomic characterization of a large number of clinical glioma samples using a variety of technologies to measure gene expression, chromosomal copy number alterations, somatic and germline mutations, DNA methylation, microRNA, and proteomic changes. Classification of gliomas on the basis of gene expression has revealed six major subtypes and provided insights into the underlying biology of each subtype. Integration of genome-wide data from different technologies has been used to identify many potential protein targets in this disease, while increasing the reliability and biological interpretability of results. Mapping genomic changes onto both known and inferred cellular networks represents the next level of analysis, and has yielded proteins with key roles in tumorigenesis. Ultimately, the information gained from these approaches will be used to create customized therapeutic regimens for each patient based on the unique genomic signature of the individual tumor. In this Review, we describe efforts to characterize gliomas using genomic data, and consider how insights gained from these analyses promise to increase understanding of the biological underpinnings of the disease and lead the way to new therapeutic strategies.
C1 [Riddick, Gregory; Fine, Howard A.] NINDS, Neuro Oncol Branch, NCI, NIH, Bethesda, MD 20892 USA.
RP Fine, HA (reprint author), NINDS, Neuro Oncol Branch, NCI, NIH, Bloch Bldg,9030 Old Georgetown Rd, Bethesda, MD 20892 USA.
EM hfine@mail.nih.gov
NR 106
TC 44
Z9 47
U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4758
EI 1759-4766
J9 NAT REV NEUROL
JI Nat. Rev. Neurol.
PD AUG
PY 2011
VL 7
IS 8
BP 439
EP 450
DI 10.1038/nrneurol.2011.100
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA 803YK
UT WOS:000293618800008
PM 21727940
ER
PT J
AU Wallen, GR
Cusack, G
Parada, S
Miller-Davis, C
Cartledge, T
Yates, J
AF Wallen, Gwenyth R.
Cusack, Georgie
Parada, Suzan
Miller-Davis, Claiborne
Cartledge, Tannia
Yates, Jan
TI Evaluating a hybrid web-based basic genetics course for health
professionals
SO NURSE EDUCATION TODAY
LA English
DT Article
DE Genetics education; WEBLEI; Web-based nursing education
ID NURSING-EDUCATION; GENOMIC MEDICINE; CORE COMPETENCES; RECOMMENDATIONS;
PRIMER
AB Health professionals, particularly nurses, continue to struggle with the expanding role of genetics information in the care of their patients. This paper describes an evaluation study of the effectiveness of a hybrid basic genetics course for healthcare professionals combining web-based learning with traditional face-to-face instructional techniques. A multidisciplinary group from the National Institutes of Health (NIH) created "Basic Genetics Education for Healthcare Providers" (BGEHCP). This program combined 7 web-based self-education modules with monthly traditional face-to-face lectures by genetics experts. The course was pilot tested by 186 healthcare providers from various disciplines with 69% (n = 129) of the class registrants enrolling in a pre-post evaluation trial. Outcome measures included critical thinking knowledge items and a Web-based Learning Environment Inventory (WEBLEI). Results indicated a significant (p < 0.001) change in knowledge scores. WEBLEI scores indicated program effectiveness particularly in the area of convenience, access and the course structure and design. Although significant increases in overall knowledge scores were achieved, scores in content areas surrounding genetic risk identification and ethical issues regarding genetic testing reflected continued gaps in knowledge. Web-based genetics education may help overcome genetics knowledge deficits by providing access for health professionals with diverse schedules in a variety of national and international settings. Published by Elsevier Ltd.
C1 [Wallen, Gwenyth R.; Cusack, Georgie; Parada, Suzan; Miller-Davis, Claiborne; Cartledge, Tannia] NIH, Ctr Clin, Nursing Serv, Bethesda, MD 20892 USA.
[Cusack, Georgie; Parada, Suzan; Miller-Davis, Claiborne; Cartledge, Tannia] NIH, Ctr Clin, Patient Care Serv, Bethesda, MD 20892 USA.
RP Wallen, GR (reprint author), NIH, Ctr Clin, Nursing Serv, 10 Ctr Dr,Room 2B14,MSC-1151, Bethesda, MD 20892 USA.
EM GWallen@cc.nih.gov; GCusack@cc.nih.gov; SParada@cc.nih.gov;
CDavis@cc.nih.gov; TCartledge@cc.nih.gov; jmyates@comcast.net
FU National Institutes of Health, Clinical Center, Nursing Research and
Translational Science, Nursing and Patient Care Services
FX We gratefully acknowledge Dr. Paul Hoernes Somerset, previously at the
National Institutes of Health Clinical Center, for his leadership and
expertise in the development of the electronic media and graphics for
the basic genetic modules and to Linda McCullagh, RN, MPH for her
support and collaboration during the study. We are also grateful for the
invaluable genetic expertise and mentorship provided by Dr. Donna
Krasnewich, Dr. Alan Guttmacher, and Dr. Jean Jenkins of the National
Human Genome Research Institute during this study. This work was
supported by the National Institutes of Health, Clinical Center, Nursing
Research and Translational Science, Nursing and Patient Care Services.
NR 29
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U1 1
U2 3
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0260-6917
EI 1532-2793
J9 NURS EDUC TODAY
JI Nurse Educ. Today
PD AUG
PY 2011
VL 31
IS 6
BP 638
EP 642
DI 10.1016/j.nedt.2010.11.001
PG 5
WC Education, Scientific Disciplines; Nursing
SC Education & Educational Research; Nursing
GA 801JL
UT WOS:000293434600020
PM 21106279
ER
PT J
AU Liew, G
Campbell, S
Klein, R
Klein, BEK
Sharrett, AR
Cotch, MF
Wang, JJ
Wong, TY
AF Liew, Gerald
Campbell, Stephen
Klein, Ronald
Klein, Barbara E. K.
Sharrett, A. Richey
Cotch, Mary Frances
Wang, Jie Jin
Wong, Tien Y.
TI Ten-Year Longitudinal Changes in Retinal Microvascular Lesions The
Atherosclerosis Risk in Communities Study
SO OPHTHALMOLOGY
LA English
DT Article
ID CORONARY-HEART-DISEASE; HYPERTENSIVE RETINOPATHY; ABNORMALITIES;
POPULATION; MORTALITY; EYE; STROKE; SIGNS; HOORN
AB Objective: There are limited data on the natural history and longitudinal changes of retinal microvascular lesions. We examined 10-year changes in retinal microvascular lesions, focusing on those related to hypertension and shown to predict development of cardiovascular disease.
Design: Prospective cohort.
Participants: We included 1120 middle-aged participants without diabetes of the Atherosclerosis Risk in Communities (ARIC) Study in 1993 to 1995 and again 10 years later in 2003 to 2005.
Methods: Retinal microvascular lesions were graded from retinal photographs using the same protocol at both examinations, with changes (incidence or disappearance) adjudicated by a side-by-side comparison of photographs. The study sample was stratified by carotid intima media thickness (IMT) and ARIC field center; thus, all analyses were weighted by these factors. Persons with diabetes were excluded because the frequency and pathophysiology of diabetic retinal lesions is different.
Main Outcome Measures: Incidence and disappearance rates of lesions.
Results: The 10-year incidence of focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy in persons without diabetes was 3.4% (95% confidence interval [CI], 2.3-4.9), 2.5% (95% CI, 1.6-3.9), and 2.2% (95% CI, 1.3-3.5) respectively. Over the 10-year period, of 32, 219, and 24 eyes with focal arteriolar narrowing, AV nicking and retinopathy at baseline, 50.3% (95% CI, 28.6-71.9), 40.7% (95% CI, 32.7-49.4), and 65.9% (95% CI, 42.4-83.5), respectively, disappeared. Higher baseline plasma fibrinogen and white cell counts were associated with incident focal arteriolar narrowing; antihypertensive medication use was associated with incident AV nicking, and higher diastolic blood pressure, carotid IMT, and white cell counts were associated with incident retinopathy. Higher fasting serum glucose was not significantly associated with incident retinopathy, although this may be related to the small number of lesions (odds ratio, 5.88; 95% CI, 0.74-46.64 per standard deviation difference).
Conclusions: In this sample of middle-aged adults, new retinal microvascular lesions appeared at a rate between 2% and 4% over 10 years. A high percentage of lesions (>= 40%) disappeared over the same period, suggesting considerable remodeling in the retinal microvasculature.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2011; 118: 1612-1618 (C) 2011 by the American Academy of Ophthalmology.
C1 [Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117595, Singapore.
[Liew, Gerald; Wang, Jie Jin] Univ Sydney, Ctr Vis Res, Sydney, NSW 2006, Australia.
[Liew, Gerald; Wang, Jie Jin; Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3010, Australia.
[Campbell, Stephen] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Sharrett, A. Richey] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Wong, TY (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, 11 3rd Hosp Ave, Singapore 117595, Singapore.
EM ophwty@nus.edu.sg
RI Wang, Jie Jin/P-1499-2014;
OI Wang, Jie Jin/0000-0001-9491-4898; Cotch, Mary
Frances/0000-0002-2046-4350; Klein, Ronald/0000-0002-4428-6237
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];
NHBLI [R21-HL077166]; National Institutes of Health [Z01EY000426];
Australian National Health and Medical Research Council Centre for
Clinical Research Excellence [529923]; Singapore National Medical
Research Council [STaR/0003/2008]
FX Supported by National Heart, Lung, and Blood Institute contracts
N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021, and N01-HC-55022. Additional support was provided by NHBLI
grant R21-HL077166 (TYW) and the National Institutes of Health
Intramural Research Award Z01EY000426 (MFC), the Australian National
Health and Medical Research Council Centre for Clinical Research
Excellence #529923 (TYW) and the Singapore National Medical Research
Council STaR/0003/2008 (TYW). CERA receives Operation Infrastructure
Support for the Victorian Government.
NR 32
TC 8
Z9 9
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD AUG
PY 2011
VL 118
IS 8
BP 1612
EP 1618
DI 10.1016/j.ophtha.2011.01.003
PG 7
WC Ophthalmology
SC Ophthalmology
GA 800TT
UT WOS:000293390900019
PM 21529953
ER
PT J
AU Coghill, M
Ambalavanan, N
Chatburn, RL
Hibberd, PL
Wright, LL
Carlo, WA
AF Coghill, Matthew
Ambalavanan, Namasivayam
Chatburn, Robert L.
Hibberd, Patricia L.
Wright, Linda L.
Carlo, Waldemar A.
CA Eunice Kennedy Shriver Natl Inst
Global Network Womens Childrens
TI Accuracy of a Novel System for Oxygen Delivery to Small Children
SO PEDIATRICS
LA English
DT Article
DE Venturi; infants; mortality; pneumonia; developing countries;
entrainment
ID EMERGENCY CARDIOVASCULAR CARE; PAPUA-NEW-GUINEA;
CARDIOPULMONARY-RESUSCITATION; DEVELOPING-COUNTRIES;
PERINATAL-MORTALITY; RESPIRATORY FAILURE; NASAL CANNULA; INFANTS; AIR;
PERFORMANCE
AB OBJECTIVE: Oxygen therapy for infants and small children in developing countries is often not available. Entrainment devices may provide an accurate and precise concentration of oxygen when used at the flow rates appropriate for infants and small children.
METHODS: A continuously adjustable entrainment device was tested to determine the concentrations and flows of oxygen delivered by using low inlet flow rates suitable for therapy for infants and small children and 3 distinct oxygen delivery systems that varied in their resistive load.
RESULTS: The use of long and large bore, low resistance tubing (similar to a mask) resulted in the delivery of oxygen concentrations that tracked closely (accurate and precise) to values indicated by the entrainment device. The directly connected system with lower resistance (similar to a hood) produced a similar profile of concentrations and flow rates to the large bore tubing but with even greater accuracy. The use of a long and narrow tubing with higher resistance (similar to a cannula) did not deliver accurate oxygen concentrations. In fact, this high-resistance system failed to work as intended, and instead of entraining air, a large proportion (sometimes >50%) of the oxygen delivered to the entrainment device was ejected through its vents.
CONCLUSIONS: Entrainment devices can deliver accurate oxygen concentrations at low flow rates if used with low resistance delivery systems; however, entrainment devices are not suitable for use with high resistance delivery systems such as a standard nasal cannula. Pediatrics 2011;128:e382-e387
C1 [Coghill, Matthew; Ambalavanan, Namasivayam; Carlo, Waldemar A.] Univ Alabama, Dept Pediat, Birmingham, AL 35233 USA.
[Chatburn, Robert L.] Cleveland Clin, Cleveland, OH 44106 USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Carlo, WA (reprint author), Univ Alabama, Dept Pediat, 1700 6th Ave S,176F Suite 9380R, Birmingham, AL 35233 USA.
EM wcarlo@peds.uab.edu
OI Ambalavanan, Namasivayam/0000-0003-0731-9092
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development Global Network for Women's and Children's Health Research
[HD43475, HD40636]
FX This work was supported by grants from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development Global Network
for Women's and Children's Health Research (HD43475 and HD40636).
NR 38
TC 1
Z9 1
U1 0
U2 1
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD AUG
PY 2011
VL 128
IS 2
BP E382
EP E387
DI 10.1542/peds.2010-3745
PG 6
WC Pediatrics
SC Pediatrics
GA 800CK
UT WOS:000293336200015
PM 21727103
ER
PT J
AU Allen, MD
Neumann, S
Gershengorn, MC
AF Allen, Michael D.
Neumann, Susanne
Gershengorn, Marvin C.
TI Small-Molecule Thyrotropin Receptor Agonist Activates Naturally
Occurring Thyrotropin-Insensitive Mutants and Reveals Their Distinct
Cyclic Adenosine Monophosphate Signal Persistence
SO THYROID
LA English
DT Article
ID NONAUTOIMMUNE SUBCLINICAL HYPOTHYROIDISM; TSH RECEPTOR; MUTATIONS; CAMP;
RESISTANCE; CELLS; GENE
AB Background: Subclinical hypothyroidism (SHT), characterized by normal thyroid hormone levels maintained by elevated thyrotropin (TSH), predisposes patients to health problems as they age. Some cases arise from mutations of the TSH receptor (TSHR) that confer TSH resistance. This resistance might be circumvented by TSHR agonists with different modes of binding compared with TSH. We hypothesized that the recently discovered small-molecule TSHR agonist C2, with its unique mode of receptor binding, would activate mutant TSHRs associated with SHT, facilitating their study.
Materials and Methods: HEK-EM293 cells transiently expressing TSHR variants-wild-type TSHR or mutants C41S, L252P, L467P, or C600R-were analyzed for TSH or C2-induced cyclic adenosine monophosphate (cAMP) signaling to establish C2 as a mutant TSHR agonist. These cells were also pretreated with TSH or C2 to characterize each mutant receptor's ability to maintain and desensitize cAMP signaling.
Results: We showed that C2 could activate the TSH-unresponsive TSHR ectodomain mutants C41S and L252P but had no effect on the serpentine mutant L467P. We found that TSH and C2 could acutely activate the serpentine mutant C600R. Preincubation with C2 caused persistent cAMP signaling and receptor desensitization in wild-type TSHR and cAMP signal persistence with no detectable desensitization in the cases of C41S and L252P.
Conclusions: The small-molecule agonist C2 is a useful pharmacological tool for the study of mutant TSHRs. It revealed that some naturally occurring TSH-insensitive mutants can mediate induction of cAMP elevation upon stimulation with C2 and that this signal is differentially maintained within cells.
C1 [Allen, Michael D.; Neumann, Susanne; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
RP Gershengorn, MC (reprint author), NIDDK, Clin Endocrinol Branch, NIH, 50 South Dr,Bldg 50,Room 4134, Bethesda, MD 20892 USA.
EM MarvinG@intra.niddk.nih.gov
FU U.S. National Institutes of Health [1 Z01 DK011006]
FX This research was supported by the Intramural Research Program of the
U.S. National Institutes of Health (1 Z01 DK011006).
NR 16
TC 7
Z9 9
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD AUG
PY 2011
VL 21
IS 8
BP 907
EP 912
DI 10.1089/thy.2011.0025
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 801LW
UT WOS:000293441400012
PM 21745101
ER
PT J
AU O'Mara, TA
Ferguson, K
Fahey, P
Marquart, L
Yang, HP
Lissowska, J
Chanock, S
Garcia-Closas, M
Thompson, DJ
Healey, CS
Dunning, AM
Easton, DF
Webb, PM
Spurdle, AB
AF O'Mara, Tracy A.
Ferguson, Kaltin
Fahey, Paul
Marquart, Louise
Yang, Hannah P.
Lissowska, Jolanta
Chanock, Stephen
Garcia-Closas, Montserrat
Thompson, Deborah J.
Healey, Catherine S.
Dunning, Alison M.
Easton, Douglas F.
Webb, Penelope M.
Spurdle, Amanda B.
CA ANECS
TI CHEK2, MGMT, SULT1E1 and SULT1A1 Polymorphisms and Endometrial Cancer
Risk
SO TWIN RESEARCH AND HUMAN GENETICS
LA English
DT Article
DE endometrial cancer; single nucleotide polymorphism; CHEK2; MGMT;
SULT1E1; SULT1A1
ID WIDE ASSOCIATION ANALYSIS; VARIANTS
AB Several single nucleotide polymorphisms (SNPs) in candidate genes of DNA repair and hormone pathways have been reported to be associated with endometrial cancer risk. We sought to confirm these associations in two endometrial cancer case-control sample sets and used additional data from an existing genome-wide association study to prioritize an additional SNP for further study. Five SNPs from the CHEK2, MGMT, SULT1E1 and SULT1A1 genes, genotyped in a total of 1597 cases and 1507 controls from two case-control studies, the Australian National Endometrial Cancer Study and the Polish Endometrial Cancer Study, were assessed for association with endometrial cancer risk using logistic regression analysis. Imputed data was drawn for CHEK2 rs8135424 for 666 cases from the Study of Epidemiology and Risk factors in Cancer Heredity study and 5190 controls from the Wellcome Trust Case Control Consortium. We observed no association between SNPs in the MGMT, SULT1E1 and SULT1A1 genes and endometrial cancer risk. The A allele of the rs8135424 CHEK2 SNP was associated with decreased risk of endometrial cancer (adjusted per-allele OR 0.83; 95%CI 0.70-0.98; p = .03) however this finding was opposite to that previously published. Imputed data for CHEK2 rs8135424 supported the direction of effect reported in this study (OR 0.85; 95% CI 0.65-1.10). Previously reported endometrial cancer risk associations with SNPs from in genes involved in estrogen metabolism and DNA repair were not replicated in our larger study population. This study highlights the need for replication of candidate gene SNP studies using large sample groups, to confirm risk associations and better prioritize downstream studies to assess the causal relationship between genetic variants and cancer risk. Our findings suggest that the CHEK2 SNP rs8135424 be prioritized for further study as a genetic factor associated with risk of endometrial cancer.
C1 [O'Mara, Tracy A.; Ferguson, Kaltin; Webb, Penelope M.; Spurdle, Amanda B.] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia.
[O'Mara, Tracy A.] Queensland Univ Technol, Hormone Dependent Canc Program, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
[Fahey, Paul; Marquart, Louise] Queensland Inst Med Res, Stat Unit, Brisbane, Qld 4006, Australia.
[Yang, Hannah P.; Chanock, Stephen; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Thompson, Deborah J.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England.
[Healey, Catherine S.; Dunning, Alison M.] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge, England.
RP Spurdle, AB (reprint author), Queensland Inst Med Res, Genet & Populat Hlth Div, 300 Herston Rd, Brisbane, Qld 4006, Australia.
EM Amanda.Spurdle@qimr.edu.au
RI Fahey, Paul/B-7985-2013; Webb, Penelope/D-5736-2013; Nicklin,
James/F-8035-2013; Garcia-Closas, Montserrat /F-3871-2015; O'Mara,
Tracy/M-7508-2016; Spurdle, Amanda/A-4978-2011;
OI Fahey, Paul/0000-0002-6351-9876; Dunning, Alison
Margaret/0000-0001-6651-7166; Webb, Penelope/0000-0003-0733-5930;
Nicklin, James/0000-0001-5378-496X; Garcia-Closas, Montserrat
/0000-0003-1033-2650; O'Mara, Tracy/0000-0002-5436-3232; Quinn,
Michael/0000-0003-0694-3870; Spurdle, Amanda/0000-0003-1337-7897;
Lissowska, Jolanta/0000-0003-2695-5799
FU National Health and Medical Research Council (NHMRC) of Australia
[339435]; Cancer Council Queensland [4196615]; Cancer Council Tasmania
[403031, 457636]; NHMRC; Australian Postgraduate Award; Institute of
Health and Biomedical Innovation; US National Cancer Institute, Division
of Cancer Epidemiology and Genetics in the Hormonal and Reproductive
Epidemiology Branch; Cancer Research UK [C490/A11021, C8197/A10123,
C1287/A7497, C1287/A10118]; BCC [2077NovPR17]; EU
[HEALTH-F2-2009-223175]; Cancer Research Grant [C8197/A10865]; The
Joseph Mitchell Trust
FX ANECS was supported by project grants from the National Health and
Medical Research Council (NHMRC) of Australia (ID#339435), The Cancer
Council Queensland (ID#4196615) and Cancer Council Tasmania (ID#403031
and ID#457636). ABS and PMW are supported by NHMRC Senior Research
Fellowships. TOM is supported by an Australian Postgraduate Award, an
Institute of Health and Biomedical Innovation PhD Top-Up and a Smart
State PhD Award. PECS was funded by the intramural research program at
the US National Cancer Institute, Division of Cancer Epidemiology and
Genetics in the Hormonal and Reproductive Epidemiology Branch. SEARCH
was funded by Cancer Research UK grants [C490/A11021, C8197/A10123,
C1287/A7497, C1287/A10118], BCC grant [2077NovPR17] and EU FP7 COGS
[HEALTH-F2-2009-223175]. AMD was supported by Cancer Research Grant
[C8197/A10865] and The Joseph Mitchell Trust.
NR 14
TC 8
Z9 8
U1 0
U2 7
PU AUSTRALIAN ACAD PRESS
PI BOWEN HILLS
PA 32 JEAYS ST, BOWEN HILLS, QLD 4006, AUSTRALIA
SN 1832-4274
J9 TWIN RES HUM GENET
JI Twin Res. Hum. Genet.
PD AUG
PY 2011
VL 14
IS 4
BP 328
EP 332
DI 10.1375/twin.14.4.328
PG 5
WC Genetics & Heredity; Obstetrics & Gynecology
SC Genetics & Heredity; Obstetrics & Gynecology
GA 803UF
UT WOS:000293606400005
PM 21787115
ER
PT J
AU Heidari, S
Mofenson, L
Cotton, MF
Marlink, R
Cahn, P
Katabira, E
AF Heidari, Shirin
Mofenson, Lynne
Cotton, Mark F.
Marlink, Richard
Cahn, Pedro
Katabira, Elly
TI Antiretroviral Drugs for Preventing Mother-to-Child Transmission of HIV:
A Review of Potential Effects on HIV-Exposed but Uninfected Children
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Review
DE antiretroviral; PMTCT; HIV-exposed uninfected infants; childhood growth
and development; drug complications
ID TRANSCRIPTASE INHIBITOR EXPOSURE; MATERNAL-INFANT TRANSMISSION;
LOW-BIRTH-WEIGHT; INFECTED WOMEN; IN-UTERO; MITOCHONDRIAL DYSFUNCTION;
PERINATAL EXPOSURE; CONGENITAL-ABNORMALITIES; HIV-1-INFECTED WOMEN;
PRETERM DELIVERY
AB The provision of antiretroviral drugs for the prevention of mother-to-child HIV transmission has been rising sharply in low-and middle-income countries. Changes to the World Health Organization guidelines support further extension of these programs. The result will be a greatly expanded population of HIV-exposed but uninfected children with substantial exposure to antiretroviral drugs, both in utero and while breastfeeding. There are limited data on possible toxicities in this burgeoning population, and the large number of confounding factors limits any conclusions. Although the evidence on birth defects and mitochondrial toxicity remains equivocal, considerable data link protease inhibitors to preterm delivery and low birth-weight. Transient hematologic toxicities are also likely. The drug impact later in life is an open question. Larger and longer cohort studies are necessary to properly balance the risks and benefits of large-scale infant exposure to antiretroviral agents.
C1 [Heidari, Shirin] Int AIDS Soc, Dept Res Promot, CH-1216 Geneva, Switzerland.
[Mofenson, Lynne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Cotton, Mark F.] Univ Stellenbosch, Dept Paediat & Child Hlth, Cape Town, South Africa.
[Cotton, Mark F.] Tygerberg Childrens Hosp, Cape Town, South Africa.
[Marlink, Richard] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Marlink, Richard] Elizabeth Glaser Pediat AIDS Fdn, Los Angeles, CA USA.
[Cahn, Pedro] Fdn Huesped, Buenos Aires, DF, Argentina.
[Katabira, Elly] Makerere Univ, Coll Hlth Sci, Kampala, Uganda.
RP Heidari, S (reprint author), Int AIDS Soc, Dept Res Promot, 71 Ave Louis Casai, CH-1216 Geneva, Switzerland.
EM shirin.heidari@iasociety.org
OI Mofenson, Lynne/0000-0002-2818-9808
FU Abbott; Boehringer Ingelheim; Gilead; Merck; Pfizer; Tibotec;
International AIDS Society
FX S. Heidari is an employee of the International AIDS Society, which
receives unrestricted educational grants from the following
pharmaceutical companies: Abbott, Boehringer Ingelheim, Gilead, Merck,
Pfizer and Tibotec. E. Katabira and L. Mofenson have no competing
interests. M. F. Cotton is an investigator on Tibotec, GSK, and
Boehringer Ingelheim trials. R. Marlink has served as an advisor to the
BMS Foundation and the Merck Company Foundation. P. Cahn has served as
Advisory Board member in Avexa, Gilead, GSK, Myriad, Merck, Pfizer,
Pharmasset, Schering Plough, Tibotec; Investigator in Avexa, Boehringer
Ingelheim, Gilead, GSK, Roche, Merck, Pfizer, Pharmasset, Schering
Plough, Tibotec, Abbott, BMS; Speaker (content and design performed by
the speaker, no company control) for Abbott, BMS, Boehringer Ingelheim,
GSK, Merck, Pfizer, Tibotec; and Scientific Advisor for Merck Sharp &
Dohme, Pfizer, GSK, Avexa, Tibotec. He is not a shareholder, nor does he
have any commercial interest or investment in any pharmaceutical
company.; This literature review is a result of a mapping exercise and a
consultation process initiated by the International AIDS
Society-Industry Liaison forum that resulted in the Environmental Scan,
"Mapping HIV Research Priorities for Women and Children"
(http://www.iasociety.org/Web/WebContent/File/ILF_Environmental_Scan_Jul
y2010.pdf) and the Consensus Statement, "Asking the Right Question:
Advancing an HIV Research Agenda for Women and Children"
(http://www.iasociety.org/Web/WebContent/File/Consensus_Statement_Asking
_the_Right_Question_March_2010.pdf). The Consensus Statement was
released by the IAS and the following organizations: AVAC, Global
Advocacy for HIV Prevention; Boehringer Ingelheim; Clinton Health Access
Initiative; Coalition on Children Affected by AIDS; Elizabeth Glaser
Pediatric AIDS Foundation; European AIDS Treatment Group; International
Community of Women Living with HIV/AIDS; International Treatment
Preparedness Coalition; Merck; Treatment Action Group; The United
Nations Programme on HIV/AIDS (UNAIDS); The United Nations Children's
Education Fund (UNICEF); ViiV Healthcare; and WHO. The mapping exercise
was financially supported by unrestricted educational grants from
Abbott, Boehringer Ingelheim, Gilead, Merck, Pfizer, and Tibotec,
including the International AIDS Society. The authors are grateful for
their support.
NR 57
TC 46
Z9 46
U1 0
U2 8
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 AUG 1
PY 2011
VL 57
IS 4
BP 290
EP 296
DI 10.1097/QAI.0b013e318221c56a
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 782TD
UT WOS:000292033500011
PM 21602695
ER
PT J
AU Taha, TE
Li, Q
Hoover, DR
Mipando, L
Nkanaunena, K
Thigpen, MC
Taylor, A
Kumwenda, J
Fowler, MG
Mofenson, LM
Kumwenda, NI
AF Taha, Taha E.
Li, Qing
Hoover, Donald R.
Mipando, Linda
Nkanaunena, Kondwani
Thigpen, Michael C.
Taylor, Allan
Kumwenda, Johnstone
Fowler, Mary Glenn
Mofenson, Lynne M.
Kumwenda, Newton I.
TI Postexposure Prophylaxis of Breastfeeding HIV-Exposed Infants With
Antiretroviral Drugs to Age 14 Weeks: Updated Efficacy Results of the
PEPI-Malawi Trial
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE breastfeeding; infant postexposure prophylaxis; mother-to-child
transmission of HIV; PEPI-Malawi
ID INFECTED WOMEN; TRANSMISSION; MORTALITY; GASTROENTERITIS; BOTSWANA;
CHILDREN; UGANDA; BORN; RISK; MILK
AB Background: This analysis updates and extends efficacy estimates of the PEPI-Malawi trial through age 24 months at study completion in September 2009.
Methods: Infants of breastfeeding HIV-infected women were randomized at birth to the following: (1) single-dose nevirapine (NVP) + 1-week zidovudine (ZDV) (control); (2) control + extended daily NVP (ExtNVP) through 14 weeks; (3) control + extended daily NVP + ZDV (ExtNVP/ZDV) through 14 weeks. We estimated rates of HIV infection, death and HIV infection, or death using Kaplan-Meier analysis.
Results: This analysis includes 3126 infants uninfected at birth as follows: 1004 control, 1071 ExtNVP, and 1051 ExtNVP/ZDV. By 9 months, HIV infection rates were 5.0% in ExtNVP, 6.0% in ExtNVP/ZDV, and 11.1% in control (P < 0.001 comparing extended regimens with control). At age 24 months, HIV infection rates had risen to; 11% in the extended arms compared with 15.6% in the controls (P, 0.05). The rates of HIV infection or death were also significantly lower in extended arms. There were no differences in severe adverse events with the exception of higher possibly related events in the ExtNVP/ZDV arm.
Conclusions: Daily infant antiretroviral prophylaxis reduces postnatal HIV infection by similar to 70% during the period of prophylaxis. But continued HIV transmission after prophylaxis stops suggests more prolonged infant prophylaxis is needed.
C1 [Taha, Taha E.; Kumwenda, Newton I.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Li, Qing] NHGRI, Inherited Dis Branch, NIH, Baltimore, MD USA.
[Hoover, Donald R.] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA.
[Hoover, Donald R.] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ USA.
[Mipando, Linda; Nkanaunena, Kondwani] Johns Hopkins Univ, Res Project, Coll Med, Ctr Res Mothers & Children, Blantyre, Malawi.
[Thigpen, Michael C.; Taylor, Allan] Ctr Dis Control & Prevent, Natl Ctr HIV Viral Hepatitis STD & TB Prevent, Div HIV AIDS Prevent, Atlanta, GA USA.
[Kumwenda, Johnstone] Univ Malawi, Coll Med, Dept Internal Med, Blantyre, Malawi.
[Fowler, Mary Glenn] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Taha, TE (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Rm E7138,615 N Wolfe St, Baltimore, MD 21205 USA.
EM ttaha@jhsph.edu
OI Mofenson, Lynne/0000-0002-2818-9808
FU Centers for Disease Control and Prevention [5 U50 PS022061-05,
U50/CC0222061]; Eunice Kennedy Shriver National Institute of Child
Health and Human Development, National Institutes of Health; National
Human Genome Research Institute, National Institutes of Health
FX Supported by a Cooperative Agreement (# 5 U50 PS022061-05; Award #
U50/CC0222061) from the Centers for Disease Control and Prevention and
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health. Qing Li was supported in
part by the Intramural Research Program of the National Human Genome
Research Institute, National Institutes of Health.
NR 17
TC 22
Z9 22
U1 0
U2 1
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 AUG 1
PY 2011
VL 57
IS 4
BP 319
EP 325
DI 10.1097/QAI.0b013e318217877a
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 782TD
UT WOS:000292033500016
PM 21423025
ER
PT J
AU Tsai, CJ
Nussinov, R
AF Tsai, Chung-Jung
Nussinov, Ruth
TI A unified convention for biological assemblies with helical symmetry
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID ELECTRON-MICROSCOPY; FILAMENTOUS BACTERIOPHAGE; RECONSTRUCTION; CRYOEM;
A-BETA(1-40); DIFFRACTION; CORE
AB Assemblies with helical symmetry can be conveniently formulated in many distinct ways. Here, a new convention is presented which unifies the two most commonly used helical systems for generating helical assemblies from asymmetric units determined by X-ray fibre diffraction and EM imaging. A helical assembly is viewed as being composed of identical repetitive units in a one- or two-dimensional lattice, named 1-D and 2-D helical systems, respectively. The unification suggests that a new helical description with only four parameters [n(1), n(2), twist, rise], which is called the augmented 1-D helical system, can generate the complete set of helical arrangements, including coverage of helical discontinuities (seams). A unified four-parameter characterization implies similar parameters for similar assemblies, can eliminate errors in reproducing structures of helical assemblies and facilitates the generation of polymorphic ensembles from helical atomic models or EM density maps. Further, guidelines are provided for such a unique description that reflects the structural signature of an assembly, as well as rules for manipulating the helical symmetry presentation.
C1 [Tsai, Chung-Jung; Nussinov, Ruth] NCI Frederick, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Tsai, CJ (reprint author), NCI Frederick, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA.
EM tsaic@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX We would like to thank Dr Edward Egelman for discussions and in
particular for his insightful comments, which helped us in improving the
paper. This project has been funded in whole or in part with Federal
funds from the National Cancer Institute, National Institutes of Health
under contract No. HHSN261200800001E. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government. This
research was supported (in part) by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research.
NR 29
TC 0
Z9 1
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0907-4449
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD AUG
PY 2011
VL 67
BP 716
EP 728
DI 10.1107/S0907444911024024
PN 8
PG 13
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 798GF
UT WOS:000293189900006
PM 21795813
ER
PT J
AU Fischer, MJ
Go, AS
Lora, CM
Ackerson, L
Cohan, J
Kusek, JW
Mercado, A
Ojo, A
Ricardo, AC
Rosen, LK
Tao, KX
Xie, DW
Feldman, HI
Lash, JP
AF Fischer, Michael J.
Go, Alan S.
Lora, Claudia M.
Ackerson, Lynn
Cohan, Janet
Kusek, John W.
Mercado, Alejandro
Ojo, Akinlolu
Ricardo, Ana C.
Rosen, Leigh K.
Tao, Kaixiang
Xie, Dawei
Feldman, Harold I.
Lash, James P.
CA CRIC Grp
H-CRIC Study Grp
TI CKD in Hispanics: Baseline Characteristics From the CRIC (Chronic Renal
Insufficiency Cohort) and Hispanic-CRIC Studies
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Chronic kidney disease; Hispanics; epidemiology
ID NUTRITION EXAMINATION SURVEY; CHRONIC KIDNEY-DISEASE; 3RD
NATIONAL-HEALTH; UNITED-STATES; HEMODIALYSIS-PATIENTS;
DIABETIC-NEPHROPATHY; SURVIVAL ADVANTAGE; RACIAL-DIFFERENCES;
MEXICAN-AMERICANS; DIALYSIS OUTCOMES
AB Background: Little is known regarding chronic kidney disease (CKD) in Hispanics. We compared baseline characteristics of Hispanic participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies with non-Hispanic CRIC participants.
Study Design: Cross-sectional analysis.
Setting & Participants: Participants were aged 21-74 years with CKD using age-based estimated glomerular filtration rate (eGFR) at enrollment into the CRIC/H-CRIC Studies. H-CRIC included Hispanics recruited at the University of Illinois in 2005-2008, whereas CRIC included Hispanics and non-Hispanics recruited at 7 clinical centers in 2003-2007.
Factor: Race/ethnicity.
Outcomes: Blood pressure, angiotensin-converting enzyme (ACE)-inhibitor/angiotensin receptor blocker (ARB) use, and CKD-associated complications.
Measurements: Demographic characteristics, laboratory data, blood pressure, and medications were assessed using standard techniques and protocols.
Results: Of H-CRIC/CRIC participants, 497 were Hispanic, 1,650 were non-Hispanic black, and 1,638 were non-Hispanic white. Low income and educational attainment were nearly twice as prevalent in Hispanics compared with non-Hispanics (P < 0.01). Hispanics had self-reported diabetes (67%) more frequently than non-Hispanic blacks (51%) and whites (40%; P < 0.01). Blood pressure > 130/80 mm Hg was more common in Hispanics (62%) than blacks (57%) and whites (35%; P < 0.05), and abnormalities in hematologic, metabolic, and bone metabolism parameters were more prevalent in Hispanics (P < 0.05), even after stratifying by entry eGFR. Hispanics had the lowest use of ACE inhibitors/ARBs among the high-risk subgroups, including participants with diabetes, proteinuria, and blood pressure > 130/80 mm Hg. Mean eGFR was lower in Hispanics (39.6 mL/min/1.73 m(2)) than in blacks (43.7 mL/min/1.73 m(2)) and whites (46.2 mL/min/1.73 m(2)), whereas median proteinuria was higher in Hispanics (protein excretion, 0.72 g/d) than in blacks (0.24 g/d) and whites (0.12 g/d; P < 0.01).
Limitations: Generalizability; observed associations limited by residual bias and confounding.
Conclusions: Hispanics with CKD in the CRIC/H-CRIC Studies are disproportionately burdened with lower socioeconomic status, more frequent diabetes mellitus, less ACE-inhibitor/ARB use, worse blood pressure control, and more severe CKD and associated complications than their non-Hispanic counterparts. Am J Kidney Dis. 58(2): 214-227. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.
C1 [Fischer, Michael J.; Lora, Claudia M.; Cohan, Janet; Mercado, Alejandro; Ricardo, Ana C.; Lash, James P.] Jesse Brown VA Med Ctr, Chicago, IL USA.
[Fischer, Michael J.; Lora, Claudia M.; Cohan, Janet; Mercado, Alejandro; Ricardo, Ana C.; Lash, James P.] Univ Illinois, Med Ctr, Chicago, IL USA.
[Fischer, Michael J.] VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA.
[Go, Alan S.; Ackerson, Lynn] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Kusek, John W.] NIDDK, NIH, Bethesda, MD USA.
[Ojo, Akinlolu] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Rosen, Leigh K.; Tao, Kaixiang; Xie, Dawei; Feldman, Harold I.] Univ Penn, Ctr Clin Epidemiol & Biostatist, Philadelphia, PA 19104 USA.
[Feldman, Harold I.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
RP Fischer, MJ (reprint author), Hines VA Hosp, Ctr Management Complex Chron Care, 5000 S 5th Ave 151H, Hines, IL 60141 USA.
EM fischerm@uic.edu
FU NIDDK [5U01DK060990, 5U01DK060902, R01 DK072231]; National Institutes of
Health (NIH) [UL1 RR-025005]; General Clinical Research Center (GCRC)
[M01 RR-16500]; UL1 RR-024989; GCRC [M01 RR-000042]; CTSA [UL1
RR-024986, M01 RR-013987-06, UL1 RR-024134, UL1 RR-024131,
5K24DK002651]; [RR-05096]
FX In addition to funding under a cooperative agreement from the NIDDK
(5U01DK060990, and 5U01DK060902) and R01 DK072231 (H-CRIC), this work
was supported in part by the following institutional Clinical
Translational Science Awards (CT-SAs) and other National Institutes of
Health (NIH) grants: UL1 RR-025005 (Johns Hopkins University), General
Clinical Research Center (GCRC) grant M01 RR-16500 (University of
Maryland), UL1 RR-024989 (CaseWestern Reserve University Clinical and
Translational Science Collaborative [University Hospitals of Cleveland,
Cleveland Clinic Foundation, and MetroHealth]), GCRC M01 RR-000042
(University of Michigan), CTSA UL1 RR-024986, M01 RR-013987-06
(University of Illinois at Chicago Clinical Research Center), RR-05096
(Tulane/LSU/Charity Hospital General Clinical Research Center), CTSA UL1
RR-024134 (University of Pennsylvania), UL1 RR-024131 (Kaiser NCRR
UCSF-CTSI), 5K24DK002651. Additional support provided by the National
Center for Minority Health and Health Disparities, NIH, and Department
of Veterans Affairs Health Services Research and Development Service
(Career Development Award to Dr Fischer).
NR 44
TC 47
Z9 47
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 AUG
PY 2011
VL 58
IS 2
BP 214
EP 227
DI 10.1053/j.ajkd.2011.05.010
PG 14
WC Urology & Nephrology
SC Urology & Nephrology
GA 795WU
UT WOS:000293010000011
PM 21705121
ER
PT J
AU Blair, E
de Groot, J
Nelson, KB
AF Blair, Eve
de Groot, Jan
Nelson, Karin B.
TI Placental infarction identified by macroscopic examination and risk of
cerebral palsy in infants at 35 weeks of gestational age and over
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE infarction; growth restriction; placenta; preeclampsia
ID PERINATAL ARTERIAL STROKE; NEONATAL ENCEPHALOPATHY; CHORIOAMNIONITIS;
HISTOLOGY
AB OBJECTIVE: We sought to investigate whether placental infarction determined by macroscopic examination was associated with risk of cerebral palsy (CP).
STUDY DESIGN: This was a population-based study of macroscopic placental infarcts in singletons >35 weeks' gestational age, in 158 perinatal deaths, 445 infants with CP, and 491 controls matched with CP cases for gestational age.
RESULTS: Placental infarcts were recorded in 2.0% of controls, 4.4% of deaths (relative risk [RR], 2.2; 95% confidence interval [CI], 0.8-5.6]), 5.2% of infants with CP (P < .05, RR, 2.5; 95% CI, 1.2-5.3), and 8.4% with spastic quadriplegic CP (P = .0026; RR, 4.4; 95% CI, 1.8-10.6). In children with CP, unlike controls, placental infarction was associated with reduced fetal growth, older maternal age, more prior miscarriages, and poor neonatal condition, but not with maternal preeclampsia.
CONCLUSION: Placental infarction identified by macroscopic examination was associated with increased risk of CP and the CP subtype, spastic quadriplegic CP. Antecedents of placental infarction differed in children with CP compared with control children.
C1 [Blair, Eve; de Groot, Jan] Univ Western Australia, Ctr Child Hlth Res, Telethon Inst Child Hlth Res, Perth, WA 6009, Australia.
[Blair, Eve; de Groot, Jan] Sch Paediat & Child Hlth, Perth, WA, Australia.
[Nelson, Karin B.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Nelson, Karin B.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
RP Blair, E (reprint author), Univ Western Australia, Ctr Child Hlth Res, Telethon Inst Child Hlth Res, Perth, WA 6009, Australia.
FU National Health and Medical Research Council of Australia [353514]
FX Support was provided by the National Health and Medical Research Council
of Australia under program Grant 353514, approved by the Princess
Margaret Hospital/King Edward Memorial Hospital Ethics Committee, the
Confidentiality of Health Information Committee of the Western Australia
Department of Health, and individual hospital and regional ethics
committees, where required.
NR 31
TC 4
Z9 4
U1 0
U2 6
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 AUG
PY 2011
VL 205
IS 2
AR 124.e1
DI 10.1016/j.ajog.2011.05.022
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 798ON
UT WOS:000293219400022
PM 21722872
ER
PT J
AU Manuck, TA
Lai, YL
Meis, PJ
Dombrowski, MP
Sibai, B
Spong, CY
Rouse, DJ
Durnwald, CP
Caritis, SN
Wapner, RJ
Mercer, BM
Ramin, SM
AF Manuck, Tracy A.
Lai, Yinglei
Meis, Paul J.
Dombrowski, Mitchell P.
Sibai, Baha
Spong, Catherine Y.
Rouse, Dwight J.
Durnwald, Celeste P.
Caritis, Steve N.
Wapner, Ronald J.
Mercer, Brian M.
Ramin, Susan M.
TI Progesterone receptor polymorphisms and clinical response to
17-alpha-hydroxyprogesterone caproate
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 genetic polymorphisms; progesterone receptor; recurrent preterm birth;
17-alpha hydroxyprogesterone caproate
ID SPONTANEOUS PRETERM BIRTH; GENE POLYMORPHISMS; OVARIAN-CANCER; INCREASED
RISK; DELIVERY; WOMEN; PREVENTION; WHITE; ASSOCIATION; PREMATURITY
AB OBJECTIVE: Seventeen-alpha-hydroxyprogesterone caproate (17-OHPC) reduces recurrent preterm birth (PTB). We hypothesized that single nucleotide polymorphisms in the human progesterone receptor (PGR) affect response to 17-OHPC in the prevention of recurrent PTB.
STUDY DESIGN: We conducted secondary analysis of a study of 17-OHPC vs placebo for recurrent PTB prevention. Twenty PGR gene single nucleotide polymorphisms were studied. Multivariable logistic regression assessed for an interaction between PGR genotype and treatment status in modulating the risk of recurrent PTB.
RESULTS: A total of 380 women were included; 253 (66.6%) received 17-OHPC and 127 (33.4%) received placebo. In all, 61.1% of women were African American. Multivariable logistic regression demonstrated significant treatment-genotype interactions (either a beneficial or harmful treatment response) for African Americans delivering <37 weeks' gestation for rs471767 and rs578029, and for Hispanics/Caucasians delivering <37 weeks' gestation for rs500760 and <32 weeks' gestation for rs578029, rs503362, and rs666553.
CONCLUSION: The clinical efficacy and safety of 17-OHPC for recurrent PTB prevention may be altered by PGR gene polymorphisms.
C1 [Spong, Catherine Y.] NICHHD, Bethesda, MD 20892 USA.
[Manuck, Tracy A.; Lai, Yinglei; Meis, Paul J.; Dombrowski, Mitchell P.; Sibai, Baha; Spong, Catherine Y.; Rouse, Dwight J.; Durnwald, Celeste P.; Caritis, Steve N.; Wapner, Ronald J.; Mercer, Brian M.; Ramin, Susan M.] Eunice Kennedy Shriver NICHD Maternal Fetal Med U, Bethesda, MD USA.
[Lai, Yinglei] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Manuck, Tracy A.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Meis, Paul J.] Wake Forest Univ Hlth Sci, Dept Obstet & Gynecol, Winston Salem, NC USA.
[Dombrowski, Mitchell P.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Sibai, Baha] Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA.
[Rouse, Dwight J.] Brown Univ, Sch Med, Dept Obstet & Gynecol, Providence, RI 02912 USA.
[Durnwald, Celeste P.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
[Caritis, Steve N.] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA.
[Wapner, Ronald J.] Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA.
[Mercer, Brian M.] Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA.
[Ramin, Susan M.] Univ Texas Houston, Dept Obstet & Gynecol, Houston, TX USA.
RP Manuck, TA (reprint author), 30 North 1900 East,Room 2B200, Salt Lake City, UT 84132 USA.
EM tracy.manuck@hsc.utah.edu
OI caritis, steve/0000-0002-2169-0712
FU NICHD NIH HHS [HD27860, HD21410, HD21414, HD27861, HD27869, HD27915,
HD27917, HD34116, HD34136, HD34208, HD34210, HD36801, HD40500, HD40512,
HD40544, HD40560, U01 HD036801, U10 HD021410, U10 HD027860, U10
HD027869, U10 HD027905, U10 HD027915, U10 HD027917, U10 HD034116, U10
HD034122, U10 HD034136, U10 HD034208, U10 HD034208-16, U10 HD034208-17,
U10 HD036801, U10 HD040500, U10 HD040512, U10 HD040544, U10 HD040560,
UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208, UG1 HD040500,
UG1 HD040512, UG1 HD040544, UG1 HD040560]
NR 38
TC 13
Z9 14
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD AUG
PY 2011
VL 205
IS 2
AR 135.e1
DI 10.1016/j.ajog.2011.03.048
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 798ON
UT WOS:000293219400027
PM 21600550
ER
PT J
AU Pacheco, LD
Hankins, GD
Costantine, MM
Anderson, GD
Pawelczyk, E
Nowicki, S
Nowicki, BJ
AF Pacheco, Luis D.
Hankins, Gary D.
Costantine, Maged M.
Anderson, Garland D.
Pawelczyk, Edyta
Nowicki, Stella
Nowicki, Bogdan J.
TI The Role of Human Decay-Accelerating Factor in the Pathogenesis of
Preterm Labor
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE Preterm labor; complement activation; decay-accelerating factor
ID COMPLEMENT REGULATORY PROTEIN; HUMAN TROPHOBLAST; ESCHERICHIA-COLI;
EXPRESSION; INFECTION; CELLS; CD55
AB Complement activation is thought to contribute to the pathogenesis of preterm labor (PTL). Decay-accelerating factor (DAF) is a natural complement pathway inhibitor. Our hypothesis was that DAF expression on maternal white blood cells (WBCs) in women with preterm labor is elevated compared with women with no preterm labor. Our secondary objective was to determine if differences in upregulation of DAF levels correlated with clinical outcomes. Serial blood samples were obtained from 30 patients with a clinical diagnosis of PTL and a control group of 30 pregnant individuals (same gestational age range) to determine DAF expression in peripheral WBCs in both groups. DAF expression was higher in women with PTL (less than 37 weeks) compared with the control group without PTL. Subjects with PTL who delivered before 34 weeks had less DAF expression and different kinetics of expression compared with those carrying pregnancies beyond 34 weeks. These data suggest that women with a clinical diagnosis of preterm labor have increased DAF expression on peripheral WBCs. Furthermore, it appears that failure to elevate DAF expression is associated with a risk of early premature delivery.
C1 [Pacheco, Luis D.; Hankins, Gary D.; Costantine, Maged M.; Anderson, Garland D.] Univ Texas Med Branch Galveston, Dept Obstet & Gynecol, Div Maternal Fetal Med, Galveston, TX 77555 USA.
[Nowicki, Stella; Nowicki, Bogdan J.] Meharry Med Coll, Dept Obstet & Gynecol, Nashville, TN 37208 USA.
[Nowicki, Stella; Nowicki, Bogdan J.] Meharry Med Coll, Dept Microbial Pathogenesis & Immune Response, Nashville, TN 37208 USA.
[Pawelczyk, Edyta] NIH, Expt Neuroimaging Sect, Ctr Clin, Bethesda, MD 20892 USA.
RP Pacheco, LD (reprint author), Univ Texas Med Branch Galveston, Dept Obstet & Gynecol, Div Maternal Fetal Med, 301 Univ Blvd, Galveston, TX 77555 USA.
EM ldpachec@utmb.edu
FU NICHD [HD41687]
FX This work is supported by NICHD grant HD41687 awarded to Bogdan Nowicki.
NR 17
TC 6
Z9 6
U1 0
U2 2
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD AUG
PY 2011
VL 28
IS 7
BP 565
EP 570
DI 10.1055/s-0031-1274510
PG 6
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 797QS
UT WOS:000293143000010
PM 21380985
ER
PT J
AU Laughon, SK
Powers, RW
Roberts, JM
Parana, S
Catov, J
AF Laughon, S. Katherine
Powers, Robert W.
Roberts, James M.
Parana, Sarah
Catov, Janet
TI Caffeine and Insulin Resistance in Pregnancy
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE Caffeine; insulin resistance; paraxanthine
ID GLUCOSE-TOLERANCE TEST; GESTATIONAL DIABETES-MELLITUS; HOMEOSTASIS MODEL
ASSESSMENT; COFFEE CONSUMPTION; INDUCED IMPAIRMENT; INGESTION; HUMANS;
PREECLAMPSIA; SENSITIVITY; PREVALENCE
AB Outside pregnancy, acute caffeine consumption is associated with insulin resistance. We investigated if during pregnancy plasma concentrations of caffeine and its metabolite, paraxanthine, were associated with insulin resistance. Caffeine, paraxanthine, glucose, and insulin were measured and insulin resistance estimated by homeostasis model assessment (HOMA) in banked samples from 251 fasting subjects at mean gestational age of 20.3 +/- 2.0 weeks. Analysis of covariance and adjusted logistic regression were performed. Most (96.4%) women had caffeine and/or paraxanthine present. Caffeine concentrations in the upper two quartiles (> 266 ng/mL) were associated with threefold higher odds of having higher insulin resistance estimated by log HOMA >= 75th percentile (third quartile odds ratio [OR], 3.02; 95% confidence interval [CI]: 1.21 to 7.54 and fourth quartile OR, 2.95; 95% CI: 1.19 to 7.31). Paraxanthine concentrations in the upper quartile (> 392 ng/mL) were also associated with threefold higher odds of having higher insulin resistance (OR, 3.04; 95% CI: 1.28 to 7.25). Adjusted mean HOMA in the first caffeine-to-paraxanthine ratio quartile was 1.5 +/- 2.2 versus 1.3 +/- 2.3 in the fourth quartile (p < 0.01). Both high caffeine and paraxanthine concentrations were associated with insulin resistance, but slow versus fast metabolism did not make an important difference.
C1 [Laughon, S. Katherine; Powers, Robert W.; Roberts, James M.; Catov, Janet] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Roberts, James M.; Catov, Janet] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Roberts, James M.] Univ Pittsburgh, Clin & Translat Res Inst, Pittsburgh, PA 15261 USA.
[Roberts, James M.; Parana, Sarah; Catov, Janet] Magee Womens Res Inst, Pittsburgh, PA USA.
RP Laughon, SK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM laughonsk@mail.nih.gov
OI Grantz, Katherine/0000-0003-0276-8534
FU Magee-Womens Health Foundation; Pregnancy Exposures and Preeclampsia
Prevention Study Magee-Womens Hospital Clinical; NIH [P01 HD030367];
University of Pittsburgh [UL1 RR024153]
FX This research is supported by the Irene McLenahan Young Investigators
Research Fund of the Magee-Womens Health Foundation, the Pregnancy
Exposures and Preeclampsia Prevention Study Magee-Womens Hospital
Clinical, NIH P01 HD030367, and the Translational Research Center funded
by the University of Pittsburgh Clinical and Translational Science
Award, UL1 RR024153.
NR 34
TC 2
Z9 3
U1 1
U2 3
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD AUG
PY 2011
VL 28
IS 7
BP 571
EP 577
DI 10.1055/s-0031-1274511
PG 7
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 797QS
UT WOS:000293143000011
PM 21380987
ER
PT J
AU Fee, E
Brown, TM
AF Fee, Elizabeth
Brown, Theodore M.
TI Louis I. Harris (1882-1939): A Bold but Now Little Known Early Twentieth
Century Public Health Leader
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Biographical-Item
C1 [Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20894 USA.
[Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY USA.
[Brown, Theodore M.] Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA.
RP Fee, E (reprint author), NIH, Hist Med Div, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM changb@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 3
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 AUG
PY 2011
VL 101
IS 8
BP 1404
EP 1405
DI 10.2105/AJPH.2010.192518
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 797SD
UT WOS:000293149500015
PM 21680934
ER
PT J
AU Fee, E
Brown, TM
AF Fee, Elizabeth
Brown, Theodore M.
TI Leona Baumgartner (1902-1991): Leader in Domestic and International
Public Health
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Biographical-Item
C1 [Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20894 USA.
[Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY USA.
[Brown, Theodore M.] Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA.
RP Fee, E (reprint author), NIH, Hist Med Div, Natl Lib Med, 8600 Rockville Pile, Bethesda, MD 20894 USA.
EM eliza-beth_fee@nlm.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 4
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 AUG
PY 2011
VL 101
IS 8
BP 1409
EP 1409
DI 10.2105/AJPH.2010.300015
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 797SD
UT WOS:000293149500017
PM 21680917
ER
PT J
AU Hoenen, T
Groseth, A
de Kok-Mercado, F
Kuhn, JH
Wahl-Jensen, V
AF Hoenen, Thomas
Groseth, Allison
de Kok-Mercado, Fabian
Kuhn, Jens H.
Wahl-Jensen, Victoria
TI Minigenomes, transcription and replication competent virus-like
particles and beyond: Reverse genetics systems for filoviruses and other
negative stranded hemorrhagic fever viruses
SO ANTIVIRAL RESEARCH
LA English
DT Review
DE Reverse genetics; Virus-like particles; Minigenome; Minireplicon; Viral
hemorrhagic fever; Filoviruses
ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; RNA-POLYMERASE-I; DEFECTIVE
INTERFERING PARTICLES; VESICULAR STOMATITIS-VIRUS; GREEN FLUORESCENT
PROTEIN; ARENAVIRUS-LIKE PARTICLES; VIRAL GENOME REPLICATION; N-TERMINAL
REGION; INFLUENZA-A-VIRUS; EBOLA-VIRUS
AB Reverse-genetics systems are powerful tools enabling researchers to study the replication cycle of RNA viruses, including filoviruses and other hemorrhagic fever viruses, as well as to discover new antivirals. They include full-length clone systems as well as a number of life cycle modeling systems. Full-length clone systems allow for the generation of infectious, recombinant viruses, and thus are an important tool for studying the virus replication cycle in its entirety. In contrast, life cycle modeling systems such as minigenome and transcription and replication competent virus-like particle systems can be used to simulate and dissect parts of the virus life cycle outside of containment facilities. Minigenome systems are used to model viral genome replication and transcription, whereas transcription and replication competent virus-like particle systems also model morphogenesis and budding as well as infection of target cells. As such, these modeling systems have tremendous potential to further the discovery and screening of new antivirals targeting hemorrhagic fever viruses. This review provides an overview of currently established reverse genetics systems for hemorrhagic fever-causing negative-sense RNA viruses, with a particular emphasis on filoviruses, and the potential application of these systems for antiviral research. (C) 2011 Elsevier B.V. All rights reserved.
C1 [de Kok-Mercado, Fabian; Kuhn, Jens H.; Wahl-Jensen, Victoria] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD 21702 USA.
[Hoenen, Thomas; Groseth, Allison] Univ Marburg, Dept Virol, Marburg, Germany.
[Hoenen, Thomas; Groseth, Allison] NIAID, Virol Lab, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT USA.
RP Wahl-Jensen, V (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA.
EM victoria.jensen@nih.gov
RI Kuhn, Jens H./B-7615-2011;
OI Kuhn, Jens H./0000-0002-7800-6045; Hoenen, Thomas/0000-0002-5829-6305
FU NIAID [HHSN2722002000161]; NIH, NIAID; Schering Foundation; Canadian
Institutes of Health Research
FX The content of this publication does not necessarily reflect the views
or policies of the US Department of Health and Human Services or of the
institutions and companies affiliated with the authors. JHK and VW-J
performed this work as an employee of Tunnell Consulting, Inc., a
subcontractor to Battelle Memorial Institute under its prime contract
with NIAID, under Contract No. HHSN2722002000161.; The authors thank
Friedemann Weber, Hideki Ebihara, Heinz Feldmann, Peter Jahrling and
Stephan Becker for their ideas and discussion. This research was
supported in part by the Intramural Research Program of the NIH, NIAID,
as well as by fellowships from the Schering Foundation (TH) and the
Canadian Institutes of Health Research (AG).
NR 126
TC 34
Z9 35
U1 1
U2 25
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
J9 ANTIVIR RES
JI Antiviral Res.
PD AUG
PY 2011
VL 91
IS 2
BP 195
EP 208
DI 10.1016/j.antiviral.2011.06.003
PG 14
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA 799XT
UT WOS:000293320600016
PM 21699921
ER
PT J
AU Matthijnssens, J
Ciarlet, M
McDonald, SM
Attoui, H
Banyai, K
Brister, JR
Buesa, J
Esona, MD
Estes, MK
Gentsch, JR
Iturriza-Gomara, M
Johne, R
Kirkwood, CD
Martella, V
Mertens, PPC
Nakagomi, O
Parreno, V
Rahman, M
Ruggeri, FM
Saif, LJ
Santos, N
Steyer, A
Taniguchi, K
Patton, JT
Desselberger, U
Van Ranst, M
AF Matthijnssens, Jelle
Ciarlet, Max
McDonald, Sarah M.
Attoui, Houssam
Banyai, Krisztian
Brister, J. Rodney
Buesa, Javier
Esona, Mathew D.
Estes, Mary K.
Gentsch, Jon R.
Iturriza-Gomara, Miren
Johne, Reimar
Kirkwood, Carl D.
Martella, Vito
Mertens, Peter P. C.
Nakagomi, Osamu
Parreno, Viviana
Rahman, Mustafizur
Ruggeri, Franco M.
Saif, Linda J.
Santos, Norma
Steyer, Andrej
Taniguchi, Koki
Patton, John T.
Desselberger, Ulrich
Van Ranst, Marc
TI Uniformity of rotavirus strain nomenclature proposed by the Rotavirus
Classification Working Group (RCWG)
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID GROUP-A ROTAVIRUS; FULL GENOMIC ANALYSIS; GROUP-B ROTAVIRUSES; GROUP-C
ROTAVIRUSES; HUMAN WA-LIKE; BOVINE ROTAVIRUS; MOLECULAR
CHARACTERIZATION; PORCINE ROTAVIRUS; SEQUENCE-ANALYSIS; INTERSPECIES
TRANSMISSION
AB In April 2008, a nucleotide-sequence-based, complete genome classification system was developed for group A rotaviruses (RVs). This system assigns a specific genotype to each of the 11 genome segments of a particular RV strain according to established nucleotide percent cutoff values. Using this approach, the genome of individual RV strains are given the complete descriptor of Gx-P[x]-Ix-Rx-Cx-Mx-Ax-Nx-Tx-Ex-Hx. The Rotavirus Classification Working Group (RCWG) was formed by scientists in the field to maintain, evaluate and develop the RV genotype classification system, in particular to aid in the designation of new genotypes. Since its conception, the group has ratified 51 new genotypes: as of April 2011, new genotypes for VP7 (G20-G27), VP4 (P[28]-P[35]), VP6 (I12-I16), VP1 (R5-R9), VP2 (C6-C9), VP3 (M7-M8), NSP1 (A15-A16), NSP2 (N6-N9), NSP3 (T8-T12), NSP4 (E12-E14) and NSP5/6 (H7-H11) have been defined for RV strains recovered from humans, cows, pigs, horses, mice, South American camelids (guanaco), chickens, turkeys, pheasants, bats and a sugar glider. With increasing numbers of complete RV genome sequences becoming available, a standardized RV strain nomenclature system is needed, and the RCWG proposes that individual RV strains are named as follows: RV group/species of origin/country of identification/common name/year of identification/G- and P-type. In collaboration with the National Center for Biotechnology Information (NCBI), the RCWG is also working on developing a RV-specific resource for the deposition of nucleotide sequences. This resource will provide useful information regarding RV strains, including, but not limited to, the individual gene genotypes and epidemiological and clinical information. Together, the proposed nomenclature system and the NCBI RV resource will offer highly useful tools for investigators to search for, retrieve, and analyze the ever-growing volume of RV genomic data.
C1 [Matthijnssens, Jelle; Van Ranst, Marc] Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, Lab Clin & Epidemiol Virol, B-3000 Louvain, Belgium.
[Ciarlet, Max] Novartis Vaccines & Diagnost Inc, Clin Res & Dev, Cambridge, MA 02139 USA.
[McDonald, Sarah M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Attoui, Houssam; Mertens, Peter P. C.] Inst Anim Hlth, Vector Borne Dis Program, Pirbright GU24 0NF, Surrey, England.
[Banyai, Krisztian] Hungarian Acad Sci, Vet Med Res Inst, H-1143 Budapest, Hungary.
[Brister, J. Rodney] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Buesa, Javier] Univ Valencia, Dept Microbiol & Ecol, Sch Med, Valencia 46010, Spain.
[Esona, Mathew D.; Gentsch, Jon R.] Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
[Estes, Mary K.] Baylor Coll Med, Dept Mol Virol & Microbiol & Med GI, Houston, TX 77030 USA.
[Iturriza-Gomara, Miren] Hlth Protect Agcy, Enter Virus Unit, Virus Reference Dept, Ctr Infect, London, England.
[Johne, Reimar] Fed Inst Risk Assessment, Berlin, Germany.
[Kirkwood, Carl D.] Royal Childrens Hosp, Enter Virus Res Grp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia.
[Martella, Vito] Univ Bari, Dept Vet Publ Hlth, Bari, Italy.
[Nakagomi, Osamu] Nagasaki Univ, Dept Mol Microbiol & Immunol, Nagasaki 8528523, Japan.
[Parreno, Viviana] INTA Castelar, Inst Virol, CICVyA, Buenos Aires, DF, Argentina.
[Rahman, Mustafizur] ICDDR B, Virol Lab, Dhaka 1212, Bangladesh.
[Ruggeri, Franco M.] Ist Super Sanita, Dept Vet Publ Hlth & Food Safety, I-00161 Rome, Italy.
[Saif, Linda J.] Ohio State Univ, Food Anim Hlth Res Program, Ohio Agr Res & Dev Ctr, Wooster, OH 44691 USA.
[Santos, Norma] Univ Fed Rio de Janeiro, Inst Microbiol, Dept Virol, BR-21941 Rio De Janeiro, Brazil.
[Steyer, Andrej] Univ Ljubljana, Fac Med, Inst Microbiol & Immunol, Ljubljana 1104, Slovenia.
[Taniguchi, Koki] Fujita Hlth Univ, Sch Med, Dept Virol & Parasitol, Aichi 4701192, Japan.
[Desselberger, Ulrich] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England.
RP Matthijnssens, J (reprint author), Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, Lab Clin & Epidemiol Virol, Minderbroedersstr 10, B-3000 Louvain, Belgium.
EM jelle.matthijnssens@uz.kuleuven.ac.be
RI rahman, mustafizur/E-6918-2010; Iturriza Gomara, Miren/B-4351-2013;
Ruggeri, Franco/B-5707-2013; Patton, John/P-1390-2014; Matthijnssens,
Jelle/A-6770-2015; Buesa, Javier/D-8927-2014; Santos, Norma/H-6986-2015;
Matthijnssens, Jelle/B-8634-2016; Institute, Pirbright/K-4476-2014;
Martella, Vito/K-3146-2016
OI Mertens, Peter/0000-0002-3438-3738; Banyai,
Krisztian/0000-0002-6270-1772; Steyer, Andrej/0000-0001-6819-2406; Van
Ranst, Marc/0000-0002-1674-4157; Iturriza Gomara,
Miren/0000-0001-5816-6423; Buesa, Javier/0000-0002-3328-3428; Santos,
Norma/0000-0002-5123-9172; Martella, Vito/0000-0002-5740-6947
FU FWO ('Fonds voor Wetenschappelijk Onderzoek'); National Institute of
Allergy and Infectious Diseases, National Institutes of Health;
Hungarian Scientific Research Fund [OTKA PD76364]; Spanish Ministry of
Science [FUN-C-FOOD CSD2007-063]; Deutsche Forschungsgemeinschaft
[JO369/4-1]; NHMRC [607347]; Ministry of Health; Ministry of Health, CCM
"Rotanet-Italy''
FX J. Matthijnssens is supported by an FWO ('Fonds voor Wetenschappelijk
Onderzoek') postdoctoral fellowship. S. McDonald and J. Patton are
supported by the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases, National Institutes of Health. K.
Banyai was supported by the Hungarian Scientific Research Fund (OTKA
PD76364). J. Buesa is supported by the Consolider-Ingenio 2010 Program
(FUN-C-FOOD CSD2007-063) of the Spanish Ministry of Science. R. Johne is
supported by a grant from the Deutsche Forschungsgemeinschaft
(JO369/4-1). CD Kirkwood is supported by an NHMRC Career Development
Award (607347). V. Martella was supported by the Ministry of Health,
Ricerca finalizzata 2007 "Zoonosi e infezioni virali esotiche:
fronteggiare le emergenze attraverso un approccio integrato fra medicina
umana e veterinaria''. F. M. Ruggeri is supported by the Ministry of
Health, CCM "Rotanet-Italy'' Programme.
NR 106
TC 398
Z9 421
U1 4
U2 34
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
EI 1432-8798
J9 ARCH VIROL
JI Arch. Virol.
PD AUG
PY 2011
VL 156
IS 8
BP 1397
EP 1413
DI 10.1007/s00705-011-1006-z
PG 17
WC Virology
SC Virology
GA 798TW
UT WOS:000293236100010
PM 21597953
ER
PT J
AU Funk, JA
Gohlke, J
Kraft, AD
McPherson, CA
Collins, JB
Harry, GJ
AF Funk, Jason A.
Gohlke, Julia
Kraft, Andrew D.
McPherson, Christopher A.
Collins, Jennifer B.
Harry, G. Jean
TI Voluntary exercise protects hippocampal neurons from trimethyltin
injury: Possible role of interleukin-6 to modulate tumor necrosis factor
receptor-mediated neurotoxicity
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Exercise; Hippocampus; Neuroinflammation; Neuroprotection;
Interleukin-6; TNF alpha; Trimethyltin
ID NF-KAPPA-B; ASTROCYTE-TARGETED EXPRESSION; TNF-ALPHA; IN-VIVO; OXIDATIVE
STRESS; DENTATE GYRUS; UNPHOSPHORYLATED STAT3; INDUCED APOPTOSIS;
GENE-EXPRESSION; MESSENGER-RNA
AB In the periphery, exercise induces interleukin (IL)-6 to downregulate tumor necrosis factor (TNF), elevate interleukin-1 receptor antagonist (IL-1 RA), decreasing inflammation. Exercise also offers neuroprotection and facilitates brain repair. IL-6 production in the hippocampus following exercise suggests the potential of a similar protective role as in the periphery to down-regulate TNF alpha and inflammation. Using a chemical-induced model of hippocampal dentate granule cell death (trimethyltin, TMT 2.4 mg/kg, ip) dependent upon TNF receptor signaling, we demonstrate neuroprotection in mice with 2 weeks access to running wheel. Exercise attenuated neuronal death and diminished elevations in TNFa, TNF receptor 1, myeloid differentiation primary response gene (MyD) 88, transforming growth factor p, chemokine (CC motif) ligand 2 (CCL2), and CCL3. Elevated mRNA levels for IL-1 alpha, IL-1 RA, occurred with injury and protection. mRNA and protein levels of IL-6 and neuronal expression of IL-6 receptor a, were elevated with injury and protection. Microarray pathway analysis supported an up-regulation of TNFa cell death signaling pathways with TMT and inhibition by exercise. IL-6 pathway recruitment occurred in both conditions. IL-6 downstream signal events differed in the level of STAT3 activation. Exercise did not increase mRNA levels of brain derived neurotrophic factor, nerve growth factor, or glial derived neurotrophic factor. In IL-6 deficient mice, exercise did not attenuate TMT-induced tremor and a diminished level of neuroprotection was observed. These data suggest a contributory role for IL-6 induced by exercise for neuroprotection in the CNS similar to that seen in the periphery. Published by Elsevier Inc.
C1 [Funk, Jason A.; Kraft, Andrew D.; McPherson, Christopher A.; Harry, G. Jean] Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Gohlke, Julia] Univ Alabama Birmingham, Dept Environm Hlth Sci, Birmingham, AL USA.
[Collins, Jennifer B.] Natl Inst Environm Hlth Sci, Div Extramural Res & Training, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Harry, GJ (reprint author), Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, NIH, US Dept HHS, POB 12233,MD C1-04, Res Triangle Pk, NC 27709 USA.
EM harry@niehs.nih.gov
OI Gohlke, Julia/0000-0002-6984-2893
FU Division of Intramural Research, NIEHS/NIH [1Z01ES101623, N01-ES-65554];
Research Triangle Institute, RTP, NC
FX The authors thank the NIEHS Microarray Core for their expert assistant
with the microarray analysis and Dr. Sue Edelstein for graphics support.
This study was supported by the Division of Intramural Research,
NIEHS/NIH under project #1Z01ES101623 and contract #N01-ES-65554,
Research Triangle Institute, RTP, NC.
NR 65
TC 36
Z9 38
U1 0
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD AUG
PY 2011
VL 25
IS 6
BP 1063
EP 1077
DI 10.1016/j.bbi.2011.03.012
PG 15
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 799SI
UT WOS:000293306000003
PM 21435392
ER
PT J
AU Rossi, CC
Van de Water, J
Rogers, SJ
Amaral, DG
AF Rossi, Christy C.
Van de Water, Judy
Rogers, Sally J.
Amaral, David G.
TI Detection of plasma autoantibodies to brain tissue in young children
with and without autism spectrum disorders
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Autism; Autoantibody; Interneurons; Immunohistochemistry; Child behavior
checklist
ID PERVASIVE DEVELOPMENTAL DISORDERS; ANTIBRAIN ANTIBODIES; FETAL-BRAIN;
IMMUNE-RESPONSE; ACTIVATION; PROTEINS; GENETICS
AB Autism spectrum disorders (ASDs) are characterized by impaired language and social skills, often with restricted interests and stereotyped behaviors. A previous investigation of blood plasma from children with ASDs (mean age = 51/2 years) demonstrated that 21% of samples contained autoantibodies that reacted intensely with GABAergic Golgi neurons of the cerebellum while no samples from non-sibling, typically developing children showed similar staining (Wills et al., 2009). In order to characterize the clinical features of children positive for these autoantibodies, we analyzed plasma samples from children enrolled in the Autism Phenome Project, a multidisciplinary project aimed at identifying subtypes of ASD. Plasma from male and female children (mean age = 3.2 years) was analyzed immunohistochemically for the presence of autoantibodies using histological sections of macaque monkey brain. Immunoreactivity to cerebellar Golgi neurons and other presumed interneurons was observed for some samples but there was no difference in the rate of occurrence of these autoantibodies between children with ASD and their typically developing peers. Staining of neurons, punctate profiles in the molecular layer of the dentate gyrus, and neuronal nuclei were also observed. Taken together, 42% of controls and subjects with ASD demonstrated immunoreactivity to some neural element. Interestingly, children whose plasma reacted to brain tissue had scores on the Child Behavior Checklist (CBCL) that indicated increased behavioral and emotional problems. Children whose plasma was immunoreactive with neuronal cell bodies scored higher on multiple CBCL scales. These studies indicate that additional research into the genesis and prevalence of brain-directed autoantibodies is warranted. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Rossi, Christy C.; Rogers, Sally J.; Amaral, David G.] Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA.
[Rossi, Christy C.; Van de Water, Judy; Rogers, Sally J.; Amaral, David G.] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA.
[Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA.
[Van de Water, Judy] Univ Calif Davis, NIEHS Ctr Childrens Environm Hlth, Davis, CA 95616 USA.
[Amaral, David G.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA.
[Amaral, David G.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA.
RP Amaral, DG (reprint author), Univ Calif Davis, MIND Inst, 2825 50th St, Sacramento, CA 95817 USA.
EM dgamaral@ucdavis.edu
FU NIH [MH41479, MH089626, MH073124]; NARSAD
FX This research was supported by NIH grants MH41479, MH089626, MH073124
and by a grant from NARSAD. Primate tissue was acquired from the
California National Primate Research Center, RR000169. We would like to
thank the laboratory of Dr. Cynthia L. Bethea for helpful advice
regarding the use of the Vector Avidin Biotin blocking kit, Jose Rosa
for assistance with tissue mounting and immunohistochemical processing,
Lou Ann Barnett for coordinating data collected as part of the Autism
Phenome Project, and the entire APP team for their contributions toward
enrolling the children and collecting the samples analyzed in this
study. We also thank the families that are participating in the Autism
Phenome Project.
NR 32
TC 24
Z9 24
U1 2
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD AUG
PY 2011
VL 25
IS 6
BP 1123
EP 1135
DI 10.1016/j.bbi.2011.02.011
PG 13
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 799SI
UT WOS:000293306000009
PM 21420487
ER
PT J
AU Hanson, MS
Piknova, B
Keszler, A
Diers, AR
Wang, XD
Gladwin, MT
Hillery, CA
Hogg, N
AF Hanson, Madelyn S.
Piknova, Barbora
Keszler, Agnes
Diers, Anne R.
Wang, Xunde
Gladwin, Mark T.
Hillery, Cheryl A.
Hogg, Neil
TI Methaemalbumin formation in sickle cell disease: effect on oxidative
protein modification and HO-1 induction
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE methaemalbumin; methaemoglobin; haem; sickle cell disease; haem
oxygenase 1
ID HUMAN-SERUM-ALBUMIN; ELECTRON-SPIN-RESONANCE; LOW-DENSITY-LIPOPROTEIN;
HEME OXYGENASE-1; NITRIC-OXIDE; PULMONARY-HYPERTENSION;
MOLECULAR-MECHANISMS; GEL ELECTROPHORESIS; HEMOGLOBIN; ANTIOXIDANT
AB Normally, cell free haemoglobin is bound by haptoglobin and efficiently cleared. However, the chronic haemolysis in sickle cell disease (SCD) overwhelms haptoglobin binding capacity and protein turnover, resulting in elevated cell free haemoglobin. Cell free haemoglobin acts as both a scavenger of vasoactive nitric oxide and a pro-oxidant. In addition, methaemoglobin (metHb) releases the haem moiety, which can bind to albumin to form methaemalbumin (metHSA). This study used electron paramagnetic resonance to detect metHSA in SCD plasma and demonstrated that haptoglobin prevents haem transfer from metHb to HSA. MetHSA may either provide a second line of defence against haemoglobin/haem-mediated oxidation or contribute to the pro-oxidant environment of SCD plasma. We demonstrated that HSA inhibited oxidative protein modification induced by metHb. Additionally, we showed that while metHb induced haem oxygenase 1 (HO-1), an indicator of oxidative stress, HSA attenuated metHb induction of this enzyme, thereby limiting the potential benefits of HO-1. Furthermore, HO-1 induction by metHSA was less than HO-1 induction by equimolar metHb not bound to albumin. Our findings confirm the presence of metHSA in SCD and suggest that haem transfer from metHb to HSA reduces the oxidative effects of free haemoglobin/ haem on endothelium with both beneficial (reduced protein oxidation) and potentially harmful (reduced HO-1 induction) outcomes.
C1 [Hanson, Madelyn S.; Piknova, Barbora; Keszler, Agnes; Diers, Anne R.; Hogg, Neil] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA.
[Hanson, Madelyn S.; Piknova, Barbora; Keszler, Agnes; Diers, Anne R.; Hogg, Neil] Med Coll Wisconsin, Redox Biol Program, Milwaukee, WI 53226 USA.
[Wang, Xunde] NHLBI, Pulmonaty & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Gladwin, Mark T.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
[Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA.
[Hillery, Cheryl A.] Med Coll Wisconsin, Dept Pediat, Div Hematol & Oncol, Milwaukee, WI 53226 USA.
[Hillery, Cheryl A.] Blood Ctr SE Wisconsin Inc, Milwaukee, WI 53233 USA.
RP Hogg, N (reprint author), Med Coll Wisconsin, Dept Biophys, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM nhogg@mcw.edu
FU National Heart, Lung, and Blood Institute [HL-090503, HL-081139,
HL-44612, HL-098032, HL-096973]; National Institute of Diabetes and
Digestive and Kidney Diseases [RC1DK0850852]; NIH [P41 EB001980-34,
1-UL1-RR031973]; Hemophilia Center of Western Pennsylvania
FX This work was supported by National Heart, Lung, and Blood Institute
grants HL-090503 (NH, CAH), HL-081139 (CAH), HL-44612 (CAH), HL-098032
(MTG), HL-096973 (MTG), and a National Institute of Diabetes and
Digestive and Kidney Diseases grant RC1DK0850852 (MTG) as well as the
National Biomedical EPR Center funded by NIH grant P41 EB001980-34 and
the Hemophilia Center of Western Pennsylvania (MTG). The collection of
human samples was supported by Clinical and Translational Science Award
(CTSA) 1-UL1-RR031973 from the NIH.
NR 43
TC 8
Z9 8
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD AUG
PY 2011
VL 154
IS 4
BP 502
EP 511
DI 10.1111/j.1365-2141.2011.08738.x
PG 10
WC Hematology
SC Hematology
GA 798VC
UT WOS:000293239300011
PM 21595649
ER
PT J
AU Machado, RF
Hildesheim, M
Mendelsohn, L
Remaley, AT
Kato, GJ
Gladwin, MT
AF Machado, Roberto F.
Hildesheim, Mariana
Mendelsohn, Laurel
Remaley, Alan T.
Kato, Gregory J.
Gladwin, Mark T.
TI NT-pro brain natriuretic peptide levels and the risk of death in the
cooperative study of sickle cell disease
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE sickle cell disease; pulmonary hypertension; brain natriuretic peptide;
biomarkers; survival
ID NITRIC-OXIDE BIOAVAILABILITY; PULMONARY-ARTERY PRESSURES;
PLASMA-CONCENTRATIONS; FETAL-HEMOGLOBIN; HYPERTENSION; CHILDREN;
HEMOLYSIS; ADOLESCENTS; MORTALITY; SURVIVAL
AB Epidemiological studies support a hypothesis that pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) that is associated with a high risk of death and evolves as a complication of haemolytic anaemia. This fundamental hypothesis has been recently challenged and remains controversial. In order to further test this hypothesis in a large and independent cohort of SCD patients we obtained plasma samples from the Cooperative Study of Sickle Cell Disease (CSSCD) for analysis of a biomarker, N-terminal-pro brain natriuretic peptide (NT-proBNP), which is elevated in the setting of pulmonary arterial and venous hypertension. A NT-pro-BNP value previously identified to predict PH in adults with SCD was used to determine the association between the risk of mortality in 758 CSSCD participants (428 children and 330 adults). An abnormally high NT-proBNP level >= 160 ng/l was present in 27.6% of adult SCD patients. High levels were associated with markers of haemolytic anaemia, such as low haemoglobin level (P < 0.001), high lactate dehydrogenase (P < 0.001), and high total bilirubin levels (P < 0.007). A NT-proBNP level >= 160 ng/l was an independent predictor of mortality (RR 6.24, 95% CI 2.9-13.3, P < 0.0001). These findings provide further support for an association between haemolytic anaemia and cardiovascular complications in this patient population.
C1 [Machado, Roberto F.] Univ Illinois, Sect Pulm Crit Care Med Sleep & Allergy, Chicago, IL 60612 USA.
[Hildesheim, Mariana; Mendelsohn, Laurel; Kato, Gregory J.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Hildesheim, Mariana; Mendelsohn, Laurel; Remaley, Alan T.; Kato, Gregory J.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Gladwin, Mark T.] Univ Pittsburgh, Hemostasis & Vasc Biol Res Inst, Pittsburgh, PA USA.
RP Machado, RF (reprint author), Univ Illinois, Sect Pulm Crit Care Med Sleep & Allergy, 840 S Wood St,Room 920-N,Clin Sci Bldg,MC 719, Chicago, IL 60612 USA.
EM machador@uic.edu
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU National Institutes of Health; NHLBI [K23HL098454]; US Government;
Ikaria INO Therapeutics; Institute of Transfusion Medicine; Hemophilia
Center of Western Pennsylvania; NIDDK; NIAMS of the National Institutes
of health (NIH) [R01HL098032, RO1HL096973, RC1DK085852, P30AR058910]
FX This study was supported by National Institutes of Health Intramural
Research Funds. Roberto Machado receives grant support from the NHLBI
(K23HL098454). Mark T. Gladwin has received research support in the form
of a Collaborative Research and Development Agreement between the US
Government and Ikaria INO Therapeutics and is listed as a co-inventor on
a US Government Patent for the use of nitrite salts for cardiovascular
indications. Dr Gladwin receives grant support from the Institute of
Transfusion Medicine, the Hemophilia Center of Western Pennsylvania and
Federal funding by the NHLBI, NIDDK and NIAMS of the National Institutes
of health (NIH grants R01HL098032, RO1HL096973, RC1DK085852,
P30AR058910).
NR 48
TC 22
Z9 22
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD AUG
PY 2011
VL 154
IS 4
BP 512
EP 520
DI 10.1111/j.1365-2141.2011.08777.x
PG 9
WC Hematology
SC Hematology
GA 798VC
UT WOS:000293239300012
PM 21689089
ER
PT J
AU Somlo, G
Lashkari, A
Bellamy, W
Zimmerman, TM
Tuscano, JM
O'Donnell, MR
Mohrbacher, AF
Forman, SJ
Frankel, P
Chen, HX
Doroshow, JH
Gandara, DR
AF Somlo, George
Lashkari, Ashkan
Bellamy, William
Zimmerman, Todd M.
Tuscano, Joseph M.
O'Donnell, Margaret R.
Mohrbacher, Ann F.
Forman, Stephen J.
Frankel, Paul
Chen, Helen X.
Doroshow, James H.
Gandara, David R.
TI Phase II randomized trial of bevacizumab versus bevacizumab and
thalidomide for relapsed/refractory multiple myeloma: a California
Cancer Consortium trial
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Letter
DE multiple myeloma; bevacizumab; thalidomide; vascular endothelial growth
factor; angiogenesis
ID ANGIOGENESIS
C1 [Somlo, George; Lashkari, Ashkan] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA.
[Somlo, George; O'Donnell, Margaret R.] City Hope Canc Ctr, Duarte, CA USA.
[Bellamy, William] Univ Arkansas, Dept Pathol, Little Rock, AR 72204 USA.
[Zimmerman, Todd M.] Univ Chicago, Dept Hematol, Chicago, IL 60637 USA.
[Tuscano, Joseph M.; Gandara, David R.] Univ Calif Davis, Ctr Canc, Div Hematol & Oncol, Sacramento, CA 95817 USA.
[Mohrbacher, Ann F.] Univ So Calif, Div Hematol, Los Angeles, CA USA.
[Frankel, Paul] City Hope Natl Med Ctr, Dept Informat Sci, Duarte, CA USA.
[Chen, Helen X.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Somlo, G (reprint author), City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA.
EM gsomlo@coh.org
FU NCI NIH HHS [N01CM62209, N01 CM062209, N01-CM-62209]
NR 10
TC 17
Z9 19
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD AUG
PY 2011
VL 154
IS 4
BP 533
EP 535
DI 10.1111/j.1365-2141.2011.08623.x
PG 4
WC Hematology
SC Hematology
GA 798VC
UT WOS:000293239300017
PM 21517811
ER
PT J
AU Russell, JT
AF Russell, James T.
TI Imaging calcium signals in vivo: a powerful tool in physiology and
pharmacology
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Review
DE calcium imaging; in vivo imaging; calcium indicators
ID GREEN FLUORESCENT PROTEINS; RECOMBINANT SEMISYNTHETIC AEQUORINS;
GENETICALLY ENCODED INDICATORS; ZEBRAFISH OLFACTORY-BULB;
NEURONAL-ACTIVITY; NEURAL ACTIVITY; 2-PHOTON MICROSCOPE; BLOOD-FLOW;
BIOLUMINESCENT REPORTERS; CA2+ DYNAMICS
AB The design and engineering of organic fluorescent Ca2+ indicators approximately 30 years ago opened the door for imaging cellular Ca2+ signals with a high degree of temporal and spatial resolution. Over this time, Ca2+ imaging has revolutionized our approaches for tissue-level spatiotemporal analysis of functional organization and has matured into a powerful tool for in situ imaging of cellular activity in the living animal. In vivo Ca2+ imaging with temporal resolution at the millisecond range and spatial resolution at micrometer range has been achieved through novel designs of Ca2+ sensors, development of modern microscopes and powerful imaging techniques such as two-photon microscopy. Imaging Ca2+ signals in ensembles of cells within tissue in 3D allows for analysis of integrated cellular function, which, in the case of the brain, enables recording activity patterns in local circuits. The recent development of miniaturized compact, fibre-optic-based, mechanically flexible microendoscopes capable of two-photon microscopy opens the door for imaging activity in awake, behaving animals. This development is poised to open a new chapter in physiological experiments and for pharmacological approaches in the development of novel therapies.
C1 NICHD, Lab Cellular & Mol Neurophysiol, NIH, Sect Cell Biol & Signal Transduct, Bethesda, MD 20892 USA.
RP Russell, JT (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, NIH, Sect Cell Biol & Signal Transduct, Bldg 49,Room 5A-22,49 Convent Dr,MSC 4480, Bethesda, MD 20892 USA.
EM james@helix.nih.gov
NR 154
TC 16
Z9 18
U1 6
U2 43
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD AUG
PY 2011
VL 163
IS 8
SI SI
BP 1605
EP 1625
DI 10.1111/j.1476-5381.2010.00988.x
PG 21
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 797AC
UT WOS:000293093600004
PM 20718728
ER
PT J
AU Ocean, AJ
Christos, P
Sparano, JA
Matulich, D
Kaubish, A
Siegel, A
Sung, M
Ward, MM
Hamel, N
Espinoza-Delgado, I
Yen, Y
Lane, ME
AF Ocean, Allyson J.
Christos, Paul
Sparano, Joseph A.
Matulich, Dan
Kaubish, Andreas
Siegel, Abby
Sung, Max
Ward, Maureen M.
Hamel, Nancy
Espinoza-Delgado, Igor
Yen, Yun
Lane, Maureen E.
TI Phase II trial of the ribonucleotide reductase inhibitor
3-aminopyridine-2-carboxaldehydethiosemicarbazone plus gemcitabine in
patients with advanced biliary tract cancer
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Biliary tract cancer; Gemcitabine;
3-aminopyridine-2-Carboxaldehydethiosemicarbazone; Ribonucleotide
reductase
ID THIOSEMICARBAZONE 3-AP; TRIAPINE; CELLS; COMBINATION; CARCINOMA;
CISPLATIN; CHOLANGIOCARCINOMA; GALLBLADDER; HYDROXYUREA; CHECKPOINT
AB 3-Aminopyridine-2-carboxaldehydethiosemicarbazone (3-AP) is a novel small molecule ribonucleotide reductase (RR) inhibitor which is more potent than hydroxyurea, the prototype of RR inhibitors. 3-AP enhances the cellular uptake and DNA incorporation of gemcitabine in tumor cell lines. We evaluated the combination of 3-AP plus gemcitabine in advanced biliary tract adenocarcinoma.
Thirty-three patients with advanced adenocarcinoma of the gall bladder or biliary tract received gemcitabine (1,000 mg/m(2) on days 1, 8, and 15 every 28 days) 1 h after completing a 4-h infusion of 3-AP given at a dose of 105 mg/m(2) in patients with normal liver function (stratum A) or 80 mg/m(2) if abnormal liver function (stratum B). The trial was designed to determine whether the response rate was at least 30% in stratum A and 20% in stratum B.
Objective response occurred in 3 of 23 patients (13%, 95% confidence intervals [CI] 3, 34%) with normal liver function, and in 0 of 10 patients with abnormal liver function. The most common grade 3-4 adverse events in all patients included neutropenia (42%), infection (33%), thrombocytopenia (27%), anemia (18%), and fatigue (15%). Fine needle aspiration of tumor samples obtained before and 24 h after 3-AP therapy showed increased R2 mRNA expression by in situ RT-PCR, suggesting RR inhibition.
Despite evidence for RR inhibition in vivo, the 3-AP plus gemcitabine combination is not likely to be associated with a response rate exceeding 30% in patients with adenocarcinoma of the biliary tract.
C1 [Sparano, Joseph A.; Matulich, Dan; Kaubish, Andreas] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Ocean, Allyson J.; Christos, Paul; Ward, Maureen M.; Hamel, Nancy; Lane, Maureen E.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA.
[Siegel, Abby] Columbia Univ, New York Presbyterian Hosp, New York, NY USA.
[Sung, Max] Mt Sinai Sch Med, New York, NY USA.
[Espinoza-Delgado, Igor] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Yen, Yun] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
RP Sparano, JA (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
EM jsparano@montefiore.org
FU National Institute of Health, National Cancer Institute [N01-CM-62204];
NIH [24XS07, P6254]
FX This study was performed by the New York Cancer Consortium
(www.newyorkcancerconsortium.org), and was supported by a contract from
the National Institute of Health, National Cancer Institute
(N01-CM-62204 [PI: Joseph A. Sparano]) and NIH Subcontract 24XS07, P6254
(PI: Maureen E. Lane).
NR 34
TC 10
Z9 10
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD AUG
PY 2011
VL 68
IS 2
BP 379
EP 388
DI 10.1007/s00280-010-1481-z
PG 10
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 797NC
UT WOS:000293133600014
PM 20981545
ER
PT J
AU Jia, L
Gorman, GS
Coward, LU
Noker, PE
McCormick, D
Horn, TL
Harder, JB
Muzzio, M
Prabhakar, B
Ganesh, B
Das Gupta, TK
Beattie, CW
AF Jia, Lee
Gorman, Gregory S.
Coward, Lori U.
Noker, Patricia E.
McCormick, David
Horn, Thomas L.
Harder, J. Brooks
Muzzio, Miguel
Prabhakar, Bellur
Ganesh, Balaji
Das Gupta, Tapas K.
Beattie, Craig W.
TI Preclinical pharmacokinetics, metabolism, and toxicity of azurin-p28
(NSC745104) a peptide inhibitor of p53 ubiquitination
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Azurin; p28; Pharmacokinetics; Toxicology; Chemotherapeutic
ID REDOX PROTEIN AZURIN; SPECIFICITY; APOPTOSIS; CANCER; CELLS; MICE
AB Purpose Characterize the preclinical pharmacokinetics, metabolic profile, multi-species toxicology, and antitumor efficacy of azurin-p28 (NSC 745104), an amphipathic, 28 amino acid fragment (aa 50-77) of the copper containing redox protein azurin that preferentially enters cancer cells and is currently under development for treatment of p53-positive solid tumors.
Methods An LC/MS/MS assay was developed, validated, and applied to liver microsomes, serum, and tumor cells to assess cellular uptake and metabolic stability. Pharmacokinetics was established after administration of a single intravenous dose of p28 in preclinical species undergoing chronic toxicity testing. Antitumor efficacy was assessed on human tumor xenografts. A human therapeutic dose was predicted based on efficacy and pharmacokinetic parameters.
Results p28 is stable, showed tumor penetration consistent with selective entry into tumor cells and significantly inhibited p53-positive tumor growth. Renal clearance, volume of distribution, and metabolic profile of p28 was relatively similar among species. p28 was non-immunogenic and non-toxic in mice and non-human primates (NHP). The no observed adverse effect level (NOAEL) was 120 mg/kg iv in female mice. A NOAEL was not established for male mice due to decreased heart and thymus weights that was reversible and did not result in limiting toxicity. In contrast, the NOAEL for p28 in NHP was defined as the highest dose (120 mg/kg/dose; 1,440 mg/m(2)/dose) studied. The maximum-tolerated dose (MTD) for subchronic administration of p28 to mice is > 240 mg/kg/dose (720 mg/m(2)/dose), while the MTD for subchronic administration of p28 to Cynomolgous sp. is > 120 mg/kg (1,440 mg/m(2)/dose). The efficacious (murine) dose of p28 was 10 mg/kg ip per day.
Conclusions p28 does not exhibit preclinical immunogenicity or toxicity, has a similar metabolic profile among species, and is therapeutic in xenograft models.
C1 [Das Gupta, Tapas K.; Beattie, Craig W.] CDG Therapeut, Chicago, IL USA.
[Jia, Lee] Natl Canc Inst, Dev Therapeut Program, Bethesda, MD 20852 USA.
[Gorman, Gregory S.; Coward, Lori U.] Samford Univ, Birmingham, AL 35229 USA.
[Noker, Patricia E.] So Res Inst, Birmingham, AL 35205 USA.
[McCormick, David; Horn, Thomas L.; Harder, J. Brooks; Muzzio, Miguel] IIT, Res Inst, Chicago, IL 60616 USA.
[Prabhakar, Bellur; Ganesh, Balaji] UIC COM, Dept Microbiol & Immunol, Chicago, IL USA.
RP Beattie, CW (reprint author), CDG Therapeut, Chicago, IL USA.
EM cbeattie@uic.edu
FU CDG Therapeutics; NCI RAID; NCI [N01-CM-52203]
FX Research supported by CDG Therapeutics, the NCI RAID program and by NCI
N01-CM-52203.
NR 10
TC 15
Z9 15
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD AUG
PY 2011
VL 68
IS 2
BP 513
EP 524
DI 10.1007/s00280-010-1518-3
PG 12
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 797NC
UT WOS:000293133600028
PM 21085965
ER
PT J
AU Ming, M
Feng, L
Shea, CR
Soltani, K
Zhao, BZ
Han, WN
Smart, RC
Trempus, CS
He, YY
AF Ming, Mei
Feng, Li
Shea, Christopher R.
Soltani, Keyoumars
Zhao, Baozhong
Han, Weinong
Smart, Robert C.
Trempus, Carol S.
He, Yu-Ying
TI PTEN Positively Regulates UVB-Induced DNA Damage Repair
SO CANCER RESEARCH
LA English
DT Article
ID NUCLEOTIDE EXCISION-REPAIR; UBIQUITIN LIGASE COMPLEX; ACTIVATED
PROTEIN-KINASE; NONMELANOMA SKIN-CANCER; XERODERMA-PIGMENTOSUM; INDUCED
UBIQUITYLATION; H2AX PHOSPHORYLATION; HUMAN KERATINOCYTES; AKT;
SUPPRESSION
AB Nonmelanoma skin cancer is the most common cancer in the United States, where DNA-damaging ultraviolet B (UVB) radiation from the sun remains the major environmental risk factor. However, the critical genetic targets of UVB radiation are undefined. Here we show that attenuating PTEN in epidermal keratinocytes is a predisposing factor for UVB-induced skin carcinogenesis in mice. In skin papilloma and squamous cell carcinoma (SCC), levels of PTEN were reduced compared with skin lacking these lesions. Likewise, there was a reduction in PTEN levels in human premalignant actinic keratosis and malignant SCCs, supporting a key role for PTEN in human skin cancer formation and progression. PTEN downregulation impaired the capacity of global genomic nucleotide excision repair (GG-NER), a critical mechanism for removing UVB-induced mutagenic DNA lesions. In contrast to the response to ionizing radiation, PTEN downregulation prolonged UVB-induced growth arrest and increased the activation of the Chk1 DNA damage pathway in an AKT-independent manner, likely due to reduced DNA repair. PTEN loss also suppressed expression of the key GG-NER protein xeroderma pigmentosum C (XPC) through the AKT/p38 signaling axis. Reconstitution of XPC levels in PTEN-inhibited cells restored GG-NER capacity. Taken together, our findings define PTEN as an essential genomic gatekeeper in the skin through its ability to positively regulate XPC-dependent GG-NER following DNA damage. Cancer Res; 71(15); 5287-95. (c) 2011 AACR.
C1 [Ming, Mei; Shea, Christopher R.; Soltani, Keyoumars; Han, Weinong; He, Yu-Ying] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA.
[Feng, Li; Zhao, Baozhong; Trempus, Carol S.] Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC USA.
[Smart, Robert C.] N Carolina State Univ, Cell Signaling & Canc Grp, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA.
RP He, YY (reprint author), Univ Chicago, Dept Med, Dermatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM yyhe@medicine.bsd.uchicago.edu
RI Zhao, Baozhong/B-5865-2011
FU NIH [ES016936]; University of Chicago Comprehensive Cancer Center [P30
CA014599]; CTSA [NIH UL1RR024999]; NIH/NIEHS; UC
FX This work was supported by NIH grant ES016936 (Y.Y. He), the University
of Chicago Comprehensive Cancer Center Pilot program (P30 CA014599), the
CTSA (NIH UL1RR024999), the NIH/NIEHS intramural program, and UC Friends
of Dermatology Research Funds.
NR 41
TC 37
Z9 37
U1 0
U2 10
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 AUG 1
PY 2011
VL 71
IS 15
BP 5287
EP 5295
DI 10.1158/0008-5472.CAN-10-4614
PG 9
WC Oncology
SC Oncology
GA 799ET
UT WOS:000293267600025
PM 21771908
ER
PT J
AU Fernando, RI
Castillo, MD
Litzinger, M
Hamilton, DH
Palena, C
AF Fernando, Romaine I.
Castillo, Marianne D.
Litzinger, Mary
Hamilton, Duane H.
Palena, Claudia
TI IL-8 Signaling Plays a Critical Role in the Epithelial-Mesenchymal
Transition of Human Carcinoma Cells
SO CANCER RESEARCH
LA English
DT Article
ID BREAST-CARCINOMA; TUMOR-GROWTH; METASTATIC PHENOTYPE; SERUM
INTERLEUKIN-8; MALIGNANT-MELANOMA; PROSTATE-CANCER; STEM-CELLS;
IN-VITRO; EXPRESSION; PROGRESSION
AB The switch of tumor cells from an epithelial to a mesenchymal-like phenotype [designated as epithelial-to-mesenchymal transition (EMT)] is known to induce tumor cell motility and invasiveness, therefore promoting metastasis of solid carcinomas. Although multiple studies have focused on elucidating the signaling events that initiate this phenotypic switch, there has been so far no characterization of the pattern of soluble mediators released by tumor cells undergoing EMT, and the potential impact that this phenotypic switch could have on the remodeling of the tumor microenvironment. Here we show that induction of EMT in human carcinoma cells via overexpression of the transcription factor Brachyury is associated with enhanced secretion of multiple cytokines, chemokines, and angiogenic factors and, in particular, with the induction of the IL-8/IL-8R axis. Our results also indicate the essential role of interleukin 8 (IL-8) signaling for the acquisition and/or maintenance of the mesenchymal and invasive features of Brachyury-overexpressing tumor cells and show that IL-8 secreted by tumor cells undergoing EMT could potentiate tumor progression by inducing adjacent epithelial tumor cells into EMT. Altogether, our results emphasize the potential role of EMT in the modulation of the tumor microenvironment via secretion of multiple soluble mediators and suggest that IL-8 signaling blockade may provide a means of targeting mesenchymal-like, invasive tumor cells. Cancer Res; 71(15); 5296-306. (C) 2011 AACR.
C1 [Fernando, Romaine I.; Castillo, Marianne D.; Litzinger, Mary; Hamilton, Duane H.; Palena, Claudia] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Palena, C (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B14,MSC 1750, Bethesda, MD 20892 USA.
EM palenac@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, NIH
FX The work was supported by Intramural Research Program of the Center for
Cancer Research, National Cancer Institute, NIH.
NR 44
TC 119
Z9 129
U1 1
U2 10
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 AUG 1
PY 2011
VL 71
IS 15
BP 5296
EP 5306
DI 10.1158/0008-5472.CAN-11-0156
PG 11
WC Oncology
SC Oncology
GA 799ET
UT WOS:000293267600026
PM 21653678
ER
PT J
AU Kato, J
Zhu, JF
Liu, CY
Stylianou, M
Hoffmann, V
Lizak, MJ
Glasgow, CG
Moss, J
AF Kato, Jiro
Zhu, Jianfeng
Liu, Chengyu
Stylianou, Mario
Hoffmann, Victoria
Lizak, Martin J.
Glasgow, Connie G.
Moss, Joel
TI ADP-Ribosylarginine Hydrolase Regulates Cell Proliferation and
Tumorigenesis
SO CANCER RESEARCH
LA English
DT Article
ID HUMAN NEUTROPHIL PEPTIDE-1; ADENINE-DINUCLEOTIDE NAD; SKELETAL-MUSCLE;
SUBSTRATE-SPECIFICITY; TURKEY ERYTHROCYTES; CYCLE CONTROL; RIBOSYLATION;
RIBOSYLTRANSFERASE; CANCER; P53
AB Protein ADP-ribosylation is a reversible posttranslational modification of uncertain significance in cancer. In this study, we evaluated the consequences for cancer susceptibility in the mouse of a genetic deletion of the enzyme responsible for removing mono-ADP-ribose moieties from arginines in cellular proteins. Specifically, we analyzed cancer susceptibility in animals lacking the ADP-ribosylarginine hydrolase (ARH1) that cleaves the ADP ribose-protein bond. ARH1(-/-) cells or ARH1(-/-) cells overexpressing an inactive mutant ARH1 protein (ARH1(-/-) +dm) had higher proliferation rates than either wild-type ARH1(+/+) cells or ARH1(-/-) cells engineered to express the wild-type ARH1 enzyme. More significantly, ARH1(-/-) and ARH1(+/-) mice spontaneously developed lymphomas, adenocarcinomas, and metastases more frequently than wild-type ARH1(+/+) mice. In ARH1(+/-) mice, we documented in all arising tumors mutation of the remaining wild-type allele (or loss of heterozygosity), illustrating the strict correlation that existed between tumor formation and absence of ARH1 gene function. Our findings show that proper control of protein ADP-ribosylation levels affected by ARH1 is essential for cancer suppression. Cancer Res; 71(15); 5327-35. (C) 2011 AACR.
C1 [Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Chengyu] NHLBI, Transgen Mouse Core Facil, Bethesda, MD 20892 USA.
[Stylianou, Mario] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Hoffmann, Victoria] NIH, Diagnost & Res Serv Branch, Div Vet Resources, Bethesda, MD 20892 USA.
[Lizak, Martin J.] NIH, Mouse Imaging Facil, Bethesda, MD 20892 USA.
RP Moss, J (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA.
EM mossj@nhlbi.nih.gov
FU NIH, National Heart, Lung, and Blood Institute
FX This research was supported by the Intramural Research Program of the
NIH, National Heart, Lung, and Blood Institute.
NR 37
TC 17
Z9 17
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 1
PY 2011
VL 71
IS 15
BP 5327
EP 5335
DI 10.1158/0008-5472.CAN-10-0733
PG 9
WC Oncology
SC Oncology
GA 799ET
UT WOS:000293267600029
PM 21697277
ER
PT J
AU Voortman, J
Schetter, AJ
Harris, CC
Giaccone, G
AF Voortman, Johannes
Schetter, Aaron J.
Harris, Curtis C.
Giaccone, Giuseppe
TI MicroRNA Expression and Outcome in Resected NSCLC-Response
SO CANCER RESEARCH
LA English
DT Letter
ID CELL LUNG-CANCER; TRIAL BIOLOGIC PROGRAM; ADJUVANT CHEMOTHERAPY
C1 [Voortman, Johannes; Giaccone, Giuseppe] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Schetter, Aaron J.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
NR 4
TC 0
Z9 0
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 AUG 1
PY 2011
VL 71
IS 15
BP 5358
EP 5359
DI 10.1158/0008-5472.CAN-11-1205
PG 2
WC Oncology
SC Oncology
GA 799ET
UT WOS:000293267600033
ER
PT J
AU Urick, ME
Chung, EJ
Shield, WP
Gerber, N
White, A
Sowers, A
Thetford, A
Camphausen, K
Mitchell, J
Citrin, DE
AF Urick, Mary Ellen
Chung, Eun Joo
Shield, William P., III
Gerber, Naamit
White, Ayla
Sowers, Anastasia
Thetford, Angela
Camphausen, Kevin
Mitchell, James
Citrin, Deborah E.
TI Enhancement of 5-Fluorouracil-induced In Vitro and In Vivo
Radiosensitization with MEK Inhibition
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SIGNAL-REGULATED KINASE; PANCREATIC-CANCER CELLS; HUMAN COLON-CANCER;
AZD6244 ARRY-142886; COLORECTAL-CANCER; SURVIVIN EXPRESSION; THERAPEUTIC
TARGET; ENDOTHELIAL-CELLS; CARCINOMA-CELLS; DOWN-REGULATION
AB Purpose: Gastrointestinal cancers frequently exhibit mutational activation of the Ras/MAPK pathway, which is implicated in resistance to ionizing radiation (IR) and chemotherapy. Concurrent radiotherapy and 5-fluorouracil (5-FU) based chemotherapy is commonly used for treatment of gastrointestinal malignancies. We previously reported radiosensitization with selumetinib, an inhibitor of MEK1/2. The purpose of the current study was to evaluate if selumetinib could enhance radiosensitivity induced by 5-FU.
Experimental Design: Clonogenic survival assays were carried out with the HT29 (colorectal), HCT116 (colorectal), and MiaPaca-2 (pancreatic) cell lines using pre-IR treatment with selumetinib, 5-FU and 5-FU+selumetinib. Cell proliferation was determined using a tetrazolium conversion assay. Mitotic catastrophe and DNA repair were analyzed using immunocytochemistry. Flow cytometry was used to analyze cell cycle and apoptosis. Growth delay was used to determine effects of 5-FU+selumetinib on in vivo tumor radiosensitivity.
Results: Pre-IR treatment with 5-FU+selumetinib significantly decreased clonogenic survival compared with either agent alone. Dose modifying factors at a surviving fraction of 0.1 for 5-FU+selumetinib was 1.78, 1.52, and 1.3 for HT29, HCT116, and MiaPaca-2, respectively. Cell proliferation was decreased by treatment with selumetinib+5-FU as compared with single agent treatment regardless of treatment sequencing. Enhancement of 5-FU cytotoxicity and 5-FU mediated radiosensitization with selumetinib treatment was accompanied by an increase in mitotic catastrophe and apoptosis, and reductions in Stat3 phosphorylation and survivin expression. In vivo, an additive growth delay was observed with 5-FU+selumetinib+3Gy versus 5-FU+3Gy and selumetinib alone.
Conclusion: These data suggest that selumetinib can be used with 5-FU to augment radiation response. Clin Cancer Res; 17(15); 5038-47. (C)2011 AACR.
C1 [Urick, Mary Ellen; Chung, Eun Joo; Shield, William P., III; Gerber, Naamit; White, Ayla; Camphausen, Kevin; Citrin, Deborah E.] NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Sowers, Anastasia; Thetford, Angela; Mitchell, James] NIH, Radiat Biol Branch, Bethesda, MD 20892 USA.
RP Citrin, DE (reprint author), NCI, Radiat Oncol Branch, Bldg 10 CRC,B2-3500, Bethesda, MD 20892 USA.
EM citrind@mail.nih.gov
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 41
TC 10
Z9 10
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 1
PY 2011
VL 17
IS 15
BP 5038
EP 5047
DI 10.1158/1078-0432.CCR-11-0358
PG 10
WC Oncology
SC Oncology
GA 800CH
UT WOS:000293335800016
PM 21690569
ER
PT J
AU Zielinski, R
Lyakhov, I
Hassan, M
Kuban, M
Shafer-Weaver, K
Gandjbakhche, A
Capala, J
AF Zielinski, Rafal
Lyakhov, Ilya
Hassan, Moinuddin
Kuban, Monika
Shafer-Weaver, Kimberly
Gandjbakhche, Amir
Capala, Jacek
TI HER2-Affitoxin: A Potent Therapeutic Agent for the Treatment of
HER2-Overexpressing Tumors
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID METASTATIC BREAST-CANCER; BINDING AFFIBODY MOLECULE; IN-VIVO;
MONOCLONAL-ANTIBODY; MALIGNANT-TUMORS; HER2 EXPRESSION; HER2-POSITIVE
TUMORS; ANTICANCER AGENT; IMMUNOTOXIN; CHEMOTHERAPY
AB Purpose: Cancers overexpressing the HER2/neu gene are usually more aggressive and are associated with poor prognosis. Although trastuzumab has significantly improved the outcome, many tumors do not respond or acquire resistance to current therapies. To provide an alternative HER2-targeted therapy, we have developed and characterized a novel recombinant protein combining an HER2-specific Affibody and modified Pseudomonas aeruginosa exotoxin A (PE 38), which, after binding to HER2, is internalized and delivered to the cytosol of the tumor cell, where it blocks protein synthesis by ADP ribosylation of eEF-2.
Experimental Design: The effect of the Affitoxin on cell viability was assessed using CellTiter-Glo (Promega). To assess HER2-specific efficacy, athymic nude mice bearing BT-474 breast cancer, SK-OV-3 ovarian cancer, and NCI-N87 gastric carcinoma xenografts were treated with the Affitoxin (HER2- or Tag-specific), which was injected every third day. Affitoxin immunogenicity in female BALB/c mice was investigated using standard antibody production and splenocyte proliferation assays.
Results: In vitro experiments proved that HER2-Affitoxin is a potent agent that eliminates HER2-overexpressing cells at low picomolar concentrations. Therapeutic efficacy studies showed complete eradication of relatively large BT-474 tumors and significant effects on SK-OV-3 and NCI-N87 tumors. HER2-Affitoxin cleared quickly from circulation (T(1/2) < 10 minutes) and was well tolerated by mice at doses of 0.5 mg/kg and below. Immunogenicity studies indicated that HER2-Affitoxin induced antibody development after the third injected dose.
Conclusions: Our findings showed that HER2-Affitoxin is an effective anticancer agent and a potential candidate for clinical studies. Clin Cancer Res; 17(15); 5071-81. (C)2011 AACR.
C1 [Capala, Jacek] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hassan, Moinuddin; Gandjbakhche, Amir] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Analyt & Funct Biophoton, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD USA.
[Zielinski, Rafal] John Paul II Catholic Univ Lublin, Dept Mol Biol, Lublin, Poland.
[Lyakhov, Ilya] NCI Frederick, Prot Chem Lab, Frederick, MD USA.
[Shafer-Weaver, Kimberly] NCI Frederick, Lab Cell Mediated Immun, SAIC Frederick Inc, Frederick, MD USA.
RP Capala, J (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room B3B37D, Bethesda, MD 20892 USA.
EM capalaj@mail.nih.gov
FU Center for Cancer Research; National Cancer Institute; Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH;
Breast Cancer Research; National Cancer Institute, NIH [N01-CO-12400,
N01-CO-12401]
FX This research was supported in part by the Center for Cancer Research,
an Intramural Research Program of the National Cancer Institute, and by
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH. Additional support came from the Breast Cancer
Research Stamp Fund awarded through competitive peer review and was
funded in part with Federal funds from the National Cancer Institute,
NIH, under contracts N01-CO-12400 and N01-CO-12401.
NR 37
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Z9 19
U1 0
U2 7
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 AUG 1
PY 2011
VL 17
IS 15
BP 5071
EP 5081
DI 10.1158/1078-0432.CCR-10-2887
PG 11
WC Oncology
SC Oncology
GA 800CH
UT WOS:000293335800019
PM 21791637
ER
PT J
AU Weniger, MA
Rizzatti, EG
Perez-Galan, P
Liu, DL
Wang, QY
Munson, PJ
Raghavachari, N
White, T
Tweito, MM
Dunleavy, K
Ye, YH
Wilson, WH
Wiestner, A
AF Weniger, Marc A.
Rizzatti, Edgar G.
Perez-Galan, Patricia
Liu, Delong
Wang, Qiuyan
Munson, Peter J.
Raghavachari, Nalini
White, Therese
Tweito, Megan M.
Dunleavy, Kieron
Ye, Yihong
Wilson, Wyndham H.
Wiestner, Adrian
TI Treatment-Induced Oxidative Stress and Cellular Antioxidant Capacity
Determine Response to Bortezomib in Mantle Cell Lymphoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; PROTEASOME
INHIBITORS INDUCE; MULTIPLE-MYELOMA CELLS; NF-KAPPA-B; CANCER-CELLS; ER
STRESS; SIGNALING PATHWAY; REDOX HOMEOSTASIS; INDUCED APOPTOSIS
AB Purpose: Proteasome inhibition disrupts protein homeostasis and induces apoptosis. Up to 50% of patients with relapsed mantle cell lymphoma (MCL) respond to bortezomib. We used gene expression profiling to investigate the connection between proteasome inhibition, cellular response, and clinical efficacy.
Experimental Design: We assessed transcriptional changes in primary tumor cells from five patients during treatment with bortezomib in vivo, and in 10 MCL cell lines exposed to bortezomib in vitro, on Affymetrix microarrays. Key findings were confirmed by western blotting.
Results: MCL cell lines exposed to bortezomib in vitro showed upregulation of endoplasmic reticulum and oxidative stress response pathways. Gene expression changes were strongest in bortezomib-sensitive cells and these cells were also more sensitive to oxidative stress induced by H2O2. Purified tumor cells obtained at several timepoints during bortezomib treatment in 5 previously untreated patients with leukemic MCL showed strong activation of the antioxidant response controlled by NRF2. Unexpectedly, activation of this homeostatic program was significantly stronger in tumors with the best clinical response. Consistent with its proapoptotic function, we found upregulation of NOXA in circulating tumor cells of responding patients. In resistant cells, gene expression changes in response to bortezomib were limited and upregulation of NOXA was absent. Interestingly, at baseline, bortezomib-resistant cells displayed a relatively higher expression of the NRF2 gene-expression signature than sensitive cells (P < 0.001).
Conclusion: Bortezomib triggers an oxidative stress response in vitro and in vivo. High cellular antioxidant capacity contributes to bortezomib resistance. Clin Cancer Res; 17(15); 5101-12. (C)2011 AACR.
C1 [Weniger, Marc A.; Rizzatti, Edgar G.; Perez-Galan, Patricia; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Delong; Munson, Peter J.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Wang, Qiuyan; Ye, Yihong] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Raghavachari, Nalini] NHLBI, Gene Express Core Facil, Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[White, Therese; Tweito, Megan M.; Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Rizzatti, Edgar G.] Fleury Med & Saude, Sao Paulo, Brazil.
RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wiestnera@mail.nih.gov
FU National Institutes of Health; National, Heart, Lung and Blood
Institute; National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, the National, Heart, Lung and Blood
Institute, and the National Cancer Institute as well as through a Bench
to Bedside award by the National Institutes of Health.
NR 47
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U2 3
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 AUG 1
PY 2011
VL 17
IS 15
BP 5101
EP 5112
DI 10.1158/1078-0432.CCR-10-3367
PG 12
WC Oncology
SC Oncology
GA 800CH
UT WOS:000293335800022
PM 21712452
ER
PT J
AU DuBois, SG
Shusterman, S
Ingle, AM
Ahern, CH
Reid, JM
Wu, B
Baruchel, S
Glade-Bender, J
Ivy, P
Grier, HE
Adamson, PC
Blaney, SM
AF DuBois, Steven G.
Shusterman, Suzanne
Ingle, Ashish M.
Ahern, Charlotte H.
Reid, Joel M.
Wu, Bing
Baruchel, Sylvain
Glade-Bender, Julia
Ivy, Percy
Grier, Holcombe E.
Adamson, Peter C.
Blaney, Susan M.
TI Phase I and Pharmacokinetic Study of Sunitinib in Pediatric Patients
with Refractory Solid Tumors: A Children's Oncology Group Study
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TYROSINE KINASE INHIBITOR; RENAL-CELL CARCINOMA; GASTROINTESTINAL
STROMAL TUMORS; CIRCULATING ENDOTHELIAL-CELLS; GROWTH-FACTOR RECEPTOR;
ANTITUMOR-ACTIVITY; INTERFERON-ALPHA; MALATE SU11248; VIVO ANTITUMOR;
CANCER
AB Purpose: Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor. The purpose of this study was to determine the recommended phase 2 dose, pharmacokinetics, pharmacodynamic effects, and preliminary antitumor activity of sunitinib in a pediatric population.
Experimental Design: Patients who were 2 to 21 years of age with refractory solid tumors were eligible if they had measurable or evaluable disease and met baseline organ function requirements. Patients received sunitinib once daily for 28 days followed by a 14-day break between each cycle. Dose levels of 15 and 20 mg/m(2)/d were evaluated, with dose escalation based on a 3 + 3 design. Sunitinib pharmacokinetics and biomarkers of angiogenesis were also evaluated during the first cycle.
Results: Twenty-three patients were treated (median age 13.9 years; range, 3.9-20.6 years). The most common toxicities were neutropenia, thrombocytopenia, elevated liver transaminases, gastrointestinal symptoms, and fatigue. Two patients developed dose-limiting reductions in cardiac ejection fraction prompting a protocol amendment to exclude patients with previous exposure to anthracyclines or cardiac radiation. In patients without these cardiac risk factors, the maximum tolerated dose (MTD) was 15 mg/m(2)/d. Steady-state plasma concentrations were reached by day 7. No objective responses were observed. Four patients with sarcoma and glioma had stable disease for 2 to 9 cycles.
Conclusions: Cardiac toxicity precluded determination of a recommended dose for pediatric patients with previous anthracycline or cardiac radiation exposure. The MTD of sunitinib for patients without risk factors for cardiac toxicity is 15 mg/m(2)/d for 28 days followed by a 14-day break. Clin Cancer Res; 17(15); 5113-22. (C)2011 AACR.
C1 [DuBois, Steven G.] Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA.
[Shusterman, Suzanne; Grier, Holcombe E.] Childrens Hosp Boston, Dana Farber Canc Inst, Dept Pediat, Boston, MA USA.
[Shusterman, Suzanne; Grier, Holcombe E.] Harvard Univ, Sch Med, Boston, MA USA.
[Ingle, Ashish M.] Childrens Oncol Grp Operat Ctr, Arcadia, CA USA.
[Ahern, Charlotte H.] Dan L Duncan Canc Ctr, Div Biostat, Houston, TX USA.
[Ahern, Charlotte H.; Blaney, Susan M.] Baylor Coll Med, Houston, TX 77030 USA.
[Blaney, Susan M.] Texas Childrens Canc Ctr, Dept Pediat, Houston, TX USA.
[Reid, Joel M.] Mayo Coll Med, Dept Pharmacol, Rochester, MN USA.
[Wu, Bing; Baruchel, Sylvain] Hosp Sick Children, Dept Hematol Oncol, Toronto, ON M5G 1X8, Canada.
[Glade-Bender, Julia] Morgan Stanley Childrens Hosp, Dept Pediat, New York, NY USA.
[Glade-Bender, Julia] Columbia Univ, Sch Med, New York, NY USA.
[Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Adamson, Peter C.] Childrens Hosp Philadelphia, Dept Oncol, Philadelphia, PA 19104 USA.
[Adamson, Peter C.] Univ Penn, Philadelphia, PA 19104 USA.
RP DuBois, SG (reprint author), Univ Calif San Francisco, Sch Med, Dept Pediat, 505 Parnassus Ave,M646, San Francisco, CA 94143 USA.
EM duboiss@peds.ucsf.edu
FU Campini Foundation; Pfizer; NIH/NCRR/OD [KL2 RR024130]; NCI [U01
CA97452]
FX This work was supported by the Campini Foundation, Pfizer, NIH/NCRR/OD
UCSF-CTSI grant number KL2 RR024130, and NCI U01 CA97452.
NR 45
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U1 0
U2 2
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 AUG 1
PY 2011
VL 17
IS 15
BP 5113
EP 5122
DI 10.1158/1078-0432.CCR-11-0237
PG 10
WC Oncology
SC Oncology
GA 800CH
UT WOS:000293335800023
PM 21690570
ER
PT J
AU Kummar, S
Raffeld, M
Juwara, L
Horneffer, Y
Strassberger, A
Allen, D
Steinberg, SM
Rapisarda, A
Spencer, SD
Figg, WD
Chen, XH
Turkbey, IB
Choyke, P
Murgo, AJ
Doroshow, JH
Melillo, G
AF Kummar, Shivaani
Raffeld, Mark
Juwara, Lamin
Horneffer, Yvonne
Strassberger, Agnes
Allen, Deborah
Steinberg, Seth M.
Rapisarda, Annamaria
Spencer, Shawn D.
Figg, William D.
Chen, Xiaohong
Turkbey, Ismail Baris
Choyke, Peter
Murgo, Anthony J.
Doroshow, James H.
Melillo, Giovanni
TI Multihistology, Target-Driven Pilot Trial of Oral Topotecan as an
Inhibitor of Hypoxia-Inducible Factor-1 alpha in Advanced Solid Tumors
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID FACTOR 1-ALPHA; UNFAVORABLE PROGNOSIS; TOPOISOMERASE-I; CANCER-THERAPY;
OVEREXPRESSION; XENOGRAFTS; EXPRESSION; CARCINOMA; 104864-A; GROWTH
AB Purpose: Hypoxia-inducible factor 1 (HIF-1) alpha is frequently overexpressed in human tumors and is associated with angiogenesis and metastasis. Topotecan, a topoisomerase I inhibitor, has been shown to inhibit HIF-1 alpha expression in preclinical models. We designed a pilot trial to measure HIF-1 alpha inhibition in tumor biopsies from patients with advanced solid tumors overexpressing HIF-1 alpha, after treatment with oral topotecan.
Experimental Design: Topotecan was administered orally at 1.6 mg/m(2) once daily for 5 days/week for 2 weeks, in 28-day cycles. Objectives were to determine inhibition of expression of HIF-1 alpha and HIF-1 target genes in tumor; to assess tumor blood flow by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI); and to measure pharmacokinetics. Tumor biopsies were collected at baseline and during the second cycle of treatment.
Results: Sixteen patients were enrolled. The dose of topotecan was reduced to 1.2 mg/m(2)/day due to myelosuppression. Seven patients had paired tumor biopsies. In 4 patients, HIF-1 alpha nuclear staining became undetectable after treatment (7.5%-50% staining at baseline). Decreased levels of VEGF and GLUT-1 mRNA were measured in 4 patients; the changes were concordant with reduction in HIF-1 alpha in 3 patients. Decreased tumor blood flow and permeability were observed by DCE-MRI in 7 of 10 patients after 1 cycle. One patient had a partial response accompanied by inhibition of HIF-1 alpha in tumor and reduction in tumor blood flow on DCE-MRI.
Conclusions: This multihistology, target assessment trial of a small molecule inhibitor of HIF-1 alpha showed that topotecan could decrease HIF-1 alpha expression in advanced solid tumors. Clin Cancer Res; 17(15); 5123-31. (C)2011 AACR.
C1 [Rapisarda, Annamaria; Spencer, Shawn D.; Melillo, Giovanni] Natl Canc Inst Frederick, App Dev Res Support Directorate, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
[Kummar, Shivaani; Raffeld, Mark; Horneffer, Yvonne; Strassberger, Agnes; Allen, Deborah; Steinberg, Seth M.; Figg, William D.; Chen, Xiaohong; Turkbey, Ismail Baris; Choyke, Peter; Doroshow, James H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kummar, Shivaani; Murgo, Anthony J.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Juwara, Lamin] Natl Canc Inst Frederick, Clin Monitoring Res Program, Frederick, MD 21702 USA.
RP Melillo, G (reprint author), Natl Canc Inst Frederick, App Dev Res Support Directorate, Sci Applicat Int Corp Frederick Inc, POB B, Frederick, MD 21702 USA.
EM melillog@mail.nih.gov
RI Figg Sr, William/M-2411-2016
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Center for Cancer Research; Division of Cancer
Treatment and Diagnosis of the National Cancer Institute
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported by the Center for Cancer Research and the
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute.
NR 21
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U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 1
PY 2011
VL 17
IS 15
BP 5123
EP 5131
DI 10.1158/1078-0432.CCR-11-0682
PG 9
WC Oncology
SC Oncology
GA 800CH
UT WOS:000293335800024
PM 21673063
ER
PT J
AU Lee, D
Milman, G
Barnes, AJ
Goodwin, RS
Hirvonen, J
Huestis, MA
AF Lee, Dayong
Milman, Garry
Barnes, Allan J.
Goodwin, Robert S.
Hirvonen, Jussi
Huestis, Marilyn A.
TI Oral Fluid Cannabinoids in Chronic, Daily Cannabis Smokers during
Sustained, Monitored Abstinence
SO CLINICAL CHEMISTRY
LA English
DT Article
ID GC-MS-MS; PHARMACOKINETIC PROPERTIES; MOTOR-VEHICLE;
DELTA(9)-TETRAHYDROCANNABINOL; DRUGS; MARIJUANA; ABUSE; USERS;
METABOLISM; TETRAHYDROCANNABINOL
AB BACKGROUND: Oral fluid (OF) is an accepted alternative biological matrix for drug treatment, workplace, and DUID (driving under the influence of drugs) investigations, but establishing the cannabinoid OF detection window and concentration cutoff criteria are important.
METHODS: Cannabinoid concentrations were quantified in OF from chronic, daily cannabis smokers during monitored abstinence. Delta(9)-tetrahydrocannabinol (THC)(3), cannabidiol (CBD), cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) were determined in daily OF samples collected with the Quantisal (TM) device. GC-MS limits of quantification (LOQ) were 0.5 mu g/L for THC and CBD, 1 mu g/L for CBN, and 7.5 ng/L for THCCOOH.
RESULTS: After providing written informed consent for this institutional review board-approved study, 28 participants resided from 4 to 33 days on the secure research unit and provided 577 OF specimens. At the LOQ, THC was generally quantifiable for 48 h, whereas CBD and CBN were detected only at admission. Median THCCOOH detection time was 13 days (CI 6.4-19.6 days). Mean THC detection rates decreased from 89.3% at admission to 17.9% after 48 h, whereas THCCOOH gradually decreased from 89.3% to 64.3% within 4 days. Criteria of THC >= 2 mu g/L and THCCOOH >= 20 ng/L reduced detection to <48 h in chronic cannabis smokers. An OF THCCOOH/THC ratio <= 4 ng/mu g or presence of CBD or CBN may indicate more recent smoking.
CONCLUSIONS: THC, THCCOOH, CBD, and CBN quantification in confirmatory OF cannabinoid testing is recommended. Inclusion of multiple cannabinoid cutoffs accounted for residual cannabinoid excretion in OF from chronic, daily cannabis smokers and could reduce the potential for positive test results from passive cannabis smoke exposure and lead to greatly improved test interpretation. (C) 2011 American Association for Clinical Chemistry
C1 [Huestis, Marilyn A.] NIDA, IRP, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Hirvonen, Jussi] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Huestis, MA (reprint author), NIDA, IRP, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU National Institute on Drug Abuse, National Institutes of Health
FX Intramural Research Program of the National Institute on Drug Abuse,
National Institutes of Health.
NR 36
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U1 1
U2 19
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD AUG
PY 2011
VL 57
IS 8
BP 1127
EP 1136
DI 10.1373/clinchem.2011.164822
PG 10
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 798PN
UT WOS:000293222900009
PM 21677094
ER
PT J
AU Harrington, WE
Mutabingwa, TK
Kabyemela, E
Fried, M
Duffy, PE
AF Harrington, Whitney E.
Mutabingwa, Theonest K.
Kabyemela, Edward
Fried, Michal
Duffy, Patrick E.
TI Intermittent Treatment to Prevent Pregnancy Malaria Does Not Confer
Benefit in an Area of Widespread Drug Resistance
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID LOW-BIRTH-WEIGHT; PLASMODIUM-FALCIPARUM; SULFADOXINE-PYRIMETHAMINE;
FETAL ANEMIA; RISK-FACTORS; EFFECTIVENESS TRIAL; PLACENTAL MALARIA;
RURAL MALAWI; WOMEN; PARASITES
AB Background. Millions of African women receive sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment during pregnancy (IPTp) to avoid poor outcomes that result from malaria. However, parasites resistant to SP are widespread in parts of Africa, and IPTp may perversely exacerbate placental infections that contain SP-resistant parasites.
Methods. The study used a cross-sectional design. We determined IPTp use in a delivery cohort of 880 pregnant women in Muheza, Tanzania, by report and by plasma sulfa measurements, and we examined its effects on maternal and fetal delivery outcomes.
Results. In the overall cohort, IPTp was not associated with decreased odds of placental malaria or with increased mean maternal hemoglobin or mean birth weight. Unexpectedly, IPTp was associated with decreased cord hemoglobin level and increased risk of fetal anemia, which may be related to in utero SP exposure.
Conclusions. IPTp does not improve overall pregnancy outcomes in Muheza, Tanzania, where SP-resistant parasites predominate and may increase the odds of fetal anemia. As parasite resistance increases in a community, the overall effect of IPTp may transition from net benefit to neutral or net harm.
C1 [Fried, Michal; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
[Harrington, Whitney E.; Mutabingwa, Theonest K.; Kabyemela, Edward; Fried, Michal; Duffy, Patrick E.] Seattle Biomed Res Inst, Malaria Program, Seattle, WA 98109 USA.
[Harrington, Whitney E.; Fried, Michal; Duffy, Patrick E.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Mutabingwa, Theonest K.] Natl Inst Med Res, Dar Es Salaam, Tanzania.
RP Duffy, PE (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, Twinbrook 1,Rm 1111,5640 Fishers Ln, Rockville, MD USA.
EM patrick.duffy@nih.gov
FU Bill & Melinda Gates Foundation [29202]; Foundation for the National
Institutes of Health through the Grand Challenges in Global Health
Initiative [1364]; US National Institutes of Health Fogarty
International Center (FIC) [D43 TW005509]; National Institute of Allergy
and Infectious Diseases [R01AI52059]; National Heart, Lung, and Blood
Institute (NIH) [1F30HL096298]
FX This work was supported by the Bill & Melinda Gates Foundation (grant
29202); the Foundation for the National Institutes of Health through the
Grand Challenges in Global Health Initiative (grant 1364); the US
National Institutes of Health Fogarty International Center (FIC) (grant
D43 TW005509); the National Institute of Allergy and Infectious Diseases
(R01AI52059 to P. E. D.); and by the National Heart, Lung, and Blood
Institute (NIH Fellowship 1F30HL096298 to W. E. H.).
NR 34
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U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD AUG 1
PY 2011
VL 53
IS 3
BP 224
EP 230
DI 10.1093/cid/cir376
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 796BK
UT WOS:000293025000002
PM 21765070
ER
PT J
AU Murphy, EA
Davis, JM
Barrilleaux, TL
McClellan, JL
Steiner, JL
Carmichael, MD
Pena, MM
Hebert, JR
Green, JE
AF Murphy, E. A.
Davis, J. M.
Barrilleaux, T. L.
McClellan, J. L.
Steiner, J. L.
Carmichael, M. D.
Pena, M. M.
Hebert, J. R.
Green, J. E.
TI Benefits of exercise training on breast cancer progression and
inflammation in C3(1)SV40Tag mice
SO CYTOKINE
LA English
DT Article
DE Physical activity; Mammary tumorigenesis; Mouse models; Cytokines
ID INDUCED MAMMARY CARCINOGENESIS; TRANSGENIC MOUSE MODEL; REDUCED
ENERGY-INTAKE; PHYSICAL-ACTIVITY; CHEMOATTRACTANT PROTEIN-1;
TUMOR-GROWTH; SERUM-LEVELS; CARCINOMA; TUMORIGENESIS; PREVENTION
AB Many observational epidemiologic studies suggest an association between exercise and breast cancer risk. However, the lack of controlled experimental studies that examine this relationship and the mechanisms involved weaken the basis for inferring a causal relationship. Inflammation plays a role in breast cancer progression and exercise has been reported to reduce inflammation; however, the anti-inflammatory effects of exercise in breast cancer have yet to be established. We examined the relationship between exercise training and systemic inflammation in relation to breast cancer progression in C3(1)SV40Tag mice. Female C3(1)SV40Tag mice were assigned to either exercise (Ex) or sedentary (Sed) treatment (n = 12-14/group). Beginning at 4 wks of age mice (Ex) were run on a treadmill for 60 min/d (20 m/min and 5% grade), 6 d/wk for a period of 20 wks. Mice were examined weekly for palpable tumors, and tumor number and volume were recorded. At 24 wks of age mice were sacrificed and a more direct measure of tumor number and volume, and spleen weight was recorded. Plasma was analyzed for MCP-1 and IL-6 concentration using ELISA. Ex reduced palpable tumor number at sacrifice (24 wks) by approximately 70% (P < 0.05). Tumor volume was also reduced in Ex at 21-23 wks (P < 0.05). This reduction in tumor progression by Ex was associated with a reduction in plasma concentration of MCP-1 and IL-6, and spleen weight (P < 0.05). These data provide strong support for a beneficial effect of exercise training on tumor progression in the C3(1)SV40Tag mouse model of breast cancer that may be partly mediated by its anti-inflammatory potential. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Murphy, E. A.] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29209 USA.
[Davis, J. M.; Barrilleaux, T. L.; McClellan, J. L.; Steiner, J. L.; Carmichael, M. D.] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA.
[Pena, M. M.] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA.
[Hebert, J. R.] Univ S Carolina, Canc Prevent & Control Program, Columbia, SC 29208 USA.
[Hebert, J. R.] Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
[Green, J. E.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
RP Murphy, EA (reprint author), Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, 6439 Garners Ferry Rd, Columbia, SC 29209 USA.
EM angela.murphy@uscmed.sc.edu; markd@mailbox.sc.edu;
mooretl2@mailbox.sc.edu; mcclelll@mailbox.sc.edu; jls2tc@virginia.edu;
mdcarmic@mailbox.sc.edu; mpena@biol.sc.edu; jhebert@mailbox.sc.edu;
jegreen@mail.nih.gov
FU NIH; National Cancer Institute; Cancer Training Branch of the National
Cancer Institute [K05 CA136975]; Center for Cancer Research
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research and by
an Established Investigator Award in Cancer Prevention and Control from
the Cancer Training Branch of the National Cancer Institute to JR Hebert
(K05 CA136975).
NR 42
TC 16
Z9 16
U1 1
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD AUG
PY 2011
VL 55
IS 2
BP 274
EP 279
DI 10.1016/j.cyto.2011.04.007
PG 6
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 797VL
UT WOS:000293158100017
PM 21600785
ER
PT J
AU Lu, ZP
Bourdi, M
Li, JH
Aponte, AM
Chen, Y
Lombard, DB
Gucek, M
Pohl, LR
Sack, MN
AF Lu, Zhongping
Bourdi, Mohammed
Li, Jian H.
Aponte, Angel M.
Chen, Yong
Lombard, David B.
Gucek, Marjan
Pohl, Lance R.
Sack, Michael N.
TI SIRT3-dependent deacetylation exacerbates acetaminophen hepatotoxicity
SO EMBO REPORTS
LA English
DT Article
DE SIRT3; acetaminophen liver failure; ALDH2; mitochondrial protein
acetylation; N-acetyl-p-benzoquinoneimine
ID MITOCHONDRIAL PERMEABILITY TRANSITION; LYSINE ACETYLATION; ALDEHYDE
DEHYDROGENASE; CELL-DEATH; IN-VIVO; PROTEIN; LIVER; SIRT3;
SUSCEPTIBILITY; IDENTIFICATION
AB Acetaminophen/paracetamol-induced liver failure-which is induced by the binding of reactive metabolites to mitochondrial proteins and their disruption-is exacerbated by fasting. As fasting promotes SIRT3-mediated mitochondrial-protein deacetylation and acetaminophen metabolites bind to lysine residues, we investigated whether deacetylation predisposes mice to toxic metabolite-mediated disruption of mitochondrial proteins. We show that mitochondrial deacetylase SIRT3(-/-) mice are protected from acetaminophen hepatotoxicity, that mitochondrial aldehyde dehydrogenase 2 is a direct SIRT3 substrate, and that its deacetylation increases acetaminophen toxic-metabolite binding and enzyme inactivation. Thus, protein deacetylation enhances xenobiotic liver injury by modulating the binding of a toxic metabolite to mitochondrial proteins.
C1 [Lu, Zhongping; Li, Jian H.; Sack, Michael N.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Bourdi, Mohammed; Pohl, Lance R.] NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Aponte, Angel M.; Chen, Yong; Gucek, Marjan] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA.
[Lombard, David B.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Lombard, David B.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA.
RP Sack, MN (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10 CRC,Room 5-3150,10 Ctr Dr, Bethesda, MD 20892 USA.
EM sackm@nhlbi.nih.gov
RI Li, Jianhua/B-7671-2011; chen, yong/E-2432-2011
OI Li, Jianhua/0000-0002-5744-3182;
FU NHLBI Division of Intramural Research
FX We thank F. W. Alt and H.-L. Cheng from Harvard Medical School, USA, for
their generous gift of the C57BL/6 strain of SIRT3+/- mice.
We thank T. Finkel (NHLBI) and B.J. Song (National Institute of Alcohol
Abuse and Alcoholism) for helpful discussions, and the NHLBI Laboratory
of Animal Medicine and Surgery core facility for assistance with murine
tail-vein injection of lentivirus shRNA. This research was funded by
NHLBI Division of Intramural Research.
NR 26
TC 36
Z9 38
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1469-221X
J9 EMBO REP
JI EMBO Rep.
PD AUG
PY 2011
VL 12
IS 8
BP 840
EP 846
DI 10.1038/embor.2011.121
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 799ZP
UT WOS:000293326500020
PM 21720390
ER
PT J
AU Louis, GMB
Hediger, ML
Peterson, CM
Croughan, M
Sundaram, R
Stanford, J
Chen, Z
Fujimoto, VY
Varner, MW
Trumble, A
Giudice, LC
AF Louis, Germaine M. Buck
Hediger, Mary L.
Peterson, C. Matthew
Croughan, Mary
Sundaram, Rajeshwari
Stanford, Joseph
Chen, Zhen
Fujimoto, Victor Y.
Varner, Michael W.
Trumble, Ann
Giudice, Linda C.
CA ENDO Study Working Grp
TI Incidence of endometriosis by study population and diagnostic method:
the ENDO study
SO FERTILITY AND STERILITY
LA English
DT Article
DE Endometriosis; epidemiology; histology; incidence; laparoscopy; magnetic
resonance imaging
ID CHRONIC PELVIC PAIN; INFERTILE WOMEN; RISK; CLASSIFICATION;
EPIDEMIOLOGY; LAPAROSCOPY; PREVALENCE; FERTILE; SOCIETY
AB Objective: To estimate the incidence of endometriosis in an operative cohort of women seeking clinical care and in a matched population cohort to delineate more fully the scope and magnitude of endometriosis in the context of and beyond clinical care.
Design: Matched-exposure cohort design.
Setting: Surgical centers in the Salt Lake City, Utah, and San Francisco, California, areas.
Patient(s): The operative cohort comprised 495 women undergoing laparoscopy/laparotomy between 2007 and 2009, and the population cohort comprised 131 women from the surgical centers' catchment areas.
Intervention(s): None.
Main Outcome Measure(s): Incidence of endometriosis by diagnostic method in the operative cohort and by pelvic magnetic resonance imaged (MRI) disease in the population cohort.
Result(s): Endometriosis incidence in the operative cohort ranged by two orders of magnitude by diagnostic method: 0.7% for only histology, 7% for only MRI, and 41% for visualized disease. Endometriosis staging was skewed toward minimal (58%) and mild disease (15%). The incidence of MRI-diagnosed endometriosis was 11% in the population cohort.
Conclusion(s): Endometriosis incidence is dependent on the diagnostic method and choice of sampling framework. Conservatively, 11% of women have undiagnosed endometriosis at the population level, with implications for the design and interpretation of etiologic research. (Fertil Steril (R) 2011; 96: 360-5. (c) 2011 by American Society for Reproductive Medicine.)
C1 [Louis, Germaine M. Buck; Hediger, Mary L.; Sundaram, Rajeshwari; Chen, Zhen; Trumble, Ann] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
[Peterson, C. Matthew; Varner, Michael W.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Stanford, Joseph] Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT USA.
[Croughan, Mary; Fujimoto, Victor Y.; Giudice, Linda C.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA.
[Croughan, Mary] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM louisg@mail.nih.gov
RI Varner, Michael/K-9890-2013;
OI Varner, Michael/0000-0001-9455-3973; Sundaram,
Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health [NO1-DK-6-3428,
NO1-DK-6-3427, 10001406-02]
FX Supported by the Intramural Research Program, Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health (contracts NO1-DK-6-3428, NO1-DK-6-3427, and
10001406-02). Ethicon Endo-Surgery kindly donated the Harmonic Ace 36P
shears and scalpel blades for use in the study through a signed
materials transfer agreement with the University of Utah and the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 29
TC 53
Z9 55
U1 7
U2 9
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 AUG
PY 2011
VL 96
IS 2
BP 360
EP 365
DI 10.1016/j.fertnstert.2011.05.087
PG 6
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 795WK
UT WOS:000293008700047
ER
PT J
AU Aylor, DL
Valdar, W
Foulds-Mathes, W
Buus, RJ
Verdugo, RA
Baric, RS
Ferris, MT
Frelinger, JA
Heise, M
Frieman, MB
Gralinski, LE
Bell, TA
Didion, JD
Hua, KJ
Nehrenberg, DL
Powell, CL
Steigerwalt, J
Xie, YY
Kelada, SNP
Collins, FS
Yang, IV
Schwartz, DA
Branstetter, LA
Chesler, EJ
Miller, DR
Spence, J
Liu, EY
McMillan, L
Sarkar, A
Wang, J
Wang, W
Zhang, Q
Broman, KW
Korstanje, R
Durrant, C
Mott, R
Iraqi, FA
Pomp, D
Threadgill, D
de Villena, FPM
Churchill, GA
AF Aylor, David L.
Valdar, William
Foulds-Mathes, Wendy
Buus, Ryan J.
Verdugo, Ricardo A.
Baric, Ralph S.
Ferris, Martin T.
Frelinger, Jeff A.
Heise, Mark
Frieman, Matt B.
Gralinski, Lisa E.
Bell, Timothy A.
Didion, John D.
Hua, Kunjie
Nehrenberg, Derrick L.
Powell, Christine L.
Steigerwalt, Jill
Xie, Yuying
Kelada, Samir N. P.
Collins, Francis S.
Yang, Ivana V.
Schwartz, David A.
Branstetter, Lisa A.
Chesler, Elissa J.
Miller, Darla R.
Spence, Jason
Liu, Eric Yi
McMillan, Leonard
Sarkar, Abhishek
Wang, Jeremy
Wang, Wei
Zhang, Qi
Broman, Karl W.
Korstanje, Ron
Durrant, Caroline
Mott, Richard
Iraqi, Fuad A.
Pomp, Daniel
Threadgill, David
de Villena, Fernando Pardo-Manuel
Churchill, Gary A.
TI Genetic analysis of complex traits in the emerging Collaborative Cross
SO GENOME RESEARCH
LA English
DT Article
ID INBRED MOUSE STRAINS; SYSTEMS GENETICS; LABORATORY MOUSE; MICE;
ASSOCIATION; RESOURCE; LOCUS; MAP; POPULATIONS; DISSECTION
AB The Collaborative Cross (CC) is a mouse recombinant inbred strain panel that is being developed as a resource for mammalian systems genetics. Here we describe an experiment that uses partially inbred CC lines to evaluate the genetic properties and utility of this emerging resource. Genome-wide analysis of the incipient strains reveals high genetic diversity, balanced allele frequencies, and dense, evenly distributed recombination sites-all ideal qualities for a systems genetics resource. We map discrete, complex, and biomolecular traits and contrast two quantitative trait locus (QTL) mapping approaches. Analysis based on inferred haplotypes improves power, reduces false discovery, and provides information to identify and prioritize candidate genes that is unique to multifounder crosses like the CC. The number of expression QTLs discovered here exceeds all previous efforts at eQTL mapping in mice, and we map local eQTL at 1-Mb resolution. We demonstrate that the genetic diversity of the CC, which derives from random mixing of eight founder strains, results in high phenotypic diversity and enhances our ability to map causative loci underlying complex disease-related traits.
C1 [Aylor, David L.; Valdar, William; Foulds-Mathes, Wendy; Buus, Ryan J.; Ferris, Martin T.; Heise, Mark; Bell, Timothy A.; Didion, John D.; Hua, Kunjie; Nehrenberg, Derrick L.; Powell, Christine L.; Xie, Yuying; Miller, Darla R.; Spence, Jason; Pomp, Daniel; de Villena, Fernando Pardo-Manuel] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Verdugo, Ricardo A.; Chesler, Elissa J.; Korstanje, Ron; Churchill, Gary A.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Baric, Ralph S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Baric, Ralph S.; Frelinger, Jeff A.; Frieman, Matt B.; Gralinski, Lisa E.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
[Steigerwalt, Jill; Threadgill, David] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA.
[Kelada, Samir N. P.; Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Yang, Ivana V.; Schwartz, David A.] Natl Jewish Hlth, Denver, CO 80206 USA.
[Branstetter, Lisa A.] Oak Ridge Natl Lab, Oak Ridge, TN 37849 USA.
[Liu, Eric Yi; McMillan, Leonard; Sarkar, Abhishek; Wang, Jeremy; Wang, Wei; Zhang, Qi] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA.
[Broman, Karl W.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA.
[Durrant, Caroline; Mott, Richard] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Iraqi, Fuad A.] Tel Aviv Univ, Dept Human Microbiol, IL-69978 Tel Aviv, Israel.
RP Pomp, D (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
EM dpomp@unc.edu; threadgill@ncsu.edu; fernando@med.unc.edu;
gary.churchill@jax.org
RI Verdugo, Ricardo/A-3970-2013; Frelinger, Jeffrey/F-2448-2014; Liu, Eric
Yi/B-6221-2016; Threadgill, David/N-4425-2013;
OI Frelinger, Jeffrey/0000-0002-2503-6267; Threadgill,
David/0000-0003-3538-1635; Didion, John/0000-0002-8111-6261; Broman,
Karl/0000-0002-4914-6671
FU National Institutes of Health [GM070683, GM076468, GM067553, GM074244,
F32GM090667, T32GM07092, MH090338, T32MH076694, DK076050, U01CA105417,
U01CA134240]; Ellison Medical Foundation [AG-IA-0202-05]; U.S.
Department of Energy [DE-AC05-00OR22725]; UT-Battelle, LLC; NIDDK
[DK056350]; state of North Carolina
FX This work was supported by National Institutes of Health grants and
training grants GM070683, GM076468, GM067553, GM074244, F32GM090667,
T32GM07092, MH090338, T32MH076694, DK076050, U01CA105417, and
U01CA134240; Ellison Medical Foundation AG-IA-0202-05, and U.S.
Department of Energy under Contract DE-AC05-00OR22725 with UT-Battelle,
LLC. Some phenotypes were collected using the Animal Metabolism
Phenotyping core facility within UNC's Nutrition Obesity Research Center
(funded by NIDDK grant DK056350). Essential support was also provided by
the Dean of the UNC School of Medicine, the Lineberger Comprehensive
Cancer Center at UNC, and the University Cancer Research Fund from the
state of North Carolina. We are particularly grateful for infrastructure
support at UNC facilitated by Drs. Bill Marzluff, Terry Magnuson, and
Shelley Earp.
NR 43
TC 147
Z9 148
U1 2
U2 17
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD AUG
PY 2011
VL 21
IS 8
BP 1213
EP 1222
DI 10.1101/gr.111310.110
PG 10
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 800CG
UT WOS:000293335700002
PM 21406540
ER
PT J
AU vonHoldt, BM
Pollinger, JP
Earl, DA
Knowles, JC
Boyko, AR
Parker, H
Geffen, E
Pilot, M
Jedrzejewski, W
Jedrzejewska, B
Sidorovich, V
Greco, C
Randi, E
Musiani, M
Kays, R
Bustamante, CD
Ostrander, EA
Novembre, J
Wayne, RK
AF vonHoldt, Bridgett M.
Pollinger, John P.
Earl, Dent A.
Knowles, James C.
Boyko, Adam R.
Parker, Heidi
Geffen, Eli
Pilot, Malgorzata
Jedrzejewski, Wlodzimierz
Jedrzejewska, Bogumila
Sidorovich, Vadim
Greco, Claudia
Randi, Ettore
Musiani, Marco
Kays, Roland
Bustamante, Carlos D.
Ostrander, Elaine A.
Novembre, John
Wayne, Robert K.
TI A genome-wide perspective on the evolutionary history of enigmatic
wolf-like canids
SO GENOME RESEARCH
LA English
DT Article
ID LINKAGE DISEQUILIBRIUM; MITOCHONDRIAL-DNA; GENETIC-STRUCTURE; RED WOLF;
GRAY WOLF; POPULATION-STRUCTURE; DOMESTIC DOG; GREY WOLVES;
MICROSATELLITE LOCI; EASTERN WOLVES
AB High-throughput genotyping technologies developed for model species can potentially increase the resolution of demographic history and ancestry in wild relatives. We use a SNP genotyping microarray developed for the domestic dog to assay variation in over 48K loci in wolf-like species worldwide. Despite the high mobility of these large carnivores, we find distinct hierarchical population units within gray wolves and coyotes that correspond with geographic and ecologic differences among populations. Further, we test controversial theories about the ancestry of the Great Lakes wolf and red wolf using an analysis of haplotype blocks across all 38 canid autosomes. We find that these enigmatic canids are highly admixed varieties derived from gray wolves and coyotes, respectively. This divergent genomic history suggests that they do not have a shared recent ancestry as proposed by previous researchers. Interspecific hybridization, as well as the process of evolutionary divergence, may be responsible for the observed phenotypic distinction of both forms. Such admixture complicates decisions regarding endangered species restoration and protection.
C1 [vonHoldt, Bridgett M.; Pollinger, John P.; Knowles, James C.; Novembre, John; Wayne, Robert K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
[Earl, Dent A.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
[Boyko, Adam R.; Bustamante, Carlos D.] Stanford Sch Med, Dept Genet, Stanford, CA 94305 USA.
[Parker, Heidi; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Geffen, Eli] Tel Aviv Univ, Dept Zool, IL-69978 Tel Aviv, Israel.
[Pilot, Malgorzata] Polish Acad Sci, Museum Zool, PL-00679 Warsaw, Poland.
[Pilot, Malgorzata] Polish Acad Sci, Inst Zool, PL-00679 Warsaw, Poland.
[Jedrzejewski, Wlodzimierz; Jedrzejewska, Bogumila; Sidorovich, Vadim] Polish Acad Sci, Mammal Res Inst, PL-17230 Bialowieza, Poland.
[Greco, Claudia; Randi, Ettore] ISPRA, I-40064 Ozzano Dell Emilia, BO, Italy.
[Musiani, Marco] Univ Calgary, Fac Environm Design, Calgary, AB T2N 1N4, Canada.
[Kays, Roland] New York State Museum & Sci Serv, Albany, NY 12230 USA.
RP Wayne, RK (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
EM rwayne@ucla.edu
RI Novembre, John/G-1339-2011;
OI Greco, Claudia/0000-0002-8678-0890; Ostrander,
Elaine/0000-0001-6075-9738
FU NSF; NIH; National Human Genome Research Institute; Searle Scholars
program; Polish Ministry of Science and Higher Education; European
Nature Heritage Fund; New York State Museum; National Sciences and
Engineering Research Council
FX Grants from NSF and NIH (C. D. B., J.N., M. M., and R. K. W.), the
Intramural Program of the National Human Genome Research Institute
(E.A.O.), the Searle Scholars program (J.N.), the Polish Ministry of
Science and Higher Education (M. P. and W.J.), European Nature Heritage
Fund EURONATUR (W.J.), New York State Museum (R. K.), National Sciences
and Engineering Research Council (M. M.) supported this research. We
thank Y. Zhang and team for their permission to include 10 Chinese wolf
samples in this study. A NIH Training Grant in Genomic Analysis and
Interpretation supported B. V. H.; the Foundation for Polish Science
supported M. P. Wolf samples from Central/Eastern/Northern Europe and
Turkey were collected as a result of an ongoing project on genetic
differentiation in Eurasian wolves. We thank the project participants
(M. Shkvyrya, I. Dikiy, E. Tsingarska, S. Nowak) for their permission to
use 72 samples for this study. We acknowledge R. Hefner and the
Zoological Collection at Tel Aviv University for Israel wolf samples. We
also gratefully acknowledge Affymetrix Corporation and specifically
Zuwei Qian from Affymetrix Asia Pacific for assistance. We also want to
thank Adam Auton and Andy Reynolds for assistance with array genotyping,
Scott Livingston for comments on the manuscript, and Hua Tang for advice
with ancestry analyses.
NR 95
TC 110
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U1 12
U2 133
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD AUG
PY 2011
VL 21
IS 8
BP 1294
EP 1305
DI 10.1101/gr.116301.110
PG 12
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 800CG
UT WOS:000293335700009
PM 21566151
ER
PT J
AU Dienstag, JL
Ghany, MG
Morgan, TR
Di Bisceglie, AM
Bonkovsky, HL
Kim, HY
Seeff, LB
Szabo, G
Wright, EC
Sterling, RK
Everson, GT
Lindsay, KL
Lee, WM
Lok, AS
Morishima, C
Stoddard, AM
Everhart, JE
AF Dienstag, Jules L.
Ghany, Marc G.
Morgan, Timothy R.
Di Bisceglie, Adrian M.
Bonkovsky, Herbert L.
Kim, Hae-Young
Seeff, Leonard B.
Szabo, Gyongyi
Wright, Elizabeth C.
Sterling, Richard K.
Everson, Gregory T.
Lindsay, Karen L.
Lee, William M.
Lok, Anna S.
Morishima, Chihiro
Stoddard, Anne M.
Everhart, James E.
CA HALT-C Trial Grp
TI A Prospective Study of the Rate of Progression in Compensated,
Histologically Advanced Chronic Hepatitis C
SO HEPATOLOGY
LA English
DT Article
ID VIRUS-RELATED CIRRHOSIS; NATURAL-HISTORY; UNITED-STATES; INFECTION;
COHORT; PEGINTERFERON; SURVIVAL; FIBROSIS; OUTCOMES; THERAPY
AB The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years. Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year. Six hundred seventy-nine clinical outcomes occurred among 329 subjects. Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5% per year) than subjects with fibrosis (3.3% per year) (P < 0.0001). Child-Turcotte-Pugh (CTP) score >= 7 was the most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a CTP score >= 7, the rate of subsequent events increased to 12.9% per year, including a death rate of 10% per year. Age and sex did not influence outcome rates. Baseline platelet count was a strong predictor of all clinical outcomes. During the 8 years of follow-up, death or liver transplantation occurred among 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis. Conclusion: Among patients with advanced hepatitis C who failed peginterferon and ribavirin therapy, the rate of liver-related outcomes, including death and liver transplantation, is high, especially once the CTP score reaches at least 7. (HEPATOLOGY 2011;54:396-405)
C1 [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Seeff, Leonard B.; Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Seeff, Leonard B.; Wright, Elizabeth C.] NIDDK, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
[Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA.
[Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA.
[Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA.
[Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Kim, Hae-Young; Stoddard, Anne M.] New England Res Inst, Watertown, MA 02172 USA.
[Szabo, Gyongyi] Univ Massachusetts, Sch Med, Dept Med, Div Gastroenterol,Hepatol & Liver Ctr, Worcester, MA USA.
[Sterling, Richard K.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA.
[Everson, Gregory T.] Univ Colorado Denver, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Aurora, CO USA.
[Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA.
[Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA.
[Lok, Anna S.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA.
[Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA.
RP Dienstag, JL (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA.
EM jdienstag@partners.org
OI Yang, Shuman/0000-0002-9638-0890
FU National Institute of Diabetes & Digestive & Kidney Diseases; National
Center for Research Resources, National Institutes of Health;
Hoffmann-La Roche, Inc.
FX Supported by the National Institute of Diabetes & Digestive & Kidney
Diseases (contract numbers are listed in the Appendix). Additional
support was provided by the National Institute of Allergy and Infectious
Diseases, the National Cancer Institute, the National Center for
Minority Health and Health Disparities, and by General Clinical Research
Center and Clinical and Translational Science Center grants from the
National Center for Research Resources, National Institutes of Health
(grant numbers are listed in the Appendix). Additional funding to
conduct this study was supplied by Hoffmann-La Roche, Inc. (now
Genentech) through a Cooperative Research and Development Agreement with
the National Institutes of Health.
NR 21
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U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD AUG
PY 2011
VL 54
IS 2
BP 396
EP 405
DI 10.1002/hep.24370
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 800BT
UT WOS:000293333300004
PM 21520194
ER
PT J
AU Saeed, M
Shiina, M
Date, T
Akazawa, D
Watanabe, N
Murayama, A
Suzuki, T
Watanabe, H
Hiraga, N
Imamura, M
Chayama, K
Choi, Y
Krawczynski, K
Liang, TJ
Wakita, T
Kato, T
AF Saeed, Mohsan
Shiina, Masaaki
Date, Tomoko
Akazawa, Daisuke
Watanabe, Noriyuki
Murayama, Asako
Suzuki, Tetsuro
Watanabe, Haruo
Hiraga, Nobuhiko
Imamura, Michio
Chayama, Kazuaki
Choi, Youkyung
Krawczynski, Krzysztof
Liang, T. Jake
Wakita, Takaji
Kato, Takanobu
TI In Vivo Adaptation of Hepatitis C Virus in Chimpanzees for Efficient
Virus Production and Evasion of Apoptosis
SO HEPATOLOGY
LA English
DT Article
ID LIVER-INJURY; INFECTION; REPLICATION; PERFORIN; CYTOTOXICITY;
DETERMINANTS; PERSISTENCE; MECHANISMS; CLEARANCE; DISEASE
AB Hepatitis C virus (HCV) employs various strategies to establish persistent infection that can cause chronic liver disease. Our previous study showed that both the original patient serum from which the HCV JFH-1 strain was isolated and the cell culture-generated JFH-1 virus (JFH-1cc) established infection in chimpanzees, and that infected JFH-1 strains accumulated mutations after passage through chimpanzees. The aim of this study was to compare the in vitro characteristics of JFH-1 strains emerged in each chimpanzee at early and late stages of infection, as it could provide an insight into the phenomenon of viral persistence. We generated full-genome JFH-1 constructs with the mutations detected in patient serum-infected (JFH-1/S1 and S2) and JFH-1cc-infected (JFH-1/C) chimpanzees, and assessed their effect on replication, infectious virus production, and regulation of apoptosis in cell culture. The extracellular HCV core antigen secreted from JFH-1/S1-, S2-, and C-transfected HuH-7 cells was 2.5, 8.9, and 2.1 times higher than that from JFH-1 wild-type (JFH-1/wt) transfected cells, respectively. Single cycle virus production assay with a CD81-negative cell line revealed that the strain JFH-1/S2, isolated from the patient serum-infected chimpanzee at a later time point of infection, showed lower replication and higher capacity to assemble infectious virus particles. This strain also showed productive infection in human hepatocyte-transplanted mice. Furthermore, the cells harboring this strain displayed lower susceptibility to the apoptosis induced by tumor necrosis factor alpha or Fas ligand compared with the cells replicating JFH-1/wt. Conclusion: The ability of lower replication, higher virus production, and less susceptibility to cytokine-induced apoptosis may be important for prolonged infection in vivo. Such control of viral functions by specific mutations may be a key strategy for establishing persistent infection. (HEPATOLOGY 2011;54:425-433)
C1 [Saeed, Mohsan; Date, Tomoko; Akazawa, Daisuke; Watanabe, Noriyuki; Murayama, Asako; Suzuki, Tetsuro; Wakita, Takaji; Kato, Takanobu] Natl Inst Infect Dis, Dept Virol 2, Tokyo 1628640, Japan.
[Saeed, Mohsan; Watanabe, Haruo] Univ Tokyo, Dept Infect & Pathol, Grad Sch Med, Tokyo, Japan.
[Shiina, Masaaki] Tohoku Univ, Grad Sch Med, Div Gastroenterol, Sendai, Miyagi 980, Japan.
[Hiraga, Nobuhiko; Imamura, Michio; Chayama, Kazuaki] Hiroshima Univ, Dept Med & Mol Sci, Div Frontier Med Sci, Programs Biomed Res,Grad Sch Biomed Sci, Hiroshima, Japan.
[Choi, Youkyung; Krawczynski, Krzysztof] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA USA.
[Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
RP Kato, T (reprint author), Natl Inst Infect Dis, Dept Virol 2, Tokyo 1628640, Japan.
EM takato@nih.go.jp
FU Japan Society for the Promotion of Science; Ministry of Health, Labor,
and Welfare of Japan; Ministry of Education, Culture, Sports, Science,
and Technology; Health Sciences Foundation; NIDDK, NIH
FX Supported by grants-in-aid from the Japan Society for the Promotion of
Science, the Ministry of Health, Labor, and Welfare of Japan, and the
Ministry of Education, Culture, Sports, Science, and Technology, by the
Research on Health Sciences Focusing on Drug Innovation from the Japan
Health Sciences Foundation, and in part by the Intramural Research
Program of the NIDDK, NIH (T. J. L.).
NR 27
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U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD AUG
PY 2011
VL 54
IS 2
BP 425
EP 433
DI 10.1002/hep.24399
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 800BT
UT WOS:000293333300007
PM 21538444
ER
PT J
AU Lok, AS
Everhart, JE
Di Bisceglie, AM
Kim, HY
Hussain, M
Morgan, TR
AF Lok, Anna S.
Everhart, James E.
Di Bisceglie, Adrian M.
Kim, Hae-Young
Hussain, Munira
Morgan, Timothy R.
CA HALT-C Trial Grp
TI Occult and Previous Hepatitis B Virus Infection are Not Associated with
Hepatocellular Carcinoma in United States Patients with Chronic
Hepatitis C
SO HEPATOLOGY
LA English
DT Article
ID ACUTE VIRAL-HEPATITIS; SURFACE-ANTIGEN; LIVER-DISEASE; HBSAG
SEROCLEARANCE; RISK; DNA; HEPADNAVIRUS; COINFECTION; MAINTENANCE;
PREVALENCE
AB Previous studies have suggested that prior exposure to hepatitis B virus (HBV) infection may increase the risk of development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The aim of this study was to compare the prevalence of previous or occult HBV infection in a cohort of hepatitis B surface antigen-negative patients with histologically advanced chronic hepatitis C in the United States who did or did not develop HCC. Stored sera from 91 patients with HCC and 182 matched controls who participated in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial were tested for hepatitis B core antibody (anti-HBc), hepatitis B surface antibody, and HBV DNA. Frozen liver samples from 28 HCC cases and 55 controls were tested for HBV DNA by way of real-time polymerase chain reaction. Anti-HBc (as a marker of previous HBV infection) was present in the serum of 41.8% HCC cases and 45.6% controls (P = 0.54); anti-HBc alone was present in 16.5% of HCC cases and 24.7% of controls. HBV DNA was detected in the serum of only one control subject and no patients with HCC. HBV DNA (as a marker of occult HBV infection) was detected in the livers of 10.7% of HCC cases and 23.6% of controls (P = 0.18). Conclusion: Although almost half the patients in the HALT-C Trial had serological evidence of previous HBV infection, there was no difference in prevalence of anti-HBc in serum or HBV DNA in liver between patients who did or did not develop HCC. In the United States, neither previous nor occult HBV infection is an important factor in HCC development among patients with advanced chronic hepatitis C. (HEPATOLOGY 2011;54:434-442)
C1 [Lok, Anna S.; Hussain, Munira] Univ Michigan, Sch Med, Div Gastroenterol, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA.
[Kim, Hae-Young] New England Res Inst, Watertown, MA 02172 USA.
[Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
[Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA.
RP Lok, AS (reprint author), Univ Michigan, Sch Med, Div Gastroenterol, Dept Internal Med, 1500 E Med Ctr Dr,3912 Taubman Ctr, Ann Arbor, MI 48109 USA.
EM ASLok@umich.edu
OI Yang, Shuman/0000-0002-9638-0890
FU National Institute of Diabetes & Digestive & Kidney Diseases; National
Center for Research Resources, National Institutes of Health;
Hoffmann-La Roche, Inc.; National Institutes of Health
FX Supported by the National Institute of Diabetes & Digestive & Kidney
Diseases (contract numbers are listed in the Acknowledgment section).
Additional support was provided by the National Institute of Allergy and
Infectious Diseases, the National Cancer Institute, the National Center
for Minority Health and Health Disparities, and by General Clinical
Research Center and Clinical and Translational Science Center grants
from the National Center for Research Resources, National Institutes of
Health (grant numbers are listed in the Acknowledgment section).
Additional funding to conduct this study was supplied by Hoffmann-La
Roche, Inc. (now Genentech) through a Cooperative Research and
Development Agreement with the National Institutes of Health. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Center for
Research Resources or the National Institutes of Health.
NR 32
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U1 1
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PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD AUG
PY 2011
VL 54
IS 2
BP 434
EP 442
DI 10.1002/hep.24257
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 800BT
UT WOS:000293333300008
PM 21374690
ER
PT J
AU Welzel, TM
Graubard, BI
Zeuzem, S
El-Serag, HB
Davila, JA
McGlynn, KA
AF Welzel, Tania M.
Graubard, Barry I.
Zeuzem, Stefan
El-Serag, Hashem B.
Davila, Jessica A.
McGlynn, Katherine A.
TI Metabolic Syndrome Increases the Risk of Primary Liver Cancer in the
United States: A Study in the SEER-Medicare Database
SO HEPATOLOGY
LA English
DT Article
ID NONALCOHOLIC FATTY LIVER; HEPATOCELLULAR-CARCINOMA; EXTRAHEPATIC
CHOLANGIOCARCINOMA; NATURAL-HISTORY; DISEASE; STEATOHEPATITIS;
POPULATION; STEATOSIS; INFECTION; ADULTS
AB Incidence rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have increased in the United States. Metabolic syndrome is recognized as a risk factor for HCC and a postulated one for ICC. The magnitude of risk, however, has not been investigated on a population level in the United States. We therefore examined the association between metabolic syndrome and the development of these cancers. All persons diagnosed with HCC and ICC between 1993 and 2005 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. For comparison, a 5% sample of individuals residing in the same regions as the SEER registries of the cases was selected. The prevalence of metabolic syndrome as defined by the U. S. National Cholesterol Education Program Adult Treatment Panel III criteria, and other risk factors for HCC (hepatitis B virus, hepatitis C virus, alcoholic liver disease, liver cirrhosis, biliary cirrhosis, hemochromatosis, Wilson's disease) and ICC (biliary cirrhosis, cholangitis, cholelithiasis, choledochal cysts, hepatitis B virus, hepatitis C virus, alcoholic liver disease, cirrhosis, inflammatory bowel disease) were compared among persons who developed cancer and those who did not. Logistic regression was used to calculate odds ratios and 95% confidence intervals. The inclusion criteria were met by 3649 HCC cases, 743 ICC cases, and 195,953 comparison persons. Metabolic syndrome was significantly more common among persons who developed HCC (37.1%) and ICC (29.7%) than the comparison group (17.1%, P < 0.0001). In adjusted multiple logistic regression analyses, metabolic syndrome remained significantly associated with increased risk of HCC (odds ratio = 2.13; 95% confidence interval = 1.96-2.31, P < 0.0001) and ICC (odds ratio = 5 1.56; 95% confidence interval = 5 1.32-1.83, P < 0.0001). Conclusion: Metabolic syndrome is a significant risk factor for development of HCC and ICC in the general U. S. population. (HEPATOLOGY 2011;54:463-471)
C1 [Welzel, Tania M.; Zeuzem, Stefan] Univ Frankfurt Klinikum, Med Klin 1, D-60590 Frankfurt, Germany.
[Welzel, Tania M.; Graubard, Barry I.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[El-Serag, Hashem B.; Davila, Jessica A.] Michael E DeBakey VA Med Ctr, Sect Hlth Serv Res, Houston, TX USA.
[El-Serag, Hashem B.; Davila, Jessica A.] Michael E DeBakey VA Med Ctr, Gastroenterol Sect, Houston, TX USA.
[El-Serag, Hashem B.; Davila, Jessica A.] Baylor Coll Med, Houston, TX 77030 USA.
RP Welzel, TM (reprint author), Univ Frankfurt Klinikum, Med Klin 1, Theodor Stern Kai 7, D-60590 Frankfurt, Germany.
EM tania.welzel@kgu.de
FU Bristol-Myers Squibb; Human Genome Sciences
FX Dr. Zeuzem is a consultant for, advises, and received grants from
Bristol-Myers Squibb. He is a consultant for and advsies Bayer. He also
received grants from Human Genome Sciences.
NR 44
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U1 0
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD AUG
PY 2011
VL 54
IS 2
BP 463
EP 471
DI 10.1002/hep.24397
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 800BT
UT WOS:000293333300011
PM 21538440
ER
PT J
AU Qu, AJ
Taylor, M
Xue, X
Matsubara, T
Metzger, D
Chambon, P
Gonzalez, FJ
Shah, YM
AF Qu, Aijuan
Taylor, Matthew
Xue, Xiang
Matsubara, Tsutomu
Metzger, Daniel
Chambon, Pierre
Gonzalez, Frank J.
Shah, Yatrik M.
TI Hypoxia-Inducible Transcription Factor 2 alpha Promotes Steatohepatitis
Through Augmenting Lipid Accumulation, Inflammation, and Fibrosis
SO HEPATOLOGY
LA English
DT Article
ID FACTOR-DEPENDENT PRODUCTION; LINDAU TUMOR-SUPPRESSOR; PROFIBROTIC
MEDIATORS; METABOLIC ZONATION; LIPOPROTEIN-LIPASE; HIF-ALPHA; IN-VIVO;
LIVER; CELLS; IDENTIFICATION
AB Oxygen dynamics in the liver is a central signaling mediator controlling hepatic homeostasis, and dysregulation of cellular oxygen is associated with liver injury. Moreover, the transcription factor relaying changes in cellular oxygen levels, hypoxia-inducible factor (HIF), is critical in liver metabolism, and sustained increase in HIF signaling can lead to spontaneous steatosis, inflammation, and liver tumorigenesis. However, the direct responses and genetic networks regulated by HIFs in the liver are unclear. To help define the HIF signal-transduction pathway, an animal model of HIF overexpression was generated and characterized. In this model, overexpression was achieved by Von Hippel-Lindau (Vhl) disruption in a liver-specific temporal fashion. Acute disruption of Vhl induced hepatic lipid accumulation in an HIF-2 alpha-dependent manner. In addition, HIF-2 alpha activation rapidly increased liver inflammation and fibrosis, demonstrating that steatosis and inflammation are primary responses of the liver to hypoxia. To identify downstream effectors, a global microarray expression analysis was performed using livers lacking Vhl for 24 hours and 2 weeks, revealing a time-dependent effect of HIF on gene expression. Increase in genes involved in fatty acid synthesis were followed by an increase in fatty acid uptake-associated genes, and an inhibition of fatty acid beta-oxidation. A rapid increase in proinflammatory cytokines and fibrogenic gene expression was also observed. In vivo chromatin immunoprecipitation assays revealed novel direct targets of HIF signaling that may contribute to hypoxia-mediated steatosis and inflammation. Conclusion: These data suggest that HIF-2 alpha is a critical mediator in the progression from clinically manageable steatosis to more severe steatohepatitis and liver cancer, and may be a potential therapeutic target. (HEPATOLOGY 2011;54:472-483)
C1 [Shah, Yatrik M.] Univ Michigan, Dept Mol & Integrat Physiol, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Qu, Aijuan; Matsubara, Tsutomu; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Metzger, Daniel; Chambon, Pierre] Inst Genet & Biol Mol & Cellulaire, Dept Physiol Genet, Illkirch Graffenstaden, France.
RP Shah, YM (reprint author), Univ Michigan, Dept Mol & Integrat Physiol, Dept Internal Med, Div Gastroenterol, 1301 E Catherine St, Ann Arbor, MI 48109 USA.
EM shahy@umich.edu
RI Xue, Xiang/P-9071-2014
OI Xue, Xiang/0000-0003-4704-1814
FU National Institutes of Health [CA148828]; University of Michigan
Gastrointestinal Peptide Center; National Cancer Institute
FX This study was supported by grants from the National Institutes of
Health (CA148828), The University of Michigan Gastrointestinal Peptide
Center (to Y.M.S.), and the National Cancer Institute Intramural
Research Program.
NR 40
TC 47
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U1 2
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD AUG
PY 2011
VL 54
IS 2
BP 472
EP 483
DI 10.1002/hep.24400
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 800BT
UT WOS:000293333300012
PM 21538443
ER
PT J
AU Cook, MB
Trabert, B
McGlynn, KA
AF Cook, M. B.
Trabert, B.
McGlynn, K. A.
TI Organochlorine compounds and testicular dysgenesis syndrome: human data
SO INTERNATIONAL JOURNAL OF ANDROLOGY
LA English
DT Article
DE cryptorchidism; chlorinated hydrocarbons; hypospadias; infertility;
review; testicular neoplasms
ID ENDOCRINE-DISRUPTING CHEMICALS; ENVIRONMENTAL DDT EXPOSURE; HUMAN SEMEN
QUALITY; GERM-CELL TUMORS; POLYCHLORINATED-BIPHENYLS; REPRODUCTIVE
FUNCTION; YOUNG MEN; INTERNATIONAL TRENDS; PERINATAL VARIABLES;
CANCER-EXPERIENCES
AB Cryptorchidism, hypospadias, subfertility and testicular germ-cell tumour have been suggested to comprise a testicular dysgenesis syndrome (TDS) based on the premise that each may derive from perturbations of embryonal programming and gonadal development during foetal life. Endocrine-disrupting chemicals have been hypothesized to be associated with these disorders, given the importance of sex steroid hormones in urogenital development and homeostasis. Organochlorines are one such set of compounds which are defined as containing between one and ten covalently bonded chlorine atoms. These compounds are persistent pollutants with long half-lives, accumulate in adipose tissue when ingested, bioaccumulate and biomagnify, and have complex and variable toxicological profiles. Examples of organochlorines include dichloro-diphenyl-trichloroethane and its metabolites, polychlorinated biphenyls, and chlordane. In this comprehensive review of human epidemiologic studies which have tested for associations between organochlorines and facets of TDS, we find evidence for associations between the exposures p,p'-DDE, cis-nonachlor and trans-nonachlor with testicular germ-cell tumour. The sum of the evidence from human epidemiological studies does not indicate any association between specific organochlorines studied and cryptorchidism, hypospadias or fertility. Many other endocrine-disrupting chemicals, including additional organochlorines, have yet to be assessed in relation to disorders associated with TDS, yet study of such chemicals has strong scientific merit given the relevance of such hypotheses to urogenital development.
C1 [Cook, M. B.; Trabert, B.; McGlynn, K. A.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20852 USA.
RP Cook, MB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS Suite 550 Room 5014, Bethesda, MD 20852 USA.
EM michael.cook@nih.gov
RI Cook, Michael/A-5641-2009; Trabert, Britton/F-8051-2015
OI Cook, Michael/0000-0002-0533-7302;
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services
FX Intramural Program of the National Cancer Institute, National Institutes
of Health, Department of Health and Human Services. There are no
financial disclosures from any of the authors.
NR 83
TC 24
Z9 25
U1 0
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-6263
J9 INT J ANDROL
JI Int. J. Androl.
PD AUG
PY 2011
VL 34
IS 4
BP E68
EP E85
DI 10.1111/j.1365-2605.2011.01171.x
PN 2
PG 18
WC Andrology
SC Endocrinology & Metabolism
GA 798AX
UT WOS:000293174100010
PM 21668838
ER
PT J
AU Kratz, CP
Greene, MH
Bratslavsky, G
Shi, J
AF Kratz, C. P.
Greene, M. H.
Bratslavsky, G.
Shi, J.
TI A stratified genetic risk assessment for testicular cancer
SO INTERNATIONAL JOURNAL OF ANDROLOGY
LA English
DT Article
DE cryptorchidism; risk assessment; testicular neoplasms
ID GENOME-WIDE ASSOCIATION; GERM-CELL CANCER; SUSCEPTIBILITY LOCI;
BREAST-CANCER; VARIANTS; 5P15.33; TUMORS; PREDICTION; DISEASE; MODELS
AB Three genome-wide association studies of testicular cancer have uncovered predisposition alleles in or near KITLG, BAK1, SPRY4, TERT, ATF7IP and DMRT1. We investigated whether testicular cancer-risk alleles can be utilized in the clinical setting. We employed the receiver operating characteristic curves for genetic risk models to measure the discriminatory power of a risk variant-based risk model, and found that the newly discovered variants provided a discriminatory power of 69.2%. This suggested that about 69.2% of the time, a randomly selected patient with testicular cancer had a higher estimated risk than the risk for a randomly selected control subject. Using a multiplicative model, we estimated that white men in the top 1% of genetic risk as defined by eight risk variants had a relative risk that was 10.5-fold greater than that for the general white male population. This risk differential does not appear to be clinically useful, given the relative rarity and highly curable nature of testicular germ cell tumour (TGCT). In the authors' view, a stratified genetic risk assessment strategy might be useful, theoretically, for men who also have independent clinical risk factors for testicular cancer. Several established TGCT risk factors, such as cryptorchidism (RR = 4.8) and male infertility (SIR = 2.8) might prove useful in that context, but we currently do not know whether these testicular cancer-risk loci are associated with, or independent of, such clinical risk factors. More research is required before we can utilize testicular cancer-risk loci for clinically meaningful risk prediction.
C1 [Kratz, C. P.; Greene, M. H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Bratslavsky, G.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Shi, J.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Kratz, CP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM kratzcp@mail.nih.gov; jianxin.Shi@nih.gov
FU National Institutes of Health; National Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Institutes of Health and the National Cancer Institute. We are
grateful to Dr. Mitchell Gail for his insightful comments.
NR 30
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U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-6263
J9 INT J ANDROL
JI Int. J. Androl.
PD AUG
PY 2011
VL 34
IS 4
BP E98
EP E102
DI 10.1111/j.1365-2605.2011.01156.x
PN 2
PG 5
WC Andrology
SC Endocrinology & Metabolism
GA 798AX
UT WOS:000293174100012
PM 21564132
ER
PT J
AU Trabert, B
Stang, A
Cook, MB
Rusner, C
McGlynn, KA
AF Trabert, B.
Stang, A.
Cook, M. B.
Rusner, C.
McGlynn, K. A.
TI Impact of classification of mixed germ-cell tumours on incidence trends
of non-seminoma
SO INTERNATIONAL JOURNAL OF ANDROLOGY
LA English
DT Article
DE histology; incidence trends; mixed germ-cell tumours; testicular
germ-cell tumours
AB Seminomas and non-seminomas [embryonal carcinomas, yolk sac tumours, teratomas, choriocarcinomas, mixed germ-cell tumours (MGCT)] are the major histological types of testicular germ-cell tumours (TGCT). TGCTs composed of both seminomatous and non-seminomatous elements have been coded as their non-seminoma component in the World Health Organization classification. In the late 1980s, a provisional International Classification of Diseases for Oncology (ICD-O) morphology code for MGCT was introduced. Using data from the Surveillance, Epidemiology and End Results Program and two population-based German cancer registries, we examined the impact of MGCT classification on TGCT trends. Cases were identified using ICD-O topography (ICD-9: 186; ICD-10: C62) and morphology codes (seminoma = 9060-9062, 9064; embryonal carcinoma = 9070; yolk sack tumour = 9071; teratoma = 9080-9084, 9102; choriocarcinoma = 9100, 9101; MGCT = 9085; all non-seminoma = 9065-9102). As MGCTs and teratoma are often grouped as a single histological group, we analysed teratoma both including and excluding MGCTs. Between 1988 and 2007, incidence rates of MGCT in the US increased 407%. Rates of teratoma including MGCT increased 80%, whereas rates of teratoma excluding MGCT decreased 71%. Rates of embryonal carcinoma [-40%] and choriocarcinoma [-22%] also declined, suggesting that the code for MGCT is now being used for any mixed histology. Similar declines in incidence were observed in the German comparison populations. The declines in incidence of teratoma (excluding MGCT), embryonal carcinoma and choriocarcinoma in the US data since 1988 are likely in part because of increases in classifying any TGCT with mixed histology as MGCT. These results suggest that analysis of trends in specific histological types of non-seminoma should be interpreted cautiously.
C1 [Trabert, B.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA.
[Stang, A.; Rusner, C.] Univ Halle Wittenberg, Inst Clin Epidemiol, Halle, Saale, Germany.
RP Trabert, B (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Suite 550,6120 Execut Blvd, Rockville, MD 20852 USA.
EM trabertbl@mail.nih.gov
RI Cook, Michael/A-5641-2009; Trabert, Britton/F-8051-2015
OI Cook, Michael/0000-0002-0533-7302;
FU National Cancer Institute; German Science Foundation (DFG) [STA621/6-1]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute and by a grant of the German Science
Foundation (DFG) [grant number STA621/6-1]. The analysis was undertaken
in collaboration with C. Stegmaier (Saarland Cancer Registry) and R.
Stabenow (Common Cancer Registry).
NR 11
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-6263
J9 INT J ANDROL
JI Int. J. Androl.
PD AUG
PY 2011
VL 34
IS 4
BP E274
EP E277
DI 10.1111/j.1365-2605.2011.01187.x
PN 2
PG 4
WC Andrology
SC Endocrinology & Metabolism
GA 798AX
UT WOS:000293174100026
PM 21623833
ER
PT J
AU Trabert, B
Sigurdson, AJ
Sweeney, AM
Amato, RJ
Strom, SS
McGlynn, KA
AF Trabert, B.
Sigurdson, A. J.
Sweeney, A. M.
Amato, R. J.
Strom, S. S.
McGlynn, K. A.
TI Baldness, acne and testicular germ cell tumours
SO INTERNATIONAL JOURNAL OF ANDROLOGY
LA English
DT Article
DE acne; baldness; case-control; hospital-based; testicular germ cell
tumours
ID MALE BALDING PATTERNS; ANDROGEN RECEPTOR; HUMAN-SKIN; SEX-HORMONES;
RISK-FACTORS; CANCER; VALIDITY
AB Androgen levels during critical periods of testicular development may be involved in the aetiology of testicular germ cell tumours (TGCT). We evaluated the roles of adolescent and early adult life correlates of androgen exposure and TGCT in a hospital-based case-control study. TGCT cases (n = 187) and controls (n = 148), matched on age, race and state of residence, participated in the study. Unconditional logistic regression was used to estimate associations between TGCT and male pattern baldness, severe acne, markers of puberty onset and body size. Cases were significantly less likely to report hair loss than controls [odds ratio (OR): 0.6; 95% confidence interval (CI): 0.4, 1.0]. Amount of hair loss, increasing age at onset and increasing rate of loss were all inversely associated with TGCT (rate of hair loss: p-trend = 0.03; age at onset: p-trend = 0.03; amount of hair loss: p-trend = 0.01). History of severe acne was inversely associated with TGCT (OR: 0.5; 95% CI: 0.3, 0.9) and height was positively associated with TGCT (p-trend = 0.02). Increased endogenous androgen levels during puberty and early adulthood may be associated with a decreased risk of TGCT. Additional studies of endogenous hormone levels during puberty and early adult life are warranted, especially studies evaluating the role of androgen synthesis, metabolism and uptake.
C1 [Trabert, B.; McGlynn, K. A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA.
[Sigurdson, A. J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA.
[Sweeney, A. M.] Texas A&M Univ Syst Hlth Sci Ctr, Sch Rural Publ Hlth, Dept Epidemiol & Biostat, College Stn, TX USA.
[Amato, R. J.] Univ Texas Houston, Sch Med, Houston, TX USA.
[Strom, S. S.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
RP Trabert, B (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Suite 550,6120 Execut Blvd, Rockville, MD 20852 USA.
EM trabertbl@mail.nih.gov
RI Trabert, Britton/F-8051-2015
FU University of Texas M.D. Anderson Cancer Center (NCI) [R25-CA-57730];
National Cancer Institute
FX This work was supported by the University of Texas M.D. Anderson Cancer
Center Education Program in Cancer Prevention (NCI grant: R25-CA-57730)
and the Intramural Research Program of the National Cancer Institute.
NR 26
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U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-6263
EI 1365-2605
J9 INT J ANDROL
JI Int. J. Androl.
PD AUG
PY 2011
VL 34
IS 4
BP E59
EP E67
DI 10.1111/j.1365-2605.2010.01125.x
PN 2
PG 9
WC Andrology
SC Endocrinology & Metabolism
GA 798AX
UT WOS:000293174100009
PM 21128977
ER
PT J
AU Kreitchmann, R
Cohen, RA
Stoszek, SK
Pinto, JA
Losso, M
Pierre, R
Alarcon, J
Succi, R
Szyld, E
Abreu, T
Read, JS
AF Kreitchmann, Regis
Cohen, Rachel A.
Stoszek, Sonia K.
Pinto, Jorge A.
Losso, Marcelo
Pierre, Russell
Alarcon, Jorge
Succi, Regina
Szyld, Edgardo
Abreu, Thalita
Read, Jennifer S.
TI Mode of delivery and neonatal respiratory morbidity among HIV-exposed
newborns in Latin America and the Caribbean: NISDI Perinatal-LILAC
Studies
SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
LA English
DT Article
DE Cesarean delivery; HIV; Newborn; Respiratory distress syndrome
ID ELECTIVE CESAREAN-SECTION; VERTICAL TRANSMISSION; HIV-1-INFECTED WOMEN;
TERM; RISK; COHORT; BORN
AB Objective: To evaluate respiratory morbidity (RM) in HIV-exposed newborns according to mode of delivery. Methods: The NISDI Perinatal/LILAC prospective cohort studies enrolled HIV-infected pregnant women and their newborns in Latin America and the Caribbean. Associations between RM and delivery mode or other characteristics were evaluated. Results: Between September 2002 and December 2009, 1630 women were enrolled, and 1443 mother-infant pairs met the inclusion criteria. There were 561 vaginal (VD). 269 cesarean before labor and membrane rupture (SCS) for preventing mother-to-child transmission (SCS-PMTCT), 248 other SCS, and 365 cesarean after labor and/or ruptured membranes (NSCS) deliveries. In total, 108 (7.5%) newborns had RM: 49 had respiratory distress syndrome (RDS), 39 had transient tachypnea (ITN), and 28 had other events (7 newborns had >1 RM event). Delivery mode was associated with RDS (P<0.005) and TIN (P<0.001). The proportion with RDS and UN was lowest for VD (1.6% and 0.5%, respectively), highest for NSCS (4.9% and 4.7%), and intermediate for SCS-PMTCT (3.0% and 2.6%). Newborns with RDS or TIN were hospitalized longer (median +1 day) than those without. A minority required ventilatory support (RDS, 24.5%-28.6%; UN, 2.6%-15.4%). Conclusions: SCS-PMTCT is relatively safe for newborns of HIV-infected women. (C) 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Kreitchmann, Regis] Irmandade Santa Casa de Misericordia Porto Alegre, Porto Alegre, RS, Brazil.
[Cohen, Rachel A.; Stoszek, Sonia K.] Westat Corp, Rockville, MD USA.
[Pinto, Jorge A.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil.
[Losso, Marcelo] Hosp Gen Agudos Jose Maria Ramos Mejia, Buenos Aires, DF, Argentina.
[Pierre, Russell] Univ W Indies, Dept Obstet Gynecol & Child Hlth, Pediat & Perinatal HIVAIDS Program, Kingston 7, Jamaica.
[Alarcon, Jorge] Univ San Marcos, Lima, Peru.
[Succi, Regina] Univ Fed Sao Paulo, Div Pediat Infect Dis, Sao Paulo, Brazil.
[Szyld, Edgardo] Hosp Diego Paroissien, FUNDASAMIN, Buenos Aires, DF, Argentina.
[Abreu, Thalita] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil.
[Read, Jennifer S.] NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH, Bethesda, MD USA.
RP Kreitchmann, R (reprint author), Rua Prof Annes Dias 285,1 Andar, BR-90020090 Porto Alegre, RS, Brazil.
EM regis.kr@terra.com.br
OI Alarcon, Jorge/0000-0002-0800-2380
FU NICHD [N01-HD-3-3345, HHSN267200800001C]
FX NICHD: Rohan Hazra, Lynne Mofenson, Jennifer S. Read, Heather Watts,
Carol Worrell (Eunice Kennedy Shriver National Institute of Child Health
and Human Development, Bethesda, Maryland, USA). Supported by NICHD
Contract # N01-HD-3-3345 (2002-2007) and by NICHD Contract #
HHSN267200800001C (NICHD Control #: N01-HD-8-0001) (2007-2012).
NR 20
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U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0020-7292
J9 INT J GYNECOL OBSTET
JI Int. J. Gynecol. Obstet.
PD AUG
PY 2011
VL 114
IS 2
BP 91
EP 96
DI 10.1016/j.ijgo.2011.02.008
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 799WK
UT WOS:000293316600001
PM 21620404
ER
PT J
AU Bernstein, DI
Kissling, GE
Hershey, GK
Yucesoy, B
Johnson, VJ
Cartier, A
Gautrin, D
Sastre, J
Boulet, LP
Malo, JL
Quirce, S
Tarlo, SM
Langmeyer, S
Luster, MI
Lummus, ZL
AF Bernstein, David I.
Kissling, Grace E.
Hershey, Gurjit Khurana
Yucesoy, Berran
Johnson, Victor J.
Cartier, Andre
Gautrin, Denyse
Sastre, Joaquin
Boulet, Louis-Philippe
Malo, Jean-Luc
Quirce, Santiago
Tarlo, Susan M.
Langmeyer, Stacy
Luster, Michael I.
Lummus, Zana L.
TI Hexamethylene diisocyanate asthma is associated with genetic
polymorphisms of CD14, IL-13, and IL-4 receptor alpha
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID OCCUPATIONAL ASTHMA; IL4RA
C1 [Bernstein, David I.; Langmeyer, Stacy; Lummus, Zana L.] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA.
[Kissling, Grace E.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Hershey, Gurjit Khurana] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Yucesoy, Berran; Johnson, Victor J.; Luster, Michael I.] NIOSH, CDC, Hlth Effects Lab Div, Morgantown, WV USA.
[Cartier, Andre; Gautrin, Denyse; Malo, Jean-Luc] Univ Montreal, Hop Sacre Coeur, Quebec City, PQ, Canada.
[Sastre, Joaquin; Quirce, Santiago] Univ Autonoma Madrid, Dept Allergy, E-28049 Madrid, Spain.
[Boulet, Louis-Philippe] Univ Laval, Hop Laval, Ste Foy, PQ G1K 7P4, Canada.
[Tarlo, Susan M.] Univ Toronto, Toronto, ON M5S 1A1, Canada.
RP Bernstein, DI (reprint author), Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA.
EM Bernstdd@ucmail.uc.edu
FU Intramural NIH HHS [Z01 ES045005-11]; NIEHS NIH HHS [Z01 ES045005,
Z01-ES045005]; NIOSH CDC HHS [1-R01 OH008795, R01 OH008795]
NR 9
TC 10
Z9 10
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 AUG
PY 2011
VL 128
IS 2
BP 418
EP 420
DI 10.1016/j.jaci.2011.03.007
PG 4
WC Allergy; Immunology
SC Allergy; Immunology
GA 799IQ
UT WOS:000293280800027
PM 21489615
ER
PT J
AU Marsh, AA
Finger, EC
Schechter, JC
Jurkowitz, ITN
Reid, ME
Blair, RJR
AF Marsh, Abigail A.
Finger, Elizabeth C.
Schechter, Julia C.
Jurkowitz, Ilana T. N.
Reid, Marguerite E.
Blair, R. J. R.
TI Adolescents with psychopathic traits report reductions in physiological
responses to fear
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Psychopathy; emotion; fear; antisocial behavior; autonomic; adolescence;
conduct disorder
ID CALLOUS-UNEMOTIONAL TRAITS; SCHOOL-AGE; EMOTION; INDIVIDUALS; CHILDREN;
RESONANCE; BEHAVIOR; AMYGDALA; RECOGNITION; EXPRESSIONS
AB Background: Psychopathy is characterized by profound affective deficits, including shallow affect and reduced empathy. Recent research suggests that these deficits may apply particularly to negative emotions, or to certain negative emotions such as fear. Despite increased focus on the cognitive and neural underpinnings of psychopathy, little is known about how psychopathy is associated with emotional deficits across a range of emotions. In addition, the relationship between psychopathy and the subjective experience of emotion has not yet been assessed. Methods: Eighteen 10-17-year-olds with psychopathic traits and 24 comparison children and adolescents reported on their subjective experiences of emotion during five recent emotionally evocative life events, following a paradigm developed by Scherer and colleagues (Scherer & Wallbott, 1994). Group comparisons were then performed to assess variations in subjective experiences across emotions. Results: As predicted, psychopathy was associated with reductions in the subjective experience of fear relative to other emotions. Children and adolescents with psychopathic traits reported fewer symptoms associated with sympathetic nervous system arousal during fear-evoking experiences. Conclusions: Rather than being related to uniformly impoverished emotional experience, psychopathic traits appear to be associated with greater deficits in subjective experiences of fear. This pattern of responding supports and extends previous observations that psychopathy engenders deficits in fear learning, physiological responses to threats, and the recognition of fear in others.
C1 [Marsh, Abigail A.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA.
[Marsh, Abigail A.; Schechter, Julia C.; Jurkowitz, Ilana T. N.; Reid, Marguerite E.; Blair, R. J. R.] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA.
[Finger, Elizabeth C.] Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada.
RP Marsh, AA (reprint author), Georgetown Univ, Dept Psychol, 37th & O St NW, Washington, DC 20057 USA.
EM aam72@georgetown.edu
RI Finger, Elizabeth/B-6453-2015
FU NIMH/NIH
FX This research was supported by the Intramural Research Program of the
NIMH/NIH.
NR 44
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U1 5
U2 34
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9630
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD AUG
PY 2011
VL 52
IS 8
BP 834
EP 841
DI 10.1111/j.1469-7610.2010.02353.x
PG 8
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 798BW
UT WOS:000293177400003
PM 21155775
ER
PT J
AU Kim, P
Feldman, R
Mayes, LC
Eicher, V
Thompson, N
Leckman, JF
Swain, JE
AF Kim, Pilyoung
Feldman, Ruth
Mayes, Linda C.
Eicher, Virginia
Thompson, Nancy
Leckman, James F.
Swain, James E.
TI Breastfeeding, brain activation to own infant cry, and maternal
sensitivity
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Breastfeeding; infancy; maternal sensitivity; mother-infant interaction;
neuroimaging
ID SOCIAL-EMOTIONAL DEVELOPMENT; COGNITIVE-DEVELOPMENT; POSTPARTUM PERIOD;
NEURAL BASIS; MOTHERS; CHILD; SYNCHRONY; PARENT; ATTACHMENT; BEHAVIOR
AB Background: Research points to the importance of breastfeeding for promoting close mother-infant contact and social-emotional development. Recent functional magnetic resonance imaging (fMRI) studies have identified brain regions related to maternal behaviors. However, little research has addressed the neurobiological mechanisms underlying the relationship between breastfeeding and maternal behavior in human mothers. We investigated the associations between breastfeeding, maternal brain response to own infant stimuli, and maternal sensitivity in the early postpartum. Methods: Seventeen biological mothers of healthy infants participated in two matched groups according to feeding method - exclusive breastfeeding and exclusive formula-feeding at 2-4 weeks postpartum. fMRI scanning was conducted in the first postpartum month to examine maternal brain activation in response to her own baby's cry versus control baby-cry. Dyadic interactions between mothers and infants at 3-4 months postpartum were videotaped in the home and blindly coded for maternal sensitivity. Results: In the first postpartum month, breastfeeding mothers showed greater activations in the superior frontal gyrus, insula, precuneus, striatum, and amygdala while listening to their own baby-cry as compared to formula-feeding mothers. For both breastfeeding and formula-feeding mothers, greater activations in the right superior frontal gyrus and amygdala were associated with higher maternal sensitivity at 3-4 months postpartum. Conclusions: Results suggest links between breastfeeding and greater response to infant cues in brain regions implicated in maternal-infant bonding and empathy during the early postpartum. Such brain activations may facilitate greater maternal sensitivity as infants enter their social world.
C1 [Kim, Pilyoung; Feldman, Ruth; Mayes, Linda C.; Eicher, Virginia; Thompson, Nancy; Leckman, James F.; Swain, James E.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA.
[Kim, Pilyoung] Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA.
[Feldman, Ruth] Bar Ilan Univ, Leslie & Susan Gonda Brain Sci Ctr, IL-52100 Ramat Gan, Israel.
[Mayes, Linda C.] Anna Freud Ctr, London, England.
[Swain, James E.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
RP Kim, P (reprint author), NIMH, 9000 Rockville Pike,Bldg 15K,Rm 208, Bethesda, MD 20892 USA.
EM pilyoung.kim@nih.gov
RI Swain, James/F-7270-2013
OI Swain, James/0000-0001-8440-0658
FU Ellin Bloch and Pierre Ritchie Honorary Scholarship; American
Psychological Association of Graduate Students (APAGS); College of Human
Ecology; Cornell University; US-Israel Binational Science Foundation
[2005-273]; Institute for the Study of Unlimited Love; National Alliance
for Research on Schizophrenia and Depression; National Institute of
Mental Health [K05MH076273]; National Institute of Drug Abuse
[5K05DA020091]; Associates of the Yale Child Study Center
FX This work was supported by the Ellin Bloch and Pierre Ritchie Honorary
Scholarship, the American Psychological Association of Graduate Students
(APAGS) (PK); College of Human Ecology Graduate Research Grant, Cornell
University (PK); the US-Israel Binational Science Foundation (2005-273,
RF, JFL), the Institute for the Study of Unlimited Love (JES, JFL); the
National Alliance for Research on Schizophrenia and Depression (RF,
JES), the National Institute of Mental Health (JFL: K05MH076273), the
National Institute of Drug Abuse (LCM: 5K05DA020091), and the Associates
of the Yale Child Study Center. We thank Drs. Gary W. Evans, Cindy
Hazan, and Richard Depue at Cornell University for their helpful
insights and suggestions.
NR 57
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U1 2
U2 54
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD AUG
PY 2011
VL 52
IS 8
BP 907
EP 915
DI 10.1111/j.1469-7610.2011.02406.x
PG 9
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 798BW
UT WOS:000293177400012
PM 21501165
ER
PT J
AU Redd, AD
Collinson-Streng, A
Martens, C
Ricklefs, S
Mullis, CE
Manucci, J
Tobian, AAR
Selig, EJ
Laeyendecker, O
Sewankambo, N
Gray, RH
Serwadda, D
Wawer, MJ
Porcella, SF
Quinn, TC
AF Redd, Andrew D.
Collinson-Streng, Aleisha
Martens, Craig
Ricklefs, Stacy
Mullis, Caroline E.
Manucci, Jordyn
Tobian, Aaron A. R.
Selig, Ethan J.
Laeyendecker, Oliver
Sewankambo, Nelson
Gray, Ronald H.
Serwadda, David
Wawer, Maria J.
Porcella, Stephen F.
Quinn, Thomas C.
CA Rakai Hlth Sci Program
TI Identification of HIV Superinfection in Seroconcordant Couples in Rakai,
Uganda, by Use of Next-Generation Deep Sequencing
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; DUAL INFECTION; SUBTYPES; STRAINS;
REGION; RISK
AB HIV superinfection, which occurs when a previously infected individual acquires a new distinct HIV strain, has been described in a number of populations. Previous methods to detect superinfection have involved a combination of labor-intensive assays with various rates of success. We designed and tested a next-generation sequencing (NGS) protocol to identify HIV superinfection by targeting two regions of the HIV viral genome, p24 and gp41. The method was validated by mixing control samples infected with HIV subtype A or D at different ratios to determine the inter-and intrasubtype sensitivity by NGS. This amplicon-based NGS protocol was able to consistently identify distinct intersubtype strains at ratios of 1% and intrasubtype variants at ratios of 5%. By using stored samples from the Rakai Community Cohort Study (RCCS) in Uganda, 11 individuals who were HIV seroconcordant but virally unlinked from their spouses were then tested by this method to detect superinfection between 2002 and 2005. Two female cases of HIV intersubtype superinfection (18.2%) were identified. These results are consistent with other African studies and support the hypothesis that HIV superinfection occurs at a relatively high rate. Our results indicate that NGS can be used for detection of HIV superinfection within large cohorts, which could assist in determining the incidence and the epidemiologic, virologic, and immunological correlates of this phenomenon.
C1 [Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Redd, Andrew D.; Collinson-Streng, Aleisha; Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, Immunoregulat Lab, DIR, NIH, Baltimore, MD USA.
[Martens, Craig; Ricklefs, Stacy; Selig, Ethan J.; Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,DIR,NIH, Hamilton, MT 59840 USA.
[Sewankambo, Nelson; Serwadda, David] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Gray, Ronald H.; Wawer, Maria J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Sewankambo, Nelson] Makerere Univ, Sch Med, Kampala, Uganda.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
RP Quinn, TC (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Rangos Bldg,Room 530,855 N Wolfe St, Baltimore, MD 21205 USA.
EM tquinn2@jhmi.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Sewankambo, Nelson/0000-0001-9362-053X; Laeyendecker,
Oliver/0000-0002-6429-4760
FU Division of Intramural Research, NIAID, NIH, NIAID [R01 A134826, R01
A134265]; NICHD [5P30HD06826]; World Bank, Uganda; Henry M. Jackson
Foundation; Fogarty Foundation [5D43TW00010]; Bill and Melinda Gates
Institute for Population and Reproductive Health at JHU
FX This study was supported in part by funding from the Division of
Intramural Research, NIAID, NIH, NIAID grants R01 A134826 and R01
A134265, NICHD grant 5P30HD06826, the World Bank STI Project, Uganda,
the Henry M. Jackson Foundation, the Fogarty Foundation (grant
5D43TW00010), and the Bill and Melinda Gates Institute for Population
and Reproductive Health at JHU.
NR 31
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U1 2
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD AUG
PY 2011
VL 49
IS 8
BP 2859
EP 2867
DI 10.1128/JCM.00804-11
PG 9
WC Microbiology
SC Microbiology
GA 798PE
UT WOS:000293221900012
PM 21697329
ER
PT J
AU Castle, PE
Gutierrez, EC
Leitch, SV
Maus, CE
McMillian, RA
Nussbaumer, WA
Vaughan, LM
Wheeler, CM
Gravitt, PE
Schiffman, M
AF Castle, Philip E.
Gutierrez, Erin C.
Leitch, Sharon V.
Maus, Courtney E.
McMillian, Ray A.
Nussbaumer, William A.
Vaughan, Laurence M.
Wheeler, Cosette M.
Gravitt, Patti E.
Schiffman, Mark
TI Evaluation of a New DNA Test for Detection of Carcinogenic Human
Papillomavirus
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID ATYPICAL SQUAMOUS-CELLS; RANDOMIZED-TRIAL; UNDETERMINED SIGNIFICANCE;
CYTOLOGY INTERPRETATIONS; CERVICAL PRECANCER; MANAGEMENT; CANCER; WOMEN;
PAPANICOLAOU; BETHESDA
AB Using archived specimens, we evaluated a new automated real-time PCR assay (BD Diagnostics) that detects all carcinogenic human papillomaviruses (HPV) and provides HPV genotyping for seven of them, including HPV16 and HPV18, the two most carcinogenic HPV genotypes. We found comparable results with Hybrid Capture 2 (HC2) for detection of carcinogenic HPV (n = 473) and with Linear Array and Line Blot Assay (n = 371) for detection of individual HPV genotypes.
C1 [Castle, Philip E.] Amer Soc Clin Pathol Inst, Washington, DC 20005 USA.
[Gutierrez, Erin C.; Leitch, Sharon V.; Maus, Courtney E.; McMillian, Ray A.; Nussbaumer, William A.; Vaughan, Laurence M.] BD Diagnost, Sparks, MD 21152 USA.
[Wheeler, Cosette M.] Univ New Mexico, Hlth Sci Ctr, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA.
[Gravitt, Patti E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA.
[Gravitt, Patti E.] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
[Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Castle, PE (reprint author), Amer Soc Clin Pathologists, 1225 New York Ave NW,Suite 250, Washington, DC 20005 USA.
EM philip.castle@ascp.org
FU National Cancer Institute, National Institutes of Health Department of
Health and Human Services [CN-55153, CN-55154, CN-55155, CN-55156,
CN-55157, CN-55158, CN-55159, CN-55105]; NIH, National Cancer Institute
FX The ALTS group was supported by the National Cancer Institute, National
Institutes of Health Department of Health and Human Services, contracts
CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159,
and CN-55105. Some of the equipment and supplies used in these studies
were donated or provided at reduced cost by Digene Corporation,
Gaithersburg, MD, Cytyc Corporation, Marlborough, MA, National Testing
Laboratories, Fenton, MO, DenVu, Tucson, AZ, TriPath Imaging, Inc.,
Burlington, NC, and Roche Molecular Systems Inc., Alameda, CA.; We thank
the ALTS group investigators for their help in planning and conducting
the trial. We report no conflicts of interest. This research was
supported in part by the Intramural Research Program of the NIH,
National Cancer Institute.
NR 18
TC 16
Z9 16
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD AUG
PY 2011
VL 49
IS 8
BP 3029
EP 3032
DI 10.1128/JCM.00422-11
PG 4
WC Microbiology
SC Microbiology
GA 798PE
UT WOS:000293221900045
PM 21632892
ER
PT J
AU LoRusso, PM
Boerner, SA
Hunsberger, S
AF LoRusso, Patricia M.
Boerner, Scott A.
Hunsberger, Sally
TI Clinical Development of Vascular Disrupting Agents: What Lessons Can We
Learn From ASA404?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID CELL LUNG-CANCER; TUMOR BLOOD-VESSELS; THERAPEUTIC STRATEGY; PHASE-II;
PACLITAXEL; ACID; CARBOPLATIN; VADIMEZAN; DMXAA; BEVACIZUMAB
C1 [LoRusso, Patricia M.; Boerner, Scott A.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA.
[Hunsberger, Sally] NCI, Rockville, MD USA.
RP LoRusso, PM (reprint author), Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA.
NR 29
TC 19
Z9 19
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 1
PY 2011
VL 29
IS 22
BP 2952
EP 2955
DI 10.1200/JCO.2011.36.1311
PG 5
WC Oncology
SC Oncology
GA 798PG
UT WOS:000293222200010
PM 21709201
ER
PT J
AU Maldonado, NI
Cabanillas, F
Jaffe, ES
Raffeld, M
Lozada, L
AF Maldonado, Norman I.
Cabanillas, Fernando
Jaffe, Elaine S.
Raffeld, Mark
Lozada, Luis
TI Successful Treatment of a Patient With Epstein-Barr Virus-Positive
B-Cell Lymphoproliferative Disorder Resembling Post-Transplant
Lymphoproliferative Disorder Using Single-Agent Rituximab
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID LYMPHOMATOID GRANULOMATOSIS; EFFICACY
C1 [Maldonado, Norman I.; Cabanillas, Fernando] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA.
[Cabanillas, Fernando] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Cabanillas, Fernando] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Jaffe, Elaine S.; Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Lozada, Luis] Hato Rey Pathol Associates, San Juan, PR USA.
RP Maldonado, NI (reprint author), Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA.
OI Jaffe, Elaine/0000-0003-4632-0301
NR 14
TC 3
Z9 3
U1 0
U2 1
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 AUG 1
PY 2011
VL 29
IS 22
BP E658
EP E660
DI 10.1200/JCO.2011.34.8656
PG 3
WC Oncology
SC Oncology
GA 798PG
UT WOS:000293222200007
PM 21646613
ER
PT J
AU Yu, YK
Altschul, SF
AF Yu, Yi-Kuo
Altschul, Stephen F.
TI The Complexity of the Dirichlet Model for Multiple Alignment Data
SO JOURNAL OF COMPUTATIONAL BIOLOGY
LA English
DT Article
DE alignment; computational molecular biology; dynamic programming;
multiple alignment; sequence analysis
AB A model is a set of possible theories for describing a set of data. When the data are used to select a maximum-likelihood theory, an important question is how many effectively independent theories the model contains; the log of this number is called the model's complexity. The Dirichlet model is the set of all Dirichlet distributions, which are probability densities over the space of multinomials. A Dirichlet distribution may be used to describe multiple-alignment data, consisting of n columns of letters, with c letters in each column. We here derive, in the limit of large n and c, a closed-form expression for the complexity of the Dirichlet model applied to such data. For small c, we derive as well a minor correction to this formula, which is easily calculated by Monte Carlo simulation. Although our results are confined to the Dirichlet model, they may cast light as well on the complexity of Dirichlet mixture models, which have been applied fruitfully to the study of protein multiple sequence alignments.
C1 [Yu, Yi-Kuo; Altschul, Stephen F.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Altschul, SF (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM altschul@ncbi.nlm.nih.gov
FU National Library of Medicine at the National Institutes of Health
FX We thank Drs. John Spouge and Xugang Ye for helpful conversations. This
work was supported by the Intramural Research Program of the National
Library of Medicine at the National Institutes of Health.
NR 6
TC 1
Z9 1
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1066-5277
J9 J COMPUT BIOL
JI J. Comput. Biol.
PD AUG
PY 2011
VL 18
IS 8
BP 925
EP 939
DI 10.1089/cmb.2011.0039
PG 15
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 799ID
UT WOS:000293279400001
PM 21702692
ER
PT J
AU Ye, XG
Yu, YK
Altschul, SF
AF Ye, Xugang
Yu, Yi-Kuo
Altschul, Stephen F.
TI On the Inference of Dirichlet Mixture Priors for Protein Sequence
Comparison
SO JOURNAL OF COMPUTATIONAL BIOLOGY
LA English
DT Article
DE algorithms; combinatorics; linear programming; machine learning;
statistics
AB Dirichlet mixtures provide an elegant formalism for constructing and evaluating protein multiple sequence alignments. Their use requires the inference of Dirichlet mixture priors from curated sets of accurately aligned sequences. This article addresses two questions relevant to such inference: of how many components should a Dirichlet mixture consist, and how may a maximum-likelihood mixture be derived from a given data set. To apply the Minimum Description Length principle to the first question, we extend an analytic formula for the complexity of a Dirichlet model to Dirichlet mixtures by informal argument. We apply a Gibbs-sampling based approach to the second question. Using artificial data generated by a Dirichlet mixture, we demonstrate that our methods are able to approximate well the true theory, when it exists. We apply our methods as well to real data, and infer Dirichlet mixtures that describe the data better than does a mixture derived using previous approaches.
C1 [Ye, Xugang; Yu, Yi-Kuo; Altschul, Stephen F.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Altschul, SF (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM altschul@ncbi.nlm.nih.gov
FU National Library of Medicine at the National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Library of Medicine at the National Institutes of Health.
NR 13
TC 4
Z9 4
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1066-5277
J9 J COMPUT BIOL
JI J. Comput. Biol.
PD AUG
PY 2011
VL 18
IS 8
BP 941
EP 954
DI 10.1089/cmb.2011.0040
PG 14
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 799ID
UT WOS:000293279400002
PM 21702690
ER
PT J
AU Henning, T
Fakile, Y
Phillips, C
Sweeney, E
Mitchell, J
Patton, D
Sturdevant, G
Caldwell, HD
Secor, WE
Papp, J
Hendry, RM
McNicholl, J
Kersh, E
AF Henning, Tara
Fakile, Yetunde
Phillips, Christi
Sweeney, Elizabeth
Mitchell, James
Patton, Dorothy
Sturdevant, Gail
Caldwell, Harlan D.
Secor, W. Evan
Papp, John
Hendry, R. Michael
McNicholl, Janet
Kersh, Ellen
TI Development of a pigtail macaque model of sexually transmitted
infection/HIV coinfection using Chlamydia trachomatis, Trichomonas
vaginalis, and SHIVSF162P3
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Article; Proceedings Paper
CT 28th Annual Symposium on Nonhuman Primate Models for AIDS
CY OCT 19-22, 2010
CL Tulane Natl Primate Res Ctr, New Orleans, LA
SP Agilent Technol, Capitol City Produce, Covance, Mabtech, MP Biomed, Purina Lab Diet, SPEX Sample Prep, LLC
HO Tulane Natl Primate Res Ctr
DE coinfection; genital; mucosal; non-human primate
ID HUMAN-IMMUNODEFICIENCY-VIRUS; PELVIC-INFLAMMATORY-DISEASE;
CLINICAL-MANIFESTATIONS; MACACA-NEMESTRINA; HIV-1 TRANSMISSION;
NONHUMAN-PRIMATES; GENITAL-TRACT; WOMEN; SUSCEPTIBILITY; CHALLENGES
AB Background Sexually transmitted infections (STIs) are associated with an increased risk of HIV infection. To model the interaction between STIs and HIV infection, we evaluated the capacity of the pigtail macaque model to sustain triple infection with Trichomonas vaginalis, Chlamydia trachomatis, and SHIVSF162P3.
Methods Seven SHIVSF162P3-infected pigtail macaques were inoculated with T. vaginalis only (n = 2), C. trachomatis only (n = 1), both T. vaginalis and C. trachomatis (n = 2), or control media (no STI; n = 2). Infections were confirmed by culture and/or nucleic acid testing. Genital mucosa was visualized by colposcopy.
Results Characteristic gynecologic signs were observed for both STIs, but not in control animals. Manifestations were most prominent at days 7-10 post-infection. STIs persisted between 4 and 6 weeks and were cleared with antibiotics.
Conclusions These pilot studies demonstrate the first successful STI-SHIV triple infection of pigtail macaques, with clinical presentation of genital STI symptoms similar to those observed in humans.
C1 [Henning, Tara; Sweeney, Elizabeth; Mitchell, James; Hendry, R. Michael; McNicholl, Janet; Kersh, Ellen] CDC, Div HIV AIDS Prevent, Atlanta, GA 30333 USA.
[Fakile, Yetunde; Phillips, Christi; Papp, John] CDC, Div Sexually Transmitted Dis Prevent, Atlanta, GA 30333 USA.
[Patton, Dorothy] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
[Sturdevant, Gail; Caldwell, Harlan D.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Secor, W. Evan] CDC, Div Parasit Dis & Malaria, Atlanta, GA 30333 USA.
RP Kersh, E (reprint author), 1600 Clifton Rd NE,MS A25, Atlanta, GA 30333 USA.
EM ekersh@cdc.gov
FU Intramural NIH HHS [ZIA AI000672-18]; NIAID NIH HHS [Y01 AI000681,
Y1-AI-0681-02]
NR 46
TC 18
Z9 19
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0047-2565
EI 1600-0684
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
BP 214
EP 223
DI 10.1111/j.1600-0684.2011.00488.x
PG 10
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700003
PM 21781129
ER
PT J
AU Park, H
Fukazawa, Y
Lum, R
Mahyari, E
Coombes, N
Hagen, S
Bae, JY
De los Reyes, M
Nogueron, A
Legasse, A
Sylwester, A
Axthelm, M
Piatak, M
Lifson, JD
Winston, N
McDermott, A
Montefiori, D
Picker, LJ
AF Park, Haesun
Fukazawa, Yoshinori
Lum, Richard
Mahyari, Eisa
Coombes, Noel
Hagen, Shoko
Bae, Jin Young
De los Reyes, Marcelo, III
Nogueron, Arys
Legasse, Alfred
Sylwester, Andrew
Axthelm, Mike
Piatak, Mike
Lifson, Jeff D.
Winston, Nicola
McDermott, Adrian
Montefiori, David
Picker, Louis J.
TI THE T-CELL RESPONSE AND VIRAL REPLICATION IN LYMPH NODES, NOT IN
PERIPHERAL BLOOD ARE PREDICTIVE FOR PROTECTION OF LIVE ATTENUATED SIV
VACCINE
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Park, Haesun; Fukazawa, Yoshinori; Lum, Richard; Mahyari, Eisa; Coombes, Noel; Hagen, Shoko; Bae, Jin Young; De los Reyes, Marcelo, III; Nogueron, Arys; Legasse, Alfred; Sylwester, Andrew; Axthelm, Mike; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.
[Park, Haesun; Fukazawa, Yoshinori; Lum, Richard; Mahyari, Eisa; Coombes, Noel; Hagen, Shoko; Bae, Jin Young; De los Reyes, Marcelo, III; Nogueron, Arys; Legasse, Alfred; Sylwester, Andrew; Axthelm, Mike; Picker, Louis J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
[Piatak, Mike; Lifson, Jeff D.] NCI, Retroviral Pathogenesis Lab, AIDS Vaccine Program, SAIC Frederick,Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA.
[Winston, Nicola; McDermott, Adrian] Int AIDS Vaccine Initiat, New York, NY USA.
[Montefiori, David] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 4
BP 250
EP 250
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700011
ER
PT J
AU Keele, BF
Ma, ZM
Stone, M
Qureshi, H
Fritts, L
Lifson, JD
Miller, CJ
AF Keele, Brandon F.
Ma, Zhong-Min
Stone, Mars
Qureshi, Huma
Fritts, Linda
Lifson, Jeffery D.
Miller, Christopher J.
TI PENILE INFECTION OF RHESUS MACAQUES WITH SIVMAC251 RECAPITULATES THE
EXTREME GENETIC BOTTLENECK OF MUCOSAL HIV-1 TRANSMISSION
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Keele, Brandon F.; Lifson, Jeffery D.] NCI, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA.
[Ma, Zhong-Min; Stone, Mars; Qureshi, Huma; Fritts, Linda; Miller, Christopher J.] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA.
[Ma, Zhong-Min; Stone, Mars; Qureshi, Huma; Fritts, Linda; Miller, Christopher J.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 16
BP 253
EP 254
PG 2
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700023
ER
PT J
AU Henning, T
Fakile, Y
Phillips, C
Sweeney, E
Mitchell, J
Ballard, R
Patton, D
Caldwell, HD
Secor, WE
Papp, J
Hendry, M
McNicholl, J
Kersh, E
AF Henning, Tara
Fakile, Yetunde
Phillips, Christi
Sweeney, Elizabeth
Mitchell, James
Ballard, Ron
Patton, Dorothy
Caldwell, Harlan D.
Secor, William E.
Papp, John
Hendry, Michael
McNicholl, Janet
Kersh, Ellen
TI DEVELOPMENT OF A PIG-TAILED MACAQUE MODEL OF SEXUALLY-TRANSMITTED
INFECTION/HUMAN IMMUNODEFICIENCY VIRUS COINFECTION UTILIZING CHLAMYDIA
TRACHOMATIS, TRICHOMONAS VAGINALIS, AND SHIVSF162P3
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Henning, Tara; Sweeney, Elizabeth; Mitchell, James; Hendry, Michael; McNicholl, Janet; Kersh, Ellen] CDC, Div HIV AIDS Prevent, Atlanta, GA 30333 USA.
[Fakile, Yetunde; Phillips, Christi; Ballard, Ron; Papp, John] CDC, Div Sexually Transmitted Dis Prevent, Atlanta, GA 30333 USA.
[Patton, Dorothy] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
[Caldwell, Harlan D.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Secor, William E.] CDC, Div Parasit Dis & Malaria, Atlanta, GA 30333 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 18
BP 254
EP 254
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700025
ER
PT J
AU Jordan, APO
Breed, MW
Haggarty, B
Romano, J
Aye, P
Piatak, M
Lifson, JD
Fultz, PN
Lackner, AA
Hoxie, JA
AF Jordan, Andrea P. O.
Breed, Matthew W.
Haggarty, Beth
Romano, Josephine
Aye, Pyonne
Piatak, Mike
Lifson, Jeffrey D.
Fultz, Patricia N.
Lackner, Andrew A.
Hoxie, James A.
TI DIFFERENCES BETWEEN RHESUS AND PIGTAIL MACAQUES IN PATHOGENESIS OF AN
ATTENUATED CYTOPLASMIC TAIL MUTANT OF SIVMAC239
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Jordan, Andrea P. O.; Haggarty, Beth; Romano, Josephine; Hoxie, James A.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Breed, Matthew W.; Aye, Pyonne; Lackner, Andrew A.] Tulane Natl Primate Res Ctr, Covington, LA USA.
[Piatak, Mike; Lifson, Jeffrey D.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Fultz, Patricia N.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 17
BP 254
EP 254
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700024
ER
PT J
AU Kong, R
Li, H
Lopker, M
Easlick, J
Shah, A
Decker, J
Bibollet-Ruche, F
Kiviat, N
Langedijk, H
Hahn, B
Robinson, J
Kwong, P
Shaw, G
AF Kong, Rui
Li, Hao
Lopker, Michael
Easlick, Juliet
Shah, Anita
Decker, Julie
Bibollet-Ruche, Frederic
Kiviat, Nancy
Langedijk, Hans
Hahn, Beatrice
Robinson, James
Kwong, Peter
Shaw, George
TI BROAD AND POTENT NEUTRALIZATION OF HIV-2/SIV BY ANTI-V3 AND ANTI-V4
MONOCLONAL ANTIBODIES
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Kong, Rui; Li, Hao; Lopker, Michael; Easlick, Juliet; Decker, Julie; Bibollet-Ruche, Frederic; Hahn, Beatrice; Shaw, George] Univ Alabama, Birmingham, AL USA.
[Shah, Anita; Kwong, Peter] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Kiviat, Nancy] Univ Washington, Seattle, WA 98195 USA.
[Langedijk, Hans] Pepscan Therapeut BV, Lelystad, Netherlands.
[Robinson, James] Tulane Univ, Med Ctr, New Orleans, LA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 20
BP 255
EP 255
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700027
ER
PT J
AU Klatt, NR
Harris, LD
Vinton, CL
Tabb, B
Morcock, D
Hirsch, VM
Lifson, JD
Alter, G
Estes, JD
Brenchley, JM
AF Klatt, Nichole R.
Harris, Levelle D.
Vinton, Carol L.
Tabb, Brian
Morcock, David
Hirsch, Vanessa M.
Lifson, Jeffrey D.
Alter, Galit
Estes, Jacob D.
Brenchley, Jason M.
TI SIV INFECTION RESULTS IN LOSS OF IL-17-PRODUCING NK CELLS IN MUCOSAL
TISSUES, WHICH CONTRIBUTES TO DAMAGE TO THE MUCOSAL BARRIER AND IMMUNE
ACTIVATION
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Klatt, Nichole R.; Harris, Levelle D.; Vinton, Carol L.; Hirsch, Vanessa M.; Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Tabb, Brian; Morcock, David; Lifson, Jeffrey D.; Estes, Jacob D.] NCI, AIDS & Canc Virus Program, SAICF Inc, Frederick, MD 21701 USA.
[Alter, Galit] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 23
BP 256
EP 256
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700030
ER
PT J
AU Colantonio, AD
Bimber, BN
Neidermyer, WJ
Reeves, RK
Alter, G
Altfeld, M
Johnson, RP
Carrington, M
O'Connor, DH
Evans, DT
AF Colantonio, Arnaud D.
Bimber, Benjamin N.
Neidermyer, William J., Jr.
Reeves, R. Keith
Alter, Galit
Altfeld, Marcus
Johnson, R. Paul
Carrington, Mary
O'Connor, David H.
Evans, David T.
TI KIR POLYMORPHISMS MODULATE PEPTIDE-SPECIFIC BINDING TO A COMMON MHC
CLASS I MOLECULE IN THE RHESUS MACAQUE
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Colantonio, Arnaud D.; Neidermyer, William J., Jr.; Evans, David T.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, New England Primate Res Ctr, Southborough, MA 01772 USA.
[Bimber, Benjamin N.; O'Connor, David H.] Univ Wisconsin, Dept Pathol & Lab Med, Wisconsin Natl Primate Res Ctr, Madison, WI USA.
[Reeves, R. Keith; Johnson, R. Paul] New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA.
[Alter, Galit; Altfeld, Marcus; Johnson, R. Paul; Carrington, Mary] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA.
[Carrington, Mary] NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 26
BP 257
EP 257
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700033
ER
PT J
AU Michael, JL
Keele, BF
Li, H
Wang, S
Hahn, BH
Klasse, PJ
Moore, JP
Veazey, RS
Barouch, DH
Shaw, GM
AF Michael, John L.
Keele, Brandon F.
Li, Hao
Wang, Shu
Hahn, Beatrice H.
Klasse, Per J.
Moore, John P.
Veazey, Ronald S.
Barouch, Dan H.
Shaw, George M.
TI DELAYED VIREMIA IN TWO RHESUS MACAQUES FOLLOWING INTRAVAGINAL
INOCULATION OF SIVMAC251
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Michael, John L.; Li, Hao; Wang, Shu; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Birmingham, AL USA.
[Keele, Brandon F.] NCI, Frederick, MD 21701 USA.
[Klasse, Per J.; Moore, John P.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
[Veazey, Ronald S.] Tulane Natl Primate Res Ctr, Covington, LA USA.
[Barouch, Dan H.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 28
BP 258
EP 258
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700035
ER
PT J
AU Breed, MW
Jordan, APO
Aye, P
Liu, XD
Midkiff, CC
Sugimoto, C
Haggarty, BS
Alvarez, X
Pahar, B
Kuroda, MJ
Keele, BF
Hoxie, JA
Lackner, AA
AF Breed, Matthew W.
Jordan, Andrea P. O.
Aye, Pyone
Liu, Xiangdong
Midkiff, Cecily C.
Sugimoto, Chie
Haggarty, Beth S.
Alvarez, Xavjer
Pahar, Bapi
Kuroda, Marcelo J.
Keele, Brandon F.
Hoxie, James A.
Lackner, Andrew A.
TI A COMPARISON OF PATHOLOGICAL CORRELATES OF ATTENUATED MUTANTS OF HIGHLY
PATHOGENIC SIVMAC239
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Breed, Matthew W.; Aye, Pyone; Liu, Xiangdong; Midkiff, Cecily C.; Sugimoto, Chie; Alvarez, Xavjer; Pahar, Bapi; Kuroda, Marcelo J.; Lackner, Andrew A.] Tulane Natl Primate Res Ctr, Covington, LA USA.
[Jordan, Andrea P. O.; Haggarty, Beth S.; Hoxie, James A.] Univ Penn, Philadelphia, PA 19104 USA.
[Keele, Brandon F.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 36
BP 260
EP 260
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700043
ER
PT J
AU Kirmaier, A
Wu, F
Newman, RM
Hall, LR
Morgan, JS
O'Connor, S
Marx, PA
Meythaler, M
Goldstein, S
Buckler-White, A
Kaur, A
Hirsch, VM
Johnson, WE
AF Kirmaier, Andrea
Wu, Fan
Newman, Ruchi M.
Hall, Laura R.
Morgan, Jennifer S.
O'Connor, Shelby
Marx, Preston A.
Meythaler, Mareike
Goldstein, Simoy
Buckler-White, Alicia
Kaur, Amitinder
Hirsch, Vanessa M.
Johnson, Welkin E.
TI THE RHESUS MACAQUE TRIM5 GENE AND EMERGENCE OF SIVMAC
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Kirmaier, Andrea; Hall, Laura R.; Morgan, Jennifer S.; Johnson, Welkin E.] Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA.
[Kirmaier, Andrea; Meythaler, Mareike] Univ Erlangen Nurnberg, Inst Klin & Mol Virol, Nurnberg, Germany.
[Wu, Fan; Goldstein, Simoy; Buckler-White, Alicia; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Newman, Ruchi M.] Broad Inst MIT & Harvard, Genome Sequencing & Anal Program, Cambridge, MA USA.
[O'Connor, Shelby] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA.
[Marx, Preston A.] Tulane Reg Primate Res Ctr, Covington, LA USA.
[Meythaler, Mareike; Kaur, Amitinder] Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, Southborough, MA 01772 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 49
BP 264
EP 264
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700056
ER
PT J
AU Palermo, RE
Patterson, LJ
Aicher, LD
Korth, MJ
Robert-Guroff, M
Katze, MG
AF Palermo, Robert E.
Patterson, L. J.
Aicher, Lauri D.
Korth, Marcus J.
Robert-Guroff, Marjorie
Katze, Michael G.
TI GENOMIC ANALYSIS REVEALS PRE- AND POST-CHALLENGE DIFFERENCES IN A RHESUS
MACAQUE AIDS VACCINE TRIAL: INSIGHTS INTO MECHANISMS OF VACCINE EFFICACY
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Palermo, Robert E.; Aicher, Lauri D.; Korth, Marcus J.; Katze, Michael G.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Palermo, Robert E.; Korth, Marcus J.; Katze, Michael G.] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.
[Patterson, L. J.; Robert-Guroff, Marjorie] NCI, Vaccine Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 48
BP 264
EP 264
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700055
ER
PT J
AU Foulds, KE
Lindsay, RW
Bolton, DL
Donaldson, MM
Kao, SF
Song, K
Rao, SS
Seder, RA
Roederer, M
AF Foulds, Kathryn E.
Lindsay, Ross W.
Bolton, Diane L.
Donaldson, Mitzi M.
Kao, Shing-Fen
Song, Kaimei
Rao, Srinivas S.
Seder, Robert A.
Roederer, Mario
TI TISSUE AND CELL DISTRIBUTION OF RECOMBINANT ADENOVIRUS VECTORS FOLLOWING
DIFFERENT ROUTES OF VACCINATION IN RHESUS MACAQUES
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Lindsay, Ross W.; Seder, Robert A.] NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Bolton, Diane L.; Song, Kaimei; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Rao, Srinivas S.] NIAID, Lab Anim Med, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 55
BP 266
EP 267
PG 2
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700062
ER
PT J
AU Foulds, KE
Donaldson, MM
Kao, SF
Eslamizar, L
Gee, C
Koopman, G
Lifton, M
Schmitz, JE
Sylwester, AW
Wilson, A
Roederer, M
AF Foulds, Kathryn E.
Donaldson, Mitzi M.
Kao, Shing-Fen
Eslamizar, Leila
Gee, Connie
Koopman, Gerrit
Lifton, Michelle
Schmitz, Joern E.
Sylwester, Andrew W.
Wilson, Aaron
Roederer, Mario
TI OPTIMIZATION AND QUALIFICATION OF AN 8-COLOR INTRACELLULAR CYTOKINE
STAINING ASSAY FOR THE MEASUREMENT OF T CELL RESPONSES FROM RHESUS
MACAQUES IN PRE-CLINICAL VACCINE STUDIES
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Foulds, Kathryn E.; Donaldson, Mitzi M.; Kao, Shing-Fen; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Eslamizar, Leila; Gee, Connie; Lifton, Michelle; Schmitz, Joern E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, Boston, MA 02215 USA.
[Koopman, Gerrit] Biomed Primate Res Ctr, Dept Virol, Rijswijk, Netherlands.
[Sylwester, Andrew W.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.
[Wilson, Aaron] Int AIDS Vaccine Initiat, Design Lab, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 56
BP 267
EP 267
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700063
ER
PT J
AU Whitney, JB
Lacerda, M
Luedemann, C
Hraber, P
Rao, SS
Mascola, JR
Nabel, GJ
Korber, B
Seoighe, C
Letvin, NL
AF Whitney, James B.
Lacerda, Miguel
Luedemann, Corinne
Hraber, Peter
Rao, Srinivas S.
Mascola, John R.
Nabel, Gary J.
Korber, Bette
Seoighe, Cathal
Letvin, Norman L.
TI REDUCTION OF FOUNDER/TRANSMITTED VIRUS IN VACCINATED MONKEYS AFTER
MUCOSAL SIVE660 CHALLENGE
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Whitney, James B.; Luedemann, Corinne; Letvin, Norman L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis,Dept Med, Boston, MA 02215 USA.
[Lacerda, Miguel; Seoighe, Cathal] Natl Univ Ireland, Sch Math Stat & Appl Math, Galway, Ireland.
[Hraber, Peter; Korber, Bette] Los Alamos Natl Lab, Los Alamos, NM USA.
[Rao, Srinivas S.; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 61
BP 268
EP 268
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700068
ER
PT J
AU Ourmanov, I
Zheng, YF
Forsell, MNE
Kinter, AL
Goldstein, S
Montefiori, DC
Wyatt, RT
Hirsch, VM
AF Ourmanov, Ilnour
Zheng, Yanfang
Forsell, Mattias N. E.
Kinter, Audrey L.
Goldstein, Simoy
Montefiori, David C.
Wyatt, Richard T.
Hirsch, Vanessa M.
TI STUDIES OF ENV-BASED RECOMBINANT IMMUNOGENS AND ROLE OF NEUTRALIZING
ANTIBODY IN THE SIV MACAQUE MODEL
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Ourmanov, Ilnour; Zheng, Yanfang; Kinter, Audrey L.; Goldstein, Simoy; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, VRC, NIH, Bethesda, MD 20892 USA.
[Forsell, Mattias N. E.; Wyatt, Richard T.] NIAID, Struct Virol Sect, VRC, NIH, Bethesda, MD 20892 USA.
[Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 65
BP 269
EP 270
PG 2
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700072
ER
PT J
AU Lopker, MJ
Keele, BF
Li, H
Easlick, J
Decker, JM
Wang, S
Bibollet-Ruche, F
Piatak, M
Pal, R
Letvin, NL
Lifson, JD
Hahn, BH
Shaw, GM
AF Lopker, Michael J.
Keele, Brandon F.
Li, Hau
Easlick, Juliet
Decker, Julie M.
Wang, Shu
Bibollet-Ruche, Frederic
Piatak, Michael
Pal, Ranajit
Letvin, Norman L.
Lifson, Jeffrey D.
Hahn, Beatrice H.
Shaw, George M.
TI TRANSMITTED/FOUNDER VIRUSES FROM THE SIV-SME660 AND SIVMAC251 LINEAGES
ARE INFECTIOUS AND REPLICATION COMPETENT IN-VIVO
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Lopker, Michael J.; Li, Hau; Easlick, Juliet; Decker, Julie M.; Wang, Shu; Bibollet-Ruche, Frederic; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Birmingham, AL USA.
[Keele, Brandon F.; Piatak, Michael; Lifson, Jeffrey D.] NCI, Frederick, MD 21701 USA.
[Pal, Ranajit] Adv Biosci Labs, Kensington, MD USA.
[Letvin, Norman L.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 70
BP 271
EP 271
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700077
ER
PT J
AU Smith, LM
Parodi, LM
Hodara, VL
Ciorciari, JM
Vazquez-Santiago, F
Meeks, A
Sexton, V
Pavlakis, G
Felber, B
Giavedoni, LD
AF Smith, Lisa M.
Parodi, Laura M.
Hodara, Vida L.
Ciorciari, Juan M.
Vazquez-Santiago, Fabian
Meeks, Amber
Sexton, Valerie
Pavlakis, George
Felber, Barbara
Giavedoni, Luis D.
TI STRUCTURE AND IMMUNOGENICITY OF NOVEL VACCINES BASED ON FUSION PROTEINS
OF CD154 AND SIVGP41
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Smith, Lisa M.; Parodi, Laura M.; Hodara, Vida L.; Ciorciari, Juan M.; Vazquez-Santiago, Fabian; Meeks, Amber; Sexton, Valerie; Giavedoni, Luis D.] SW Fdn Biomed Res, Immunol Core Lab, SW Natl Primate Res Ctr, San Antonio, TX 78284 USA.
[Pavlakis, George; Felber, Barbara] NCI, Ctr Canc Res, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 69
BP 271
EP 271
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700076
ER
PT J
AU Dang, Q
Whitted, S
Goeken, R
Brown, C
Brenchley, J
Lafont, B
Buckler-White, A
Iyengar, R
Plishka, R
Hirsch, V
AF Dang, Que
Whitted, Sonya
Goeken, Robert
Brown, Charles
Brenchley, Jason
Lafont, Bernard
Buckler-White, Alicia
Iyengar, Ranjini
Plishka, Ronald
Hirsch, Vanessa
TI SIV-ENCEPHALITIS IN A CONVENTIONAL PROGRESSOR MACAQUE MODEL
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Dang, Que; Whitted, Sonya; Goeken, Robert; Brown, Charles; Brenchley, Jason; Lafont, Bernard; Buckler-White, Alicia; Iyengar, Ranjini; Plishka, Ronald; Hirsch, Vanessa] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RI Lafont, Bernard/B-7236-2014
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 87
BP 276
EP 276
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700094
ER
PT J
AU Li, H
Kraus, M
Wang, S
Grayson, T
Sun, C
Salazar, M
Chen, Y
Gautam, R
Gaufin, T
Learn, G
Bibollet-Ruche, F
Piatak, M
Estes, J
Keele, B
Lifson, J
Pandrea, I
Apetrei, C
Hahn, B
Shaw, G
AF Li, Hao
Kraus, M.
Wang, Shu
Grayson, T.
Sun, C.
Salazar, M.
Chen, Y.
Gautam, Rajeev
Gaufin, Thaidra
Learn, G.
Bibollet-Ruche, Frederic
Piatak, Michael
Estes, Jacob
Keele, Brandon
Lifson, Jeffrey
Pandrea, Ivona
Apetrei, Cristian
Hahn, Beatrice
Shaw, George
TI GENETIC CHARACTERIZATION OF NEWLY IDENTIFIED SIVSMM STRAINS FOR ANALYSIS
OF MUCOSAL TRANSMISSION AND VACCINE PROTECTION
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Li, Hao; Kraus, M.; Wang, Shu; Grayson, T.; Sun, C.; Salazar, M.; Chen, Y.; Learn, G.; Bibollet-Ruche, Frederic; Hahn, Beatrice; Shaw, George] Univ Alabama, Birmingham, AL USA.
[Gautam, Rajeev; Gaufin, Thaidra; Pandrea, Ivona; Apetrei, Cristian] Univ Pittsburgh, Pittsburgh, PA USA.
[Piatak, Michael; Estes, Jacob; Keele, Brandon; Lifson, Jeffrey] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 92
BP 277
EP 278
PG 2
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700099
ER
PT J
AU Minang, JT
Trivett, MT
Coren, LV
Piatak, M
Ohlen, C
Ott, DE
AF Minang, Jacob T.
Trivett, Matthew T.
Coren, Lori V.
Piatak, Michael, Jr.
Ohlen, Claes
Ott, David E.
TI NEF-INDEPENDENT REPLICATION OF SIVMAC239 IN PRIMARY RHESUS MACAQUE CD4+T
CELLS
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Minang, Jacob T.; Trivett, Matthew T.; Coren, Lori V.; Piatak, Michael, Jr.; Ohlen, Claes; Ott, David E.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 90
BP 277
EP 277
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700097
ER
PT J
AU Leone, A
Rohankhedkhar, M
Okoye, A
Legasse, A
Axthelm, MK
Villinger, F
Piatak, M
Lifson, JD
Assouline, B
Morre, M
Picker, LJ
Sodora, DL
AF Leone, Amanda
Rohankhedkhar, Mukta
Okoye, Afam
Legasse, Alfred
Axthelm, Michael K.
Villinger, Francois
Piatak, Michael, Jr.
Lifson, Jeffrey D.
Assouline, Brigitte
Morre, Michel
Picker, Louis J.
Sodora, Donald L.
TI INCREASED CD4+T CELL LEVELS DURING IL-7 ADMINISTRATION OF ART TREATED
SIV plus MACAQUES ARE NOT DEPENDENT ON STRONG PROLIFERATIVE RESPONSES
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Leone, Amanda; Sodora, Donald L.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Rohankhedkhar, Mukta; Okoye, Afam; Legasse, Alfred; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
[Villinger, Francois] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA.
[Villinger, Francois] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
[Assouline, Brigitte; Morre, Michel] Cytheris SA, F-92130 Issy Les Moulineaux, France.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 101
BP 280
EP 280
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700108
ER
PT J
AU Soulas, C
Autissier, PJ
Piatak, M
Lifson, JD
Williams, KC
AF Soulas, Caroline
Autissier, Patrick J.
Piatak, Michael, Jr.
Lifson, Jeffrey D.
Williams, Kenneth C.
TI DIFFERENT MODULATION AND SUSCEPTIBILITY TO INFECTION OF DENDRITIC CELLS:
LONGITUDINAL ANALYSIS OF SIV-INFECTED CD8-DEPLETED RHESUS MACAQUES
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Soulas, Caroline; Autissier, Patrick J.; Williams, Kenneth C.] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA.
[Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 107
BP 282
EP 282
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700114
ER
PT J
AU Whitney, JB
Hraber, P
Luedemann, C
Bhattacharya, T
Rao, SS
Mascola, JR
Korber, B
Nabel, GJ
Letvin, NL
AF Whitney, James B.
Hraber, Peter
Luedemann, Corinne
Bhattacharya, Tanmoy
Rao, Srinivas S.
Mascola, John R.
Korber, Bette
Nabel, Gary J.
Letvin, Norman L.
TI GENITAL TRACT SEQUESTRATION OF SIV DURING ACUTE INFECTION
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [Whitney, James B.; Luedemann, Corinne; Letvin, Norman L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis,Dept Med, Boston, MA 02215 USA.
[Hraber, Peter; Bhattacharya, Tanmoy; Korber, Bette] Los Alamos Natl Lab, Los Alamos, NM USA.
[Rao, Srinivas S.; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RI Bhattacharya, Tanmoy/J-8956-2013
OI Bhattacharya, Tanmoy/0000-0002-1060-652X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 110
BP 283
EP 283
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700117
ER
PT J
AU O'Neill, RR
Harding, JD
Watson, HL
von Kollmar, DE
Grieder, FB
AF O'Neill, Raymond R.
Harding, John D.
Watson, Harold L.
von Kollmar, Desiree E.
Grieder, Franziska B.
TI NCRR-SUPPORTED RESOURCES AND FUNDING OPPORTUNITIES FOR AIDS RESEARCH
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Meeting Abstract
C1 [O'Neill, Raymond R.; Harding, John D.; Watson, Harold L.; von Kollmar, Desiree E.; Grieder, Franziska B.] NIH, DCM, NCRR, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD AUG
PY 2011
VL 40
IS 4
MA 113
BP 284
EP 284
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 795YL
UT WOS:000293015700120
ER
PT J
AU Shea, MK
O'Donnell, CJ
Vermeer, C
Magdeleyns, EJP
Crosier, MD
Gundberg, CM
Ordovas, JM
Kritchevsky, SB
Booth, SL
AF Shea, M. Kyla
O'Donnell, Christopher J.
Vermeer, Cees
Magdeleyns, Elke J. P.
Crosier, Michael D.
Gundberg, Caren M.
Ordovas, Jose M.
Kritchevsky, Stephen B.
Booth, Sarah L.
TI Circulating Uncarboxylated Matrix Gla Protein Is Associated with Vitamin
K Nutritional Status, but Not Coronary Artery Calcium, in Older Adults
SO JOURNAL OF NUTRITION
LA English
DT Article
ID HEART-DISEASE EVENTS; VASCULAR CALCIFICATION; RISK-FACTORS; BIOCHEMICAL
MEASURES; COMPUTED-TOMOGRAPHY; MEN; WOMEN; ATHEROSCLEROSIS;
SUPPLEMENTATION; CARBOXYLASE
AB Matrix Gla protein (MGP) is a calcification inhibitor in vascular tissue that must be carboxylated by vitamin K to function. Evidence suggests circulating uncarboxylated MGP (ucMGP) is elevated in persons with disease characterized by vascular calcification. The primary purpose of this study was to determine cross-sectional and longitudinal associations between plasma ucMGP, vitamin K status, and coronary artery calcium (CAC) in older adults without coronary heart disease. Genetic determinants of ucMGP were also explored. Cross-sectional associations among baseline plasma ucMGP, vitamin K status biomarkers [plasma phylloquinone, uncarboxylated prothrombin (PIVKA-II), serum uncarboxylated osteocalcin (%ucOC)], CAC, and plausible genetic polymorphisms were examined in 438 community-dwelling adults (60-80 y, 59% women). The effect of phylloquinone supplementation (500 mu g/d) for 3 y on plasma ucMGP was determined among 374 participants. At baseline, plasma phylloquinone was lower and %ucOC and PIVKA-II were greater across higher plasma ucMGP quartiles (all P < 0.001, age-adjusted). Major allele homozygotes for MGP rs1800801 and rs4236 had higher plasma ucMGP than heterozygotes or minor allele homozygotes. (P <= 0.004). The decrease in plasma ucMGP was greater in the 190 participants who received phylloquinone (mean +/- SD) (-345 +/- 251 pmol/L) than in the 184 who did not (-40 +/- 196 pmol/L) (P < 0.0001). CAC did not differ according to ucMGP quartile (P = 0.35, age-adjusted). In the phylloquinone-supplemented group, the 3-y change in ucMGP was not associated with the 3-y change in CAC [unstandard beta (SE) = -0.02 (0.02); P = 0.44]. Plasma ucMGP was associated with vitamin K status biomarkers and was reduced following phylloquinone supplementation, suggesting it may be a useful marker of vitamin K status in vascular tissue. Plasma ucMGP did not reflect CAC in healthy older adults. J. Nutr. 141: 1529-1534, 2011.
C1 [Ordovas, Jose M.; Booth, Sarah L.] Tufts Univ, USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Shea, M. Kyla; Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC 27157 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA.
[Vermeer, Cees; Magdeleyns, Elke J. P.] Maastricht Univ, NL-6200 Maastricht, Netherlands.
[Crosier, Michael D.] Framingham State Univ, Framingham, MA 01702 USA.
[Gundberg, Caren M.] Yale Univ, Sch Med, New Haven, CT 06511 USA.
[Ordovas, Jose M.] Ctr Nacl Invest Cardiovasc, Madrid 28029, Spain.
RP Booth, SL (reprint author), Tufts Univ, USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
EM sarah.booth@tufts.edu
OI Vermeer, Cees/0000-0002-2300-8561; Kritchevsky,
Stephen/0000-0003-3336-6781
FU USDA, Agricultural Research Service under Cooperative Agreement
[58-1950-7-707]; NIH [AG14759, AG23914, HL69272, T32HL69772,
P30AG021332-08]; AHA [09CRP2070013, 0515605T]
FX Supported by the USDA, Agricultural Research Service under Cooperative
Agreement No. 58-1950-7-707, the NIH (AG14759, AG23914, HL69272,
T32HL69772, and P30AG021332-08), and the AHA (09CRP2070013 and
0515605T). Any opinions, findings, conclusions, or recommendations
expressed in this publication are those of the authors and do not
necessarily reflect the view of the USDA.
NR 32
TC 39
Z9 39
U1 0
U2 3
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD AUG
PY 2011
VL 141
IS 8
BP 1529
EP 1534
DI 10.3945/jn.111.139634
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 796KE
UT WOS:000293049400018
PM 21628633
ER
PT J
AU Lin, YH
Shah, S
Salem, N
AF Lin, Yu Hong
Shah, Samit
Salem, Norman, Jr.
TI Altered essential fatty acid metabolism and composition in rat liver,
plasma, heart and brain after microalgal DHA addition to the diet
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Alpha-linolenic acid; Linoleic acid; Docosahexaenoic acid;
Docosapentaenoic acid; Essential fatty acid; Stable isotope; GC/MS;
Metabolism
ID ALPHA-LINOLENIC-ACID; DOCOSAHEXAENOIC ACID; EICOSAPENTAENOIC ACID;
ARACHIDONIC-ACID; TERM INFANTS; DOCOSAPENTAENOIC ACID; SUPPLEMENTATION;
CONVERSION; N-3; EXPRESSION
AB To investigate the effect of docosahexaenoic acid (DHA) without other highly unsaturated fatty acids (HUFA) on n-3 and n-6 essential fatty acid (EFA) metabolism and fatty acid composition in mammals, a stable isotope tracer technique was used in adult rats fed diets with or without 1.3% of algal DHA in a base diet containing 15% of linoleic acid and 3% of alpha-linolenic acid over 8 weeks. The rats were administered orally a mixed oil containing 48 mg/kg body weight of deuterated linoleic and alpha-linolenic acids and euthanized at 4, 8, 24, 96, 168, 240, 360 and 600 h after administration of the isotopes. Fatty acid compositions and the concentrations of deuterated precursors and their respective metabolites were determined in rat liver, plasma, heart and brain as a function of time. DHA, docosapentaenoic acid and eicosapentaenoic acid in the n-3 EFA family were significantly increased in all organs tested in the DHA-fed group, ranging from 5% to 200% greater in comparison with the control group. The accumulation of the metabolites, deuterated-DHA and deuterated-docosapentaenoic acid n-6 was greatly decreased by 1.5- to 2.5-fold in the dietary DHA group. In summary, feeding preformed DHA led to a marked increase in n-3 HUFA content of rat organs at the expense of n-6 HUFA and also prevented the accumulation of newly synthesized deuterated end products. This is the first study which has isolated the effects of DHA on the de novo metabolism on both the n-6 and n-3 EFA pathways. Published by Elsevier Inc.
C1 [Lin, Yu Hong; Shah, Samit; Salem, Norman, Jr.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
RP Salem, N (reprint author), Martek Biosci Corp, 6480 Dobbin Rd, Columbia, MD 21045 USA.
EM nsalem@martek.com
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health
FX This project was funded by the Intramural Research Program of the
National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health.
NR 44
TC 11
Z9 12
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD AUG
PY 2011
VL 22
IS 8
BP 758
EP 765
DI 10.1016/j.jnutbio.2010.06.008
PG 8
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 799CE
UT WOS:000293260300007
PM 21111595
ER
PT J
AU Heinonen, M
Hemmes, A
Salmenkivi, K
Abdelmohsen, K
Vilen, ST
Laakso, M
Leidenius, M
Salo, T
Hautaniemi, S
Gorospe, M
Heikkila, P
Haglund, C
Ristimaki, A
AF Heinonen, Mira
Hemmes, Annabrita
Salmenkivi, Kaisa
Abdelmohsen, Kotb
Vilen, Suvi-Tuuli
Laakso, Marko
Leidenius, Marjut
Salo, Tuula
Hautaniemi, Sampsa
Gorospe, Myriam
Heikkila, Paivi
Haglund, Caj
Ristimaki, Ari
TI Role of RNA binding protein HuR in ductal carcinoma in situ of the
breast
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE HuR; Drosophila embryonic lethal abnormal vision protein; breast cancer;
atypical ductal hyperplasia; ductal carcinoma in situ; carcinogenesis;
pre-malignant
ID INCREASED CYCLOOXYGENASE-2 EXPRESSION; POSTTRANSCRIPTIONAL
GENE-REGULATION; INDEPENDENT PROGNOSTIC-FACTOR; ELAV-LIKE PROTEIN;
MESSENGER-RNA; CANCER CELLS; OVARIAN-CARCINOMA; EPITHELIAL-CELLS;
STABILITY; OVEREXPRESSION
AB HuR is a ubiquitously expressed RNA-binding protein that modulates gene expression at the post-transcriptional level. It is predominantly nuclear, but can shuttle between the nucleus and the cytoplasm. While in the cytoplasm HuR can stabilize its target transcripts, many of which encode proteins involved in carcinogenesis. While cytoplasmic HuR expression is a marker of reduced survival in breast cancer, its role in precursor lesions of malignant diseases is unclear. To address this we explored HuR expression in atypical ductal hyperplasia (ADH) and in ductal in situ carcinomas (DCIS). We show that cytoplasmic HuR expression is elevated in both ADH and DCIS when compared to normal controls, and that this expression associated with high grade, progesterone receptor negativity and microinvasion and/or tumour-positive sentinel nodes of the DCIS. To study the mechanisms of HuR in breast carcinogenesis, HuR expression was silenced in an immortalized breast epithelial cell line (184B5Me), which led to reduction in anchorage-independent growth, increased programmed cell death and inhibition of invasion. In addition, we identified two novel target transcripts (CTGF and RAB31) that are regulated by HuR and that bind HuR protein in this cell line. Our results show that HuR is aberrantly expressed at early stages of breast carcinogenesis and that its inhibition can lead to suppression of this process. ArrayExpress Accession No. E-MEXP-3035. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
C1 [Heinonen, Mira; Hemmes, Annabrita; Laakso, Marko; Hautaniemi, Sampsa; Ristimaki, Ari] Univ Helsinki, Res Program Unit, FIN-00014 Helsinki, Finland.
[Heinonen, Mira; Hemmes, Annabrita; Salmenkivi, Kaisa; Heikkila, Paivi; Haglund, Caj; Ristimaki, Ari] Univ Helsinki, Cent Hosp, HUSLAB, Dept Pathol, FIN-00014 Helsinki, Finland.
[Heinonen, Mira; Hemmes, Annabrita; Salmenkivi, Kaisa; Heikkila, Paivi; Haglund, Caj; Ristimaki, Ari] Univ Helsinki, Cent Hosp, Haartman Inst, FIN-00014 Helsinki, Finland.
[Abdelmohsen, Kotb; Gorospe, Myriam] NIA, LMBI, IRP, NIH, Baltimore, MD 21224 USA.
[Vilen, Suvi-Tuuli] Univ Helsinki, Inst Dent, Biomedicum Helsinki, FIN-00014 Helsinki, Finland.
[Laakso, Marko; Hautaniemi, Sampsa] Univ Helsinki, Computat Syst Lab, Biomedicum Helsinki, FIN-00014 Helsinki, Finland.
[Laakso, Marko; Hautaniemi, Sampsa] Univ Helsinki, Inst Biomed, Biomedicum Helsinki, FIN-00014 Helsinki, Finland.
[Leidenius, Marjut] Univ Helsinki, Cent Hosp, Breast Surg Unit, FIN-00014 Helsinki, Finland.
[Salo, Tuula] Univ Oulu, Dept Diagnost & Oral, Oulu, Finland.
[Haglund, Caj] Univ Helsinki, Cent Hosp, Dept Surg, FIN-00014 Helsinki, Finland.
RP Ristimaki, A (reprint author), Univ Helsinki, Res Program Unit, Room B529B,POB 63,Haartmaninkatu 8, FIN-00014 Helsinki, Finland.
EM ari.ristimaki@helsinki.fi
RI Hautaniemi, Sampsa/A-3122-2009;
OI Hautaniemi, Sampsa/0000-0002-7749-2694; abdelmohsen,
Kotb/0000-0001-6240-5810
FU Helsinki University; Sigrid Juselius Foundation; Finnish Cancer
Organization; Finnish Cultural Foundation; Paulo Foundation; NIA-IRP of
the National Institutes of Health, USA
FX We thank Paivi Peltokangas and Tuire Koski for excellent technical
assistance, Johanna Partanen and Juha Klefstrom for help with the virus
constructs, and Siina Junnila and Outi Monni for help with the
Affymetrix array analysis. MH is a student in the Biomedical Helsinki
Graduate School and ML in the Finnish Doctoral Programme in
Computational Sciences. The authors are grateful for funding from
Helsinki University Central Hospital Research Funds (to AR and CH), the
Sigrid Juselius Foundation (to AR and CH), the Finnish Cancer
Organization (to AR), the Finnish Cultural Foundation (to MH), the Paulo
Foundation (to MH) and NIA-IRP of the National Institutes of Health, USA
(to KA and MG).
NR 45
TC 22
Z9 22
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3417
J9 J PATHOL
JI J. Pathol.
PD AUG
PY 2011
VL 224
IS 4
BP 529
EP 539
DI 10.1002/path.2889
PG 11
WC Oncology; Pathology
SC Oncology; Pathology
GA 799HE
UT WOS:000293276600011
PM 21480233
ER
PT J
AU Hashkes, PJ
Wright, BM
Lauer, MS
Worley, SE
Tang, AS
Roettcher, PA
Bowyer, SL
AF Hashkes, Philip J.
Wright, Bridget M.
Lauer, Michael S.
Worley, Sarah E.
Tang, Anne S.
Roettcher, Philip A.
Bowyer, Suzanne L.
TI Survival Rates of Children With Acute Lymphoblastic Leukemia Presenting
to a Pediatric Rheumatologist in the United States
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Article
DE outcome; mortality; survival; pediatric rheumatology; children; acute
lymphoblastic leukemia
ID CHILDHOOD-CANCER SURVIVOR; PROGNOSTIC-SIGNIFICANCE; BONE INVOLVEMENT;
ARTHRITIS; MANIFESTATIONS; ASSOCIATION; PAIN; MALIGNANCIES; MORTALITY;
DIAGNOSIS
AB Background: Approximately 30% of pediatric acute lymphoblastic leukemia patients present with musculoskeletal symptoms and are often referred first to a pediatric rheumatologist. We examined the survival and causes of death of these patients presenting to a pediatric rheumatologist and compared the rates with that reported in the hematology-oncology literature.
Procedure: We used the Pediatric Rheumatology Disease Registry, including 49,023 patients from 62 centers, newly diagnosed between 1992 and 2001. Identifiers were matched with the Social Security Death Index censored for March 2005. Deaths were confirmed by death certificates, referring physicians, and medical records. Causes of death were derived by chart review or from the death certificate.
Results: There were 7 deaths of 89 patients (7.9%, 95% confidence interval: 3.9%-15.4%) with acute lymphoblastic leukemia with a 5-year survival rate of 95.5% (88.3 to 98.3) and 10-year survival rate of 89.8% (79.0% to 95.2%). The causes of death were sepsis (bacterial and/or fungal) in 4 (57%) patients, the disease in 2 (29%) and post bone-marrow transplantation in 1 (14%).
Conclusion: The overall survival of patients with acute lymphoblastic leukemia seen first by pediatric rheumatologists is higher than the range reported in the pediatric oncology literature for the same period of diagnosis.
C1 [Hashkes, Philip J.] Shaare Zedek Med Ctr, Unit Pediat Rheumatol, IL-91031 Jerusalem, Israel.
[Hashkes, Philip J.] Cleveland Clin, Sect Pediat Rheumatol, Cleveland, OH 44106 USA.
[Wright, Bridget M.] Childrens Hosp MCCG, Macon, GA USA.
[Lauer, Michael S.] NHLBI, Bethesda, MD 20892 USA.
[Worley, Sarah E.; Tang, Anne S.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH USA.
[Roettcher, Philip A.] Indiana Univ, Bloomington, IN 47405 USA.
[Bowyer, Suzanne L.] James W Riley Hosp, Sect Pediat Rheumatol, Indianapolis, IN USA.
RP Hashkes, PJ (reprint author), Shaare Zedek Med Ctr, Unit Pediat Rheumatol, POB 3235, IL-91031 Jerusalem, Israel.
EM hashkesp@szmc.org.il
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
FU Northeast Ohio Chapter of the Arthritis Foundation
FX This study was funded by a grant from the Northeast Ohio Chapter of the
Arthritis Foundation.
NR 39
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1077-4114
EI 1536-3678
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD AUG
PY 2011
VL 33
IS 6
BP 424
EP 428
DI 10.1097/MPH.0b013e31820998c4
PG 5
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 798AB
UT WOS:000293171000017
PM 21572344
ER
PT J
AU Zhang, Y
Li, SZ
Marenco, S
Shen, J
AF Zhang, Yan
Li, Shizhe
Marenco, Stefano
Shen, Jun
TI Quantitative Measurement of N-Acetyl-aspartyl-glutamate at 3 T Using
TE-Averaged PRESS Spectroscopy and Regularized Lineshape Deconvolution
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE N-acetyl-aspartate; N-acetyl-aspartyl-glutamate; short echo time PRESS;
TE-averaged PRESS; deconvolution; regularization
ID MAGNETIC-RESONANCE-SPECTROSCOPY; HUMAN BRAIN; EDDY CURRENTS;
NMR-SPECTRA; QUANTIFICATION; ACETYLASPARTYLGLUTAMATE; SCLEROSIS; QUALITY
AB This article introduces regularized lineshape deconvolution in conjunction with TE-averaged PRESS spectroscopy to measure N-acetyl-aspartyl-glutamate (NAAG). Averaging different echo times suppressed the signals of multiplets from strongly coupled spin systems near 2 ppm; thus, minimizing the interfering signals to detect the acetyl proton signal of NAAG. Signal distortion was corrected by lineshape deconvolution, and Tikhonov regularization was introduced to reduce noise amplification arising from deconvolution; as a result, spectral resolution was enhanced without significantly sacrificing signal-to-noise ratio (SNR). This new approach was used to measure NAAG in the two regions of interest of healthy volunteers, dominated by gray matter and white matter, respectively. The acetyl proton signal of NAAG was directly quantified by fitting the deconvoluted spectra to a Voigt-lineshape spectral model function, yielding the NAAG-N-acetyl-aspartate (NAA) ratios of 0.11 +/- 0.02 for the gray matter voxels (n = 8) and 0.18 +/- 0.02 for the white matter voxels (n = 12). Magn Reson Med 66:307-313,2011. (C) 2011 Wiley-Liss, Inc.
C1 [Shen, Jun] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Zhang, Yan; Li, Shizhe; Shen, Jun] NIMH, MR Spect Core Facil, NIH, Bethesda, MD 20892 USA.
[Marenco, Stefano] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
RP Shen, J (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shenj@mail.nih.gov
RI Marenco, Stefano/A-2409-2008
OI Marenco, Stefano/0000-0002-2488-2365
FU NIH, NIMH
FX The authors are grateful to Ms. Christine Rebsch for her help in data
acquisition, and Ms. Ioline Henter, National Institute of Mental Health,
for her excellent editorial assistance. This work was supported by the
intramural research program, the NIH, NIMH.
NR 30
TC 14
Z9 14
U1 1
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD AUG
PY 2011
VL 66
IS 2
BP 307
EP 313
DI 10.1002/mrm.23029
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 799AV
UT WOS:000293256800001
PM 21656565
ER
PT J
AU Souto, G
Donapetry, C
Calvino, J
Adeva, MM
AF Souto, Gema
Donapetry, Cristobal
Calvino, Jesus
Adeva, Maria M.
TI Metabolic Acidosis-Induced Insulin Resistance and Cardiovascular Risk
SO METABOLIC SYNDROME AND RELATED DISORDERS
LA English
DT Review
ID DEPENDENT DIABETES-MELLITUS; URINARY ALBUMIN EXCRETION;
CORONARY-HEART-DISEASE; NUTRITION EXAMINATION SURVEY;
GLOMERULAR-FILTRATION-RATE; RANDOMIZED CLINICAL-TRIAL; SERUM ANION GAP;
NONDIABETIC SUBJECTS; RENAL-FUNCTION; MICROALBUMINURIA PREDICTS
AB Microalbuminuria has been conclusively established as an independent cardiovascular risk factor, and there is evidence of an association between insulin resistance and microalbuminuria, the former preceding the latter in prospective studies. It has been demonstrated that even the slightest degree of metabolic acidosis produces insulin resistance in healthy humans. Many recent epidemiological studies link metabolic acidosis indicators with insulin resistance and systemic hypertension. The strongly acidogenic diet consumed in developed countries produces a lifetime acidotic state, exacerbated by excess body weight and aging, which may result in insulin resistance, metabolic syndrome, and type 2 diabetes, contributing to cardiovascular risk, along with genetic causes, lack of physical exercise, and other factors. Elevated fruits and vegetables consumption has been associated with lower diabetes incidence. Diseases featuring severe atheromatosis and elevated cardiovascular risk, such as diabetes mellitus and chronic kidney failure, are typically characterized by a chronic state of metabolic acidosis. Diabetic patients consume particularly acidogenic diets, and deficiency of insulin action generates ketone bodies, creating a baseline state of metabolic acidosisworsened by inadequate metabolic control, which creates a vicious circle by inducing insulin resistance. Even very slight levels of chronic kidney insufficiency are associated with increased cardiovascular risk, which may be explained at least in part by deficient acid excretory capacity of the kidney and consequent metabolic acidosis-induced insulin resistance.
C1 [Souto, Gema] NIH, Ctr Clin, Washington, DC USA.
[Donapetry, Cristobal; Calvino, Jesus; Adeva, Maria M.] Hosp Gen Juan Cardona, La Coruna, Spain.
RP Adeva, MM (reprint author), Ave Che Guevara,31 Portal B-3 A, La Coruna 15172, Spain.
EM madevaa@yahoo.com
NR 74
TC 31
Z9 31
U1 3
U2 9
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-4196
J9 METAB SYNDR RELAT D
JI Metab. Syndr. Relat. Disord.
PD AUG
PY 2011
VL 9
IS 4
BP 247
EP 253
DI 10.1089/met.2010.0108
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 798OM
UT WOS:000293219200002
PM 21352078
ER
PT J
AU Shively, SB
Falke, EA
Li, J
Tran, MGB
Thompson, ER
Maxwell, PH
Roessler, E
Oldfield, EH
Lonser, RR
Vortmeyer, AO
AF Shively, Sharon B.
Falke, Eric A.
Li, Jie
Tran, Maxine G. B.
Thompson, Eli R.
Maxwell, Patrick H.
Roessler, Erich
Oldfield, Edward H.
Lonser, Russell R.
Vortmeyer, Alexander O.
TI Developmentally arrested structures preceding cerebellar tumors in von
Hippel-Lindau disease
SO MODERN PATHOLOGY
LA English
DT Article
DE hemangioblastoma; tumor precursors; von Hippel-Lindau disease
ID CENTRAL-NERVOUS-SYSTEM; STEM-CELL FUNCTION; EMBRYONIC-DEVELOPMENT;
SUPPRESSOR PROTEIN; VHL DEFICIENCY; HYPOXIA; GENE; HEMANGIOBLASTOMAS;
OXYGEN; HIF
AB There is increasing evidence that suggests that knockout of tumor-suppressor gene function causes developmental arrest and protraction of cellular differentiation. In the peripheral nervous system of patients with the tumor-suppressor gene disorder, von Hippel-Lindau disease, we have demonstrated developmentally arrested structural elements composed of hemangioblast progenitor cells. Some developmentally arrested structural elements progress to a frank tumor, hemangioblastoma. However, in von Hippel-Lindau disease, hemangioblastomas are frequently observed in the cerebellum, suggesting an origin in the central nervous system. We performed a structural and topographic analysis of cerebellar tissues obtained from von Hippel-Lindau disease patients to identify and characterize developmentally arrested structural elements in the central nervous system. We examined the entire cerebella of five tumor-free von Hippel-Lindau disease patients and of three non-von Hippel-Lindau disease controls. In all, 9 cerebellar developmentally arrested structural elements were detected and topographically mapped in 385 blocks of von Hippel-Lindau disease cerebella. No developmentally arrested structural elements were seen in 214 blocks from control cerebella. Developmentally arrested structural elements are composed of poorly differentiated cells that express hypoxia-inducible factor (HIF)2 alpha, but not HIF1 alpha or brachyury, and preferentially involve the molecular layer of the dorsum cerebelli. For the first time, we identify and characterize developmentally arrested structural elements in the central nervous system of von Hippel-Lindau patients. We provide evidence that developmentally arrested structural elements in the cerebellum are composed of developmentally arrested hemangioblast progenitor cells in the molecular layer of the dorsum cerebelli. Modern Pathology (2011) 24, 1023-1030; doi: 10.1038/modpathol.2011.61; published online 15 April 2011
C1 [Falke, Eric A.; Li, Jie; Vortmeyer, Alexander O.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
[Shively, Sharon B.; Thompson, Eli R.; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Shively, Sharon B.] George Washington Univ, Dept Mol Med, Inst Biomed Sci, Washington, DC USA.
[Tran, Maxine G. B.] Cambridge Res Inst, CRUK Urooncol Res Grp, Li Ka Shing Ctr, Cambridge, England.
[Maxwell, Patrick H.] UCL, Div Med, London, England.
[Roessler, Erich] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Oldfield, Edward H.] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA.
RP Vortmeyer, AO (reprint author), Yale Univ, Sch Med, Dept Pathol, 416A Lauder Hall,310 Cedar St, New Haven, CT 06520 USA.
EM alexander.vortmeyer@yale.edu
RI Maxwell, Patrick/C-5557-2008
OI Maxwell, Patrick/0000-0002-0338-2679
FU NIH; Yale University
FX This research was supported by the Intramural Research Program of the
NIH and Yale University. Sharon B. Shively is a doctoral student in the
Molecular and Cellular Oncology Program of the Institute for Biomedical
Sciences at the George Washington University and the Graduate
Partnerships Program at the NIH. This work is from a dissertation to be
presented to the George Washington University in partial fulfillment of
the requirements for the PhD degree. The human tissue was obtained from
the NICHD Brain and Tissue Bank for Developmental Disorders at the
University of Maryland, Baltimore, MD. The role of the NICHD Brain and
Tissue Bank is to distribute tissue, and, therefore, cannot endorse the
studies performed or the interpretation of results. We thank Robert
Vigorito and Robert Johnson for their invaluable tissue procurement at
the University of Maryland. We are grateful to Willie Young, Jim Rainey,
and Dr David Kleiner at Autopsy Service, Laboratory of Pathology, NCI;
to Silke Williams for tissue samples; and to Ethan Tyler for the medical
illustration.
NR 51
TC 10
Z9 10
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD AUG
PY 2011
VL 24
IS 8
BP 1023
EP 1030
DI 10.1038/modpathol.2011.61
PG 8
WC Pathology
SC Pathology
GA 799ZM
UT WOS:000293326000001
PM 21499240
ER
PT J
AU Kang, JH
Tsai-Morris, CH
Dufau, ML
AF Kang, Jung-Hoon
Tsai-Morris, Chon-Hwa
Dufau, Maria L.
TI Complex Formation and Interactions between Transcription Factors
Essential for Human Prolactin Receptor Gene Transcription
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTIONS; RESONANCE ENERGY-TRANSFER; BREAST-CANCER
CELLS; ESTROGEN-RECEPTOR; PROMOTER UTILIZATION; ALTERNATIVE EXONS-1;
INHIBITORY-ACTION; SHORT FORMS; C/EBP-BETA; FACTOR SP1
AB The protein association of estrogen receptor alpha ER alpha with DNA-bound SP1 and C/EBP beta is essential for the 17 beta-estradiol (E2)-induced activation of human prolactin receptor (hPRLR) gene transcription. Protein-protein interaction and complex formation at the hPIII promoter of hPRLR was investigated. The basic region and leucine zipper (bZIP) of C/EBP beta, zinc finger (ZF) motifs of SP1, and the DNA binding domain of ER alpha were identified as regions responsible for the interactions between transfactors. The E2-induced interaction was confirmed by bioluminescence resonance energy transfer (BRET) assays of live cells. The combination of BRET/bimolecular luminescence complementation assay revealed that ER alpha exists as a constitutive homodimer, and E2 induced a change(s) in ER alpha homodimer conformation favorable for its association with C/EBP beta and SP1. Chromatin immunoprecipitation and small interfering RNA knockdown of members of the complex in breast cancer cells demonstrated the endogenous recruitment of components of the complex onto the hPIII promoter of the hPRLR gene. SP1 is the preferred transfactor for the recruitment of ER alpha to the complex that facilitates the C/EBP beta association. The E2/ER alpha-induced hPRLR transcription was demonstrated in ER alpha-negative breast cancer cells. This study indicates that the enhanced complex formation of ER alpha dimer with SP1 and C/EBP beta by E2 has an essential role in the transcriptional activation of the hPRLR gene.
C1 [Kang, Jung-Hoon; Tsai-Morris, Chon-Hwa; Dufau, Maria L.] Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Dufau, ML (reprint author), Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bldg 49,Rm 6A-36, Bethesda, MD 20892 USA.
EM dufaum@mail.nih.gov
FU NICHD, National Institutes of Health
FX This work was supported by the Intramural Research program of the NICHD,
National Institutes of Health.
NR 29
TC 7
Z9 7
U1 0
U2 2
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 AUG
PY 2011
VL 31
IS 16
BP 3208
EP 3222
DI 10.1128/MCB.05337-11
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 797ZU
UT WOS:000293170200002
PM 21670145
ER
PT J
AU Huang, L
Fu, HQ
Lin, CM
Conner, AL
Zhang, Y
Aladjem, MI
AF Huang, Liang
Fu, Haiqing
Lin, Chii Mei
Conner, Amy L.
Zhang, Ya
Aladjem, Mirit I.
TI Prevention of Transcriptional Silencing by a Replicator-Binding Complex
Consisting of SWI/SNF, MeCP1, and hnRNP C1/C2
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID BETA-GLOBIN LOCUS; PRIMARY ERYTHROID-CELLS; CONTROL REGION;
CHROMATIN-STRUCTURE; DNA-REPLICATION; HISTONE MODIFICATION; REPRESSES
TRANSCRIPTION; ACTIVATION REGION; INITIATION SITES; MAMMALIAN-CELLS
AB Transcriptional silencing selectively impedes gene expression. Silencing is often accompanied by replication delay and can be prevented by replicator sequences. Here we report a replicator-binding protein complex involved in the prevention of transcriptional silencing. The protein complex interacts with an essential asymmetric region within the human beta-globin Rep-P replicator and includes hnRNP C1/C2, SWI/SNF complex, and MeCP1, which are members of the locus control region (LCR)-associated remodeling complex (LARC). Interaction between LARC and Rep-P prevented transcriptional silencing and replication delay. Transgenes that did not contain the asymmetric LARC-binding region of Rep-P replicated late and exhibited stable silencing that could not be affected by a DNA methylation inhibitor. In contrast, transgenes that contain a mutation of the asymmetric region of Rep-P that could not bind LARC exhibited a silent state that could transiently be reactivated by DNA demethylation. The effect of DNA demethylation was transient, and prolonged exposure to a methylation inhibitor induced distinct, stable, methylation-independent silencing. These observations suggest that the interaction of LARC complex with replicators plays a role in preventing gene silencing and provides support for a novel, epigenetic mechanism of resistance to methylation inhibitors.
C1 [Huang, Liang; Fu, Haiqing; Lin, Chii Mei; Conner, Amy L.; Zhang, Ya; Aladjem, Mirit I.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Aladjem, MI (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 5056,37 Convent Dr, Bethesda, MD 20892 USA.
EM aladjemm@mail.nih.gov
RI Huang, Liang/B-2831-2013; Aladjem, Mirit/G-2169-2010
OI Huang, Liang/0000-0003-1663-7025; Aladjem, Mirit/0000-0002-1875-3110
FU Center for Cancer Research, NCI, NIH
FX This study was supported by the Intramural Research Program of the
Center for Cancer Research, NCI, NIH.
NR 57
TC 12
Z9 12
U1 0
U2 1
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 AUG
PY 2011
VL 31
IS 16
BP 3472
EP 3484
DI 10.1128/MCB.05587-11
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 797ZU
UT WOS:000293170200022
PM 21690294
ER
PT J
AU Zatz, M
AF Zatz, Marion
TI A view from the NIH bridge: perspectives of a program officer
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
AB This essay is written from my perspective as a program officer for research and training activities at the National Institute of General Medical Sciences (NIGMS) for almost 27 yr. It gives a bird's-eye view of the job of a program officer, which includes providing advice to applicants and grantees, making funding recommendations, overseeing grantees' progress, facilitating scientific opportunities in specific areas of program responsibility, and shaping NIGMS and National Institutes of Health (NIH) policy. I have highlighted the numerous rewards of serving as a program officer, as well as some of the difficulties. For those who may be considering a position as an NIH program officer now or in the future, I've also described the qualities and qualifications that are important for such a career choice. Finally, this essay addresses some of the challenges for the NIH and the research community in the years ahead as we simultaneously face exciting scientific opportunities and tighter budgets.
C1 Natl Inst Gen Med Sci, NIH, Bethesda, MD 20892 USA.
RP Zatz, M (reprint author), Natl Inst Gen Med Sci, NIH, Bethesda, MD 20892 USA.
EM zatzm@nigms.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
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 AUG 1
PY 2011
VL 22
IS 15
BP 2661
EP 2663
DI 10.1091/mbc.E11-04-0346
PG 3
WC Cell Biology
SC Cell Biology
GA 798QT
UT WOS:000293227200001
PM 21799136
ER
PT J
AU Justice, NJ
Blount, AL
Pelosi, E
Schlessinger, D
Vale, W
Bilezikjian, LM
AF Justice, Nicholas J.
Blount, Amy L.
Pelosi, Emanuele
Schlessinger, David
Vale, Wylie
Bilezikjian, Louise M.
TI Impaired FSH beta Expression in the Pituitaries of Foxl2 Mutant Animals
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID FOLLICLE-STIMULATING-HORMONE; HOMEODOMAIN TRANSCRIPTION FACTOR;
GONADOTROPIN-RELEASING-HORMONE; SUBUNIT GENE-EXPRESSION; BONE
MORPHOGENETIC PROTEIN-2; ACTIVIN-A; FORKHEAD TRANSCRIPTION; SMAD
PROTEINS; IN-VIVO; ACTIVATION
AB Forkhead box L2 (FoxL2) is required for ovarian development and differentiation. FoxL2 is also expressed in the pituitary where it has been implicated in the development and regulation of gonadotropes, which secrete LH and FSH, the endocrine signals that regulate folliculogenesis in the ovary and spermatogenesis in the testis. Here, we show that FoxL2 is not required for the specification of gonadotropes; the pituitaries of Foxl2 mutant mice contain normal numbers of gonadotropes that express glycoprotein alpha subunit and LH beta. Whereas the specification of gonadotropes and all other hormonal cell types is normal in the pituitaries of Foxl2 mutant animals, FSH beta levels are severely impaired in both male and female animals, suggesting that FoxL2 is required for normal Fshb expression. The size of the pituitary is reduced in proportion to the smaller body size of Foxl2 mutants, with a concomitant increase in the pituitary cellular density. In primary pituitary cultures, activin induces FSH secretion and Fshb mRNA expression in cells from wild-type mice. In cells from Foxl2 mutant mice, however, FSH secretion is not detected, and activin is unable to drive Fshb expression, suggesting that the mechanism of activin-dependent activation of Fshb transcription is impaired. However, a small number of gonadotropes in the ventromedial region of the pituitaries from Foxl2 mutant mice maintain FSH beta expression, suggesting that a FoxL2- and activin-independent mechanism can drive Fshb transcription. These data indicate that, in addition to its role in the ovary, FoxL2 function in the pituitary is required for normal expression of FSH. (Molecular Endocrinology 25: 1404-1415, 2011)
C1 [Justice, Nicholas J.; Blount, Amy L.; Vale, Wylie; Bilezikjian, Louise M.] Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA.
[Blount, Amy L.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
[Pelosi, Emanuele; Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
RP Bilezikjian, LM (reprint author), Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM Bilezikjian@salk.edu
FU NICHD [2R01HD046941]; NIH, National Institute on Aging; Clayton Medical
Research Foundation, Inc.
FX This work was supported by Grant 2R01HD046941 awarded by the NICHD. This
research was also supported in part by the Intramural Research Program
of the NIH, National Institute on Aging. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NICHD or the NIH. The work was supported in part
by the Clayton Medical Research Foundation, Inc. W.V. is a Clayton
Medical Research Foundation, Inc. Senior Investigator and is the Helen
McLoraine Professor of Molecular Neurobiology.
NR 47
TC 20
Z9 21
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD AUG
PY 2011
VL 25
IS 8
BP 1404
EP 1415
DI 10.1210/me.2011-0093
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 798YD
UT WOS:000293247200012
PM 21700720
ER
PT J
AU Gunay-Aygun, M
Falik-Zaccai, TC
Vilboux, T
Zivony-Elboum, Y
Gumruk, F
Cetin, M
Khayat, M
Boerkoel, CF
Kfir, N
Huang, Y
Maynard, D
Dorward, H
Berger, K
Kleta, R
Anikster, Y
Arat, M
Freiberg, AS
Kehrel, BE
Jurk, K
Cruz, P
Mullikin, JC
White, JG
Huizing, M
Gahl, WA
AF Gunay-Aygun, Meral
Falik-Zaccai, Tzipora C.
Vilboux, Thierry
Zivony-Elboum, Yifat
Gumruk, Fatma
Cetin, Mualla
Khayat, Morad
Boerkoel, Cornelius F.
Kfir, Nehama
Huang, Yan
Maynard, Dawn
Dorward, Heidi
Berger, Katherine
Kleta, Robert
Anikster, Yair
Arat, Mutlu
Freiberg, Andrew S.
Kehrel, Beate E.
Jurk, Kerstin
Cruz, Pedro
Mullikin, Jim C.
White, James G.
Huizing, Marjan
Gahl, William A.
TI NBEAL2 is mutated in gray platelet syndrome and is required for
biogenesis of platelet alpha-granules
SO NATURE GENETICS
LA English
DT Article
ID PROTEINS
AB Gray platelet syndrome (GPS) is an autosomal recessive bleeding disorder that is characterized by large platelets that lack alpha-granules. Here we show that mutations in NBEAL2 (neurobeachin-like 2), which encodes a BEACH/ARM/WD40 domain protein, cause GPS and that megakaryocytes and platelets from individuals with GPS express a unique combination of NBEAL2 transcripts. Proteomic analysis of sucrose-gradient subcellular fractions of platelets indicated that NBEAL2 localizes to the dense tubular system (endoplasmic reticulum) in platelets.
C1 [Gunay-Aygun, Meral; Vilboux, Thierry; Boerkoel, Cornelius F.; Huang, Yan; Maynard, Dawn; Dorward, Heidi; Berger, Katherine; Kleta, Robert; Huizing, Marjan; Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Gunay-Aygun, Meral; Gahl, William A.] US Natl Inst Hlth, Off Rare Dis Res, Bethesda, MD USA.
[Falik-Zaccai, Tzipora C.; Zivony-Elboum, Yifat; Khayat, Morad; Kfir, Nehama] Western Galilee Hosp, Inst Human Genet, Nahariyya, Israel.
[Falik-Zaccai, Tzipora C.] Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Haifa, Israel.
[Gumruk, Fatma; Cetin, Mualla] Hacettepe Univ Childrens Hosp, Pediat Hematol Unit, Ankara, Turkey.
[Anikster, Yair] Edmond & Lily Safra Childrens Hosp, Sheba Med Ctr, Metab Dis Unit, Tel Aviv, Israel.
[Anikster, Yair] Sackler Sch Med, Tel Aviv, Israel.
[Arat, Mutlu] Ankara Univ, Fac Med, Dept Hematol, TR-06100 Ankara, Turkey.
[Freiberg, Andrew S.] Penn State Hershey Childrens Hosp, Div Pediat Hematol Oncol, Hershey, PA USA.
[Kehrel, Beate E.; Jurk, Kerstin] Univ Hosp Munster, Dept Anaesthesiol & Intens Care Expt & Clin Haemo, Munster, Germany.
[Cruz, Pedro; Mullikin, Jim C.] US Natl Inst Hlth NIH, Intramural Sequencing Ctr, NIH, Bethesda, MD USA.
[White, James G.] Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA.
RP Gunay-Aygun, M (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM mgaygun@mail.nih.gov
FU National Human Genome Research Institute; NIH Clinical Center; Israeli
Ministry of Justice [84/2004, 85/2004, 9090-25/2007]
FX We thank all of our subjects with GPS and their families for their
cooperation; the NIH Intramural Sequencing Center for performing the
whole-exome sequencing and analysis; A. Nurden for the French patient;
I. Bernardini and R. Fisher for technical assistance; H. Edwards, L.
Riley, K. Patzel, P. Tanpaiboon, J. Chezar and J. Manaster for DNA
sequencing assistance; T. Markello for the SNP array; and I. Maric, S.
Gucer and I. Kuzu for assistance with bone marrow slides. This study was
supported by the Intramural Research Programs of the National Human
Genome Research Institute and the NIH Clinical Center and by the Israeli
Ministry of Justice; Izvonot Fund, grants 84/2004, 85/2004 and
9090-25/2007 to T.C.F.-Z.
NR 15
TC 95
Z9 97
U1 2
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD AUG
PY 2011
VL 43
IS 8
BP 732
EP 734
DI 10.1038/ng.883
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 798CD
UT WOS:000293178300006
PM 21765412
ER
PT J
AU Kilpelainen, TO
Zillikens, MC
Stancakova, A
Finucane, FM
Ried, JS
Langenberg, C
Zhang, WH
Beckmann, JS
Luan, JA
Vandenput, L
Styrkarsdottir, U
Zhou, YH
Smith, AV
Zhao, JH
Amin, N
Vedantam, S
Shin, SY
Haritunians, T
Fu, M
Feitosa, MF
Kumari, M
Halldorsson, BV
Tikkanen, E
Mangino, M
Hayward, C
Song, C
Arnold, AM
Aulchenko, YS
Oostra, BA
Campbell, H
Cupples, LA
Davis, KE
Doring, A
Eiriksdottir, G
Estrada, K
Fernandez-Real, JM
Garcia, M
Gieger, C
Glazer, NL
Guiducci, C
Hofman, A
Humphries, SE
Isomaa, B
Jacobs, LC
Jula, A
Karasik, D
Karlsson, MK
Khaw, KT
Kim, LJ
Kivimaki, M
Klopp, N
Kuhnel, B
Kuusisto, J
Liu, YM
Ljunggren, O
Lorentzon, M
Luben, RN
McKnight, B
Mellstrom, D
Mitchell, BD
Mooser, V
Moreno, JM
Mannisto, S
O'Connell, JR
Pascoe, L
Peltonen, L
Peral, B
Perola, M
Psaty, BM
Salomaa, V
Savage, DB
Semple, RK
Skaric-Juric, T
Sigurdsson, G
Song, KS
Spector, TD
Syvanen, AC
Talmud, PJ
Thorleifsson, G
Thorsteinsdottir, U
Uitterlinden, AG
van Duijn, CM
Vidal-Puig, A
Wild, SH
Wright, AF
Clegg, DJ
Schadt, E
Wilson, JF
Rudan, I
Ripatti, S
Borecki, IB
Shuldiner, AR
Ingelsson, E
Jansson, JO
Kaplan, RC
Gudnason, V
Harris, TB
Groop, L
Kiel, DP
Rivadeneira, F
Walker, M
Barroso, I
Vollenweider, P
Waeber, G
Chambers, JC
Kooner, JS
Soranzo, N
Hirschhorn, JN
Stefansson, K
Wichmann, HE
Ohlsson, C
O'Rahilly, S
Wareham, NJ
Speliotes, EK
Fox, CS
Laakso, M
Loos, RJF
AF Kilpelainen, Tuomas O.
Zillikens, M. Carola
Stancakova, Alena
Finucane, Francis M.
Ried, Janina S.
Langenberg, Claudia
Zhang, Weihua
Beckmann, Jacques S.
Luan, Jian'an
Vandenput, Liesbeth
Styrkarsdottir, Unnur
Zhou, Yanhua
Smith, Albert Vernon
Zhao, Jing-Hua
Amin, Najaf
Vedantam, Sailaja
Shin, So-Youn
Haritunians, Talin
Fu, Mao
Feitosa, Mary F.
Kumari, Meena
Halldorsson, Bjarni V.
Tikkanen, Emmi
Mangino, Massimo
Hayward, Caroline
Song, Ci
Arnold, Alice M.
Aulchenko, Yurii S.
Oostra, Ben A.
Campbell, Harry
Cupples, L. Adrienne
Davis, Kathryn E.
Doering, Angela
Eiriksdottir, Gudny
Estrada, Karol
Manuel Fernandez-Real, Jose
Garcia, Melissa
Gieger, Christian
Glazer, Nicole L.
Guiducci, Candace
Hofman, Albert
Humphries, Steve E.
Isomaa, Bo
Jacobs, Leonie C.
Jula, Antti
Karasik, David
Karlsson, Magnus K.
Khaw, Kay-Tee
Kim, Lauren J.
Kivimaeki, Mika
Klopp, Norman
Kuehnel, Brigitte
Kuusisto, Johanna
Liu, Yongmei
Ljunggren, Osten
Lorentzon, Mattias
Luben, Robert N.
McKnight, Barbara
Mellstrom, Dan
Mitchell, Braxton D.
Mooser, Vincent
Maria Moreno, Jose
Mannisto, Satu
O'Connell, Jeffery R.
Pascoe, Laura
Peltonen, Leena
Peral, Belen
Perola, Markus
Psaty, Bruce M.
Salomaa, Veikko
Savage, David B.
Semple, Robert K.
Skaric-Juric, Tatjana
Sigurdsson, Gunnar
Song, Kijoung S.
Spector, Timothy D.
Syvanen, Ann-Christine
Talmud, Philippa J.
Thorleifsson, Gudmar
Thorsteinsdottir, Unnur
Uitterlinden, Andre G.
van Duijn, Cornelia M.
Vidal-Puig, Antonio
Wild, Sarah H.
Wright, Alan F.
Clegg, Deborah J.
Schadt, Eric
Wilson, James F.
Rudan, Igor
Ripatti, Samuli
Borecki, Ingrid B.
Shuldiner, Alan R.
Ingelsson, Erik
Jansson, John-Olov
Kaplan, Robert C.
Gudnason, Vilmundur
Harris, Tamara B.
Groop, Leif
Kiel, Douglas P.
Rivadeneira, Fernando
Walker, Mark
Barroso, Ines
Vollenweider, Peter
Waeber, Gerard
Chambers, John C.
Kooner, Jaspal S.
Soranzo, Nicole
Hirschhorn, Joel N.
Stefansson, Kari
Wichmann, H-Erich
Ohlsson, Claes
O'Rahilly, Stephen
Wareham, Nicholas J.
Speliotes, Elizabeth K.
Fox, Caroline S.
Laakso, Markku
Loos, Ruth J. F.
TI Genetic variation near IRS1 associates with reduced adiposity and an
impaired metabolic profile
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; INSULIN-RECEPTOR SUBSTRATE-1; BODY-MASS INDEX;
ADIPOCYTE DIFFERENTIATION; ADULT OBESITY; FTO GENE; LOCI; RESISTANCE;
EXPRESSION; MIGRATION
AB Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between similar to 2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 x 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 x 10(-11)) and one near SPRY2 (P = 3 x 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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[Zillikens, M. Carola; Estrada, Karol; Jacobs, Leonie C.; Uitterlinden, Andre G.; Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Zillikens, M. Carola; Estrada, Karol; Hofman, Albert; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Rivadeneira, Fernando] NGI, NCHA, Leiden, Netherlands.
[Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Ried, Janina S.; Doering, Angela; Gieger, Christian; Klopp, Norman; Kuehnel, Brigitte; Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Zhang, Weihua; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.
[Beckmann, Jacques S.] Univ Lausanne Hosp, Dept Med Genet, Lausanne, Switzerland.
[Vandenput, Liesbeth; Lorentzon, Mattias; Mellstrom, Dan; Ohlsson, Claes] Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden.
[Styrkarsdottir, Unnur; Halldorsson, Bjarni V.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] DeCODE Genet, Reykjavik, Iceland.
[Zhou, Yanhua; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Smith, Albert Vernon; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Heart Prevent Clin, Kopavogur, Iceland.
[Smith, Albert Vernon; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland.
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[Vedantam, Sailaja; Guiducci, Candace; Hirschhorn, Joel N.; Speliotes, Elizabeth K.] Broad Inst, Metab Initiat, Cambridge, MA USA.
[Vedantam, Sailaja; Guiducci, Candace; Hirschhorn, Joel N.; Speliotes, Elizabeth K.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Shin, So-Youn; Peltonen, Leena; Barroso, Ines; Soranzo, Nicole] Wellcome Trust Sanger Inst, Cambridge, England.
[Haritunians, Talin] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Fu, Mao; Mitchell, Braxton D.; O'Connell, Jeffery R.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Feitosa, Mary F.; Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA.
[Kumari, Meena] UCL, Dept Epidemiol, Genet Epidemiol Grp, London, England.
[Halldorsson, Bjarni V.] Reykjavik Univ, Reykjavik, Iceland.
[Tikkanen, Emmi; Peltonen, Leena; Perola, Markus; Ripatti, Samuli] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Mangino, Massimo; Spector, Timothy D.] Kings Coll London, London WC2R 2LS, England.
[Hayward, Caroline; Wright, Alan F.] MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Song, Ci; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Arnold, Alice M.; McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Campbell, Harry; Wild, Sarah H.; Wilson, James F.; Rudan, Igor] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Davis, Kathryn E.; Clegg, Deborah J.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Touchstone Diabet Ctr, Dallas, TX 75390 USA.
[Manuel Fernandez-Real, Jose; Maria Moreno, Jose] Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Inst Invest Biomed Girona, Dept Diabet Endocrinol & Nutr, Girona, Spain.
[Garcia, Melissa; Kim, Lauren J.; Harris, Tamara B.] NIA, Intramural Res Program, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Glazer, Nicole L.; McKnight, Barbara; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Glazer, Nicole L.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Humphries, Steve E.; Talmud, Philippa J.] UCL, Dept Med, Ctr Cardiovasc Genet, London, England.
[Isomaa, Bo] Folkhalsan Res Ctr, Helsinki, Finland.
[Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland.
[Jula, Antti] Natl Inst Hlth & Welf, Populat Studies Unit, Helsinki, Finland.
[Karasik, David; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA.
[Karlsson, Magnus K.] Malmo Univ Hosp, Dept Orthopaed, Malmo, Sweden.
[Khaw, Kay-Tee; Luben, Robert N.] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England.
[Kivimaeki, Mika] UCL, Dept Epidemiol & Publ Hlth, London, England.
[Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Ljunggren, Osten] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Mooser, Vincent; Song, Kijoung S.] GlaxoSmithKline, Genet Res & Dev, King Of Prussia, PA USA.
[Mannisto, Satu; Salomaa, Veikko] Natl Inst Hlth & Welf, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland.
[Pascoe, Laura; Walker, Mark] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Peral, Belen] CSIC, Inst Invest Biomed, Madrid, Spain.
[Peral, Belen] Univ Autonoma Madrid, Madrid, Spain.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Savage, David B.; Semple, Robert K.; Vidal-Puig, Antonio; Barroso, Ines; O'Rahilly, Stephen] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England.
[Skaric-Juric, Tatjana] Inst Anthropol Res, Zagreb, Croatia.
[Sigurdsson, Gunnar] Univ Hosp, Dept Endocrinol & Metab, Reykjavik, Iceland.
[Sigurdsson, Gunnar; Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Sci Life Lab, Uppsala, Sweden.
[van Duijn, Cornelia M.] CMSB, NGI, Leiden, Netherlands.
[Schadt, Eric] Pacific Biosci, Menlo Pk, CA USA.
[Schadt, Eric] Sage Bionetworks, Seattle, WA USA.
[Rudan, Igor] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia.
[Rudan, Igor] Gen Info Ltd, Zagreb, Croatia.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
[Ingelsson, Erik] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden.
[Jansson, John-Olov] Univ Gothenburg, Dept Physiol, Inst Neurosci & Physiol, Sahlgrenska Acad, Gothenburg, Sweden.
[Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
[Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Groop, Leif] Lund Univ, Dept Clin Sci, Ctr Diabet, Malmo, Sweden.
[Vollenweider, Peter; Waeber, Gerard] Univ Lausanne Hosp, Dept Internal Med, Lausanne, Switzerland.
[Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London, England.
[Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Fox, Caroline S.] NHLBI, Boston, MA USA.
RP Loos, RJF (reprint author), MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England.
EM ruth.loos@mrc-epid.cam.ac.uk
RI Wilson, James F/A-5704-2009; Rivadeneira, Fernando/O-5385-2015;
Beckmann, Jacques S /A-9772-2008; Skaric-Juric, Tatjana/H-5997-2011;
Kivimaki, Mika/B-3607-2012; Kilpelainen, Tuomas/F-8569-2012; Rudan,
Igor/I-1467-2012; Colaus, PsyColaus/K-6607-2013; Aulchenko,
Yurii/M-8270-2013; Moreno-Navarrete, Jose Maria/H-9772-2015; Gudnason,
Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Smith,
Albert/K-5150-2015; mangino, massimo/F-5134-2011; Hayward,
Caroline/M-8818-2016; Feitosa, Mary/K-8044-2012;
OI Wilson, James F/0000-0001-5751-9178; Rivadeneira,
Fernando/0000-0001-9435-9441; Beckmann, Jacques S /0000-0002-9741-1900;
Rudan, Igor/0000-0001-6993-6884; Aulchenko, Yurii/0000-0002-7899-1575;
Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti,
Samuli/0000-0002-0504-1202; Smith, Albert/0000-0003-1942-5845; mangino,
massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550;
Feitosa, Mary/0000-0002-0933-2410; Cupples, L.
Adrienne/0000-0003-0273-7965; Soranzo, Nicole/0000-0003-1095-3852; Song,
Ci/0000-0002-0947-9068; Kivimaki, Mika/0000-0002-4699-5627; Talmud,
Philippa/0000-0002-5560-1933; Halldorsson, Bjarni/0000-0003-0756-0767;
Vandenput, Liesbeth/0000-0002-1712-6131; Mitchell,
Braxton/0000-0003-4920-4744; Fernandez-Real, Jose
Manuel/0000-0002-7442-9323; Mannisto, Satu/0000-0002-8668-3046; Luben,
Robert/0000-0002-5088-6343; Humphries, Stephen E/0000-0002-8221-6547;
Gieger, Christian/0000-0001-6986-9554; Semple,
Robert/0000-0001-6539-3069; Kiel, Douglas/0000-0001-8474-0310; PERAL,
BELEN/0000-0003-4984-4020; Karasik, David/0000-0002-8826-0530
FU Academy of Finland [10404, 124243, 129680, 129494, 141005, 213506];
Agency for Health Care Policy Research [HS06516]; Althingi (the
Icelandic Parliament); American Heart Association [10SDG269004];
AstraZeneca; Baltimore Geriatric Research Education and Clinical
Centers; Biocentrum Helsinki Foundation; Biotechnology and Biological
Sciences Research Council [G20234]; British Heart Foundation
[PG/07/133/24260, RG/08/008, SP/04/002, SP/07/007/23671]; CamStrad;
Cancer Research UK; Cedars-Sinai Board of Governors' Chair in Medical
Genetics; Centre for Medical Systems Biology (The Netherlands); Centre
Hospitalier Universitaire Vaudois (Lausanne); Croatian Ministry of
Science, Education and Sport [196-1962766-2747, 216-1080315-0302,
309-0061194-2023]; Department of Health (UK); Department of Veterans
Affairs (USA); Emil and Vera Cornell Foundation; Erasmus Medical Center
(Rotterdam); Erasmus University (Rotterdam); European Commission
[FP7/2007-2013, FP7-KBBE-2010-4-266408, HEALTH-F2-2007-201681,
HEALTH-F2-2008-201865-GEFOS, HEALTH-F4-2007-201413,
HEALTH-F4-2007-201550, LSHG-CT-2006-018947, LSHG-CT-2006-01947,
LSHM-CT-2003-503041, LSHM-CT-2004-512013, QLG1-CT-2001-01252,
QLG2-CT-2002-01254]; Finnish Diabetes Foundation; Finnish Diabetes
Research Foundation; Finnish Foundation for Cardiovascular Research;
Finnish Heart Foundation; Finnish Medical Society; Folkhalsan Research
Foundation; Food Standards Agency (UK); Foundation for Life and Health
in Finland; German Bundesministerium fur Forschung und Technology
[01AK803A-H, 01IG07015G]; German Federal Ministry of Education and
Research; German National Genome Research Network [NGFN-2, NGFNPlus:
01GS0823]; Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Goteborg
Medical Society; Gyllenberg Foundation; Health and Safety Executive
(UK); Health Care Center in Vasa; Health Care Center in Narpes; Health
Care Center in Korsholm; Hjartavernd (the Icelandic Heart Association);
John D. and Catherine T. MacArthur Foundation; Knut and Alice Wallenberg
Foundation; Leenaards Foundation; Ludwig-Maximilians Universitat
Munchen; Lundberg Foundation; Medical Research Council (UK); Men's
Associates of Hebrew SeniorLife; Ministerio de Ciencia e Innovacion
(Spain) [SAF-2009, SAF-2008-02073]; Ministry for Health, Welfare and
Sports (The Netherlands); Ministry of Education (Finland); Ministry of
Education, Culture and Science (The Netherlands); Municipal Health Care
Center and Hospital in Jakobstad; Municipality of Rotterdam; Narpes
Health Care Foundation; National Institute for Health Research (UK);
Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging
[050-060-810]; Netherlands Organisation for Scientific Research
[175.010.2005.011, 911-03-012]; Netherlands Organization for the Health
Research and Development; Nordic Center of Excellence in Disease
Genetics; Novo Nordisk Foundation; Ollqvist Foundation; Paavo Nurmi
Foundation; Perklen Foundation; Petrus and Augusta Hedlunds Foundation;
Research Institute for Diseases in the Elderly [014-93-015, RIDE2];
Robert Dawson Evans Endowment; Royal Society (UK); Sahlgrenska Center
for Cardiovascular and Metabolic Research [A305:188]; Sahlgrenska
University Hospital Foundation (ALF/LUA); Science Funding programme
(UK); Scottish Executive Health Department; Sigrid Juselius Foundation;
State of Bavaria; Stroke Association (UK); Swedish Cultural Foundation
in Finland; Swedish Foundation for Strategic Research; Swedish Research
Council [K2010-54X-09894-19-3, K2010-52X-20229-05-3, 2006-3832]; Swedish
Strategic Foundation; Swiss Institute of Bioinformatics; Swiss National
Science Foundation [3100AO-116323/1, 310000-112552, 33CSCO-122661];
TEKES [1510/31/06]; Torsten and Ragnar Soderberg's Foundation; United
Kingdom NIHR Cambridge Biomedical Research Centre; University of
Lausanne; University of Maryland General Clinical Research Center [M01
RR 16500]; Uppsala University
FX A full list of Acknowledgments appears in the Supplementary Note.
Funding was provided by Academy of Finland (10404, 124243, 129680,
129494, 141005 and 213506); Agency for Health Care Policy Research
(HS06516); Althingi (the Icelandic Parliament); American Heart
Association (10SDG269004); AstraZeneca; Baltimore Geriatric Research
Education and Clinical Centers; Biocentrum Helsinki Foundation;
Biotechnology and Biological Sciences Research Council (G20234); British
Heart Foundation (PG/07/133/24260, RG/08/008, SP/04/002,
SP/07/007/23671); CamStrad; Cancer Research UK; Cedars-Sinai Board of
Governors' Chair in Medical Genetics; Centre for Medical Systems Biology
(The Netherlands); Centre Hospitalier Universitaire Vaudois (Lausanne);
Croatian Ministry of Science, Education and Sport (196-1962766-2747,
216-1080315-0302 and 309-0061194-2023); Department of Health (UK);
Department of Veterans Affairs (USA); Emil and Vera Cornell Foundation;
Erasmus Medical Center (Rotterdam); Erasmus University (Rotterdam);
European Commission (DG XII, FP7/2007-2013, FP7-KBBE-2010-4-266408,
HEALTH-F2-2007-201681, HEALTH-F2-2008-201865-GEFOS,
HEALTH-F4-2007-201413, HEALTH-F4-2007-201550, LSHG-CT-2006-018947,
LSHG-CT-2006-01947, LSHM-CT-2003-503041, LSHM-CT-2004-512013,
QLG1-CT-2001-01252 and QLG2-CT-2002-01254); Finnish Diabetes Foundation;
Finnish Diabetes Research Foundation; Finnish Foundation for
Cardiovascular Research; Finnish Heart Foundation; Finnish Medical
Society; Folkhalsan Research Foundation; Food Standards Agency (UK);
Foundation for Life and Health in Finland; German Bundesministerium fur
Forschung und Technology (01AK803A-H and 01IG07015G); German Federal
Ministry of Education and Research; German National Genome Research
Network (NGFN-2 and NGFNPlus: 01GS0823); Giorgi-Cavaglieri Foundation;
GlaxoSmithKline; Goteborg Medical Society; Gyllenberg Foundation; Health
and Safety Executive (UK); Health Care Centers in Vasa, Narpes and
Korsholm; Hjartavernd (the Icelandic Heart Association); John D. and
Catherine T. MacArthur Foundation; Knut and Alice Wallenberg Foundation;
Leenaards Foundation; Ludwig-Maximilians Universitat Munchen; Lundberg
Foundation; Medical Research Council (UK); Men's Associates of Hebrew
SeniorLife; Ministerio de Ciencia e Innovacion (Spain) (SAF-2009 and
SAF-2008-02073); Ministry for Health, Welfare and Sports (The
Netherlands); Ministry of Education (Finland); Ministry of Education,
Culture and Science (The Netherlands); Municipal Health Care Center and
Hospital in Jakobstad; Municipality of Rotterdam; Narpes Health Care
Foundation; National Institute for Health Research (UK); US National
Institutes of Health (USA) (AG13196, DK063491, K23-DK080145,
M01-RR00425, N01-AG12100, N01-AG62101, N01-AG62103, N01-AG62106,
N01-HC15103, N01-HC25195, N01-HC35129, N01-HC45133, N01-HC55222,
N01-HC75150, N01-HC85079 through N01-HC85086, P30-DK072488,
R01-AG031890-01, R01-AG18728, R01-AG032098-01A1, R01-AR/AG41398,
R01-AR046838, R01-DK06833603, R01-DK075787, R01-DK07568102,
R01-HL036310-20A2, R01-HL087652, R01-HL08770003, R01-HL088119,
U01-HL080295, U01-HL72515 and U01-HL84756); Netherlands Genomics
Initiative/Netherlands Consortium for Healthy Aging (050-060-810);
Netherlands Organisation for Scientific Research (175.010.2005.; 011 and
911-03-012); Netherlands Organization for the Health Research and
Development; Nordic Center of Excellence in Disease Genetics; Novo
Nordisk Foundation; Ollqvist Foundation; Paavo Nurmi Foundation; Perklen
Foundation; Petrus and Augusta Hedlunds Foundation; Research Institute
for Diseases in the Elderly (01-93-015; RIDE2); Robert Dawson Evans
Endowment; Royal Society (UK); Sahlgrenska Center for Cardiovascular and
Metabolic Research (A305:188); Sahlgrenska University Hospital
Foundation (ALF/LUA); Science Funding programme (UK); Scottish Executive
Health Department; Sigrid Juselius Foundation; State of Bavaria; Stroke
Association (UK); Swedish Cultural Foundation in Finland; Swedish
Foundation for Strategic Research; Swedish Research Council
(K2010-54X-09894-19-3, K2010-52X-20229-05-3 and 2006-3832); Swedish
Strategic Foundation; Swiss Institute of Bioinformatics; Swiss National
Science Foundation (3100AO-116323/1, 310000-112552 and 33CSCO-122661);
TEKES (1510/31/06); Torsten and Ragnar Soderberg's Foundation; United
Kingdom NIHR Cambridge Biomedical Research Centre; University of
Lausanne; University of Maryland General Clinical Research Center (M01
RR 16500); Uppsala University; Vastra Gotaland Foundation; and Wellcome
Trust (077016/Z/05/Z, 084723/Z/08/Z and 091746/Z/10/Z).
NR 51
TC 120
Z9 124
U1 4
U2 25
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD AUG
PY 2011
VL 43
IS 8
BP 753
EP U58
DI 10.1038/ng.866
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 798CD
UT WOS:000293178300011
PM 21706003
ER
PT J
AU Evans, DM
Spencer, CCA
Pointon, JJ
Su, Z
Harvey, D
Kochan, G
Opperman, U
Dilthey, A
Pirinen, M
Stone, MA
Appleton, L
Moutsianis, L
Leslie, S
Wordsworth, T
Kenna, TJ
Karaderi, T
Thomas, GP
Ward, MM
Weisman, MH
Farrar, C
Bradbury, LA
Danoy, P
Inman, RD
Maksymowych, W
Gladman, D
Rahman, P
Morgan, A
Marzo-Ortega, H
Bowness, P
Gaffney, K
Gaston, JSH
Smith, M
Bruges-Armas, J
Couto, AR
Sorrentino, R
Paladini, F
Ferreira, MA
Xu, HJ
Liu, Y
Jiang, L
Lopez-Larrea, C
Diaz-Pena, R
Lopez-Vazquez, A
Zayats, T
Band, G
Bellenguez, C
Blackburn, H
Blackwell, JM
Bramon, E
Bumpstead, SJ
Casas, JP
Corvin, A
Craddock, N
Deloukas, P
Dronov, S
Duncanson, A
Edkins, S
Freeman, C
Gillman, M
Gray, E
Gwilliam, R
Hammond, N
Hunt, SE
Jankowski, J
Jayakumar, A
Langford, C
Liddle, J
Markus, HS
Mathew, CG
McCann, OT
McCarthy, MI
Palmer, CNA
Peltonen, L
Plomin, R
Potter, SC
Rautanen, A
Ravindrarajah, R
Ricketts, M
Samani, N
Sawcer, SJ
Strange, A
Trembath, RC
Viswanathan, AC
Waller, M
Weston, P
Whittaker, P
Widaa, S
Wood, NW
McVean, G
Reveille, JD
Wordsworth, BP
Brown, MA
Donnelly, P
AF Evans, David M.
Spencer, Chris C. A.
Pointon, Jennifer J.
Su, Zhan
Harvey, David
Kochan, Grazyna
Opperman, Udo
Dilthey, Alexander
Pirinen, Matti
Stone, Millicent A.
Appleton, Louise
Moutsianis, Loukas
Leslie, Stephen
Wordsworth, Tom
Kenna, Tony J.
Karaderi, Tugce
Thomas, Gethin P.
Ward, Michael M.
Weisman, Michael H.
Farrar, Claire
Bradbury, Linda A.
Danoy, Patrick
Inman, Robert D.
Maksymowych, Walter
Gladman, Dafna
Rahman, Proton
Morgan, Ann
Marzo-Ortega, Helena
Bowness, Paul
Gaffney, Karl
Gaston, J. S. Hill
Smith, Malcolm
Bruges-Armas, Jacome
Couto, Ana-Rita
Sorrentino, Rosa
Paladini, Fabiana
Ferreira, Manuel A.
Xu, Huji
Liu, Yu
Jiang, Lei
Lopez-Larrea, Carlos
Diaz-Pena, Roberto
Lopez-Vazquez, Antonio
Zayats, Tetyana
Band, Gavin
Bellenguez, Celine
Blackburn, Hannah
Blackwell, Jenefer M.
Bramon, Elvira
Bumpstead, Suzannah J.
Casas, Juan P.
Corvin, Aiden
Craddock, Nicholas
Deloukas, Panos
Dronov, Serge
Duncanson, Audrey
Edkins, Sarah
Freeman, Colin
Gillman, Matthew
Gray, Emma
Gwilliam, Rhian
Hammond, Naomi
Hunt, Sarah E.
Jankowski, Janusz
Jayakumar, Alagurevathi
Langford, Cordelia
Liddle, Jennifer
Markus, Hugh S.
Mathew, Christopher G.
McCann, Owen T.
McCarthy, Mark I.
Palmer, Colin N. A.
Peltonen, Leena
Plomin, Robert
Potter, Simon C.
Rautanen, Anna
Ravindrarajah, Radhi
Ricketts, Michelle
Samani, Nilesh
Sawcer, Stephen J.
Strange, Amy
Trembath, Richard C.
Viswanathan, Ananth C.
Waller, Matthew
Weston, Paul
Whittaker, Pamela
Widaa, Sara
Wood, Nicholas W.
McVean, Gilean
Reveille, John D.
Wordsworth, B. Paul
Brown, Matthew A.
Donnelly, Peter
CA Australo-Anglo-Amer Spondyloarthri
Wellcome Trust Case Control Consor
Spondyloarthrit Res Consortium Can
TI Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis
implicates peptide handling in the mechanism for HLA-B27 in disease
susceptibility
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; GENETIC
ASSOCIATION; TRIMS PRECURSORS; AMINOPEPTIDASE; RISK; HLA; POPULATION;
PROMOTES; CELLS
AB Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 x 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 x 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.
C1 [Spencer, Chris C. A.; Su, Zhan; Band, Gavin; Bellenguez, Celine; Freeman, Colin; Strange, Amy; McVean, Gilean; Donnelly, Peter] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Evans, David M.; Dilthey, Alexander; Pirinen, Matti; Zayats, Tetyana] Univ Bristol, Sch Social & Community Med, Med Res Council MRC Ctr Causal Anal Translat Epid, Bristol, Avon, England.
[Pointon, Jennifer J.; Harvey, David; Appleton, Louise; Wordsworth, Tom; Karaderi, Tugce; Farrar, Claire; Bowness, Paul; Wordsworth, B. Paul] Nuffield Orthopaed Ctr, Natl Inst Hlth Res Musculoskeletal Biomed Res Uni, Oxford OX3 7LD, England.
[Kochan, Grazyna; Opperman, Udo] Univ Oxford, Struct Genom Consortium, Oxford, England.
[Stone, Millicent A.] Univ Bath, Bath BA2 7AY, Avon, England.
[Moutsianis, Loukas] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
[Leslie, Stephen] Univ Oxford, Dept Clin Pharmacol, Oxford, England.
[Kenna, Tony J.; Thomas, Gethin P.; Bradbury, Linda A.; Danoy, Patrick; Brown, Matthew A.] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld, Australia.
[Ward, Michael M.] NIAMSD, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA.
[Weisman, Michael H.] Cedars Sinai Med Ctr, Dept Med Rheumatol, Los Angeles, CA 90048 USA.
[Inman, Robert D.; Gladman, Dafna] Univ Toronto, Toronto, ON, Canada.
[Maksymowych, Walter] Univ Alberta, Dept Med, Edmonton, AB, Canada.
[Rahman, Proton] Mem Univ Newfoundland, St John, NF, Canada.
[Morgan, Ann; Marzo-Ortega, Helena] Univ Leeds, NIHR, Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England.
[Gaffney, Karl] Norfolk & Norwich Univ Hosp, Dept Rheumatol, Norwich, Norfolk, England.
[Gaston, J. S. Hill] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England.
[Smith, Malcolm] Repatriat Gen Hosp, Adelaide, SA, Australia.
[Bruges-Armas, Jacome; Couto, Ana-Rita] Hosp Santo Espirito, Serv Especializado Epidemiol & Biol Mol, Terceira, The Azores, Portugal.
[Bruges-Armas, Jacome] Univ Porto, Inst Mol & Cell Biol IBMC, Genet & Arthrit Res Grp, P-4100 Oporto, Portugal.
[Sorrentino, Rosa; Paladini, Fabiana] Univ Roma La Sapienza, Dept Biol & Biotechnol Charles Darwin, Rome, Italy.
[Ferreira, Manuel A.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Xu, Huji; Liu, Yu; Jiang, Lei] Second Mil Med Univ Hosp, Shanghai Changzheng Hosp, Dept Rheumatol & Immunol, Shanghai, Peoples R China.
[Lopez-Larrea, Carlos; Diaz-Pena, Roberto; Lopez-Vazquez, Antonio; Blackburn, Hannah] Hosp Univ Cent Asturias, Dept Immunol, Oviedo, Spain.
[Bramon, Elvira; Bumpstead, Suzannah J.; Deloukas, Panos; Dronov, Serge; Edkins, Sarah; Gillman, Matthew; Gray, Emma; Gwilliam, Rhian; Hammond, Naomi; Hunt, Sarah E.; Jayakumar, Alagurevathi; Langford, Cordelia; Liddle, Jennifer; McCann, Owen T.; Peltonen, Leena; Potter, Simon C.; Rautanen, Anna; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Whittaker, Pamela; Widaa, Sara] Wellcome Trust Sanger Inst, Cambridge, England.
[Blackwell, Jenefer M.] Univ Western Australia, Ctr Child Hlth Res, Telethon Inst Child Hlth Res, Perth, WA 6009, Australia.
[Blackwell, Jenefer M.] Addenbrookes Hosp, Cambridge Inst Med Res, Genet & Infect Lab, Cambridge, England.
[Casas, Juan P.] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England.
[Corvin, Aiden] Trinity Coll Dublin, Inst Mol Med, Neuropsychiat Genet Res Grp, Dublin, Ireland.
[Craddock, Nicholas] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales.
[Duncanson, Audrey] Wellcome Trust Res Labs, London, England.
[Jankowski, Janusz] Barts & London Queen Marys Sch Med & Dent, Ctr Gastroenterol, London, England.
[Markus, Hugh S.] St Georges Univ London, London, England.
[Mathew, Christopher G.; Trembath, Richard C.] Kings Coll London, Div Genet & Mol Med, London WC2R 2LS, England.
[McCarthy, Mark I.] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England.
[Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Dundee DD1 9SY, Scotland.
[Plomin, Robert] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England.
[Samani, Nilesh] Univ Leicester, Glenfield Gen Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
[Sawcer, Stephen J.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England.
[Viswanathan, Ananth C.] Moorfields Eye Hosp NHS Fdn Trust, Glaucoma Res Unit, London, England.
[Viswanathan, Ananth C.] UCL, Inst Ophthalmol, Dept Genet, London, England.
[Wood, Nicholas W.] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
RP Donnelly, P (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
EM matt.brown@uq.edu.au; peter.donnelly@well.ox.ac.uk
RI Palmer, Colin/C-7053-2008; Kochan, Grazyna/A-1094-2009; Kenna,
Tony/A-6035-2011; Deloukas, Panos/B-2922-2013; Evans, David/H-6325-2013;
Thomas, Gethin/A-3624-2011; Ferreira, Manuel/D-3609-2013; Wood,
Nicholas/C-2505-2009; Jankowski, Janusz/H-2706-2012; Blackwell,
Jenefer/H-3015-2015; Mathew, Christopher/G-3434-2015;
OI Trembath, Richard/0000-0003-0550-3400; Evans, David/0000-0003-0663-4621;
Pirinen, Matti/0000-0002-1664-1350; bowness, paul/0000-0003-4597-0484;
Corvin, Aiden/0000-0001-6717-4089; Kenna, Tony/0000-0001-6844-3463;
Armas, Jacome/0000-0001-7671-6521; Couto Rendeiro, Ana
Rita/0000-0002-3600-2812; Hunt, Sarah/0000-0002-8350-1235; Potter,
Simon/0000-0003-4208-4102; Gillman, Matthew/0000-0002-2340-6930; Plomin,
Robert/0000-0002-0756-3629; Diaz-Pena, Roberto/0000-0002-0114-2292;
McVean, Gil/0000-0002-5012-4162; Sorrentino, Rosa/0000-0002-9632-2383;
Palmer, Colin/0000-0002-6415-6560; Deloukas, Panos/0000-0001-9251-070X;
Wood, Nicholas/0000-0002-9500-3348; Jankowski,
Janusz/0000-0003-2130-9181; Mathew, Christopher/0000-0003-4178-1838;
Brown, Matthew A/0000-0003-0538-8211
FU Wellcome Trust [083948/Z/07/Z, 076113, 068545/Z/02]; National Institute
of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [P01-052915,
R01-AR046208]; University of Texas at Houston Clinical and Translational
Science [UL1RR024188]; Cedars-Sinai General Clinical Research Centre
[MO1-RR00425]; Intramural Research Program; NIAMS/US National Institutes
of Health; Rebecca Cooper Foundation (Australia); Arthritis Research UK
[19536, 18797]; Oxford Comprehensive Biomedical Research Centre
[A91202]; Arthritis Society (Canada); Lions Medical Research Foundation
fellowship; National Health and Medical Research Council (Australia);
National Health and Medical Research Council (Australia) [566938,
569829]; Australian Cancer Research Foundation; Rebecca Cooper Medical
Research Foundation; Wolfson-Royal Society Merit Award; National
Institute for Health Research (NIHR); Oxford Musculoskeletal Biomedical
Research Unit; NIHR Thames Valley Comprehensive Local Research Network;
Medical Research Council [G0000934]; Canadian Institutes for Health
Research; Canadian Foundation for Innovation; Genome Canada through the
Ontario Genomics Institute; GlaxoSmithKline; Karolinska Institutet; Knut
and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario
Ministry for Research and Innovation; Merck Co., Inc.; Novartis Research
Foundation; Swedish Agency for Innovation Systems; Swedish Foundation
for Strategic Research
FX We would like to thank all participating subjects with ankylosing
spondylitis and healthy individuals who provided the DNA and clinical
information necessary for this study. The Wellcome Trust Case Control
Consortium 2 project is funded by the Wellcome Trust (083948/Z/07/Z). We
also thank S. Bertrand, J. Bryant, S. L. Clark, J. S. Conquer, T.
Dibling, J. C. Eldred, S. Gamble, C. Hind, A. Wilk, C. R. Stribling and
S. Taylor of the Wellcome Trust Sanger Institute's Sample and Genotyping
Facilities for technical assistance. The TASC study was funded by the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) grants P01-052915 and R01-AR046208. Funding was also received
from the University of Texas at Houston Clinical and Translational
Science Awards grant UL1RR024188, Cedars-Sinai General Clinical Research
Centre grant MO1-RR00425, Intramural Research Program, NIAMS/US National
Institutes of Health and Rebecca Cooper Foundation (Australia). This
study was funded, in part, by Arthritis Research UK (Grants 19536 and
18797), by the Wellcome Trust (grant number 076113) and by the Oxford
Comprehensive Biomedical Research Centre ankylosing spondylitis chronic
disease cohort (theme code: A91202). The Spondyloarthritis Research
Consortium of Canada (SPARCC) was funded by a National Research
Initiative Award from the Arthritis Society (Canada). G. P. T. was
funded by a Lions Medical Research Foundation fellowship. M. A. B. is
funded by a National Health and Medical Research Council (Australia)
Principal Research Fellowship, and support for this study was received
from a National Health and Medical Research Council (Australia) program
grant (566938) and project grant (569829) and from the Australian Cancer
Research Foundation and Rebecca Cooper Medical Research Foundation. P.
Donnelly was supported in part by a Wolfson-Royal Society Merit Award.
We are also very grateful for the invaluable support received from the
National Ankylosing Spondylitis Society (UK) and Spondyloarthritis
Association of America in case recruitment. Additional financial and
technical support for subject recruitment was provided by the National
Institute for Health Research (NIHR), Oxford Musculoskeletal Biomedical
Research Unit and NIHR Thames Valley Comprehensive Local Research
Network. We acknowledge use of the British 1958 Birth Cohort DNA
collection, funded by the Medical Research Council grant G0000934 and
the Wellcome Trust grant 068545/Z/02, and we thank W. Bodmer and B.
Winney for use of the People of the British Isles DNA collection, which
was funded by the Wellcome Trust. We would like to thank A. Mathieu
(Cagliari University) and S. Brown (Cedars-Sinai Hospital) for providing
samples. The Structural Genomics Consortium is a registered charity
(number 1097737) that receives funds from the Canadian Institutes for
Health Research, the Canadian Foundation for Innovation, Genome Canada
through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska
Institutet, the Knut and Alice Wallenberg Foundation, the Ontario
Innovation Trust, the Ontario Ministry for Research and Innovation,
Merck & Co., Inc., the Novartis Research Foundation, the Swedish Agency
for Innovation Systems, the Swedish Foundation for Strategic Research
and the Wellcome Trust.
NR 51
TC 306
Z9 315
U1 5
U2 53
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD AUG
PY 2011
VL 43
IS 8
BP 761
EP U67
DI 10.1038/ng.873
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 798CD
UT WOS:000293178300012
PM 21743469
ER
PT J
AU Kote-Jarai, Z
Al Olama, AA
Giles, GG
Severi, G
Schleutker, J
Weischer, M
Campa, D
Riboli, E
Key, T
Gronberg, H
Hunter, DJ
Kraft, P
Thun, MJ
Ingles, S
Chanock, S
Albanes, D
Hayes, RB
Neal, DE
Hamdy, FC
Donovan, JL
Pharoah, P
Schumacher, F
Henderson, BE
Stanford, JL
Ostrander, EA
Sorensen, KD
Dork, T
Andriole, G
Dickinson, JL
Cybulski, C
Lubinski, J
Spurdle, A
Clements, JA
Chambers, S
Aitken, J
Gardiner, RAF
Thibodeau, SN
Schaid, D
John, EM
Maier, C
Vogel, W
Cooney, KA
Park, JY
Cannon-Albright, L
Brenner, H
Habuchi, T
Zhang, HW
Lu, YJ
Kaneva, R
Muir, K
Benlloch, S
Leongamornlert, DA
Saunders, EJ
Tymrakiewicz, M
Mahmud, N
Guy, M
O'Brien, LT
Wilkinson, RA
Hall, AL
Sawyer, EJ
Dadaev, T
Morrison, J
Dearnaley, DP
Horwich, A
Huddart, RA
Khoo, VS
Parker, CC
Van As, N
Woodhouse, CJ
Thompson, A
Christmas, T
Ogden, C
Cooper, CS
Lophatonanon, A
Southey, MC
Hopper, JL
English, DR
Wahlfors, T
Tammela, TLJ
Klarskov, P
Nordestgaard, BG
Roder, MA
Tybjaerg-Hansen, A
Bojesen, SE
Travis, R
Canzian, F
Kaaks, R
Wiklund, F
Aly, M
Lindstrom, S
Diver, WR
Gapstur, S
Stern, MC
Corral, R
Virtamo, J
Cox, A
Haiman, CA
Le Marchand, L
FitzGerald, L
Kolb, S
Kwon, EM
Karyadi, DM
Orntoft, TF
Borre, M
Meyer, A
Serth, J
Yeager, M
Berndt, SI
Marthick, JR
Patterson, B
Wokolorczyk, D
Batra, J
Lose, F
McDonnell, SK
Joshi, AD
Shahabi, A
Rinckleb, AE
Ray, A
Sellers, TA
Lin, HY
Stephenson, RA
Farnham, J
Muller, H
Rothenbacher, D
Tsuchiya, N
Narita, S
Cao, GW
Slavov, C
Mitev, V
Easton, DF
Eeles, RA
AF Kote-Jarai, Zsofia
Al Olama, Ali Amin
Giles, Graham G.
Severi, Gianluca
Schleutker, Johanna
Weischer, Maren
Campa, Daniele
Riboli, Elio
Key, Tim
Gronberg, Henrik
Hunter, David J.
Kraft, Peter
Thun, Michael J.
Ingles, Sue
Chanock, Stephen
Albanes, Demetrius
Hayes, Richard B.
Neal, David E.
Hamdy, Freddie C.
Donovan, Jenny L.
Pharoah, Paul
Schumacher, Fredrick
Henderson, Brian E.
Stanford, Janet L.
Ostrander, Elaine A.
Sorensen, Karina Dalsgaard
Dork, Thilo
Andriole, Gerald
Dickinson, Joanne L.
Cybulski, Cezary
Lubinski, Jan
Spurdle, Amanda
Clements, Judith A.
Chambers, Suzanne
Aitken, Joanne
Gardiner, R. A. Frank
Thibodeau, Stephen N.
Schaid, Dan
John, Esther M.
Maier, Christiane
Vogel, Walther
Cooney, Kathleen A.
Park, Jong Y.
Cannon-Albright, Lisa
Brenner, Hermann
Habuchi, Tomonori
Zhang, Hong-Wei
Lu, Yong-Jie
Kaneva, Radka
Muir, Ken
Benlloch, Sara
Leongamornlert, Daniel A.
Saunders, Edward J.
Tymrakiewicz, Malgorzata
Mahmud, Nadiya
Guy, Michelle
O'Brien, Lynne T.
Wilkinson, Rosemary A.
Hall, Amanda L.
Sawyer, Emma J.
Dadaev, Tokhir
Morrison, Jonathan
Dearnaley, David P.
Horwich, Alan
Huddart, Robert A.
Khoo, Vincent S.
Parker, Christopher C.
Van As, Nicholas
Woodhouse, Christopher J.
Thompson, Alan
Christmas, Tim
Ogden, Chris
Cooper, Colin S.
Lophatonanon, Aritaya
Southey, Melissa C.
Hopper, John L.
English, Dallas R.
Wahlfors, Tiina
Tammela, Teuvo L. J.
Klarskov, Peter
Nordestgaard, Borge G.
Roder, M. Andreas
Tybjaerg-Hansen, Anne
Bojesen, Stig E.
Travis, Ruth
Canzian, Federico
Kaaks, Rudolf
Wiklund, Fredrik
Aly, Markus
Lindstrom, Sara
Diver, W. Ryan
Gapstur, Susan
Stern, Mariana C.
Corral, Roman
Virtamo, Jarmo
Cox, Angela
Haiman, Christopher A.
Le Marchand, Loic
FitzGerald, Liesel
Kolb, Suzanne
Kwon, Erika M.
Karyadi, Danielle M.
Orntoft, Torben Falck
Borre, Michael
Meyer, Andreas
Serth, Juergen
Yeager, Meredith
Berndt, Sonja I.
Marthick, James R.
Patterson, Briony
Wokolorczyk, Dominika
Batra, Jyotsna
Lose, Felicity
McDonnell, Shannon K.
Joshi, Amit D.
Shahabi, Ahva
Rinckleb, Antje E.
Ray, Ana
Sellers, Thomas A.
Lin, Hui-Yi
Stephenson, Robert A.
Farnham, James
Muller, Heiko
Rothenbacher, Dietrich
Tsuchiya, Norihiko
Narita, Shintaro
Cao, Guang-Wen
Slavov, Chavdar
Mitev, Vanio
Easton, Douglas F.
Eeles, Rosalind A.
CA UK Genetic Prostate Canc Study Col
UK ProtecT Study Collaborators
Australian Prostate Canc BioResour
PRACTCTICAL Consortium
TI Seven prostate cancer susceptibility loci identified by a multi-stage
genome-wide association study
SO NATURE GENETICS
LA English
DT Article
ID SEQUENCE VARIANTS; HEIGHT; FGF10
AB Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 x 10(-8) to P = 2.7 x 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining similar to 25% of the familial risk in this disease, have now been identified.
C1 [Kote-Jarai, Zsofia; Leongamornlert, Daniel A.; Saunders, Edward J.; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Guy, Michelle; O'Brien, Lynne T.; Wilkinson, Rosemary A.; Hall, Amanda L.; Sawyer, Emma J.; Dadaev, Tokhir; Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Cooper, Colin S.; Eeles, Rosalind A.] Inst Canc Res, Surrey, England.
[Al Olama, Ali Amin; Pharoah, Paul; Benlloch, Sara; Morrison, Jonathan; Easton, Douglas F.] Univ Cambridge, Strangeways Lab, Ctr Canc Genet Epidemiol, Cambridge, England.
[Giles, Graham G.; Severi, Gianluca; English, Dallas R.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia.
[Giles, Graham G.; Severi, Gianluca; Hopper, John L.; English, Dallas R.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Carlton, Vic 3053, Australia.
[Schleutker, Johanna] Univ Tampere, Inst Biomed Technol, FIN-33101 Tampere, Finland.
[Schleutker, Johanna] Tampere Univ Hosp, Ctr Lab Med, Tampere, Finland.
[Weischer, Maren] Herlev Univ Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.
[Campa, Daniele; Canzian, Federico; Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.
[Key, Tim; Travis, Ruth] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
[Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Hunter, David J.; Kraft, Peter; Lindstrom, Sara] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Thun, Michael J.; Diver, W. Ryan; Gapstur, Susan] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Chanock, Stephen; Albanes, Demetrius; Yeager, Meredith; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA.
[Chanock, Stephen] NCI, Core Genotyping Facil, SAIC Frederick Inc, NIH, Gaithersburg, MD USA.
[Hayes, Richard B.] NYU, Dept Environm Med, Div Epidemiol, Langone Med Ctr,Canc Inst, New York, NY 10016 USA.
[Neal, David E.] Univ Cambridge, Addenbrookes Hosp, Cambridge CB2 2QQ, England.
[Neal, David E.] Canc Res UK Cambridge Res Inst, Li Ka Shing Ctr, Cambridge, England.
[Hamdy, Freddie C.] Univ Oxford, Nuffield Dept Surg, Oxford, England.
[Hamdy, Freddie C.] Univ Oxford, John Radcliffe Hosp, Fac Med Sci, Oxford OX3 9DU, England.
[Donovan, Jenny L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Schumacher, Fredrick; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Stanford, Janet L.; FitzGerald, Liesel; Kolb, Suzanne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Stanford, Janet L.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA.
[Ostrander, Elaine A.; Kwon, Erika M.; Karyadi, Danielle M.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Sorensen, Karina Dalsgaard; Orntoft, Torben Falck] Aarhus Univ Hosp, Dept Mol Med, Skejby, Denmark.
[Dork, Thilo; Meyer, Andreas; Serth, Juergen] Hannover Med Sch, D-3000 Hannover, Germany.
[Andriole, Gerald] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Dickinson, Joanne L.; Marthick, James R.; Patterson, Briony] Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas, Australia.
[Cybulski, Cezary; Lubinski, Jan; Wokolorczyk, Dominika] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
[Spurdle, Amanda; Lose, Felicity] Queensland Inst Med Res, Mol Canc Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Clements, Judith A.; Batra, Jyotsna] Queensland Univ Technol, Australian Prostate Canc Res Ctr Queensland, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
[Clements, Judith A.; Batra, Jyotsna] Queensland Univ Technol, Sch Life Sci, Brisbane, Qld 4001, Australia.
[Clements, Judith A.; Batra, Jyotsna] Queensland Univ Technol, Sch Publ Hlth, Brisbane, Qld 4001, Australia.
[Chambers, Suzanne] Griffith Univ, Griffith Hlth Inst, Gold Coast, Qld, Australia.
[Aitken, Joanne] Canc Council Queensland, Viertel Ctr Res Canc Control, Brisbane, Qld, Australia.
[Gardiner, R. A. Frank] Univ Queensland, Clin Res Ctr, Brisbane, Qld, Australia.
[Thibodeau, Stephen N.; Schaid, Dan; McDonnell, Shannon K.] Mayo Clin, Rochester, MN USA.
[John, Esther M.; Joshi, Amit D.; Shahabi, Ahva] Canc Prevent Inst Calif, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Maier, Christiane; Rinckleb, Antje E.] Univ Hosp Ulm, Dept Urol, Ulm, Germany.
[Maier, Christiane; Vogel, Walther; Rinckleb, Antje E.] Univ Hosp Ulm, Inst Human Genet, Ulm, Germany.
[Cooney, Kathleen A.; Ray, Ana] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Cooney, Kathleen A.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI USA.
[Park, Jong Y.; Sellers, Thomas A.; Lin, Hui-Yi] Univ S Florida, H Lee Moffitt Canc Ctr, Div Canc Prevent & Control, Tampa, FL 33682 USA.
[Cannon-Albright, Lisa; Farnham, James] Univ Utah, Sch Med, Dept Internal Med, Div Genet Epidemiol, Salt Lake City, UT USA.
[Cannon-Albright, Lisa] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA.
[Brenner, Hermann; Muller, Heiko; Rothenbacher, Dietrich] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany.
[Habuchi, Tomonori; Tsuchiya, Norihiko; Narita, Shintaro] Akita Univ, Grad Sch Med, Dept Urol, Akita 010, Japan.
[Zhang, Hong-Wei; Cao, Guang-Wen] Second Mil Med Univ, Dept Epidemiol, Shanghai, Peoples R China.
[Lu, Yong-Jie] Queen Mary Univ London, Barts Canc Inst, Ctr Mol Oncol & Imaging, London, England.
[Kaneva, Radka; Mitev, Vanio] Med Univ Sofia, Mol Med Ctr, Sofia, Bulgaria.
[Kaneva, Radka; Mitev, Vanio] Med Univ Sofia, Dept Med Chem & Biochem, Sofia, Bulgaria.
[Muir, Ken; Lophatonanon, Aritaya] Univ Warwick, Coventry CV4 7AL, W Midlands, England.
[Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Van As, Nicholas; Woodhouse, Christopher J.; Thompson, Alan; Christmas, Tim; Ogden, Chris; Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv Fdn Trust, London, England.
[Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Van As, Nicholas; Woodhouse, Christopher J.; Thompson, Alan; Christmas, Tim; Ogden, Chris; Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv Fdn Trust, Surrey, England.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia.
[Wahlfors, Tiina; Tammela, Teuvo L. J.] Tampere Univ Hosp, Dept Urol, Tampere, Finland.
[Wahlfors, Tiina; Tammela, Teuvo L. J.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Klarskov, Peter] Copenhagen Univ Hosp, Herlev Hosp, Dept Urol, Herlev, Denmark.
[Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark.
[Roder, M. Andreas] Copenhagen Univ Hosp, Rigshosp, Dept Urol, Copenhagen, Denmark.
[Tybjaerg-Hansen, Anne; Bojesen, Stig E.] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
[Aly, Markus] Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Div Urol, Stockholm, Sweden.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Cox, Angela] Univ Sheffield, Dept Oncol, Sheffield, S Yorkshire, England.
[Le Marchand, Loic] Univ Hawaii, John A Burns Sch Med, Dept Med, Program Epidemiol,Canc Ctr, Honolulu, HI 96822 USA.
[Borre, Michael] Aarhus Univ Hosp, Dept Urol, Skejby, Denmark.
[Stephenson, Robert A.] Huntsman Canc Inst, Salt Lake City, UT USA.
[Slavov, Chavdar] Med Univ Sofia, Dept Urol, Sofia, Bulgaria.
[Slavov, Chavdar] Med Univ Sofia, Aleksandrovska Univ Hosp, Sofia, Bulgaria.
RP Eeles, RA (reprint author), Inst Canc Res, Surrey, England.
EM rosalind.eeles@icr.ac.uk
RI Campa, Daniele/K-1617-2016; Brenner, Hermann/B-4627-2017; Batra,
Jyotsna/B-4130-2011; Dork, Thilo/J-8620-2012; Albanes,
Demetrius/B-9749-2015; Dickinson, Joanne/J-7728-2014; Chambers,
Suzanne/H-5957-2012; Spurdle, Amanda/A-4978-2011;
OI Campa, Daniele/0000-0003-3220-9944; Brenner,
Hermann/0000-0002-6129-1572; Dadaev, Tokhir/0000-0002-8268-0438;
Saunders, Ed/0000-0003-4343-3570; van As, Nicholas/0000-0001-6829-8788;
Lose, Felicity/0000-0001-8337-3547; Roder, Martin
Andreas/0000-0002-0019-5333; Eeles, Rosalind/0000-0002-3698-6241;
Spurdle, Amanda/0000-0003-1337-7897; Farnham, James/0000-0002-8213-949X;
Neal, David/0000-0002-6033-5086; Leongamornlert,
Daniel/0000-0002-3486-3168; Hayes, Richard/0000-0002-0918-661X;
albright, lisa/0000-0003-2602-3668; Cox, Angela/0000-0002-5138-1099;
Giles, Graham/0000-0003-4946-9099; Sorensen, Karina
Dalsgaard/0000-0002-4902-5490; Clements, Judith/0000-0001-6026-1964;
English, Dallas/0000-0001-7828-8188; Ostrander,
Elaine/0000-0001-6075-9738
FU Cancer Research UK [10118, 10124, 10588, A10119, A10124]; Medical
Research Council [G0900871]; NCI NIH HHS [R01 CA128813, P30 CA042014,
R01 CA056678, R01 CA072818, R01 CA082664, R01 CA084979, R01 CA092579]
NR 23
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD AUG
PY 2011
VL 43
IS 8
BP 785
EP U96
DI 10.1038/ng.882
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 798CD
UT WOS:000293178300015
PM 21743467
ER
PT J
AU Bello, EP
Mateo, Y
Gelman, DM
Noain, D
Shin, JH
Low, MJ
Alvarez, VA
Lovinger, DM
Rubinstein, M
AF Bello, Estefania P.
Mateo, Yolanda
Gelman, Diego M.
Noain, Daniela
Shin, Jung H.
Low, Malcolm J.
Alvarez, Veronica A.
Lovinger, David M.
Rubinstein, Marcelo
TI Cocaine supersensitivity and enhanced motivation for reward in mice
lacking dopamine D-2 autoreceptors
SO NATURE NEUROSCIENCE
LA English
DT Article
ID RECEPTOR-DEFICIENT MICE; CONDITIONED PLACE PREFERENCE; D2 RECEPTORS;
FEEDBACK MECHANISM; LOCOMOTOR-ACTIVITY; MUTANT MICE; RELEASE; MOUSE;
TRANSPORTER; ABSENCE
AB Dopamine (DA) D-2 receptors expressed in DA neurons (D-2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D-2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in vivo contribution of D-2 autoreceptors to DA-mediated behaviors. We found that midbrain DA neurons from mice deficient in D-2 autoreceptors (Drd2(loxP/loxP); Dat(+/IRES-cre), referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D-2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D-2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine.
C1 [Bello, Estefania P.; Gelman, Diego M.; Noain, Daniela; Rubinstein, Marcelo] Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol, Buenos Aires, DF, Argentina.
[Mateo, Yolanda; Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, US Natl Inst Hlth, Bethesda, MD USA.
[Shin, Jung H.; Alvarez, Veronica A.] NIAAA, Sect Neuronal Struct, Lab Integrat Neurosci, US Natl Inst Hlth, Bethesda, MD USA.
[Low, Malcolm J.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI USA.
[Rubinstein, Marcelo] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Buenos Aires, DF, Argentina.
RP Rubinstein, M (reprint author), Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol, Buenos Aires, DF, Argentina.
EM mrubins@dna.uba.ar
RI Alvarez, Veronica /E-9745-2015
OI Alvarez, Veronica /0000-0003-2611-8675
FU Howard Hughes Medical Institute; Universidad de Buenos Aires; Agencia
Nacional de Promocion Cientifica y Tecnologica; National Science
Foundation [INT-9901278]; US National Institutes of Health
[R01-MH61326]; Consejo Nacional de Investigaciones Cientificas y
Tecnicas, Argentina; Division of Intramural Clinical and Biological
Research of the National Institute on Alcohol Abuse and Alcoholism;
National Institute of Neurological Disorders and Stroke
FX We thank J. Sztein, G. Levin, C. Backman, V. Rodriguez, R. Lorenzo, S.
Nemirovsky, M. Peper, S. Merani, C. Carbone, F. Maschi and M. Baetscher
for their scientific and technical assistance. This work was supported
in part by an International Research Scholar Grant of the Howard Hughes
Medical Institute (M.R.), Universidad de Buenos Aires (M.R.) and Agencia
Nacional de Promocion Cientifica y Tecnologica (M.R.), National Science
Foundation grant INT-9901278 (M.J.L. and M.R.) and US National
Institutes of Health grant R01-MH61326 (M.J.L.). E.P.B., D.N. and D.M.G.
received doctoral fellowships from the Consejo Nacional de
Investigaciones Cientificas y Tecnicas, Argentina. Y.M., J.H.S., V.A.A.
and D.M.L. were supported by the Division of Intramural Clinical and
Biological Research of the National Institute on Alcohol Abuse and
Alcoholism. J.H.S. and V.A.A. received support from the Intramural
Program of the National Institute of Neurological Disorders and Stroke.
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD AUG
PY 2011
VL 14
IS 8
BP 1033
EP U128
DI 10.1038/nn.2862
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 797KC
UT WOS:000293123700017
PM 21743470
ER
PT J
AU Driscoll, I
Espeland, MA
Wassertheil-Smoller, S
Gaussoin, SA
Ding, JZ
Granek, IA
Ockene, JK
Phillips, LS
Yaffe, K
Resnick, SM
AF Driscoll, Ira
Espeland, Mark A.
Wassertheil-Smoller, Sylvia
Gaussoin, Sarah A.
Ding, Jingzhong
Granek, Iris A.
Ockene, Judith K.
Phillips, Lawrence S.
Yaffe, Kristine
Resnick, Susan M.
CA Women's Hlth Initiative Study
TI Weight Change and Cognitive Function: Findings From the Women's Health
Initiative Study of Cognitive Aging
SO OBESITY
LA English
DT Article
ID BODY-MASS INDEX; MIDLIFE BLOOD-PRESSURE; VASCULAR RISK-FACTORS;
ALZHEIMER-DISEASE; POSTMENOPAUSAL WOMEN; INCIDENT DEMENTIA;
OLDER-ADULTS; OBESITY; ADIPOSITY; HYPERTENSION
AB Although studies exploring relationships between obesity and cognitive impairment in the elderly are conflicting, literature suggests that overweight and obesity may be protective against cognitive impairment and dementia in older women. We examine the associations between changes in weight and waist circumference (WC) with global and domain-specific cognitive function in a large, well-defined cohort of 2,283 older, postmenopausal women (aged 65-79) prospectively followed through the Women's Health Initiative (WHI) Study of Cognitive Aging (WHISCA). We assessed the associations between changes in weight and WC collected up to 5 years before WHISCA enrollment and mean levels of global and domain-specific cognitive performance across an average of 5.4 years of subsequent follow-up. There was a lack of associations between weight and cognition in women who remained stable or gained weight. The only significant relationships observed were in association with weight loss (P <= 0.05), most likely signaling incipient disease. Moreover, cognition was not related to changes in WC. Relationships were largely independent of initial BMI, self-reported caloric intake or dieting. The lack of associations between weight gain and cognition in women is consistent with the existing literature.
C1 [Driscoll, Ira; Resnick, Susan M.] NIA, Lab Personal & Cognit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Espeland, Mark A.; Gaussoin, Sarah A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Ding, Jingzhong] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA.
[Granek, Iris A.] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA.
[Ockene, Judith K.] Univ Massachusetts, Div Prevent & Behav Med, Worcester, MA 01605 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Phillips, Lawrence S.] Emory Univ, Sch Med, Div Endocrinol, Atlanta, GA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Driscoll, I (reprint author), NIA, Lab Personal & Cognit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM driscolli@mail.nih.gov; resnicks@mail.nih.gov
FU National Institute on Aging [N01-AG-9-2115]; National Institutes of
Health, National Institute on Aging; National Heart, Lung, and Blood
Institute, National Institutes of Health, U.S. Department of Health and
Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13,
32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; National
Institute on Aging, National Institutes of Health
FX Funding/-support: WHISCA is funded by the National Institute on Aging
Contract N01-AG-9-2115 and is supported in part by the Intramural
Research Program of the National Institutes of Health, National
Institute on Aging. The WHI program is funded by the National Heart,
Lung, and Blood Institute, National Institutes of Health, U.S.
Department of Health and Human Services, through Contracts N01WH22110,
24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
42107-26, 42129-32, and 44221. Wyeth Pharmaceuticals, Inc., St Davids,
Pennsylvania, provided the active and placebo hormone therapy
formulations. Drs Driscoll and Resnick are supported by the Intramural
Research Program, National Institute on Aging, National Institutes of
Health.
NR 40
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U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD AUG
PY 2011
VL 19
IS 8
BP 1595
EP 1600
DI 10.1038/oby.2011.23
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 797XI
UT WOS:000293163000009
PM 21394095
ER
PT J
AU Wang, GJ
Geliebter, A
Volkow, ND
Telang, FW
Logan, J
Jayne, MC
Galanti, K
Selig, PA
Han, H
Zhu, W
Wong, CT
Fowler, JS
AF Wang, Gene-Jack
Geliebter, Allan
Volkow, Nora D.
Telang, Frank W.
Logan, Jean
Jayne, Millard C.
Galanti, Kochavi
Selig, Peter A.
Han, Hao
Zhu, Wei
Wong, Christopher T.
Fowler, Joanna S.
TI Enhanced Striatal Dopamine Release During Food Stimulation in Binge
Eating Disorder
SO OBESITY
LA English
DT Article
ID TEST MEAL INTAKE; DORSAL STRIATUM; ORBITOFRONTAL CORTEX; HUMAN BRAIN;
RAT MODEL; REWARD; OBESITY; RESTRICTION; EATERS; METABOLISM
AB Subjects with binge eating disorder (BED) regularly consume large amounts of food in short time periods. The neurobiology of BED is poorly understood. Brain dopamine, which regulates motivation for food intake, is likely to be involved. We assessed the involvement of brain dopamine in the motivation for food consumption in binge eaters. Positron emission tomography (PET) scans with [(11)C]raclopride were done in 10 obese BED and 8 obese subjects without BED. Changes in extracellular dopamine in the striatum in response to food stimulation in food-deprived subjects were evaluated after placebo and after oral methylphenidate (MPH), a drug that blocks the dopamine reuptake transporter and thus amplifies dopamine signals. Neither the neutral stimuli (with or without MPH) nor the food stimuli when given with placebo increased extracellular dopamine. The food stimuli when given with MPH significantly increased dopamine in the caudate and putamen in the binge eaters but not in the nonbinge eaters. Dopamine increases in the caudate were significantly correlated with the binge eating scores but not with BMI. These results identify dopamine neurotransmission in the caudate as being of relevance to the neurobiology of BED. The lack of correlation between BMI and dopamine changes suggests that dopamine release per se does not predict BMI within a group of obese individuals but that it predicts binge eating.
C1 [Wang, Gene-Jack; Logan, Jean; Wong, Christopher T.; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Wang, Gene-Jack; Fowler, Joanna S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Geliebter, Allan; Galanti, Kochavi; Selig, Peter A.] Columbia Univ, St Lukes Roosevelt Hosp, New York Obes Res Ctr, New York, NY USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
[Volkow, Nora D.; Telang, Frank W.; Jayne, Millard C.] NIAAA, Bethesda, MD USA.
[Han, Hao; Zhu, Wei] SUNY Stony Brook, Dept Stat & Appl Math, Stony Brook, NY 11794 USA.
RP Wang, GJ (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
EM gjwang@bnl.gov
RI Han, Hao/D-5618-2015;
OI Han, Hao/0000-0002-9387-7279; Logan, Jean/0000-0002-6993-9994
FU National Institute of Health [R01DA6278, R01DA06891]; National Institute
on Alcoholism and Alcohol Abuse [Z01AA000550, M01RR10710]; Orexigen
Therapeutics Inc.; [R01DK068603]; [R001DK074046]
FX The positron emission tomography (PET) study was carried out at
Brookhaven National Laboratory with infrastructure support from the U.S.
Department of Energy OBER (DE-ACO2-76CH00016) and under support in part
by the National Institute of Health: R01DA6278 (G.-J.W.), R01DA06891
(G.-J.W), Intramural Research Program of the National Institute on
Alcoholism and Alcohol Abuse, Z01AA000550 (N.D.V., F.T., M.J.) and
M01RR10710 (the General Clinical Research Center of Stony Brook
University). The study components at St Luke's-Roosevelt Hospital were
supported in part by R01DK068603 (A.G.) and R001DK074046 (A. G.). The
recruitment and psychological screening were at St Luke's-Roosevelt
Hospital. We thank David Schlyer and Michael Schueller for cyclotron
operations; Donald Warner, David Alexoff and Paul Vaska for PET
operations; Richard Ferrieri, Colleen Shea, Youwen Xu, Lisa Muench and
Payton King for radiotracer preparation and analysis, Karen
Apelskog-Torres for study protocol preparation, and Barbara Hubbard and
Pauline Carter for patient care.; G.-J.W. reports having received
lecture fees from and research funding from Orexigen Therapeutics Inc.;
J.S.F., A.G., K.G., H.H., M.J., J.L., P.S., F.T., N.D.V., C.T.W., W.Z.
declared no conflict of interest.
NR 40
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD AUG
PY 2011
VL 19
IS 8
BP 1601
EP 1608
DI 10.1038/oby.2011.27
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 797XI
UT WOS:000293163000010
PM 21350434
ER
PT J
AU Shea, MK
Nicklas, BJ
Marsh, AP
Houston, DK
Miller, GD
Isom, S
Miller, ME
Carr, JJ
Lyles, MF
Harris, TB
Kritchevsky, SB
AF Shea, M. Kyla
Nicklas, Barbara J.
Marsh, Anthony P.
Houston, Denise K.
Miller, Gary D.
Isom, Scott
Miller, Michael E.
Carr, J. Jeffrey
Lyles, Mary F.
Harris, Tamara B.
Kritchevsky, Stephen B.
TI The Effect of Pioglitazone and Resistance Training on Body Composition
in Older Men and Women Undergoing Hypocaloric Weight Loss
SO OBESITY
LA English
DT Article
ID EPICARDIAL FAT THICKNESS; TYPE-2 DIABETIC-PATIENTS; ABDOMINAL FAT;
PERICARDIAL FAT; MUSCLE MASS; INSULIN SENSITIVITY; METABOLIC SYNDROME;
AEROBIC EXERCISE; OBESITY; REDUCTION
AB Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPAR.-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65-79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 +/- 3.8 kg/m(2)) and women (n = 40, BMI = 33.3 +/- 4.9 kg/m(2)) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 x 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (-1,160 vs. -647 cm(3), P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (-104 vs. -298 cm(3), P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: -43 vs. -88 cm(3), P = 0.005; women: -34 vs. -59 cm(3), P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.
C1 [Shea, M. Kyla; Nicklas, Barbara J.; Houston, Denise K.; Lyles, Mary F.; Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC 27103 USA.
[Marsh, Anthony P.; Miller, Gary D.] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA.
[Isom, Scott; Miller, Michael E.; Carr, J. Jeffrey] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Kritchevsky, SB (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC 27103 USA.
EM skritche@wfubmc.edu
RI Carr, John/A-1938-2012;
OI Carr, John/0000-0002-4398-8237; Kritchevsky, Stephen/0000-0003-3336-6781
FU Wake Forest University Claude D. Pepper Older Americans Independence
Center [P30-AG21332]; Takeda Pharmaceuticals North America
FX This work was supported by the Wake Forest University Claude D. Pepper
Older Americans Independence Center (P30-AG21332) and Takeda
Pharmaceuticals North America. The authors declared no conflict of
interest.
NR 41
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U1 5
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD AUG
PY 2011
VL 19
IS 8
BP 1636
EP 1646
DI 10.1038/oby.2010.327
PG 11
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 797XI
UT WOS:000293163000015
PM 21233810
ER
PT J
AU Schmidt, LS
Thomsen, M
Weikop, P
Dencker, D
Wess, J
Woldbye, DPD
Wortwein, G
Fink-Jensen, A
AF Schmidt, Lene S.
Thomsen, Morgane
Weikop, Pia
Dencker, Ditte
Wess, Juergen
Woldbye, David P. D.
Wortwein, Gitta
Fink-Jensen, Anders
TI Increased cocaine self-administration in M-4 muscarinic acetylcholine
receptor knockout mice
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Acetylcholine; Muscarinic; M-4; Knockout; Self-administration; Cocaine
ID MUTANT MICE; RAT-BRAIN; OUT MICE; DOPAMINE; ADDICTION; PHENOTYPE;
SHIRPA; MOUSE; D1; M4
AB Rationale The reinforcing effects of cocaine are mediated by the mesolimbic dopamine system. Behavioral and neurochemical studies have shown that the cholinergic muscarinic M-4 receptor subtype plays an important role in regulation of dopaminergic neurotransmission.
Objectives Here we investigated for the first time the involvement of M-4 receptors in the reinforcing effects of cocaine using chronic intravenous cocaine self-administration in extensively backcrossed M-4 receptor knockout (M-4(-/-)) mice.
Methods We evaluated acquisition of cocaine self-administration in experimentally naive mice. Both cocaine selfadministration and food-maintained operant behavior were evaluated under fixed ratio 1 (FR 1) and progressive ratio (PR) schedules of reinforcement. In addition, cocaine-induced dopamine release and cocaine-induced hyperactivity were evaluated.
Results M-4(-/-) mice earned significantly more cocaine reinforcers and reached higher breaking points than their wildtype littermates (M-4(+/+)) at intermediate doses of cocaine under both FR 1 and PR schedules of reinforcement. Under the PR schedule, M-4(-/-) mice exhibited significantly higher response rates at the lowest liquid food concentration. In accordance with these results, cocaine-induced dopamine efflux in the nucleus accumbens and hyperlocomotion were increased in M-4(-/-) mice compared to M-4(+/+) mice.
Conclusions Our data suggest that M-4 receptors play an important role in regulation of the reward circuitry and may serve as a new target in the medical treatment of drug addiction.
C1 [Fink-Jensen, Anders] Univ Copenhagen, Lab Neuropsychiat, DK-2100 Copenhagen, Denmark.
[Fink-Jensen, Anders] Univ Copenhagen, Psychiat Ctr Copenhagen, DK-2100 Copenhagen, Denmark.
[Schmidt, Lene S.; Weikop, Pia; Dencker, Ditte; Woldbye, David P. D.; Wortwein, Gitta; Fink-Jensen, Anders] Rigshosp Univ Hosp, Lab Neuropsychiat, Copenhagen, Denmark.
[Woldbye, David P. D.] Univ Copenhagen, Dept Neurosci & Pharmacol, DK-2100 Copenhagen, Denmark.
[Thomsen, Morgane] Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02178 USA.
[Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA.
RP Fink-Jensen, A (reprint author), Univ Copenhagen, Lab Neuropsychiat, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.
EM a.fink-jensen@dadlnet.dk
OI Wortwein, Gitta/0000-0001-6981-7885
FU Ivan Nielsen Foundation; Lundbeck Foundation
FX The Ivan Nielsen Foundation and the Lundbeck Foundation supported the
present work. We thank Pernille Clausen for expert technical assistance.
NR 43
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U1 2
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PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD AUG
PY 2011
VL 216
IS 3
BP 367
EP 378
DI 10.1007/s00213-011-2225-4
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 795TO
UT WOS:000292998900006
PM 21373792
ER
PT J
AU Banks, ML
Roma, PG
Folk, JE
Rice, KC
Negus, SS
AF Banks, Matthew L.
Roma, Peter G.
Folk, John E.
Rice, Kenner C.
Negus, S. Stevens
TI Effects of the delta-opioid agonist SNC80 on the abuse liability of
methadone in rhesus monkeys: a behavioral economic analysis
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Self-administration; Methadone; Cocaine; Behavioral economics; SNC80;
Monkey; Demand curve; Mu-opioid; Delta opioid
ID REINFORCING STRENGTH; THERMAL NOCICEPTION; CHOICE PROCEDURE; FOOD
CHOICE; MU; COCAINE; MODULATION; HEROIN; ANTINOCICEPTION; REMIFENTANIL
AB Rationale Delta-opioid agonists enhance the antinociceptive efficacy of methadone and other mu-opioid agonists. However, relatively little is known about the degree to which delta agonists might enhance the abuse-related effects of mu agonists.
Objective This study used a behavioral economic approach to examine effects of the delta agonist SNC80 [(+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N,N-diethylbenzamide] on the reinforcing effects of methadone in a drug self-administration assay. Interactions between SNC80 and cocaine were also examined for comparison.
Methods Rhesus monkeys (n=4), surgically implanted with indwelling intravenous catheters, were tested in two phases. In phase 1, drug self-administration dose-effect curves for methadone (0.0032-0.1 mg/kg/injection (inj)) and cocaine (0.0032-0.32 mg/kg/inj) alone were determined under a fixed-ratio 10 (FR 10) schedule of reinforcement. In phase 2, FR values were increased every 3 days (FR 1-FR 1800) during availability of methadone alone (0.032 mg/kg/inj) and in combination with varying proportions of SNC80 (0.1:1, 0.3:1, and 0.9:1 SNC80/methadone) or of cocaine alone (0.032 mg/kg/inj) and in combination with varying proportions of SNC80 (0.33:1, 1: 1, and 3: 1 SNC80/cocaine). Demand curves related drug intake to FR price, and measures of reinforcement were derived.
Results Methadone and cocaine alone each functioned as a reinforcer. SNC80 did not alter measures of reinforcement for either methadone or cocaine.
Conclusions SNC80 at proportions previously shown to enhance methadone-induced antinociception did not enhance the abuse-related effects of methadone. These results support the proposition that delta agonists may selectively enhance mu agonist analgesic effects without enhancing mu agonist abuse liability.
C1 [Banks, Matthew L.; Negus, S. Stevens] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA.
[Roma, Peter G.] Inst Behav Resources, Baltimore, MD USA.
[Roma, Peter G.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA.
[Folk, John E.; Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, NIH, DHHS, Bethesda, MD 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
RI Banks, Matthew/K-4429-2014
OI Banks, Matthew/0000-0003-4949-5246
FU National Institutes of Health [R01-DA011460, T32-DA007027]
FX We appreciate the technical assistance of Jennifer Gough. This research
was supported by National Institutes of Health grants R01-DA011460 and
T32-DA007027.
NR 33
TC 13
Z9 13
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD AUG
PY 2011
VL 216
IS 3
BP 431
EP 439
DI 10.1007/s00213-011-2235-2
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 795TO
UT WOS:000292998900012
PM 21369752
ER
PT J
AU Albaugh, DL
Rinker, JA
Baumann, MH
Sink, JR
Riley, AL
AF Albaugh, Daniel L.
Rinker, Jennifer A.
Baumann, Michael H.
Sink, Jacquelyn R.
Riley, Anthony L.
TI Rats preexposed to MDMA display attenuated responses to its aversive
effects in the absence of persistent monoamine depletions
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE MDMA; Ecstasy; Conditioned taste-aversion; HPLC; Preexposure; Tolerance;
Behavior; Rats; Male
ID CONDITIONED TASTE-AVERSIONS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA;
METHYLENEDIOXYMETHAMPHETAMINE MDMA; COCAINE PREEXPOSURE; RHESUS-MONKEYS;
ECSTASY MDMA; MORPHINE PREEXPOSURE; DRUG PRETREATMENT; D-AMPHETAMINE;
EXPOSURE
AB Rationale The abuse potential of a given drug may be mediated by both its rewarding and aversive effects, the latter of which are often far less characterized.
Objectives Using the conditioned taste-aversion (CTA) preparation, the present experiments examined changes in the aversive effects of the commonly used recreational drug MDMA following repeated drug exposures.
Methods Experiment 1 used three varying doses of MDMA (1.0, 1.8, and 3.2 mg/kg) to determine a dose that produced taste aversions of intermediate strength. Experiments 2 and 3 characterized the effects of repeated preexposures to MDMA (1.8 or 3.2 mg/kg) on taste aversions induced by MDMA (1.8 mg/kg). Additionally, levels of several monoamines and metabolites were analyzed in frontal cortex and caudate-putamen from subjects in Experiment 3 to assess for persistent monoamine depletions.
Results MDMA induced dose-dependent taste aversions. Preexposure to MDMA (at both doses) resulted in an attenuation of MDMA-induced taste aversions. These effects were not likely due to persistent monoamine depletions, as subjects preexposed to the higher MDMA dose did not differ from controls in levels of monoamines or metabolites in either brain region examined.
Conclusions Prior MDMA experience weakened the ability of MDMA to induce taste aversions. This attenuation of MDMA's aversive effects may occur with low doses that do not persistently alter monoamine levels.
C1 [Albaugh, Daniel L.; Rinker, Jennifer A.; Riley, Anthony L.] American Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA.
[Baumann, Michael H.; Sink, Jacquelyn R.] Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, Baltimore, MD 21224 USA.
RP Albaugh, DL (reprint author), American Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA.
EM albaugh@email.unc.edu
OI Rinker, Jennifer/0000-0003-3738-3693
FU Mellon Foundation; National Institute on Drug Abuse/National Institutes
of Health/Public Health Service/US Department of Health and Human
Services
FX This research was supported by a grant from the Mellon Foundation to A.
L. R. and by intramural funds from the National Institute on Drug
Abuse/National Institutes of Health/Public Health Service/US Department
of Health and Human Services.
NR 77
TC 3
Z9 3
U1 5
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD AUG
PY 2011
VL 216
IS 3
BP 441
EP 449
DI 10.1007/s00213-011-2241-4
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 795TO
UT WOS:000292998900013
PM 21373786
ER
PT J
AU Jansen, SA
AF Jansen, Sanaz A.
TI Ductal Carcinoma In Situ: Detection, Diagnosis, and Characterization
with Magnetic Resonance Imaging
SO SEMINARS IN ULTRASOUND CT AND MRI
LA English
DT Article
ID CONTRAST-ENHANCED MRI; RANDOMIZED CONTROLLED-TRIAL; INVASIVE
BREAST-CARCINOMA; HIGH FAMILIAL RISK; SURGICAL ADJUVANT BREAST;
SKIN-SPARING MASTECTOMY; TRANSGENIC MOUSE MODEL; BRCA MUTATION CARRIERS;
TUMOR SIZE CORRELATION; TERM-FOLLOW-UP
AB Ductal carcinoma in situ (DCIS) is a preinvasive malignancy that currently accounts for over 20% of newly diagnosed breast cancers in the US. This article reviews how clinical magnetic resonance imaging methods are being implemented for the detection, diagnosis and characterization of DCIS. Research strategies that are being pursued to help realize the full potential for magnetic resonance imaging to improve the outcomes of patients diagnosed with DCIS are discussed. Semin Ultrasound CT MRI 32:306-318 (c) 2011 Elsevier Inc. All rights reserved.
C1 NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
RP Jansen, SA (reprint author), NCI, Mouse Canc Genet Program, Bldg 560,Rm 32-24,1050 Boyles St, Frederick, MD 21702 USA.
EM jansensa@mail.nih.gov
NR 143
TC 7
Z9 10
U1 0
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0887-2171
EI 1558-5034
J9 SEMIN ULTRASOUND CT
JI Semin. Ultrasound CT MRI
PD AUG
PY 2011
VL 32
IS 4
BP 306
EP 318
DI 10.1053/j.sult.2011.02.007
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 799TX
UT WOS:000293310100007
PM 21782121
ER
PT J
AU Lu, CX
Cheng, SY
AF Lu, Changxue
Cheng, Sheue-yann
TI Extranuclear signaling of mutated thyroid hormone receptors in promoting
metastatic spread in thyroid carcinogenesis
SO STEROIDS
LA English
DT Review
DE Thyroid hormone receptors; Thyroid hormone receptor mutants; Mouse
model; Thyroid cancer; Carcinogenesis; Extranuclear signaling
ID FOCAL ADHESION KINASE; BETA-RECEPTOR; MOUSE MODEL; INTEGRIN RECEPTOR;
TUMOR PROGRESSION; NUCLEAR RECEPTORS; ACTIN DYNAMICS; CANCER CELLS;
EXPRESSION; CARCINOMA
AB Thyroid hormone receptors (TRs) mediate the critical activities of the thyroid hormone (T3) in growth, development, and differentiation. Decreased expression and/or somatic mutations of TRs have been shown to be associated with several types of human cancers including liver, breast, lung, and thyroid. A direct demonstration that TR beta mutants could function as oncogenes is evidenced by the spontaneous development of follicular thyroid carcinoma similar to human cancer in a knockin mouse model harboring a mutated TR beta (denoted as PV; Thrb(PV/PV) mice). PV is a dominant negative mutation identified in a patient with resistance to thyroid hormone. Analysis of altered gene expression and molecular studies cif thyroid carcinogenesis in Thrb(PV/PV) mice show that the oncogenic activity of PV is mediated by both nucleus-initiated transcription and extranuclear actions to alter gene expression and signaling transduction activity. This article focuses on recent findings of novel extranuclear actions of PV that affect signaling cascades and thereby the invasiveness, migration, and motility of thyroid tumor cells. These findings have led to identification of potential molecular targets for treatment of metastatic thyroid cancer. Published by Elsevier Inc.
C1 [Lu, Changxue; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX We regret any reference omissions due to length limitation. We wish to
thank all colleagues and collaborators who have contributed to the work
described in this review. The present research was supported by the
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health.
NR 52
TC 7
Z9 8
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-128X
EI 1878-5867
J9 STEROIDS
JI Steroids
PD AUG
PY 2011
VL 76
IS 9
SI SI
BP 885
EP 891
DI 10.1016/j.steroids.2011.03.016
PG 7
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 799YH
UT WOS:000293322200011
PM 21473875
ER
PT J
AU Hejtmancik, JF
AF Hejtmancik, J. Fielding
TI Size matters, but how much?
SO TRANSLATIONAL RESEARCH
LA English
DT Editorial Material
C1 [Hejtmancik, J. Fielding] NEI, Rockville, MD USA.
RP Hejtmancik, JF (reprint author), 5635 Fishers Lane,RM 1120, Rockville, MD 20852 USA.
EM f3h@helix.nih.gov
NR 8
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 1931-5244
J9 TRANSL RES
JI Transl. Res.
PD AUG
PY 2011
VL 158
IS 2
BP 82
EP 84
DI 10.1016/j.trsl.2011.03.006
PG 3
WC Medical Laboratory Technology; Medicine, General & Internal; Medicine,
Research & Experimental
SC Medical Laboratory Technology; General & Internal Medicine; Research &
Experimental Medicine
GA 796MH
UT WOS:000293054900002
PM 21757151
ER
PT J
AU Zaghloul, KA
Schramm, J
AF Zaghloul, Kareem A.
Schramm, Johannes
TI Surgical management of glioneuronal tumors with drug-resistant epilepsy
SO ACTA NEUROCHIRURGICA
LA English
DT Review
DE Glioneuronal tumors; Ganglioglioma; DNT; Epilepsy
ID TEMPORAL-LOBE EPILEPSY; DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR;
LONG-TERM SEIZURE; INTRACTABLE EPILEPSY; BRAIN-TUMORS; FOCAL EPILEPSIES;
INTRAOPERATIVE ELECTROCORTICOGRAPHY; EPILEPTOGENIC GANGLIOGLIOMAS;
FUNCTIONAL CONNECTIVITY; CORTICAL DYSPLASIA
AB In this review, we discuss the options for the surgical management of glioneuronal tumors (GNTs) associated with drug-resistant epilepsy, with an emphasis on the surgical issues involved in addressing the epileptogenic nature of these lesions. We briefly summarize the pathological hallmarks of these lesions in order to outline how these tumors contribute to seizure activity. Understanding the pathophysiology of these lesions is important in discussing the advantages and disadvantages of different surgical strategies. There have been a number of studies that have investigated the utility of different surgical approaches in improving seizure outcome, and we highlight some of these studies in order to shed light on surgical issues related to these tumors.
C1 [Schramm, Johannes] Univ Bonn, Dept Neurosurg, D-53105 Bonn, Germany.
[Zaghloul, Kareem A.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Schramm, J (reprint author), Univ Bonn, Dept Neurosurg, Sigmund Freud Str 25, D-53105 Bonn, Germany.
EM Johannes.Schramm@ukb.uni-bonn.de
NR 72
TC 7
Z9 7
U1 0
U2 4
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0001-6268
J9 ACTA NEUROCHIR
JI Acta Neurochir.
PD AUG
PY 2011
VL 153
IS 8
BP 1551
EP 1559
DI 10.1007/s00701-011-1050-1
PG 9
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 794TU
UT WOS:000292925000001
PM 21603887
ER
PT J
AU Mills, JL
Carter, TC
Scott, JM
Troendle, JF
Gibney, ER
Shane, B
Kirke, PN
Ueland, PM
Brody, LC
Molloy, AM
AF Mills, James L.
Carter, Tonia C.
Scott, John M.
Troendle, James F.
Gibney, Eileen R.
Shane, Barry
Kirke, Peadar N.
Ueland, Per M.
Brody, Lawrence C.
Molloy, Anne M.
TI Do high blood folate concentrations exacerbate metabolic abnormalities
in people with low vitamin B-12 status?
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID FOLIC-ACID FORTIFICATION; COGNITIVE IMPAIRMENT; MICROBIOLOGICAL ASSAY;
METHYLMALONIC ACID; TOTAL HOMOCYSTEINE; AUTOMATED-ASSAY; OLDER
AMERICANS; ANEMIA; SERUM; DEFICIENCY
AB Background: In elderly individuals with low serum vitamin B-12, those who have high serum folate have been reported to have greater abnormalities in the following biomarkers for vitamin B-12 deficiency: low hemoglobin and elevated total homocysteine (tHcy) and methylmalonic acid (MMA). This suggests that folate exacerbates vitamin B-12-related metabolic abnormalities.
Objective: We determined whether high serum folate in individuals with low serum vitamin B-12 increases the deleterious effects of low vitamin B-12 on biomarkers of vitamin B-12 cellular function.
Design: In this cross-sectional study, 2507 university students provided data on medical history and exposure to folic acid and vitamin B-12 supplements. Blood was collected to measure serum and red blood cell folate (RCF), hemoglobin, plasma tHcy, and MMA, holotranscobalamin, and ferritin in serum.
Results: In subjects with low vitamin B-12 concentrations (<148 pmol/L), those who had high folate concentrations (>30 nmol/L; group 1) did not show greater abnormalities in vitamin B-12 cellular function in any area than did those with lower folate concentrations (<= 30 nmol/L; group 2). Group 1 had significantly higher holotranscobalamin and RCF, significantly lower tHcy, and nonsignificantly lower (P = 0.057) MMA concentrations than did group 2. The groups did not differ significantly in hemoglobin or ferritin. Compared with group 2, group 1 had significantly higher mean intakes of folic acid and vitamin B-12 from supplements and fortified food.
Conclusions: In this young adult population, high folate concentrations did not exacerbate the biochemical abnormalities related to vitamin B-12 deficiency. These results provide reassurance that folic acid in fortified foods and supplements does not interfere with vitamin B-12 metabolism at the cellular level in a healthy population. Am J Clin Nutr 2011;94:495-500.
C1 [Mills, James L.; Carter, Tonia C.; Troendle, James F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
[Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Scott, John M.; Gibney, Eileen R.; Molloy, Anne M.] Trinity Coll Dublin, Sch Biochem & Immunol, Dublin, Ireland.
[Molloy, Anne M.] Trinity Coll Dublin, Sch Med, Dublin, Ireland.
[Shane, Barry] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Kirke, Peadar N.] Hlth Res Board Ireland, Child Hlth Epidemiol Unit, Dublin, Ireland.
[Ueland, Per M.] Univ Bergen, Pharmacol Sect, Inst Med, Bergen, Norway.
[Ueland, Per M.] Haukeland Hosp, Lab Clin Biochem, N-5021 Bergen, Norway.
RP Mills, JL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
EM jamesmills@nih.gov
RI Ueland, Per/C-7340-2013;
OI Molloy, Anne/0000-0002-1688-9049
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development
FX Supported by the Intramural Research Program of the National Institutes
of Health, Eunice Kennedy Shriver National Institute of Child Health and
Human Development.
NR 17
TC 23
Z9 23
U1 0
U2 6
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 AUG
PY 2011
VL 94
IS 2
BP 495
EP 500
DI 10.3945/ajcn.111.014621
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 794TT
UT WOS:000292924900018
PM 21653798
ER
PT J
AU Muzhingi, T
Gadaga, TH
Siwela, AH
Grusak, MA
Russell, RM
Tang, GW
AF Muzhingi, Tawanda
Gadaga, Tendekayi H.
Siwela, Andrew H.
Grusak, Michael A.
Russell, Robert M.
Tang, Guangwen
TI Yellow maize with high beta-carotene is an effective source of vitamin A
in healthy Zimbabwean men
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID IONIZATION MASS-SPECTROMETRY; ISOTOPE REFERENCE METHOD;
CHEMICAL-IONIZATION; MONGOLIAN GERBILS; CHINESE ADULTS; EQUIVALENCE;
CONVERSION; RETINOL; HUMANS; BIOAVAILABILITY
AB Background: The bioconversion efficiency of yellow maize beta-carotene to retinol in humans is unknown.
Objective: The objective of this study was to determine the vitamin A value of yellow maize beta-carotene in humans.
Design: High beta-carotene-containing yellow maize was grown in a hydroponic medium with 23 atom% (2)H(2)O during grain development. Yellow maize beta-carotene showed the highest abundance of enrichment as [(2)H(9)]beta-carotene. Eight healthy Zimbabwean men volunteered for the study. On day 1 after a fasting blood draw, subjects consumed 300 g yellow maize porridge containing 1.2 mg beta-carotene, 20 g butter, and a 0.5-g corn oil capsule. On day 8, fasting blood was drawn, and subjects consumed 1 mg [(13)C(10)]retinyl acetate in a 0.5-g corn oil capsule and 300 g white maize porridge with 20 g butter. Thirty-six blood samples were collected from each subject over 36 d. Concentrations and enrichments of retinol and beta-carotene in labeled doses and serum were determined with the use of HPLC, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry.
Results: The area under the curve (AUC) of retinol from 1.2 mg yellow maize beta-carotene was 72.9 nmol.d, and the AUC of retinol from 1 mg retinyl acetate (13)C(10) was 161.1 nmol.d. The conversion factor of yellow maize beta-carotene to retinol by weight was 3.2 +/- 1.5 to 1.
Conclusion: In 8 healthy Zimbabwean men, 300 g cooked yellow maize containing 1.2 mg beta-carotene that was consumed with 20.5 g fat showed the same vitamin A activity as 0.38 mg retinol and provided 40-50% of the adult vitamin A Recommended Dietary Allowance. This trial was registered at clinicaltrials.gov as NCT00636038. Am J Clin Nutr 2011;94:510-9.
C1 [Tang, Guangwen] Tufts Univ, Carotenoids & Hlth Lab, Jean Mayer USDA Agr Res Serv Human Nutr Res Ctr A, Boston, MA 02111 USA.
[Gadaga, Tendekayi H.] Univ Swaziland, Dept Environm Hlth Sci, Mbabane, Swaziland.
[Siwela, Andrew H.] Natl Univ Sci & Technol, Dept Appl Biol & Biochem, Bulawayo, Zimbabwe.
[Grusak, Michael A.] Baylor Coll Med, Dept Pediat, USDA Agr Res Serv Childrens Nutr Res Ctr, Houston, TX 77030 USA.
[Russell, Robert M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Tang, GW (reprint author), Tufts Univ, Carotenoids & Hlth Lab, Jean Mayer USDA Agr Res Serv Human Nutr Res Ctr A, Boston, MA 02111 USA.
EM guangwen.tang@tufts.edu
RI Muzhingi, Tawanda/F-2459-2012
FU USDA-Agricultural Research Service [58-1950-9-001, 58-6250-0-008,,
58-1950-7-707]; Nutricia Research Foundation, Netherlands; Pioneer
Hi-Bred International, Johnston, IA; USDA
FX Supported in part by the USDA-Agricultural Research Service, under
Cooperative Agreements 58-1950-9-001, 58-6250-0-008, and 58-1950-7-707
and through funding from the Nutricia Research Foundation, Netherlands,
and Pioneer Hi-Bred International, Johnston, IA.; We thank all the
volunteers who took part in this study in Bulawayo, Zimbabwe; the cooks
and dieticians in the Metabolic Research Unit at USDA-Agricultural
Research Service HNRCA at Tufts University in Boston; David Dworak and
Chee-Ming Li in the Plant Physiology Laboratory at the USDA-Agricultural
Research Service CNRC in Houston, TX; and the nurses and staff at the
National University of Science and Technology, Bulawayo, Zimbabwe. We
also thank our funding agencies, Nutricia Research Foundation in
Netherlands; the USDA; and Pioneer Hi-Bred International, Johnston, IA.
This study was also helped by HarvestPlus research teams at the
International Maize and Wheat Improvement Center in Mexico and by
Torbert Rocheford at Purdue University.
NR 51
TC 34
Z9 34
U1 2
U2 11
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 AUG
PY 2011
VL 94
IS 2
BP 510
EP 519
DI 10.3945/ajcn.110.006486
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 794TT
UT WOS:000292924900020
PM 21715509
ER
PT J
AU Bailey, RL
Carmel, R
Green, R
Pfeiffer, CM
Cogswell, ME
Osterloh, JD
Sempos, CT
Yetley, EA
AF Bailey, Regan L.
Carmel, Ralph
Green, Ralph
Pfeiffer, Christine M.
Cogswell, Mary E.
Osterloh, John D.
Sempos, Christopher T.
Yetley, Elizabeth A.
TI Monitoring of vitamin B-12 nutritional status in the United States by
using plasma methylmalonic acid and serum vitamin B-12
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID TOTAL HOMOCYSTEINE CONCENTRATIONS; COBALAMIN DEFICIENCY;
NATIONAL-HEALTH; BIOCHEMICAL INDICATORS; COGNITIVE IMPAIRMENT; FOLATE
DEFICIENCIES; ELDERLY POPULATION; PREVALENCE; FORTIFICATION; DIAGNOSIS
AB Background: Various definitions, criteria, tests, and cutoffs have been used to define vitamin B-12 status; however, a need exists for the systematic study of vitamin B-12 status in the United States because of concerns about high folic acid intakes and the potential for associated adverse effects.
Objective: The objective was to determine the effect of different cutoff choices on outcomes and of the different degrees of serum vitamin B-12 status, definable by the concurrent use of a functional and circulating marker as the first steps to developing a data-based consensus on the biochemical diagnosis of vitamin B-12 deficiency.
Design: Data from NHANES, a nationally representative cross-sectional survey, were examined for adults aged >19 y (mean +/- SD age: 45 +/- 1 y) from 1999 to 2004 (n = 12,612).
Results: Commonly used cutoffs had a greater effect on prevalence estimates of low vitamin B-12 status with the use of vitamin B-12 than with the use of methylmalonic acid (MMA; 3-26% and 2-6%, respectively). A cutoff of >148 pmol/L for vitamin B-12 and of <= 210 nmol/L for MMA resulted in significant misclassifications. Approximately 1% of adults had a clear vitamin B-12 deficiency (low vitamin B-12 and elevated MMA); 92% of adults had adequate vitamin B-12 status. A high percentage of younger women characterized the group with low vitamin B-12 and normal MMA (2% of adults) and may have falsely reflected low vitamin B-12. Adults with elevated MMA (5%) only were demographically similar (ie, by age and race) to the deficient group and may have included some individuals with early vitamin B-12 deficiency.
Conclusions: These analyses indicate the challenges of assessing vitamin B-12 status when uncertainties exist about the appropriate cutoffs. Future studies should determine definable endpoints to achieve this goal. Am J Clin Nutr 2011;94:552-61.
C1 [Bailey, Regan L.; Sempos, Christopher T.; Yetley, Elizabeth A.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Carmel, Ralph] New York Methodist Hosp, Dept Med, Brooklyn, NY USA.
[Carmel, Ralph] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
[Green, Ralph] Univ Calif Davis, Med Ctr, Dept Pathol & Lab Med, Sacramento, CA 95817 USA.
[Pfeiffer, Christine M.; Osterloh, John D.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA.
[Cogswell, Mary E.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
RP Bailey, RL (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,2B03, Bethesda, MD 20892 USA.
EM baileyr@mail.nih.gov
FU NIH [DK32640]
FX RC was supported by NIH grant DK32640.
NR 46
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U1 3
U2 8
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 AUG
PY 2011
VL 94
IS 2
BP 552
EP 561
DI 10.3945/ajcn.111.015222
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 794TT
UT WOS:000292924900025
PM 21677051
ER
PT J
AU Raiten, DJ
Namaste, S
Brabin, B
Combs, G
L'Abbe, MR
Wasantwisut, E
Darnton-Hill, I
AF Raiten, Daniel J.
Namaste, Sorrel
Brabin, Bernard
Combs, Gerald, Jr.
L'Abbe, Mary R.
Wasantwisut, Emorn
Darnton-Hill, Ian
TI Executive summary-Biomarkers of Nutrition for Development: Building a
Consensus
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID MALNUTRITION
AB The ability to develop evidence-based clinical guidance and effective programs and policies to achieve global health promotion and disease prevention goals depends on the availability of valid and reliable data. With specific regard to the role of food and nutrition in achieving those goals, relevant data are developed with the use of biomarkers that reflect nutrient exposure, status, and functional effect. A need exists to promote the discovery, development, and use of biomarkers across a range of applications. In addition, a process is needed to harmonize the global health community's decision making about what biomarkers are best suited for a given use under specific conditions and settings. To address these needs, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, organized a conference entitled "Biomarkers of Nutrition for Development: Building a Consensus," which was hosted by the International Atomic Energy Agency. Partners included key multilateral, US agencies and public and private organizations. The assembly endorsed the utility of this initiative and the need for the BOND (Biomarkers of Nutrition for Development) project to continue. A consensus was reached on the requirement to develop a process to inform the community about the relative strengths or weaknesses and specific applications of various biomarkers under defined conditions. The articles in this supplement summarize the deliberations of the 4 working groups: research, clinical, policy, and programmatic. Also described are content presentations on the harmonization processes, the evidence base for biomarkers for 5 case-study micronutrients, and new frontiers in science and technology. Am J Clin Nutr 2011; 94(suppl): 633S-50S.
C1 [Raiten, Daniel J.; Namaste, Sorrel] NICHHD, NIH, Bethesda, MD 20892 USA.
[Brabin, Bernard] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England.
[Combs, Gerald, Jr.] USDA, Grand Forks Human Nutr Res Ctr, Grand Forks, ND USA.
[L'Abbe, Mary R.] Univ Toronto, Fac Med, Dept Nutr Sci, Toronto, ON, Canada.
[Wasantwisut, Emorn] Mahidol Univ, Inst Nutr, Phutthamonthon, Nakhon Pathom, Thailand.
[Darnton-Hill, Ian] Univ Sydney, Boden Inst Obes Nutr & Exercise, Sydney, NSW 2006, Australia.
[Darnton-Hill, Ian] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
RP Raiten, DJ (reprint author), NICHHD, NIH, 6100 Execut Blvd,Room 4B-11, Bethesda, MD 20892 USA.
EM raitend@mail.nih.gov
FU Bill and Melinda Gates Foundation [OPP1003253]; PepsiCo
FX Supported by the Bill and Melinda Gates Foundation (grant no.
OPP1003253) and a restricted gift from PepsiCo to the Eunice Kennedy
Shriver National Institute of Child Health and Human Development to
support this meeting.; The authors' responsibilities were as follows-GC:
drafted the Research Working Group (WG) report; BB: drafted the Clinical
WG report; EW: drafted the Program WG report; MRL: drafted the Policy WG
report; DJR and SN: wrote the manuscript; ID-H: reviewed the manuscript;
and DJR: had primary responsibility for final content. The
nongovernmental contributors to this meeting included the Bill and
Melinda Gates Foundation (BMGF) obtained through a competitive
conference grant application process. Once awarded, the BMGF was
informed of the progress of the conference and received a final report
as the required "deliverable.'' Additional support came in the form of a
restricted gift to the NICHD gift fund from PepsiCo to support this
workshop and did not reflect any obligation on the part of the NICHD to
PepsiCo for the planning or outcome of this meeting. The authors
declared no conflicts of interest.
NR 10
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U2 9
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 AUG
PY 2011
VL 94
IS 2
BP 633S
EP 647S
DI 10.3945/ajcn.110.008227
PG 15
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 794TT
UT WOS:000292924900043
PM 21733880
ER
PT J
AU Hamilton, CM
Strader, LC
Pratt, JG
Maiese, D
Hendershot, T
Kwok, RK
Hammond, JA
Huggins, W
Jackman, D
Pan, HQ
Nettles, DS
Beaty, TH
Farrer, LA
Kraft, P
Marazita, ML
Ordovas, JM
Pato, CN
Spitz, MR
Wagener, D
Williams, M
Junkins, HA
Harlan, WR
Ramos, EM
Haines, J
AF Hamilton, Carol M.
Strader, Lisa C.
Pratt, Joseph G.
Maiese, Deborah
Hendershot, Tabitha
Kwok, Richard K.
Hammond, Jane A.
Huggins, Wayne
Jackman, Dean
Pan, Huaqin
Nettles, Destiney S.
Beaty, Terri H.
Farrer, Lindsay A.
Kraft, Peter
Marazita, Mary L.
Ordovas, Jose M.
Pato, Carlos N.
Spitz, Margaret R.
Wagener, Diane
Williams, Michelle
Junkins, Heather A.
Harlan, William R.
Ramos, Erin M.
Haines, Jonathan
TI The PhenX Toolkit: Get the Most From Your Measures
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE environmental exposure; epidemiologic methods; genetic research;
genetics; genome-wide association study; meta-analysis as topic;
phenotype; research design
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; GENETIC-VARIATION;
HUMAN-DISEASES; METAANALYSIS; RISK; DATABASE; TRAITS; LOINC
AB The potential for genome-wide association studies to relate phenotypes to specific genetic variation is greatly increased when data can be combined or compared across multiple studies. To facilitate replication and validation across studies, RTI International (Research Triangle Park, North Carolina) and the National Human Genome Research Institute (Bethesda, Maryland) are collaborating on the consensus measures for Phenotypes and eXposures (PhenX) project. The goal of PhenX is to identify 15 high-priority, well-established, and broadly applicable measures for each of 21 research domains. PhenX measures are selected by working groups of domain experts using a consensus process that includes input from the scientific community. The selected measures are then made freely available to the scientific community via the PhenX Toolkit. Thus, the PhenX Toolkit provides the research community with a core set of high-quality, well-established, low-burden measures intended for use in large-scale genomic studies. PhenX measures will have the most impact when included at the experimental design stage. The PhenX Toolkit also includes links to standards and resources in an effort to facilitate data harmonization to legacy data. Broad acceptance and use of PhenX measures will promote cross-study comparisons to increase statistical power for identifying and replicating variants associated with complex diseases and with gene-gene and gene-environment interactions.
C1 [Hamilton, Carol M.; Strader, Lisa C.; Pratt, Joseph G.; Maiese, Deborah; Hendershot, Tabitha; Hammond, Jane A.; Huggins, Wayne; Jackman, Dean; Pan, Huaqin; Nettles, Destiney S.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Junkins, Heather A.; Ramos, Erin M.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Beaty, Terri H.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial & Dent Genet, Dept Oral Biol, Pittsburgh, PA USA.
[Ordovas, Jose M.] Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Pato, Carlos N.] Univ So Calif, Zilkha Neurogenet Inst, Altadena, CA USA.
[Spitz, Margaret R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Wagener, Diane] RTI Int, San Diego, CA USA.
[Williams, Michelle] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA.
[Harlan, William R.] NIH, Off Director, Chevy Chase, MD USA.
[Haines, Jonathan] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN USA.
[Kwok, Richard K.; Nettles, Destiney S.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
RP Hamilton, CM (reprint author), RTI Int, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA.
EM chamilton@rti.org
RI Haines, Jonathan/C-3374-2012; Strader, Lisa/H-3083-2013; Kwok,
Richard/B-6907-2017;
OI Kwok, Richard/0000-0002-6794-8360; Farrer, Lindsay/0000-0001-5533-4225;
Ordovas, Jose/0000-0002-7581-5680
FU National Human Genome Research Institute [U01 HG004597-01]
FX This work was supported by the National Human Genome Research Institute
(award U01 HG004597-01).
NR 29
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U2 20
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 AUG 1
PY 2011
VL 174
IS 3
BP 253
EP 260
DI 10.1093/aje/kwr193
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 796UG
UT WOS:000293077600001
PM 21749974
ER
PT J
AU Hamilton, CM
Strader, LC
Pratt, JG
Maiese, D
Hendershot, T
Kwok, RK
Hammond, JA
Huggins, W
Jackman, D
Pan, HQ
Nettles, DS
Beaty, TH
Farrer, LA
Kraft, P
Marazita, ML
Ordovas, JM
Pato, CN
Spitz, MR
Wagener, D
Williams, M
Junkins, HA
Harlan, WR
Ramos, EM
Haines, J
AF Hamilton, Carol M.
Strader, Lisa C.
Pratt, Joseph G.
Maiese, Deborah
Hendershot, Tabitha
Kwok, Richard K.
Hammond, Jane A.
Huggins, Wayne
Jackman, Dean
Pan, Huaqin
Nettles, Destiney S.
Beaty, Terri H.
Farrer, Lindsay A.
Kraft, Peter
Marazita, Mary L.
Ordovas, Jose M.
Pato, Carlos N.
Spitz, Margaret R.
Wagener, Diane
Williams, Michelle
Junkins, Heather A.
Harlan, William R.
Ramos, Erin M.
Haines, Jonathan
TI Hamilton et al. Respond to "Consolidating Data Harmonization"
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
C1 [Hamilton, Carol M.; Strader, Lisa C.; Pratt, Joseph G.; Maiese, Deborah; Hendershot, Tabitha; Hammond, Jane A.; Huggins, Wayne; Jackman, Dean; Pan, Huaqin; Nettles, Destiney S.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Junkins, Heather A.; Ramos, Erin M.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Beaty, Terri H.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial & Dent Genet, Dept Oral Biol, Pittsburgh, PA USA.
[Ordovas, Jose M.] Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Pato, Carlos N.] Univ So Calif, Zilkha Neurogenet Inst, Altadena, CA USA.
[Spitz, Margaret R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Wagener, Diane] RTI Int, San Diego, CA USA.
[Williams, Michelle] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA.
[Harlan, William R.] NIH, Off Director, Chevy Chase, MD USA.
[Haines, Jonathan] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN USA.
[Kwok, Richard K.; Nettles, Destiney S.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
RP Hamilton, CM (reprint author), RTI Int, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA.
EM chamilton@rti.org
RI Strader, Lisa/H-3083-2013; Kwok, Richard/B-6907-2017;
OI Kwok, Richard/0000-0002-6794-8360; Farrer, Lindsay/0000-0001-5533-4225;
Ordovas, Jose/0000-0002-7581-5680
NR 2
TC 1
Z9 1
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2011
VL 174
IS 3
BP 265
EP 266
DI 10.1093/aje/kwr191
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 796UG
UT WOS:000293077600003
ER
PT J
AU Kabagambe, EK
Judd, SE
Howard, VJ
Zakai, NA
Jenny, NS
Hsieh, M
Warnock, DG
Cushman, M
AF Kabagambe, Edmond K.
Judd, Suzanne E.
Howard, Virginia J.
Zakai, Neil A.
Jenny, Nancy S.
Hsieh, Matthew
Warnock, David G.
Cushman, Mary
TI Inflammation Biomarkers and Risk of All-Cause Mortality in the Reasons
for Geographic and Racial Differences in Stroke Cohort
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE biological markers; cohort studies; C-reactive protein; inflammation;
leukocytes; mortality; prospective studies
ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; LEUKOCYTE COUNT;
CARDIOVASCULAR-HEALTH; POSTMENOPAUSAL WOMEN; ASSOCIATION; MEN; US;
PREDICTORS; ALBUMIN
AB Inflammation biomarkers, including higher high-sensitivity C-reactive protein (hsCRP) levels, higher white blood cell (WBC) counts, and lower serum albumin levels, are associated with an increased risk of all-cause mortality. Many studies have examined these biomarkers individually, but less is known about their joint association with mortality. hsCRP, WBC count, and serum albumin were measured at baseline in the Reasons for Geographic and Racial Differences in Stroke Study cohort members, who were enrolled in 2003-2007. Over 4.5 years, there were 1,062 deaths in 17,845 participants. High-risk categories were defined as hsCRP or WBC levels above the 75th percentile (5.1 mg/L and 6.9 x 10(9) cells/L, respectively) and albumin levels below the 25th percentile (4.00 g/dL). The authors derived 4 groups that corresponded to 0 (n = 8,341), 1 (n = 6,277), 2 (n = 2,635), or 3 (n = 592) biomarkers in the high-risk category. After adjustment for age, sex, waist circumference, race, region, smoking, alcohol use, income, educational level, physical activity frequency, and medical history and compared with those with no biomarkers in the high-risk category, the hazard ratios for all-cause mortality for 1, 2, and 3 biomarkers in the high-risk category were 1.56 (95% confidence interval: 1.33, 1.82), 2.19 (95% confidence interval: 1.84, 2.62), and 2.96 (95% confidence interval: 2.30, 3.80), respectively (P(trend) < 0.0001). Adding the 3 inflammation biomarkers to a fully adjusted model improved risk discrimination by 23.7% (95% confidence interval: 9.3, 39.9). Measurement of more than 1 biomarker is more useful in risk prediction than single biomarkers.
C1 [Kabagambe, Edmond K.; Howard, Virginia J.] Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Judd, Suzanne E.] Univ Alabama, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA.
[Zakai, Neil A.; Cushman, Mary] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
[Zakai, Neil A.; Jenny, Nancy S.; Cushman, Mary] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Hsieh, Matthew] NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA.
[Warnock, David G.] Univ Alabama, Div Nephrol, Dept Med, Sch Med, Birmingham, AL 35294 USA.
RP Kabagambe, EK (reprint author), Univ Alabama, Sch Publ Hlth, Dept Epidemiol, 1665 Univ Blvd, Birmingham, AL 35294 USA.
EM edmondk@uab.edu
OI Kabagambe, Edmond/0000-0002-8993-3186
FU National Institute of Neurological Disorders and Stroke [U01 NS041588];
American Heart Association [0635323N]; Amgen Corporation
FX This research project was supported by cooperative agreement U01
NS041588 from the National Institute of Neurological Disorders and
Stroke. E. K. K. was supported by National Scientist Development grant
0635323N from the American Heart Association. Additional funding was
provided by an investigator-initiated grant-in-aid from Amgen
Corporation.
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2011
VL 174
IS 3
BP 284
EP 292
DI 10.1093/aje/kwr085
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 796UG
UT WOS:000293077600006
PM 21685411
ER
PT J
AU Aschebrook-Kilfoy, B
Cross, AJ
Stolzenberg-Solomon, RZ
Schatzkin, A
Hollenbeck, AR
Sinha, R
Ward, MH
AF Aschebrook-Kilfoy, Briseis
Cross, Amanda J.
Stolzenberg-Solomon, Rachael Z.
Schatzkin, Arthur
Hollenbeck, Albert R.
Sinha, Rashmi
Ward, Mary H.
TI Pancreatic Cancer and Exposure to Dietary Nitrate and Nitrite in the
NIH-AARP Diet and Health Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE diet; nitrates; nitrites; nitroso compounds; pancreatic neoplasms
ID N-NITROSO COMPOUNDS; RETIRED-PERSONS DIET; PAST MEDICAL HISTORY;
RISK-FACTORS; VEGETABLE CONSUMPTION; AMERICAN-ASSOCIATION;
NATIONAL-INSTITUTES; NUTRITIONAL FACTORS; EXOCRINE PANCREAS;
BLADDER-CANCER
AB Nitrate and nitrite are precursors of N-nitroso compounds, which induce tumors of the pancreas in animals. The authors evaluated the relation of dietary nitrate and nitrite to pancreatic cancer risk in the NIH-AARP Diet and Health Study. Nitrate and nitrite intakes were assessed at baseline using a 124-item food frequency questionnaire. During approximately 10 years of follow-up between 1995 and 2006, 1,728 incident pancreatic cancer cases were identified. There was no association between total nitrate or nitrite intake and pancreatic cancer in men or women. However, men in the highest quintile of summed nitrate/nitrite intake from processed meat had a nonsignificantly elevated risk of pancreatic cancer (hazard ratio = 1.18, 95% confidence interval: 0.95, 1.47; P-trend = 0.11). The authors observed a stronger increase in risk among men for nitrate/nitrite intake from processed meat at ages 12-13 years (highest quintile vs. lowest: hazard ratio = 1.32, 95% confidence interval: 0.99, 1.76; P-trend = 0.11), though the relation did not achieve statistical significance. The authors found no associations between adult or adolescent nitrate or nitrite intake from processed meats and pancreatic cancer among women. These results provide modest evidence that processed meat sources of dietary nitrate and nitrite may be associated with pancreatic cancer among men and provide no support for the hypothesis in women.
C1 [Aschebrook-Kilfoy, Briseis; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Cross, Amanda J.; Stolzenberg-Solomon, Rachael Z.; Schatzkin, Arthur; Sinha, Rashmi] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Aschebrook-Kilfoy, B (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS 8111, Bethesda, MD 20892 USA.
EM kilfoyb@mail.nih.gov
RI Aschebrook-Kilfoy, Briseis/A-2537-2012; Sinha, Rashmi/G-7446-2015
OI Sinha, Rashmi/0000-0002-2466-7462
FU National Institutes of Health, National Cancer Institute
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute.
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2011
VL 174
IS 3
BP 305
EP 315
DI 10.1093/aje/kwr092
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 796UG
UT WOS:000293077600008
PM 21685410
ER
PT J
AU Weinberg, CR
AF Weinberg, Clarice R.
TI SHOULD GRAPHS OF RISK OR RATE RATIOS BE PLOTTED ON A LOG SCALE? REPLY
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
C1 Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Weinberg, CR (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA.
EM weinber2@niehs.nih.gov
NR 1
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PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2011
VL 174
IS 3
BP 377
EP 377
DI 10.1093/aje/kwr157
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 796UG
UT WOS:000293077600018
ER
PT J
AU Van Domelen, DR
Koster, A
Caserotti, P
Brychta, RJ
Chen, KY
McClain, JJ
Troiano, RP
Berrigan, D
Harris, TB
AF Van Domelen, Dane R.
Koster, Annemarie
Caserotti, Paolo
Brychta, Robert J.
Chen, Kong Y.
McClain, James J.
Troiano, Richard P.
Berrigan, David
Harris, Tamara B.
TI Employment and Physical Activity in the U.S.
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID UNITED-STATES; AMERICAN-COLLEGE; SPORTS-MEDICINE; PUBLIC-HEALTH;
LEISURE-TIME; RECOMMENDATION; ACCELEROMETER; PREVALENCE; PATTERNS;
OBESITY
AB Background: Physical inactivity is a risk factor for obesity, cardiovascular disease, hypertension, and other chronic diseases that are increasingly prevalent in the U. S. and worldwide. Time at work represents a major portion of the day for employed people.
Purpose: To determine how employment status (full-time, part-time, or not employed) and job type (active or sedentary) are related to daily physical activity levels in American adults.
Methods: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) were collected in 2003-2004 and analyzed in 2010. Physical activity was measured using Actigraph uniaxial accelerometers, and participants aged 20-60 years with >= days of monitoring were included (N = 1826). Accelerometer variables included mean counts/minute during wear time and proportion of wear time spent in various intensity levels.
Results: In men, full-time workers were more active than healthy nonworkers (p = 0.004), and in weekday-only analyses, even workers with sedentary jobs were more active (p = 0.03) and spent less time sedentary (p < 0.001) than nonworkers. In contrast with men, women with full-time sedentary jobs spent more time sedentary (p = 0.008) and had less light and lifestyle intensity activity than healthy nonworkers on weekdays. Within full-time workers, those with active jobs had greater weekday activity than those with sedentary jobs (22% greater in men, 30% greater in women).
Conclusions: In men, full-time employment, even in sedentary occupations, is positively associated with physical activity compared to not working, and in both genders job type has a major bearing on daily activity levels. (Am J Prev Med 2011;41(2):136-145) (C) 2011 Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine.
C1 [Van Domelen, Dane R.; Koster, Annemarie; Caserotti, Paolo; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Brychta, Robert J.; Chen, Kong Y.] NIDDKD, Bethesda, MD 20892 USA.
[McClain, James J.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA.
[Koster, Annemarie] Maastricht Univ Med Ctr, Dept Internal Med, Sch Publ Hlth & Primary Care, Maastricht, Netherlands.
RP Harris, TB (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA.
EM harrista@nia.nih.gov
RI Koster, Annemarie/E-7438-2010;
OI Van Domelen, Dane/0000-0003-0051-7790; Troiano,
Richard/0000-0002-6807-989X; Chen, Kong/0000-0002-0306-1904
FU NIH, National Institute on Aging
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging.
NR 27
TC 40
Z9 41
U1 0
U2 14
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 AUG
PY 2011
VL 41
IS 2
BP 136
EP 145
DI 10.1016/j.amepre.2011.03.019
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 795FL
UT WOS:000292958900004
PM 21767720
ER
PT J
AU Healy, GN
Clark, BK
Winkler, EAH
Gardiner, PA
Brown, WJ
Matthews, CE
AF Healy, Genevieve N.
Clark, Bronwyn K.
Winkler, Elisabeth A. H.
Gardiner, Paul A.
Brown, Wendy J.
Matthews, Charles E.
TI Measurement of Adults' Sedentary Time in Population-Based Studies
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID PHYSICAL-ACTIVITY QUESTIONNAIRE; TELEVISION VIEWING TIME; TEST-RETEST
RELIABILITY; ENERGY-EXPENDITURE; ACTIVITY MONITOR; CHINESE VERSION;
METABOLIC RISK; UNITED-STATES; SITTING TIME; SELF-REPORT
AB Sedentary time (too much sitting) increasingly is being recognized as a distinct health risk behavior. This paper reviews the reliability and validity of self-reported and device-based sedentary time measures and provides recommendations for their use in population-based studies. The focus is on instruments that have been used in free-living, population-based research in adults. Data from the 2003-2006 National Health and Nutrition Examination Survey are utilized to compare the descriptive epidemiology of sedentary time that arises from the use of different sedentary time measures. A key recommendation from this review is that, wherever possible, population-based monitoring of sedentary time should incorporate both self-reported measures (to capture important domain-and behavior-specific sedentary time information) and device-based measures (to measure both total sedentary time and patterns of sedentary time accumulation). (Am J Prev Med 2011;41(2):216-227) (C) 2011 American Journal of Preventive Medicine
C1 [Healy, Genevieve N.; Clark, Bronwyn K.; Winkler, Elisabeth A. H.; Gardiner, Paul A.] Univ Queensland, Sch Populat Hlth, Canc Prevent Res Ctr, Brisbane, Qld, Australia.
[Brown, Wendy J.] Univ Queensland, Sch Human Movement Studies, Brisbane, Qld, Australia.
[Healy, Genevieve N.] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia.
[Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Healy, GN (reprint author), Univ Queensland, Sch Populat Hlth, Canc Prevent Res Ctr, Herston Rd, Herston, Qld 4006, Australia.
EM g.healy@uq.edu.au
RI Gardiner, Paul/F-2751-2010; Healy, Genevieve/A-7408-2008; Clark,
Bronwyn/F-8028-2010; Brown, Wendy/G-2201-2010; matthews,
Charles/E-8073-2015
OI Gardiner, Paul/0000-0002-8072-2673; Healy,
Genevieve/0000-0001-7093-7892; Clark, Bronwyn/0000-0001-7527-4311;
Brown, Wendy/0000-0001-9093-4509; matthews, Charles/0000-0001-8037-3103
FU NHMRC [569861, 569940]; National Heart Foundation of Australia [PH 08B
3905]; Australian Postgraduate Award; Queensland Health Core Research
Infrastructure grant
FX GNH is supported by a NHMRC (No. 569861)/National Heart Foundation of
Australia (PH 08B 3905) Postdoctoral Fellowship. BKC is supported by an
Australian Postgraduate Award and Queensland Health Core Research
Infrastructure grant. EAHW and PAG are supported by a Queensland Health
Core Research Infrastructure grant and by NHMRC Program Grant funding
(No. 569940). NHANES data used in this study were collected by the
National Center for Health Statistics, CDC.
NR 75
TC 173
Z9 175
U1 3
U2 40
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 AUG
PY 2011
VL 41
IS 2
BP 216
EP 227
DI 10.1016/j.amepre.2011.05.005
PG 12
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 795FL
UT WOS:000292958900014
PM 21767730
ER
PT J
AU Bradley, CJ
Lansdorp-Vogelaar, I
Yabroff, R
Dahman, B
Mariotto, A
Feuer, EJ
Brown, ML
AF Bradley, Cathy J.
Lansdorp-Vogelaar, Iris
Yabroff, Robin
Dahman, Bassam
Mariotto, Angela
Feuer, Eric J.
Brown, Martin L.
TI Productivity Savings from Colorectal Cancer Prevention and Control
Strategies
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID FLUOROURACIL PLUS LEUCOVORIN; III COLON-CANCER; ADJUVANT THERAPY;
UNITED-STATES; PHYSICAL-ACTIVITY; POOLED ANALYSIS; FOLINIC ACID;
STAGE-II; IRINOTECAN; OXALIPLATIN
AB Background: Lost productivity represents a considerable portion of the total economic burden of colorectal cancer (CRC), but cost-effectiveness studies of CRC prevention and control have not included these costs and therefore underestimate potential savings from CRC prevention and control.
Purpose: To use microsimulation modeling study to estimate and project productivity costs of CRC and to model the savings from four approaches to reducing CRC incidence and mortality: risk factor reduction, improved screening, improved treatment, and a simultaneous approach where all three strategies are implemented.
Methods: A model was developed to project productivity losses from CRC using the U. S. population with CRC incidence and mortality projected through the year 2020. Outcome measures were CRC mortality, morbidity, and productivity savings.
Results: With 2005 levels in risk factors, screening, and treatment, 48,748 CRC deaths occurred in 2010, amounting to $21 billion of lost productivity. Using prevention and treatment strategies simultaneously, 3586 deaths could have been avoided in 2010, leading to a savings of $1.4 billion. Cumulatively, by 2020, simultaneous strategies that reduce risk factors and increase screening and treatment could result in 101,353 deaths avoided and $33.9 billion in savings in reduced productivity loss. Improved screening rates alone led to nearly $14.7 billion in savings between 2005 and 2020, followed by risk factor reduction ($12.4 billion) and improved treatment ($8.4 billion).
Conclusions: The savings in productivity loss from strategies to reduce CRC incidence and mortality are substantial, providing evidence that CRC prevention and control strategies are likely to be cost-saving. (Am J Prev Med 2011;41(2):e5-e14) (C) 2011 American Journal of Preventive Medicine
C1 [Bradley, Cathy J.; Dahman, Bassam] Virginia Commonwealth Univ, Dept Healthcare Policy & Res, Richmond, VA 23113 USA.
[Bradley, Cathy J.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23113 USA.
[Lansdorp-Vogelaar, Iris] Univ Med Ctr Rotterdam, Dept Publ Hlth, Erasmus MC, Rotterdam, Netherlands.
[Yabroff, Robin; Brown, Martin L.] NCI, Hlth Serv & Econ Branch, Surveillance Res Program, Bethesda, MD 20892 USA.
[Mariotto, Angela] NCI, Appl Res Program, Data Modeling Branch, Surveillance Res Program, Bethesda, MD 20892 USA.
[Feuer, Eric J.] NCI, Stat Methodol & Applicat Branch, Surveillance Res Program, Bethesda, MD 20892 USA.
RP Bradley, CJ (reprint author), Virginia Commonwealth Univ, Dept Healthcare Policy & Res, 830 E Main St,Box 980430, Richmond, VA 23113 USA.
EM cjbradley@vcu.edu
OI Yabroff, K. Robin/0000-0003-0644-5572
FU National Cancer Institute
FX This research was supported by National Cancer Institute contracts with
C.J.B and I.L.-V. The authors thank Chris Zeruto, Information Management
Services, for programming support using the National Health Interview
Study.
NR 40
TC 9
Z9 10
U1 0
U2 3
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 AUG
PY 2011
VL 41
IS 2
BP E5
EP E14
DI 10.1016/j.amepre.2011.04.008
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 795FL
UT WOS:000292958900001
PM 21767717
ER
PT J
AU Sever, ML
Salo, PM
Haynes, AK
Zeldin, DC
AF Sever, Michelle L.
Salo, Paeivi M.
Haynes, Amber K.
Zeldin, Darryl C.
TI Inner-City Environments and Mitigation of Cockroach Allergen
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Editorial Material
ID ASTHMA; EXPOSURE; CHILDREN; HOMES; INTERVENTION; SENSITIVITY; MORBIDITY
C1 [Sever, Michelle L.; Salo, Paeivi M.; Haynes, Amber K.; Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
RP Sever, ML (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, POB 12233,MD CU-04,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM sever@niehs.nih.gov
OI Sever, Michelle/0000-0002-2435-1214
NR 13
TC 2
Z9 2
U1 0
U2 3
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 AUG
PY 2011
VL 41
IS 2
SU 1
BP S55
EP S56
DI 10.1016/j.amepre.2011.05.007
PG 2
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 793ZQ
UT WOS:000292863400006
PM 21767738
ER
PT J
AU Johansen, CT
Wang, J
Lanktree, MB
McIntyre, AD
Ban, MR
Martins, RA
Kennedy, BA
Hassell, RG
Visser, ME
Schwartz, SM
Voight, BF
Elosua, R
Salomaa, V
O'Donnell, CJ
Dallinga-Thie, GM
Anand, SS
Yusuf, S
Huff, MW
Kathiresan, S
Cao, H
Hegele, RA
AF Johansen, Christopher T.
Wang, Jian
Lanktree, Matthew B.
McIntyre, Adam D.
Ban, Matthew R.
Martins, Rebecca A.
Kennedy, Brooke A.
Hassell, Reina G.
Visser, Maartje E.
Schwartz, Stephen M.
Voight, Benjamin F.
Elosua, Roberto
Salomaa, Veikko
O'Donnell, Christopher J.
Dallinga-Thie, Geesje M.
Anand, Sonia S.
Yusuf, Salim
Huff, Murray W.
Kathiresan, Sekar
Cao, Henian
Hegele, Robert A.
TI An Increased Burden of Common and Rare Lipid-Associated Risk Alleles
Contributes to the Phenotypic Spectrum of Hypertriglyceridemia
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE lipoproteins; genetic risk scores; genetic variation;
hypertriglyceridemia; pleiotropy
ID GENOME-WIDE ASSOCIATION; NONFASTING TRIGLYCERIDES; HYPERLIPOPROTEINEMIA
PHENOTYPES; MYOCARDIAL-INFARCTION; LIPOPROTEIN-LIPASE; HEART-DISEASE;
POPULATION; DEFICIENCY; VARIANTS; DETERMINANTS
AB Objective-Earlier studies have suggested that a common genetic architecture underlies the clinically heterogeneous polygenic Fredrickson hyperlipoproteinemia (HLP) phenotypes defined by hypertriglyceridemia (HTG). Here, we comprehensively analyzed 504 HLP-HTG patients and 1213 normotriglyceridemic controls and confirmed that a spectrum of common and rare lipid-associated variants underlies this heterogeneity.
Methods and Results-First, we demonstrated that genetic determinants of plasma lipids and lipoproteins, including common variants associated with plasma triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from the Global Lipids Genetics Consortium were associated with multiple HLP-HTG phenotypes. Second, we demonstrated that weighted risk scores composed of common TG-associated variants were distinctly increased across all HLP-HTG phenotypes compared with controls; weighted HDL-C and LDL-C risk scores were also increased, although to a less pronounced degree with some HLP-HTG phenotypes. Interestingly, decomposition of HDL-C and LDL-C risk scores revealed that pleiotropic variants (those jointly associated with TG) accounted for the greatest difference in HDL-C and LDL-C risk scores. The APOE E2/E2 genotype was significantly overrepresented in HLP type 3 versus other phenotypes. Finally, rare variants in 4 genes accumulated equally across HLP-HTG phenotypes.
Conclusion-HTG susceptibility and phenotypic heterogeneity are both influenced by accumulation of common and rare TG-associated variants. (Arterioscler Thromb Vasc Biol. 2011; 31: 1916-1926.)
C1 [Hegele, Robert A.] Univ Western Ontario, Blackburn Cardiovasc Genet Lab, Robarts Res Inst, Dept Biochem, London, ON N6A 5K8, Canada.
[Johansen, Christopher T.; Huff, Murray W.; Hegele, Robert A.] Univ Western Ontario, Dept Med, Schulich Sch Med & Dent, London, ON N6A 5K8, Canada.
[Visser, Maartje E.; Dallinga-Thie, Geesje M.] Acad Med Ctr Amsterdam, Dept Expt Vasc Med, Amsterdam, Netherlands.
[Visser, Maartje E.; Dallinga-Thie, Geesje M.] Acad Med Ctr Amsterdam, Dept Vasc Med, Amsterdam, Netherlands.
[Schwartz, Stephen M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Voight, Benjamin F.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Voight, Benjamin F.; Kathiresan, Sekar] Broad Inst Massachusetts Inst Technol & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Elosua, Roberto] Inst Municipal Invest Med, E-08003 Barcelona, Spain.
[Elosua, Roberto] CIBER Epidemiol & Salud Publ, Barcelona, Spain.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Chron Dis Epidemiol Unit, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland.
[O'Donnell, Christopher J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Anand, Sonia S.; Yusuf, Salim] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
RP Hegele, RA (reprint author), Univ Western Ontario, Blackburn Cardiovasc Genet Lab, Robarts Res Inst, Dept Biochem, London, ON N6A 5K8, Canada.
EM hegele@robarts.ca
RI Voight, Benjamin/F-1775-2011; Hegele, Robert/G-3301-2011;
OI Lanktree, Matthew/0000-0002-5750-6286; ELOSUA,
ROBERTO/0000-0001-8235-0095
FU Canadian Institutes of Health Research (CIHR) [MOP-13430, MOP-79523,
CTP-79853]; University of Western Ontario; Jacob J. Wolfe Distinguished
Medical Research Chair at the University of Western Ontario; Edith
Schulich Vinet Canada Research Chair in Human Genetics (Tier I); Martha
G. Blackburn Chair in Cardiovascular Research; Heart and Stroke
Foundation of Ontario [NA-6059, T-6018, PRG-4854]; Pfizer; Genome Canada
through the Ontario Genomics Institute
FX Dr Johansen is supported by the Canadian Institutes of Health Research
(CIHR) Banting and Best Canada Graduate Scholarship Doctoral Research
Award and the University of Western Ontario MD/PhD program, and is a
CIHR fellow in Vascular Research. Dr Hegele is supported by the Jacob J.
Wolfe Distinguished Medical Research Chair at the University of Western
Ontario; the Edith Schulich Vinet Canada Research Chair in Human
Genetics (Tier I); the Martha G. Blackburn Chair in Cardiovascular
Research; and operating grants from the CIHR (MOP-13430, MOP-79523,
CTP-79853), the Heart and Stroke Foundation of Ontario (NA-6059, T-6018,
PRG-4854), the Pfizer Jean Davignon Distinguished Cardiovascular and
Metabolic Research Award, and Genome Canada through the Ontario Genomics
Institute.
NR 29
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U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD AUG
PY 2011
VL 31
IS 8
BP 1916
EP U460
DI 10.1161/ATVBAHA.111.226365
PG 21
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 794RH
UT WOS:000292918500028
PM 21597005
ER
PT J
AU Giulianelli, S
Herschkowitz, JI
Patel, V
Lamb, CA
Gutkind, JS
Molinolo, A
Perou, CM
Lanari, C
AF Giulianelli, Sebastian
Herschkowitz, Jason I.
Patel, Vyomesh
Lamb, Caroline A.
Silvio Gutkind, J.
Molinolo, Alfredo
Perou, Charles M.
Lanari, Claudia
TI MPA-induced gene expression and stromal and parenchymal gene expression
profiles in luminal murine mammary carcinomas with different hormonal
requirements
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Epithelium; Tumor stroma; DNA microarray analysis
ID BREAST-CANCER CELLS; FIBROBLAST-GROWTH-FACTOR; RECEPTOR ISOFORM RATIO;
PROGESTERONE-RECEPTOR; TUMOR-GROWTH; MATRIX METALLOPROTEINASES; KINASE
PATHWAYS; ID PROTEINS; IN-VITRO; ESTROGEN
AB Over the past several years, we have been interested in understanding the mechanisms by which mammary carcinomas acquire hormone independence. We demonstrated that carcinoma associated fibroblasts participate in the ligand-independent activation of progesterone receptors inducing tumor growth. In this study, we used DNA microarrays to compare the gene expression profiles of tumors from the MPA mouse breast cancer model, one hormone-dependent (C4-HD) and one hormone-independent (C4-HI), using whole tumor samples or laser-captured purified stromal and epithelial cells obtained from the same tumors. The expression of selected genes was validated by immunohistochemistry and immunofluorescence assays. We identified 413 genes specifically expressed in tumor stroma. Eighty-five percent of these genes were upregulated, whereas the remaining 15% were downregulated in C4-HI relative to their expression in the C4-HD tumor stroma. Several matrix metallopeptidases were overexpressed in the C4-HI tumor microenvironment. On the other hand, 1100 genes were specifically expressed in the tumor parenchyma. Among them, the 29% were upregulated, whereas the remaining 71% were downregulated in C4-HI relative to C4-HD tumor epithelium. Steap, Pdgfc, Runx2, Cxcl9, and Sdf2 were among the genes with high expression in the C4-HI tumor parenchyma. Interestingly, Fgf2 was one of the few genes upregulated by MPA in C4-HD tumors, confirming its pivotal role in regulating tumor growth in this model. In conclusion, we demonstrate herein a gene expression profile that distinguishes both the epithelial and the stromal cells in mammary tumors with different hormone dependence, supporting the hypothesis that the tumor-associated stroma may contribute to hormone-independent tumor growth.
C1 [Giulianelli, Sebastian; Lamb, Caroline A.; Lanari, Claudia] Consejo Nacl Invest Cient & Tecn, Lab Hormonal Carcinogenesis, Inst Biol & Med Expt, RA-1033 Buenos Aires, DF, Argentina.
[Herschkowitz, Jason I.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Patel, Vyomesh; Silvio Gutkind, J.; Molinolo, Alfredo] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA.
[Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
RP Lanari, C (reprint author), Consejo Nacl Invest Cient & Tecn, Lab Hormonal Carcinogenesis, Inst Biol & Med Expt, Vuelta Obligado 2490,C1428ADN, RA-1033 Buenos Aires, DF, Argentina.
EM clanari@dna.uba.ar
RI Gutkind, J. Silvio/A-1053-2009;
OI Perou, Charles/0000-0001-9827-2247
FU Avon Foundation; UICC; Fundacion Sales, SECyT [PICT 2005, 2007-932];
CONICET [PIP 5351]
FX We are very grateful to Julieta Bolado for excellent technical support
and to Laboratorios Craveri (Buenos Aires, Argentina) for providing MPA.
SG received an award from Avon Foundation for data presented at the AACR
Annual Meeting 2008, and an ICRETT Fellowship from the UICC permitting
training in Dr Perou's laboratory. This work was supported by Fundacion
Sales, SECyT (PICT 2005 and 2007-932), and CONICET (PIP 5351) to CL.
NR 83
TC 7
Z9 7
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD AUG
PY 2011
VL 129
IS 1
BP 49
EP 67
DI 10.1007/s10549-010-1185-4
PG 19
WC Oncology
SC Oncology
GA 794EQ
UT WOS:000292878700005
PM 20890655
ER
PT J
AU Schairer, C
Brown, LM
Mai, PL
AF Schairer, Catherine
Brown, Linda M.
Mai, Phuong L.
TI Inflammatory breast cancer: high risk of contralateral breast cancer
compared to comparably staged non-inflammatory breast cancer
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Inflammatory breast cancer; Contralateral breast cancer; Absolute risk
ID RECEPTOR STATUS; RECURRENCE; SURVIVAL; BIOLOGY; WECARE
AB Inflammatory breast cancer (IBC), the most lethal form of breast cancer, has characteristics linked to higher risk of contralateral breast cancer. However, no large studies have examined risk of contralateral breast cancer following IBC. We calculated absolute risk of invasive contralateral breast cancer among 5,631 IBC and 174,634 comparably staged non-IBC first breast cancer cases who survived at least 2 months following diagnosis and were reported to 13 Surveillance, Epidemiology, and End Results (SEER) registries between January 1, 1973 and December 31, 2006. We considered that contralateral cancers occurring within 2-23 months of first cancer diagnosis may more likely be metastatic/recurrent disease and those occurring 2 or more years after diagnosis independent primaries. Absolute risk of contralateral breast cancer was generally greater following IBC than regional/distant non-IBC, regardless of age and hormone receptor status of first cancer diagnosis. Much of the increase in absolute risk following IBC occurred within 2-23 months of first cancer diagnosis, while the risk for non-IBC occurred more gradually over time since diagnosis. For instance, among women first diagnosed before age 50, absolute risks following IBC and non-IBC were 4.9 vs. 1.1% at 2 years, 6.0 vs. 2.2% at 5 years, and 7.7 vs. 6.1% at 20 years after diagnosis. However, patterns of higher risk following IBC than non-IBC were also evident for at least 10-15 years in the subcohort of women who survived at least 24 months without a contralateral cancer. In conclusion, our results suggest that IBC has higher risk of cancer in the contralateral breast than comparably staged non-IBC, possibly due to both metastatic/recurrent disease and independent primaries.
C1 [Schairer, Catherine; Mai, Phuong L.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA.
[Brown, Linda M.] RTI Int, Rockville, MD USA.
RP Schairer, C (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 6120 Execut Blvd,Room 8026,MSC 7244, Rockville, MD 20852 USA.
EM schairec@exchange.nih.gov
FU Division of Cancer Epidemiology and Genetics; Division of Cancer
Prevention, National Cancer Institute, National Institutes of Health,
Department of Health and Human Services
FX The authors thank Nathan Appel at IMS, Inc. and David Check at the
National Cancer Institute for computer support. This study was supported
by the Intramural Research Program of the Division of Cancer
Epidemiology and Genetics and contracts from the Division of Cancer
Prevention, National Cancer Institute, National Institutes of Health,
Department of Health and Human Services.
NR 27
TC 13
Z9 15
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD AUG
PY 2011
VL 129
IS 1
BP 117
EP 124
DI 10.1007/s10549-010-1324-y
PG 8
WC Oncology
SC Oncology
GA 794EQ
UT WOS:000292878700011
PM 21390499
ER
PT J
AU Cox, B
Ballard-Barbash, R
Broeders, M
Dowling, E
Malila, N
Shumak, R
Taplin, S
Buist, D
Miglioretti, D
AF Cox, Brian
Ballard-Barbash, Rachel
Broeders, Mireille
Dowling, Emily
Malila, Nea
Shumak, Rene
Taplin, Stephen
Buist, Diana
Miglioretti, Diana
TI Recording of hormone therapy and breast density in breast screening
programs: summary and recommendations of the International Cancer
Screening Network (vol 124, pg 793, 2010)
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Correction
C1 [Cox, Brian] Univ Otago, Hugh Adam Canc Epidemiol Unit, Dept Prevent & Social Med, Dunedin Sch Med, Dunedin 9054, New Zealand.
[Ballard-Barbash, Rachel; Dowling, Emily; Taplin, Stephen] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Broeders, Mireille] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & Hlth Technol Assessment, NL-6500 HB Nijmegen, Netherlands.
[Malila, Nea] Finnish Canc Registry, Mass Screening Registry, Helsinki 00130, Finland.
[Malila, Nea] Univ Tampere, Tampere Sch Publ Hlth, FIN-33101 Tampere, Finland.
[Shumak, Rene] Ontario Breast Screening Program, Toronto, ON MN 6G9, Canada.
[Buist, Diana; Miglioretti, Diana] Grp Hlth Res Inst, Seattle, WA 98101 USA.
RP Cox, B (reprint author), Univ Otago, Hugh Adam Canc Epidemiol Unit, Dept Prevent & Social Med, Dunedin Sch Med, Dunedin 9054, New Zealand.
EM brian.cox@otago.ac.nz
RI Broeders, Mireille/C-8820-2015
NR 1
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD AUG
PY 2011
VL 129
IS 1
BP 297
EP 298
DI 10.1007/s10549-010-0979-8
PG 2
WC Oncology
SC Oncology
GA 794EQ
UT WOS:000292878700038
ER
PT J
AU Jain, L
Woo, S
Gardner, ER
Dahut, WL
Kohn, EC
Kummar, S
Mould, DR
Giaccone, G
Yarchoan, R
Venitz, J
Figg, WD
AF Jain, Lokesh
Woo, Sukyung
Gardner, Erin R.
Dahut, William L.
Kohn, Elise C.
Kummar, Shivaani
Mould, Diane R.
Giaccone, Giuseppe
Yarchoan, Robert
Venitz, Juergen
Figg, William D.
TI Population pharmacokinetic analysis of sorafenib in patients with solid
tumours
SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE CYP3A4; population pharmacokinetics; sorafenib; tyrosine kinase
inhibitor; UGT1A9
ID FACTOR RECEPTOR INHIBITOR; DAYS ON/7 DAYS; PHASE-I; RAF KINASE;
CANCER-PATIENTS; POLYMORPHISMS; UGT1A9; SAFETY; CYTOCHROME-P450;
BAY-43-9006
AB AIMS
To characterize the pharmacokinetics (PK) of sorafenib in patients with solid tumours and to evaluate the possible effects of demographic, clinical and pharmacogenetic (CYP3A4*1B, CYP3A5*3C, UGT1A9*3 and UGT1A9*5) covariates on the disposition of sorafenib.
METHODS
PK were assessed in 111 patients enrolled in five phase I and II clinical trials, where sorafenib 200 or 400 mg was administered twice daily as a single agent or in combination therapy. All patients were genotyped for polymorphisms in metabolic enzymes for sorafenib. Population PK analysis was performed by using nonlinear mixed effects modelling (NONMEM). The final model was validated using visual predictive checks and nonparametric bootstrap analysis.
RESULTS
A one compartment model with four transit absorption compartments and enterohepatic circulation (EHC) adequately described sorafenib disposition. Baseline bodyweight was a statistically significant covariate for distributional volume, accounting for 4% of inter-individual variability (IIV). PK model parameter estimates (range) for an 80 kg patient were clearance 8.13 l h(-1) (3.6-22.3 l h(-1)), volume 213 l (50-1000 l), mean absorption transit time 1.98 h (0.5-13 h), fraction undergoing EHC 50% and average time to gall bladder emptying 6.13 h.
CONCLUSIONS
Overall, population PK analysis was consistent with known biopharmaceutical/PK characteristics of oral sorafenib. No clinically important PK covariates were identified.
C1 [Figg, William D.] NCI, Med Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Jain, Lokesh; Woo, Sukyung; Figg, William D.] NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
[Gardner, Erin R.] SAIC Frederick Inc, NCI Frederick, Clin Pharmacol Program, Frederick, MD 21702 USA.
[Mould, Diane R.] Project Res Inc, Phoenixville, PA 19460 USA.
[Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Venitz, Juergen; Figg, William D.] Virginia Commonwealth Univ, Sch Pharm, Dept Pharmaceut, Richmond, VA 23298 USA.
RP Figg, WD (reprint author), NCI, Med Oncol Branch, CCR, NIH, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016; Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
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 HHSN261200800001E (ERG). This work was supported by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 35
TC 46
Z9 46
U1 2
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0306-5251
J9 BRIT J CLIN PHARMACO
JI Br. J. Clin. Pharmacol.
PD AUG
PY 2011
VL 72
IS 2
BP 294
EP 305
DI 10.1111/j.1365-2125.2011.03963.x
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 790RH
UT WOS:000292606400013
PM 21392074
ER
PT J
AU Yao, S
Till, C
Kristal, AR
Goodman, PJ
Hsing, AW
Tangen, CM
Platz, EA
Stanczyk, FZ
Reichardt, JKV
Tang, L
Neuhouser, ML
Santella, RM
Figg, WD
Price, DK
Parnes, HL
Lippman, SM
Thompson, IM
Ambrosone, CB
Hoque, A
AF Yao, Song
Till, Cathee
Kristal, Alan R.
Goodman, Phyllis J.
Hsing, Ann W.
Tangen, Catherine M.
Platz, Elizabeth A.
Stanczyk, Frank Z.
Reichardt, Juergen K. V.
Tang, Li
Neuhouser, Marian L.
Santella, Regina M.
Figg, William D.
Price, Douglas K.
Parnes, Howard L.
Lippman, Scott M.
Thompson, Ian M.
Ambrosone, Christine B.
Hoque, Ashraful
TI Serum estrogen levels and prostate cancer risk in the prostate cancer
prevention trial: a nested case-control study
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Prostate cancer; Etiology; Estrogen; Estradiol; Nested case-control
study
ID ENDOGENOUS SEX-HORMONES; STEROID-HORMONES; FINASTERIDE; ANDROGENS;
AROMATASE; TESTOSTERONE; METAANALYSIS; MALIGNANCY; GLAND
AB Finasteride reduces prostate cancer risk by blocking the conversion of testosterone to dihydrotestosterone. However, whether finasteride affects estrogens levels or change in estrogens affects prostate cancer risk is unknown.
These questions were investigated in a case-control study nested within the prostate cancer prevention trial (PCPT) with 1,798 biopsy-proven prostate cancer cases and 1,798 matched controls.
Among men on placebo, no relationship of serum estrogens with risk of prostate cancer was found. Among those on finasteride, those in the highest quartile of baseline estrogen levels had a moderately increased risk of Gleason score < 7 prostate cancer (for estrone, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.06-2.15; for estradiol, OR = 1.50, 95% CI = 1.03-2.18). Finasteride treatment increased serum estrogen concentrations; however, these changes were not associated with prostate cancer risk.
Our findings confirm those from previous studies that there are no associations of serum estrogen with prostate cancer risk in untreated men. In addition, finasteride results in a modest increase in serum estrogen levels, which are not related to prostate cancer risk. Whether finasteride is less effective in men with high serum estrogens, or finasteride interacts with estrogen to increase cancer risk, is uncertain and warrants further investigation.
C1 [Hoque, Ashraful] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA.
[Yao, Song; Tang, Li; Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Till, Cathee; Kristal, Alan R.; Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
[Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Stanczyk, Frank Z.] Univ So Calif, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA.
[Stanczyk, Frank Z.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Reichardt, Juergen K. V.] James Cook Univ, Sch Pharm & Mol Sci, Townsville, Qld, Australia.
[Santella, Regina M.] Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA.
[Figg, William D.; Price, Douglas K.] NCI, Med Oncol Branch & Affiliates, Bethesda, MD 20892 USA.
[Parnes, Howard L.] NCI, Canc Prevent Div, Prostate & Urol Canc Res Grp, Bethesda, MD 20892 USA.
[Lippman, Scott M.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA.
[Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
RP Hoque, A (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, 1155 Herman P Pressler,CPB6-3494,Unit 1360, Houston, TX 77030 USA.
EM ahoque@mdanderson.org
RI Yao, Song/A-2534-2012; Figg Sr, William/M-2411-2016;
OI Kristal, Alan/0000-0002-7329-1617; Reichardt,
Juergen/0000-0001-6458-2773
FU National Cancer Institute [P01 CA108964, R03 CA117490, CA054174,
CA37429]
FX Funded in part by grants P01 CA108964, R03 CA117490, CA054174 and
CA37429 from the National Cancer Institute.
NR 32
TC 16
Z9 16
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD AUG
PY 2011
VL 22
IS 8
BP 1121
EP 1131
DI 10.1007/s10552-011-9787-7
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 794VB
UT WOS:000292928300005
PM 21667068
ER
PT J
AU Shanker, A
Marincola, F
AF Shanker, Anil
Marincola, Francesco M.
TI Cooperativity of adaptive and innate immunity: implications for cancer
therapy
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Review
DE Innate immunity; Adaptive T cells; Natural killer cells; Effector
function; Immune regulation; Cancer immunotherapy
ID CD8(+) T-CELLS; NATURAL-KILLER-CELLS; C VIRUS-INFECTION;
TUMOR-NECROSIS-FACTOR; GENE-SPECIFIC CONTROL; IN-VIVO; DENDRITIC CELLS;
ADIPOSE-TISSUE; COLORECTAL-CANCER; IFN-GAMMA
AB The dichotomy of immunology into innate and adaptive immunity has created conceptual barriers in appreciating the intrinsic two-way interaction between immune cells. An emerging body of evidence in various models of immune rejection, including cancer, indicates an indispensable regulation of innate effector functions by adaptive immune cells. This bidirectional cooperativity in innate and adaptive immune functions has broad implications for immune responses in general and for regulating the tumor-associated inflammation that overrides the protective antitumor immunity. Mechanistic understanding of this two-way immune cross-talk could provide insights into novel strategies for designing better immunotherapy approaches against cancer and other diseases that normally defy immune control.
C1 [Shanker, Anil] Meharry Med Coll, Sch Med, Lab Lymphocyte Funct, Dept Biochem & Canc Biol, Nashville, TN 37208 USA.
[Shanker, Anil] Vanderbilt Univ, Dept Canc Biol, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
[Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA.
RP Shanker, A (reprint author), Meharry Med Coll, Sch Med, Lab Lymphocyte Funct, Dept Biochem & Canc Biol, Nashville, TN 37208 USA.
EM ashanker@mmc.edu
OI Shanker, Anil/0000-0001-6372-3669
FU National Cancer Institute [U54 CA091408]; National Institutes of Health
FX AS is supported by funds from the U54 CA091408 grant from the National
Cancer Institute to the Meharry Medical College-Vanderbilt-Ingram Cancer
Center partnership in eliminating cancer disparities. FMM is fully
supported by the intramural grants from the National Institutes of
Health. The authors wish to thank Dr. Allison Bierly (NCI-Frederick) and
Dr. Anshu Malhotra for carefully going through the manuscript.
NR 144
TC 18
Z9 19
U1 1
U2 6
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 AUG
PY 2011
VL 60
IS 8
BP 1061
EP 1074
DI 10.1007/s00262-011-1053-z
PG 14
WC Oncology; Immunology
SC Oncology; Immunology
GA 795KP
UT WOS:000292973400001
PM 21656157
ER
PT J
AU Sayers, TJ
AF Sayers, Thomas J.
TI Targeting the extrinsic apoptosis signaling pathway for cancer therapy
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Review
DE TRAIL; Bortezomib; Extrinsic apoptosis; Proteasome inhibition; Death
receptors
ID TRAIL-INDUCED APOPTOSIS; PROTEASOME INHIBITION; TUMOR-CELL; C-FLIP;
MEDIATED APOPTOSIS; LIGAND APO2L/TRAIL; INDUCE APOPTOSIS; DEATH
RECEPTORS; CARCINOMA-CELLS; UP-REGULATION
AB The extrinsic apoptosis pathway is triggered by the binding of death ligands of the tumor necrosis factor (TNF) family to their appropriate death receptors (DRs) on the cell surface. One TNF family member, TNF-related apoptosis-inducing ligand (TRAIL or Apo2L), seems to preferentially cause apoptosis of transformed cells and can be systemically administered in the absence of severe toxicity. Therefore, there has been enthusiasm for the use of TRAIL or agonist antibodies to the TRAIL DR4 and DR5 in cancer therapy. Nonetheless, many cancer cells are very resistant to TRAIL apoptosis in vitro. Therefore, there is much interest in identifying compounds that can be combined with TRAIL to amplify its apoptotic effects. In this review, I will provide a brief overview of apoptosis signaling by TRAIL and discuss apoptosis-sensitizing agents, focusing mainly on the proteasome inhibitor bortezomib (VELCADE) and some novel sensitizers that we have recently identified. Alternative ways to administer TRAIL or DR agonist antibodies as therapeutic agents will also be described. Finally, I will discuss some of the gaps in our understanding of TRAIL apoptosis signaling and suggest some research directions that may provide additional information for optimizing the targeting of the extrinsic apoptosis pathway for future cancer therapy.
C1 NCI, SAIC Frederick Inc, Expt Immunol Lab, Ctr Canc Res,Canc & Inflammat Program, Frederick, MD 21702 USA.
RP Sayers, TJ (reprint author), NCI, SAIC Frederick Inc, Expt Immunol Lab, Ctr Canc Res,Canc & Inflammat Program, Frederick, MD 21702 USA.
EM sayerst@mail.nih.gov
RI Sayers, Thomas/G-4859-2015
FU National Cancer Institute, National Institutes of Health
[HSN261200800001E]; Center for Cancer Research, National Cancer
Institute, National Institutes of Health
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 HSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations implies endorsement by the US Government.
This Research was supported [in part] by the Intramural Research Program
of the Center for Cancer Research, National Cancer Institute, National
Institutes of Health. Thanks to Alan Brooks, Candace Thompson, Richard
Pompei, Drs Nancy Booth, and Curtis Henrich for their assistance with
this work and Andrew Sayers for help with the artwork.
NR 59
TC 91
Z9 95
U1 2
U2 40
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 AUG
PY 2011
VL 60
IS 8
BP 1173
EP 1180
DI 10.1007/s00262-011-1008-4
PG 8
WC Oncology; Immunology
SC Oncology; Immunology
GA 795KP
UT WOS:000292973400012
PM 21626033
ER
PT J
AU Ligthart, L
de Vries, B
Smith, AV
Ikram, MA
Amin, N
Hottenga, JJ
Koelewijn, SC
Kattenberg, VM
de Moor, MHM
Janssens, ACJW
Aulchenko, YS
Oostra, BA
de Geus, EJC
Smit, JH
Zitman, FG
Uitterlinden, AG
Hofman, A
Willemsen, G
Nyholt, DR
Montgomery, GW
Terwindt, GM
Gudnason, V
Penninx, BWJH
Breteler, M
Ferrari, MD
Launer, LJ
van Duijn, CM
van den Maagdenberg, AMJM
Boomsma, DI
AF Ligthart, Lannie
de Vries, Boukje
Smith, Albert V.
Ikram, M. Arfan
Amin, Najaf
Hottenga, Jouke-Jan
Koelewijn, Stephany C.
Kattenberg, V. Mathijs
de Moor, Marleen H. M.
Janssens, A. Cecile J. W.
Aulchenko, Yurii S.
Oostra, Ben A.
de Geus, Eco J. C.
Smit, Johannes H.
Zitman, Frans G.
Uitterlinden, Andre G.
Hofman, Albert
Willemsen, Gonneke
Nyholt, Dale R.
Montgomery, Grant W.
Terwindt, Gisela M.
Gudnason, Vilmundur
Penninx, Brenda W. J. H.
Breteler, Monique
Ferrari, Michel D.
Launer, Lenore J.
van Duijn, Cornelia M.
van den Maagdenberg, Arn M. J. M.
Boomsma, Dorret I.
CA Dutch Icelandic Migraine Genetics
TI Meta-analysis of genome-wide association for migraine in six
population-based European cohorts
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE migraine; meta-analysis; genome-wide association; population-based
ID FAMILIAL HEMIPLEGIC MIGRAINE; DELETION POLYMORPHISM; TYPICAL MIGRAINE;
COMMON MIGRAINE; CHROMOSOME 4Q24; AURA; GENE; SUSCEPTIBILITY; MTHFR;
ENTITIES
AB Migraine is a common neurological disorder with a genetically complex background. This paper describes a meta-analysis of genome-wide association (GWA) studies on migraine, performed by the Dutch-Icelandic migraine genetics (DICE) consortium, which brings together six population-based European migraine cohorts with a total sample size of 10 980 individuals (2446 cases and 8534 controls). A total of 32 SNPs showed marginal evidence for association at a P-value<10(-5). The best result was obtained for SNP rs9908234, which had a P-value of 8.00 x 10(-8). This top SNP is located in the nerve growth factor receptor (NGFR) gene. However, this SNP did not replicate in three cohorts from the Netherlands and Australia. Of the other 31 SNPs, 18 SNPs were tested in two replication cohorts, but none replicated. In addition, we explored previously identified candidate genes in the meta-analysis data set. This revealed a modest gene-based significant association between migraine and the metadherin (MTDH) gene, previously identified in the first clinic-based GWA study (GWAS) for migraine (Bonferroni-corrected gene-based P-value=0.026). This finding is consistent with the involvement of the glutamate pathway in migraine. Additional research is necessary to further confirm the involvement of glutamate. European Journal of Human Genetics (2011) 19, 901-907; doi:10.1038/ejhg.2011.48; published online 30 March 2011
C1 [Ligthart, Lannie; Hottenga, Jouke-Jan; Kattenberg, V. Mathijs; de Moor, Marleen H. M.; de Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands.
[Ligthart, Lannie] EMGO Inst Hlth & Care Res EMGO, Amsterdam, Netherlands.
[de Vries, Boukje; Koelewijn, Stephany C.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Smith, Albert V.; Gudnason, Vilmundur] Heart Prevent Clin & Res Inst, Iceland Heart Assoc, Kopavogur, Iceland.
[Amin, Najaf; Janssens, A. Cecile J. W.; Aulchenko, Yurii S.; Oostra, Ben A.; Breteler, Monique; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands.
[Amin, Najaf; Janssens, A. Cecile J. W.; Aulchenko, Yurii S.; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Clin Genet, Genet Epidemiol Unit, Rotterdam, Netherlands.
[Smit, Johannes H.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Smit, Johannes H.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Zitman, Frans G.; Penninx, Brenda W. J. H.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Nyholt, Dale R.] Queensland Inst Med Res, Neurogenet Lab, Brisbane, Qld 4006, Australia.
[Montgomery, Grant W.] Queensland Inst Med Res, Mol Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Terwindt, Gisela M.; Ferrari, Michel D.] Leiden Univ, Dept Neurol, Med Ctr, Leiden, Netherlands.
[Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Penninx, Brenda W. J. H.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands.
[Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Ligthart, L (reprint author), Vrije Univ Amsterdam, Dept Biol Psychol, Van der Boechorststr 1, NL-1081 BT Amsterdam, Netherlands.
EM rsl.ligthart@psy.vu.nl
RI Ligthart, Lannie/H-4600-2011; Nyholt, Dale/C-8384-2013; Aulchenko,
Yurii/M-8270-2013; Breteler, Monique /J-5058-2014; Gudnason,
Vilmundur/K-6885-2015; de Geus, Eco/M-9318-2015; Montgomery,
Grant/B-7148-2008; Smith, Albert/K-5150-2015;
OI Janssens, A Cecile/0000-0002-6153-4976; Aulchenko,
Yurii/0000-0002-7899-1575; Gudnason, Vilmundur/0000-0001-5696-0084; de
Geus, Eco/0000-0001-6022-2666; Montgomery, Grant/0000-0002-4140-8139;
Smith, Albert/0000-0003-1942-5845; Ikram, Mohammad
Arfan/0000-0003-0372-8585
FU NIH [N01-AG-12100]; NIA; Hjartavernd (the Icelandic Heart Association);
Althingi (the Icelandic Parliament); The Netherlands Organization for
Scientific Research (NWO) [903-52-291, Vici 918.56.602, 907-00-217];
Erasmus MC; Netherlands Genomics Initiative (NGI); EUROSPAN (European
Special Populations Research Network) through the European Commission
[018947, LSHG-CT-2006-01947]; Centre for Medical Systems Biology (CMSB1
and CMSB2); Netherlands Organization for Scientific Research (NWO:
MagW/ZonMW): [904-61-090, NWO 985-10-002, 904 61 193, 480-04-004,
400-05-717, Addiction-31160008, 40-0056-98-9032, SPI 56-464-14192];
CMSB: Center for Medical Systems Biology (NWO Genomics);
NBIC/BioAssist/RK/2008.024; BBMRI -NL: Biobanking and Biomolecular
Resources Research Infrastructure [184.021.007]; VU University:
Institute for Health and Care Research (EMGO+) and Neuroscience Campus
Amsterdam (NCA); European Science Foundation (ESF): Genomewide analyses
of European twin and population cohorts [EU/QLRT-2001-01254]; European
Community [FP7/2007-2013: ENGAGE (HEALTH-F4-2007-201413)]; European
Science Council (ERC); Genetics of Mental Illness [230374]; Rutgers
University [NIMH U24 MH068457-06]; Collaborative study of the genetics
of DZ twinning [NIH R01D0042157-01A]; Genetic Association Information
Network; public-private partnership between the NIH and Pfizer Inc.;
Affymetrix Inc.; Abbott Laboratories; Netherlands Organization for
Health Research and Development (ZonMw) [10-000-1002]; VU University
Medical Center; GGZ inGeest; Arkin; Leiden University Medical Center;
GGZ Rivierduinen; University Medical Center Groningen; Lentis; GGZ
Friesland; GGZ Drenthe; Scientific Institute for Quality of Health Care
(IQ Healthcare); Netherlands Institute for Health Services Research
(NIVEL); Netherlands Institute of Mental Health and Addiction (Trimbos);
Genetic Association Information Network (GAIN) of the Foundation for the
US National Institutes of Health (NTR1/NESDA); Spinozapremie [NWO/SPI
56-464-14192]; Erasmus Medical Center; Erasmus University; Rotterdam;
Research Institute for Diseases in the Elderly (RIDE); Ministry of
Education, Culture and Science; Ministry for Health, Welfare and Sports;
European Commission (DG XII); Netherlands Genomics Initiative
(NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA);
Municipality of Rotterdam; Netherlands Organization of Scientific
Research NWO [175.010.2005.011, 911-03-012]; Research Institute for
Diseases in the Elderly (RIDE and RIDE2); Netherlands Genomics
Initiative (NGI)/Netherlands Organization for Scientific Research (NWO)
[050-060-810]; Australian National Health and Medical Research Council
(NHMRC) [241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036,
442915, 442981, 496739, 552485, 552498]; Australian Research Council
[A7960034, A79906588, A79801419, DP0212016, DP0343921]
FX The Age, Gene/Environment Susceptibility Reykjavik Study is funded by
NIH contract N01-AG-12100, the NIA Intramural Research Program,
Hjartavernd (the Icelandic Heart Association) and the Althingi (the
Icelandic Parliament). The Erasmus Rucphen Family was supported by
grants from The Netherlands Organization for Scientific Research (NWO),
Erasmus MC and the Netherlands Genomics Initiative (NGI)-sponsored
Center of Medical Systems Biology (CMSB). The genotyping for the ERF
study was supported by EUROSPAN (European Special Populations Research
Network) through the European Commission FP6 STRP grant (018947;
LSHG-CT-2006-01947). The ERF study was further supported by grants from
the Netherlands Organisation for Scientific Research (NWO) (903-52-291,
M. D. F., Vici 918.56.602, M. D. F, 907-00-217 G. M. T.), Erasmus MC,
the Centre for Medical Systems Biology (CMSB1 and CMSB2), and the
Netherlands Genomics Initiative (NGI). We are grateful to all patients
and their relatives, general practitioners and neurologists for their
contributions and to P Veraart for her help in genealogy, Jeannette
Vergeer for the supervision of the laboratory work and P Snijders for
his help in data collection. For NESDA and NTR, funding was obtained
from the Netherlands Organization for Scientific Research (NWO:
MagW/ZonMW): Genetic basis of anxiety and depression (904-61-090);
Genetics of individual differences in smoking initiation and persistence
(NWO 985-10-002); Resolving cause and effect in the association between
exercise and well-being (904 61 193); Twin family database for behavior
genomics studies (480-04-004); Twin research focusing on behavior
(400-05-717); Genetic determinants of risk behavior in relation to
alcohol use and alcohol use disorder (Addiction-31160008);
Genotype/phenotype database for behavior genetic and genetic
epidemiological studies (40-0056-98-9032); Spinozapremie (SPI
56-464-14192); CMSB: Center for Medical Systems Biology (NWO Genomics);
NBIC/BioAssist/RK/2008.024); BBMRI -NL: Biobanking and Biomolecular
Resources Research Infrastructure (184.021.007); the VU University:
Institute for Health and Care Research (EMGO+) and Neuroscience Campus
Amsterdam (NCA); the European Science Foundation (ESF): Genomewide
analyses of European twin and population cohorts (EU/QLRT-2001-01254);
European Community's Seventh Framework Program (FP7/2007-2013): ENGAGE
(HEALTH-F4-2007-201413); the European Science Council (ERC) Genetics of
Mental Illness (230374); Rutgers University Cell and DNA Repository
cooperative agreement (NIMH U24 MH068457-06); Collaborative study of the
genetics of DZ twinning (NIH R01D0042157-01A); the Genetic Association
Information Network, a public-private partnership between the NIH and
Pfizer Inc., Affymetrix Inc. and Abbott Laboratories. The infrastructure
for the NESDA study (http://www.nesda.nl) is funded through the
Geestkracht program of the Netherlands Organization for Health Research
and Development (ZonMw, Grant number 10-000-1002) and is supported by
participating universities and mental health care organizations (VU
University Medical Center, GGZ inGeest, Arkin, Leiden University Medical
Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis,
GGZ Friesland, GGZ Drenthe, Scientific Institute for Quality of Health
Care (IQ Healthcare), Netherlands Institute for Health Services Research
(NIVEL) and Netherlands Institute of Mental Health and Addiction
(Trimbos)).; SNP genotyping was funded by the Genetic Association
Information Network (GAIN) of the Foundation for the US National
Institutes of Health (NT1/NESDA) and the Spinozapremie (NWO/SPI
56-464-14192; NTR2). Statistical analyses were partly carried out on the
Genetic Cluster Computer (NWO 480-05-003). The Rotterdam Study (I, I,
and II) are funded by Erasmus Medical Center and Erasmus University,
Rotterdam, Netherlands Organization for the Health Research and
Development (ZonMw), the Research Institute for Diseases in the Elderly
(RIDE), the Ministry of Education, Culture and Science, the Ministry for
Health, Welfare and Sports, the European Commission (DG XII), the
Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium
for Healthy Aging (NCHA) and the Municipality of Rotterdam. The
generation and management of GWAS genotype data for the Rotterdam Study
is supported by the Netherlands Organization of Scientific Research NWO
Investments (nr. 175.010.2005.011, 911-03-012). The Rotterdam Study is
funded by Erasmus Medical Center and Erasmus University, Rotterdam,
Netherlands Organization for the Health Research and Development
(ZonMw), the Research Institute for Diseases in the Elderly (RIDE and
RIDE2), the Ministry of Education, Culture and Science, the Ministry for
Health, Welfare and Sports, the European Commission (DG XII), the
Municipality of Rotterdam and the Netherlands Genomics Initiative
(NGI)/Netherlands Organization for Scientific Research (NWO) project nr.
050-060-810. We thank Pascal Arp, Mila Jhamai, Dr Michael Moorhouse,
Marijn Verkerk and Sander Bervoets for their help in creating the GWAS
database. We are grateful to the study participants, the staff from the
Rotterdam Study and the participating general practioners and
pharmacists. For the Australian cohort, we thank the Australian National
Health and Medical Research Council (NHMRC; Grants 241944, 339462,
389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496739,
552485 and 552498) and the Australian Research Council (A7960034,
A79906588, A79801419, DP0212016 and DP0343921) for funding. GWM and DRN
are supported by the NHMRC Fellowship and the Australian Research
Council Future Fellowship Schemes. We thank N Martin, P Visscher, D
Duffy, A Henders, B Usher, E Souzeau, A Kuot, A McMellon, MJ Wright, MJ
Campbell, A Caracella, L Bowdler, S Smith, S Gordon, B Haddon, D Smyth,
H Beeby, O Zheng and B Chapman for their input into project management,
databases, phenotype collection, and sample collection, processing and
genotyping.
NR 58
TC 47
Z9 48
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD AUG
PY 2011
VL 19
IS 8
BP 901
EP 907
DI 10.1038/ejhg.2011.48
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 795FC
UT WOS:000292957600017
PM 21448238
ER
PT J
AU Schully, SD
Yu, W
McCallum, V
Benedicto, CB
Dong, LM
Wulf, A
Clyne, M
Khoury, MJ
AF Schully, Sheri D.
Yu, Wei
McCallum, Victoria
Benedicto, Camilla B.
Dong, Linda M.
Wulf, Anja
Clyne, Melinda
Khoury, Muin J.
TI Cancer GAMAdb: database of cancer genetic associations from
meta-analyses and genome-wide association studies
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE cancer; meta-analyses; pooled analyses; GWAS
ID EPIDEMIOLOGY; KNOWLEDGE; DISEASE
AB In the field of cancer, genetic association studies are among the most active and well-funded research areas, and have produced hundreds of genetic associations, especially in the genome-wide association studies (GWAS) era. Knowledge synthesis of these discoveries is the first critical step in translating the rapidly emerging data from cancer genetic association research into potential applications for clinical practice. To facilitate the effort of translational research on cancer genetics, we have developed a continually updated database named Cancer Genome-wide Association and Meta Analyses database that contains key descriptive characteristics of each genetic association extracted from published GWAS and meta-analyses relevant to cancer risk. Here we describe the design and development of this tool with the aim of aiding the cancer research community to quickly obtain the current updated status in cancer genetic association studies. European Journal of Human Genetics (2011) 19, 928-930; doi:10.1038/ejhg.2011.53; published online 13 April 2011
C1 [Schully, Sheri D.; Benedicto, Camilla B.; Khoury, Muin J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Yu, Wei; Wulf, Anja; Clyne, Melinda; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[McCallum, Victoria] NCI, Off Workforce Dev, Bethesda, MD 20892 USA.
[Dong, Linda M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Schully, SD (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Executive Blvd,Suite 5124,MSC 7393, Bethesda, MD 20892 USA.
EM schullys@mail.nih.gov
RI Liao, Linda/B-3960-2011
NR 8
TC 12
Z9 12
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD AUG
PY 2011
VL 19
IS 8
BP 928
EP 930
DI 10.1038/ejhg.2011.53
PG 3
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 795FC
UT WOS:000292957600022
PM 21487441
ER
PT J
AU Sidorova, NY
Muradymov, S
Rau, DC
AF Sidorova, Nina Y.
Muradymov, Shakir
Rau, Donald C.
TI Solution parameters modulating DNA binding specificity of the
restriction endonuclease EcoRV
SO FEBS JOURNAL
LA English
DT Article
DE DNA-protein specific binding; equilibrium competition; gel
electrophoresis; restriction endonucleases; water activity
ID DEGENERATE RECOGNITION SEQUENCES; PVUII ENDONUCLEASE; NONSPECIFIC DNA;
GEL-ELECTROPHORESIS; CRYSTAL-STRUCTURE; OSMOTIC-STRESS; WATER RELEASE;
METAL-IONS; SITE; CLEAVAGE
AB The DNA binding stringency of restriction endonucleases is crucial for their proper function. The X-ray structures of the specific and non-cognate complexes of the restriction nuclease EcoRV are considerably different suggesting significant differences in the hydration and binding free energies. Nonetheless, the majority of studies performed at pH 7.5, optimal for enzymatic activity, have found a < 10-fold difference between EcoRV binding constants to the specific and nonspecific sequences in the absence of divalent ions. We used a recently developed self-cleavage assay to measure EcoRV-DNA competitive binding and to evaluate the influence of water activity, pH and salt concentration on the binding stringency of the enzyme in the absence of divalent ions. We find the enzyme can readily distinguish specific and nonspecific sequences. The relative specific-nonspecific binding constant increases strongly with increasing neutral solute concentration and with decreasing pH. The difference in number of associated waters between specific and nonspecific DNA-EcoRV complexes is consistent with the differences in the crystal structures. Despite the large pH dependence of the sequence specificity, the osmotic pressure dependence indicates little change in structure with pH. The large osmotic pressure dependence means that measurement of protein-DNA specificity in dilute solution cannot be directly applied to binding in the crowded environment of the cell. In addition to divalent ions, water activity and pH are key parameters that strongly modulate binding specificity of EcoRV.
C1 [Sidorova, Nina Y.; Muradymov, Shakir; Rau, Donald C.] NIH, Lab Phys & Struct Biol, Program Phys Biol, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Sidorova, NY (reprint author), 9 Mem Dr,Bld 9,Rm 1E-108,MSC 0924, Bethesda, MD 20892 USA.
EM sidorova@mail.nih.gov
FU NICHD, National Institutes of Health
FX We greatly appreciate the generous gift of Escherichia coli strain CSH50
(pMetB) and plasmid mix pBSKSRVD/pMetB from Dr Andrea Prota and Dr Fritz
Winkler (Paul Scherrer Institut, Switzerland). We are deeply grateful to
Dr Galina Obmolova (Centocor) and Dr Andrea Prota for their valuable
advice regarding EcoRV purification. This work was supported by the
Intramural Research Program of the NICHD, National Institutes of Health.
NR 42
TC 7
Z9 7
U1 0
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD AUG
PY 2011
VL 278
IS 15
BP 2713
EP 2727
DI 10.1111/j.1742-4658.2011.08198.x
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 794WZ
UT WOS:000292933300010
PM 21624054
ER
PT J
AU Chiang, HS
Maric, M
AF Chiang, Hao-Sen
Maric, Maja
TI Lysosomal thiol reductase negatively regulates autophagy by altering
glutathione synthesis and oxidation
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Autophagy; GILT; GSH; ROS; SOD2
ID MITOCHONDRIAL PERMEABILITY TRANSITION; MNSOD GENE-EXPRESSION;
NF-KAPPA-B; CELL-DEATH; REDOX REGULATION; CUTTING EDGE; CANCER-CELLS;
IN-VIVO; PROTEIN; DISEASE
AB Redox regulation is critical for a number of cellular functions and has been implicated in the etiology and progression of several diseases, such as cardiovascular diseases, neurodegenerative diseases, and cancer. It has been shown that, in the absence of gamma-interferon inducible lysosomal thiol reductase (GILT), cells are under increased oxidative stress with higher superoxide levels and decreased stability, expression, and function of mitochondrial manganese superoxide dismutase (SOD2). Here, we further elucidate the role of GILT in the homeostatic regulation of oxidative stress. We show that GILT-deficient fibroblasts exhibit reduced glutathione levels, shift in GSSG/GSH ratio toward the oxidized form, and accumulate dysfunctional mitochondria. Redox-sensitive pathways involving Erk1/2 activation and nuclear high mobility group box 1 (HMGB1) protein cytosolic translocation are both activated and associated with increased autophagy in GILT-/- fibroblasts. We hypothesize that these events are responsible for degrading the damaged mitochondria and mitochondrial SOD2 in the absence of GILT. This is the first time to our knowledge that a lysosomal enzyme has been implicated in global effects within the cell. Published by Elsevier Inc.
C1 [Chiang, Hao-Sen; Maric, Maja] Georgetown Univ, Dept Microbiol & Immunol, Med Ctr, Washington, DC 20057 USA.
RP Maric, M (reprint author), NIAID, Div Extramural Activ, NIH, Bethesda, MD 20892 USA.
EM mam254@gmail.com
OI CHIANG, HAO-SEN/0000-0001-5041-9705
NR 90
TC 23
Z9 23
U1 2
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG 1
PY 2011
VL 51
IS 3
BP 688
EP 699
DI 10.1016/j.freeradbiomed.2011.05.015
PG 12
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 793XJ
UT WOS:000292856900012
PM 21640818
ER
PT J
AU Ganini, D
Christoff, M
Ehrenshaft, M
Kadiiska, MB
Mason, RP
Bechara, EJH
AF Ganini, Douglas
Christoff, Marcelo
Ehrenshaft, Marilyn
Kadiiska, Maria B.
Mason, Ronald P.
Bechara, Etelvino J. H.
TI Myoglobin-H2O2 catalyzes the oxidation of beta-ketoacids to
alpha-dicarbonyls: Mechanism and implications in ketosis
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Myoglobin; Acetoacetate; 2-Methylacetoacetate; Free radicals; Triplet
carbonyls; Methylglyoxal; Diacetyl; Ketosis
ID GLYCATION END-PRODUCTS; CULTURED U937 MONOCYTES; TYPE-2
DIABETIC-NEPHROPATHY; HYDROGEN-PEROXIDE; HORSERADISH-PEROXIDASE; XYLENOL
ORANGE; RENAL-FUNCTION; RAT MODEL; ACETOACETATE; METHYLGLYOXAL
AB Acetoacetate (AA) and 2-methylacetoacetate (MAA) are accumulated in metabolic disorders such as diabetes and isoleucinemia. Here we examine the mechanism of AA and MAA aerobic oxidation initiated by myoglobin (Mb)/H2O2. We propose a chemiluminescent route involving a dioxetanone intermediate whose thermolysis yields triplet alpha-dicarbonyl species (methylglyoxal and diacetyl). The observed ultraweak chemiluminescence increased linearly on raising the concentration of either Mb (10-500 mu M) or AA (10-100 mM). Oxygen uptake studies revealed that MAA is almost a 100-fold more reactive than AA. EPR spin-trapping studies with MNP/MAA revealed the intermediacy of an alpha-carbon-centered radical and acetyl radical. The latter radical, probably derived from triplet diacetyl, is totally suppressed by sorbate, a well-known quencher of triplet carbonyls. Furthermore, an EPR signal assignable to MNP-AA(center dot) adduct was observed and confirmed by isotope effects. Oxygen consumption and a-dicarbonyl yield were shown to be dependent on AA or MAA concentrations (1-50 mM) and on H2O2 or tert-butOOH added to the Mb-containing reaction mixtures. That ferrylMb is involved in a peroxidase cycle acting on the substrates is suggested by the reaction pH profiles and immunospin-trapping experiments. The generation of radicals and triplet dicarbonyl products by Mb/H2O2/beta-ketoacids may contribute to the adverse health effects of ketogenic unbalance. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Bechara, Etelvino J. H.] Univ Fed Sao Paulo, Dept Ciencias Exatas & Terra, Inst Ciencias Ambientais Quim & Farmaceut, BR-00972270 Diadema, SP, Brazil.
[Ganini, Douglas; Christoff, Marcelo; Bechara, Etelvino J. H.] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo, Brazil.
[Ehrenshaft, Marilyn; Kadiiska, Maria B.; Mason, Ronald P.] Natl Inst Environm Hlth Sci, Free Rad Metab Grp, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Bechara, EJH (reprint author), Univ Fed Sao Paulo, Dept Ciencias Exatas & Terra, Inst Ciencias Ambientais Quim & Farmaceut, Rua Prof Artur Riedel 275, BR-00972270 Diadema, SP, Brazil.
EM ejhbechara@gmail.com
RI 3, INCT/H-4497-2013; Redoxoma, Inct/H-9962-2013; Bechara,
Etelvino/M-6251-2013
OI Bechara, Etelvino/0000-0001-9526-2529
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Conselho
Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Instituto
Nacional de Ciencia e Tecnologia (INCT) Redoxoma; National Institute of
Environmental Health Sciences (NIEHS)
FX This work was supported by grants from the Fundacao de Amparo a Pesquisa
do Estado de Sao Paulo (FAPESP), the Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq), the Instituto Nacional
de Ciencia e Tecnologia (INCT) Redoxoma, and Intramural Research Program
of the National Institute of Environmental Health Sciences (NIEHS). We
acknowledge Dr. Ann Motten for editing this manuscript.
NR 67
TC 4
Z9 4
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG 1
PY 2011
VL 51
IS 3
BP 733
EP 743
DI 10.1016/j.freeradbiomed.2011.05.002
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 793XJ
UT WOS:000292856900017
PM 21609760
ER
PT J
AU Davis, RM
Sowers, AL
DeGraff, W
Bernardo, M
Thetford, A
Krishna, MC
Mitchell, JB
AF Davis, Ryan M.
Sowers, Anastasia L.
DeGraff, William
Bernardo, Marcelino
Thetford, Angela
Krishna, Murali C.
Mitchell, James B.
TI A novel nitroxide is an effective brain redox imaging contrast agent and
in vivo radioprotector
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Radioprotection; Redox imaging; Blood-brain-barrier-permeable contrast
agents; Nitroxides; Magnetic resonance imaging
ID ELECTRON-PARAMAGNETIC-RESONANCE; GLUTATHIONE LEVELS; ESR SPECTROSCOPY;
OXIDATIVE STRESS; FREE-RADICALS; ANTIOXIDANT DEFENSE; PROSTATE-CANCER;
DOSE-ESCALATION; MDMA ECSTASY; MOUSE MODEL
AB Individuals are exposed to ionizing radiation during medical procedures and nuclear disasters, and this exposure can be carcinogenic, toxic, and sometimes fatal. Drugs that protect individuals from the adverse effects of radiation may therefore be valuable countermeasures against the health risks of exposure. In the current study, the LD50/30 (the dose resulting in 50% of exposed mice surviving 30 days after exposure) was determined in control C3H mice and mice treated with the nitroxide radioprotectors Tempol, 3-CP, 16c, 22c, and 23c. The pharmacokinetics of 22c and 23c were measured with magnetic resonance imaging (MRI) in the brain, blood, submandibular salivary gland, liver, muscle, tongue, and myocardium. It was found that 23c was the most effective radioprotector of the five studied: 23c increased the LD50/30 in mice from 7.9 +/- 0.15 Gy (treated with saline) to 11.47 +/- 0.13 Gy (an increase of 45%). Additionally, MRI-based pharmacokinetic studies revealed that 23c is an effective redox imaging agent in the mouse brain, and that 23c may allow functional imaging of the myocardium. The data in this report suggest that 23c is currently the most potent known nitroxide radioprotector, and that it may also be useful as a contrast agent for functional imaging. Published by Elsevier Inc.
C1 [Davis, Ryan M.; Sowers, Anastasia L.; DeGraff, William; Thetford, Angela; Krishna, Murali C.; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bernardo, Marcelino] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Davis, RM (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, Bldg 10,Room B3-B69,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ryan.m.davis@duke.edu
FU NIAID; Center of Cancer Research, National Cancer Institute, NIH
FX This research was supported by the NIAID Medical Countermeasures against
Radiological and Nuclear Threats Program and the Intramural Research
Program of the Center of Cancer Research, National Cancer Institute,
NIH.
NR 48
TC 24
Z9 25
U1 2
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG 1
PY 2011
VL 51
IS 3
BP 780
EP 790
DI 10.1016/j.freeradbiomed.2011.05.019
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 793XJ
UT WOS:000292856900022
PM 21664459
ER
PT J
AU Butler, J
Kalogeropoulos, AP
Georgiopoulou, VV
Bibbins-Domingo, K
Najjar, SS
Sutton-Tyrrell, KC
Harris, TB
Kritchevsky, SB
Lloyd-Jones, DM
Newman, AB
Psaty, BM
AF Butler, Javed
Kalogeropoulos, Andreas P.
Georgiopoulou, Vasiliki V.
Bibbins-Domingo, Kirsten
Najjar, Samer S.
Sutton-Tyrrell, Kim C.
Harris, Tamara B.
Kritchevsky, Stephen B.
Lloyd-Jones, Donald M.
Newman, Anne B.
Psaty, Bruce M.
TI Systolic blood pressure and incident heart failure in the elderly. The
Cardiovascular Health Study and the Health, Ageing and Body Composition
Study
SO HEART
LA English
DT Article
ID LEFT-VENTRICULAR HYPERTROPHY; MYOCARDIAL-INFARCTION; MULTIPLE
IMPUTATION; DIABETES-MELLITUS; PULSE PRESSURE; OLDER PERSONS;
RISK-FACTORS; DISEASE; HYPERTENSION; MORTALITY
AB Background The exact form of the association between systolic blood pressure (SBP) and heart failure (HF) risk in the elderly remains incompletely defined, especially in individuals not receiving antihypertensive drugs.
Objective To examine the association between SBP and HF risk in the elderly.
Design Competing-risks proportional hazards modelling of incident HF risk, using 10-year follow-up data from two NIH-sponsored cohort studies: the Cardiovascular Health Study (inception: 1989-90 and 1992-3) and the Health ABC Study (inception: 1997-8).
Setting Community-based cohorts.
Participants 4408 participants (age, 72.8 (4.9) years; 53.1% women, 81.7% white; 18.3% black) without prevalent HF and not receiving antihypertensive drugs at baseline.
Main outcome measures Incident HF, defined as first adjudicated hospitalisation for HF.
Results Over 10 years, 493 (11.2%) participants developed HF. Prehypertension (120-139 mm Hg), stage 1 (140-159 mm Hg), and stage 2 (>= 160 mm Hg) hypertension were associated with escalating HF risk; HRs versus optimal SBP (<120 mm Hg) in competing-risks models controlling for clinical characteristics were 1.63 (95% CI 1.23 to 2.16; p=0.001), 2.21 (95% CI 1.65 to 2.96; p<0.001) and 2.60 (95% CI 1.85 to 3.64; p<0.001), respectively. Overall 255/493 (51.7%) HF events occurred in participants with SBP <140 mm Hg at baseline. Increasing SBP was associated with higher HF risk in women than in men; no race-SBP interaction was seen. In analyses with continuous SBP, HF risk had a continuous positive association with SBP to levels as low as 113 mm Hg in men and 112 mm Hg in women.
Conclusions There is a continuous positive association between SBP and HF risk in the elderly for levels of SBP as low as <115 mm Hg; over half of incident HF events occur in individuals with SBP <140 mm Hg.
C1 [Butler, Javed] Emory Univ, Emory Clin Cardiovasc Res Inst, Dept Med, Atlanta, GA 30322 USA.
[Bibbins-Domingo, Kirsten] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Bibbins-Domingo, Kirsten] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Bibbins-Domingo, Kirsten] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Najjar, Samer S.] Washington Hosp Ctr, MedStar Hlth Res Inst, Washington, DC 20010 USA.
[Sutton-Tyrrell, Kim C.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Dept Med Geriatr & Gerontol, Winston Salem, NC 27109 USA.
[Lloyd-Jones, Donald M.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
RP Butler, J (reprint author), Emory Univ, Emory Clin Cardiovasc Res Inst, Dept Med, 1462 Clifton Rd NE,Suite 504, Atlanta, GA 30322 USA.
EM javed.butler@emory.edu
RI Lloyd-Jones, Donald/C-5899-2009; Newman, Anne/C-6408-2013;
Kalogeropoulos, Andreas/A-9494-2009;
OI Newman, Anne/0000-0002-0106-1150; Kalogeropoulos,
Andreas/0000-0002-1284-429X; Kritchevsky, Stephen/0000-0003-3336-6781
FU National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
U01 HL080295]; National Institute of Neurological Disorders and Stroke
(Cardiovascular Health Study); National Institute of Ageing (Health ABC
Study) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIH, National
Institute on Ageing; Emory University; NIH, National Center for Research
Resources [UL1 RR025008]
FX This research was supported by contract numbers N01-HC-85079 through
N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133, grant U01 HL080295 from the National Heart, Lung, and
Blood Institute, with additional contribution from the National
Institute of Neurological Disorders and Stroke (Cardiovascular Health
Study), and contract numbers N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106
from the National Institute of Ageing (Health ABC Study). A full list of
the Cardiovascular Health Study investigators and institutions can be
found at http://www.chs-nhlbi.org/pi.htm. This research was also
supported in part by the Intramural Research Program of the NIH,
National Institute on Ageing, by an Emory University Heart and Vascular
Board grant entitled 'Novel Risk Markers and Prognosis Determination in
Heart Failure', and by PHS Grant UL1 RR025008 from the Clinical and
Translational Science Award program, NIH, National Center for Research
Resources.
NR 47
TC 22
Z9 23
U1 0
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
EI 1468-201X
J9 HEART
JI Heart
PD AUG
PY 2011
VL 97
IS 16
BP 1304
EP 1311
DI 10.1136/hrt.2011.225482
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 794QD
UT WOS:000292914900006
PM 21636845
ER
PT J
AU Boyles, AL
Ballard, JL
Gorman, EB
McConnaughey, DR
Cabrera, RM
Wilcox, AJ
Lie, RT
Finnell, RH
AF Boyles, A. L.
Ballard, J. L.
Gorman, E. B.
McConnaughey, D. R.
Cabrera, R. M.
Wilcox, A. J.
Lie, R. T.
Finnell, R. H.
TI Association between inhibited binding of folic acid to folate receptor a
in maternal serum and folate-related birth defects in Norway
SO HUMAN REPRODUCTION
LA English
DT Article
DE neural tube defects; oral facial clefts; folic acid; folate receptor;
maternal autoantibodies
ID NEURAL-TUBE DEFECTS; NORWEGIAN MOTHER; CHILD COHORT; ORAL CLEFTS;
AUTOANTIBODIES; RISK; PREVENTION; PREGNANCY; PALATE; WOMEN
AB BACKGROUND: Folic acid intake during pregnancy can reduce the risk of neural tube defects (NTDs) and perhaps also oral facial clefts. Maternal autoantibodies to folate receptors can impair folic acid binding. We explored the relationship of these birth defects to inhibition of folic acid binding to folate receptor alpha (FR alpha), as well as possible effects of parental demographics or prenatal exposures.
METHODS: We conducted a nested case-control study within the Norwegian Mother and Child Cohort Study. The study included mothers of children with an NTD (n = 11), cleft lip with or without cleft palate (CL/P, n 72), or cleft palate only (CPO, n = 27), and randomly selected mothers of controls (n = 221). The inhibition of folic acid binding to FR alpha was measured in maternal plasma collected around 17 weeks of gestation. On the basis of prior literature, the maternal age, gravidity, education, smoking, periconception folic acid supplement use and milk consumption were considered as potential confounding factors.
RESULTS: There was an increased risk of NTDs with increased binding inhibition [adjusted odds ratio (aOR) 1.4, 95% confidence interval (CI) 1.0-1.8]. There was no increased risk of oral facial clefts from inhibited folic acid binding to FR alpha (CL/P aOR 0.7, 95% CI 0.6-1.0; CPO aOR 1.1, 95% CI 0.8-1.4). No association was seen between smoking, folate supplementation or other cofactors and inhibition of folic acid binding to FR alpha.
CONCLUSIONS: Inhibition of folic acid binding to FR alpha in maternal plasma collected during pregnancy was associated with increased risk of NTDs but not oral facial clefts.
C1 [Boyles, A. L.; Wilcox, A. J.] NIEHS, Epidemiol Branch, NIH, Durham, NC 27709 USA.
[Ballard, J. L.] Texas A&M Inst Genom Med, College Stn, TX 77843 USA.
[Gorman, E. B.] Texas A&M Univ, Inst Biosci & Technol, Ctr Environm & Genet Med, Hlth Sci Ctr, Houston, TX 77030 USA.
[McConnaughey, D. R.] Westat Corp, Durham, NC 27703 USA.
[Cabrera, R. M.; Finnell, R. H.] Univ Texas Austin, Dell Pediat Res Inst, Dept Nutr Sci, Austin, TX 78723 USA.
[Lie, R. T.] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, N-5020 Bergen, Norway.
[Finnell, R. H.] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA.
RP Boyles, AL (reprint author), NIEHS, Epidemiol Branch, NIH, Durham, NC 27709 USA.
EM boylesa@niehs.nih.gov
OI Boyles, Abee/0000-0002-8711-2077
FU NIH, National Institute of Environmental Health Sciences; U.S. National
Institutes of Health [DE016315, NS050249]; Albert and Margaret Alkek
Foundation
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences; U.S. National
Institutes of Health Grant Numbers DE016315 and NS050249; and the Albert
and Margaret Alkek Foundation.
NR 29
TC 13
Z9 13
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD AUG
PY 2011
VL 26
IS 8
BP 2232
EP 2238
DI 10.1093/humrep/der144
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 793QD
UT WOS:000292837300037
PM 21576080
ER
PT J
AU Germain, RN
AF Germain, Ronald N.
TI Uncovering the Role of Invariant Chain in Controlling MHC Class II
Antigen Capture
SO JOURNAL OF IMMUNOLOGY
LA English
DT Editorial Material
ID MAJOR HISTOCOMPATIBILITY COMPLEX; IMMUNE-RESPONSE GENES; HLA-DR
MOLECULES; T-LYMPHOCYTES; PEPTIDE BINDING; MICE LACKING; TRANSPORT;
REGION; INHIBITION; ACTIVATION
C1 NIAID, Lab Syst Biol, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA.
RP Germain, RN (reprint author), NIAID, Lab Syst Biol, Lymphocyte Biol Sect, NIH, Bldg 10,Room 11N311,10 Ctr Drive,MSC 1892, Bethesda, MD 20892 USA.
EM rgermain@nih.gov
FU Intramural NIH HHS [ZIA AI000545-22]
NR 33
TC 7
Z9 9
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 AUG 1
PY 2011
VL 187
IS 3
BP 1073
EP 1075
DI 10.4049/jimmunol.1101663
PG 3
WC Immunology
SC Immunology
GA 794CY
UT WOS:000292874200003
PM 21772033
ER
PT J
AU Kashyap, M
Rochman, Y
Spolski, R
Samsel, L
Leonard, WJ
AF Kashyap, Mohit
Rochman, Yrina
Spolski, Rosanne
Samsel, Leigh
Leonard, Warren J.
TI Thymic Stromal Lymphopoietin Is Produced by Dendritic Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN EPITHELIAL-CELLS; BLOOD MONOCYTES; CUTTING EDGE; FLT3 LIGAND;
IN-VITRO; RECEPTOR; TSLP; INFLAMMATION; ASTHMA; CHEMOKINES
AB Thymic stromal lymphopoietin (TSLP) is a type 1 cytokine that contributes to lymphopoiesis and the development of asthma and atopic dermatitis. TSLP acts on multiple lineages, including dendritic cells (DCs), T cells, NKT cells, eosinophils, and mast cells, mediating proliferation and survival and linking innate and adaptive immune responses. TSLP is produced by a range of cells, including epithelial cells, fibroblasts, stromal cells, and keratinocytes. DCs are important primary targets of TSLP, and we unexpectedly demonstrated that DCs also produce TSLP in response to TLR stimulation and that this is augmented by IL-4. Moreover, we demonstrated that when mice were challenged with house dust mite extract, lung CD11c(+) DCs expressed TSLP mRNA at an even higher level than did epithelial cells. These data suggested that DCs not only respond to TSLP but also are a source of TSLP during pathogen and/or allergen encounter. The Journal of Immunology, 2011, 187: 1207-1211.
C1 [Kashyap, Mohit; Rochman, Yrina; Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 7B05,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM wjl@helix.nih.gov
RI Kashyap, Mohit/F-4534-2011
FU National Heart, Lung, and Blood Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program, National
Heart, Lung, and Blood Institute, National Institutes of Health.
NR 36
TC 61
Z9 64
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 1
PY 2011
VL 187
IS 3
BP 1207
EP 1211
DI 10.4049/jimmunol.1100355
PG 5
WC Immunology
SC Immunology
GA 794CY
UT WOS:000292874200020
PM 21690322
ER
PT J
AU Wang, XH
Meyers, C
Wang, HK
Chow, LT
Zheng, ZM
AF Wang, Xiaohong
Meyers, Craig
Wang, Hsu-Kun
Chow, Louise T.
Zheng, Zhi-Ming
TI Construction of a Full Transcription Map of Human Papillomavirus Type 18
during Productive Viral Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NEGATIVE REGULATORY ELEMENT; POLYADENYLATION FACTOR CPSF-73;
MESSENGER-RNA POLYADENYLATION; IN-SITU HYBRIDIZATION; GENE-EXPRESSION;
CELL-LINE; LIFE-CYCLE; EPITHELIAL DIFFERENTIATION; HUMAN KERATINOCYTES;
POLY(A) POLYMERASE
AB Human papillomavirus type 18 (HPV18) is the second most common oncogenic HPV genotype, responsible for similar to 15% of cervical cancers worldwide. In this study, we constructed a full HPV18 transcription map using HPV18-infected raft tissues derived from primary human vaginal or foreskin keratinocytes. By using 5' rapid amplification of cDNA ends (RACE), we mapped two HPV18 transcription start sites (TSS) for early transcripts at nucleotide (nt) 55 and nt 102 and the HPV18 late TSS frequently at nt 811, 765, or 829 within the E7 open reading frame (ORF) of the virus genome. HPV18 polyadenylation cleavage sites for early and late transcripts were mapped to nt 4270 and mainly to nt 7299 or 7307, respectively, by using 3' RACE. Although all early transcripts were cleaved exclusively at a single cleavage site, HPV18 late transcripts displayed the heterogeneity of 3' ends, with multiple minor cleavage sites for late RNA polyadenylation. HPV18 splice sites/splice junctions for both early and late transcripts were identified by 5' RACE and primer walking techniques. Five 5' splice sites (donor sites) and six 3' splice sites (acceptor sites) that are highly conserved in other papillomaviruses were identified in the HPV18 genome. HPV18 L1 mRNA translates a L1 protein of 507 amino acids (aa), smaller than the 568 aa residues previously predicted. Collectively, a full HPV18 transcription map constructed from this report will lead us to further understand HPV18 gene expression and virus oncogenesis.
C1 [Wang, Xiaohong; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Meyers, Craig] Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA USA.
[Wang, Hsu-Kun; Chow, Louise T.] Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL USA.
RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Sect, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, 10 Ctr Dr,Rm 6N106, Bethesda, MD 20892 USA.
EM zhengt@exchange.nih.gov
FU NCI, Center for Cancer Research, National Institutes of Health; NIH [R01
AI057988-01, CA83679]
FX This work was supported by the Intramural Research Program of the NCI,
Center for Cancer Research, National Institutes of Health, and NIH grant
R01 AI057988-01 to C. Meyers and NIH grant CA83679 to L. T. Chow.
NR 92
TC 34
Z9 37
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2011
VL 85
IS 16
BP 8080
EP 8092
DI 10.1128/JVI.00670-11
PG 13
WC Virology
SC Virology
GA 794TB
UT WOS:000292923100012
PM 21680515
ER
PT J
AU Fusaro, A
Monne, I
Salviato, A
Valastro, V
Schivo, A
Amarin, NM
Gonzalez, C
Ismail, MM
Al-Ankari, AR
Al-Blowi, MH
Khan, OA
Ali, ASM
Hedayati, A
Garcia, JG
Ziay, GM
Shoushtari, A
Al Qahtani, KN
Capua, I
Holmes, EC
Cattoli, G
AF Fusaro, Alice
Monne, Isabella
Salviato, Annalisa
Valastro, Viviana
Schivo, Alessia
Amarin, Nadim Mukhles
Gonzalez, Carlos
Ismail, Mahmoud Moussa
Al-Ankari, Abdu-Rahman
Al-Blowi, Mohamed Hamad
Khan, Owais Ahmed
Ali, Ali Safar Maken
Hedayati, Afshin
Garcia Garcia, Juan
Ziay, Ghulam M.
Shoushtari, Abdolhamid
Al Qahtani, Kassem Nasser
Capua, Ilaria
Holmes, Edward C.
Cattoli, Giovanni
TI Phylogeography and Evolutionary History of Reassortant H9N2 Viruses with
Potential Human Health Implications
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID INFLUENZA-A VIRUSES; AVIAN INFLUENZA; SOUTHEASTERN CHINA;
GENETIC-CHARACTERIZATION; PHYLOGENETIC ANALYSIS; CONTINUING EVOLUTION;
HUMAN INFECTION; SOUTHERN CHINA; HONG-KONG; POULTRY
AB Avian influenza viruses of the H9N2 subtype have seriously affected the poultry industry of the Far and Middle East since the mid-1990s and are considered one of the most likely candidates to cause a new influenza pandemic in humans. To understand the genesis and epidemiology of these viruses, we investigated the spatial and evolutionary dynamics of complete genome sequences of H9N2 viruses circulating in nine Middle Eastern and Central Asian countries from 1998 to 2010. We identified four distinct and cocirculating groups (A, B, C, and D), each of which has undergone widespread inter- and intrasubtype reassortments, leading to the generation of viruses with unknown biological properties. Our analysis also suggested that eastern Asia served as the major source for H9N2 gene segments in the Middle East and Central Asia and that in this geographic region within-country evolution played a more important role in shaping viral genetic diversity than migration between countries. The genetic variability identified among the H9N2 viruses was associated with specific amino acid substitutions that are believed to result in increased transmissibility in mammals, as well as resistance to antiviral drugs. Our study highlights the need to constantly monitor the evolution of H9N2 viruses in poultry to better understand the potential risk to human health posed by these viruses.
C1 [Fusaro, Alice; Monne, Isabella; Salviato, Annalisa; Valastro, Viviana; Schivo, Alessia; Capua, Ilaria; Cattoli, Giovanni] OIE FAO, Ist Zooprofilatt Sperimentale Venezie, Dept Res & Dev, I-35020 Padua, Italy.
[Fusaro, Alice; Monne, Isabella; Salviato, Annalisa; Valastro, Viviana; Schivo, Alessia; Capua, Ilaria; Cattoli, Giovanni] OIE Collaborating Ctr Dis Human Anim Interface, Natl Reference Lab Newcastle Dis & Avian Influenz, I-35020 Padua, Italy.
[Amarin, Nadim Mukhles] Boehringer Ingelheim GmbH & Co KG, Dubai, U Arab Emirates.
[Gonzalez, Carlos] Boehringer Ingelheim SA CV, Mexico City, DF, Mexico.
[Ismail, Mahmoud Moussa; Al-Ankari, Abdu-Rahman] King Faisal Univ, Coll Vet Med & Anim Resources, Al Hasa, Saudi Arabia.
[Ismail, Mahmoud Moussa] Kafrelsheikh Univ, Dept Poultry Dis, Coll Vet Med, Kafrelsheikh City, Egypt.
[Al-Blowi, Mohamed Hamad] Minist Agr, Riyadh, Saudi Arabia.
[Khan, Owais Ahmed] Texas A&M Univ, Coll Vet Med, College Stn, TX 77843 USA.
[Ali, Ali Safar Maken] UN, Iran Food & Agr Org, Off Anim Hlth, Tehran, Iran.
[Hedayati, Afshin] Iran Vet Org, Tehran, Iran.
[Garcia Garcia, Juan] FAO, Emergency Ctr Control Transboundary Anim Dis, Santiago, Chile.
[Ziay, Ghulam M.] Cent Vet Diagnost & Res Lab, Kabul, Afghanistan.
[Shoushtari, Abdolhamid] Razi Vaccine & Serum Res Inst, Dept Avian Dis, Karaj, Iran.
[Al Qahtani, Kassem Nasser] Minist Environm, Dept Anim Resources, Doha, Qatar.
[Holmes, Edward C.] Penn State Univ, Mueller Lab, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Fusaro, A (reprint author), OIE FAO, Ist Zooprofilatt Sperimentale Venezie, Dept Res & Dev, Viale Univ 10, I-35020 Padua, Italy.
EM afusaro@izsvenezie.it
RI Vaccine & Serum Research Institute, Razi /A-3892-2017;
OI Fusaro, Alice/0000-0002-8213-5472; Holmes, Edward/0000-0001-9596-3552
FU Italian Ministry of Health [RC IZS VE 14/09]; Food & Agricultural
Organization of the United Nations [41097]; NIH [GM080533-04]
FX We thank Boehringer Ingelheim Vetmedica for its assistance in
facilitating exchange of information, data sharing, sample submissions,
and financial support. Part of this work was financially supported by
the Italian Ministry of Health through RC IZS VE 14/09 and by the Food &
Agricultural Organization of the United Nations (LoA PR n. 41097) and
has been conducted in the framework of EU project FLUTRAIN. Edward C.
Holmes was funded in part by NIH grant GM080533-04.
NR 51
TC 63
Z9 64
U1 1
U2 17
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2011
VL 85
IS 16
BP 8413
EP 8421
DI 10.1128/JVI.00219-11
PG 9
WC Virology
SC Virology
GA 794TB
UT WOS:000292923100044
PM 21680519
ER
PT J
AU Ramchandani, VA
Umhau, J
Pavon, FJ
Ruiz-Velasco, V
Margas, W
Sun, H
Damadzic, R
Eskay, R
Schoor, M
Thorsell, A
Schwandt, ML
Sommer, WH
George, DT
Parsons, LH
Herscovitch, P
Hommer, D
Heilig, M
AF Ramchandani, V. A.
Umhau, J.
Pavon, F. J.
Ruiz-Velasco, V.
Margas, W.
Sun, H.
Damadzic, R.
Eskay, R.
Schoor, M.
Thorsell, A.
Schwandt, M. L.
Sommer, W. H.
George, D. T.
Parsons, L. H.
Herscovitch, P.
Hommer, D.
Heilig, M.
TI A genetic determinant of the striatal dopamine response to alcohol in
men
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE alcohol; dopamine; opioids; reward; polymorphism; positron emission
tomography
ID OPIOID-RECEPTOR GENE; SINGLE-NUCLEOTIDE POLYMORPHISM; STRESSFUL LIFE
EVENTS; FAMILY HISTORY; FUNCTIONAL POLYMORPHISM; NALTREXONE RESPONSE;
A118G POLYMORPHISM; NUCLEUS-ACCUMBENS; DRINKING HISTORY; RHESUS MACAQUES
AB Excessive alcohol use, a major cause of morbidity and mortality, is less well understood than other addictive disorders. Dopamine release in ventral striatum is a common element of drug reward, but alcohol has an unusually complex pharmacology, and humans vary greatly in their alcohol responses. This variation is related to genetic susceptibility for alcoholism, which contributes more than half of alcoholism risk. Here, we report that a functional OPRM1 A118G polymorphism is a major determinant of striatal dopamine responses to alcohol. Social drinkers recruited based on OPRM1 genotype were challenged in separate sessions with alcohol and placebo under pharmacokinetically controlled conditions, and examined for striatal dopamine release using positron emission tomography and [C-11]-raclopride displacement. A striatal dopamine response to alcohol was restricted to carriers of the minor 118G allele. To directly establish the causal role of OPRM1 A118G variation, we generated two humanized mouse lines, carrying the respective human sequence variant. Brain microdialysis showed a fourfold greater peak dopamine response to an alcohol challenge in h/mOPRM1-118GG than in h/mOPRM1-118AA mice. OPRM1 A118G variation is a genetic determinant of dopamine responses to alcohol, a mechanism by which it likely modulates alcohol reward. Molecular Psychiatry (2011) 16, 809-817; doi:10.1038/mp.2010.56; published online 18 May 2010
C1 [Ramchandani, V. A.; Umhau, J.; Sun, H.; Damadzic, R.; Eskay, R.; Thorsell, A.; Schwandt, M. L.; Sommer, W. H.; George, D. T.; Hommer, D.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Pavon, F. J.; Parsons, L. H.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA.
[Ruiz-Velasco, V.; Margas, W.] Penn State Univ, Coll Med, Dept Anesthesiol, Hershey, PA USA.
[Schoor, M.] TaconicArtemis GmbH, Cologne, Germany.
[Sommer, W. H.] Cent Inst Mental Hlth, D-6800 Mannheim, Germany.
[Herscovitch, P.] NIH, PET Dept, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
EM markus.heilig@mail.nih.gov
RI Schwandt, Melanie/L-9866-2016;
OI Pavon, Francisco Javier/0000-0002-5256-8904; Thorsell,
Annika/0000-0003-3535-3845
FU NIAAA Division of Intramural Clinical and Biological Research; NIAAA
[AA014619]; Consejeria de Innovacion y Ciencia [PAI 433/06]
FX This work was supported by the NIAAA Division of Intramural Clinical and
Biological Research (Heilig, Hommer, George and Ramchandani), and Grants
AA014619 from NIAAA (Parsons) and PAI 433/06 from Consejeria de
Innovacion y Ciencia (Pavon). We gratefully acknowledge data analysis by
M Kerich and R Momenan, biochemical analysis by E Singley and PET data
collection by C Jones, S Kumar, S Eappen, and J Issa.
NR 59
TC 119
Z9 120
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD AUG
PY 2011
VL 16
IS 8
BP 809
EP 817
DI 10.1038/mp.2010.56
PG 9
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 795UQ
UT WOS:000293001800006
PM 20479755
ER
PT J
AU Volkow, ND
Tomasi, D
Wang, GJ
Fowler, JS
Telang, F
Goldstein, RZ
Alia-Klein, N
Woicik, P
Wong, C
Logan, J
Millard, J
Alexoff, D
AF Volkow, N. D.
Tomasi, D.
Wang, G-J
Fowler, J. S.
Telang, F.
Goldstein, R. Z.
Alia-Klein, N.
Woicik, P.
Wong, C.
Logan, J.
Millard, J.
Alexoff, D.
TI Positive emotionality is associated with baseline metabolism in
orbitofrontal cortex and in regions of the default network
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE brain glucose metabolism; brain imaging; personality; prefrontal cortex;
substance use disorder; vulnerability
ID ANTERIOR CINGULATE CORTEX; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL
GLUCOSE-METABOLISM; NEUROBIOLOGICAL BASIS; DECISION-MAKING; SUBSTANCE
USE; DRUG-ABUSE; BRAIN; ADDICTION; COCAINE
AB Positive emotionality (PEM) (personality construct of well-being, achievement/motivation, social and closeness) has been associated with striatal dopamine D2 receptor availability in healthy controls. As striatal D2 receptors modulate activity in orbitofrontal cortex (OFC) and cingulate (brain regions that process natural and drug rewards), we hypothesized that these regions underlie PEM. To test this, we assessed the correlation between baseline brain glucose metabolism (measured with positron emission tomography and [(18)F] fluoro-deoxyglucose) and scores on PEM (obtained from the multidimensional personality questionnaire or MPQ) in healthy controls (n = 47). Statistical parametric mapping (SPM) analyses revealed that PEM was positively correlated (P(c) < 0.05, voxel corrected) with metabolism in various cortical regions that included orbitofrontal (Brodman area, BA 11, 47) and cingulate (BA 23, 32) and other frontal (BA 10, 9), parietal (precuneus, BA 40) and temporal (BA 20, 21) regions that overlap with the brain's default mode network (DMN). Correlations with the other two main MPQ personality dimensions (negative emotionality and constraint) were not significant (SPM P(c) < 0.05). Our results corroborate an involvement of orbitofrontal and cingulate regions in PEM, which is considered a trait that protects against substance use disorders. As dysfunction of OFC and cingulate is a hallmark of addiction, these findings support a common neural basis underlying protective personality factors and brain dysfunction underlying substance use disorders. In addition, we also uncovered an association between PEM and baseline metabolism in regions from the DMN, which suggests that PEM may relate to global cortical processes that are active during resting conditions (introspection, mind wandering). Molecular Psychiatry (2011) 16, 818-825; doi:10.1038/mp.2011.30; published online 12 April 2011
C1 [Volkow, N. D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA.
[Volkow, N. D.; Tomasi, D.; Telang, F.; Millard, J.] NIAAA, Bethesda, MD USA.
[Wang, G-J; Fowler, J. S.; Goldstein, R. Z.; Alia-Klein, N.; Woicik, P.; Wong, C.; Logan, J.; Alexoff, D.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
RP Volkow, ND (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5274,MSC 9581, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
RI Tomasi, Dardo/J-2127-2015
FU National Institutes of Health [AA 09481]
FX This research was supported by the National Institutes of Health
(Intramural Research Program of the National Institute on Alcoholism and
Alcohol Abuse and Grant AA 09481). We thank David Schlyer for cyclotron
operations, Colleen Shea and Youwen Xu for radiotracer synthesis,
Pauline Carter for nursing care, Karen Apelskog for protocol
coordination and Ruben Baler and Linda Thomas for editorial assistance.
NR 44
TC 22
Z9 22
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD AUG
PY 2011
VL 16
IS 8
BP 818
EP 825
DI 10.1038/mp.2011.30
PG 8
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 795UQ
UT WOS:000293001800007
PM 21483434
ER
PT J
AU Conejero-Goldberg, C
Hyde, TM
Chen, S
Dreses-Werringloer, U
Herman, MM
Kleinman, JE
Davies, P
Goldberg, TE
AF Conejero-Goldberg, C.
Hyde, T. M.
Chen, S.
Dreses-Werringloer, U.
Herman, M. M.
Kleinman, J. E.
Davies, P.
Goldberg, T. E.
TI Molecular signatures in post-mortem brain tissue of younger individuals
at high risk for Alzheimer's disease as based on APOE genotype
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE AD; APOE; microarray; gene expression; human brain
ID CELL-CYCLE EVENTS; GENE-EXPRESSION; AMYLOID-BETA; NEURODEGENERATIVE
DISEASES; MITOCHONDRIAL DYSFUNCTION; NEUROFIBRILLARY TANGLES;
NEUROTROPHIC FACTOR; BIOLOGICAL-ACTIVITY; RECEPTOR SUBUNITS; OXIDATIVE
STRESS
AB Alzheimer's disease (AD) is a neurodegenerative condition characterized histopathologically by neuritic plaques and neurofibrillary tangles. The objective of this transcriptional profiling study was to identify both neurosusceptibility and intrinsic neuroprotective factors at the molecular level, not confounded by the downstream consequences of pathology. We thus studied post-mortem cortical tissue in 28 cases that were non-APOE4 carriers (called the APOE3 group) and 13 cases that were APOE4 carriers. As APOE genotype is the major genetic risk factor for late-onset AD, the former group was at low risk for development of the disease and the latter group was at high risk for the disease. Mean age at death was 42 years and none of the brains had histopathology diagnostic of AD at the time of death. We first derived interregional difference scores in expression between cortical tissue from a region relatively invulnerable to AD (primary somatosensory cortex, BA 1/2/3) and an area known to be susceptible to AD pathology (middle temporal gyrus, BA 21). We then contrasted the magnitude of these interregional differences in between-group comparisons of the APOE3 (low risk) and APOE4 (high risk) genotype groups. We identified 70 transcripts that differed significantly between the groups. These included EGFR, CNTFR, CASP6, GRIA2, CTNNB1, FKBPL, LGALS1 and PSMC5. Using real-time quantitative PCR, we validated these findings. In addition, we found regional differences in the expression of APOE itself. We also identified multiple Kyoto pathways that were disrupted in the APOE4 group, including those involved in mitochondrial function, calcium regulation and cell-cycle reentry. To determine the functional significance of our transcriptional findings, we used bioinformatics pathway analyses to demonstrate that the molecules listed above comprised a network of connections with each other, APOE, and APP and MAPT. Overall, our results indicated that the abnormalities that we observed in single transcripts and in signaling pathways were not the consequences of diagnostic plaque and tangle pathology, but preceded it and thus may be a causative link in the long molecular prodrome that results in clinical AD. Molecular Psychiatry (2011) 16, 836-847; doi:10.1038/mp.2010.57; published online 18 May 2010
C1 [Conejero-Goldberg, C.; Chen, S.; Dreses-Werringloer, U.; Davies, P.; Goldberg, T. E.] Feinstein Inst Med Res, Litwin Zucker Res Ctr Study Alzheimers Dis, Manhasset, NY 11030 USA.
[Hyde, T. M.; Herman, M. M.; Kleinman, J. E.] NIMH, Sect Neuropathol, GCAPP, IRP,NIH, Bethesda, MD 20892 USA.
[Davies, P.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.
[Goldberg, T. E.] Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA.
RP Conejero-Goldberg, C (reprint author), Feinstein Inst Med Res, Litwin Zucker Res Ctr Study Alzheimers Dis, 350 Community Dr, Manhasset, NY 11030 USA.
EM cgoldber@nshs.edu
OI Davies, Peter/0000-0002-8015-1997
FU Eisai/Pfizer; Applied Neurosolutions
FX TG has consulted for Merck and GSK. He receives royalties for use of a
cognitive test battery in clinical trials, the BACS. He has received an
investigator initiated grant from Eisai/Pfizer. PD has received research
support from and served as a consultant to Applied Neurosolutions. The
remaining authors declare no conflict of interest.
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD AUG
PY 2011
VL 16
IS 8
BP 836
EP 847
DI 10.1038/mp.2010.57
PG 12
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 795UQ
UT WOS:000293001800009
PM 20479757
ER
PT J
AU Piton, A
Gauthier, J
Hamdan, FF
Lafreniere, RG
Yang, Y
Henrion, E
Laurent, S
Noreau, A
Thibodeau, P
Karemera, L
Spiegelman, D
Kuku, F
Duguay, J
Destroismaisons, L
Jolivet, P
Cote, M
Lachapelle, K
Diallo, O
Raymond, A
Marineau, C
Champagne, N
Xiong, L
Gaspar, C
Riviere, JB
Tarabeux, J
Cossette, P
Krebs, MO
Rapoport, JL
Addington, A
DeLisi, LE
Mottron, L
Joober, R
Fombonne, E
Drapeau, P
Rouleau, GA
AF Piton, A.
Gauthier, J.
Hamdan, F. F.
Lafreniere, R. G.
Yang, Y.
Henrion, E.
Laurent, S.
Noreau, A.
Thibodeau, P.
Karemera, L.
Spiegelman, D.
Kuku, F.
Duguay, J.
Destroismaisons, L.
Jolivet, P.
Cote, M.
Lachapelle, K.
Diallo, O.
Raymond, A.
Marineau, C.
Champagne, N.
Xiong, L.
Gaspar, C.
Riviere, J-B
Tarabeux, J.
Cossette, P.
Krebs, M-O
Rapoport, J. L.
Addington, A.
DeLisi, L. E.
Mottron, L.
Joober, R.
Fombonne, E.
Drapeau, P.
Rouleau, G. A.
TI Systematic resequencing of X-chromosome synaptic genes in autism
spectrum disorder and schizophrenia
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE autism spectrum disorder; schizophrenia; X chromosome; synaptic genes;
rare variants
ID LINKED MENTAL-RETARDATION; MONOAMINE-OXIDASE-B; GENOMEWIDE SCREEN;
SUSCEPTIBILITY LOCI; LINKAGE DISEQUILIBRIUM; POSTSYNAPTIC DENSITY;
ANGELMAN SYNDROME; PROTEIN FAMILY; MUTATIONS; ASSOCIATION
AB Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions in a fraction of cases. In addition, for both disorders, males are either more significantly or more severely affected than females, which may be explained in part by X-linked genetic factors. Therefore, we directly sequenced 111 X-linked synaptic genes in individuals with ASD (n = 142; 122 males and 20 females) or SCZ (n = 143; 95 males and 48 females). We identified > 200 non-synonymous variants, with an excess of rare damaging variants, which suggest the presence of disease-causing mutations. Truncating mutations in genes encoding the calcium-related protein IL1RAPL1 (already described in Piton et al. Hum Mol Genet 2008) and the monoamine degradation enzyme monoamine oxidase B were found in ASD and SCZ, respectively. Moreover, several promising non-synonymous rare variants were identified in genes encoding proteins involved in regulation of neurite outgrowth and other various synaptic functions (MECP2, TM4SF2/TSPAN7, PPP1R3F, PSMD10, MCF2, SLITRK2, GPRASP2, and OPHN1). Molecular Psychiatry (2011) 16, 867-880; doi:10.1038/mp.2010.54; published online 18 May 2010
C1 [Piton, A.; Gauthier, J.; Lafreniere, R. G.; Yang, Y.; Henrion, E.; Laurent, S.; Noreau, A.; Thibodeau, P.; Karemera, L.; Spiegelman, D.; Kuku, F.; Duguay, J.; Destroismaisons, L.; Jolivet, P.; Cote, M.; Lachapelle, K.; Diallo, O.; Raymond, A.; Marineau, C.; Xiong, L.; Gaspar, C.; Riviere, J-B; Tarabeux, J.; Cossette, P.; Rouleau, G. A.] Univ Montreal, Dept Med, Ctr Excellence Neur, CHUM Res Ctr, Montreal, PQ H2L 4M1, Canada.
[Hamdan, F. F.; Rouleau, G. A.] CHU St Justine Res Ctr, Montreal, PQ, Canada.
[Champagne, N.; Drapeau, P.] Univ Montreal, Dept Pathol & Cell Biol, Montreal, PQ H2L 4M1, Canada.
[Champagne, N.; Drapeau, P.] Univ Montreal, Grp Rech Syst Nerveux Cent, Montreal, PQ H2L 4M1, Canada.
[Krebs, M-O] Univ Paris 05, INSERM, U796, F-75252 Paris, France.
[Krebs, M-O] Ctr Hosp St Anne, Paris, France.
[Rapoport, J. L.; Addington, A.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[DeLisi, L. E.] VA Boston Healthcare Syst, Brockton, MA USA.
[DeLisi, L. E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA.
[DeLisi, L. E.] NYU, Dept Psychiat, Langone Med Ctr, New York, NY 10016 USA.
[Mottron, L.] CETEDUM, Montreal, PQ, Canada.
[Joober, R.] McGill Univ, Douglas Mental Hlth Univ Inst, Dept Psychiat, Montreal, PQ, Canada.
[Fombonne, E.] Montreal Childrens Hosp, Dept Psychiat, Montreal, PQ H3H 1P3, Canada.
RP Rouleau, GA (reprint author), Univ Montreal, Dept Med, Ctr Excellence Neur, CHUM Res Ctr, 1560 Sherbrooke E,Room Y-3633, Montreal, PQ H2L 4M1, Canada.
EM guy.rouleau@umontreal.ca
RI piton, amelie/F-1201-2013
OI piton, amelie/0000-0003-0408-7468
FU Genome Canada; Genome Quebec; Universite de Montreal
FX We thank the families involved in our study and the recruitment
coordinators (Anne Desjarlais, Caroline Poulin, and Sabrina Diab). We
thank Annie Levert, Judith St-Onge, and Isabelle Bachand for performing
DNA extraction and paternity and identity testing. We are thankful for
the efforts of the members of the McGill University and Genome Quebec
Innovation Centre Sequencing (Pierre Lepage, Sebastien Brunet, and Hao
Fan Yam) and Bioinformatic (Louis Letourneau and Louis Dumond Joseph)
groups. This work was supported by a grant from Genome Canada and Genome
Quebec and was cofunded by Universite de Montreal, for the
'Synapse-to-disease' (S2D) project.
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U1 4
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD AUG
PY 2011
VL 16
IS 8
BP 867
EP 880
DI 10.1038/mp.2010.54
PG 14
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 795UQ
UT WOS:000293001800012
ER
PT J
AU Lai, AY
Wade, PA
AF Lai, Anne Y.
Wade, Paul A.
TI Cancer biology and NuRD: a multifaceted chromatin remodelling complex
SO NATURE REVIEWS CANCER
LA English
DT Review
ID DNA METHYLTRANSFERASE GENE; EMBRYONIC STEM-CELLS; HISTONE DEACETYLASE;
MI-2/NURD COMPLEX; TRANSCRIPTIONAL REPRESSION; BREAST-CANCER; BINDING
DOMAIN; PERICENTROMERIC HETEROCHROMATIN; IMMUNODEFICIENCY SYNDROME;
TUMOR-METASTASIS
AB The nucleosome remodelling and histone deacetylase (NuRD; also known as Mi-2) complex regulates gene expression at the level of chromatin. The NuRD complex has been identified - using both genetic and molecular analyses - as a key determinant of differentiation in mouse embryonic stem cells and during development in various model systems. Similar to other chromatin remodellers, such as SWI/SNF and Polycomb complexes, NuRD has also been implicated in the regulation of transcriptional events that are integral to oncogenesis and cancer progression. Emerging molecular details regarding the recruitment of NuRD to specific loci during development, and the modulation of these events in cancer, are used to illustrate how the inappropriate localization of the complex could contribute to tumour biology.
C1 [Lai, Anne Y.; Wade, Paul A.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
RP Wade, PA (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, 111 TW Alexander Dr,MD D4-04, Res Triangle Pk, NC 27709 USA.
EM wadep2@niehs.nih.gov
FU US National Institute of Environmental Health Sciences, NIH
[Z01ES101965]
FX The authors would like to thank members of the Wade laboratory for
critical comments and suggestions for this manuscript. They apologize to
those whose work is not cited owing to space limitations. The authors'
research is funded by the Intramural Research Program of the US National
Institute of Environmental Health Sciences, NIH (Project number
Z01ES101965 to P.A.W.).
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD AUG
PY 2011
VL 11
IS 8
BP 588
EP 596
DI 10.1038/nrc3091
PG 9
WC Oncology
SC Oncology
GA 795TH
UT WOS:000292998200012
PM 21734722
ER
PT J
AU Reizis, B
Colonna, M
Trinchieri, G
Barrat, F
Gilliet, M
AF Reizis, Boris
Colonna, Marco
Trinchieri, Giorgio
Barrat, Franck
Gilliet, Michel
TI Plasmacytoid dendritic cells: one-trick ponies or workhorses of the
immune system?
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Article
ID TRANSCRIPTION FACTOR E2-2; T-CELLS; ANTIGEN-PRESENTATION; VIRUS;
INFILTRATION; INTERFERON; TOLERANCE; RESPONSES; SUBSETS; DNA
AB Plasmacytoid dendritic cells (pDCs) were first described as interferon-producing cells and, for many years, their overlapping characteristics with both lymphocytes and classical dendritic cells (cDCs) created confusion over their exact ontogeny. In this Viewpoint article, Nature Reviews Immunology asks five leaders in the field to discuss their thoughts on the development and functions of pDCs - do these cells serve mainly as a major source of type I interferons or do they also make other important contributions to immune responses?
C1 [Reizis, Boris] Columbia Univ, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Colonna, Marco] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Barrat, Franck] Dynavax Technol Corp, Berkeley, CA 94710 USA.
[Gilliet, Michel] Univ Hosp Lausanne CHUV, Dept Dermatol, CH-1011 Lausanne, Switzerland.
RP Reizis, B (reprint author), Columbia Univ, Dept Microbiol & Immunol, 701 W 168th St, New York, NY 10032 USA.
EM bvr2101@columbia.edu; mcolonna@pathology.wustl.edu;
trinchig@mail.nih.gov; fbarrat@dynavax.com; Michel.Gilliet@chuv.ch
OI Colonna, Marco/0000-0001-5222-4987; Reizis, Boris/0000-0003-1140-7853
FU US National Institutes of Health [AI085439, AI072571]
FX B.R. is supported by US National Institutes of Health grants AI085439
and AI072571.
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD AUG
PY 2011
VL 11
IS 8
BP 558
EP U82
DI 10.1038/nri3027
PG 9
WC Immunology
SC Immunology
GA 796RN
UT WOS:000293069600015
PM 21779033
ER
PT J
AU Hsu, AL
Sinaii, N
Segars, J
Nieman, LK
Stratton, P
AF Hsu, Albert L.
Sinaii, Ninet
Segars, James
Nieman, Lynnette K.
Stratton, Pamela
TI Relating Pelvic Pain Location to Surgical Findings of Endometriosis
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT 57th Annual Meeting of the Society-for-Gynecologic-Investigation
CY MAR 24-27, 2010
CL Orlando, FL
SP Soc Gynecol Invest
ID DEEP INFILTRATING ENDOMETRIOSIS; CONSCIOUS PAIN; LOCAL-ANESTHESIA;
CONTROLLED-TRIAL; LAPAROSCOPY; WOMEN; DIAGNOSIS; MICROLAPAROSCOPY;
DYSMENORRHEA; MANAGEMENT
AB OBJECTIVE: To study whether pain location is related to lesion location in women with chronic pelvic pain and biopsy-proven endometriosis.
METHODS: A secondary analysis was performed to compare self-reported pain location with recorded laparoscopy findings for location and characteristics of all visible lesions. All lesions were excised. Endometriosis was diagnosed using histopathology criteria. The pelvic area was divided into three anterior and two posterior regions. Lesion depth, number of lesions or endometriomas, and disease burden (defined as sum of lesion sizes, or single compared with multiple lesions) were determined for each region. Data were analyzed using t tests, Fisher exact tests, and logistic regression modeling, with P values corrected for multiple comparisons using the step-down Bonferroni method.
RESULTS: Women with endometriosis (n = 96) had lower body mass indexes, were more likely to be white, had more previous surgeries, and had more frequent menstrual pain and incapacitation than did chronic pain patients without endometriosis (n = 37). Overall, few patients had deeply infiltrating lesions (n = 38). Dysuria was associated with superficial bladder peritoneal lesions. Other lesions or endometriomas were not associated with pain in the same anatomic locations. Lesion depth, disease burden, and number of lesions or endometriomas were not associated with pain.
CONCLUSION: In this group of women with biopsyproven endometriosis, few had deeply infiltrating lesions or endometriomas. Dysuria and midline anterior pain were the only symptoms associated with the location of superficial endometriosis lesions. The lack of relationship between pain and superficial lesion location raises questions about how these lesions relate to pain.
C1 [Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bethesda, MD 20892 USA.
NIH, Ctr Clin, Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA.
George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA.
RP Stratton, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bldg 10,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM strattop@mail.nih.gov
FU Intramural NIH HHS [Z01 HD008728-08]
NR 30
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD AUG
PY 2011
VL 118
IS 2
BP 223
EP 230
DI 10.1097/AOG.0b013e318223fed0
PN 1
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 795FB
UT WOS:000292956900005
PM 21775836
ER
PT J
AU Zhang, J
Branch, DW
Ramirez, MM
Laughon, SK
Reddy, U
Hoffman, M
Bailit, J
Kominiarek, M
Chen, Z
Hibbard, JU
AF Zhang, Jun
Branch, D. Ware
Ramirez, Mildred M.
Laughon, S. Katherine
Reddy, Uma
Hoffman, Mathew
Bailit, Jennifer
Kominiarek, Michelle
Chen, Zhen
Hibbard, Judith U.
TI Oxytocin Regimen for Labor Augmentation, Labor Progression, and
Perinatal Outcomes
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
AB OBJECTIVE: To examine the effects and safety of high-dose (compared with low-dose) oxytocin regimen for labor augmentation on perinatal outcomes.
METHODS: Data from the Consortium on Safe Labor were used. A total of 15,054 women from six hospitals were eligible for the analysis. Women were grouped based on their oxytocin starting dose and incremental dosing of 1, 2, and 4 milliunits/min. Duration of labor and a number of maternal and neonatal outcomes were compared among these three groups stratified by parity. Multivariable logistic regression and generalized linear mixed model were used to adjust for potential confounders.
RESULTS: Oxytocin regimen did not affect the rate of cesarean delivery or other perinatal outcomes. Compared with 1 milliunit/min, the regimens starting with 2 milliunits/min and 4 milliunits/min reduced the duration of first stage by 0.8 hours (95% confidence interval 0.5-1.1) and 1.3 hours (1.0-1.7), respectively, in nulliparous women. No effect was observed on the second stage of labor. Similar patterns were observed in multiparous women. High-dose regimen was associated with a reduced risk of meconium stain, chorioamnionitis, and newborn fever in multiparous women.
CONCLUSION: High-dose oxytocin regimen (starting dose at 4 milliunits/min and increment of 4 millliunits/min) is associated with a shorter duration of first-stage of labor for all parities without increasing the cesarean delivery rate or adversely affecting perinatal outcomes. (Obstet Gynecol 2011;118:249-56) DOI: 10.1097/AOG.0b013e3182220192
C1 [Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE, Shanghai 200092, Peoples R China.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai 200092, Peoples R China.
Intermt Healthcare, Salt Lake City, UT USA.
Univ Utah, Salt Lake City, UT USA.
Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
Christiana Care Hlth Syst, Newark, DE USA.
Metrohlth Med Ctr, Cleveland, OH USA.
Univ Illinois, Chicago, IL USA.
RP Zhang, J (reprint author), Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE, 1665 Kong Jiang Rd, Shanghai 200092, Peoples R China.
EM junjimzhang@gmail.com
OI Grantz, Katherine/0000-0003-0276-8534
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health [HHSN267200603425C]
FX The data included in this article were obtained from the Consortium on
Safe Labor, which was supported by the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, through contract
HHSN267200603425C.
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U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD AUG
PY 2011
VL 118
IS 2
BP 249
EP 256
DI 10.1097/AOG.0b013e3182220192
PN 1
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 795FB
UT WOS:000292956900008
PM 21775839
ER
PT J
AU Spong, CY
Mercer, BM
D'Alton, M
Kilpatrick, S
Blackwell, S
Saade, G
AF Spong, Catherine Y.
Mercer, Brian M.
D'Alton, Mary
Kilpatrick, Sarah
Blackwell, Sean
Saade, George
TI Timing of Indicated Late-Preterm and Early-Term Birth
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID CLASSIC CESAREAN DELIVERY; PLACENTA-PREVIA; PERINATAL OUTCOMES; NEONATAL
OUTCOMES; DECISION-ANALYSIS; FETAL-DEATH; ACCRETA; STRATEGIES; RISK;
GESTATION
AB The growing public health awareness of prematurity and its complications has prompted careful evaluation of the timing of deliveries by clinicians and hospitals. Preterm birth is associated with significant morbidity and mortality, and affects more than half a million births in the United States each year. In some situations, however, a late-preterm or early-term birth is the optimal outcome for the mother, child, or both owing to conditions that can result in worse outcomes if pregnancy is allowed to continue. These conditions may be categorized as placental, maternal, or fetal, including conditions such as placenta previa, preeclampsia, and multiple gestations. Some risks associated with early delivery are common to all conditions, including prematurity-related morbidities (eg, respiratory distress syndrome and intraventricular hemorrhage) as well as maternal intrapartum morbidities such as failed induction and cesarean delivery. However, when continuation of the pregnancy is associated with more risks such as hemorrhage, uterine rupture, and stillbirth, preterm delivery maybe indicated. In February 2011, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Society for Maternal-Fetal Medicine held a workshop titled "Timing of Indicated Late Preterm and Early Term Births." The goal of the workshop was to synthesize the available information regarding conditions that may result in medically indicated late-preterm and early-term births to determine the potential risks and benefits of delivery compared with continued pregnancy, determine the optimal gestational age for delivery of affected pregnancies when possible, and inform future research regarding these issues. Based on available data and expert opinion, optimal timing for delivery for specific conditions was determined by consensus. (Obstet Gynecol 2011;118:323-33) DOI: 10.1097/AOG.0b013e3182255999
C1 [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA.
Metrohlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH USA.
Columbia Univ, New York, NY USA.
Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
Univ Texas Hlth Sci Ctr Houston, Dept Obstet Gynecol & Reprod Sci, Houston, TX USA.
Univ Texas Med Branch Galveston, Galveston, TX USA.
RP Spong, CY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, 6100 Execut Blvd,Rm 4B03,MSC 7510, Bethesda, MD 20892 USA.
EM spongc@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 33
TC 180
Z9 190
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD AUG
PY 2011
VL 118
IS 2
BP 323
EP 333
DI 10.1097/AOG.0b013e3182255999
PN 1
PG 11
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 795FB
UT WOS:000292956900018
PM 21775849
ER
PT J
AU Laughon, SK
Zhang, J
Reddy, UM
AF Laughon, S. Katherine
Zhang, Jun
Reddy, Uma M.
TI Using a Simplified Bishop Score to Predict Vaginal Delivery Reply
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Letter
C1 [Laughon, S. Katherine] NICHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE, Shanghai 200030, Peoples R China.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai 200030, Peoples R China.
[Reddy, Uma M.] NICHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA.
RP Laughon, SK (reprint author), NICHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
NR 2
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD AUG
PY 2011
VL 118
IS 2
BP 360
EP 360
DI 10.1097/AOG.0b013e318226442d
PN 1
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 795FB
UT WOS:000292956900031
ER
PT J
AU Dworkin, RH
Turk, DC
Basch, E
Berger, A
Cleeland, C
Farrar, JT
Haythornthwaite, JA
Jensen, MP
Kerns, RD
Markman, J
Porter, L
Raja, SN
Ross, E
Todd, K
Wallace, M
Woolf, CJ
AF Dworkin, Robert H.
Turk, Dennis C.
Basch, Ethan
Berger, Ann
Cleeland, Charles
Farrar, John T.
Haythornthwaite, Jennifer A.
Jensen, Mark P.
Kerns, Robert D.
Markman, John
Porter, Linda
Raja, Srinivasa N.
Ross, Edgar
Todd, Knox
Wallace, Mark
Woolf, Clifford J.
TI Considerations for extrapolating evidence of acute and chronic pain
analgesic efficacy
SO PAIN
LA English
DT Review
ID LOW-BACK-PAIN; INDUCED PERIPHERAL NEUROPATHY; CLINICAL-PRACTICE
GUIDELINE; RANDOMIZED CONTROLLED-TRIAL; PHARMACOLOGICAL MANAGEMENT;
POSTHERPETIC NEURALGIA; EMPIRICAL-EVIDENCE; DOUBLE-BLIND; AMITRIPTYLINE;
PLACEBO
C1 [Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA.
[Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA.
[Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
[Basch, Ethan] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Berger, Ann] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Cleeland, Charles] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Farrar, John T.] Univ Penn, Dept Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Haythornthwaite, Jennifer A.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA.
[Jensen, Mark P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Kerns, Robert D.] Yale Univ, Dept Psychiat, VA Connecticut Healthcare Syst, Pain Res Informat Med Comorbid & Educ Ctr, New Haven, CT 06520 USA.
[Kerns, Robert D.] Yale Univ, Dept Neurol, VA Connecticut Healthcare Syst, Pain Res Informat Med Comorbid & Educ Ctr, New Haven, CT 06520 USA.
[Kerns, Robert D.] Yale Univ, Dept Psychol, VA Connecticut Healthcare Syst, Pain Res Informat Med Comorbid & Educ Ctr, New Haven, CT 06520 USA.
[Markman, John] Univ Rochester, Dept Neurosurg, Sch Med & Dent, Rochester, NY USA.
[Raja, Srinivasa N.] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA.
[Ross, Edgar] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Ross, Edgar; Woolf, Clifford J.] Harvard Univ, Sch Med, Boston, MA USA.
[Todd, Knox] Beth Israel Deaconess Med Ctr, Dept Pain Med & Palliat Care, New York, NY 10003 USA.
[Wallace, Mark] Univ Calif San Diego, Dept Anesthesiol, San Diego, CA 92103 USA.
[Woolf, Clifford J.] Childrens Hosp, Boston, MA 02115 USA.
RP Dworkin, RH (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA.
EM robert_dworkin@urmc.rochester.edu
OI Yang, Shuman/0000-0002-9638-0890
FU United States Food and Drug Administration
FX The workshop on which this article is based was convened and funded by
the United States Food and Drug Administration. Other than reimbursement
of travel expenses to attend the workshop, none of the authors received
any compensation for their participation in the workshop and in article
preparation. None of the authors have financial conflicts of interest
related to the material in this article. No official endorsement by the
US Department of Veterans Affairs, US Food and Drug Administration, or
US National Institutes of Health should be inferred.
NR 40
TC 18
Z9 18
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD AUG
PY 2011
VL 152
IS 8
BP 1705
EP 1708
DI 10.1016/j.pain.2011.02.026
PG 4
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 793ZG
UT WOS:000292862400008
PM 21396781
ER
PT J
AU Hansen, RR
Nielsen, CK
Nasser, A
Thomsen, SIM
Eghorn, LF
Pham, Y
Schulenburg, C
Syberg, S
Ding, M
Stojilkovic, SS
Jorgensen, NR
Heegaard, AM
AF Hansen, Rikke Rie
Nielsen, Christian K.
Nasser, Arafat
Thomsen, Stine I. M.
Eghorn, Laura F.
Yen Pham
Schulenburg, Cecilia
Syberg, Susanne
Ding, Ming
Stojilkovic, Stanko S.
Jorgensen, Niklas R.
Heegaard, Anne-Marie
TI P2X7 receptor-deficient mice are susceptible to bone cancer pain
SO PAIN
LA English
DT Article
DE Bone cancer pain; P2X7 receptor; IL-1 beta
ID P2X(7) RECEPTOR; NEUROPATHIC PAIN; SPINAL-CORD; IN-VIVO; NEUROCHEMICAL
CHANGES; PURINERGIC RECEPTORS; OSTEOCLAST FORMATION; MURINE MODELS;
KNOCKOUT MICE; NERVE-FIBERS
AB The purinergic P2X7 receptor is implicated in both neuropathic and inflammatory pain, and has been suggested as a possible target in pain treatment. However, the specific role of the P2X7 receptor in bone cancer pain is unknown. We demonstrated that BALB/cJ P2X7 receptor knockout (P2X7R KO) mice were susceptible to bone cancer pain and moreover had an earlier onset of pain-related behaviours compared with cancer-bearing, wild-type mice. Furthermore, acute treatment with the selective P2X7 receptor antagonist, A-438079, failed to alleviate pain-related behaviours in models of bone cancer pain with and without astrocyte activation (BALB/cJ or C3H mice inoculated with 4T1 mammary cancer cells or NCTC 2472 osteosarcoma cells, respectively), suggesting that astrocytic P2X7 receptors play a negligible role in bone cancer pain. The results support the hypothesis that bone cancer pain is a separate pain state compared with those of neuropathic and inflammatory pain. However, the recent discovery of a P2X7 receptor splice variant expressed in the knockout mice used for this study complicates the interpretation of the results. The P2X7 splice variant receptor was detected in the spinal cord but not in osteoclasts of the P2X7R KO mouse. Further experiments are needed to elucidate the exact role of the P2X7 receptors in bone cancer pain. (C) 2011 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
C1 [Hansen, Rikke Rie; Nielsen, Christian K.; Nasser, Arafat; Thomsen, Stine I. M.; Eghorn, Laura F.; Yen Pham; Schulenburg, Cecilia; Heegaard, Anne-Marie] Univ Copenhagen, Fac Pharmaceut Sci, Dept Pharmacol & Pharmacotherapy, DK-2100 Copenhagen, Denmark.
[Syberg, Susanne; Jorgensen, Niklas R.] Glostrup Cty Hosp, Res Ctr Glostrup, Ctr Ageing & Osteoporosis, Glostrup, Denmark.
[Ding, Ming] Univ So Denmark, Odense Univ Hosp, Odense, Denmark.
[Stojilkovic, Stanko S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Heegaard, AM (reprint author), Univ Copenhagen, Fac Pharmaceut Sci, Dept Pharmacol & Pharmacotherapy, Univ Pk 2, DK-2100 Copenhagen, Denmark.
EM amhe@farma.ku.dk
RI Jorgensen, Niklas/B-6003-2012;
OI Syberg, Susanne/0000-0003-4999-4950
FU The Danish Council of Independent Research, Medical Sciences; The
Beckett Foundation; A.P. Moller og Hustru Chastine Mc-Kinney Mollers
Fond til almene Formaal
FX The research described in this paper was supported in part by The Danish
Council of Independent Research, Medical Sciences; The Beckett
Foundation, and A.P. Moller og Hustru Chastine Mc-Kinney Mollers Fond
til almene Formaal. The C57BL/6 P2X7R KO mice were kindly provided by
Ivana Novak, Faculty of Science, Copenhagen University, Copenhagen,
Denmark.
NR 54
TC 31
Z9 34
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD AUG
PY 2011
VL 152
IS 8
BP 1766
EP 1776
DI 10.1016/j.pain.2011.03.024
PG 11
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 793ZG
UT WOS:000292862400016
PM 21565445
ER
PT J
AU Hancock, DB
Haberg, SE
Furu, K
Whitworth, KW
Nafstad, P
Nystad, W
London, SJ
AF Hancock, Dana B.
Haberg, Siri E.
Furu, Kari
Whitworth, Kristina W.
Nafstad, Per
Nystad, Wenche
London, Stephanie J.
TI Oral contraceptive pill use before pregnancy and respiratory outcomes in
early childhood
SO PEDIATRIC ALLERGY AND IMMUNOLOGY
LA English
DT Article
DE oral contraceptives; pregnancy; respiratory tract; wheezing; asthma;
cohort studies
ID ASTHMA; PROGESTINS; DISEASES; HORMONE; HEALTH; WOMEN; LIFE
AB Background: Oral contraceptive pills (OCPs) are often used soon before, and sometimes during, pregnancy. A few studies have suggested that OCP use before pregnancy may increase risks for childhood respiratory outcomes, but data are inconclusive. No studies have analyzed the two types of OCPs, estrogen-progestin combined pills and progestin-only pills, separately.
Methods: In the Norwegian Mother and Child Cohort Study (MoBa), we prospectively examined associations of OCP use before pregnancy, by type, with lower respiratory tract infections in 60,225 children followed to 6 months old, lower respiratory tract infections and wheezing in 42,520 children followed to 18 months old, and asthma in 24,472 children followed to 36 months old. We used logistic regression to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) crudely and with adjustment for a wide range of potential confounders.
Result: Combined pills were used much more commonly than progestin-only pills. Taking combined pills before pregnancy was not associated with lower respiratory tract infections, wheezing, or asthma. Progestin-only pill use in the year before pregnancy had a slight positive association with wheezing at 6-8 months old [adjusted OR (95% CI) = 1.19 (1.05-1.34)].
Conclusion: Our finding that combined pill use before pregnancy was not related to respiratory outcomes should provide reassurance to the vast majority of mothers using OCPs before becoming pregnant. The small association with progestin-only pill use and early respiratory outcomes may reflect uncontrolled confounding or other bias. Nonetheless, it does suggest that these two types of pills should be examined separately in future analyses of respiratory and other childhood outcomes.
C1 [Hancock, Dana B.; Whitworth, Kristina W.; London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Haberg, Siri E.; Furu, Kari; Nafstad, Per; Nystad, Wenche] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway.
[Furu, Kari] Univ Tromso, Dept Pharm, Tromso, Norway.
[Nafstad, Per] Univ Oslo, Fac Med, Dept Gen Practice & Community Med, Oslo, Norway.
[London, Stephanie J.] NIEHS, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP London, SJ (reprint author), 111 TW Alexander Dr,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM london2@niehs.nih.gov
RI Hancock, Dana/D-8577-2012;
OI Hancock, Dana/0000-0003-2240-3604; London, Stephanie/0000-0003-4911-5290
FU NIH, National Institute of Environmental Health Sciences [Z01-ES-49019];
National Institute of Environmental Health Sciences [ES044008];
Norwegian Ministry of Health; National Institute of Environmental Health
Sciences (National Institutes of Health, USA) [N01-ES-85433]; National
Institute of Neurological Disorders and Stroke (National Institutes of
Health, USA) [1 U01-NS-047537]; Norwegian Research Council/FUGE
[151918/S10]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences
(Z01-ES-49019). This work was also supported by contract no. ES044008
with the National Institute of Environmental Health Sciences. The
Norwegian Mother and Child Cohort Study is supported by the Norwegian
Ministry of Health and the National Institute of Environmental Health
Sciences (National Institutes of Health, USA, grant no. N01-ES-85433),
the National Institute of Neurological Disorders and Stroke (National
Institutes of Health, USA, grant no. 1 U01-NS-047537), and the Norwegian
Research Council/FUGE (grant no. 151918/S10).
NR 29
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0905-6157
J9 PEDIAT ALLERG IMM-UK
JI Pediatr. Allergy Immunol.
PD AUG
PY 2011
VL 22
IS 5
BP 528
EP 536
DI 10.1111/j.1399-3038.2010.01135.x
PG 9
WC Allergy; Immunology; Pediatrics
SC Allergy; Immunology; Pediatrics
GA 794WF
UT WOS:000292931300012
PM 21294776
ER
PT J
AU Bauer, CR
Lambert, BL
Bann, CM
Lester, BM
Shankaran, S
Bada, HS
Whitaker, TM
Lagasse, LL
Hammond, J
Higgins, RD
AF Bauer, Charles R.
Lambert, Brittany L.
Bann, Carla M.
Lester, Barry M.
Shankaran, Seetha
Bada, Henrietta S.
Whitaker, Toni M.
Lagasse, Linda L.
Hammond, Jane
Higgins, Rosemary D.
TI Long-Term Impact of Maternal Substance Use During Pregnancy and
Extrauterine Environmental Adversity: Stress Hormone Levels of
Preadolescent Children
SO PEDIATRIC RESEARCH
LA English
DT Article
ID PRENATAL COCAINE EXPOSURE; SALIVARY CORTISOL-LEVELS;
SOCIOECONOMIC-STATUS; LIFE-STYLE; CHILDHOOD; RISK; PATHOPHYSIOLOGY;
HYPOCORTISOLISM; ADOLESCENTS; REACTIVITY
AB Prenatal cocaine exposure (PCE) is associated with blunted stress responsivity within the extrauterine environment. This study investigated the association between PCE and diurnal salivary cortisol levels in preadolescent children characterized by high biological and/or social risk (n = 725). Saliva samples were collected at their home. Analyses revealed no group differences in basal evening or morning cortisol levels; however, children with higher degrees of PCE exhibited blunted overnight increases in cortisol, controlling for additional risk factors. Race and caregiver depression were also associated with diurnal cortisol patterns. Although repeated PCE may contribute to alterations in the normal or expected stress response later in life, sociodemographic and environmental factors are likewise important in understanding hormone physiology, especially as more time elapses from the PCE. Anticipating the potential long-term medical, developmental, or behavioral effects of an altered ability to mount a normal protective cortisol stress response is essential in optimizing the outcomes of children with PCE. (Pediatr Res 70: 213-219, 2011)
C1 [Bauer, Charles R.; Lambert, Brittany L.] Univ Miami, Dept Pediat, Miami, FL 33136 USA.
[Bann, Carla M.; Hammond, Jane] RTI Int, Stat & Epidemiol, Res Triangle Pk, NC 27709 USA.
[Lester, Barry M.; Lagasse, Linda L.] Brown Univ, Women & Infants Hosp Rhode Isl, Dept Pediat, Warren Alpert Med Sch, Providence, RI 02903 USA.
[Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
[Bada, Henrietta S.] Univ Kentucky Hosp, Dept Pediat, Lexington, KY 40506 USA.
[Whitaker, Toni M.] Univ Tennessee, Hlth Sci Ctr, Boling Ctr Dev Disabil, Memphis, TN 38105 USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20852 USA.
RP Bauer, CR (reprint author), Univ Miami, Dept Pediat C 208, Leonard M Miller Sch Med, Clin Res Bldg,1120 NW 14th St,Suite 1216, Miami, FL 33136 USA.
EM cbauer@med.miami.edu
FU National Institutes of Health through the National Institute on Drug
Abuse; Eunice Kennedy Shriver National Institute of Child Health and
Human Development; National Institute of Mental Health; Administration
on Children, Youth, and Families; Center for Substance Abuse and
Treatment, US Department of Health and Human Services; Brown University
Warren Alpert Medical School Women & Infants Hospital of Rhode Island
[U10 DA24119, U10 HD27904, N01 HD23159]; National Institute on Drug
Abuse; RTI International [U10 HD36790]; University of Miami Holtz
Children's Hospital [U10 DA24118, U10 HD21397]; University of Tennessee
[U10 DA24128, U10 HD21415, U10 HD42638]; Wayne State University Hutzel
Women's Hospital; Children's Hospital of Michigan [U10 DA24117, U10
HD21385]
FX Support for the Maternal Lifestyle Study was provided by the National
Institutes of Health through the National Institute on Drug Abuse and
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development, with supplemental funding from the National Institute of
Mental Health, the Administration on Children, Youth, and Families and
the Center for Substance Abuse and Treatment, US Department of Health
and Human Services.; The following individuals, in addition to those
listed as authors, and federal funding grants contributed to this
study:; Brown University Warren Alpert Medical School Women & Infants
Hospital of Rhode Island (U10 DA24119, U10 HD27904, N01 HD23159):
Margarita Andrade, Laura Dietz, Katherine Halloran, Seamus Hearne,
Matthew Hinkley, Melissa Hooks, Melissa Kupchak, Richard Lin, Jing Liu,
Cynthia Miller-Loncar, Sandra Muldowney, Geidy Nolasco, Lia O'Brien,
Matt Pescosolido, Sonia Tobon, Jean Twomey.; Eunice Kennedy Shriver
National Institute of Child Health and Human Development: Rosemary D.
Higgins, Linda L. Wright.; National Institute on Drug Abuse: Nicolette
Borek. RTI International (U10 HD36790): W. Kenneth Poole, Abhik Das,
Debra Fleischmann.; University of Miami Holtz Children's Hospital (U10
DA24118, U10 HD21397): Carmel Azemar, Tonya Barriere-Perez, Miriam
Borges, Janine Closius, Khania Contreras, Diedre Gallop, Edgar Garcia,
Susan Gauthier, Ann L. Graziotti, Wendy Griffin, Rafael Guzman,
Elizabeth Jacque, Brittany Lambert, Jennifer Lewis, Michelle Lugo,
Soraya Melegi-Diaz, Daniel S. Messinger, Amy Mur Worth, Mary Triolo,
Yamille Valdez.; University of Tennessee (U10 DA24128, U10 HD21415, U10
HD42638): Regina Barnes, Ashley Bayne, Teresa Beck, Beth Brewer, Vickie
Brewer, Charlotte C. Bursi, Gail Campbell, Kelly Chapman, Vivian
Crawford, Sheila Dempsey, Daneen Deptula, Claudia Duncan, Betty Eady,
Levy A. Eymard, Mary Georgeson, Sandra Grimes, Wendy Hadley, Denise
Head, Tracy Hopkins Golightly, Tina Hudson, Lillie Hughey, Lisa Jackson,
Vickie Jones, Sheldon B. Korones, Debris Lee, Pamela LeNoue, Laura
Manejwala, Sue Meewes, AlanE. Miller, Laura Murphy, Sidney Omduff, Beth
Owens, Mario C. Petersen, Leanne Plumlee Pollard, Jonathan Rowland,
Angelyn Sherrod, Michelle Silcox Miller, Andrea Simmons, Nanise
Tomtinson, Chandra Ward, Toni Whitaker, Lucia White, Marilyn Williams,
Kimberly A. Yolton.; Wayne State University Hutzel Women's Hospital and
Children's Hospital of Michigan (U10 DA24117, U10 HD21385): Catherine
Bartholomay, Jay Ann Nelson, Suzanne Deprez Piziali, Lisa Sulkowski,
Nicole Walker, Eunice Woldt.
NR 33
TC 8
Z9 8
U1 1
U2 4
PU INT PEDIATRIC RESEARCH FOUNDATION, INC
PI BALTIMORE
PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA
SN 0031-3998
J9 PEDIATR RES
JI Pediatr. Res.
PD AUG
PY 2011
VL 70
IS 2
BP 213
EP 219
PG 7
WC Pediatrics
SC Pediatrics
GA 795CP
UT WOS:000292949400018
PM 21546861
ER
PT J
AU Zhao, HY
Magone, MT
Schuck, P
AF Zhao, Huaying
Magone, M. Teresa
Schuck, Peter
TI The role of macromolecular crowding in the evolution of lens crystallins
with high molecular refractive index
SO PHYSICAL BIOLOGY
LA English
DT Article
ID SCALED-PARTICLE THEORY; CONCENTRATED HEMOGLOBIN-SOLUTIONS; DIVISION
PROTEIN FTSZ; BOVINE SERUM-ALBUMIN; GAMMA-D-CRYSTALLIN; EYE-LENS;
ALPHA-CRYSTALLIN; SICKLE HEMOGLOBIN; SELF-ASSOCIATION; BETA-CRYSTALLINS
AB Crystallins are present in the lens at extremely high concentrations in order to provide transparency and generate a high refractive power of the lens. The crystallin families prevalent in the highest density lens tissues are gamma-crystallins in vertebrates and S-crystallins in cephalopods. As shown elsewhere, in parallel evolution, both have evolved molecular refractive index increments 5-10% above those of most proteins. Although this is a small increase, it is statistically very significant and can be achieved only by very unusual amino acid compositions. In contrast, such a molecular adaptation to aid in the refractive function of the lens did not occur in crystallins that are preferentially located in lower density lens tissues, such as vertebrate alpha-crystallin and taxon-specific crystallins. In the current work, we apply a model of non-interacting hard spheres to examine the thermodynamic contributions of volume exclusion at lenticular protein concentrations. We show that the small concentration decrease afforded by the higher molecular refractive index increment of crystallins can amplify nonlinearly to produce order of magnitude differences in chemical activities, and lead to reduced osmotic pressure and the reduced propensity for protein aggregation. Quantitatively, this amplification sets in only at protein concentrations as high as those found in hard lenses or the nucleus of soft lenses, in good correspondence to the observed crystallin properties in different tissues and different species. This suggests that volume exclusion effects provide the evolutionary driving force for the unusual refractive properties and the unusual amino acid compositions of gamma-crystallins and S-crystallins.
C1 [Zhao, Huaying; Magone, M. Teresa; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
EM schuckp@mail.nih.gov
RI Zhao, Huaying/F-5716-2012;
OI Schuck, Peter/0000-0002-8859-6966
FU National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health
FX We thank Dr Allen Minton for helpful discussions and critical reading of
the manuscript. This work was supported by the Intramural Research
Program of the National Institute of Biomedical Imaging and
Bioengineering, National Institutes of Health.
NR 89
TC 7
Z9 7
U1 1
U2 20
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1478-3967
EI 1478-3975
J9 PHYS BIOL
JI Phys. Biol.
PD AUG
PY 2011
VL 8
IS 4
AR 046004
DI 10.1088/1478-3975/8/4/046004
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 795GK
UT WOS:000292961900014
PM 21566271
ER
PT J
AU Dinse, GE
Umbach, DM
AF Dinse, Gregg E.
Umbach, David M.
TI Characterizing non-constant relative potency
SO REGULATORY TOXICOLOGY AND PHARMACOLOGY
LA English
DT Article
DE Dose conversion; Dose response; ED50; Hill model; Non-similar
dose-response curves; Relative potency factor
ID DIOXIN-LIKE COMPOUNDS; TOXIC EQUIVALENCY FACTORS; CYP1A2
ENZYME-ACTIVITY; DOSE-RESPONSE CURVES; BIOASSAYS; INDUCTION; FAMILIES;
MODEL
AB Relative potency plays an important role in toxicology. Estimates of relative potency are used to rank chemicals by their effects, to calculate equivalent doses of test chemicals compared to a standard, and to weight contributions of constituent chemicals when evaluating mixtures. Typically relative potency is characterized by a constant dilution factor, even when non-similar dose-response curves indicate that constancy is inappropriate. Improperly regarding relative potency as constant may distort conclusions and potentially mislead investigators or policymakers. We consider a more general approach that allows relative potency to vary as a function of dose, response, or response quantile. Distinct functions can be defined, each generalizing different but equivalent descriptions of constant relative potency. When two chemicals have identical response limits, these functions all carry fundamentally equivalent information; otherwise, relative potency as a function of response quantile is distinct and embodies a modified definition of relative potency. Which definition is preferable depends on whether one views any differences in response limits as intrinsic to the chemicals or as extrinsic, arising from idiosyncrasies of data sources. We illustrate these ideas with constructed examples and real data. Relative potency functions offer a unified and principled description of relative potency for non-similar dose-response curves. Published by Elsevier Inc.
C1 [Dinse, Gregg E.; Umbach, David M.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Dinse, GE (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Mail Drop A3-03,POB 12233,Bldg 101,Room A-349,111, Res Triangle Pk, NC 27709 USA.
EM dinse@niehs.nih.gov; umbach@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [Z01-ES-102685]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences
(Z01-ES-102685). The NIH had no involvement in the study design;
collection, analysis and interpretation of data; writing of the
manuscript; or decision to submit the manuscript for publication. The
authors declare that there are no conflicts of interest.
NR 22
TC 2
Z9 2
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0273-2300
J9 REGUL TOXICOL PHARM
JI Regul. Toxicol. Pharmacol.
PD AUG
PY 2011
VL 60
IS 3
BP 342
EP 353
DI 10.1016/j.yrtph.2011.05.002
PG 12
WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology
SC Legal Medicine; Pharmacology & Pharmacy; Toxicology
GA 795AM
UT WOS:000292943900009
PM 21601607
ER
PT J
AU Straub, DM
Arrington-Sanders, R
Harris, DR
Willard, N
Kapogiannis, B
Emmanuel, P
Futterman, D
Ellen, JM
AF Straub, Diane M.
Arrington-Sanders, Renata
Harris, D. Robert
Willard, Nancy
Kapogiannis, Bill
Emmanuel, Patricia
Futterman, Donna
Ellen, Jonathan M.
CA Adolescent Trials Network HIV AIDS
TI Correlates of HIV Testing History Among Urban Youth Recruited Through
Venue-Based Testing in 15 US Cities
SO SEXUALLY TRANSMITTED DISEASES
LA English
DT Article
ID AFRICAN-AMERICAN ADOLESCENTS; RISK ADOLESCENTS; UNITED-STATES;
YOUNG-ADULTS; PREVALENCE; POPULATION; PREDICTORS; SERVICES; SAMPLE; MEN
AB Background: Adolescents and young adults comprise disproportionately high percentages of individuals living with human immunodeficiency virus (HIV) and those with undiagnosed HIV. Our objective was to determine factors associated with history of HIV testing and receipt of results among a sample of urban, high-risk, sexually active adolescents in 15 US cities.
Methods: A total of 20 to 30 sexually active youths, aged 12 to 24 years, were recruited to participate in an anonymous survey and HIV antibody testing at 2 to 3 venues per city identified by young men who have sex with men, young women of color, or intravenous drug users.
Results: Of the 1457 participants, 72% reported having been previously tested for HIV (89% of whom were aware of their test results). Our sample was diverse in terms of gender, race/ethnicity, and sexual orientation. Factors found to be predictive of testing typically reflect high risk for HIV, except for some high-risk partner characteristics, including having had a partner that made the youth have sex without a condom or had a partner with unknown HIV status. Factors associated with knowledge of serostatus are reported. HIV testing seems to be more associated with sexually transmitted infection testing services than with primary care.
Conclusions: More strategies are needed that increase testing, including targeting partners of high-risk individuals, insuring receipt of test results, and increasing testing in primary care settings.
C1 [Straub, Diane M.] Univ S Florida, Div Adolescent Med, Dept Pediat, Tampa, FL 33606 USA.
[Arrington-Sanders, Renata; Willard, Nancy; Ellen, Jonathan M.] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA.
[Harris, D. Robert] Westat Corp, Rockville, MD USA.
[Kapogiannis, Bill] NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA.
[Futterman, Donna] Montefiore Med Ctr, Bronx, NY 10467 USA.
RP Straub, DM (reprint author), Univ S Florida, Div Adolescent Med, Dept Pediat, 2 Tampa Gen Circle,Suite 500, Tampa, FL 33606 USA.
EM dstraub@health.usf.edu
FU National Institute of Child Health and Human Development; National
Institutes on Drug Abuse, Mental Health and Alcohol Abuse and Alcoholism
FX The Adolescent Trials Network for HIV/AIDS Interventions (ATN) and
Connect to Protect were funded, at the time of this study, through the
National Institute of Child Health and Human Development (Bill
Kapogiannis, Audrey Rogers, Robert Nugent, Leslie Serchuck, Sonia Lee),
with supplemental funding from the National Institutes on Drug Abuse
(Nicolette Borek), Mental Health (Andrew Forsyth, Pim Brouwers), and
Alcohol Abuse and Alcoholism (Kendall Bryant).
NR 24
TC 11
Z9 11
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-5717
J9 SEX TRANSM DIS
JI Sex. Transm. Dis.
PD AUG
PY 2011
VL 38
IS 8
BP 691
EP 696
DI 10.1097/OLQ.0b013e318214bb70
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA 792PP
UT WOS:000292759900003
PM 21758020
ER
PT J
AU Eggleston, E
Rogers, SM
Turner, CF
Miller, WC
Roman, AM
Hobbs, MM
Erbelding, E
Tan, S
Villarroel, MA
Ganapathi, L
AF Eggleston, Elizabeth
Rogers, Susan M.
Turner, Charles F.
Miller, William C.
Roman, Anthony M.
Hobbs, Marcia M.
Erbelding, Emily
Tan, Sylvia
Villarroel, Maria A.
Ganapathi, Laxminarayana
TI Chlamydia trachomatis Infection Among 15-to 35-Year-Olds in Baltimore,
MD
SO SEXUALLY TRANSMITTED DISEASES
LA English
DT Article
ID UNITED-STATES; T-ACASI; PREVALENCE; ADOLESCENTS; PATTERNS; ADULTS; BIAS;
STD
AB Background: Chlamydia trachomatis (Ct) is the most frequently reported infectious disease in the United States. This article reports population and subpopulation prevalence estimates of Ct and correlates of infection among 15- to 35-year-olds in Baltimore, MD.
Methods: The Monitoring STIs Survey Program (MSSP) monitored sexually transmitted infection (STI) prevalence among probability samples of residents of Baltimore, a city with high STI rates. MSSP respondents completed telephone audio computer-assisted self-interviews and provided biospecimens for STI testing.
Results: Among 2120 Baltimore residents aged 15 to 35 years, the estimated prevalence of chlamydia was 3.9% (95% confidence interval [CI]: 2.8, 5.0). Prevalence was 5.8% (95% CI: 4.1, 7.6) among black MSSP respondents versus 0.7% (95% CI: 0.0, 1.4) among nonblack respondents; all but 4 infections detected were among black respondents. Sexual behaviors and other factors associated with infection were far more prevalent among black than nonblack Baltimore residents. Racial disparities persisted after adjustment for sociodemographic, behavioral, and health factors.
Conclusion: The MSSP highlights a higher Ct prevalence among young people in Baltimore than in the United States overall, with notable racial disparities in infection and associated risk behaviors. Public health efforts are needed to improve the diagnosis and treatment of asymptomatic infections in this population.
C1 [Eggleston, Elizabeth; Rogers, Susan M.; Tan, Sylvia; Villarroel, Maria A.] Res Triangle Inst, Stat & Epidemiol Div, Washington, DC 20015 USA.
[Turner, Charles F.] CUNY, Queens Coll, Flushing, NY USA.
[Turner, Charles F.] Grad Ctr, Flushing, NY USA.
[Miller, William C.; Hobbs, Marcia M.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Roman, Anthony M.] Univ Massachusetts, Surg Res Ctr, Boston, MA 02125 USA.
[Erbelding, Emily] NIH, Div Aids, Bethesda, MD 20892 USA.
[Villarroel, Maria A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Ganapathi, Laxminarayana] Res Triangle Inst, Res Comp Div, Res Triangle Pk, NC 27709 USA.
RP Eggleston, E (reprint author), Res Triangle Inst, Stat & Epidemiol Div, 701 13th St NW,Suite 750, Washington, DC 20015 USA.
EM eeggleston@hotmail.com
RI Miller, William/H-4800-2014
OI Miller, William/0000-0002-1934-7827
FU NIH [R01HD047163]
FX Supported by NIH grant R01HD047163 to Research Triangle Institute.
NR 21
TC 16
Z9 16
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-5717
J9 SEX TRANSM DIS
JI Sex. Transm. Dis.
PD AUG
PY 2011
VL 38
IS 8
BP 743
EP 749
DI 10.1097/OLQ.0b013e318214c149
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA 792PP
UT WOS:000292759900011
PM 21844726
ER
PT J
AU Hudson, LD
Romm, E
Berndt, JA
Nielsen, JA
AF Hudson, Lynn D.
Romm, Elena
Berndt, Jo Ann
Nielsen, Joseph A.
TI A tool for examining the role of the zinc finger myelin transcription
factor 1 (Myt1) in neural development: Myt1 knock-in mice
SO TRANSGENIC RESEARCH
LA English
DT Article
DE Oligodendrocytes; Transcriptional networks; Corepressors;
Myelinogenesis; Zinc finger transcription factors
ID ISLET-CELL DIFFERENTIATION; CENTRAL-NERVOUS-SYSTEM; DNA-BINDING PROTEIN;
OLIGODENDROCYTE LINEAGE; GENE-EXPRESSION; MOUSE; NEURONS; REPORTER;
OLIG2; FORM
AB The Myt1 family of transcription factors is unique among the many classes of zinc finger proteins in how the zinc-stabilized fingers contact the DNA helix. To examine the function of Myt1 in the developing nervous system, we generated mice in which Myt1 expression was replaced by an enhanced Green Fluorescent Protein fused to a Codon-improved Cre recombinase as a protein reporter. Myt1 knock-in mice die at birth, apparently due to improper innervation of their lungs. Elimination of Myt1 did not significantly affect the number or distribution of neural precursor cells that normally express Myt1 in the embryonic spinal cord. Nor was the general pattern of differentiated neurons altered in the embryonic spinal cord. The Myt1 knock-in mice should provide an important tool for identifying the in vivo targets of Myt1 action and unraveling the role of this structurally distinct zinc finger protein in neural development.
C1 [Hudson, Lynn D.; Romm, Elena; Berndt, Jo Ann; Nielsen, Joseph A.] NINDS, Sect Dev Genet, NIH, Bethesda, MD 20892 USA.
RP Hudson, LD (reprint author), NINDS, Sect Dev Genet, NIH, Bldg 1,Room 228, Bethesda, MD 20892 USA.
EM hudsonl1@od.nih.gov
FU National Institute of Neurological Disorders and Stroke (NINDS)/National
Institutes of Health [1 Z01 NS002528]
FX The authors thank Dr. Eva Mezey for insights on quantitative
immunohistochemistry, Wayne Rasband for assistance with the imageJ
program, and Dr. Heinz Arnheiter for training and access to his
computerized Filemaker-based animal breeding database program. Dr. Gabor
Lovas' insights on the phenotype of the knock-in mice are gratefully
acknowledged. This work was supported by National Institute of
Neurological Disorders and Stroke (NINDS)/National Institutes of Health
intramural funds to LDH for project# 1 Z01 NS002528.
NR 32
TC 5
Z9 5
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-8819
J9 TRANSGENIC RES
JI Transgenic Res.
PD AUG
PY 2011
VL 20
IS 4
BP 951
EP 961
DI 10.1007/s11248-010-9470-x
PG 11
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 794FM
UT WOS:000292880900020
PM 21267777
ER
PT J
AU Gordon, IK
Camphausen, K
AF Gordon, Ira K.
Camphausen, Kevin
TI Circulating osteoprotegrin predicts breast cancer bone metastasis
SO BIOMARKERS IN MEDICINE
LA English
DT News Item
C1 [Gordon, Ira K.; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, CRC, Bethesda, MD 20892 USA.
RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, NIH, CRC, 10 Ctr Dr,Bldg 10,Room B2-3561, Bethesda, MD 20892 USA.
EM camphauk@mail.nih.gov
NR 0
TC 0
Z9 0
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 1752-0363
J9 BIOMARK MED
JI Biomark. Med.
PD AUG
PY 2011
VL 5
IS 4
BP 423
EP 424
PG 2
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 836VB
UT WOS:000296141300009
ER
PT J
AU Gordon, IK
Camphausen, K
AF Gordon, Ira K.
Camphausen, Kevin
TI The quest for Engrailed as a urinary biomarker in prostate cancer
SO BIOMARKERS IN MEDICINE
LA English
DT News Item
C1 [Gordon, Ira K.; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, CRC, Bethesda, MD 20892 USA.
RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, NIH, CRC, 10 Ctr Dr,Bldg 10,Room B2-3561, Bethesda, MD 20892 USA.
EM camphauk@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1752-0363
J9 BIOMARK MED
JI Biomark. Med.
PD AUG
PY 2011
VL 5
IS 4
BP 423
EP 423
PG 1
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 836VB
UT WOS:000296141300008
ER
PT J
AU Gordon, IK
Camphausen, K
AF Gordon, Ira K.
Camphausen, Kevin
TI Marking successful Met inhibition in Met-driven cancer
SO BIOMARKERS IN MEDICINE
LA English
DT News Item
C1 [Gordon, Ira K.; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, CRC, Bethesda, MD 20892 USA.
RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, NIH, CRC, 10 Ctr Dr,Bldg 10,Room B2-3561, Bethesda, MD 20892 USA.
EM camphauk@mail.nih.gov
NR 0
TC 0
Z9 0
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 1752-0363
J9 BIOMARK MED
JI Biomark. Med.
PD AUG
PY 2011
VL 5
IS 4
BP 424
EP 424
PG 1
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 836VB
UT WOS:000296141300011
ER
PT J
AU Gordon, IK
Camphausen, K
AF Gordon, Ira K.
Camphausen, Kevin
TI New proteomic approach to identifying cancer biomarkers
SO BIOMARKERS IN MEDICINE
LA English
DT News Item
C1 [Gordon, Ira K.; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, CRC, Bethesda, MD 20892 USA.
RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, NIH, CRC, 10 Ctr Dr,Bldg 10,Room B2-3561, Bethesda, MD 20892 USA.
EM camphauk@mail.nih.gov
NR 0
TC 0
Z9 0
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 1752-0363
J9 BIOMARK MED
JI Biomark. Med.
PD AUG
PY 2011
VL 5
IS 4
BP 424
EP 424
PG 1
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 836VB
UT WOS:000296141300010
ER
PT J
AU Gordon, IK
Camphausen, K
AF Gordon, Ira K.
Camphausen, Kevin
TI Could circulating leukocyte DNA methylation diagnose pancreatic cancer?
SO BIOMARKERS IN MEDICINE
LA English
DT News Item
C1 [Gordon, Ira K.; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, CRC, Bethesda, MD 20892 USA.
RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, NIH, CRC, 10 Ctr Dr,Bldg 10,Room B2-3561, Bethesda, MD 20892 USA.
EM camphauk@mail.nih.gov
NR 0
TC 0
Z9 0
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 1752-0363
J9 BIOMARK MED
JI Biomark. Med.
PD AUG
PY 2011
VL 5
IS 4
BP 425
EP 425
PG 1
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 836VB
UT WOS:000296141300012
ER
PT J
AU Erlinge, D
Hogberg, C
Gidlof, O
Deflorian, F
Jacobson, KA
Olde, B
AF Erlinge, D.
Hogberg, C.
Gidlof, O.
Deflorian, F.
Jacobson, K. A.
Olde, B.
TI Farnesyl pyrophosphate is an endogenous antagonist to ADP-stimulated
P2Y12 receptor-mediated platelet aggregation
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 [Erlinge, D.] Univ Lund Hosp, S-22185 Lund, Sweden.
[Hogberg, C.; Gidlof, O.; Olde, B.] Lund Univ, Skane Univ Hosp, Lund, Sweden.
[Deflorian, F.; Jacobson, K. A.] NIH, Diabet Unit, Bethesda, MD 20892 USA.
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2011
VL 32
SU 1
BP 252
EP 252
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V28TI
UT WOS:000208702702373
ER
PT J
AU Stefansdottir, H
Arnar, DO
Aspelund, T
Sigurdsson, S
Launer, LJ
Gudnason, V
AF Stefansdottir, H.
Arnar, D. O.
Aspelund, T.
Sigurdsson, S.
Launer, L. J.
Gudnason, V.
TI Atrial fibrillation is associated with brain atrophy independent of
cerebral infarction: the AGES-reykjavik study
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 [Stefansdottir, H.; Arnar, D. O.] Landspitali Natl Univ Hosp Iceland, Reykjavik, Iceland.
[Aspelund, T.; Sigurdsson, S.; Gudnason, V.] Iceland Heart Assoc, Reykjavik, Iceland.
[Launer, L. J.] NIA, Bethesda, MD 20892 USA.
RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084
NR 0
TC 0
Z9 0
U1 1
U2 3
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 AUG
PY 2011
VL 32
SU 1
BP 319
EP 319
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V28TI
UT WOS:000208702703017
ER
PT J
AU Mccomb, C
Payne, A
Barrett, R
Smith, C
Casey, M
Mcclure, J
Oldroyd, K
Wen, H
Foster, J
Berry, C
AF Mccomb, C.
Payne, A.
Barrett, R.
Smith, C.
Casey, M.
Mcclure, J.
Oldroyd, K.
Wen, H.
Foster, J.
Berry, C.
TI Measurement of left ventricular strain with strain-encoded MRI (DENSE)
is feasible and informative in patients with recent or chronic
myocardial infarction
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 [Mccomb, C.; Foster, J.] NHS Greater Glasgow & Clyde, Glasgow, Lanark, Scotland.
[Payne, A.; Oldroyd, K.] Golden Jubilee Natl Hosp, Glasgow, Lanark, Scotland.
[Barrett, R.; Smith, C.; Casey, M.; Mcclure, J.; Berry, C.] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
[Wen, H.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2011
VL 32
SU 1
BP 369
EP 369
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V28TI
UT WOS:000208702703207
ER
PT J
AU Fischer, R
Spallek, B
Qadri, F
Konkel, A
Marko, L
Luft, FC
Zeldin, DC
Schirdewan, A
Muller, DN
Schunck, WH
AF Fischer, R.
Spallek, B.
Qadri, F.
Konkel, A.
Marko, L.
Luft, F. C.
Zeldin, D. C.
Schirdewan, A.
Muller, D. N.
Schunck, W. H.
TI CYP2J2 overexpression prevents remodeling and atrial fibrillation in
chronic beta-adrenergic hypertrophy
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 [Fischer, R.; Schirdewan, A.] Charite Campus Benjamin Franklin, Ctr Cardiovasc Med 11, Berlin, Germany.
[Spallek, B.; Qadri, F.; Marko, L.; Luft, F. C.; Muller, D. N.] Charite Campus Berlin Buch, Expt & Clin Res Ctr, Berlin, Germany.
[Konkel, A.; Schunck, W. H.] Max Delbruck Ctr Mol Med, Berlin, Germany.
[Zeldin, D. C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2011
VL 32
SU 1
BP 473
EP 473
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V28TI
UT WOS:000208702703602
ER
PT J
AU Laek, B
Szklo, M
Mcclelland, R
Ding, J
Tsai, M
Bluemke, DA
Tracy, R
Matsushita, K
AF Laek, B.
Szklo, M.
Mcclelland, R.
Ding, J.
Tsai, M.
Bluemke, D. A.
Tracy, R.
Matsushita, K.
TI The association of pathogens with progression of coronary artery
calcium: the Multi-Ethnic Study of Atherosclerosis (MESA)
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 [Laek, B.; Szklo, M.; Matsushita, K.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Mcclelland, R.] Univ Washington, Seattle, WA 98195 USA.
[Ding, J.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Tsai, M.] Univ Minnesota, Minneapolis, MN USA.
[Bluemke, D. A.] NIH, Bethesda, MD 20892 USA.
[Tracy, R.] Univ Vermont, Colchester, VT USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2011
VL 32
SU 1
BP 518
EP 519
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V28TI
UT WOS:000208702704165
ER
PT J
AU Turton, P
Sussex, B
Mckay, D
Gadag, V
Chockalingam, A
Fodor, JG
AF Turton, P.
Sussex, B.
Mckay, D.
Gadag, V.
Chockalingam, A.
Fodor, J. G.
TI Changes in cholesterol levels over an 18-year period in a random sample
of Canadians residing in Newfoundland: effect of diet versus
pharmacotherapy
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 [Turton, P.; Fodor, J. G.] Univ Ottawa, Inst Heart, Ottawa, ON, Canada.
[Sussex, B.; Mckay, D.; Gadag, V.] Mem Univ Newfoundland, St John, NF, Canada.
[Chockalingam, A.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 AUG
PY 2011
VL 32
SU 1
BP 540
EP 540
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V28TI
UT WOS:000208702704250
ER
PT J
AU Khademi, H
Kamangar, F
Islami, F
Pourshams, A
Abnet, C
Boffetta, P
Brennan, P
Fuster, V
Malekzadeh, R
Vedanthan, R
AF Khademi, H.
Kamangar, F.
Islami, F.
Pourshams, A.
Abnet, C.
Boffetta, P.
Brennan, P.
Fuster, V.
Malekzadeh, R.
Vedanthan, R.
TI Opium use increases risk of cardiovascular death: Golestan Cohort Study
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 [Khademi, H.; Islami, F.; Pourshams, A.; Malekzadeh, R.] Tehran Univ Med Siences, Shariati Hosp, Tehran, Iran.
[Kamangar, F.; Abnet, C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Boffetta, P.; Fuster, V.; Vedanthan, R.] Mt Sinai Sch Med, New York, NY USA.
[Brennan, P.] Int Agcy Res Canc, F-69372 Lyon, France.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 AUG
PY 2011
VL 32
SU 1
BP 548
EP 549
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V28TI
UT WOS:000208702704282
ER
PT J
AU Redheuil, A
Mousseaux, E
Yu, WC
Kachenoura, N
Perdrix, L
Bluemke, D
Lima, JAC
AF Redheuil, A.
Mousseaux, E.
Yu, W. C.
Kachenoura, N.
Perdrix, L.
Bluemke, D.
Lima, J. A. C.
TI Relationship between proximal aortic stiffness assessed with CMR and
left ventricular diastolic function in asymptomatic subjects with
preserved left ventricular ejection fraction
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 [Redheuil, A.; Mousseaux, E.; Perdrix, L.] Univ Paris 05, European Hosp Georges Pompidou, INSERM, U678, Paris, France.
[Yu, W. C.] Natl Yang Ming Univ, Taipei 112, Taiwan.
[Kachenoura, N.] INSERM, U678, Paris, France.
[Bluemke, D.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Lima, J. A. C.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 AUG
PY 2011
VL 32
SU 1
BP 616
EP 617
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V28TI
UT WOS:000208702704550
ER
PT J
AU Saksena, S
Slee, A
Waldo, A
Freemantle, N
Reynolds, M
Rosenberg, Y
Grant, S
Thomas, E
Kuo, E
Wyse, G
AF Saksena, S.
Slee, A.
Waldo, A.
Freemantle, N.
Reynolds, M.
Rosenberg, Y.
Grant, S.
Thomas, E.
Kuo, E.
Wyse, G.
TI Assessment of individual antiarrhythmic drug therapies compared to rate
control using propensity score matched analyses in the AFFIRM trial
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 [Saksena, S.; Slee, A.; Grant, S.; Thomas, E.; Kuo, E.] Electrophysiol Res Fdn, Warren, NJ USA.
[Waldo, A.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Freemantle, N.] Univ Birmingham, Birmingham, W Midlands, England.
[Reynolds, M.] Harvard Univ, Boston, MA 02115 USA.
[Rosenberg, Y.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Wyse, G.] Lubin Cardiovasc Inst, Calgary, AB, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 AUG
PY 2011
VL 32
SU 1
BP 624
EP 625
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V28TI
UT WOS:000208702704580
ER
PT J
AU Goto, K
Iso, T
Hanaoka, H
Suga, T
Matsui, H
Arai, M
Endo, K
Gonzalez, FJ
Kurabayashi, M
AF Goto, K.
Iso, T.
Hanaoka, H.
Suga, T.
Matsui, H.
Arai, M.
Endo, K.
Gonzalez, F. J.
Kurabayashi, M.
TI PPAR-gamma regulates trans-endothelial fatty acid transport via
induction of fatty acid binding protein 4 in capillary endothelial cells
in heart, red skeletal muscles and adipose tissue
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 [Goto, K.; Iso, T.; Hanaoka, H.; Suga, T.; Matsui, H.; Arai, M.; Endo, K.; Kurabayashi, M.] Gunma Univ, Sch Med, Gunma, Japan.
[Gonzalez, F. J.] NIH, NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2011
VL 32
SU 1
BP 687
EP 687
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V28TI
UT WOS:000208702705193
ER
PT J
AU Ernande, L
Wen, H
Bergerot, C
Thibault, H
Moulin, P
Ovize, M
Derumeaux, G
Croisille, P
AF Ernande, L.
Wen, H.
Bergerot, C.
Thibault, H.
Moulin, P.
Ovize, M.
Derumeaux, G.
Croisille, P.
TI Cine Displacement ENcoding imaging with Stimulated Echoes (cine-DENSE)
confirms radial, circumferential and longitudinal systolic myocardial
dysfunction in asymptomatic patients with type 2 diabetes
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 [Ernande, L.; Bergerot, C.; Thibault, H.; Moulin, P.; Ovize, M.; Derumeaux, G.; Croisille, P.] Univ Hosp Lyon, Hosp Louis Pradel, Lyon, France.
[Wen, H.] NIH, Bethesda, MD 20892 USA.
RI Croisille, Pierre/H-4928-2014; Wen, Han/G-3081-2010
OI Croisille, Pierre/0000-0003-4019-3460; Wen, Han/0000-0001-6844-2997
NR 0
TC 0
Z9 0
U1 0
U2 2
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 AUG
PY 2011
VL 32
SU 1
BP 985
EP 986
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V28TI
UT WOS:000208702707179
ER
PT J
AU Schmidt, AC
Schaap-Nutt, A
Bartlett, EJ
Schomacker, H
Boonyaratanakornkit, J
Karron, RA
Collins, PL
AF Schmidt, Alexander C.
Schaap-Nutt, Anne
Bartlett, Emmalene J.
Schomacker, Henrick
Boonyaratanakornkit, Jim
Karron, Ruth A.
Collins, Peter L.
TI Progress in the development of human parainfluenza virus vaccines
SO EXPERT REVIEW OF RESPIRATORY MEDICINE
LA English
DT Review
DE acute respiratory illness; clinical trial; intranasal; live-attenuated;
parainfluenza virus vaccine; pediatric; vaccine
ID RESPIRATORY SYNCYTIAL VIRUS; AFRICAN-GREEN MONKEYS; AMINO-ACID
SUBSTITUTIONS; LIVE ATTENUATED VACCINE; L-POLYMERASE PROTEIN; FUSION F
PROTEIN; CD8(+) T-CELLS; REVERSE GENETICS; PARA-INFLUENZA;
YOUNG-CHILDREN
AB In children under 5 years of age, human parainfluenza viruses (HPIVs) as a group are the second most common etiology of acute respiratory illness leading to hospitalization, surpassed only by respiratory syncytial virus but ahead of influenza viruses. Using reverse genetics systems for HPIV serotypes 1, 2 and 3 (HPIV1, 2 and 3), several live-attenuated HPIVs have been generated and evaluated as intranasal vaccines in adults and in children. Two vaccines against HPIV3 were found to be well tolerated, infectious and immunogenic in Phase I trials in HPIV3-seronegative infants and children and should progress to proof-of-concept trials. Vaccines against HPIV1 and HPIV2 are less advanced and have just entered pediatric trials.
C1 [Schmidt, Alexander C.; Schaap-Nutt, Anne; Bartlett, Emmalene J.; Schomacker, Henrick; Boonyaratanakornkit, Jim; Collins, Peter L.] NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Karron, Ruth A.] Johns Hopkins Univ, Ctr Immunizat Res, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Schmidt, AC (reprint author), NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM schmidta@niaid.nih.gov
FU MedImmune
FX Alexander C Schmidt, Emmalene J Bartlett and Peter L Collins are
inventors on PIV patents and patent applications. NIAID and MedImmune
have a cooperative research and development agreement in place for the
development of RSV, PIV and HMPV vaccines. NIAID receives royalties (not
related to Ply vaccines) from MedImmune. Alexander C Schmidt is an
Associate Scientist at NIAID and the Project Officer responsible for
translational and clinical PIV vaccine development. The authors have no
other relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 101
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U1 1
U2 7
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1747-6348
J9 EXPERT REV RESP MED
JI Expert Rev. Respir. Med.
PD AUG
PY 2011
VL 5
IS 4
BP 515
EP 526
DI 10.1586/ERS.11.32
PG 12
WC Respiratory System
SC Respiratory System
GA 056RG
UT WOS:000312508200014
PM 21859271
ER
PT J
AU Ni, N
Nikolaitchik, OA
Dilley, KA
Chen, JB
Galli, A
Fu, W
Prasad, VVSP
Ptak, RG
Pathak, VK
Hu, WS
AF Ni, Na
Nikolaitchik, Olga A.
Dilley, Kari A.
Chen, Jianbo
Galli, Andrea
Fu, William
Prasad, V. V. S. P.
Ptak, Roger G.
Pathak, Vinay K.
Hu, Wei-Shau
TI Mechanisms of Human Immunodeficiency Virus Type 2 RNA Packaging:
Efficient trans Packaging and Selection of RNA Copackaging Partners
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MURINE LEUKEMIA-VIRUS; HIV-1 INTERSUBTYPE RECOMBINATION; HIGH NEGATIVE
INTERFERENCE; GENOMIC RNA; IN-VITRO; RETROVIRAL RNA;
GENETIC-RECOMBINATION; LENTIVIRUS VECTORS; INITIATION SIGNAL;
MESSENGER-RNA
AB Human immunodeficiency virus type 2 (HIV-2) has been reported to have a distinct RNA packaging mechanism, referred to as cis packaging, in which Gag proteins package the RNA from which they were translated. We examined the progeny generated from dually infected cell lines that contain two HIV-2 proviruses, one with a wild-type gag/gag-pol and the other with a mutant gag that cannot express functional Gag/Gag-Pol. Viral titers and RNA analyses revealed that mutant viral RNAs can be packaged at efficiencies comparable to that of viral RNA from which wild-type Gag/Gag-Pol is translated. These results do not support the cis-packaging hypothesis but instead indicate that trans packaging is the major mechanism of HIV-2 RNA packaging. To further characterize the mechanisms of HIV-2 RNA packaging, we visualized HIV-2 RNA in individual particles by using fluorescent protein-tagged RNA-binding proteins that specifically recognize stem-loop motifs in the viral genomes, an assay termed single virion analysis. These studies revealed that >90% of the HIV-2 particles contained viral RNAs and that RNAs derived from different viruses were copackaged frequently. Furthermore, the frequencies of heterozygous particles in the viral population could be altered by changing a 6-nucleotide palindromic sequence at the 5'-untranslated region of the HIV-2 genome. This finding indicates that selection of copackaging RNA partners occurs prior to encapsidation and that HIV-2 Gag proteins primarily package one dimeric RNA rather than two monomeric RNAs. Additionally, single virion analyses demonstrated a similar RNA distribution in viral particles regardless of whether both viruses had a functional gag or one of the viruses had a nonfunctional gag, providing further support for the trans-packaging hypothesis. Together, these results revealed mechanisms of HIV-2 RNA packaging that are, contrary to previous studies, in many respects surprisingly similar to those of HIV-1.
C1 [Ni, Na; Nikolaitchik, Olga A.; Dilley, Kari A.; Chen, Jianbo; Galli, Andrea; Prasad, V. V. S. P.; Pathak, Vinay K.; Hu, Wei-Shau] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Fu, William; Ptak, Roger G.] So Res Inst, Dept Infect Dis Res, Frederick, MD 21701 USA.
RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Room 336, Frederick, MD 21702 USA.
EM Wei-Shau.Hu@nih.gov
RI Chen, Jianbo/N-3737-2014;
OI Chen, Jianbo/0000-0001-6491-6577; Galli, Andrea/0000-0002-4404-430X
FU NIH National Cancer Institute Center for Cancer Research; NIH
FX This research was supported in part by the Intramural Research Program
of the NIH National Cancer Institute Center for Cancer Research and by
IATAP funding from NIH.
NR 50
TC 14
Z9 14
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2011
VL 85
IS 15
BP 7603
EP 7612
DI 10.1128/JVI.00562-11
PG 10
WC Virology
SC Virology
GA 788LV
UT WOS:000292447300014
PM 21613401
ER
PT J
AU Boyd, L
Hajjar, C
O'Connell, K
AF Boyd, Lynn
Hajjar, Connie
O'Connell, Kevin
TI Time-lapse Microscopy of Early Embryogenesis in Caenorhabditis elegans
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Developmental Biology; Issue 54; Live embryo imaging; fertilization;
meiosis; nematode; fluorescent protein; lysotracker; Caenorhabditis
elegans; C. elegans
AB Caenorhabditis elegans has often been used as a model system in studies of early developmental processes. The transparency of the embryos, the genetic resources, and the relative ease of transformation are qualities that make C. elegans an excellent model for early embryogenesis. Laser-based confocal microscopy and fluorescently labeled tags allow researchers to follow specific cellular structures and proteins in the developing embryo. For example, one can follow specific organelles, such as lysosomes or mitochondria, using fluorescently labeled dyes. These dyes can be delivered to the early embryo by means of microinjection into the adult gonad. Also, the localization of specific proteins can be followed using fluorescent protein tags. Examples are presented here demonstrating the use of a fluorescent lysosomal dye as well as fluorescently tagged histone and ubiquitin proteins. The labeled histone is used to visualize the DNA and thus identify the stage of the cell cycle. GFP-tagged ubiquitin reveals the dynamics of ubiquitinated vesicles in the early embryo. Observations of labeled lysosomes and GFP:: ubiquitin can be used to determine if there is colocalization between ubiquitinated vesicles and lysosomes. A technique for the microinjection of the lysosomal dye is presented. Techniques for generating transgenenic strains are presented elsewhere (1, 2). For imaging, embryos are cut out of adult hermaphrodite nematodes and mounted onto 2% agarose pads followed by time-lapse microscopy on a standard laser scanning confocal microscope or a spinning disk confocal microscope. This methodology provides for the high resolution visualization of early embryogenesis.
C1 [Boyd, Lynn; Hajjar, Connie] Univ Alabama Huntsville, Dept Biol Sci, Huntsville, AL 35899 USA.
[O'Connell, Kevin] NIDDK, NIH, Bethesda, MD USA.
RP Boyd, L (reprint author), Univ Alabama Huntsville, Dept Biol Sci, Huntsville, AL 35899 USA.
EM boydl@uah.edu
FU National Institutes of Health [R15 GM065444-03]; Intramural Research
Program of the National Institutes of Health (NIH); National Institute
of Diabetes and Digestive and Kidney Diseases; NSF award [DBI-0923402]
FX We would like to acknowledge funding from the National Institutes of
Health (R15 GM065444-03 to L.B.) and the Intramural Research Program of
the National Institutes of Health (NIH) and the National Institute of
Diabetes and Digestive and Kidney Diseases (K. O.). An NSF award
(DBI-0923402) funded the acquisition of the LSM700 confocal microscope.
We would also like to acknowledge general assistance and helpful
comments on the manuscript from Dr. Andy Golden. Credit goes to the
entire C. elegans community for sharing resources, protocols, and ideas.
NR 14
TC 1
Z9 1
U1 1
U2 1
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD AUG
PY 2011
IS 54
AR UNSP e2852
DI 10.3791/2852
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36MD
UT WOS:000209215100020
ER
PT J
AU Plenz, D
Stewart, CV
Shew, W
Yang, HD
Klaus, A
Bellay, T
AF Plenz, Dietmar
Stewart, Craig V.
Shew, Woodrow
Yang, Hongdian
Klaus, Andreas
Bellay, Tim
TI Multi-electrode Array Recordings of Neuronal Avalanches in Organotypic
Cultures
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
AB The cortex is spontaneously active, even in the absence of any particular input or motor output. During development, this activity is important for the migration and differentiation of cortex cell types and the formation of neuronal connections1. In the mature animal, ongoing activity reflects the past and the present state of an animal into which sensory stimuli are seamlessly integrated to compute future actions. Thus, a clear understanding of the organization of ongoing i.e. spontaneous activity is a prerequisite to understand cortex function.
Numerous recording techniques revealed that ongoing activity in cortex is comprised of many neurons whose individual activities transiently sum to larger events that can be detected in the local field potential (LFP) with extracellular microelectrodes, or in the electroencephalogram (EEG), the magnetoencephalogram (MEG), and the BOLD signal from functional magnetic resonance imaging (fMRI). The LFP is currently the method of choice when studying neuronal population activity with high temporal and spatial resolution at the mesoscopic scale (several thousands of neurons). At the extracellular microelectrode, locally synchronized activities of spatially neighbored neurons result in rapid deflections in the LFP up to several hundreds of microvolts. When using an array of microelectrodes, the organizations of such deflections can be conveniently monitored in space and time.
Neuronal avalanches describe the scale-invariant spatiotemporal organization of ongoing neuronal activity in the brain2,3. They are specific to the superficial layers of cortex as established in vitro4,5, in vivo in the anesthetized rat 6, and in the awake monkey7. Importantly, both theoretical and empirical studies2,8-10 suggest that neuronal avalanches indicate an exquisitely balanced critical state dynamics of cortex that optimizes information transfer and information processing.
In order to study the mechanisms of neuronal avalanche development, maintenance, and regulation, in vitro preparations are highly beneficial, as they allow for stable recordings of avalanche activity under precisely controlled conditions. The current protocol describes how to study neuronal avalanches in vitro by taking advantage of superficial layer development in organotypic cortex cultures, i.e. slice cultures, grown on planar, integrated microelectrode arrays (MEA; see also 11-14).
C1 [Plenz, Dietmar; Stewart, Craig V.; Shew, Woodrow; Yang, Hongdian; Klaus, Andreas; Bellay, Tim] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA.
RP Plenz, D (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA.
EM plenzd@mail.nih.gov
RI Yang, Hongdian/D-1450-2015;
OI Shew, Woodrow/0000-0003-0679-1766; Klaus, Andreas/0000-0002-4133-351X
FU Division of Intramural Research Program (DIRP) of the National Institute
of Mental Health, National Institutes of Health
FX This study was funded by the Division of Intramural Research Program
(DIRP) of the National Institute of Mental Health, National Institutes
of Health.
NR 34
TC 6
Z9 6
U1 0
U2 0
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD AUG
PY 2011
IS 54
AR UNSP e2949
DI 10.3791/2949
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36MD
UT WOS:000209215100034
ER
PT J
AU Smith, AM
Durbic, T
Oh, J
Urbanus, M
Proctor, M
Heisler, LE
Giaever, G
Nislow, C
AF Smith, Andrew M.
Durbic, Tanja
Oh, Julia
Urbanus, Malene
Proctor, Michael
Heisler, Lawrence E.
Giaever, Guri
Nislow, Corey
TI Competitive Genomic Screens of Barcoded Yeast Libraries
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Biochemistry; Issue 54; chemical biology; chemogenomics; chemical
probes; barcode microarray; next generation sequencing
AB By virtue of advances in next generation sequencing technologies, we have access to new genome sequences almost daily. The tempo of these advances is accelerating, promising greater depth and breadth. In light of these extraordinary advances, the need for fast, parallel methods to define gene function becomes ever more important. Collections of genome-wide deletion mutants in yeasts and E. coli have served as workhorses for functional characterization of gene function, but this approach is not scalable, current gene-deletion approaches require each of the thousands of genes that comprise a genome to be deleted and verified. Only after this work is complete can we pursue high-throughput phenotyping. Over the past decade, our laboratory has refined a portfolio of competitive, miniaturized, high-throughput genome-wide assays that can be performed in parallel. This parallelization is possible because of the inclusion of DNA 'tags', or 'barcodes,' into each mutant, with the barcode serving as a proxy for the mutation and one can measure the barcode abundance to assess mutant fitness. In this study, we seek to fill the gap between DNA sequence and barcoded mutant collections. To accomplish this we introduce a combined transposon disruption-barcoding approach that opens up parallel barcode assays to newly sequenced, but poorly characterized microbes. To illustrate this approach we present a new Candida albicans barcoded disruption collection and describe how both microarray-based and next generation sequencing-based platforms can be used to collect 10,000 - 1,000,000 gene-gene and drug-gene interactions in a single experiment.
C1 [Smith, Andrew M.; Urbanus, Malene; Nislow, Corey] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 1A1, Canada.
[Smith, Andrew M.; Urbanus, Malene; Nislow, Corey] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada.
[Smith, Andrew M.; Durbic, Tanja; Urbanus, Malene; Heisler, Lawrence E.; Giaever, Guri; Nislow, Corey] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 1A1, Canada.
[Durbic, Tanja; Heisler, Lawrence E.; Nislow, Corey] Univ Toronto, Donnelly Sequencing Ctr, Toronto, ON M5S 1A1, Canada.
[Oh, Julia] Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD USA.
[Proctor, Michael] Stanford Univ, Sch Med, Stanford Genome Technol Ctr, Stanford, CA 94305 USA.
[Giaever, Guri] Univ Toronto, Dept Pharmaceut Sci, Toronto, ON M5S 1A1, Canada.
RP Nislow, C (reprint author), Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 1A1, Canada.
EM corey.nislow@utoronto.ca
OI Nislow, Corey/0000-0002-4016-8874
FU National Human Genome Research Institute [HG000205]; CIHR [MOP-84305];
Canadian Cancer Society [020380]; Stanford Genome Training Program
(National Human Genome Research Institute) [T32 HG00044]; National
Institutes of Health [P01 GH000205]; NHGRI [RO1 HG003317]; Canadian
Foundation for Innovation; University of Toronto
FX We thank Ron Davis, Adam Deutschbauer, and the entire HIP HOP laboratory
at the University of Toronto for discussions and advice. C.N. is
supported by grants from the National Human Genome Research Institute
(Grant Number HG000205), RO1 HG003317, CIHR MOP-84305, and Canadian
Cancer Society (#020380). J.O. was supported by the Stanford Genome
Training Program (Grant Number T32 HG00044 from the National Human
Genome Research Institute) and the National Institutes of Health (Grant
Number P01 GH000205). GG is supported by the NHGRI RO1 HG003317 and the
Canadian Cancer Society, Grant # 020380, TD and the Donnelly Sequencing
Centre is supported in part by grants from the Canadian Foundation for
Innovation to Drs. Brenda Andrews and Jack Greenblatt. A.M.S. is
supported by a University of Toronto Open Fellowship.
NR 20
TC 5
Z9 5
U1 2
U2 4
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD AUG
PY 2011
IS 54
AR UNSP e2864
DI 10.3791/2864
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36MD
UT WOS:000209215100022
ER
PT J
AU Langholz, B
Skolnik, JM
Barrett, JS
Renbarger, J
Seibel, NL
Zajicek, A
Arndt, CAS
AF Langholz, Bryan
Skolnik, Jeffrey M.
Barrett, Jeffrey S.
Renbarger, Jamie
Seibel, Nita L.
Zajicek, Anne
Arndt, Carola A. S.
TI Dactinomycin and Vincristine Toxicity in the Treatment of Childhood
Cancer: A Retrospective Study From the Children's Oncology Group
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE hepatic toxicity; neuropathy; rhabdomyosarcoma; risk estimation; Wilms
tumor
ID TUMOR STUDY-GROUP; WILMS-TUMOR; PHARMACOKINETICS; POPULATION; LEUKEMIA
AB Background. Dactinomycin (AMD) and vincristine (VCR) have been used for the treatment of childhood cancer over the past 40 years butevidence-based dosing guidance is lacking. Methods. Patient AMD and VCR dose and drug-related adverse event (AE) information from four rhabdomyosarcoma (RMS) and two Wilms tumor (WT) studies were assembled. Statistical modeling was used to account for differences in AE data collection across studies, develop rate models for grade 3/4 CTCAE v3 hepatic-(AMD) and neuro-(VCR) toxicity, assess variation in toxicity rates over age and other factors, and predict toxicity risk under current dosing guidelines. Results. For the same dose/body size, AMD toxicity rates were higher in patients <1 year than older patients and VCR toxicity rates increased with age. The statistical model provided estimates for AMD and VCR toxicity risk under current dosing schedules and indicated that patients of smaller body size were at lower risk of VCR toxicity than larger patients of the same age. The rate of AMD toxicity was highest early in treatment and was lower in patients who tolerated initial AMD without toxicity. Conclusion. The observed decrease in AMD toxicity rate with cumulative dose may indicate sensitivity in a subgroup of patients while the observed increase in VCR toxicity risk with age may indicate changing sensitivity to VCR. Current dosing practices result in a fairly uniform toxicity profile within age group. However, PK/PD studies should be done to provide further provide further information on best dosing guidelines. Pediatr Blood Cancer 2011; 57: 252-257. (C) 2010 Wiley-Liss, Inc.
C1 [Langholz, Bryan] Univ So Calif, Childrens Oncol Grp, Los Angeles, CA USA.
[Langholz, Bryan] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Skolnik, Jeffrey M.; Barrett, Jeffrey S.] Childrens Hosp Philadelphia, Div Clin Pharmacol & Therapeut, Philadelphia, PA 19104 USA.
[Renbarger, Jamie] Indiana Univ Sch Med, Indianapolis, IN USA.
[Seibel, Nita L.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Zajicek, Anne] NICHHD, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA.
[Arndt, Carola A. S.] Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN USA.
RP Langholz, B (reprint author), Childrens Oncol Grp, 440 E Huntington Dr,4th Floor, Arcadia, CA 91006 USA.
EM langholz@usc.edu
FU National Cancer Institute [U10CA098543]
FX Grant sponsor: The National Cancer Institute; Grant number: U10CA098543.
NR 15
TC 19
Z9 19
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD AUG
PY 2011
VL 57
IS 2
BP 252
EP 257
DI 10.1002/pbc.22882
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 786JE
UT WOS:000292301400013
PM 21671362
ER
PT J
AU Spong, CY
Willinger, M
AF Spong, Catherine Y.
Willinger, Marian
TI Foreword: Disparities in Perinatal Medicine: Focus in Infant Mortality,
Stillbirth, and Preterm Birth
SO SEMINARS IN PERINATOLOGY
LA English
DT Editorial Material
C1 [Spong, Catherine Y.; Willinger, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Spong, CY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd,Rm 4B03,MSC 7510, Bethesda, MD 20892 USA.
NR 3
TC 1
Z9 1
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0146-0005
J9 SEMIN PERINATOL
JI Semin. Perinatol.
PD AUG
PY 2011
VL 35
IS 4
BP 199
EP 199
DI 10.1053/j.semperi.2011.02.016
PG 1
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 812UI
UT WOS:000294318000001
PM 21798399
ER
PT J
AU Gacchina, C
Brothers, T
Ramamurthi, A
AF Gacchina, Carmen
Brothers, Thomas
Ramamurthi, Anand
TI Evaluating Smooth Muscle Cells from CaCl2-Induced Rat Aortal Expansions
as a Surrogate Culture Model for Study of Elastogenic Induction of Human
Aneurysmal Cells
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID MATRIX METALLOPROTEINASES; PERIARTERIAL APPLICATION; HYALURONAN
OLIGOMERS; ELASTIN DEGRADATION; CALCIUM-CHLORIDE; IN-VITRO;
REGENERATION; CALPONIN; CUES; CALCIFICATION
AB Regression of abdominal aortic aneurysms (AAAs) via regeneration of new elastic matrix is constrained by poor elastin synthesis by adult vascular cells and absence of methods to stimulate the same. We recently showed hyaluronan oligomers (HA-o) and TGF-beta 1 (termed elastogenic factors) to enhance elastin synthesis and matrix formation by healthy rat aortic smooth muscle cells (RASMCs). We also determined that these factors could likewise elastogenically induce aneurysmal RASMCs isolated from periadventitial CaCl2-injury induced rat AAAs (aRASMCs). However, the factor doses should be increased for these diseased cell types, as even when induced, elastic matrix amounts are roughly one order of magnitude lower than those produced by healthy RASMCs. We presently investigate the dose-specific elastogenic effects of HA-o (0-20 mu g/mL) and TGF-beta 1 (0-10 ng/mL) factors on aRASMCs and compare their phenotype and elastogenic responses to those of human AAA-derived SMCs (aHASMCs); we seek to determine whether aRASMCs are appropriate surrogate cell types to study in the context of inducing elastic matrix regeneration within human AAAs. The periadventitial CaCl2-injury model of AAAs exhibits many of the pathological characteristics of human AAAs, including similarities in terms of decreased SMC contractile activity, enhanced proliferation, and reduced elastogenic capacity of aneurysmal SMCs (relative to healthy SMCs) when isolated and expanded in culture. Both aRASMCs and aHASMCs can be elastogenically stimulated by HA-o and TGF-beta 1 and show broadly similar trends in their dose-specific responses to these factors. However, compared with aHASMCs, aRASMCs appear to be far less elastogenically inducible. This may be due to differences in maturity of the AAAs studied, with the CaCl2-injury induced aortal expansion barely qualifying as an aneurysm and the human AAA representing a more well-developed condition. Further study of SMCs from stage-matched CaCl2-injury induced rat aortal expansions and human AAAs will be necessary to more rigorously evaluate their basal and induced elastogenic responses.
C1 [Ramamurthi, Anand] Cleveland Clin, Dept Biomed Engn, Cleveland, OH 44195 USA.
[Gacchina, Carmen; Ramamurthi, Anand] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Gacchina, Carmen; Ramamurthi, Anand] Clemson Univ, Dept Bioengn, Clemson, SC USA.
[Brothers, Thomas] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA.
RP Ramamurthi, A (reprint author), Cleveland Clin, Dept Biomed Engn, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM ramamua@ccf.org
FU National Institutes of Health [C06RR018823, R21EB006078-01A1,
RO1HL0092051-01A1, R01HL0092051-01S, T32 HL007260]
FX This study was funded by the National Institutes of Health C06RR018823
(Dooley L), R21EB006078-01A1, RO1HL0092051-01A1, and R01HL0092051-01S
(Ramamurthi A). Gacchina C was supported by a National Institutes of
Health predoctoral award T32 HL007260. The authors would like to
acknowledge Emily Ongstad (Clemson University) for help with survival
animal surgeries and transmission electron microscopy and Partha Deb
(Clemson University) and Richard Peppler (Medical University of South
Carolina) for assistance with flow cytometry.
NR 39
TC 11
Z9 12
U1 0
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD AUG
PY 2011
VL 17
IS 15-16
BP 1945
EP 1958
DI 10.1089/ten.tea.2010.0475
PG 14
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 798OB
UT WOS:000293217700005
PM 21417692
ER
PT J
AU Chen, ZC
Moayeri, M
Purcell, R
AF Chen, Zhaochun
Moayeri, Mahtab
Purcell, Robert
TI Monoclonal Antibody Therapies against Anthrax
SO TOXINS
LA English
DT Review
DE Bacillus anthracis; anti-PA mAbs; anti-LF mAbs; anti-EF mAbs;
anti-capsule mAbs; post-exposure treatment of anthrax; a cocktail of
mAbs
ID PROTECTIVE ANTIGEN-ANTIBODY; LETHAL TOXIN CHALLENGE; GLUTAMIC ACID
CAPSULE; BACILLUS-ANTHRACIS; INHALATION ANTHRAX; EDEMA FACTOR;
GUINEA-PIGS; IN-VITRO; POSTEXPOSURE PROPHYLAXIS; POTENT NEUTRALIZATION
AB Anthrax is a highly lethal infectious disease caused by the spore-forming bacterium Bacillus anthracis. It not only causes natural infection in humans but also poses a great threat as an emerging bioterror agent. The lethality of anthrax is primarily attributed to the two major virulence factors: toxins and capsule. An extensive effort has been made to generate therapeutically useful monoclonal antibodies to each of the virulence components: protective antigen (PA), lethal factor (LF) and edema factor (EF), and the capsule of B. anthracis. This review summarizes the current status of anti-anthrax mAb development and argues for the potential therapeutic advantage of a cocktail of mAbs that recognize different epitopes or different virulence factors.
C1 [Chen, Zhaochun; Purcell, Robert] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Moayeri, Mahtab] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
RP Chen, ZC (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM zchen@niaid.nih.gov; mmoayeri@niaid.nih.gov; rpurcell@niaid.nih.gov
FU NIH, NIAID
FX The research from our laboratories was supported by the Intramural
Research Program of the NIH, NIAID.
NR 86
TC 36
Z9 40
U1 3
U2 16
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2072-6651
J9 TOXINS
JI Toxins
PD AUG
PY 2011
VL 3
IS 8
BP 1004
EP 1019
DI 10.3390/toxins3081004
PG 16
WC Toxicology
SC Toxicology
GA 995AU
UT WOS:000307978900006
PM 22069754
ER
PT J
AU Milman, G
Barnes, AJ
Schwope, DM
Schwilke, EW
Goodwin, RS
Kelly, DL
Gorelick, DA
Huestis, MA
AF Milman, Garry
Barnes, Allan J.
Schwope, David M.
Schwilke, Eugene W.
Goodwin, Robert S.
Kelly, Deana L.
Gorelick, David A.
Huestis, Marilyn A.
TI Cannabinoids and metabolites in expectorated oral fluid after 8 days of
controlled around-the-clock oral THC administration
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Oral fluid; Expectoration; Cannabinoids; Delta(9)-tetrahydrocannabinol;
Dronabinol
ID MASS-SPECTROMETRY; DELTA(9)-TETRAHYDROCANNABINOL; SALIVA; DRUGS; ABUSE;
PLASMA; URINE; HAIR; DELTA-9-TETRAHYDROCANNABINOL; DISPOSITION
AB Oral fluid (OF) is an increasingly accepted matrix for drug testing programs, but questions remain about its usefulness for monitoring cannabinoids. Expectorated OF specimens (n = 360) were obtained from 10 adult daily cannabis smokers before, during, and after 37 20-mg oral Delta(9)-tetrahydrocannabinol (THC) doses over 9 days to characterize cannabinoid disposition in this matrix. Specimens were extracted and analyzed by gas chromatography-mass spectrometry with electron-impact ionization for THC, 11-hydroxy-THC, cannabidiol, and cannabinol, and negative chemical ionization for 11-nor-9-carboxy-THC (THCCOOH). Linear ranges for THC, 11-hydroxy-THC, and cannabidiol were 0.25-50 ng/mL; cannabinol 1-50 ng/mL; and THCCOOH 5-500 pg/mL. THCCOOH was the most prevalent analyte in 344 specimens (96.9%), with concentrations up to 1,390.3 pg/mL. 11-hydroxy-THC, cannabidiol, and cannabinol were detected in 1, 1, and 3 specimens, respectively. THC was detected in only 13.8% of specimens. The highest THC concentrations were obtained at admission (median 1.4 ng/mL, range 0.3-113.6) from previously self-administered smoked cannabis. A total of 2.5 and 3.7% of specimens were THC-positive at the recommended Substance Abuse and Mental Health Services Administration (2 ng/mL) and Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) (1 ng/mL) confirmation cutoffs, respectively. THC is currently the only analyte for monitoring cannabis exposure in OF; however, these data indicate chronic therapeutic oral THC administration and illicit oral THC use are unlikely to be identified with current guidelines. Measurement of THCCOOH may improve the detection and interpretation of OF cannabinoid tests and minimize the possibility of OF contamination from passive inhalation of cannabis smoke.
C1 [Milman, Garry; Barnes, Allan J.; Schwope, David M.; Schwilke, Eugene W.; Goodwin, Robert S.; Gorelick, David A.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Kelly, Deana L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU NIH, National Institute on Drug; NIDA Residential Research Support
Services [HHSN271200599091, N01Da-5-9909]
FX Supported by the Intramural Research Program, NIH, National Institute on
Drug and NIDA Residential Research Support Services Contract
HHSN271200599091 CADB Contract No N01Da-5-9909. We thank clinical
research teams from the NIDA clinical program, the Johns Hopkins
Behavioral Pharmacology Research Unit, and the Maryland Psychiatric
Research Center Treatment Research Program.
NR 27
TC 15
Z9 15
U1 1
U2 13
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD AUG
PY 2011
VL 401
IS 2
BP 599
EP 607
DI 10.1007/s00216-011-5066-4
PG 9
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 789WX
UT WOS:000292550900019
PM 21637933
ER
PT J
AU Foraker, RE
Rose, KM
Kucharska-Newton, AM
Ni, HY
Suchindran, CM
Whitsel, EA
AF Foraker, Randi E.
Rose, Kathryn M.
Kucharska-Newton, Anna M.
Ni, Hanyu
Suchindran, Chirayath M.
Whitsel, Eric A.
TI Variation in Rates of Fatal Coronary Heart Disease by Neighborhood
Socioeconomic Status: The Atherosclerosis Risk in Communities
Surveillance (1992-2002)
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Out-of-Hospital Death; Surveillance; Socioeconomic Status
ID DISPARITIES GEOCODING PROJECT; HOSPITAL CARDIAC-ARREST; TRENDS; HEALTH;
MORTALITY; DEATH; INEQUALITIES; POPULATION; SURVIVAL; CHOICE
AB PURPOSE: Racial and gender disparities in out-of-hospital deaths from coronary heart disease (CHD) have been well-documented, yet disparities by neighborhood socioeconomic status (nSES) have been less systematically studied in US population-based surveillance efforts.
METHODS: We examined the association of nSES, classified into tertiles, with 3,743 out-of-hospital fatal CHD events, and a subset of 2,191 events classified as sudden, among persons aged 35 to 74 years in four US communities under surveillance by the Atherosclerosis Risk in Communities (ARIC). Poisson generalized linear mixed models generated age-, race- (white, black) and gender-specific standardized mortality rate ratios and 95% confidence intervals (RR, 95% CI).
RESULTS: Regardless of nSES measure used, inverse associations of nSES with all out-of-hospital fatal CHD and sudden fatal CHD were seen in all race-gender groups. The magnitude of these associations was larger among women than men. Further, among blacks, associations of low nSES (vs. high nSES) were stronger for sudden cardiac deaths (SCD) than for all out-of-hospital fatal CHD.
CONCLUSIONS: Low nSES was associated with an increased risk of out-of-hospital CHD death and SCD. Measures of the neighborhood context are useful tools in population-based surveillance efforts for documenting and monitoring socioeconomic disparities in mortality over time. Ann Epidemiol 2011;21:580-588. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Foraker, Randi E.] Ohio State Univ, Div Epidemiol, Coll Publ Hlth, Columbus, OH 43210 USA.
[Rose, Kathryn M.] SRA Int, Durham, NC USA.
[Kucharska-Newton, Anna M.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Suchindran, Chirayath M.] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Whitsel, Eric A.] Univ N Carolina, Dept Med, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Ni, Hanyu] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Foraker, RE (reprint author), Ohio State Univ, Div Epidemiol, Coll Publ Hlth, 320 W 10th Ave, Columbus, OH 43210 USA.
EM rforaker@cph.osu.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 The Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by the 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). The authors thank the staff
of the ARIC study for their important contributions.
NR 27
TC 18
Z9 18
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD AUG
PY 2011
VL 21
IS 8
BP 580
EP 588
DI 10.1016/j.annepidem.2011.03.004
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 793GQ
UT WOS:000292808800004
PM 21524592
ER
PT J
AU Lockhart, SR
Zimbeck, AJ
Baddley, JW
Marr, KA
Andes, DR
Walsh, TJ
Kauffman, CA
Kontoyiannis, DP
Ito, JI
Pappas, PG
Chiller, T
AF Lockhart, Shawn R.
Zimbeck, Alicia J.
Baddley, John W.
Marr, Kieren A.
Andes, David R.
Walsh, Thomas J.
Kauffman, Carol A.
Kontoyiannis, Dimitrios P.
Ito, James I.
Pappas, Peter G.
Chiller, Tom
TI In Vitro Echinocandin Susceptibility of Aspergillus Isolates from
Patients Enrolled in the Transplant-Associated Infection Surveillance
Network
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID INVASIVE FUNGAL-INFECTIONS; ANTIFUNGAL AGENTS; RECIPIENTS;
ANIDULAFUNGIN; CASPOFUNGIN; TRANSNET
AB We determined the echinocandin minimum effective concentration (MEC) values for caspofungin, micafungin, and anidulafungin against 288 Aspergillus isolates prospectively collected from transplant patients with proven or probable invasive aspergillosis between 2001 and 2006 as part of the Transplant-Associated Infection Surveillance Network (TRANSNET). We demonstrated that the vast majority of Aspergillus isolates had MEC values at or below the epidemiological cutoff values for caspofungin, micafungin, and anidulafungin, including those from patients who had received caspofungin.
C1 [Lockhart, Shawn R.; Zimbeck, Alicia J.; Chiller, Tom] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA 30333 USA.
[Baddley, John W.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA.
[Baddley, John W.] Birmingham Vet Affairs Med Ctr, Dept Med, Infect Dis Sect, Birmingham, AL USA.
[Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
[Andes, David R.] Univ Wisconsin, Dept Med, Div Infect Dis, Madison, WI USA.
[Walsh, Thomas J.] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA.
[Walsh, Thomas J.] New York Presbyterian Hosp, New York, NY USA.
[Walsh, Thomas J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Kauffman, Carol A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA.
[Ito, James I.] City Hope Natl Med Ctr, Dept Med, Div Infect Dis, Duarte, CA 91010 USA.
[Pappas, Peter G.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA.
RP Lockhart, SR (reprint author), Ctr Dis Control & Prevent, Mycot Dis Branch, 1600 Clifton Rd,Mailstop G-11, Atlanta, GA 30333 USA.
EM gyi2@cdc.gov
FU Association of Public Health Laboratories (APHL); Astellas; Pfizer;
Merck; Schering-Plough; Enzon
FX A.J.Z. was supported by the Association of Public Health Laboratories
(APHL). TRANSNET was sponsored by Astellas, Pfizer, Merck, and
Schering-Plough. This work was funded by a grant from Merck. Potential
conflicts of interest are as follows: P.G.P. receives research support
and is an ad hoc advisor for Merck, Pfizer, and Astellas; J.W.B.
received research grants from Merck, Astellas, and Pfizer and is a
consultant/advisor for Merck and Pfizer; J.I.I. received honoraria for
speakers' activities from Astellas, Cubist, Merck, and Pfizer and is a
consultant for Sigma Tau; D.R.A. has received grants from and is a
consultant for Merck, Astellas, and Pfizer; C.A.K. receives research
support from Merck and chairs a data adjudication committee for Pfizer;
K.A.M. received research grants from Merck, Astellas, and Pfizer and is
on the advisory board or is consulting for Astellas, Basilea, Merck, and
Pfizer; D.P.K. received research support and honoraria from
Schering-Plough, Pfizer, Astellas, Enzon, and Merck; T.J.W. is in
consultation with iCo, Vestagen, Trius, and Sigma Tau. All other authors
have no potential conflicts.
NR 17
TC 13
Z9 13
U1 0
U2 1
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 AUG
PY 2011
VL 55
IS 8
BP 3944
EP 3946
DI 10.1128/AAC.00428-11
PG 3
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 792HV
UT WOS:000292733800040
PM 21670187
ER
PT J
AU Koffarnus, MN
Newman, AH
Grundt, P
Rice, KC
Woods, JH
AF Koffarnus, Mikhail N.
Newman, Amy H.
Grundt, Peter
Rice, Kenner C.
Woods, James H.
TI Effects of selective dopaminergic compounds on a delay-discounting task
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Article
DE ABT-724; delay discounting; dopamine; impulsive choice; impulsivity;
intertemporal choice; rat; SCH 23390; self-control
ID DEFICIT HYPERACTIVITY DISORDER; NUCLEUS-ACCUMBENS CORE; INTER-TEMPORAL
CHOICE; OPIOID-DEPENDENT OUTPATIENTS; ORBITAL PREFRONTAL CORTEX;
SELF-CONTROL CHOICES; ACID-INDUCED LESIONS; IMPULSIVE CHOICE;
D-AMPHETAMINE; RAT-BRAIN
AB Impulsivity is widely regarded as a multidimensional trait that encompasses two or more distinct patterns of behavior, and dopaminergic systems are implicated in the expression of impulsive behavior in both humans and animal subjects. Impulsive choice, or the tendency to choose rewards associated with relatively little or no delay, has been extensively studied in humans and animal subjects using delay-discounting tasks. Here, delay-discounting procedures were used to assess the effects of receptor-selective dopaminergic agonists, antagonists, and dopamine transporter ligands on choices of immediate versus delayed sucrose pellets. The effects of d-amphetamine, GBR 12909, apomorphine, SKF 81297, sumanirole, pramipexole, ABT-724, SCH 23390, L-741,626, PG01037, and L-745,870 were assessed in 24 Sprague-Dawley rats. The only drugs to affect impulsive choice selectively without altering undelayed choice were the D(1)-like antagonist, SCH 23390 (0.01 mg/kg), and the D(4) partial agonist, ABT-724 (3.2 mg/kg), which both increased impulsive choice. The shared effects of these compounds may be explained by their localization within the prefrontal cortex on different groups of neurons. None of the selective agonists and antagonists tested reduced impulsive choice, so further research is needed to determine if direct dopaminergic agonists or antagonists may be therapeutically useful in the treatment of impulse-control disorders. Behavioural Pharmacology 22: 300-311 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Koffarnus, Mikhail N.] Johns Hopkins Univ, Sch Med, Behav Pharmacol Res Unit, Baltimore, MD 21224 USA.
[Newman, Amy H.] Univ Minnesota, Natl Inst Drug Abuse, Intramural Res Program, Duluth, MN 55812 USA.
[Grundt, Peter] Univ Minnesota, Dept Chem & Biochem, Duluth, MN 55812 USA.
[Rice, Kenner C.] Univ Michigan, NIAAA, Intramural Res Program, Ann Arbor, MI 48109 USA.
[Woods, James H.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
RP Koffarnus, MN (reprint author), Johns Hopkins Univ, Sch Med, Behav Pharmacol Res Unit, 5200 Eastern Ave,Suite W142, Baltimore, MD 21224 USA.
EM mkoffar1@jhmi.edu
FU USPHS/NIDA [R01 DA015449, R01 DA020669, T32 DA007267]; National
Institute on Drug Abuse; National Institute on Alcohol Abuse and
Alcoholism
FX The authors thank Aaron Chadderdon, Alexa Cohen, Bruce Kaczmarek,
Elizabeth Kossak, Jenny Montgomery, Collette Rothe, Sarah Snider, Nhu
Truong, and J. Cao (Medicinal Chemistry Section, NIDA-IRP) for technical
assistance; and Gail Winger, Jeremiah Bertz, and Nhu Truong for advice
and help with manuscript preparation. This research was supported by
USPHS/NIDA Grants R01 DA015449, R01 DA020669, and T32 DA007267; and a
portion of this study was also supported by the Intramural Research
Programs of the National Institute on Drug Abuse and the National
Institute on Alcohol Abuse and Alcoholism. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institute on Drug Abuse, the National
Institute on Alcohol Abuse and Alcoholism, or the National Institutes of
Health.
NR 79
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U1 3
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0955-8810
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD AUG
PY 2011
VL 22
IS 4
BP 300
EP 311
DI 10.1097/FBP.0b013e3283473bcb
PG 12
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 791QW
UT WOS:000292680700003
PM 21694584
ER
PT J
AU Ma, SJ
Yang, LJ
Romero, R
Cui, YH
AF Ma, Shujie
Yang, Lijian
Romero, Roberto
Cui, Yuehua
TI Varying coefficient model for gene-environment interaction: a non-linear
look
SO BIOINFORMATICS
LA English
DT Article
ID SPLINE ESTIMATION; LONGITUDINAL DATA; CONFIDENCE BANDS; POLYMORPHISM
AB Motivation: The genetic basis of complex traits often involves the function of multiple genetic factors, their interactions and the interaction between the genetic and environmental factors. Gene-environment (GxE) interaction is considered pivotal in determining trait variations and susceptibility of many genetic disorders such as neurodegenerative diseases or mental disorders. Regression-based methods assuming a linear relationship between a disease response and the genetic and environmental factors as well as their interaction is the commonly used approach in detecting GxE interaction. The linearity assumption, however, could be easily violated due to non-linear genetic penetrance which induces non-linear GxE interaction.
Results: In this work, we propose to relax the linear GxE assumption and allow for non-linear GxE interaction under a varying coefficient model framework. We propose to estimate the varying coefficients with regression spline technique. The model allows one to assess the non-linear penetrance of a genetic variant under different environmental stimuli, therefore help us to gain novel insights into the etiology of a complex disease. Several statistical tests are proposed for a complete dissection of GxE interaction. A wild bootstrap method is adopted to assess the statistical significance. Both simulation and real data analysis demonstrate the power and utility of the proposed method. Our method provides a powerful and testable framework for assessing non-linear GxE interaction.
C1 [Ma, Shujie; Yang, Lijian; Cui, Yuehua] Michigan State Univ, Dept Stat & Probabil, E Lansing, MI 48824 USA.
[Ma, Shujie] Univ Calif Riverside, Dept Stat, Riverside, CA 92507 USA.
[Yang, Lijian] Soochow Univ, Sch Math Sci, Ctr Adv Stat & Econometr Res, Suzhou 215006, Peoples R China.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI 48201 USA.
RP Cui, YH (reprint author), Michigan State Univ, Dept Stat & Probabil, E Lansing, MI 48824 USA.
EM cui@stt.msu.edu
RI Yang, Lijian/E-1848-2011
OI Yang, Lijian/0000-0003-3894-873X
FU National Science Foundation [DMS-0707031, DMS-0706518, DMS-1007594];
Jiangsu-Specially Appointed Professor Program, Jiangsu Province, China;
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX National Science Foundation DMS-0707031, DMS-0706518, and DMS-1007594;
Jiangsu-Specially Appointed Professor Program, Jiangsu Province, China;
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
NR 30
TC 20
Z9 20
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD AUG 1
PY 2011
VL 27
IS 15
BP 2119
EP 2126
DI 10.1093/bioinformatics/btr318
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 792VO
UT WOS:000292778700014
PM 21690105
ER
PT J
AU Danecek, P
Auton, A
Abecasis, G
Albers, CA
Banks, E
DePristo, MA
Handsaker, RE
Lunter, G
Marth, GT
Sherry, ST
McVean, G
Durbin, R
AF Danecek, Petr
Auton, Adam
Abecasis, Goncalo
Albers, Cornelis A.
Banks, Eric
DePristo, Mark A.
Handsaker, Robert E.
Lunter, Gerton
Marth, Gabor T.
Sherry, Stephen T.
McVean, Gilean
Durbin, Richard
CA 1000 Genomes Project Anal Grp
TI The variant call format and VCFtools
SO BIOINFORMATICS
LA English
DT Article
AB The variant call format (VCF) is a generic format for storing DNA polymorphism data such as SNPs, insertions, deletions and structural variants, together with rich annotations. VCF is usually stored in a compressed manner and can be indexed for fast data retrieval of variants from a range of positions on the reference genome. The format was developed for the 1000 Genomes Project, and has also been adopted by other projects such as UK10K, dbSNP and the NHLBI Exome Project. VCFtools is a software suite that implements various utilities for processing VCF files, including validation, merging, comparing and also provides a general Perl API.
C1 [Danecek, Petr; Albers, Cornelis A.; Durbin, Richard] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
[Auton, Adam; Lunter, Gerton; McVean, Gilean] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Abecasis, Goncalo] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Banks, Eric; DePristo, Mark A.; Handsaker, Robert E.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02141 USA.
[Marth, Gabor T.] Boston Coll, Dept Biol, Boston, MA 02467 USA.
[Sherry, Stephen T.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[McVean, Gilean] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
RP Durbin, R (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England.
EM rd@sanger.ac.uk
RI Fromer, Menachem/G-2116-2012; Abecasis, Goncalo/B-7840-2010; Khurana,
Ekta/C-4933-2013; de Bakker, Paul/B-8730-2009; Ye, Kai/B-3640-2012;
Albers, Kees/A-4170-2015; Lunter, Gerton/H-4939-2016; Dahl,
Andreas/E-3783-2017;
OI Abecasis, Goncalo/0000-0003-1509-1825; Herrero,
Javier/0000-0001-7313-717X; Clarke, Laura/0000-0002-5989-6898; McVean,
Gil/0000-0002-5012-4162; Kersey, Paul/0000-0002-7054-800X; Walter,
Klaudia/0000-0003-4448-0301; Birney, Ewan/0000-0001-8314-8497; Zerbino,
Daniel/0000-0001-5350-3056; Lunter, Gerton/0000-0002-3798-2058; Dunstan,
Sarah/0000-0001-7873-933X; Marioni, John/0000-0001-9092-0852; Fromer,
Menachem/0000-0003-3749-4342; de Bakker, Paul/0000-0001-7735-7858;
Albers, Kees/0000-0003-4115-3727; Dahl, Andreas/0000-0002-2668-8371;
Gallo, Carla/0000-0001-8348-0473; Durbin, Richard/0000-0002-9130-1006;
Sebat, Jonathan/0000-0002-9087-526X; Haraksingh,
Rajini/0000-0002-6644-8874
FU Medical Research Council, UK; British Heart Foundation
[RG/09/012/28096]; Wellcome Trust [090532/Z/09/Z, 075491/Z/04]; National
Human Genome Research Institute [54 HG003067, R01 HG004719, U01
HG005208]; National Institutes of Health; National Library of Medicine
FX Medical Research Council, UK; British Heart Foundation (grant
RG/09/012/28096); Wellcome Trust (grants 090532/Z/09/Z and 075491/Z/04);
National Human Genome Research Institute (grants 54 HG003067, R01
HG004719 and U01 HG005208); Intramural Research Program of the National
Institutes of Health, the National Library of Medicine.
NR 4
TC 954
Z9 965
U1 18
U2 108
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD AUG 1
PY 2011
VL 27
IS 15
BP 2156
EP 2158
DI 10.1093/bioinformatics/btr330
PG 3
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 792VO
UT WOS:000292778700023
PM 21653522
ER
PT J
AU Luna, A
Sunshine, ML
van Iersel, MP
Aladjem, MI
Kohn, KW
AF Luna, Augustin
Sunshine, Margot L.
van Iersel, Martijn P.
Aladjem, Mirit I.
Kohn, Kurt W.
TI PathVisio-MIM: PathVisio plugin for creating and editing Molecular
Interaction Maps (MIMs)
SO BIOINFORMATICS
LA English
DT Article
ID BIOLOGICAL PATHWAYS; SYSTEMS BIOLOGY
AB Motivation: A plugin for the Java-based PathVisio pathway editor has been developed to help users draw diagrams of bioregulatory networks according to the Molecular Interaction Map (MIM) notation. Together with the core PathVisio application, this plugin presents a simple to use and cross-platform application for the construction of complex MIM diagrams with the ability to annotate diagram elements with comments, literature references and links to external databases. This tool extends the capabilities of the PathVisio pathway editor by providing both MIM-specific glyphs and support for a MIM-specific markup language file format for exchange with other MIM-compatible tools and diagram validation.
C1 [Luna, Augustin; Sunshine, Margot L.; Aladjem, Mirit I.; Kohn, Kurt W.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Luna, Augustin] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
RP Luna, A (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM augustin@mail.nih.gov; margot@discover.nci.nih.gov
RI van Iersel, Martijn/E-9105-2010; Aladjem, Mirit/G-2169-2010
OI van Iersel, Martijn/0000-0002-5877-4338; Aladjem,
Mirit/0000-0002-1875-3110
FU NIH, National Cancer Institute, Center for Cancer Research; Netherlands
Consortium for Systems Biology (NCSB), which is part of the Netherlands
Genomics Initiative/Netherlands Organisation for Scientific Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research and the
Netherlands Consortium for Systems Biology (NCSB), which is part of the
Netherlands Genomics Initiative/Netherlands Organisation for Scientific
Research.
NR 5
TC 8
Z9 8
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD AUG 1
PY 2011
VL 27
IS 15
BP 2165
EP 2166
DI 10.1093/bioinformatics/btr336
PG 2
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 792VO
UT WOS:000292778700027
PM 21636591
ER
PT J
AU Diyabalanage, T
Ratnayake, R
Wilson, JA
Henrich, CJ
Beutler, JA
Colburn, NH
McMahon, JB
Gustafson, KR
AF Diyabalanage, Thushara
Ratnayake, Ranjala
Wilson, Jennifer A.
Henrich, Curtis J.
Beutler, John A.
Colburn, Nancy H.
McMahon, James B.
Gustafson, Kirk R.
TI Nothospondin, a new AP-1 inhibitory quassinoid from the Cameroonian
plant Nothospondias staudtii
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Quassinoid; Nothospondias staudtii; Simaroubaceae; Transcription factor;
AP-1
ID CANCER PREVENTION
AB A high throughput screen for inhibitors of the oncogenic transcription factor activator protein-1 (AP-1) was applied to the NCI repository of natural product extracts. The liphophilic extract of the plant Nothospondias staudtii (Simaroubaceae) displayed significant AP-1 inhibition. Bioassay-guided fractionation of the extract lead to a new quassinoid named nothospondin (1), and the known compound glaucarubinone (2). The structure of 1 was elucidated by spectroscopic methods. Compounds 1 and 2 showed potent, dose-dependent AP-1 inhibition at noncytotoxic concentrations. Published by Elsevier Ltd.
C1 [Diyabalanage, Thushara; Ratnayake, Ranjala; Wilson, Jennifer A.; Henrich, Curtis J.; Beutler, John A.; McMahon, James B.; Gustafson, Kirk R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Henrich, Curtis J.] NCI, SAIC Frederick, Frederick, MD 21702 USA.
[Colburn, Nancy H.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
RP Gustafson, KR (reprint author), NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM gustafki@mail.nih.gov
RI Beutler, John/B-1141-2009
OI Beutler, John/0000-0002-4646-1924
FU NIH, NCI, CCR; NCI, NIH [HHSN261200800001E]
FX We thank D. Newman (NCI) and T. McCloud (SAIC-Frederick) for the plant
extract and M. Dyba and S. Terasova (Biophysics Resource, SBL,
NCI-Frederick) for assistance with the HRLCMS studies. This research was
supported in part by the Intramural Research Program of NIH, NCI, CCR.
This project was also funded in part with Federal funds from the NCI,
NIH, under Contract HHSN261200800001E. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products or organizations imply endorsement by the US Government.
NR 11
TC 3
Z9 3
U1 0
U2 5
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 AUG 1
PY 2011
VL 21
IS 15
BP 4397
EP 4399
DI 10.1016/j.bmcl.2011.06.044
PG 3
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 792GR
UT WOS:000292729900004
PM 21733691
ER
PT J
AU Lezin, G
Kuehn, MR
Brunelli, L
AF Lezin, George
Kuehn, Michael R.
Brunelli, Luca
TI Hofmeister Series Salts Enhance Purification of Plasmid DNA by Non-Ionic
Detergents
SO BIOTECHNOLOGY AND BIOENGINEERING
LA English
DT Article
DE plasmid DNA purification; non-ionic detergents; Hofmeister salts
ID PHASE-SEPARATION; HYDROPHOBIC INTERACTIONS; TRITON X-114; PRECIPITATION;
MEMBRANE; PROTEINS; COMPLEXES; ENDOTOXIN; REMOVAL
AB Ion-exchange chromatography is the standard technique used for plasmid DNA purification, an essential molecular biology procedure. Non-ionic detergents (NIDs) have been used for plasmid DNA purification, but it is unclear whether Hofmeister series salts (HSS) change the solubility and phase separation properties of specific NIDs, enhancing plasmid DNA purification. After scaling-up NID-mediated plasmid DNA isolation, we established that NIDs in HSS solutions minimize plasmid DNA contamination with protein. In addition, large-scale NID/HSS solutions eliminated lipopolysaccharides (LPS) contamination of plasmid DNA more effectively than Qiagen ion-exchange columns. Large-scale NID isolation/NID purification generated increased yields of high-quality DNA compared to alkali isolation/column purification. This work characterizes how HSS enhance NID-mediated plasmid DNA purification, and demonstrates that NID phase transition is not necessary for LPS removal from plasmid DNA. Specific NIDs such as IGEPAL CA-520 can be utilized for rapid, inexpensive, and efficient laboratory-based large-scale plasmid DNA purification, outperforming Qiagen-based column procedures. Biotechnol. Bioeng. 2011;108: 1872-1882. (C) 2011 Wiley Periodicals, Inc.
C1 [Brunelli, Luca] Univ Utah, Dept Pediat, Div Neonatol, Salt Lake City, UT 84112 USA.
[Lezin, George; Kuehn, Michael R.] NCI, Lab Prot Dynam & Signaling, NIH, NCI Frederick, Frederick, MD 21702 USA.
RP Brunelli, L (reprint author), Univ Utah, Dept Pediat, Div Neonatol, Salt Lake City, UT 84112 USA.
EM mkuehn@mail.nih.gov; luca.brunelli@genetics.utah.edu
RI Kuehn, Michael/A-4573-2014
OI Kuehn, Michael/0000-0002-7703-9160
FU Division of Neonatology, Department of Pediatrics; Children's Health
Research Center at The University of Utah; Primary Children's Medical
Center Foundation; American Heart Association [09BGIA2251076]; National
Institutes of Health; National Cancer Institute; Center for Cancer
Research
FX Contract grant sponsor: Division of Neonatology, Department of
Pediatrics; Contract grant sponsor: Children's Health Research Center at
The University of Utah; Contract grant sponsor: Primary Children's
Medical Center Foundation Innovative Grant; Contract grant sponsor:
American Heart Association; Contract grant number: 09BGIA2251076;
Contract grant sponsor: National Institutes of Health; Contract grant
sponsor: National Cancer Institute; Contract grant sponsor: Center for
Cancer Research
NR 23
TC 0
Z9 1
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-3592
EI 1097-0290
J9 BIOTECHNOL BIOENG
JI Biotechnol. Bioeng.
PD AUG
PY 2011
VL 108
IS 8
BP 1872
EP 1882
DI 10.1002/bit.23116
PG 11
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 790PV
UT WOS:000292602600013
PM 21351074
ER
PT J
AU Conde-Agudelo, A
Papageorghiou, AT
Kennedy, SH
Villar, J
AF Conde-Agudelo, A.
Papageorghiou, A. T.
Kennedy, S. H.
Villar, J.
TI Novel biomarkers for the prediction of the spontaneous preterm birth
phenotype: a systematic review and meta-analysis
SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
LA English
DT Review
DE Biomarker; meta-analysis; prediction; preterm birth; systematic review
ID FACTOR-BINDING PROTEIN-1; C-REACTIVE-PROTEIN; MIDTRIMESTER
AMNIOTIC-FLUID; HUMAN CHORIONIC-GONADOTROPIN; GENETIC AMNIOCENTESIS;
CERVICAL SECRETIONS; SERUM RELAXIN; PAPP-A; INTERLEUKIN-8
CONCENTRATIONS; BIOCHEMICAL MARKERS
AB Background Being able to predict preterm birth is important, as it may allow a high-risk population to be selected for future interventional studies and help in understanding the pathways that lead to preterm birth.
Objective To investigate the accuracy of novel biomarkers to predict spontaneous preterm birth in women with singleton pregnancies and no symptoms of preterm labour.
Search strategy Electronic searches in PubMed, Embase, Cinahl, Lilacs, and Medion, references of retrieved articles, and conference proceedings. No language restrictions were applied.
Selection criteria Observational studies that evaluated the accuracy of biomarkers proposed in the last decade to predict spontaneous preterm birth in asymptomatic women. We excluded studies in which biomarkers were evaluated in women with preterm labour.
Data collection and analysis Two reviewers independently extracted data on study characteristics, quality, and accuracy. Data were arranged in 2 x 2 contingency tables and synthesised separately for spontaneous preterm birth before 32, 34, and 37 weeks of gestation. We used bivariate meta-analysis to estimate pooled sensitivities and specificities, and calculated likelihood ratios (LRs).
Main results A total of 72 studies, including 89 786 women and evaluating 30 novel biomarkers, met the inclusion criteria. Only three biomarkers (proteome profile and prolactin in cervicovaginal fluid, and matrix metalloproteinase-8 in amniotic fluid) had positive LRs > 10. However, each of these biomarkers was evaluated in only one small study. Four biomarkers had a moderate predictive accuracy (interleukin-6 and angiogenin, in amniotic fluid; human chorionic gonadotrophin and phosphorylated insulin-like growth factor binding protein-1, in cervicovaginal fluid). The remaining biomarkers had low predictive accuracies.
Conclusions None of the biomarkers evaluated in this review meet the criteria to be considered a clinically useful test to predict spontaneous preterm birth. Further large, prospective cohort studies are needed to evaluate promising biomarkers such as a proteome profile in cervicovaginal fluid.
C1 [Conde-Agudelo, A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Conde-Agudelo, A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.
[Papageorghiou, A. T.; Kennedy, S. H.; Villar, J.] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford OX3 9DU, England.
[Papageorghiou, A. T.; Kennedy, S. H.; Villar, J.] Green Templeton Coll, Oxford Maternal & Perinatal Hlth Inst, Oxford, England.
RP Villar, J (reprint author), Univ Oxford, John Radcliffe Hosp, Womens Ctr, Nuffield Dept Obstet & Gynaecol, Oxford OX3 9DU, England.
EM jose.villar@obs-gyn.ox.ac.uk
FU Oxford Partnership Comprehensive Biomedical Research Centre; Department
of Health NIHR Biomedical Research Centres
FX AP and SK are supported by the Oxford Partnership Comprehensive
Biomedical Research Centre, with funding from the Department of Health
NIHR Biomedical Research Centres funding scheme.
NR 108
TC 64
Z9 65
U1 1
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1470-0328
J9 BJOG-INT J OBSTET GY
JI BJOG
PD AUG
PY 2011
VL 118
IS 9
BP 1042
EP 1054
DI 10.1111/j.1471-0528.2011.02923.x
PG 13
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 791GL
UT WOS:000292652900003
PM 21401853
ER
PT J
AU Kunos, G
Tam, J
AF Kunos, George
Tam, Joseph
TI The case for peripheral CB1 receptor blockade in the treatment of
visceral obesity and its cardiometabolic complications
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Review
DE diet-induced obesity; metabolic syndrome; endocannabinoids; anandamide;
2-arachidonoylglycerol; peripheral CB1 receptors
ID DIET-INDUCED OBESITY; CARDIOVASCULAR RISK-FACTORS; ADIPOSE-TISSUE;
FOOD-INTAKE; ENDOCANNABINOID SYSTEM; ENERGY-BALANCE; BODY-WEIGHT;
TRANSCRIPTIONAL REGULATION; MITOCHONDRIAL BIOGENESIS; ANTAGONIST
RIMONABANT
AB In this review, we consider the role of endocannabinoids and cannabinoid-1 (CB1) cannabinoid receptors in metabolic regulation and as mediators of the thrifty phenotype that underlies the metabolic syndrome. We survey the actions of endocannabinoids on food intake and body weight, as well as on the metabolic complications of visceral obesity, including fatty liver, insulin resistance and dyslipidemias. Special emphasis is placed on weighing the relative importance of CB1 receptors located in peripheral tissues versus the central nervous system in mediating the metabolic effects of endocannabinoids. Finally, we review recent observations that indicate that peripherally restricted CB1 receptor antagonists retain efficacy in reducing weight and improving metabolic abnormalities in mouse models of obesity without causing behavioural effects predictive of neuropsychiatric side effects in humans.
C1 [Kunos, George; Tam, Joseph] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
RP Kunos, G (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
EM george.kunos@nih.gov
FU National Institutes of Health (National Institute on Alcohol Abuse and
Alcoholism)
FX Work in the authors' laboratory was supported by the National Institutes
of Health (intramural funds from National Institute on Alcohol Abuse and
Alcoholism to G. Kunos).
NR 88
TC 55
Z9 56
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD AUG
PY 2011
VL 163
IS 7
SI SI
BP 1423
EP 1431
DI 10.1111/j.1476-5381.2011.01352.x
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 791GM
UT WOS:000292653000009
PM 21434882
ER
PT J
AU Chen, J
Sobue, T
Utreja, A
Kalajzic, Z
Xu, M
Kilts, T
Young, M
Wadhwa, S
AF Chen, J.
Sobue, T.
Utreja, A.
Kalajzic, Z.
Xu, M.
Kilts, T.
Young, M.
Wadhwa, S.
TI Sex Differences in Chondrocyte Maturation in the Mandibular Condyle from
a Decreased Occlusal Loading Model
SO CALCIFIED TISSUE INTERNATIONAL
LA English
DT Article
DE Temporomandibular joint; Mouse model; Mechanical loading;
Fibrocartilage; Subchondral bone
ID PERIOSTEAL BONE-FORMATION; TEMPOROMANDIBULAR-JOINT; ARTICULAR-CARTILAGE;
ESTROGEN-RECEPTORS; MATRIX PROTEINS; GROWING-RATS; DISORDERS; PAIN;
EXPRESSION; PLAYERS
AB Temporomandibular joint disorders (TMDs) predominantly afflict women of childbearing age. Defects in mechanical loading-induced temporomandibular joint (TMJ) remodeling are believed to be a major etiological factor in the development of TMD. The goal of this study was to determine if there are sex differences in CD-1 and C57BL/6 mice exposed to a decreased occlusal loading TMJ remodeling model. Male and female CD-1 and C57BL/6 mice, 21 days old, were each divided into two groups. They were fed either a normal pellet diet (normal loading) or a soft diet and had their incisors trimmed out of occlusion (decreased occlusal loading) for 4 weeks. The mandibular condylar cartilage was evaluated by histology, and the subchondral bone was evaluated by micro-CT analysis. Gene expression from both was evaluated by real-time PCR analysis. In both strains and sexes of mice, decreased occlusal loading caused similar effects in the subchondral bone, decreases in bone volume and total volume compared with their normal loading controls. However, in both strains, decreased occlusal loading caused a significant decrease in the expression of collagen type II (Col2) and Sox9 only in female mice, but not in male mice, compared with their normal loading controls. Decreased occlusal loading causes decreased bone volume in both sexes and a decrease in early chondrocyte maturation exclusively in female mice.
C1 [Chen, J.; Sobue, T.; Utreja, A.; Kalajzic, Z.; Wadhwa, S.] Univ Connecticut, Ctr Hlth, Dept Craniofacial Sci, Div Orthodont,Sch Dent Med, Farmington, CT 06030 USA.
[Xu, M.] Univ Connecticut, Ctr Hlth, Sch Med, New England Musculoskeletal Inst, Farmington, CT 06030 USA.
[Kilts, T.; Young, M.] NIDCR, Mol Biol Bones & Teeth Sect, Craniofacial & Skeletal Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA.
RP Sobue, T (reprint author), Univ Connecticut, Ctr Hlth, Dept Craniofacial Sci, Div Orthodont,Sch Dent Med, 263 Farmington Ave, Farmington, CT 06030 USA.
EM jingchen@gde.uchc.edu; sobue@uchc.edu; utreja@student.uchc.edu;
zkalajzic@uchc.edu; mxu@nso.uchc.edu; tkilts@mail.nih.gov;
mayoung@mail.nih.gov; wadhwa@uchc.edu
FU National Institute of Dental and Craniofacial Research, National
Institutes of Health [5K22DE017193, 1R01DE020097]
FX This work was supported by 5K22DE017193 (S. W.) and 1R01DE020097 (S. W.)
from the National Institute of Dental and Craniofacial Research,
National Institutes of Health.
NR 39
TC 10
Z9 11
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0171-967X
J9 CALCIFIED TISSUE INT
JI Calcif. Tissue Int.
PD AUG
PY 2011
VL 89
IS 2
BP 123
EP 129
DI 10.1007/s00223-011-9498-9
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 792KP
UT WOS:000292743700004
PM 21597908
ER
PT J
AU Lebson, L
Wang, T
Jiang, Q
Whartenby, KA
AF Lebson, L.
Wang, T.
Jiang, Q.
Whartenby, K. A.
TI Induction of the glucocorticoid-induced leucine zipper gene limits the
efficacy of dendritic cell vaccines
SO CANCER GENE THERAPY
LA English
DT Article
DE dendritic cell vaccine; GILZ; dendritic cell; immunotherapy; tumor
vaccine
ID CLINICAL-RESPONSES; TUMOR LYSATE; VACCINATION; CANCER; TRIAL; LEUKEMIA;
DEATH; IMMUNOTHERAPY; DEXAMETHASONE; ACTIVATION
AB Dendritic cell (DC) vaccines have shown great promise in generating antitumor immune responses but have generally fallen short of producing durable cures. Determining mechanisms by which these vaccines fail will provide one strategy toward improving their success. Several manipulations of DCs have improved their migration and longevity, but the immune inhibitory environment surrounding tumors provides a powerful suppressive influence. To determine the mechanisms by which DCs at the site of the tumor convert to a suppressive phenotype, we evaluated pathways in DCs that become expressed at the tumor site. Our results revealed that tumors lead to induction of the glucocorticoid-induced leucine zipper (GILZ) gene in DCs, and that this gene is critical for the development of tumor-induced tolerance of both DCs and T cells. Previous data suggested that GILZ is a pivotal gene in the balance between activation and tolerance of DCs. Our new data show that GILZ is highly upregulated in DCs in the tumor microenvironment in vivo and that blockade of this gene in DC vaccines significantly improves long-term survival. These results suggest that GILZ may be an ideal candidate gene to target for novel immune-based tumor therapies. Cancer Gene Therapy (2011) 18, 563-570; doi:10.1038/cgt.2011.23; published online 6 May 2011
C1 [Lebson, L.; Whartenby, K. A.] Johns Hopkins Univ, Sch Med, Dept Neurol & Oncol, Baltimore, MD 21231 USA.
[Wang, T.] NCI, LCMB, NIH, Bethesda, MD 20892 USA.
[Jiang, Q.] Qiagen, Frederick, MD USA.
[Whartenby, K. A.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA.
RP Whartenby, KA (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol & Oncol, Baltimore, MD 21231 USA.
EM Whartenby@jhmi.edu
FU [R01CA111989]
FX This work was funded by R01CA111989.
NR 36
TC 5
Z9 8
U1 1
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 AUG
PY 2011
VL 18
IS 8
BP 563
EP 570
DI 10.1038/cgt.2011.23
PG 8
WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Research & Experimental Medicine
GA 793IB
UT WOS:000292812700004
PM 21546924
ER
PT J
AU Zhang, L
Chang, L
Yu, LL
Liu, JC
Chen, JJ
Li, XW
Lazarus, LH
Li, TY
AF Zhang, Liang
Chang, Lei
Yu, Lei Lei
Liu, Jin Chun
Chen, Jia Jia
Li, Xiao Wen
Lazarus, Lawrence H.
Li, Ting You
TI Endomorphin analogues with balanced affinity for both mu- and
delta-opioid receptors
SO CHINESE CHEMICAL LETTERS
LA English
DT Article
DE Endomorphin; Opioid; Analgesics
ID POTENT; ANTAGONISTS; AGONISTS; LIGANDS
AB Analogues of endomorphin and tripeptides modified at positions 4 and 3, respectively, with various phenylalanine analogues were synthesized and their affinities for opioid receptors were evaluated. Most of the peptides exhibited potent mu-receptor affinity and selectivity, among them, compound 7 (Dmt-Pro-Tmp-Tmp-NH(2)) exhibited potent affinity for both mu- and delta-receptors (K(i)mu = 0.47 nmol/L, K(i)delta = 1.63 nmol/L). (C) 2011 Ting You Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
C1 [Zhang, Liang; Chang, Lei; Yu, Lei Lei; Liu, Jin Chun; Chen, Jia Jia; Li, Xiao Wen; Li, Ting You] Nanjing Med Univ, Sch Pharm, Nanjing 210029, Peoples R China.
[Lazarus, Lawrence H.] Natl Inst Environm Hlth Sci, Med Chem Grp, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
RP Li, TY (reprint author), Nanjing Med Univ, Sch Pharm, Nanjing 210029, Peoples R China.
EM litingyou@yahoo.com.cn
FU NIH; NIEHS; [08KJB350002]; [08NMUZ028]
FX This work was supported by grants 08KJB350002 and 08NMUZ028, and in part
by the Intramural Research Program of the NIH and NIEHS.
NR 11
TC 3
Z9 6
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1001-8417
J9 CHINESE CHEM LETT
JI Chin. Chem. Lett.
PD AUG
PY 2011
VL 22
IS 8
BP 907
EP 910
DI 10.1016/j.cclet.2011.01.035
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 789RW
UT WOS:000292535000007
ER
PT J
AU Bras, JM
Singleton, AB
AF Bras, J. M.
Singleton, A. B.
TI Exome sequencing in Parkinson's disease
SO CLINICAL GENETICS
LA English
DT Review
DE exome sequencing; genetics; genomics; Parkinson's disease
ID HUMAN GENOME; MUTATIONS; GENE; ASSOCIATION; IDENTIFICATION; DIAGNOSIS;
CAPTURE
AB Exome sequencing is rapidly becoming a fundamental tool for genetics and functional genomics laboratories. This methodology has enabled the discovery of novel pathogenic mutations causing mendelian diseases that had, until now, remained elusive. In this review, we discuss not only how we envisage exome sequencing being applied to a complex disease, such as Parkinson's disease, but also what are the known caveats of this approach.
C1 [Bras, J. M.] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Singleton, A. B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Bras, JM (reprint author), UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
EM j.bras@ion.ucl.ac.uk
RI Singleton, Andrew/C-3010-2009; Bras, Jose/A-1428-2011;
OI Bras, Jose/0000-0001-8186-0333
FU Medical Research Council; Wellcome Trust Disease Centre; National
Institute on Aging, National Institutes of Health, Department of Health
and Human Services [Z01 AG000958-08]
FX This study was supported in part by the Medical Research Council and
Wellcome Trust Disease Centre and by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health,
Department of Health and Human Services; project number Z01 AG000958-08.
NR 35
TC 9
Z9 10
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD AUG
PY 2011
VL 80
IS 2
SI SI
BP 104
EP 109
DI 10.1111/j.1399-0004.2011.01722.x
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 791FS
UT WOS:000292650800002
PM 21651510
ER
PT J
AU Rossi, S
Hallett, M
Rossini, PM
Pascual-Leone, A
AF Rossi, Simone
Hallett, Mark
Rossini, Paolo M.
Pascual-Leone, Alvaro
TI Screening questionnaire before TMS: An update
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Letter
C1 [Rossi, Simone] Univ Siena, Dipartimento Neurosci, Sez Neurol, I-53100 Siena, Italy.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Rossini, Paolo M.] Casa Cura S Raffaele, Cassino, Italy.
[Rossini, Paolo M.] Univ Campus Biomed, Rome, Italy.
[Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA.
[Pascual-Leone, Alvaro] Harvard Univ, Sch Med, Boston, MA USA.
RP Rossi, S (reprint author), Univ Siena, Dipartimento Neurosci, Sez Neurol, I-53100 Siena, Italy.
EM rossisimo@unisi.it
RI Rossini, Paolo /D-4994-2013;
OI Rossini, Paolo /0000-0003-2665-534X; rossi, simone/0000-0001-6697-9459
NR 1
TC 71
Z9 71
U1 0
U2 11
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD AUG
PY 2011
VL 122
IS 8
BP 1686
EP 1686
DI 10.1016/j.clinph.2010.12.037
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 791AX
UT WOS:000292633300030
PM 21227747
ER
PT J
AU Silbermann, M
Khleif, A
Tuncer, M
Pitsillides, B
Shad, A
Oberman, A
ElShami, M
Gultekin, M
Daher, M
Tarawneh, M
Harford, J
AF Silbermann, Michael
Khleif, Amal
Tuncer, Murat
Pitsillides, Barbara
Shad, Aziza
Oberman, Amitai
ElShami, Mohammad
Gultekin, Murat
Daher, Michel
Tarawneh, Mohammed
Harford, Joe
TI Can We Overcome the Effect of Conflicts in Rendering Palliative Care? An
Introduction to the Middle Eastern Cancer Consortium (MECC)
SO CURRENT ONCOLOGY REPORTS
LA English
DT Article
DE Cancer; Palliative care; Political conflicts; Cultural and traditional
disparities
ID BRIDGE; PEACE
AB The Middle East has been experiencing an ongoing political conflict for the past several decades. This situation has been characterized by hostility often leading to violence of all sources. At times, such a conflict led to the outbreak of a military war, which was followed by an enmity between religious, ethnic, cultural, and national populations. In such environmental situations, palliative care professionals often confront major challenges including bias, mistrust, and mutual suspicion between patients and their treating clinicians. In order to overcome such obstacles, while rendering palliative care services, all professionals involved need careful planning and execution of their treatment plans. The latter is however possible, and sometimes successful even across lines of conflict, thereby promoting understanding, mutual respect, and tolerance between the involved communities and individuals.
C1 [Silbermann, Michael] Technion Israel Inst Technol, Middle E Canc Consortium, Haifa, Israel.
[Khleif, Amal] Al Sadeel Soc, West Bank, Bethlehem, Israel.
[Tuncer, Murat; Gultekin, Murat] Minist Hlth, Ankara, Turkey.
[Pitsillides, Barbara] Cyprus Assoc Canc Patients & Friends, Nicosia, Cyprus.
[Shad, Aziza] Georgetown Univ Hosp, Lombardi Canc Ctr, INCTR, Washington, DC 20007 USA.
[Oberman, Amitai] Poria Med Ctr, Tiberias, Israel.
[ElShami, Mohammad] Cairo Univ, Cairo, Egypt.
[Daher, Michel] St George Univ Hosp, Beirut, Lebanon.
[Tarawneh, Mohammed] Minist Hlth, Amman, Jordan.
[Harford, Joe] NCI, Bethesda, MD 20892 USA.
RP Silbermann, M (reprint author), Technion Israel Inst Technol, Middle E Canc Consortium, Haifa, Israel.
EM cancer@mecc-research.com
FU National Cancer Institute (NCI), Bethesda, MD, USA
FX We thank our colleagues in the Middle East, Europe, and the United
States for their support, encouragement, and involvement in MECC
cross-border health initiatives. This initiative is sponsored by the
National Cancer Institute (NCI), Bethesda, MD, USA. Contributions to
MECC activities were received from the Ministries of Health in Nicosia,
Cyprus, and Ankara, Turkey; the SUVAK Foundation, Ankara, Turkey; the
International Union Against Cancer (UICC), Geneva, Switzerland; the
Middle East Regional Cooperation (MERC) Program, US Agency for
International Development (USAID), Washington, DC; the Oncology Nursing
Society (ONS), Pittsburgh, PA, USA; and the American Cancer Society
(ACS), Atlanta, GA, USA.
NR 20
TC 5
Z9 5
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3790
J9 CURR ONCOL REP
JI Curr. Oncol. Rep.
PD AUG
PY 2011
VL 13
IS 4
BP 302
EP 307
DI 10.1007/s11912-011-0174-z
PG 6
WC Oncology
SC Oncology
GA 788UI
UT WOS:000292469500010
PM 21538041
ER
PT J
AU Voon, V
Mehta, AR
Hallett, M
AF Voon, Valerie
Mehta, Arpan R.
Hallett, Mark
TI Impulse control disorders in Parkinson's disease: recent advances
SO CURRENT OPINION IN NEUROLOGY
LA English
DT Article
DE dopamine agonists; impulse control disorders; impulsivity; Parkinson's
disease; pathological gambling
ID COMPULSIVE SPECTRUM BEHAVIORS; STRIATAL DOPAMINE RELEASE; RESTLESS LEGS
SYNDROME; SUBTHALAMIC NUCLEUS; WITHDRAWAL SYNDROME; REWARD; STIMULATION;
RISK; ADDICTION; AGONISTS
AB Purpose of review
The aim is to review the recent advances in the epidemiology and pathophysiology of impulse control disorders (ICDs) in Parkinson's disease.
Recent findings
Large cross-sectional and case-control multicentre studies show that ICDs in Parkinson's disease are common, with a frequency of 13.6%. These behaviours are associated with impaired functioning and with depressive, anxiety and obsessive symptoms, novelty seeking and impulsivity. Behavioural subtypes demonstrate differences in novelty seeking and impulsivity, suggesting pathophysiological differences. Observational and neurophysiological studies point towards a potential mechanistic overlap between behavioural (ICDs) and motor (dyskinesias) dopaminergic sequelae. Converging data suggest dopamine agonists in ICDs appear to enhance learning from rewarding outcomes and impulsive choice. ICD patients also have enhanced risk preference and impaired working memory. Neuroimaging data point towards enhanced bottom-up ventral striatal dopamine release to incentive cues, gambling tasks and reward prediction, and possible inhibition of top-down orbitofrontal influences. Dopamine agonist-related ventral striatal hypoactivity to risk is consistent with impaired risk evaluation.
Summary
Recent large-scale studies and converging findings are beginning to provide an understanding of mechanisms underlying ICDs in Parkinson's disease, which can guide prevention of these behaviours and optimize therapeutic approaches.
C1 [Voon, Valerie] Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge CB2 0SZ, England.
[Mehta, Arpan R.] Univ Cambridge, Dept Med, Cambridge CB2 0SZ, England.
[Hallett, Mark] NINDS, NIH, Bethesda, MD 20892 USA.
RP Voon, V (reprint author), Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Herchel Smith Bldg,Forvie Site,Robinson Way, Cambridge CB2 0SZ, England.
EM vv247@cam.ac.uk
FU Wellcome Trust; NINDS
FX V.V. is funded by the Wellcome Trust. M.H. is supported by the NINDS
Intramural Program.
NR 60
TC 80
Z9 80
U1 2
U2 25
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1350-7540
J9 CURR OPIN NEUROL
JI Curr. Opin. Neurol.
PD AUG
PY 2011
VL 24
IS 4
BP 324
EP 330
DI 10.1097/WCO.0b013e3283489687
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 789FB
UT WOS:000292498600003
PM 21725242
ER
PT J
AU Furey, ML
AF Furey, Maura L.
TI The prominent role of stimulus processing: cholinergic function and
dysfunction in cognition
SO CURRENT OPINION IN NEUROLOGY
LA English
DT Article
DE acetylcholine; cognition; stimulus processing
ID CEREBRAL-BLOOD-FLOW; CORTICAL ACETYLCHOLINE-RELEASE; MAJOR DEPRESSIVE
DISORDER; HUMAN EXTRASTRIATE CORTEX; CAT VISUAL-CORTEX; WORKING-MEMORY;
ALZHEIMERS-DISEASE; SELECTIVE ATTENTION; CLINICAL DEPRESSION; SUSTAINED
ATTENTION
AB Purpose of review
The present review develops a framework from which to understand the role of the cholinergic system in healthy cognition and in cognitive dysfunction. Traditionally, the cholinergic system has been thought to have direct influence on cognitive processes such as working memory and attention. Although the influence of cholinergic function on stimulus processing has been long appreciated, the notion that cholinergic effects on stimulus processing is the mechanism by which acetylcholine influences cognitive processes has only more recently been considered.
Recent findings
Literature supporting the hypothesis that cholinergic modulation influences cognitive functions through stimulus processing mechanisms has been growing for over a decade. Recent conceptualizations of the developing literature have argued for a new interpretation to an old and developing literature.
Summary
The argument that cholinergic function modulates cognitive processes by direct effects on basic stimulus processing extends to cognitive dysfunction in neuropathological conditions including dementia and mood disorders. Memory and attention deficits observed in these and other conditions can be understood by evaluating the impact of cholinergic dysfunction on stimulus processing, rather than on the cognitive function in general.
C1 NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
RP Furey, ML (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, NIH, 15K North Dr,Bldg 15K,Room 115B, Bethesda, MD 20892 USA.
RI Furey, Maura/H-5273-2013
FU NIA/National Institutes of Health; National Institute of Mental
Health/NIH
FX The author would like to thank the many colleagues who have collaborated
on various aspects of work that is reflected in this review, with
particular thanks to Drs James Haxby, Pietro Pietrini, and Emiliano
Ricciardi. The author would also like to thank Drs Emiliano Ricciardi
and Allison Nugent for comments on the article. The work presented here
associated with the author was supported by the intramural research
programs of the NIA/National Institutes of Health and the National
Institute of Mental Health/NIH. A use-patent application for the use of
scopolamine as an antidepressant agent has been filed by the NIMH/NIH.
NR 103
TC 22
Z9 22
U1 6
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1350-7540
J9 CURR OPIN NEUROL
JI Curr. Opin. Neurol.
PD AUG
PY 2011
VL 24
IS 4
BP 364
EP 370
DI 10.1097/WCO.0b013e328348bda5
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 789FB
UT WOS:000292498600009
PM 21725241
ER
PT J
AU Duyn, JH
Koretsky, AP
AF Duyn, Jeff H.
Koretsky, Alan P.
TI Novel frontiers in ultra-structural and molecular MRI of the brain
SO CURRENT OPINION IN NEUROLOGY
LA English
DT Article
DE brain; cellular imaging; cytoarchitecture; high field MRI; tract tracing
ID MANGANESE-ENHANCED MRI; MAGNETIC-RESONANCE TRACKING; SINGLE
MAMMALIAN-CELLS; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD-INJURY; IN-VIVO
DETECTION; ALZHEIMERS-DISEASE; MULTIPLE-SCLEROSIS; CONTRAST AGENTS;
IRON-OXIDE
AB Purpose of review
Recent developments in the MRI of the brain continue to expand its use in basic and clinical neuroscience. This review highlights some areas of recent progress.
Recent findings
Higher magnetic field strengths and improved signal detectors have allowed improved visualization of the various properties of the brain, facilitating the anatomical definition of function-specific areas and their connections. For example, by sensitizing the MRI signal to the magnetic susceptibility of tissue, it is starting to become possible to reveal the laminar structure of the cortex and identify millimeter-scale fiber bundles. Using exogenous contrast agents, and innovative ways to manipulate contrast, it is becoming possible to highlight specific fiber tracts and cell populations. These techniques are bringing us closer to understanding the evolutionary blueprint of the brain, improving the detection and characterization of disease, and help to guide treatment.
Summary
Recent MRI techniques are leading to more detailed and more specific contrast in the study of the brain.
C1 [Duyn, Jeff H.; Koretsky, Alan P.] NIH, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA.
RP Duyn, JH (reprint author), NIH, Lab Funct & Mol Imaging, Bldg 10, Bethesda, MD 20892 USA.
EM jhd@helix.nih.gov
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU Intramural NIH HHS [ZIA NS002989-11]
NR 123
TC 11
Z9 11
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1350-7540
J9 CURR OPIN NEUROL
JI Curr. Opin. Neurol.
PD AUG
PY 2011
VL 24
IS 4
BP 386
EP 393
DI 10.1097/WCO.0b013e328348972a
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 789FB
UT WOS:000292498600012
PM 21734576
ER
PT J
AU Croce, J
Range, R
Wu, SY
Miranda, E
Lhomond, G
Peng, JCF
Lepage, T
McClay, DR
AF Croce, Jenifer
Range, Ryan
Wu, Shu-Yu
Miranda, Esther
Lhomond, Guy
Peng, Jeff Chieh-fu
Lepage, Thierry
McClay, David R.
TI Wnt6 activates endoderm in the sea urchin gene regulatory network
SO DEVELOPMENT
LA English
DT Article
DE Sea urchin; Wnt pathway; Gene regulatory networks; Wnt6; Dishevelled;
beta-Catenin; Maternal determinants; Endomesoderm
ID ANIMAL-VEGETAL AXIS; NUCLEAR BETA-CATENIN;
STRONGYLOCENTROTUS-PURPURATUS; PARACENTROTUS-LIVIDUS; SIGNALING PATHWAY;
EMBRYO; EXPRESSION; MESODERM; SPECIFICATION; ARCHENTERON
AB In the sea urchin, entry of beta-catenin into the nuclei of the vegetal cells at 4th and 5th cleavages is necessary for activation of the endomesoderm gene regulatory network. Beyond that, little is known about how the embryo uses maternal information to initiate specification. Here, experiments establish that of the three maternal Wnts in the egg, Wnt6 is necessary for activation of endodermal genes in the endomesoderm GRN. A small region of the vegetal cortex is shown to be necessary for activation of the endomesoderm GRN. If that cortical region of the egg is removed, addition of Wnt6 rescues endoderm. At a molecular level, the vegetal cortex region contains a localized concentration of Dishevelled (Dsh) protein, a transducer of the canonical Wnt pathway; however, Wnt6 mRNA is not similarly localized. Ectopic activation of the Wnt pathway, through the expression of an activated form of beta-catenin, of a dominant-negative variant of GSK-3 beta or of Dsh itself, rescues endomesoderm specification in eggs depleted of the vegetal cortex. Knockdown experiments in whole embryos show that absence of Wnt6 produces embryos that lack endoderm, but those embryos continue to express a number of mesoderm markers. Thus, maternal Wnt6 plus a localized vegetal cortical molecule, possibly Dsh, is necessary for endoderm specification; this has been verified in two species of sea urchin. The data also show that Wnt6 is only one of what are likely to be multiple components that are necessary for activation of the entire endomesoderm gene regulatory network.
C1 [Wu, Shu-Yu; Miranda, Esther; McClay, David R.] Duke Univ, French Family Sci Ctr, Dept Biol, Durham, NC 27708 USA.
[Croce, Jenifer; Lhomond, Guy; Lepage, Thierry] CNRS, UMR7009, UPMC, Observ Oceanol Villefranche Sur Mer, F-06230 Villefranche Sur Mer, France.
[Range, Ryan] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
[Peng, Jeff Chieh-fu] Univ Miami, Dept Biol, Cox Sci Ctr, Coral Gables, FL 33124 USA.
RP McClay, DR (reprint author), Duke Univ, French Family Sci Ctr, Dept Biol, Durham, NC 27708 USA.
EM dmcclay@duke.edu
FU NSF [IOS 0754323]; CNRS; UPMC (University Pierre et Marie Curie - Paris
VI); ANR; ARC [4801]; Feidelson family; NIH [HD 14483, GM 81883]
FX The Dsh construct was provided by C. Ettensohn; the dominant-negative
GSK-3 construct was provided by C. Gache. J.C.P. was supported by NSF
grant IOS 0754323. Support in France for this work was provided by the
CNRS and the UPMC (University Pierre et Marie Curie - Paris VI) (to J.C.
and T. L.), by ANR and ARC grants (ARC grant 4801) (to T. L.) and by the
Feidelson family fund (to D. R. M.). In the USA, support was provided by
NIH (HD 14483 and GM 81883 to D. R. M.). Deposited in PMC for release
after 12 months.
NR 51
TC 27
Z9 27
U1 1
U2 15
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 AUG 1
PY 2011
VL 138
IS 15
BP 3297
EP 3306
DI 10.1242/dev.058792
PG 10
WC Developmental Biology
SC Developmental Biology
GA 791AO
UT WOS:000292632400019
PM 21750039
ER
PT J
AU Tsau, C
Ito, M
Gromova, A
Hoffman, MP
Meech, R
Makarenkova, HP
AF Tsau, Cindy
Ito, Masataka
Gromova, Anastasia
Hoffman, Matthew P.
Meech, Robyn
Makarenkova, Helen P.
TI Barx2 and Fgf10 regulate ocular glands branching morphogenesis by
controlling extracellular matrix remodeling
SO DEVELOPMENT
LA English
DT Article
DE Barx2; Fgf10; Harderian gland; Lacrimal gland; Meibomian glands;
Submandibular gland; Mouse
ID HOMEODOMAIN PROTEIN; HARDERIAN-GLAND; LACRIMAL GLAND; HOMEOBOX GENE;
IN-VITRO; EPITHELIAL MORPHOGENESIS; DEVELOPING KIDNEY; LIMB DEVELOPMENT;
OVARIAN-CANCER; URETERAL BUD
AB The lacrimal gland (LG) develops through branching morphogenesis and produces secretions, including tears, that lubricate and protect the ocular surface. Despite the prevalence of LG disorders such as dry eye, relatively little is known about the regulation of LG development. In this study, we show that the homeobox transcription factor Barx2 is highly expressed in conjunctival epithelium, eyelids and ocular [lacrimal, harderian (HG), and meibomian (MG)] glands and is necessary for normal ocular gland and eyelid development. Barx(2-/-) mice show defective LG morphogenesis, absence of the HG, and defects in MG and eyelid fusion. Ex vivo antisense assays confirm the requirement for Barx2 in LG bud elongation and branching. Gene expression profiles reveal decreased expression of several adhesion and matrix remodeling molecules in Barx(2-/-) LGs. In culture, Barx2 regulates expression of matrix metalloproteinases (MMPs) and epithelial cell migration through the extracellular matrix. Fibroblast growth factors are crucial regulators of LG development and we show that Barx2 is required for Fgf10-induced LG bud elongation and that both Barx2 and Fgf10 cooperate in the regulation of MMPs. Together, these data suggest a mechanism for the effects of loss of Barx2 on ocular gland development. Intriguingly, salivary glands that also express a high level of Barx2 develop normally in Barx(2-/-) mice and do not show altered levels of MMPs. Thus, the function of Barx2 is specific to ocular gland development. Based on our data, we propose a functional network involving Barx2, Fgf10 and MMPs that plays an essential role in regulating branching morphogenesis of the ocular glands.
C1 [Tsau, Cindy; Gromova, Anastasia; Makarenkova, Helen P.] Inst Neurosci, San Diego, CA 92121 USA.
[Ito, Masataka] Natl Def Med Coll, Dept Dev Anat & Regenerat Biol, Saitama 3598513, Japan.
[Gromova, Anastasia; Makarenkova, Helen P.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Hoffman, Matthew P.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Meech, Robyn] Flinders Univ S Australia, Dept Clin Pharmacol, Bedford Pk, SA 5042, Australia.
RP Makarenkova, HP (reprint author), Inst Neurosci, San Diego, CA 92121 USA.
EM hmakarenk@scripps.edu
FU National Eye Institute at National Institutes of Health [1 R21
EY021292-01]; Neurosciences Research Foundation; Sjogren's Syndrome
Foundation; National Defense Medical College (Japan); National Institute
for Dental and Craniofacial Research at the National Institutes of
Health
FX H. P. M. was supported by a National Eye Institute at National
Institutes of Health Grant 1 R21 EY021292-01, by the Neurosciences
Research Foundation and by the Sjogren's Syndrome Foundation; M. I. was
supported by a grant from National Defense Medical College (Japan); M.
P. H. was supported by the Intramural Research Program of the National
Institute for Dental and Craniofacial Research at the National
Institutes of Health. Deposited in PMC for release after 12 months.
NR 62
TC 22
Z9 24
U1 1
U2 9
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 AUG 1
PY 2011
VL 138
IS 15
BP 3307
EP 3317
DI 10.1242/dev.066241
PG 11
WC Developmental Biology
SC Developmental Biology
GA 791AO
UT WOS:000292632400020
PM 21750040
ER
PT J
AU Xu, H
Behra, M
Burgess, S
Chen, SH
Lin, F
AF Xu, Hui
Behra, Martine
Burgess, Shawn
Chen, Songhai
Lin, Fang
TI Src64 regulates myosin regulatory light chain during basal closure of
the Drosophila cellular blastoderm
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Xu, Hui; Chen, Songhai] Univ Iowa, Iowa City, IA USA.
[Behra, Martine] Univ Puerto Rico, San Juan, PR 00936 USA.
[Burgess, Shawn] NHGRI, NIH, Bethesda, MD 20892 USA.
[Lin, Fang] Univ Iowa Anat & Cell Biol, Iowa City, IA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 20
BP 108
EP 109
DI 10.1016/j.ydbio.2011.05.031
PG 2
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400026
ER
PT J
AU Xu, H
Behra, M
Burgess, S
Chen, SH
Lin, F
AF Xu, Hui
Behra, Martine
Burgess, Shawn
Chen, Songhai
Lin, Fang
TI Gbetagamma signaling is essential for migration of the posterior lateral
line primordium in zebrafish
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Xu, Hui; Chen, Songhai] Univ Iowa, Iowa City, IA USA.
[Behra, Martine] Univ Puerto Rico, San Juan, PR 00936 USA.
[Burgess, Shawn] NHGRI, NIH, Bethesda, MD 20892 USA.
[Lin, Fang] Univ Iowa Anat & Cell Biol, Iowa City, IA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 18
BP 108
EP 108
DI 10.1016/j.ydbio.2011.05.029
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400024
ER
PT J
AU Brody, T
Kuzin, A
Kundu, M
Ross, J
Tyson, L
Amar, Y
Odenwald, WF
AF Brody, Thomas
Kuzin, Alexander
Kundu, Mukta
Ross, Jermaine
Tyson, Leonard
Amar, Yavatkar
Odenwald, Ward F.
TI Web based algorithms EvoPrinter and cis-Decoder reveal functional
sequences in enhancers and complex networks of transcription factor
interactions required for gene regulation
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Brody, Thomas; Kuzin, Alexander; Kundu, Mukta; Ross, Jermaine; Odenwald, Ward F.] NINDS, NIH, Neural Cell Fate Determinants Sect, Bethesda, MD 20892 USA.
[Tyson, Leonard] NINDS, NIH, DIR, ITP, Bethesda, MD 20892 USA.
[Amar, Yavatkar] Div INTRAML RESCH HNQ2, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 24
BP 110
EP 110
DI 10.1016/j.ydbio.2011.05.036
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400030
ER
PT J
AU Chitnis, A
Nogare, DD
AF Chitnis, Ajay
Nogare, Damian Dalle
TI A computational model reveals the remarkable patterning potential of the
Wnt-FGF gene regulatory network in the posterior lateral line primordium
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Chitnis, Ajay; Nogare, Damian Dalle] NICHD, NIH, Mol Genet Lab, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 27
BP 111
EP 111
DI 10.1016/j.ydbio.2011.05.039
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400033
ER
PT J
AU Dymecki, S
Ray, R
Brust, R
Jensen, P
Kim, JC
Corcoran, A
Richerson, G
Nattie, E
AF Dymecki, Susan
Ray, Russell
Brust, Rachael
Jensen, Patricia
Kim, Jun Chul
Corcoran, Andrea
Richerson, George
Nattie, Eugene
TI Redefining brain serotonergic neurons by genetic lineage and selective
in vivo silencing
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Dymecki, Susan] Harvard Med Sch Genet, Boston, MA USA.
[Ray, Russell; Brust, Rachael] Harvard Univ, Sch Med, Boston, MA USA.
[Jensen, Patricia] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Kim, Jun Chul] Univ Toronto, Toronto, ON, Canada.
[Corcoran, Andrea; Nattie, Eugene] Dartmouth Med Sch, Lebanon, NH USA.
[Richerson, George] UI Hosp & Clin, Iowa City, IA USA.
OI Brust, Rachael/0000-0001-5375-6731
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 37
BP 117
EP 117
DI 10.1016/j.ydbio.2011.05.054
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400042
ER
PT J
AU Naiche, LA
Arora, R
Papaioannou, V
Lewandoski, M
AF Naiche, L. A.
Arora, Ripla
Papaioannou, Virginia
Lewandoski, Mark
TI Lineage tracing of Tbx4-expressing cells reveals cryptic developmental
decisions
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Naiche, L. A.] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA.
[Arora, Ripla; Papaioannou, Virginia] Columbia Univ, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 38
BP 117
EP 117
DI 10.1016/j.ydbio.2011.05.055
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400043
ER
PT J
AU Wei, Z
Angerer, R
Angerer, LM
AF Wei, Zheng
Angerer, Robert
Angerer, Lynne M.
TI Neurons develop in situ in foregut endoderm of sea urchin embryos
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Wei, Zheng; Angerer, Robert; Angerer, Lynne M.] NIDCR, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 40
BP 118
EP 118
DI 10.1016/j.ydbio.2011.05.057
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400045
ER
PT J
AU Driver, EC
Mann, Z
Kelley, M
AF Driver, Elizabeth C.
Mann, Zoe
Kelley, Matthew
TI Live imaging of cell movement in the developing cochlea confirms periods
of convergence and extension
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Driver, Elizabeth C.] NIDCD, NIH, Sect Dev Neurosci, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 111
BP 140
EP 140
DI 10.1016/j.ydbio.2011.05.135
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400110
ER
PT J
AU Fujita, M
Cha, Y
Van, P
Roman, B
Weinstein, B
AF Fujita, Misato
Cha, Young
Van Pham
Roman, Beth
Weinstein, Brant
TI Cranial vessel formation in the developing zebrafish
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Fujita, Misato; Cha, Young; Van Pham; Weinstein, Brant] NIH, Bethesda, MD 20892 USA.
[Roman, Beth] Univ Pittsburgh, Pittsburgh, PA USA.
OI Roman, Beth/0000-0002-1250-1705
NR 0
TC 0
Z9 0
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 176
BP 159
EP 159
DI 10.1016/j.ydbio.2011.05.590
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400173
ER
PT J
AU Deng, XH
Wu, D
AF Deng, Xiaohong
Wu, Doris
TI Fate-mapping the vestibular neurogenic region in the developing chicken
otic cup using lipophilic dyes
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Deng, Xiaohong] NIDCD, NIH, Mol Biol Lab, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 248
BP 179
EP 179
DI 10.1016/j.ydbio.2011.05.202
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400242
ER
PT J
AU Evsen, L
Uchikawa, M
Sugahara, S
Kondoh, H
Wu, D
AF Evsen, Lale
Uchikawa, Masanori
Sugahara, Satoko
Kondoh, Hisato
Wu, Doris
TI Sox2 and Ngn1 regulate the neurogenic fate in the developing inner ear
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Evsen, Lale] NIDCD, NIH, College Pk, MD USA.
[Uchikawa, Masanori; Sugahara, Satoko; Kondoh, Hisato] Grad Sch Frontier Biosci, Osaka, Japan.
[Wu, Doris] Natl Inst Deafness & Other Commun Disorders, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 247
BP 179
EP 179
DI 10.1016/j.ydbio.2011.05.201
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400241
ER
PT J
AU Forni, PE
Taylor-Burds, C
Melvin, VS
Williams, T
Wray, S
AF Forni, Paolo Emanuele
Taylor-Burds, Carlor
Melvin, Vida Senkus
Williams, Trevor
Wray, Susan
TI Neural crest and ectodermal contributions to the development of the
nasal placode
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Forni, Paolo Emanuele] NINDS, NIH, Cellular & Dev Neurobiol Sect, Bethesda, MD 20892 USA.
[Taylor-Burds, Carlor; Wray, Susan] NINDS, CDNS, NIH, Bethesda, MD USA.
[Melvin, Vida Senkus; Williams, Trevor] Dept Craniofacial Biol, Denver, CO USA.
[Melvin, Vida Senkus; Williams, Trevor] Dept Cell & Dev Biol, Denver, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 268
BP 185
EP 185
DI 10.1016/j.ydbio.2011.05.222
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400262
ER
PT J
AU Coate, T
Goodrich, L
Kelley, M
AF Coate, Thomas
Goodrich, Lisa
Kelley, Matthew
TI Imaging and analysis of interactions between individually labeled spiral
ganglion neurons and hair cells in the developing mammalian cochlea
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Coate, Thomas; Kelley, Matthew] NIDCD, NIH, Bethesda, MD USA.
[Goodrich, Lisa] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 324
BP 200
EP 200
DI 10.1016/j.ydbio.2011.05.280
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400313
ER
PT J
AU Sethi, AJ
AF Sethi, Aditya J.
TI Endomesoderm segregation involves cross talk between Notch and Wnt
pathways through multiple intersecting regulatory circuits
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Sethi, Aditya J.] NIH NIDCR Dev Mech Unit, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 336
BP 204
EP 204
DI 10.1016/j.ydbio.2011.05.293
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400325
ER
PT J
AU Peluso, C
Umulis, D
Kim, YJ
O'Connor, M
Serpe, M
AF Peluso, Carolyn
Umulis, David
Kim, Young-Jun
O'Connor, Michael
Serpe, Mihaela
TI Formation and interpretation of the BMP morphogen gradient in the
Drosophila embryo
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Peluso, Carolyn; Kim, Young-Jun; Serpe, Mihaela] NICHD, NIH, Bethesda, MD USA.
[Umulis, David] Purdue Univ, W Lafayette, IN 47907 USA.
[O'Connor, Michael] Univ Minnesota, Minneapolis, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 346
BP 207
EP 207
DI 10.1016/j.ydbio.2011.05.303
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400335
ER
PT J
AU May-Simera, H
Rachel, R
Yoon, BYB
Friedman, T
Swaroop, A
Kelley, M
AF May-Simera, Helen
Rachel, Rivka
Yoon, Byung Byung Yoon
Friedman, Thomas
Swaroop, Anand
Kelley, Matthew
TI Reciprocal rescue of sensory cell cilia defects by CEP290 and BBS6
(MKKS) alleles
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [May-Simera, Helen] NIH NIDCD, Bethesda, MD USA.
[Rachel, Rivka; Swaroop, Anand] NEI, NIH, Bethesda, MD 20892 USA.
[Yoon, Byung Byung Yoon; Friedman, Thomas] NIDCD, NIH, Rockville, MD USA.
[Kelley, Matthew] NIDCD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 408
BP 224
EP 224
DI 10.1016/j.ydbio.2011.05.367
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400393
ER
PT J
AU Hunter, C
Cohen, T
Ediger, B
Wilcox, C
Dixit, S
Westphal, H
Stein, R
May, C
AF Hunter, Chad
Cohen, Tsadok
Ediger, Benjamin
Wilcox, Crystal
Dixit, Shilpy
Westphal, Heiner
Stein, Roland
May, Catherine
TI The LIM co-factor Ldb1 is enriched in pancreatic islet cells and
required for proper cell development and function
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Hunter, Chad; Dixit, Shilpy; Stein, Roland] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Cohen, Tsadok] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Ediger, Benjamin; Wilcox, Crystal; May, Catherine] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Westphal, Heiner] Kennedy Shriver Natl Inst Child Hlth & Human Dev, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 462
BP 240
EP 241
DI 10.1016/j.ydbio.2011.05.424
PG 2
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400444
ER
PT J
AU Roeseler, DA
Sachdev, S
Joshi, T
Hwang, CH
Xu, D
Hannink, M
Waters, S
AF Roeseler, David A.
Sachdev, Shrikesh
Joshi, Trupti
Hwang, ChanHo
Xu, Dong
Hannink, Mark
Waters, Samuel
TI GBX2 target gene identification reveals Usher syndrome genes PCD15 and
USH2A
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Roeseler, David A.] Univ Missouri Biol Sci, Columbia, MO USA.
[Sachdev, Shrikesh; Joshi, Trupti; Xu, Dong; Hannink, Mark; Waters, Samuel] Univ Missouri, Columbia, MO USA.
[Hwang, ChanHo] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 507
BP 253
EP 253
DI 10.1016/j.ydbio.2011.05.569
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400488
ER
PT J
AU Chalamalasetty, RB
Dunty, WC
Biris, KK
Beisaw, A
Feigenbaum, L
Yoon, JK
Kyba, M
Yamaguchi, TP
AF Chalamalasetty, Ravindra B.
Dunty, William C., Jr.
Biris, Kristin K.
Beisaw, Arica
Feigenbaum, Lionel
Yoon, Jeong K.
Kyba, Michael
Yamaguchi, Terry P.
TI The Wnt/bcatenin target, Mesogenin1 (Msgn1), directly regulates the
Notch pathway during mammalian somitogensis
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Chalamalasetty, Ravindra B.; Dunty, William C., Jr.; Biris, Kristin K.; Beisaw, Arica; Feigenbaum, Lionel] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 528
BP 259
EP 259
DI 10.1016/j.ydbio.2011.05.493
PG 1
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400507
ER
PT J
AU Roeseler, D
Sachdev, S
Joshi, T
Hwang, CH
Xu, D
Hannink, M
Waters, S
AF Roeseler, David
Sachdev, Shrikesh
Joshi, Trupti
Hwang, ChanHo
Xu, Dong
Hannink, Mark
Waters, Samuel
TI GBX2 target gene identification reveals Usher syndrome genes PCD15 and
USH2A
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 21-25, 2011
CL Chicago, IL
SP Soc Dev Biol
C1 [Roeseler, David; Sachdev, Shrikesh; Joshi, Trupti; Xu, Dong; Hannink, Mark; Waters, Samuel] Univ Missouri, Columbia, MO USA.
[Hwang, ChanHo] NIDCD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2011
VL 356
IS 1
MA 551
BP 264
EP 265
DI 10.1016/j.ydbio.2011.05.516
PG 2
WC Developmental Biology
SC Developmental Biology
GA 792XT
UT WOS:000292784400528
ER
PT J
AU Luther, JM
Luo, P
Kreger, MT
Brissova, M
Dai, C
Whitfield, TT
Kim, HS
Wasserman, DH
Powers, AC
Brown, NJ
AF Luther, J. M.
Luo, P.
Kreger, M. T.
Brissova, M.
Dai, C.
Whitfield, T. T.
Kim, H. S.
Wasserman, D. H.
Powers, A. C.
Brown, N. J.
TI Aldosterone decreases glucose-stimulated insulin secretion in vivo in
mice and in murine islets
SO DIABETOLOGIA
LA English
DT Article
DE Aldosterone; Aldosterone synthase; Diabetes mellitus; Glucose clamp
technique; Insulin; Mineralocorticoid receptor; Pancreatic beta cells;
Renin-angiotensin-aldosterone system
ID RENIN-ANGIOTENSIN SYSTEM; MINERALOCORTICOID RECEPTOR;
PLASMA-ALDOSTERONE; PRIMARY HYPERALDOSTERONISM; CARDIOVASCULAR-SYSTEM;
ENDOCRINE PANCREAS; METABOLIC SYNDROME; CONSCIOUS MOUSE; BLOOD-PRESSURE;
HYPERTENSION
AB Aldosterone concentrations increase in obesity and predict the onset of diabetes. We investigated the effects of aldosterone on glucose homeostasis and insulin secretion in vivo and in vitro.
We assessed insulin sensitivity and insulin secretion in aldosterone synthase-deficient (As [also known as Cyp11b2](-/-)) and wild-type mice using euglycaemic-hyperinsulinaemic and hyperglycaemic clamps, respectively. We also conducted studies during high sodium intake to normalise renin activity and potassium concentration in As (-/-) mice. We subsequently assessed the effect of aldosterone on insulin secretion in vitro in the presence or absence of mineralocorticoid receptor antagonists in isolated C57BL/6J islets and in the MIN6 beta cell line.
Fasting glucose concentrations were reduced in As (-/-) mice compared with wild-type. During hyperglycaemic clamps, insulin and C-peptide concentrations increased to a greater extent in As (-/-) than in wild-type mice. This was not attributable to differences in potassium or angiotensin II, as glucose-stimulated insulin secretion was enhanced in As (-/-) mice even during high sodium intake. There was no difference in insulin sensitivity between As (-/-) and wild-type mice in euglycaemic-hyperinsulinaemic clamp studies. In islet and MIN6 beta cell studies, aldosterone inhibited glucose- and isobutylmethylxanthine-stimulated insulin secretion, an effect that was not blocked by mineralocorticoid receptor antagonism, but was prevented by the superoxide dismutase mimetic tempol.
We demonstrated that aldosterone deficiency or excess modulates insulin secretion in vivo and in vitro via reactive oxygen species and in a manner that is independent of mineralocorticoid receptors. These findings provide insight into the mechanism of glucose intolerance in conditions of relative aldosterone excess.
C1 [Luther, J. M.; Luo, P.; Kreger, M. T.; Brown, N. J.] Vanderbilt Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Nashville, TN 37232 USA.
[Luther, J. M.] Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol & Hypertens, Nashville, TN 37232 USA.
[Brissova, M.; Dai, C.; Powers, A. C.] Vanderbilt Univ, Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Nashville, TN 37232 USA.
[Whitfield, T. T.] Univ Tennessee, Sch Med, Memphis, TN USA.
[Kim, H. S.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA.
[Wasserman, D. H.; Powers, A. C.] Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
[Wasserman, D. H.] Vanderbilt Univ, Med Ctr, NIH Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA.
[Wasserman, D. H.; Powers, A. C.] Vanderbilt Univ, Med Ctr, Diabet Res Training Ctr, Nashville, TN 37232 USA.
[Powers, A. C.] VA Tennessee Valley Healthcare Syst, Nashville, TN USA.
RP Luther, JM (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Div Clin Pharmacol, 2200 Pierce Ave,560 RRB, Nashville, TN 37232 USA.
EM James.Luther@Vanderbilt.edu
RI luo, pengcheng/F-7992-2011;
OI Luther, James/0000-0001-7225-2897
FU Juvenile Diabetes Research Foundation International; VA Research
Service; NIH [DK081662, DK66636, DK69603, DK68854, HL067308, HL060906,
HL07738, DK072473, DK089572]; Vanderbilt Mouse Metabolic Phenotyping
Center [DK59637]; Vanderbilt Diabetes Research and Training Center
[DK20593]
FX The authors gratefully acknowledge the excellent technical assistance of
T. Ansari and C. Malabanan. We thank A. Golovin at the Vanderbilt
University Islet Procurement and Analysis Core for performing islet
isolation and assessing islet insulin secretion. We thank the Vanderbilt
University Hormone Assay Core for performing insulin assays. We also
thank C. Gomez-Sanchez for generously providing anti-MR antibodies. This
work was supported by the Juvenile Diabetes Research Foundation
International, the VA Research Service, the NIH (DK081662, DK66636,
DK69603, DK68854, HL067308, HL060906, HL07738, DK072473, DK089572), the
Vanderbilt Mouse Metabolic Phenotyping Center (DK59637) and the
Vanderbilt Diabetes Research and Training Center (DK20593).
NR 50
TC 29
Z9 30
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
EI 1432-0428
J9 DIABETOLOGIA
JI Diabetologia
PD AUG
PY 2011
VL 54
IS 8
BP 2152
EP 2163
DI 10.1007/s00125-011-2158-9
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 790BC
UT WOS:000292562500025
PM 21519965
ER
PT J
AU Young, MJ
Longley, MJ
Li, FY
Kasiviswanathan, R
Wong, LJ
Copeland, WC
AF Young, Matthew J.
Longley, Matthew J.
Li, Fang-Yuan
Kasiviswanathan, Rajesh
Wong, Lee-Jun
Copeland, William C.
TI Biochemical analysis of human POLG2 variants associated with
mitochondrial disease
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID DNA-POLYMERASE-GAMMA; TRANSFER-RNA SYNTHETASES; PROGRESSIVE EXTERNAL
OPHTHALMOPLEGIA; COMPARATIVE GENOMIC HYBRIDIZATION; ACCESSORY SUBUNIT;
PROCESSIVITY FACTOR; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; CATALYTIC
SUBUNIT; MUTATIONS
AB Defects in mitochondrial DNA (mtDNA) maintenance comprise an expanding repertoire of polymorphic diseases caused, in part, by mutations in the genes encoding the p140 mtDNA polymerase (POLG), its p55 accessory subunit (POLG2) or the mtDNA helicase (C10orf2). In an exploration of nuclear genes for mtDNA maintenance linked to mitochondrial disease, eight heterozygous mutations (six novel) in POLG2 were identified in one control and eight patients with POLG-related mitochondrial disease that lacked POLG mutations. Of these eight mutations, we biochemically characterized seven variants [c.307G>A (G103S); c.457C>G (L153V); c.614C>G (P205R); c.1105A>G (R369G); c.1158T>G (D386E); c.1268C>A (S423Y); c.1423_1424delTT (L475DfsX2)] that were previously uncharacterized along with the wild-type protein and the G451E pathogenic variant. These seven mutations encode amino acid substitutions that map throughout the protein, including the p55 dimer interface and the C-terminal domain that interacts with the catalytic subunit. Recombinant proteins harboring these alterations were assessed for stimulation of processive DNA synthesis, binding to the p140 catalytic subunit, binding to dsDNA and self-dimerization. Whereas the G103S, L153V, D386E and S423Y proteins displayed wild-type behavior, the P205R and R369G p55 variants had reduced stimulation of processivity and decreased affinity for the catalytic subunit. Additionally, the L475DfsX2 variant, which possesses a C-terminal truncation, was unable to bind the p140 catalytic subunit, unable to bind dsDNA and formed aberrant oligomeric complexes. Our biochemical analysis helps explain the pathogenesis of POLG2 mutations in mitochondrial disease and emphasizes the need to quantitatively characterize the biochemical consequences of newly discovered mutations before classifying them as pathogenic.
C1 [Li, Fang-Yuan; Wong, Lee-Jun] Baylor Coll Med, Dept Mol & Human Genet, Mitochondrial Diagnost Lab, Houston, TX 77030 USA.
[Young, Matthew J.; Longley, Matthew J.; Kasiviswanathan, Rajesh; Copeland, William C.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Wong, LJ (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Mitochondrial Diagnost Lab, 1 Baylor Plaza,NAB 2015, Houston, TX 77030 USA.
EM ljwong@bcm.edu; copelan1@niehs.nih.gov
RI Kasiviswanathan, Rajesh/D-2744-2012
FU NIH, National Institute of Environmental Health Sciences [ES 065078]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (ES 065078).
NR 46
TC 26
Z9 26
U1 0
U2 1
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 AUG 1
PY 2011
VL 20
IS 15
BP 3052
EP 3066
DI 10.1093/hmg/ddr209
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 790AD
UT WOS:000292560000014
PM 21555342
ER
PT J
AU Chellas-Gery, B
Wolf, K
Tisoncik, J
Hackstadt, T
Fields, KA
AF Chellas-Gery, B.
Wolf, K.
Tisoncik, J.
Hackstadt, T.
Fields, K. A.
TI Biochemical and Localization Analyses of Putative Type III Secretion
Translocator Proteins CopB and CopB2 of Chlamydia trachomatis Reveal
Significant Distinctions
SO INFECTION AND IMMUNITY
LA English
DT Article
ID OUTER-MEMBRANE PROTEIN; EARLY-CYCLE DEVELOPMENT; GENOME SEQUENCE;
DEVELOPMENTAL CYCLE; EFFECTOR PROTEINS; INCLUSION MEMBRANE;
PLASMA-MEMBRANE; PNEUMONIAE; SYSTEM; IDENTIFICATION
AB Chlamydia spp. are among the many pathogenic Gram-negative bacteria that employ a type III secretion system (T3SS) to overcome host defenses and exploit available resources. Significant progress has been made in elucidating contributions of T3S to the pathogenesis of these medically important, obligate intracellular parasites, yet important questions remain. Chief among these is how secreted effector proteins traverse eukaryotic membranes to gain access to the host cytosol. Due to a complex developmental cycle, it is possible that chlamydiae utilize a different complement of proteins to accomplish translocation at different stages of development. We investigated this possibility by extending the characterization of C. trachomatis CopB and CopB2. CopB is detected early during infection but is depleted and not detected again until about 20 h postinfection. In contrast, CopB2 was detectible throughout development. CopB is associated with the inclusion membrane. Biochemical and ectopic expression analyses were consistent with peripheral association of CopB2 with inclusion membranes. This interaction correlated with development and required both chlamydial de novo protein synthesis and T3SS activity. Collectively, our data indicate that it is unlikely that CopB serves as the sole chlamydial translocation pore and that CopB2 is capable of association with the inclusion membrane.
C1 [Chellas-Gery, B.; Wolf, K.; Fields, K. A.] Univ Miami, Dept Microbiol & Immunol, Miller Sch Med, Miami, FL 33101 USA.
[Tisoncik, J.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Hackstadt, T.] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Fields, KA (reprint author), Univ Miami, Dept Microbiol & Immunol, Miller Sch Med, Miami, FL 33101 USA.
EM Kfields@med.miami.edu
FU National Institutes of Health, NIAID [AI065530]
FX This work was supported by Public Health Service grants from the
National Institutes of Health, NIAID (AI065530), to K. Fields. T.
Hackstadt was supported by the Intramural Research Program of the
NIAID/NIH.
NR 59
TC 11
Z9 11
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 AUG
PY 2011
VL 79
IS 8
BP 3036
EP 3045
DI 10.1128/IAI.00159-11
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 792SS
UT WOS:000292770300008
PM 21606186
ER
PT J
AU Ziegler, AG
Pflueger, M
Winkler, C
Achenbach, P
Akolkar, B
Krischer, JP
Bonifacio, E
AF Ziegler, Anette-G.
Pflueger, Maren
Winkler, Christiane
Achenbach, Peter
Akolkar, Beena
Krischer, Jeffrey P.
Bonifacio, Ezio
TI Accelerated progression from islet autoimmunity to diabetes is causing
the escalating incidence of type 1 diabetes in young children
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE Type 1 diabetes; Islet autoimmunity; Incidence; Progression
ID ANTIBODY STANDARDIZATION PROGRAM; GLUTAMIC-ACID DECARBOXYLASE; GUERIN
VACCINATION; POSITIVE RELATIVES; FINNISH CHILDREN; AUTOANTIBODIES;
PREDICTION; ASSAYS; ONSET; RISK
AB The incidence of type 1 diabetes is rising worldwide, particularly in young children. Since type 1 diabetes is preceded by autoimmunity to islet antigens, there must be a consequent increase in the incidence of islet autoimmunity in young children or a more rapid rate of progression to diabetes once islet autoimmunity initiates. This study was to determine whether the incidence of islet autoimmunity or the rate of progression from autoimmunity to diabetes onset has changed over a 20-year period in children genetically predisposed to type 1 diabetes. Between 1989 and 2010, children who were first-degree relatives of patients with type 1 diabetes and who were born in Germany were prospectively followed from birth without intervention. A total of 324 children (BABYDIAB study) born between 1989 and 2000 and 216 children (TEDDY study) born between 2004 and 2010 with matched HLA genotypes were recruited before age 3 months and included for analysis. Children were followed for the development of autoantibodies to insulin, GAD, and IA-2, and for progression to diabetes. The cumulative frequency of diabetes by age 4 years was 2.5% (95% CI 0.8-4.2%) in BABYDIAB children and 6.2% (95% CI 2.3-10.1%) in TEDDY children (p = 0.03). The cumulative frequency of islet autoantibodies by age 4 years was similar in the children from both studies (11.3% vs 13.9%). Progression to diabetes from the development of islet autoantibodies was markedly increased in autoantibody-positive children from the more recently recruited TEDDY cohort (50% progression within 85.2 months for BABYDIAB children vs 9.6 months for TEDDY children: p = 0.009), also if children were further selected on the basis of high-risk HLA genotypes or the development of autoantibodies to multiple islet antigens (p = 0.01). The findings suggest that recent increasing incidence of type 1 diabetes in young children could be due to weakening of mechanisms that normally regulate autoimmune destruction of islet beta cells. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Ziegler, Anette-G.; Achenbach, Peter] Helmholtz Ctr Munich, Diabet Res Inst, D-85764 Neuherberg, Germany.
[Ziegler, Anette-G.; Pflueger, Maren; Winkler, Christiane; Achenbach, Peter] Helmholtz Ctr Munich, Forschergrp Diabet eV, D-85764 Neuherberg, Germany.
[Akolkar, Beena] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA.
[Krischer, Jeffrey P.] Univ S Florida, Coll Med, Dept Pediat, Tampa, FL 33612 USA.
[Bonifacio, Ezio] Tech Univ Dresden, Ctr Regenerat Therapies Dresden, D-01307 Dresden, Germany.
RP Ziegler, AG (reprint author), Helmholtz Ctr Munich, Diabet Res Inst, Ingolstaedter Landstr 1, D-85764 Neuherberg, Germany.
EM anziegler@lrz.uni-muenchen.de
RI Bonifacio, Ezio/E-7700-2010; Ziegler, Anette-Gabriele/M-4614-2014;
Achenbach, Peter/M-9867-2014
OI Bonifacio, Ezio/0000-0002-8704-4713; Ziegler,
Anette-Gabriele/0000-0002-6290-5548; Achenbach,
Peter/0000-0001-6720-2684
FU German Federal Ministry of Education and Research (BMBF) [BABYDIAB
01KD89030, 1KD9601, FKZ 01GI0805-07]; Juvenile Diabetes Research
Foundation (BABYDIAB) [JDRF 1-2006-665, P.A. 11-2005-1117]; National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [63829,
63861, 63821, 63865, 63863, 63836, 63790]; DFG-Center for Regenerative
Therapies Dresden, Cluster of Excellence [FZ 111]
FX This study was supported by grants from the German Federal Ministry of
Education and Research (BMBF, BABYDIAB 01KD89030 and 1KD9601, and
Competence Network for Diabetes mellitus FKZ 01GI0805-07), by the
Juvenile Diabetes Research Foundation (BABYDIAB JDRF 1-2006-665, P.A.
11-2005-1117), and by the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK, 63829, 63861, 63821, 63865, 63863, 63836 and
63790). Ezio Bonifacio is supported by the DFG-Center for Regenerative
Therapies Dresden, Cluster of Excellence (FZ 111).
NR 23
TC 40
Z9 41
U1 0
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
J9 J AUTOIMMUN
JI J. Autoimmun.
PD AUG
PY 2011
VL 37
IS 1
BP 3
EP 7
DI 10.1016/j.jaut.2011.02.004
PG 5
WC Immunology
SC Immunology
GA 792CC
UT WOS:000292717100002
PM 21376535
ER
PT J
AU Dautin, N
Bernstein, HD
AF Dautin, Nathalie
Bernstein, Harris D.
TI Residues in a Conserved alpha-Helical Segment Are Required for Cleavage
but Not Secretion of an Escherichia coli Serine Protease Autotransporter
Passenger Domain
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID OUTER-MEMBRANE; BACTERIAL AUTOTRANSPORTER; TRANSLOCATOR DOMAIN;
CRYSTAL-STRUCTURE; VIRULENCE FACTOR; PROTEINS; IDENTIFICATION;
BIOGENESIS; MECHANISM; DETERMINANTS
AB Autotransporters are a superfamily of virulence factors produced by Gram-negative bacteria that are comprised of an N-terminal extracellular domain (passenger domain) and a C-terminal beta barrel domain (beta domain) that resides in the outer membrane (OM). The beta domain promotes the translocation of the passenger domain across the OM by an unknown mechanism. Available evidence indicates that an alpha-helical segment that spans the passenger domain-beta domain junction is embedded inside the beta domain at an early stage of assembly. Following its secretion, the passenger domain of the serine protease autotransporters of the Enterobacteriaceae (SPATEs) and the pertactin family of Bordetella pertussis autotransporters is released from the beta domain through an intrabarrel autoproteolytic cleavage of the alpha-helical segment. Although the mutation of conserved residues that surround the cleavage site has been reported to impair both the translocation and cleavage of the passenger domain of a SPATE called Tsh, we show here that the mutation of the same residues in another SPATE (EspP) affects only passenger domain cleavage. Our results strongly suggest that the conserved residues are required to position the alpha-helical segment for the cleavage reaction and are not required to promote passenger domain secretion.
C1 [Dautin, Nathalie; Bernstein, Harris D.] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 5,Room 201, Bethesda, MD 20892 USA.
EM harris_bernstein@nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 40
TC 9
Z9 9
U1 2
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD AUG
PY 2011
VL 193
IS 15
BP 3748
EP 3756
DI 10.1128/JB.05070-11
PG 9
WC Microbiology
SC Microbiology
GA 791WF
UT WOS:000292698100007
PM 21642456
ER
PT J
AU Zhang, YJ
Kao, WWY
Pelosi, E
Schlessinger, D
Liu, CY
AF Zhang, Yujin
Kao, Winston W. -Y.
Pelosi, Emanuele
Schlessinger, David
Liu, Chia-Yang
TI Notch gain of function in mouse periocular mesenchyme downregulates
FoxL2 and impairs eyelid levator muscle formation, leading to congenital
blepharophimosis
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE BPES; FoxL2; Neural crest; Notch signaling; Eyelid; Morphogenesis
ID TRANSCRIPTION FACTOR FOXL2; TRANSGENIC MICE; CELL DIFFERENTIATION;
INVERSUS SYNDROME; GENE; PROLIFERATION; EXPRESSION; COMPLEX
AB Notch signaling is pivotal for the morphogenesis and homeostasis of many tissues. We found that aberrant Notch activation in mouse neural-crest-derived periocular mesenchymal cells (POMCs), which contribute to the formation of corneal and eyelid stroma, results in blepharophimosis. Compound transgenic mice overexpressing the Notch1 intracellular domain (N1-ICD) in POMCs (POMC(N1-ICD)) showed relatively minor effects on the cornea, but increased cell apoptosis and decreased cell proliferation during eyelid morphogenesis. Eyelid closure at E15.5 and eyelid formation at birth were incomplete. In further analyses, overexpression of N1-ICD impaired eyelid levator smooth muscle formation by downregulating the transcription factor FoxL2. This is similar to the effect of haploinsufficiency of FOXL2 in humans, which results in type II BPES (blepharophimosis, ptosis and epicanthus inversus syndrome). In vitro studies showed that FoxL2 expression is augmented by a low dose of N1-ICD but was downregulated by a high dose, depending on the extent of Hes-1 and Hey-1 activation. Moreover, transfection of CMV-FoxL2 enhanced alpha-SMA promoter activity. These data strongly imply that a physiologically low level of Notch1 is crucial for proper FoxL2 expression in POMCs, which is, in turn, essential for Mueller muscle formation and normal eyelid development.
C1 [Zhang, Yujin; Kao, Winston W. -Y.; Liu, Chia-Yang] Univ Cincinnati, Edith J Crawley Vis Res Ctr, Dept Ophthalmol, Coll Med, Cincinnati, OH 45267 USA.
[Pelosi, Emanuele; Schlessinger, David] NIA, Genet Lab, NIH Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Liu, CY (reprint author), Univ Cincinnati, Edith J Crawley Vis Res Ctr, Dept Ophthalmol, Coll Med, Cincinnati, OH 45267 USA.
EM Liucg@uc.edu
OI Pelosi, Emanuele/0000-0003-1890-9821
FU NIH/NEI RO1 [EY12486, EY13755]; Research Prevent Blindness; Ohio Lions
Foundation for Eye Research; NIH, National Institute on Aging
FX We thank the reviewers for their instructive comments and suggestions.
We thank Nadean Brown (Cincinnati Childrens Hospital) for providing the
anti-Hes-1 antibody. This work was supported by grants from NIH/NEI RO1
# EY12486 (C.Y.L.) and EY13755 (W.W.K.), Research Prevent Blindness,
Ohio Lions Foundation for Eye Research, and the Intramural Research
Program of the NIH, National Institute on Aging. Deposited in PMC for
release after 12 months.
NR 35
TC 10
Z9 10
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 AUG 1
PY 2011
VL 124
IS 15
BP 2561
EP 2572
DI 10.1242/jcs.085001
PG 12
WC Cell Biology
SC Cell Biology
GA 793LA
UT WOS:000292822400006
PM 21730020
ER
PT J
AU Cawley, NX
Portela-Gomes, G
Lou, H
Loh, YP
AF Cawley, Niamh X.
Portela-Gomes, Guida
Lou, Hong
Loh, Y. Peng
TI Yapsin 1 immunoreactivity in alpha-cells of human pancreatic islets:
implications for the processing of human proglucagon by mammalian
aspartic proteases
SO JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; LOBE SECRETORY VESICLES; CONVERTING-ENZYME;
SACCHAROMYCES-CEREVISIAE; PRO-OPIOMELANOCORTIN; FUNCTIONAL-ROLE; YEAST;
PROHORMONE; CLEAVAGE; PITUITARY
AB Yapsin 1 is an aspartic protease from Saccharomyces cerevisiae and belongs to a class of aspartic proteases that demonstrate specificity for basic amino acids. It is capable of processing prohormone substrates at specific basic residue cleavage sites, similar to that of the prohormone convertases, to generate bioactive peptide hormones. An antibody raised against yapsin 1 was previously shown to immunostain endocrine cells of rat pituitary and brain as well as lysates from bovine pituitary secretory granules demonstrating the existence of yapsin 1-like aspartic proteases in mammalian endocrine tissues, potentially involved in peptide hormone production. Here, we show the specific staining of yapsin 1 immunoreactivity in the alpha-cells of human pancreatic islets. No staining was observed in the beta- or delta-cells, indicating a specificity of the staining for glucagon-producing and not insulin-or somatostatin-producing cells. Purified yapsin 1 was also shown to process proglucagon into glucagon in vitro, demonstrating that the prototypical enzyme of this subclass of enzymes can correctly process proglucagon to glucagon. These findings suggest the existence of a yapsin 1-like enzyme exclusively in the alpha-cells of the islets of Langerhans in humans, which may play a role in the production of glucagon in that tissue. Journal of Endocrinology (2011) 210, 181-187
C1 [Cawley, Niamh X.; Lou, Hong; Loh, Y. Peng] Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Portela-Gomes, Guida] Univ Lisbon, Dept Gastroenterol, P-1699 Lisbon, Portugal.
RP Cawley, NX (reprint author), Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
EM cawleyn@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH
FX This research is supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH.
NR 35
TC 3
Z9 3
U1 0
U2 1
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 AUG
PY 2011
VL 210
IS 2
BP 181
EP 187
DI 10.1530/JOE-11-0121
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 792QR
UT WOS:000292764400007
PM 21632904
ER
PT J
AU Zaykin, DV
AF Zaykin, D. V.
TI Optimally weighted Z-test is a powerful method for combining
probabilities in meta-analysis
SO JOURNAL OF EVOLUTIONARY BIOLOGY
LA English
DT Article
DE combining P-values; meta-analysis
ID INDEPENDENT TESTS; P-VALUES
AB The inverse normal and Fisher's methods are two common approaches for combining P-values. Whitlock demonstrated that a weighted version of the inverse normal method, or 'weighted Z-test', is superior to Fisher's method for combining P-values for one-sided T-tests. The problem with Fisher's method is that it does not take advantage of weighting and loses power to the weighted Z-test when studies are differently sized. This issue was recently revisited by Chen, who observed that Lancaster's variation of Fisher's method had higher power than the weighted Z-test. Nevertheless, the weighted Z-test has comparable power to Lancaster's method when its weights are set to square roots of sample sizes. Power can be further improved when additional information is available. Although there is no single approach that is the best in every situation, the weighted Z-test enjoys certain properties that make it an appealing choice as a combination method for meta-analysis.
C1 [Zaykin, D. V.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Zaykin, DV (reprint author), NIEHS, NIH, 111 TW Alexander Dr,South Bldg 101,Mail Drop A3-0, Res Triangle Pk, NC 27709 USA.
EM zaykind@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences. I express my
appreciation for comments and suggestions by Professors Michael Whitlock
and Allen Moore and by an anonymous reviewer.
NR 13
TC 41
Z9 41
U1 2
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1010-061X
EI 1420-9101
J9 J EVOLUTION BIOL
JI J. Evol. Biol.
PD AUG
PY 2011
VL 24
IS 8
BP 1836
EP 1841
DI 10.1111/j.1420-9101.2011.02297.x
PG 6
WC Ecology; Evolutionary Biology; Genetics & Heredity
SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics &
Heredity
GA 791WN
UT WOS:000292699200021
PM 21605215
ER
PT J
AU Mei, H
Rice, TK
Gu, D
Hixson, JE
Jaquish, CE
Zhao, Q
Chen, JC
Cao, J
Li, J
Kelly, TN
Rao, DC
He, J
AF Mei, H.
Rice, T. K.
Gu, D.
Hixson, J. E.
Jaquish, C. E.
Zhao, Qi
Chen, J-C
Cao, J.
Li, J.
Kelly, T. N.
Rao, D. C.
He, J.
TI Genetic correlation of blood pressure responses to dietary sodium and
potassium intervention and cold pressor test in chinese population
SO JOURNAL OF HUMAN HYPERTENSION
LA English
DT Article
DE blood pressure; cold pressor test; salt sensitivity; heritability;
genetic correlation
ID CARDIOVASCULAR RISK-FACTORS; TRAIT LINKAGE ANALYSIS; SALT-SENSITIVITY;
HYPERTENSION; HERITABILITY; POLYMORPHISMS; METAANALYSIS; PREDICTOR;
INTERSALT; AMERICANS
AB We examined the genetic association between blood pressure (BP) responses to dietary sodium and potassium intervention and to cold pressor test (CPT) in a large family-based dietary feeding study. The dietary intervention and CPT were conducted among 1906 participants in rural China. The dietary intervention included three 7-day periods of low-sodium feeding (51.3mmol per day), high-sodium feeding (307.8mmol per day) and high-sodium feeding plus potassium supplementation (60 mmol per day). BP responses to high-sodium intervention had strong genetic correlations (rho(G)) with both BP responses to low sodium (rho(G) = -0.43 to -0.54, P-values = 0.0005 to 0.03) and to potassium supplementation (rho(G) = 0.41 to -0.49, P-values = 0.001 to 0.005) interventions. Most environmental correlations between BP responses to various dietary interventions were significant. The rho(G) between BP responses to CPT and to high-sodium intervention and potassium supplementation were statistically significant. For example, the rho(G) between maximum BP responses to CPT and BP responses to high-sodium intervention was 0.37 (P = 0.006) for systolic BP (SBP) and 0.41 (P = 0.002) for diastolic BP (DBP). The rho(G) between maximum BP responses to CPT and BP responses to potassium intervention was -0.42 (P = 0.001) for SBP and -0.46 (P = 0.001) for SBP. Our study suggests that there are common genetic determinants that influence BP responses to dietary sodium and potassium interventions and to CPT. Journal of Human Hypertension (2011) 25, 500-508; doi: 10.1038/jhh.2010.88; published online 23 September 2010
C1 [Mei, H.; Zhao, Qi; Kelly, T. N.; He, J.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA.
[Rice, T. K.; Rao, D. C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Gu, D.; Chen, J-C; Cao, J.; Li, J.] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100730, Peoples R China.
[Gu, D.; Chen, J-C; Cao, J.; Li, J.] Chinese Acad Med Sci, Fu Wai Hosp, Beijing 100730, Peoples R China.
[Gu, D.; Chen, J-C; Cao, J.; Li, J.] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Gu, D.; Chen, J-C; Cao, J.; Li, J.] Chinese Natl Ctr Cardiovasc Dis, Beijing, Peoples R China.
[Hixson, J. E.] Univ Texas Sch Publ Hlth, Dept Epidemiol, Houston, TX USA.
[Jaquish, C. E.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Mei, H (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1440 Canal St,Suite 2000, New Orleans, LA 70112 USA.
EM hmei@tulane.edu
FU National Heart, Lung and Blood Institute, National Institutes of Health,
Bethesda, Maryland [U01HL072507, R01HL087263, R01HL090682]
FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is
supported by research grants (U01HL072507, R01HL087263 and R01HL090682)
from the National Heart, Lung and Blood Institute, National Institutes
of Health, Bethesda, Maryland. Upsher-Smith Laboratories Inc has
provided Klor-Con M20 potassium tablets for the GenSalt study.
NR 36
TC 3
Z9 4
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9240
J9 J HUM HYPERTENS
JI J. Hum. Hypertens.
PD AUG
PY 2011
VL 25
IS 8
BP 500
EP 508
DI 10.1038/jhh.2010.88
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 792FD
UT WOS:000292725000006
PM 20861867
ER
PT J
AU Park, S
Park, JB
Lakatta, EG
AF Park, Sungha
Park, Jeong B.
Lakatta, Edward G.
TI Association of central hemodynamics with estimated 24-h urinary sodium
in patients with hypertension
SO JOURNAL OF HYPERTENSION
LA English
DT Article
DE central pulse pressure; hypertension; pulse pressure amplification;
sodium
ID PREDICTS CARDIOVASCULAR EVENTS; PULSE PRESSURE AMPLIFICATION; MODEST
SALT REDUCTION; BLOOD-PRESSURE; WAVE REFLECTIONS; ARTERIAL
DISTENSIBILITY; STIFFNESS; DISEASE; POPULATION; EXCRETION
AB Objective High salt intake is known to be the most pivotal environmental factor in the pathogenesis of hypertension. However, the association of high sodium intake with central hemodynamics in hypertensive individuals has not been well defined. Here, we determined the association of estimated 24-h urine sodium and potassium excretion estimated from a spot urine analysis with parameters of central pulse wave analysis in 515 hypertensive individuals.
Methods Fasting spot urine samples were obtained in the early morning after the first void, and estimated 24-h urine sodium and potassium excretion were estimated from measurement of urine sodium, potassium and creatinine. Central hemodynamics and arterial stiffness parameters were assessed via pulse wave analysis of the radial artery.
Results The estimated 24-h sodium and potassium excretion values were 150+/-40 and 49+/-10 mEq, respectively. There was a step-wise decrease in pulse pressure amplification with increasing estimated 24-h urine sodium excretion. Multiple linear regression analyses revealed that both estimated 24-h urine sodium excretion and sodium/potassium ratio were independently associated with increases in central pulse pressure, augmented aortic pressure and augmentation index and were inversely associated with pulse pressure amplification.
Conclusion The estimated 24-h urinary sodium excretion is independently associated with central hemodynamics. This may provide the basis for prospective interventional studies of epidemiologic scale to determine the potential beneficial effects of reduced salt consumption on central hemodynamics. J Hypertens 29: 1502-1507 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
C1 [Park, Jeong B.] Kwandong Univ, Coll Med, Cheil Gen Hosp, Div Cardiol, Seoul 100380, South Korea.
[Park, Sungha] Yonsei Univ, Coll Med, Ctr Cardiovasc, Div Cardiol, Seoul 120749, South Korea.
[Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA.
RP Park, JB (reprint author), Kwandong Univ, Coll Med, Cheil Gen Hosp, Div Cardiol, 1-19 Mukjung Dong, Seoul 100380, South Korea.
EM mdparkjb@gmail.com
FU Ministry of Education, Science and Technology, Republic of Korea
[2010-0020766]; NIH, National Institute on Aging
FX This study was supported by a grant (2010-0020766) from the Public
Welfare and Safety Research Program through the National Research
Foundation of Korea (NRF) funded by the Ministry of Education, Science
and Technology, Republic of Korea and, in part, by the Intramural
Research Program of the NIH, National Institute on Aging.
NR 29
TC 21
Z9 21
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0263-6352
J9 J HYPERTENS
JI J. Hypertens.
PD AUG
PY 2011
VL 29
IS 8
BP 1502
EP 1507
DI 10.1097/HJH.0b013e3283486311
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 791TL
UT WOS:000292688400007
PM 21666493
ER
PT J
AU Vaccarella, S
Franceschi, S
Herrero, R
Schiffman, M
Rodriguez, AC
Hildesheim, A
Burk, RD
Plummer, M
AF Vaccarella, Salvatore
Franceschi, Silvia
Herrero, Rolando
Schiffman, Mark
Rodriguez, Ana Cecilia
Hildesheim, Allan
Burk, Robert D.
Plummer, Martyn
TI Clustering of Multiple Human Papillomavirus Infections in Women From a
Population-Based Study in Guanacaste, Costa Rica
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID HPV TYPES; CERVICAL COINFECTION; PREVALENCE SURVEYS; POOLED ANALYSIS;
DNA DETECTION; CLUSTAL-W; ACQUISITION; PERSISTENCE; RISK; CONCURRENT
AB Objective. To evaluate clustering patterns of prevalent infection with multiple human papillomavirus (HPV) types in 8365 nonhysterectomized women from the Guanacaste Study of HPV Natural History.
Methods. HPV testing was performed on cervical cells by MY09/M11 L1 degenerate consensus primer polymerase chain reaction method, with dot-blot hybridization for genotyping. Logistic regression was used to model type-specific HPV positivity, adjusted for age, lifetime number of sexual partners, and specific HPV type prevalence. Woman-level random effects were added to represent unobservable risk factors common to all HPV types.
Results. The observed-to-expected ratio for infections with 2 types was 1.16 (95% credible interval: 1.11-1.21), and for >= 3 types was 1.04 (95% credible interval: .96-1.13). The tendency of HPV types to cluster increased significantly with the genetic similarity of L1 regions. P value < .01 was observed for 2 HPV pairs: HPV-62 and -81 were found together more, while HPV-51 and -71 were found together less often than expected.
Conclusions. We found a small degree of aggregation between any HPV types and lack of clustering between specific carcinogenic types. Our data indirectly provide reassurance on lack of misclassification for the large majority of HPV types in multiple infections detected by the MY09/11 method and genotyped using dot-blot hybridization.
C1 [Vaccarella, Salvatore; Franceschi, Silvia; Plummer, Martyn] Int Agcy Res Canc, F-69372 Lyon 08, France.
[Herrero, Rolando; Rodriguez, Ana Cecilia] Fdn Inst Costarricense Invest & Ensenanza Nutr &, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica.
[Schiffman, Mark; Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Burk, Robert D.] Albert Einstein Coll Med, New York, NY USA.
RP Vaccarella, S (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
EM vaccarella@iarc.fr
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services [NO1-CP-21081, NO1-CP-33061, NO1-CP-40542,
NO1-CP-506535]; Intramural Research Program of the National Cancer
Institute; National Cancer Institute [CA78527]
FX The Guanacaste Project was supported by the National Cancer Institute,
National Institutes of Health, Department of Health and Human Services
contracts (NO1-CP-21081, NO1-CP-33061, NO1-CP-40542, and NO1-CP-506535).
A. H. and M. S. were supported by the Intramural Research Program of the
National Cancer Institute. R. D. B. was supported by the National Cancer
Institute (grant CA78527) and used the facilities available through the
Einstein Cancer Research Center and the Center for AIDS Research.
NR 25
TC 28
Z9 29
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 1
PY 2011
VL 204
IS 3
BP 385
EP 390
DI 10.1093/infdis/jir286
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 790BA
UT WOS:000292562300011
PM 21742837
ER
PT J
AU Marincola, FM
AF Marincola, Francesco M.
TI The trouble with translational medicine
SO JOURNAL OF INTERNAL MEDICINE
LA English
DT Article
DE Biomedical research; clinical research; translational medicine;
translational research
ID IMMUNOTHERAPY; IMMUNOLOGY; REJECTION; SCIENCE; RELEVANCE; MELANOMA;
VACCINE
AB Increasingly more reports in the literature are reflecting on the hurdles of effective translation from promising results of biomedical research into useful therapeutics. A recurrent theme is that good intentions are frustrated by extrinsic factors upon which 'translationalists' have little control. It is possible that the problem resides, at least in part, within the translational community itself, which has failed to prioritize the steps required to approach the problem systematically. Most importantly, there is disproportionate emphasis on bench-to-bedside efforts, rather than confronting a priori the need to increase the understanding of human pathophysiology. Thus, therapeutic concepts based on experimental conditions that may not and indeed often do not represent the nature of human genetics lead to drug development that isnot sufficiently applicable to the human condition. The damage is then amplified when these ill-fated concepts are tested in clinical trials at great cost. The use of surrogate biomarkers that could allow early assessment of efficacy currently requires long-term assessment of clinical benefit. This can delay by years or decades essential feedback about clinical efficacy. Moreover, scant effort is applied to learning whether a drug has achieved its biological endpoint, or why it failed its clinical endpoint. Thus, the feedback loop is not only delayed, but is often uninformative. As a consequence, researchers continue to produce novel therapeutic candidates based on experimental models without the essential benefit of lessons learned from previous failures. Biomedical research will succeed when drug development is guided by experience gained through informative clinical trials with the purpose of not only testing the effectiveness of treatment but also providing mechanistic insights into the differences between expected and observed results. This can only be achieved through the courageous effort of the research community to change the way biomedical research is funded, published and rewarded.
C1 [Marincola, Francesco M.] NIH, Infect Dis Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Marincola, Francesco M.] NIH, NIH Ctr Human Immunol, Bethesda, MD 20892 USA.
RP Marincola, FM (reprint author), NIH, Infect Dis Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1N226, Bethesda, MD 20892 USA.
EM FMarincola@mail.cc.nih.gov
NR 28
TC 22
Z9 24
U1 0
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0954-6820
J9 J INTERN MED
JI J. Intern. Med.
PD AUG
PY 2011
VL 270
IS 2
BP 123
EP 127
DI 10.1111/j.1365-2796.2011.02402.x
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 791FJ
UT WOS:000292649800004
PM 21575085
ER
PT J
AU Schiller, JT
Buck, CB
AF Schiller, John T.
Buck, Christopher B.
TI Cutaneous Squamous Cell Carcinoma: A Smoking Gun but Still No Suspects
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Editorial Material
ID SKIN-CANCER; POLYOMAVIRUS
AB A viral etiology for cutaneous squamous cell carcinoma (cuSCC) has long been suspected, primarily on the basis of its dramatically increased incidence in immunocompromised individuals. In this issue, Arron and colleagues report a comprehensive hunt for viral gene transcription in cuSCC. Their findings show that it is very unlikely that any currently known virus is commonly responsible for the maintenance of this cancer.
C1 [Schiller, John T.; Buck, Christopher B.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
EM schillej@mail.nih.gov
OI Buck, Christopher/0000-0003-3165-8094
NR 10
TC 8
Z9 8
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD AUG
PY 2011
VL 131
IS 8
BP 1595
EP 1596
DI 10.1038/jid.2011.151
PG 2
WC Dermatology
SC Dermatology
GA 792HA
UT WOS:000292731100004
PM 21753763
ER
PT J
AU Kautz-Neu, K
Kostka, SL
Dinges, S
Iwakura, Y
Udey, MC
von Stebut, E
AF Kautz-Neu, Kordula
Kostka, Susanna Lopez
Dinges, Stephanie
Iwakura, Yoichiro
Udey, Mark C.
von Stebut, Esther
TI A Role for Leukocyte-Derived IL-1RA in DC Homeostasis Revealed by
Increased Susceptibility of IL-1RA-Deficient Mice to Cutaneous
Leishmaniasis
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID DELAYED-TYPE HYPERSENSITIVITY; ANTAGONIST-DEFICIENT MICE; RECEPTOR
ANTAGONIST; DENDRITIC CELLS; MAJOR INFECTION; GRANULOMA-FORMATION;
CYTOKINE PRODUCTION; C57BL/6 MICE; BALB/C MICE; TNF-ALPHA
AB Dendritic cell (DC)-derived IL-1 alpha/beta plays a critical role in the induction of T helper type 1 (Th1)-dependent immunity against Leishmania. DCs from susceptible BALB/c mice produce less IL-1 alpha/beta when compared with resistant C57BL/6 mice, contributing to aberrant Th2 development and ultimate death of infected mice. We have extended our studies of the role of IL-1 in leishmaniasis using IL-1RA(-/-) BALB/c mice that are characterized by upregulated IL-1 receptor signaling. Unexpectedly, infection of IL-1RA(-/-) mice led to significantly worsened disease outcome with larger lesions, dramatically higher parasite burdens, and decreased IFN-gamma production by antigen-specific T cells. We determined that IL-1RA(-/-) DCs were more mature already in the steady state, exhibited less phagocytotic capacity, and IL-12 production in response to various stimuli was impaired. Our data suggest that in addition to effects on Th education, IL-1 alpha/beta signaling also modulates DC homeostasis with increased signaling, leading to downmodulation of IL-12 synthesis and worsened disease outcome after infection with Leishmania major. Thus, the complex regulation of various members of the IL-1 cytokine family mediated through effects on both DCs and T cells critically contributes to disease outcome against this important human pathogen.
C1 [Kautz-Neu, Kordula; Kostka, Susanna Lopez; Dinges, Stephanie; von Stebut, Esther] Johannes Gutenberg Univ Mainz, Dept Dermatol, D-55131 Mainz, Germany.
[Iwakura, Yoichiro] Univ Tokyo, Inst Med Sci, Ctr Expt Med & Syst Biol, Tokyo, Japan.
[Iwakura, Yoichiro] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol CREST, Saitama, Japan.
[Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP von Stebut, E (reprint author), Johannes Gutenberg Univ Mainz, Dept Dermatol, Langenbeckstr 1, D-55131 Mainz, Germany.
EM vonstebu@uni-mainz.de
RI Iwakura, Yoichiro/E-5457-2011
OI Iwakura, Yoichiro/0000-0002-9934-5775
FU Deutsche Forschungsgemeinschaft (DFG) [SFB490, GK1043, STE833/6-1]
FX We thank Dr Klaus Griewank for help with bone marrow chimeras and Dr
Kurt Reifenberg and staff for excellent assistance in animal
experimentation. This work was supported by grants from the Deutsche
Forschungsgemeinschaft (DFG, SFB490, GK1043, and STE833/6-1, to EvS).
NR 37
TC 5
Z9 5
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD AUG
PY 2011
VL 131
IS 8
BP 1650
EP 1659
DI 10.1038/jid.2011.99
PG 10
WC Dermatology
SC Dermatology
GA 792HA
UT WOS:000292731100013
PM 21525884
ER
PT J
AU Ahmet, I
Tae, HJ
de Cabo, R
Lakatta, EG
Talan, MI
AF Ahmet, Ismayil
Tae, Hyun-Jin
de Cabo, Rafael
Lakatta, Edward G.
Talan, Mark I.
TI Effects of calorie restriction on cardioprotection and cardiovascular
health
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Article
DE Aging; Calorie restriction; Cardioprotection; Myocardial infarction;
Cardiac function; Arterial stiffness
ID DIASTOLIC DYSFUNCTION; RATS; TOLERANCE; PREVENTION; HUMANS; IMPACT; SIZE
AB Multiple health benefits of calorie restriction (CR) and alternate day fasting (ADF) regimens are widely recognized. Experimental data concerning the effects of calorie restriction on cardiac health are more controversial, ranging from evidence that ADF protects heart from ischemic damage but results in developing of diastolic dysfunction, to reports that CR ameliorates the age-associated diastolic dysfunction. Here we investigated the effects of chronic CR on morphology and function of the cardiovascular system of aged rats and cardioprotective effect of CR against ischemic damage in the experimental rat model of MI. Cardiovascular fitness of 24-month old Fisher 344 rats maintained through life on ad libitum (AL) or CR diets was extensively evaluated via echocardiography, dobutamine stress test, pressure-volume loop analyses, pulse wave velocity measurements, and histology. Groups of 2-month old AL and 29-month old CR rats were studied for comparison. Myocardial infarction (MI) was induced by a permanent ligation of the anterior descending coronary artery in 5-month old rats maintained for 3 months on CR or AL MI size was evaluated histologically 24 hrs following coronary ligation. Cardiac remodeling was followed-up via echocardiography. Age-associated changes in 24-month old rats consisted of 33% increase of fibrosis in the myocardium and more than 2 fold increase of the collagen in the tunica media of the aorta. There was a significant decrease in the density and total number of cardiomyocytes, while their size was increased. These morphological changes were manifested in a decline of systolic and diastolic cardiac function, increase of left ventricular and aortic stiffness, and arterio-ventricular uncoupling. Tachycardic response to dobutamine challenge was absent in the old rats. Compared to AL rats, 24-month old CR rats had reduced levels of cardiac and aortic fibrosis, increased density of cardiomyocytes that were smaller in size, attenuated diastolic dysfunction, normal systolic function and arterio-ventricular coupling. Tachycardic response to dobutamine was also intact in CR 24-month old rats and aortic stiffness was reduced. Adjustment for body weight differences through ratiometric or allometric scaling did not affect the overall pattern of differences between AL and CR rats. Attenuation of morphological and functional age-associated changes in 24-month old CR rats either was not observed at all or was smaller in 29-month old CR rats. Size of MI induced by a permanent coronary ligation as well as post-MI cardiac remodeling and function were similar in CR and AL rats. CR does not increase tolerance of myocardium to ischemic damage, but attenuates the age-associated changes in the heart and major vessels. The attenuation of age-associated changes by CR cannot be explained by the effect of lower body weight but are attributable to more intimate cellular mechanisms of CR itself. Attenuation of age-associated changes by CR waned with advancing age, and is consistent with the idea that CR postponed senescence. Published by Elsevier Ltd.
C1 [Ahmet, Ismayil; Tae, Hyun-Jin; Lakatta, Edward G.; Talan, Mark I.] NIA, Lab Cardiovasc Sci, Intramural Res Program, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA.
[de Cabo, Rafael] NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Talan, MI (reprint author), NIA, Lab Cardiovasc Sci, Intramural Res Program, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM talanm@grc.nia.nih.gov
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU National Institute on Aging, NIH
FX This work was fully supported by the Intramural Research Program of the
National Institute on Aging, NIH.
NR 32
TC 29
Z9 30
U1 0
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD AUG
PY 2011
VL 51
IS 2
BP 263
EP 271
DI 10.1016/j.yjmcc.2011.04.015
PG 9
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 790HG
UT WOS:000292578500014
PM 21586294
ER
PT J
AU Stranahan, AM
Cutler, RG
Button, C
Telljohann, R
Mattson, MP
AF Stranahan, Alexis M.
Cutler, Roy G.
Button, Catherine
Telljohann, Richard
Mattson, Mark P.
TI Diet-induced elevations in serum cholesterol are associated with
alterations in hippocampal lipid metabolism and increased oxidative
stress
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE ceramide; cholesterol; high fat diet; hippocampus; sphingomyelin
ID HIGH-FAT DIET; COGNITIVE IMPAIRMENT; NEUROTROPHIC FACTOR;
INSULIN-RESISTANCE; RATS; INVOLVEMENT; CONSUMPTION; PLASTICITY; NEURONS;
DISEASE
AB The structure and function of the hippocampus, a brain region critical for learning and memory, is impaired by obesity and hyperlipidemia. Peripheral cholesterol and sphingolipids increase progressively with aging and are associated with a range of age-related diseases. However, the mechanisms linking peripheral cholesterol metabolism to hippocampal neuroplasticity remain poorly understood. To determine whether diets that elevate serum cholesterol influence lipid metabolism in the hippocampus, we maintained rats on a diet with high amounts of saturated fat and simple sugars for 3 months and then analyzed hippocampal lipid species using tandem mass spectrometry. The high fat diet was associated with increased serum and liver cholesterol and triglyceride levels, and also promoted cholesterol accumulation in the hippocampus. Increases in hippocampal cholesterol were associated with elevated galactosyl ceramide and sphingomyelin. To determine whether changes in lipid composition exerted biological effects, we measured levels of the lipid peroxidation products 4-hydroxynonenal-lysine and 4-hydroxynonenal- histidine; both were increased locally in the hippocampus, indicative of cell membrane-associated oxidative stress. Taken together, these observations support the existence of a potentially pathogenic relationship between dietary fat intake, peripheral cholesterol and triglyceride levels, brain cell sphingolipid metabolism, and oxidative stress.
C1 [Stranahan, Alexis M.; Cutler, Roy G.; Button, Catherine; Telljohann, Richard; Mattson, Mark P.] NIA, Cellular & Mol Neurosci Sect, Neurosci Lab, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Stranahan, AM (reprint author), Georgia Hlth Sci Univ, Dept Physiol, 1120 15th St,Room CA3145, Augusta, GA 30912 USA.
EM astranahan@georgiahealth.edu
RI Mattson, Mark/F-6038-2012
FU National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institute on Aging. The authors have no actual or potential
conflicts of interest.
NR 21
TC 40
Z9 41
U1 0
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2011
VL 118
IS 4
BP 611
EP 615
DI 10.1111/j.1471-4159.2011.07351.x
PG 5
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 792KT
UT WOS:000292744100014
PM 21682722
ER
PT J
AU Watts, AG
Sanchez-Watts, G
Liu, Y
Aguilera, G
AF Watts, Alan G.
Sanchez-Watts, Graciela
Liu, Ying
Aguilera, Greti
TI The Distribution of Messenger RNAs Encoding the Three Isoforms of the
Transducer of Regulated cAMP Responsive Element Binding Protein Activity
in the Rat Forebrain
SO JOURNAL OF NEUROENDOCRINOLOGY
LA English
DT Article
DE gene regulation; transcription factors; neuropeptides; hypothalamus;
telecephalon; energy metabolism
ID CORTICOTROPIN-RELEASING HORMONE; MEDIATED GENE-EXPRESSION; SENSITIVE
COINCIDENCE DETECTOR; CREB COACTIVATOR TORC2; LONG-TERM-MEMORY;
SUPRACHIASMATIC NUCLEUS; ENERGY-BALANCE; KEY REGULATOR; IN-VIVO;
TRANSCRIPTION
AB Increasing evidence indicates that the cAMP responsive element binding protein (CREB)-dependent transcriptional activation of a number of genes requires the CREB co-activator: transducer of regulated CREB activity (TORC). Because of the central importance of CREB in many brain functions, we examined the topographic distribution of TORC1, 2, and 3 mRNAs in specific regions of the rat forebrain. In situ hybridisation analysis revealed that TORC1 is the most abundant isoform in most forebrain structures, followed by TORC2 and TORC3. All three TORC isoforms were found in a number of brain nuclei, the ventricular ependyma and pia mater. Although high levels of TORC1 were widely distributed in the forebrain, TORC2 was found in discrete nuclei and TORC3 mostly in the ependyma, and pia mater. The relative expression of TORC isoforms was confirmed by quantitative reverse transcriptase-polymerase chain reaction analysis in the hippocampus and hypothalamus. In the paraventricular nucleus of the hypothalamus, TORC1 and 2 mRNAs were abundant in the parvicellular and magnocellular neuroendocrine compartments, whereas TORC3 expression was low. All three isoform mRNAs were found elsewhere in the hypothalamus, with the most prominent expression of TORC1 in the ventromedial nucleus, TORC2 in the dorsomedial and arcuate nuclei, TORCs 1 and 2 in the supraoptic nucleus, and TORC2 in the suprachiasmatic nucleus. These differential distribution patterns are consistent with complex roles for all three TORC isoforms in diverse brain structures, and provide a foundation for further studies on the mechanisms of CREB/TORC signalling on brain function.
C1 [Watts, Alan G.; Sanchez-Watts, Graciela] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
[Liu, Ying; Aguilera, Greti] NICHHD, Sect Endocrine Physiol, PDEGEN, Bethesda, MD 20892 USA.
RP Watts, AG (reprint author), Univ So Calif, Dept Biol Sci, Hedco Neurosci Bldg,MC 2520,3641 Watt Way, Los Angeles, CA 90089 USA.
EM watts@usc.edu
FU NINDS [NS029728]; NICHD
FX This project was supported by NINDS NS029728 (A.G.W.) and NICHD
intramural funds (G.A.).
NR 45
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Z9 19
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0953-8194
J9 J NEUROENDOCRINOL
JI J. Neuroendocrinol.
PD AUG
PY 2011
VL 23
IS 8
BP 754
EP 766
DI 10.1111/j.1365-2826.2011.02178.x
PG 13
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 791GV
UT WOS:000292654000010
PM 21679259
ER
PT J
AU Roiser, J
AF Roiser, J.
TI BRIDGING THE GAP BETWEEN GENES AND BEHAVIOUR: THE CASE FOR NEUROIMAGING
GENETICS
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Meeting Abstract
CT Joint Conference of the British-Neuropsychiatry-Association AGM/ Section
of Neuropsychiatry of RCPsych
CY FEB 09-11, 2011
CL Inst Child Hlth, London, ENGLAND
SP British Neuropsychiat Assoc
HO Inst Child Hlth
C1 [Roiser, J.] UCL Inst Cognit Neurosci, London, England.
[Roiser, J.] UCL NIMH NINDS Joint Doctoral Training Program Ne, Bethesda, MD USA.
[Roiser, J.] NIMH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD AUG
PY 2011
VL 82
IS 8
DI 10.1136/jnnp-2011-300504.24
PG 2
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 789TE
UT WOS:000292538400025
ER
PT J
AU Gillinov, AM
Argenziano, M
Blackstone, EH
Iribarne, A
DeRose, JJ
Ailawadi, G
Russo, MJ
Ascheim, DD
Parides, MK
Rodriguez, E
Bouchard, D
Taddei-Peters, WC
Geller, NL
Acker, MA
Gelijns, AC
AF Gillinov, A. Marc
Argenziano, Michael
Blackstone, Eugene H.
Iribarne, Alexander
DeRose, Joseph J., Jr.
Ailawadi, Gorav
Russo, Mark J.
Ascheim, Deborah D.
Parides, Michael K.
Rodriguez, Evelio
Bouchard, Denis
Taddei-Peters, Wendy C.
Geller, Nancy L.
Acker, Michael A.
Gelijns, Annetine C.
TI Designing comparative effectiveness trials of surgical ablation for
atrial fibrillation: Experience of the Cardiothoracic Surgical Trials
Network
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID MITRAL-VALVE SURGERY; RADIOFREQUENCY ABLATION; MAZE PROCEDURE; SOCIETY
AB Objective: Since the introduction of the cut-and-sew Cox maze procedure for atrial fibrillation, there has been substantial innovation in techniques for ablation. Use of alternative energy sources for ablation simplified the procedure and has resulted in dramatic increase in the number of patients with atrial fibrillation treated by surgical ablation. Despite its increasingly widespread adoption, there is lack of rigorous clinical evidence to establish this procedure as an effective clinical therapy.
Methods: This article describes a comparative effectiveness randomized trial, supported by the Cardiothoracic Surgical Clinical Trials Network, of surgical ablation with left atrial appendage closure versus left atrial appendage closure alone in patients with persistent and long-standing persistent atrial fibrillation undergoing mitral valve surgery. Nested within this trial is a further randomized comparison of 2 different lesions sets: pulmonary vein isolation and the full maze lesion set.
Results: This article addresses trial design challenges, including how best to characterize the target population, operationalize freedom from atrial fibrillation as a primary end point, account for the impact of antiarrhythmic drugs, and measure and analyze secondary end points, such as postoperative atrial fibrillation load.
Conclusions: This article concludes by discussing how insights that emerge from this trial may affect surgical practice and guide future research in this area. (J Thorac Cardiovasc Surg 2011;142:257-64)
C1 [Iribarne, Alexander; Ascheim, Deborah D.; Parides, Michael K.; Gelijns, Annetine C.] Mt Sinai Sch Med, InCHOIR, Dept Hlth Evidence & Policy, New York, NY 10029 USA.
[Gillinov, A. Marc; Blackstone, Eugene H.] Cleveland Clin, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA.
[Argenziano, Michael; Russo, Mark J.] Columbia Univ, Med Ctr, Div Cardiothorac Surg, New York, NY USA.
[DeRose, Joseph J., Jr.] Montefiore Einstein Heart Ctr, Dept Cardiovasc & Thorac Surg, New York, NY USA.
[Ailawadi, Gorav] Univ Virginia, Div Thorac & Cardiovasc Surg, Charlottesville, VA USA.
[Rodriguez, Evelio] E Carolina Univ, E Carolina Heart Inst, Dept Cardiovasc Sci, Greenville, NC USA.
[Bouchard, Denis] Univ Montreal, Montreal Heart Inst, Dept Surg, Montreal, PQ, Canada.
[Taddei-Peters, Wendy C.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Geller, Nancy L.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Acker, Michael A.] Univ Penn, Div Cardiovasc Surg, Philadelphia, PA 19104 USA.
RP Gelijns, AC (reprint author), Mt Sinai Sch Med, InCHOIR, Dept Hlth Evidence & Policy, 1 Gustave L Levy Pl,Box 1077, New York, NY 10029 USA.
EM annetine.gelijns@mssm.edu
FU National Heart, Lung and Blood Institute; Canadian Institute of Health
Research; National Institute of Neurological Diseases and Stroke
FX Supported by the National Heart, Lung and Blood Institute, the Canadian
Institute of Health Research, and the National Institute of Neurological
Diseases and Stroke.
NR 18
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Z9 9
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD AUG
PY 2011
VL 142
IS 2
BP 257
EP U380
DI 10.1016/j.jtcvs.2011.04.010
PG 10
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 792UF
UT WOS:000292775200013
PM 21616507
ER
PT J
AU Gardner, TJ
Miller, MA
O'Gara, PT
Gelijns, AC
AF Gardner, Timothy J.
Miller, Marissa A.
O'Gara, Patrick T.
Gelijns, Annetine C.
TI Building an infrastructure for clinical trials in cardiac surgery
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Editorial Material
C1 [Gelijns, Annetine C.] Mt Sinai Sch Med, InCHOIR, Dept Hlth Evidence & Policy, New York, NY 10029 USA.
[Gardner, Timothy J.] Christiana Care Hlth Syst, Ctr Heart & Vasc Hlth, Newark, DE USA.
[Miller, Marissa A.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[O'Gara, Patrick T.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
RP Gelijns, AC (reprint author), Mt Sinai Sch Med, InCHOIR, Dept Hlth Evidence & Policy, New York, NY 10029 USA.
EM annetine.gelijns@mssm.edu
FU NHLBI NIH HHS [U01 HL088942]
NR 5
TC 4
Z9 4
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD AUG
PY 2011
VL 142
IS 2
BP 265
EP 266
DI 10.1016/j.jtcvs.2011.02.035
PG 2
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 792UF
UT WOS:000292775200014
PM 21763873
ER
PT J
AU Kendall, G
Little, MP
Wakeford, R
AF Kendall, Gerald
Little, Mark P.
Wakeford, Richard
TI Numbers and proportions of leukemias in young people and adults induced
by radiation of natural origin
SO LEUKEMIA RESEARCH
LA English
DT Article
DE Leukemia; Natural radiation; Alpha radiation; Gamma radiation
ID BACKGROUND IONIZING-RADIATION; LUNG-CANCER; CHILDHOOD LEUKEMIA;
RESIDENTIAL RADON; INTERNAL EMITTERS; COLLABORATIVE ANALYSIS; INDIVIDUAL
DATA; BOMB SURVIVORS; GREAT-BRITAIN; RISKS
AB Natural sources contribute a large fraction of the radiation exposure of the general public. Under the linear no-threshold hypothesis risk decreases in proportion to decreasing dose without a threshold. We use recent estimates of doses to the red bone marrow to calculate the number and proportion of cases of leukemia in England induced by natural radiation. We calculate that about 5% of cases of leukemia, excluding chronic lymphocytic leukemia, up to the age of 80 years are induced by this background radiation. In young people up to the age of 25 years the attributable fraction is about 15%, substantially lower than a previous estimate. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Kendall, Gerald] Univ Oxford, Childhood Canc Res Grp, Oxford OX3 7LG, England.
[Little, Mark P.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Wakeford, Richard] Univ Manchester, Dalton Nucl Inst, Manchester M13 9PL, Lancs, England.
RP Kendall, G (reprint author), Univ Oxford, Childhood Canc Res Grp, Richards Bldg,Old Rd Campus, Oxford OX3 7LG, England.
EM Gerald.Kendall@ccrg.ox.ac.uk
OI Wakeford, Richard/0000-0002-2934-0987; Little, Mark/0000-0003-0980-7567
FU National Institutes of Health, the National Cancer Institute, Division
of Cancer Epidemiology and Genetics; European Commission [FP6-036465]
FX The work of MPL was supported by the Intramural Research Program of the
National Institutes of Health, the National Cancer Institute, Division
of Cancer Epidemiology and Genetics, and was also funded partially by
the European Commission under contract FP6-036465 (NOTE).
NR 28
TC 7
Z9 8
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2126
J9 LEUKEMIA RES
JI Leuk. Res.
PD AUG
PY 2011
VL 35
IS 8
BP 1039
EP 1043
DI 10.1016/j.leukres.2011.01.023
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 792ID
UT WOS:000292735300012
PM 21334745
ER
PT J
AU Boutin, A
Allen, MD
Geras-Raaka, E
Huang, WW
Neumann, S
Gershengorn, MC
AF Boutin, Alisa
Allen, Michael D.
Geras-Raaka, Elizabeth
Huang, Wenwei
Neumann, Susanne
Gershengorn, Marvin C.
TI Thyrotropin Receptor Stimulates Internalization-Independent Persistent
Phosphoinositide Signaling
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID HORMONE-RECEPTOR; TSH RECEPTOR; THYROID-FUNCTION; CYCLIC-AMP;
THYROSTIMULIN; CASCADES; CELLS; TRAFFICKING; EXPRESSION; PITUITARY
AB The thyrotropin [thyroid-stimulating hormone (TSH)] receptor (TSHR) is known to acutely and persistently stimulate cAMP signaling and at higher TSH concentrations to acutely stimulate phosphoinositide signaling. We measured persistent signaling by stimulating TSHR-expressing human embryonic kidney-EM293 cells with TSH and measuring cAMP or inositol monophosphate (IP1) production, a measure of phosphoinositide signaling, 60 min or longer after TSH removal. In contrast to persistent cAMP production, persistent IP1 production increased progressively when TSH exposure was increased from 1 to 30 min, whereas the rates of decay of persistent signaling were similar. A small-molecule agonist and a thyroid-stimulating antibody also caused persistent IP1 and cAMP signaling. A small-molecule inverse agonist and a neutral antagonist inhib-ited TSH-stimulated persistent IP1 production, whereas the inverse agonist but not the neutral antagonist inhibited persistent cAMP production. As with persistent cAMP production, persistent IP1 production was not affected when TSHR internalization was inhibited or enhanced. Moreover, Alexa546TSH- activated TSHR internalization was not accompanied by G alpha(q) coupling protein internalization. Thus, transient exposure to high concentrations of TSH causes persistent phosphoinositide and cAMP signaling that is not dependent on internalization. To our knowledge, this is the first demonstration of persistent activation by any G protein-coupled receptor (GPCR) via the G alpha(q) pathway and of two G protein-mediated pathways by any GPCR.
C1 [Boutin, Alisa; Allen, Michael D.; Geras-Raaka, Elizabeth; Neumann, Susanne; Gershengorn, Marvin C.] NIDDK, CEB, NIH, Bethesda, MD 20892 USA.
[Huang, Wenwei] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Gershengorn, MC (reprint author), NIDDK, CEB, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM marving@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
[Z01-DK011006, Z01-DK047045]; National Human Genome Research Institute;
Molecular Libraries Initiative of the Roadmap for Medical Research,
National Institutes of Health
FX This work was supported by the Intramural Research Programs of the
National Institute of Diabetes and Digestive and Kidney Diseases [Grants
Z01-DK011006, Z01-DK047045]; the National Human Genome Research
Institute; and the Molecular Libraries Initiative of the Roadmap for
Medical Research, National Institutes of Health.
NR 29
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U1 0
U2 1
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD AUG
PY 2011
VL 80
IS 2
BP 240
EP 246
DI 10.1124/mol.111.072157
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 792IA
UT WOS:000292734900003
PM 21525174
ER
PT J
AU Vedadi, M
Barsyte-Lovejoy, D
Liu, F
Rival-Gervier, S
Allali-Hassani, A
Labrie, V
Wigle, TJ
DiMaggio, PA
Wasney, GA
Siarheyeva, A
Dong, AP
Tempel, W
Wang, SC
Chen, X
Chau, I
Mangano, TJ
Huang, XP
Simpson, CD
Pattenden, SG
Norris, JL
Kireev, DB
Tripathy, A
Edwards, A
Roth, BL
Janzen, WP
Garcia, BA
Petronis, A
Ellis, J
Brown, PJ
Frye, SV
Arrowsmith, CH
Jin, J
AF Vedadi, Masoud
Barsyte-Lovejoy, Dalia
Liu, Feng
Rival-Gervier, Sylvie
Allali-Hassani, Abdellah
Labrie, Viviane
Wigle, Tim J.
DiMaggio, Peter A.
Wasney, Gregory A.
Siarheyeva, Alena
Dong, Aiping
Tempel, Wolfram
Wang, Sun-Chong
Chen, Xin
Chau, Irene
Mangano, Thomas J.
Huang, Xi-ping
Simpson, Catherine D.
Pattenden, Samantha G.
Norris, Jacqueline L.
Kireev, Dmitri B.
Tripathy, Ashutosh
Edwards, Aled
Roth, Bryan L.
Janzen, William P.
Garcia, Benjamin A.
Petronis, Arturas
Ellis, James
Brown, Peter J.
Frye, Stephen V.
Arrowsmith, Cheryl H.
Jin, Jian
TI A chemical probe selectively inhibits G9a and GLP methyltransferase
activity in cells
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID PLURIPOTENT STEM-CELLS; HISTONE METHYLTRANSFERASES; DNA METHYLATION;
LYSINE-9 METHYLATION; CHROMATIN-STRUCTURE; CANCER-CELLS; P53;
TRANSCRIPTION; REPRESSION; COMPLEXES
AB Protein lysine methyltransferases G9a and GLP modulate the transcriptional repression of a variety of genes via dimethylation of Lys9 on histone H3 (H3K9me2) as well as dimethylation of non-histone targets. Here we report the discovery of UNC0638, an inhibitor of G9a and GLP with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets. UNC0638 treatment of a variety of cell lines resulted in lower global H3K9me2 levels, equivalent to levels observed for small hairpin RNA knockdown of G9a and GLP with the functional potency of UNC0638 being well separated from its toxicity. UNC0638 markedly reduced the clonogenicity of MCF7 cells, reduced the abundance of H3K9me2 marks at promoters of known G9a-regulated endogenous genes and disproportionately affected several genomic loci encoding microRNAs. In mouse embryonic stem cells, UNC0638 reactivated G9a-silenced genes and a retroviral reporter gene in a concentration-dependent manner without promoting differentiation.
C1 [Vedadi, Masoud; Barsyte-Lovejoy, Dalia; Allali-Hassani, Abdellah; Wasney, Gregory A.; Siarheyeva, Alena; Dong, Aiping; Tempel, Wolfram; Chau, Irene; Edwards, Aled; Brown, Peter J.; Arrowsmith, Cheryl H.] Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada.
[Liu, Feng; Wigle, Tim J.; Chen, Xin; Simpson, Catherine D.; Pattenden, Samantha G.; Norris, Jacqueline L.; Kireev, Dmitri B.; Janzen, William P.; Frye, Stephen V.; Jin, Jian] Univ N Carolina, UNC Eshelman Sch Pharm, Div Med Chem & Nat Prod, Ctr Integrat Chem Biol & Drug Discovery, Chapel Hill, NC USA.
[Rival-Gervier, Sylvie; Ellis, James] SickKids Hosp, Dev & Stem Cell Biol Program, Toronto, ON, Canada.
[Ellis, James] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Rival-Gervier, Sylvie] INRA, UMR Biol Dev & Reprod 1198, Jouy En Josas, France.
[Labrie, Viviane; Wang, Sun-Chong; Petronis, Arturas] Ctr Addict & Mental Hlth, Krembil Family Epigenet Lab, Toronto, ON, Canada.
[DiMaggio, Peter A.; Garcia, Benjamin A.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
[Wang, Sun-Chong] Natl Cent Univ, Inst Syst Biol & Bioinformat, Jhongli, Taiwan.
[Mangano, Thomas J.; Huang, Xi-ping; Roth, Bryan L.] Univ N Carolina, Drug Screening Program, Natl Inst Mental Hlth Psychoact, Chapel Hill, NC USA.
[Tripathy, Ashutosh] Univ N Carolina, Dept Biochem & Biophys, UNC Macromol Interact Facil, Chapel Hill, NC USA.
[Arrowsmith, Cheryl H.] Univ Toronto, Ontario Canc Inst, Campbell Family Canc Res Inst, Toronto, ON, Canada.
[Arrowsmith, Cheryl H.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada.
RP Vedadi, M (reprint author), Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada.
EM carrow@uhnres.utoronto.ca; jianjin@unc.edu
RI Kireev, Dmitri/B-7225-2012; Rival-Gervier, Sylvie/M-7649-2014; Ellis,
James/F-4789-2011; Roth, Bryan/F-3928-2010;
OI Kireev, Dmitri/0000-0001-8479-8555; DiMaggio, Peter/0000-0003-1996-0813
FU National Institute of General Medical Sciences; US National Institutes
of Health (NIH) [RC1GM090732]; University of North Carolina at Chapel
Hill; US National Science Foundation (NSF); Ontario Research Fund;
Ontario Ministry of Health and Long-term Care; Structural Genomics
Consortium; Canadian Institutes for Health Research (CIHR) [199170,
186007, IG1-102956]; Canada Foundation for Innovation; Genome Canada
through the Ontario Genomics Institute; GlaxoSmithKline; Karolinska
Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation
Trust; Ontario Ministry for Research and Innovation; Merck Co. Inc.;
Novartis Research Foundation; Swedish Agency for Innovation Systems;
Swedish Foundation for Strategic Research; Wellcome Trust; NIH
[MH074127, MH088413, DP3DK085698, HG004535]; NSF [CBET-0941143];
American Society for Mass Spectrometry; NIH Office of the Director
[DP2OD007447]
FX We thank A. Tumber for JMJD2E assay support; J. Moffat (University of
Toronto) for the gift of shRNAs; R. Bristow (University Health Network)
for RV221 and PC3 cells; T. Hajian and F. Syeda for protein
purification; G. Senisterra for contributing to DSF and DSLS data
analysis; M. Herold for graphical design and illustration; I. Korboukh,
M. Herold and J. Yost for critical reading of the manuscript; and R.
Trump and C. Yates for helpful discussion. The research described here
was supported by the National Institute of General Medical Sciences, US
National Institutes of Health (NIH; grant RC1GM090732), the Carolina
Partnership and University Cancer Research Fund from the University of
North Carolina at Chapel Hill, the US National Science Foundation (NSF),
the Ontario Research Fund, the Ontario Ministry of Health and Long-term
Care and the Structural Genomics Consortium. The Structural Genomics
Consortium is a registered charity (number 1097737) that receives funds
from the Canadian Institutes for Health Research (CIHR), the Canada
Foundation for Innovation, Genome Canada through the Ontario Genomics
Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice
Wallenberg Foundation, the Ontario Innovation Trust, the Ontario
Ministry for Research and Innovation, Merck & Co. Inc., the Novartis
Research Foundation, the Swedish Agency for Innovation Systems, the
Swedish Foundation for Strategic Research and the Wellcome Trust. C.H.A.
holds a Canada Research Chair in Structural Genomics. V.L. is supported
by a CIHR fellowship. A.P. is supported by grants from the CIHR (199170
and 186007) and from the NIH (MH074127, MH088413, DP3DK085698 and
HG004535). A.P. is Tapscott Chair in Schizophrenia Studies and a Senior
Fellow of the Ontario Mental Health Foundation. J.E. is supported by
CIHR grant IG1-102956. B.A.G. is supported by grants from the NSF (Early
Faculty CAREER award and CBET-0941143), the American Society for Mass
Spectrometry and the NIH Office of the Director (DP2OD007447). P.A.D. is
supported by NIH postdoctoral fellowship F32 NRSA.
NR 50
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U1 12
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD AUG
PY 2011
VL 7
IS 8
BP 566
EP 574
DI 10.1038/NCHEMBIO.599
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 793LW
UT WOS:000292825400019
PM 21743462
ER
PT J
AU Sen, R
AF Sen, Ranjan
TI The origins of NF-kappa B
SO NATURE IMMUNOLOGY
LA English
DT Article
ID DNA-BINDING SUBUNIT; IMMUNOGLOBULIN GENES; ENHANCER; TRANSCRIPTION; REL;
INHIBITOR; SEQUENCES
C1 NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
RP Sen, R (reprint author), NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
EM rs465z@nih.gov
FU Intramural NIH HHS
NR 15
TC 11
Z9 12
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD AUG
PY 2011
VL 12
IS 8
BP 686
EP 688
DI 10.1038/ni.2071
PG 3
WC Immunology
SC Immunology
GA 794BT
UT WOS:000292870700003
PM 21772276
ER
PT J
AU Nakaya, HI
Wrammert, J
Lee, EK
Racioppi, L
Marie-Kunze, S
Haining, WN
Means, AR
Kasturi, SP
Khan, N
Li, GM
McCausland, M
Kanchan, V
Kokko, KE
Li, SZ
Elbein, R
Mehta, AK
Aderem, A
Subbarao, K
Ahmed, R
Pulendran, B
AF Nakaya, Helder I.
Wrammert, Jens
Lee, Eva K.
Racioppi, Luigi
Marie-Kunze, Stephanie
Haining, W. Nicholas
Means, Anthony R.
Kasturi, Sudhir P.
Khan, Nooruddin
Li, Gui-Mei
McCausland, Megan
Kanchan, Vibhu
Kokko, Kenneth E.
Li, Shuzhao
Elbein, Rivka
Mehta, Aneesh K.
Aderem, Alan
Subbarao, Kanta
Ahmed, Rafi
Pulendran, Bali
TI Systems biology of vaccination for seasonal influenza in humans
SO NATURE IMMUNOLOGY
LA English
DT Article
ID YELLOW-FEVER VACCINE; PROTEIN-KINASE-IV; PLASMA-CELL DIFFERENTIATION;
IMMUNE-RESPONSES; TRANSCRIPTION FACTOR; ANTIBODY-RESPONSES; DENDRITIC
CELLS; VIRUS VACCINES; CUTTING EDGE; T-CELLS
AB Here we have used a systems biology approach to study innate and adaptive responses to vaccination against influenza in humans during three consecutive influenza seasons. We studied healthy adults vaccinated with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). TIV induced higher antibody titers and more plasmablasts than LAIV did. In subjects vaccinated with TIV, early molecular signatures correlated with and could be used to accurately predict later antibody titers in two independent trials. Notably, expression of the kinase CaMKIV at day 3 was inversely correlated with later antibody titers. Vaccination of CaMKIV-deficient mice with TIV induced enhanced antigen-specific antibody titers, which demonstrated an unappreciated role for CaMKIV in the regulation of antibody responses. Thus, systems approaches can be used to predict immunogenicity and provide new mechanistic insights about vaccines.
C1 [Nakaya, Helder I.; Wrammert, Jens; Marie-Kunze, Stephanie; Kasturi, Sudhir P.; Khan, Nooruddin; Li, Gui-Mei; McCausland, Megan; Kanchan, Vibhu; Li, Shuzhao; Ahmed, Rafi; Pulendran, Bali] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Nakaya, Helder I.; Marie-Kunze, Stephanie; Kasturi, Sudhir P.; Khan, Nooruddin; Li, Shuzhao; Pulendran, Bali] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Wrammert, Jens; Li, Gui-Mei; McCausland, Megan; Kanchan, Vibhu; Ahmed, Rafi] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Lee, Eva K.] Georgia Inst Technol, Sch Ind & Syst Engn, Ctr Operat Res Med & Healthcare, Atlanta, GA 30332 USA.
[Racioppi, Luigi] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC USA.
[Racioppi, Luigi; Means, Anthony R.] Univ Naples Federico 2, Dept Cellular & Mol Biol & Pathol, Naples, Italy.
[Haining, W. Nicholas] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kokko, Kenneth E.] Emory Univ, Sch Med, Dept Med, Div Nephrol, Atlanta, GA USA.
[Elbein, Rivka; Mehta, Aneesh K.] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA.
[Aderem, Alan] Inst Syst Biol, Seattle, WA USA.
[Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Pulendran, Bali] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA.
RP Pulendran, B (reprint author), Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
EM bpulend@emory.edu
RI Mehta, Aneesh/B-8054-2012; Nakaya, Helder/A-1397-2010;
OI Mehta, Aneesh/0000-0002-6552-9162; Nakaya, Helder/0000-0001-5297-9108;
racioppi, luigi/0000-0002-9207-6752
FU US National Institutes of Health [U19AI090023, HHSN266200700006C,
U54AI057157, R37AI48638, R01DK057665, U19AI057266, N01 AI50025, AI30048,
AI057266, DK074701, UL1 RR025008]; Bill & Melinda Gates Foundation
[38645]; National Science Foundation (E.K.L. laboratory); Centers for
Disease Control (E.K.L. laboratory)
FX We thank B.T. Rouse and R. Compans for discussion and comments on the
manuscript, and H. Oluoch for technical assistance. Supported the US
National Institutes of Health (U19AI090023, HHSN266200700006C,
U54AI057157, R37AI48638, R01DK057665, U19AI057266 and N01 AI50025 for
the B. P. laboratory; AI30048 and AI057266 for the R.A. laboratory;
DK074701 for the A.R.M. laboratory; Intramural Research Program of the
National Institute of Allergy and Infectious Diseases for the K.S.
laboratory; and UL1 RR025008 from the Clinical and Translational Science
Award program, National Center for Research Resources for clinical
work), the Bill & Melinda Gates Foundation (Collaboration for AIDS
Vaccine Discovery 38645 to the R.A. and B.P. laboratories), the National
Science Foundation (E.K.L. laboratory) and the Centers for Disease
Control (E.K.L. laboratory).
NR 54
TC 291
Z9 294
U1 6
U2 56
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD AUG
PY 2011
VL 12
IS 8
BP 786
EP U149
DI 10.1038/ni.2067
PG 11
WC Immunology
SC Immunology
GA 794BT
UT WOS:000292870700017
PM 21743478
ER
PT J
AU Simon-Loriere, E
Holmes, EC
AF Simon-Loriere, Etienne
Holmes, Edward C.
TI Why do RNA viruses recombine?
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Article
ID HEPATITIS-C-VIRUS; HUMAN ROTAVIRUS STRAINS; INFLUENZA-A VIRUSES;
IN-VIVO; GENETIC-RECOMBINATION; SUPERINFECTION EXCLUSION; RETROVIRAL
RECOMBINATION; NONRANDOM REASSORTMENT; DELETERIOUS MUTATIONS;
PHYLOGENETIC EVIDENCE
AB Recombination occurs in many RNA viruses and can be of major evolutionary significance. However, rates of recombination vary dramatically among RNA viruses, which can range from clonal to highly recombinogenic. Here, we review the factors that might explain this variation in recombination frequency and show that there is little evidence that recombination is favoured by natural selection to create advantageous genotypes or purge deleterious mutations, as predicted if recombination functions as a form of sexual reproduction. Rather, recombination rates seemingly reflect larger-scale patterns of viral genome organization, such that recombination may be a mechanistic by-product of the evolutionary pressures acting on other aspects of virus biology.
C1 [Simon-Loriere, Etienne; Holmes, Edward C.] Penn State Univ, Dept Biol, Mueller Lab, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Mueller Lab, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM ech15@psu.edu
OI Holmes, Edward/0000-0001-9596-3552; , Etienne/0000-0001-8420-7743
FU US National Institutes of Health [R01GM080533]
FX E.C.H. is supported in part by US National Institutes of Health grant
R01GM080533.
NR 123
TC 121
Z9 121
U1 0
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD AUG
PY 2011
VL 9
IS 8
BP 617
EP 626
DI 10.1038/nrmicro2614
PG 10
WC Microbiology
SC Microbiology
GA 792PT
UT WOS:000292760600014
PM 21725337
ER
PT J
AU Tomasi, D
Volkow, ND
AF Tomasi, Dardo
Volkow, Nora D.
TI Functional connectivity hubs in the human brain
SO NEUROIMAGE
LA English
DT Article
ID RESTING-STATE FMRI; ALZHEIMERS-DISEASE; SMALL-WORLD; CORTICAL NETWORKS;
PATTERNS; SLEEP; ORGANIZATION; DYNAMICS; CORTEX; FIELD
AB Brain networks appear to have few and well localized regions with high functional connectivity density (hubs) for fast integration of neural processing, and their dysfunction could contribute to neuropsychiatric diseases. However the variability in the distribution of these brain hubs is unknown due in part to the overwhelming computational demands associated to their localization. Recently we developed a fast algorithm to map the local functional connectivity density (IFCD). Here we extend our method to map the global density (gFDC) taking advantage of parallel computing. We mapped the gFCD in the brain of 1031 subjects from the 1000 Functional Connectomes project and show that the strongest hubs are located in regions of the default mode network (DMN) and in sensory cortices, whereas subcortical regions exhibited the weakest hubs. The strongest hubs were consistently located in ventral precuneus/cingulate gyrus (previously identified by other analytical methods including IFCD) and in primary visual cortex (BA 17/18), which highlights their centrality to resting connectivity networks. In contrast and after rescaling, hubs in prefrontal regions had lower gFCD than IFCD, which suggests that their local functional connectivity (as opposed to long-range connectivity) prevails in the resting state. The power scaling of the probability distribution of gFCD hubs (as for IFCD) was consistent across research centers further corroborating the "scale-free" topology of brain networks. Within and between-subject variability for gFCD were twice than that for IFCD (20% vs. 12% and 84% vs. 34%, respectively) suggesting that gFCD is more sensitive to individual differences in functional connectivity. Published by Elsevier Inc.
C1 [Tomasi, Dardo; Volkow, Nora D.] NIAAA, Bethesda, MD 20892 USA.
[Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA.
RP Tomasi, D (reprint author), Brookhaven Natl Lab, Lab Neuroimaging LNI NIAAA, Dept Med, Bldg 490,30 Bell Ave, Upton, NY 11973 USA.
EM tomasi@bnl.gov
RI Tomasi, Dardo/J-2127-2015
FU National Institutes of Alcohol Abuse and Alcoholism [2RO1AA09481]
FX This work was accomplished with support from the National Institutes of
Alcohol Abuse and Alcoholism (2RO1AA09481).
NR 54
TC 116
Z9 118
U1 4
U2 23
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 1
PY 2011
VL 57
IS 3
SI SI
BP 908
EP 917
DI 10.1016/j.neuroimage.2011.05.024
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 792CK
UT WOS:000292717900025
PM 21609769
ER
PT J
AU Murty, VP
Sambataro, F
Radulescu, E
Altamura, M
Iudicello, J
Zoltick, B
Weinberger, DR
Goldberg, TE
Mattay, VS
AF Murty, Vishnu P.
Sambataro, Fabio
Radulescu, Eugenia
Altamura, Mario
Iudicello, Jennifer
Zoltick, Bradley
Weinberger, Daniel R.
Goldberg, Terry E.
Mattay, Venkata S.
TI Selective updating of working memory content modulates
meso-cortico-striatal activity
SO NEUROIMAGE
LA English
DT Article
ID BASAL GANGLIA; PREFRONTAL CORTEX; DOPAMINERGIC MIDBRAIN; COMPUTATIONAL
MODEL; PARKINSONS-DISEASE; NEURAL SYSTEM; BRAIN; LOAD; REPRESENTATION;
SCHIZOPHRENIA
AB Accumulating evidence from non-human primates and computational modeling suggests that dopaminergic signals arising from the midbrain (substantia nigra/ventral tegmental area) mediate striatal gating of the prefrontal cortex during the selective updating of working memory. Using event-related functional magnetic resonance imaging, we explored the neural mechanisms underlying the selective updating of information stored in working memory. Participants were scanned during a novel working memory task that parses the neurophysiology underlying working memory maintenance, overwriting, and selective updating. Analyses revealed a functionally coupled network consisting of a midbrain region encompassing the substantia nigra/ventral tegmental area, caudate, and dorsolateral prefrontal cortex that was selectively engaged during working memory updating compared to the overwriting and maintenance of working memory content. Further analysis revealed differential midbrain-dorsolateral prefrontal interactions during selective updating between low-performing and high-performing individuals. These findings highlight the role of this meso-cortico-striatal circuitry during the selective updating of working memory in humans, which complements previous research in behavioral neuroscience and computational modeling. Published by Elsevier Inc.
C1 [Murty, Vishnu P.; Sambataro, Fabio; Radulescu, Eugenia; Altamura, Mario; Iudicello, Jennifer; Zoltick, Bradley; Weinberger, Daniel R.; Mattay, Venkata S.] NIMH, Clin Brain Disorders Branch, Gene Cognit & Psychosis Branch, NIH, Bethesda, MD 20892 USA.
[Goldberg, Terry E.] Zucker Hillside Hosp, Glen Oaks, NY 11004 USA.
RP Mattay, VS (reprint author), NIMH, Clin Brain Disorders Branch, Gene Cognit & Psychosis Branch, NIH, Bethesda, MD 20892 USA.
EM vsm@mail.nih.gov
RI Sambataro, Fabio/E-3426-2010
OI Sambataro, Fabio/0000-0003-2102-416X
FU Intramural NIH HHS [Z01 MH002905-01, Z99 MH999999]
NR 54
TC 27
Z9 27
U1 2
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 1
PY 2011
VL 57
IS 3
SI SI
BP 1264
EP 1272
DI 10.1016/j.neuroimage.2011.05.006
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 792CK
UT WOS:000292717900059
PM 21596142
ER
PT J
AU Mojtabai, R
Olfson, M
Sampson, NA
Jin, R
Druss, B
Wang, PS
Wells, KB
Pincus, HA
Kessler, RC
AF Mojtabai, R.
Olfson, M.
Sampson, N. A.
Jin, R.
Druss, B.
Wang, P. S.
Wells, K. B.
Pincus, H. A.
Kessler, R. C.
TI Barriers to mental health treatment: results from the National
Comorbidity Survey Replication
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Continuity of care; mental health; treatment seeking
ID DSM-IV DISORDERS; PERCEIVED NEED; UNITED-STATES; TREATMENT SEEKING;
PROVIDER RECORDS; HELP-SEEKING; YOUNG-ADULTS; SELF-REPORTS; SERVICE USE;
1ST ONSET
AB Background. The aim was to examine barriers to initiation and continuation of treatment among individuals with common mental disorders in the US general population.
Method. Respondents in the National Comorbidity Survey Replication with common 12-month DSM-IV mood, anxiety, substance, impulse control and childhood disorders were asked about perceived need for treatment, structural barriers and attitudinal/evaluative barriers to initiation and continuation of treatment.
Results. Low perceived need was reported by 44.8% of respondents with a disorder who did not seek treatment. Desire to handle the problem on one's own was the most common reason among respondents with perceived need both for not seeking treatment (72.6%) and for dropping out of treatment (42.2%). Attitudinal/evaluative factors were much more important than structural barriers both to initiating (97.4% v. 22.2%) and to continuing (81.9% v. 31.8%) of treatment. Reasons for not seeking treatment varied with illness severity. Low perceived need was a more common reason for not seeking treatment among individuals with mild (57.0%) than moderate (39.3%) or severe (25.9%) disorders, whereas structural and attitudinal/evaluative barriers were more common among respondents with more severe conditions.
Conclusions. Low perceived need and attitudinal/evaluative barriers are the major barriers to treatment seeking and staying in treatment among individuals with common mental disorders. Efforts to increase treatment seeking and reduce treatment drop-out need to take these barriers into consideration as well as to recognize that barriers differ as a function of sociodemographic and clinical characteristics.
C1 [Sampson, N. A.; Jin, R.; Kessler, R. C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Mojtabai, R.] Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Mojtabai, R.] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA.
[Olfson, M.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Olfson, M.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Druss, B.] Emory Univ, Dept Hlth Policy & Management, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Wang, P. S.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
[Wells, K. B.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave,Suite 215, Boston, MA 02115 USA.
EM kessler@hcp.med.harvard.edu
FU National Institute of Mental Health [R01 MH070884]; John D. and
Catherine T. MacArthur Foundation; Pfizer Foundation; US Public Health
Service [R13-MH066849, R01-MH069864, R01 DA016558]; Fogarty
International Center [FIRCA R03-TW006481]; Pan American Health
Organization; Eli Lilly and Company; Ortho-McNeil Pharmaceutical, Inc.;
GlaxoSmithKline; Bristol-Myers Squibb
FX The NCS-R is carried out in conjunction with the World Health
Organization World Mental Health (WMH) Survey Initiative. We thank the
staff of the WMH Data Collection and Data Analysis Coordination Centers
for assistance with instrumentation, fieldwork and consultation on data
analysis. These activities were supported by the National Institute of
Mental Health (R01 MH070884), the John D. and Catherine T. MacArthur
Foundation, the Pfizer Foundation, the US Public Health Service
(R13-MH066849, R01-MH069864, and R01 DA016558), the Fogarty
International Center (FIRCA R03-TW006481), the Pan American Health
Organization, Eli Lilly and Company, Ortho-McNeil Pharmaceutical, Inc.,
GlaxoSmithKline, and Bristol-Myers Squibb. A complete list of WMH
publications can be found at http://www.hcp.med.harvard.edu/wmh/
NR 46
TC 111
Z9 112
U1 4
U2 38
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
EI 1469-8978
J9 PSYCHOL MED
JI Psychol. Med.
PD AUG
PY 2011
VL 41
IS 8
BP 1751
EP 1761
DI 10.1017/S0033291710002291
PG 11
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 791XZ
UT WOS:000292704400017
PM 21134315
ER
PT J
AU Miller, FG
Colloca, L
AF Miller, Franklin G.
Colloca, Luana
TI The placebo phenomenon and medical ethics: Rethinking the relationship
between informed consent and risk-benefit assessment
SO THEORETICAL MEDICINE AND BIOETHICS
LA English
DT Article
DE Placebo response; Nocebo effect; Informed consent; Risk-benefit
assessment
ID CLINICAL-PRACTICE; RANDOMIZED-TRIAL; NOCEBO; PAIN; VERTEBROPLASTY;
MECHANISMS; FRACTURES; WORDS
AB It has been presumed within bioethics that the benefits and risks of treatments can be assessed independently of information disclosure to patients as part of the informed consent process. Research on placebo and nocebo effects indicates that this is not true for symptomatic treatments. The benefits and risks that patients experience from symptomatic treatments can be shaped powerfully by information about these treatments provided by clinicians. In this paper we discuss the implications of placebo and nocebo research for risk-benefit assessment and informed consent.
C1 [Miller, Franklin G.; Colloca, Luana] NIH, Dept Bioeth Clin Ctr, Bethesda, MD 20892 USA.
[Colloca, Luana] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth Clin Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
OI Colloca, Luana/0000-0002-6503-4709
FU Intramural NIH HHS
NR 31
TC 34
Z9 36
U1 2
U2 20
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1386-7415
J9 THEOR MED BIOETH
JI Theor. Med. Bioeth.
PD AUG
PY 2011
VL 32
IS 4
BP 229
EP 243
DI 10.1007/s11017-011-9179-8
PG 15
WC Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Social Issues; Biomedical Social
Sciences
GA 789ZW
UT WOS:000292559300002
PM 21479794
ER
PT J
AU de Castro, A
Jones, HE
Johnson, RE
Gray, TR
Shakleya, DM
Huestis, MA
AF de Castro, Ana
Jones, Hendree E.
Johnson, Rolley E.
Gray, Teresa R.
Shakleya, Diaa M.
Huestis, Marilyn A.
TI Methadone, Cocaine, Opiates, and Metabolite Disposition in Umbilical
Cord and Correlations to Maternal Methadone Dose and Neonatal Outcomes
SO THERAPEUTIC DRUG MONITORING
LA English
DT Article
DE methadone; cocaine; opiates; umbilical cord; in utero drug exposure
ID CHROMATOGRAPHY-MASS SPECTROMETRY; ABSTINENCE SYNDROME; SIMULTANEOUS
QUANTIFICATION; MAINTENANCE TREATMENT; WITHDRAWAL SYNDROME; TOBACCO
EXPOSURE; DEPENDENT WOMEN; PREGNANT-WOMEN; AMNIOTIC-FLUID; FETAL
EXPOSURE
AB Objectives: The purpose was to explore methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) umbilical cord disposition, correlate with maternal methadone dose and neonatal outcomes, and evaluate the window of drug detection in umbilical cord of in utero illicit drug exposure.
Methods: Subjects comprised 19 opioid-dependent pregnant women from 2 clinical studies, one comparing methadone and buprenorphine pharmacotherapy for opioid-dependence treatment and the second examining monetary reinforcement schedules to maintain drug abstinence. Correlations were calculated for methadone and EDDP umbilical cord concentrations and maternal methadone dose, and neonatal outcomes. Cocaine- and opiate-positive umbilical cord concentrations were compared with those in placenta and meconium, and urine specimens collected throughout gestation.
Results: Significant positive correlations were found for umbilical cord methadone concentrations and methadone mean daily dose, mean dose during the third trimester, and methadone cumulative daily dose. Umbilical cord EDDP concentrations and EDDP/methadone concentration ratios were positively correlated to newborn length, peak neonatal abstinence syndrome (NAS) score, and time-to-peak NAS score. Methadone concentrations and EDDP/methadone ratios in umbilical cord and placenta were positively correlated. Meconium identified many more cocaine-and opiate-positive specimens than did umbilical cord.
Conclusions: Umbilical cord methadone concentrations were correlated to methadone doses. Also, our results indicate that methadone and EDDP concentrations might help to predict the NAS severity. Meconium proved to be more suitable than umbilical cord to detect in utero exposure to cocaine and opiates; however, umbilical cord could be useful when meconium is unavailable due to in utero or delayed expulsion.
C1 [de Castro, Ana; Gray, Teresa R.; Shakleya, Diaa M.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, NIH, Baltimore, MD 21224 USA.
[de Castro, Ana] Univ Santiago de Compostela, Toxicol Lab, Inst Forens Sci, Santiago De Compostela, Spain.
[Jones, Hendree E.] Res Triangle Inst Int, Subst Abuse Treatment Evaluat & Intervent Dept, Durham, NC USA.
[Johnson, Rolley E.] Reckitt Benckiser Pharmaceut Inc, Clin Sci & Regulatory Affairs Dept, Richmond, VA USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab IRP, NIH 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
RI DE CASTRO, ANA/M-5159-2015
OI DE CASTRO, ANA/0000-0002-9832-012X
FU Intramural Research Program (IRP); National Institute on Drug Abuse
(NIDA), National Institutes of Health (NIH) [DA12220, DA12403];
Direccion Xeral de Investigacion, Desenvolvemento e Innovacion (DXIDI),
Conselleria de Innovacion e Industria Galicia, Spain [AA-053]
FX Supported by Intramural Research Program (IRP) and Extramural Grants
DA12220 and DA12403 from the National Institute on Drug Abuse (NIDA),
National Institutes of Health (NIH). Support for A. de Castro was from
Direccion Xeral de Investigacion, Desenvolvemento e Innovacion (DXIDI),
Conselleria de Innovacion e Industria (AA-053), Galicia, Spain.
NR 52
TC 10
Z9 11
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0163-4356
J9 THER DRUG MONIT
JI Ther. Drug Monit.
PD AUG
PY 2011
VL 33
IS 4
BP 443
EP 452
DI 10.1097/FTD.0b013e31822724f0
PG 10
WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
GA 792PY
UT WOS:000292761500012
PM 21743375
ER
PT J
AU Schwaninger, AE
Meyer, MR
Barnes, AJ
Kolbrich-Spargo, EA
Gorelick, DA
Goodwin, RS
Huestis, MA
Maurer, HH
AF Schwaninger, A. E.
Meyer, M. R.
Barnes, A. J.
Kolbrich-Spargo, E. A.
Gorelick, D. A.
Goodwin, R. S.
Huestis, M. A.
Maurer, H. H.
TI Stereoselective urinary excretion kinetics of MDMA and metabolites
following controlled MDMA administration to humans
SO THERAPEUTIC DRUG MONITORING
LA English
DT Meeting Abstract
CT 12th International Congress of Therapeutic Drug Monitoring and Clinical
Toxicology
CY OCT 02-06, 2011
CL Stuttgart, GERMANY
DE MDMA; chiral excretion; urine
C1 [Schwaninger, A. E.; Meyer, M. R.; Maurer, H. H.] Univ Saarland, Inst Expt & Clin Pharmacol & Toxicol, D-6650 Homburg, Germany.
[Barnes, A. J.; Kolbrich-Spargo, E. A.; Gorelick, D. A.; Goodwin, R. S.; Huestis, M. A.] NIDA, NIH, Baltimore, MD USA.
RI Meyer, Markus/B-9293-2009
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0163-4356
J9 THER DRUG MONIT
JI Ther. Drug Monit.
PD AUG
PY 2011
VL 33
IS 4
BP 471
EP 471
PG 1
WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
GA 792PY
UT WOS:000292761500027
ER
EF