FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Woody, GE
Poole, SA
Subramaniam, G
Dugosh, K
Bogenschutz, M
Abbott, P
Patkar, A
Publicker, M
McCain, K
Potter, JS
Forman, R
Vetter, V
McNicholas, L
Blaine, J
Lynch, KG
Fudala, P
AF Woody, George E.
Poole, Sabrina A.
Subramaniam, Geetha
Dugosh, Karen
Bogenschutz, Michael
Abbott, Patrick
Patkar, Ashwin
Publicker, Mark
McCain, Karen
Potter, Jennifer Sharpe
Forman, Robert
Vetter, Victoria
McNicholas, Laura
Blaine, Jack
Lynch, Kevin G.
Fudala, Paul
TI Extended vs Short-term Buprenorphine-Naloxone for Treatment of
Opioid-Addicted Youth A Randomized Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID METHADONE-MAINTENANCE TREATMENT; DRUG-USERS; DEPENDENCE; ABUSE;
PHARMACOLOGY; NALTREXONE; INJECTION; RELAPSE
AB Context The usual treatment for opioid- addicted youth is detoxification and counseling. Extended medication- assisted therapy may be more helpful.
Objective To evaluate the efficacy of continuing buprenorphine- naloxone for 12 weeks vs detoxification for opioid- addicted youth.
Design, Setting, and Patients Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine- naloxone or a 14- day taper (detox).
Interventions Patients in the 12- week buprenorphine- naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling.
Main Outcome Measure Opioid- positive urine test result at weeks 4, 8, and 12.
Results The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioidpositive urine test results at weeks 4 and 8 but not at week 12 (chi(2)(2) = 4.93, P =. 09). At week 4, 59 detox patients had positive results ( 61%; 95% confidence interval [CI]= 47%-75%) vs 58 12- week buprenorphine- naloxone patients (26%; 95% CI= 14%- 38%). At week 8, 53 detox patients had positive results ( 54%; 95% CI= 38%- 70%) vs 52 12- week buprenorphine- naloxone patients ( 23%; 95% CI= 11%- 35%). At week 12, 53 detox patients had positive results (51%; 95% CI= 35%- 67%) vs 49 12- week buprenorphine-naloxone patients (43%; 95% CI= 29%-57%). By week 12, 16 of 78 detox patients ( 20.5%) remained in treatment vs 52 of 74 12- week buprenorphine-naloxone patients ( 70%; chi(2)(1) = 32.90, P <. 001). During weeks 1 through 12, patients in the 12- week buprenorphine- naloxone group reported less opioid use (chi(2)(1) = 18.45, P <. 001), less injecting (chi(2)(1) = 6.00, P =. 01), and less nonstudy addiction treatment (chi(2)(1) = 25.82, P <. 001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12.
Conclusions Continuing treatment with buprenorphine- naloxone improved outcome compared with short-term detoxification. Further research is necessary to assess the efficacy and safety of longer- term treatment with buprenorphine for young individuals with opioid dependence.
Trial Registration clinicaltrials. gov Identifier: NCT00078130.
C1 [Woody, George E.; Poole, Sabrina A.; Dugosh, Karen; Forman, Robert; McNicholas, Laura; Lynch, Kevin G.; Fudala, Paul] Univ Penn, Dept Psychiat, Treatment Res Inst, Philadelphia, PA 19106 USA.
[Subramaniam, Geetha] Johns Hopkins Univ, Div Child & Adolescent Psychiat, Baltimore, MD USA.
[Bogenschutz, Michael; Abbott, Patrick] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA.
[Bogenschutz, Michael] Univ New Mexico, Ctr Alcoholism Substance Abuse & Addict, Albuquerque, NM 87131 USA.
[Abbott, Patrick] Univ New Mexico, Hlth Sci Ctr, Addict Program, Albuquerque, NM 87131 USA.
[Abbott, Patrick] Univ New Mexico, Hlth Sci Ctr, Substance Abuse Program, Albuquerque, NM 87131 USA.
[Patkar, Ashwin] Duke Univ, Med Ctr, Durham, NC USA.
[Publicker, Mark] Mercy Recovery Ctr, Westbrook, ME USA.
[McCain, Karen] Duke Univ, Duke Addict Program, Durham, NC USA.
[Potter, Jennifer Sharpe] Harvard Univ, Sch Med, Boston, MA USA.
[Potter, Jennifer Sharpe] McLean Hosp, Belmont, MA 02178 USA.
[Vetter, Victoria] Childrens Hosp Philadelphia, Div Pediat Cardiol, Philadelphia, PA 19104 USA.
[Woody, George E.; McNicholas, Laura; Fudala, Paul] Vet Affairs Med Ctr, Philadelphia, PA USA.
[Blaine, Jack] NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA.
RP Woody, GE (reprint author), Univ Penn, Dept Psychiat, Treatment Res Inst, 150 S Independence Mall W,Ste 600, Philadelphia, PA 19106 USA.
EM woody@tresearch.org
RI Potter, Jennifer/C-6720-2008
OI Potter, Jennifer/0000-0002-7250-4422
FU National Institute on Drug Abuse [U10-DA013711, U10-DA015831,
U10-DA13034, K12-DA000357, U10-DA1533, U10DA13043, KO5-DA17009]
FX This study was supported by the following grants from the National
Institute on Drug Abuse: U10-DA013711 to Duke University (Dr Patkar);
U10-DA015831 to Harvard University (Dr Weiss); U10-DA13034 to Johns
Hopkins University (Dr Stitzer); K12-DA000357 (Dr Subramaniam);
U10-DA1533 to the University of New Mexico (Dr Miller); and U10DA13043
and KO5-DA17009 (Dr Woody). Reckitt Benckiser provided medication for
the study.
NR 35
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U1 2
U2 9
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD NOV 5
PY 2008
VL 300
IS 17
BP 2003
EP 2011
DI 10.1001/jama.2008.574
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 368EX
UT WOS:000260605400020
PM 18984887
ER
PT J
AU Denny, CC
Emanuel, EJ
AF Denny, Colleen C.
Emanuel, Ezekiel J.
TI US Health Aid Beyond PEPFAR The Mother & Child Campaign
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID MILLENNIUM DEVELOPMENT GOALS; COST-EFFECTIVENESS ANALYSIS;
DEVELOPING-COUNTRIES; INTERVENTIONS; STRATEGIES; HIV/AIDS
C1 [Denny, Colleen C.; Emanuel, Ezekiel J.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Emanuel, EJ (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM eemanuel@nih.gov
NR 15
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U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD NOV 5
PY 2008
VL 300
IS 17
BP 2048
EP 2051
DI 10.1001/jama.2008.556
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 368EX
UT WOS:000260605400027
PM 18984893
ER
PT J
AU Dizhoor, AM
Woodruff, ML
Olshevskaya, EV
Cilluffo, MC
Cornwall, MC
Sieving, PA
Fain, GL
AF Dizhoor, Alexander M.
Woodruff, Michael L.
Olshevskaya, Elena V.
Cilluffo, Marianne C.
Cornwall, M. Carter
Sieving, Paul A.
Fain, Gordon L.
TI Night Blindness and the Mechanism of Constitutive Signaling of Mutant
G90D Rhodopsin
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE photoreceptor; rod; transduction; adaptation; rhodopsin; vision
ID LEBER CONGENITAL AMAUROSIS; KNOCK-OUT MICE; ROD PHOTORECEPTORS; VISUAL
PIGMENT; RETINAL RODS; OPSIN ACTIVATION; MOUSE MODEL; DARK NOISE; LIGHT;
DEGENERATION
AB The G90D rhodopsin mutation is known to produce congenital night blindness in humans. This mutation produces a similar condition in mice, because rods of animals heterozygous (D+) or homozygous (D+/+) for this mutation have decreased dark current and sensitivity, reduced Ca2+, and accelerated values of tau(REC) and tau(D), similar to light-adapted wild-type (WT) rods. Our experiments indicate that G90D pigment activates the cascade, producing an equivalent background light of similar to 130 Rh-star rod(-1) for D+ and 890 Rh-star rod(-1) for D+/+. The active species of the G90D pigment could be unregenerated G90D opsin or G90D rhodopsin, either spontaneously activated (as Rh-star) or in some other form. Addition of 11-cis-retinal in lipid vesicles, which produces regeneration of both WT and G90D opsin in intact rods and ROS membranes, had no effect on the waveform or sensitivity of dark-adapted G90D responses, indicating that the active species is not G90D opsin. The noise spectra of dark-adapted G90D and WT rods are similar, and the G90D noise variance is much less than of a WT rod exposed to background light of about the same intensity as the G90D equivalent light, indicating that Rh-star is not the active species. We hypothesize that G90D rhodopsin undergoes spontaneous changes in molecular conformation which activate the transduction cascade with low gain. Our experiments provide the first indication that a mutant form of the rhodopsin molecule bound to its 11-cis-chromophore can stimulate the visual cascade spontaneously at a rate large enough to produce visual dysfunction.
C1 [Woodruff, Michael L.; Fain, Gordon L.] Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90095 USA.
[Dizhoor, Alexander M.; Olshevskaya, Elena V.] Salus Univ, Pennsylvania Coll Optometry, Hafter Res Labs, Elkins Pk, PA 19027 USA.
[Cilluffo, Marianne C.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA.
[Cornwall, M. Carter] Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA.
[Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
[Fain, Gordon L.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
[Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
RP Fain, GL (reprint author), Univ Calif Los Angeles, Dept Physiol Sci, 3836 Life Sci, Los Angeles, CA 90095 USA.
EM gfain@ucla.edu
OI Cornwall, M./0000-0002-0847-939X
FU National Institutes of Health [EY11522, EY01157, EY01844, EY 00331];
National Eye Institute; National Institute on Deafness and Other
Communication Disorders Intramural; Pennsylvania Lions Sight
Preservation Foundation; UCLA
FX This work was supported by National Institutes of Health Grants EY11522
(A. M. D.), EY01157 (M. C. C.), EY01844 (G. L. F.), and EY 00331 [Jules
Stein Eye Institute, University of California, Los Angeles (UCLA) Core,
M. L. W., G. L. F.], National Eye Institute, National Institute on
Deafness and Other Communication Disorders Intramural funding (P. A.
S.), the Pennsylvania Lions Sight Preservation Foundation (A. M. D.),
and the Microscopic Techniques Core Service Fund of UCLA (M. C. C.). A.
M. D. is the Martin and Florence Hafter Chair Professor of Pharmacology.
We thank Rosalie Crouch of the Medical University of South Carolina for
providing 11-cis retinal, Roxana Radu of the Jules Stein Eye Institute,
UCLA for assaying the purity of the retinal, Dean Bok and the members of
the Bok laboratory of the Jules Stein Eye Institute, UCLA for providing
tissue blocks of Rpe65 knock-out mice for measurement of outer segment
dimensions, and Dan Tranchina of New York University for help with
statistical testing.
NR 40
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U1 1
U2 3
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD NOV 5
PY 2008
VL 28
IS 45
BP 11662
EP 11672
DI 10.1523/JNEUROSCI.4006-08.2008
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 369AV
UT WOS:000260665900024
PM 18987202
ER
PT J
AU Lau, P
Verrier, JD
Nielsen, JA
Johnson, KR
Notterpek, L
Hudson, LD
AF Lau, Pierre
Verrier, Jonathan D.
Nielsen, Joseph A.
Johnson, Kory R.
Notterpek, Lucia
Hudson, Lynn D.
TI Identification of Dynamically Regulated MicroRNA and mRNA Networks in
Developing Oligodendrocytes
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE microRNA; posttranscriptional regulation; oligodendrocyte; PMP22;
myelin; glia
ID PERIPHERAL MYELIN PROTEIN-22; MAMMALIAN MICRORNAS; ANIMAL MICRORNAS;
GENOMIC ANALYSIS; GENE-EXPRESSION; BRAIN; DISEASE; DIFFERENTIATION;
SPECIFICATION; DROSOPHILA
AB MicroRNAs (miRNAs) play important roles in modulating gene expression at the posttranscriptional level. In postnatal oligodendrocyte lineage cells, the miRNA expression profile (" microRNAome") contains 43 miRNAs whose expression dynamically changes during the transition from A2B5(+) oligodendrocyte progenitor cells to premyelinating GalC(+) cells. The combination of microRNAome profiling with analyses of the oligodendrocyte transcriptome reveals a target bias for a class of miRNAs which includes miR-9. We show that miR-9 is downregulated during oligodendrocyte differentiation. In addition, miR-9 expression level inversely correlates with the expression of its predicted targets, among which is the peripheral myelin protein PMP22. We found that PMP22 mRNA but not protein is detectable in oligodendrocytes, whereas Schwann cells producing PMP22 protein lack miR-9. We demonstrate that miR-9 interacts with the 3' untranslated region of PMP22 and downregulates its expression. Our results support models in which miRNAs can act as guardians of the transcriptome.
C1 [Lau, Pierre; Nielsen, Joseph A.; Hudson, Lynn D.] NINDS, Sect Dev Genet, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Johnson, Kory R.] NINDS, Bioinformat Neurosci Grp, Informat Technol Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
[Verrier, Jonathan D.; Notterpek, Lucia] Univ Florida, McKnight Brain Inst, Dept Neurosci, Gainesville, FL 32610 USA.
RP Hudson, LD (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM hudsonl1@od.nih.gov
FU National Institute of Neurological Disorders and Stroke; Muscular
Dystrophy Association; McKnight Brain Institute; Joshua Benjamin Weitzel
Fund for Developmental Neurobiology
FX This work was supported by intramural funds from National Institute of
Neurological Disorders and Stroke (NINDS) (L. D. H.), the Muscular
Dystrophy Association (L. N.), the McKnight Brain Institute (L. N.), and
the Joshua Benjamin Weitzel Fund for Developmental Neurobiology (L. N.).
We thank Naser Muja (Johns Hopkins University, Baltimore, MD) for
preliminary experiments and Jo Ann Berndt (NINDS) and Elena Romm (NINDS)
for expert technical assistance. We are indebted to Dragan Maric (NINDS)
for purification of oligodendrocytes and Abdel Elkahloun (National Human
Genome Research Institute) for Affymetrix microarray processing. We are
grateful to Jim Nagle (NINDS) and Deborah Kauffman (NINDS) for their
support in DNA sequencing. We thank Christopher Brown (Applied
Biosystems) and David Armistead (Applied Biosystems) for their expertise
in real-time PCR. We thank Monique Dubois- Dalcq (NINDS) for critical
reading of this manuscript. The miRNA microarray data reported in this
study is deposited in the European Molecular Biology Laboratory/European
Bioinformatics Institute ArrayExpress database (accession E-MEXP-1589)
and the DNA microarray data in the Gene Expression Omnibus database
(accession GSE11218).
NR 43
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U1 1
U2 11
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD NOV 5
PY 2008
VL 28
IS 45
BP 11720
EP 11730
DI 10.1523/JNEUROSCI.1932-08.2008
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 369AV
UT WOS:000260665900030
PM 18987208
ER
PT J
AU Hollingshead, MG
AF Hollingshead, Melinda G.
TI Antitumor Efficacy Testing in Rodents
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID DRUG DEVELOPMENT; PRECLINICAL MODELS; MDA-MB-435 CELLS; BREAST-CANCER;
ANIMAL-MODELS; TUMOR-MODELS; IN-VITRO; MICE; PHARMACOKINETICS;
THERAPEUTICS
C1 NCI, Biol Testing Branch, Dev Therapeut Program, Fairview Ctr, Frederick, MD 21701 USA.
RP Hollingshead, MG (reprint author), NCI, Biol Testing Branch, Dev Therapeut Program, Fairview Ctr, Ste 205,1003 W 7th St, Frederick, MD 21701 USA.
EM hollingm@mail.nih.gov
NR 49
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U1 2
U2 3
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 NOV 5
PY 2008
VL 100
IS 21
DI 10.1093/jnci/djn351
PG 11
WC Oncology
SC Oncology
GA 373OQ
UT WOS:000260981900006
ER
PT J
AU Wacholder, S
Chatterjee, N
Caporaso, N
AF Wacholder, Sholom
Chatterjee, Nilanjan
Caporaso, Neil
TI Intermediacy and Gene-Environment Interaction: The Example of CHRNA5-A3
Region, Smoking, Nicotine Dependence, and Lung Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID GENOME-WIDE ASSOCIATION; PROSTATE-CANCER; ACETYLCHOLINE-RECEPTORS;
CANDIDATE GENES; SUSCEPTIBILITY; EPIDEMIOLOGY; DISEASE; RISK; LOCI; SNPS
C1 [Wacholder, Sholom; Chatterjee, Nilanjan; Caporaso, Neil] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Wacholder, S (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM WacholdS@mail.NIH.gov
NR 43
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U1 1
U2 2
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 NOV 5
PY 2008
VL 100
IS 21
DI 10.1093/jnci/djn380
PG 4
WC Oncology
SC Oncology
GA 373OQ
UT WOS:000260981900002
ER
PT J
AU Yu, L
Putnak, JR
Pletnev, AG
Markoff, L
AF Yu, Li
Putnak, J. Robert
Pletnev, Alexander G.
Markoff, Lewis
TI Attenuated West Nile viruses bearing 3 ' SL and envelope gene
substitution mutations
SO VACCINE
LA English
DT Article
DE Live West Nile vaccine; Flavivirus 3 ' SL mutation; Attenuation of
neurovirulence
ID JAPANESE ENCEPHALITIS-VIRUS; CD8(+) T-CELLS; LETHAL CHALLENGE;
MOLECULAR-BASIS; UNITED-STATES; NY99 STRAIN; GENOMIC RNA; VACCINE;
FLAVIVIRUS; NEUROVIRULENCE
AB Four viable West Nile (WN) 3'SL-mutant Viruses were evaluated for neuroinvasiveness and neurovirulence in mice. All mutants were highly attenuated for neuroinvasiveness. However, only one of these four (WNmutE virus) was significantly attenuated for neurovirulence. To attenuate WNmutE virus further, we introduced five substitution mutations into the envelope (env) gene segment in wild-type (wt) WN and WNmutE genomes, based on differences in the env gene Sequence between the live Japanese encephalitis vaccine (SA14-14-2) and its virulent parent. The env gene mutations had an attenuating effect in the context of the wt WNV genome but only a Marginal enhancing effect on the attenuation of WNmutE virus. Published by Elsevier Ltd.
C1 [Yu, Li; Markoff, Lewis] US FDA, Div Viral Prod, Lab Vector Borne Virus Dis, Bethesda, MD 20892 USA.
[Putnak, J. Robert] Walter Reed Army Inst Res, Div Communicable Dis & Immunol, Silver Spring, MD 20910 USA.
[Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Yu, L (reprint author), Bg 29A,Room 1B18,NIH Campus,8800 Rockville Pike, Bethesda, MD 20892 USA.
EM Li.Yu@fda.hhs.gov
FU National Vaccine Program
FX The authors thank Dr. V. Yamshchikov for the gift of the West Nile Virus
strain B956 infectious DNA. This work was partially supported by a grant
from the National Vaccine Program.
NR 36
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U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD NOV 5
PY 2008
VL 26
IS 47
BP 5981
EP 5988
DI 10.1016/j.vaccine.2008.08.064
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 384MZ
UT WOS:000261750200014
PM 18805457
ER
PT J
AU Vasan, RS
Demissie, S
Cupples, LA
Benjamin, EJ
White, C
Kimura, M
Gardner, JP
Cao, X
Aviv, A
Rifai, N
Wang, TJ
Levy, D
AF Vasan, Ramachandran S.
Demissie, Serkalem
Cupples, L. Adrienne
Benjamin, Emelia J.
White, Charles
Kimura, Masayuki
Gardner, Jeffrey P.
Cao, Xiaogian
Aviv, Abraham
Rifai, Nader
Wang, Thomas J.
Levy, Daniel
TI Association of Leukocyte Telomere Length With Circulating Biomarkers of
the Renin-Angiotensin-Aldosterone System: The Framingham Heart Study
Response
SO CIRCULATION
LA English
DT Letter
C1 [Vasan, Ramachandran S.; Demissie, Serkalem; Cupples, L. Adrienne; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[White, Charles] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Kimura, Masayuki; Gardner, Jeffrey P.; Cao, Xiaogian; Aviv, Abraham] Univ Med & Dent New Jersey, Ctr Human Dev & Aging, Newark, NJ 07103 USA.
[Rifai, Nader] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA.
[Wang, Thomas J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Cardiol, Boston, MA 02115 USA.
[Levy, Daniel] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD NOV 4
PY 2008
VL 118
IS 19
BP E689
EP E689
DI 10.1161/CIRCULATIONAHA.108.791111
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 368DW
UT WOS:000260602500017
ER
PT J
AU Siluk, D
Kim, HS
Cole, T
Wainer, IW
AF Siluk, Danuta
Kim, Hee Seung
Cole, Tyler
Wainer, Irving W.
TI HPLC-electrospray mass spectrometric assay for the determination of
(R,R)-fenoterol in rat plasma
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Fenoterol; HPLC-MS; SPE; Rat plasma
ID BETA-AGONISTS; FENOTEROL; DERIVATIZATION; BLOOD
AB A fast and specific liquid chromatography-mass spectrometry method for the determination of (R,R)fenoterol ((R,R)-Fen) in rat plasma has been developed and validated. (R,R)-Fen was extracted from 125 p,1 of plasma using solid phase extraction and analyzed on Atlantis HILIC Silica 3 mu m column. The mobile phase was composed of acetonitrile: ammonium acetate (pH 4.1; 20 mM) (85:15, v/v), at a flow rate of 0.2 ml/min. The lower limit of detection (LLOD) was 2 ng/ml. The procedure was validated and applied to the analysis of plasma samples from rats previously administered (R,R)-Fen in an intravenous bolus. Published by Elsevier B.V.
C1 [Siluk, Danuta] NIA, Clin Invest Lab, Gerontol Res Ctr, NIH,Bioanalyt & Drug Discovery Sect, Baltimore, MD 21224 USA.
RP Siluk, D (reprint author), NIA, Clin Invest Lab, Gerontol Res Ctr, NIH,Bioanalyt & Drug Discovery Sect, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM silukd@mail.nih.gov
FU Intramural Research Program of the National Institute on Aging/NIH
FX This work was supported by funds from the Intramural Research Program of
the National Institute on Aging/NIH.
NR 14
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U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD NOV 4
PY 2008
VL 48
IS 3
BP 960
EP 964
DI 10.1016/j.jpba.2008.05.034
PG 5
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 362KL
UT WOS:000260196500064
PM 18617349
ER
PT J
AU Mouw, T
Koster, A
Wright, ME
Blank, MM
Moore, SC
Hollenbeck, A
Schatzkin, A
AF Mouw, Traci
Koster, Annemarie
Wright, Margaret E.
Blank, Madeleine M.
Moore, Steven C.
Hollenbeck, Albert
Schatzkin, Arthur
TI Education and Risk of Cancer in a Large Cohort of Men and Women in the
United States
SO PLOS ONE
LA English
DT Article
ID SOCIOECONOMIC-STATUS; ASSOCIATION; ALCOHOL; HEALTH; LEVEL; DIET
AB Background: Education inequalities in cancer incidence have long been noted. It is not clear, however, whether such inequalities persist in the United States, especially for less common malignancies and after adjustment for individual risk factors.
Methodology/Principal Findings: Within the NIH-AARP Diet and Health Study, we examined the association between education and the risk of developing cancers in a prospective cohort of 498 455 participants who were 50-71 year old and without cancer at enrollment in 1995/96. During a maximum 8.2 years of follow-up we identified 40 443 cancers in men and 18 367 in women. In age-adjusted models, the least educated men (, high school), compared to those with the most education (post-graduate), had increased risks of developing cancers of the esophagus (RR: 2.64, 95% CI: 1.86-3.75), head and neck ( 1.98, 1.54-2.54), stomach (2.32, 1.68-3.18), colon (1.31, 1.12-1.53), rectum (1.68, 1.32-2.13), liver (1.90, 1.22-2.95), lung (3.67, 3.25-4.15), pleura (4.01, 1.91-8.42), bladder (1.56, 1.33-1.83) and combined smoking-related cancers (2.41, 2.22-2.62). In contrast, lower education level was associated with a decreased risk of melanoma of the skin (0.43, 0.35-0.54) and local prostate cancers (0.79, 0.74-0.85). Women with the least education had increased risks of colon (1.60, 1.24-2.05), lung (2.14, 1.79-2.56), kidney (1.68, 1.12-2.54) and combined smoking-related cancers (1.66, 1.43-1.92) but a lower risk of melanoma of the skin (0.33, 0.22-0.51), endometrial (0.67, 0.51-0.89) and invasive breast cancers (0.72, 0.61-0.84). Adjustment for smoking and other risk factors did not eliminate these associations, except those for cancers of the head and neck, colon, and liver in men and kidney in women.
Conclusions/Significance: We found a higher risk of malignant disease, particularly smoking-related cancers, among those in the lowest educational attainment category. Only some of the educational gradient is attributable to smoking. The persistence of substantial education inequalities in cancer incidence poses a challenge for etiologic research and public health policy.
C1 [Mouw, Traci] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, Fac Med, London, England.
[Koster, Annemarie] NIA, Lab Epidemiol, Demography, & Biomet, NIH, Bethesda, MD USA.
[Koster, Annemarie] Univ Maastricht, Fac Hlth, Med & Life Sci, Maastricht, Netherlands.
[Wright, Margaret E.] Univ Illinois, Dept Pathol, Chicago, IL 60680 USA.
[Blank, Madeleine M.; Moore, Steven C.; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
RP Mouw, T (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, Fac Med, London, England.
EM schatzka@mail.nih.gov
RI Koster, Annemarie/E-7438-2010; Moore, Steven/D-8760-2016
OI Moore, Steven/0000-0002-8169-1661
FU Intramural Research Programs at the National Cancer Institute; National
Institute on Aging, NIH
FX This research was supported (in part) by the Intramural Research
Programs at the National Cancer Institute and the National Institute on
Aging, NIH. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 23
TC 28
Z9 28
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 4
PY 2008
VL 3
IS 11
AR e3639
DI 10.1371/journal.pone.0003639
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432LJ
UT WOS:000265134300009
PM 18982064
ER
PT J
AU Seo, EJ
Liu, FR
Kawagishi-Kobayashi, M
Ung, TL
Cao, C
Dar, AC
Sicheri, F
Dever, TE
AF Seo, Eun Joo
Liu, Furong
Kawagishi-Kobayashi, Makiko
Ung, Tekly L.
Cao, Chune
Dar, Arvin C.
Sicheri, Frank
Dever, Thomas E.
TI Protein kinase PKR mutants resistant to the poxvirus pseudosubstrate K3L
protein
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE eIF2; translational control
ID VACCINIA VIRUS K3L; STRANDED-RNA BINDING; SUBSTRATE RECOGNITION;
CRYSTAL-STRUCTURE; ALPHA-SUBUNIT; GENE-PRODUCT; INITIATION
FACTOR-2-ALPHA; SACCHAROMYCES-CEREVISIAE; FUNCTIONALLY SUBSTITUTE; EIF2
ALPHA
AB As part of the mammalian cell innate immune response, the double-stranded RNA activated protein kinase PKR phosphorylates the translation initiation factor eIF2 alpha to inhibit protein synthesis and thus block viral replication. Poxviruses including vaccinia and smallpox viruses express PKR inhibitors such as the vaccinia virus K3L protein that resembles the N-terminal substrate-targeting domain of eIF2 alpha. Whereas high-level expression of human PKR was toxic in yeast, this growth inhibition was suppressed by coexpression of the K3L protein. We used this yeast assay to screen for PKR mutants that are resistant to K3L inhibition, and we identified 12 mutations mapping to the C-terminal lobe of the PKR kinase domain. The PKR mutations specifically conferred resistance to the K3L protein both in yeast and in vitro. Consistently, the PKR-D486V mutation led to nearly a 15-fold decrease in K3L binding affinity yet did not impair eIF2 alpha phosphorylation. Our results support the identification of the eIF2 alpha-binding site on an extensive face of the C-terminal lobe of the kinase domain, and they indicate that subtle changes to the PIKR kinase domain can drastically impact pseudosubstrate inhibition while leaving substrate phosphorylation intact. We propose that these paradoxical effects of the PKR mutations on pseudosubstrate vs. substrate interactions reflect differences between the rigid K3L protein and the plastic nature of eIF2 alpha around the Ser-51 phosphorylation site.
C1 [Seo, Eun Joo; Liu, Furong; Kawagishi-Kobayashi, Makiko; Ung, Tekly L.; Cao, Chune; Dever, Thomas E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Dar, Arvin C.; Sicheri, Frank] Mt Sinai Hosp, Program Syst Biol, Samuel Lunenfeld Res Inst, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
[Dar, Arvin C.; Sicheri, Frank] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
RP Dever, TE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM tdever@nih.gov
RI Sicheri, Frank/F-8856-2013;
OI Dever, Thomas/0000-0001-7120-9678
FU National Institute for Child Health and Human Development; National
Institutes of Health; National Cancer Institute of Canada; Canadian
Institutes for Health Research
FX We thank members of the laboratories of T.E.D., F.S., and Alan
Hinnebusch for advice and discussions and Alan Hinnebusch for comments
on the manuscript. We thank Eileen Chou for assistance with the genetic
characterization of the PKR mutants and Craig Cameron (Pennsylvania
State University) for the pGEX-3X-K3L plasmid. This work was supported
in part by the Intramural Research Program of the National Institute for
Child Health and Human Development, National Institutes of Health
(T.E.D.) and by grants from the National Cancer Institute of Canada (to
F.S.). A.C.D. was a recipient of a Canadian Graduate Scholarship from
the Canadian Institutes for Health Research. F.S. is a recipient of a
National Cancer Institute of Canada Scientist award.
NR 21
TC 15
Z9 17
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 4
PY 2008
VL 105
IS 44
BP 16894
EP 16899
DI 10.1073/pnas.0805524105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 372PP
UT WOS:000260913800020
PM 18971339
ER
PT J
AU Wu, JY
Purton, LE
Rodda, SJ
Chen, M
Weinstein, LS
McMahon, AP
Scadden, DT
Kronenberg, HM
AF Wu, Joy Y.
Purton, Louise E.
Rodda, Stephen J.
Chen, Min
Weinstein, Lee S.
McMahon, Andrew P.
Scadden, David T.
Kronenberg, Henry M.
TI Osteoblastic regulation of B lymphopoiesis is mediated by
G(s)alpha-dependent signaling pathways
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE B lymphocyte; G protein; osteoblast
ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW; PARATHYROID-HORMONE;
DIFFERENTIATION; RECEPTOR; MICE; NICHES; MOUSE; MAINTENANCE; DEFICIENCY
AB Osteoblasts play an increasingly recognized role in supporting hematopoietic development and recently have been implicated in the regulation of B lymphopoiesis. Here we demonstrate that heterotrimeric G protein a subunit G(s)alpha is required in cells of the osteoblast lineage for normal postnatal B lymphocyte production. Deletion of G(s)alpha early in the osteoblast lineage results in a 59% decrease in the percentage of B cell precursors in the bone marrow. Analysis of peripheral blood from mutant mice revealed a 67% decrease in the number of circulating B lymphocytes by 10 days age. Strikingly, other mature hematopoietic lineages are not decreased significantly. Mice lacking Gsa in cells of the lineage exhibit a reduction in pro-B and pre-B cells. Furthermore, interleukin (IL)-7 expression is attenuated in G(s)alpha-deficient blasts, and exogenous IL-7 is able to restore B cell populations in the bone marrow of mutant mice. Finally, the in B lymphopoiesis can be rescued by transplantation into a microenvironment. These findings confirm that osteoblasts are an important component of the B lymphocyte niche and demonstrate in vivo that G(s)alpha-dependent signaling pathways in cells of the osteoblast lineage extrinsically regulate bone marrow B lymphopoiesis, at least partially in an IL-7-dependent manner.
C1 [Wu, Joy Y.; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Purton, Louise E.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Purton, Louise E.; McMahon, Andrew P.; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Rodda, Stephen J.; McMahon, Andrew P.] Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA.
[Chen, Min; Weinstein, Lee S.] NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA.
RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
EM hkronenberg@partners.org
FU National Institutes of Health [AR053781, DK071773, HL081030, DK117940,
DK056246]; National Institute of Diabetes and Digestive and Kidney
Diseases' Intramural Research Program; National Health and Medical
Research Council of Australia [301299]; Arthritis Foundation [401683]
FX We thank Drs. Sean Wu, Carl Walkley, and Heather Fleming for discussion
and helpful suggestions; Dr. Natalie Sims for quantitation of osteoblast
surfaces; David Dombkowski and Laura Prickett for assistance with FACS
sorting; James Oh for technical assistance; and the MGH Center for
Comparative Medicine staff for caring for the mice in this study. This
work was supported in part by National Institutes of Health Grants
AR053781 (to J.Y.W.), DK071773 (to L.E.P.), HL081030 (to H.M.K. and
D.T.S.), DK117940 (to H.M.K.), and DK056246 (to A.P.M.), and by the
National Institute of Diabetes and Digestive and Kidney Diseases'
Intramural Research Program (M.C. and L.S.W.). S.R. was supported by
postdoctoral fellowships from the National Health and Medical Research
Council of Australia (301299) and the Arthritis Foundation (401683).
NR 42
TC 93
Z9 95
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 4
PY 2008
VL 105
IS 44
BP 16976
EP 16981
DI 10.1073/pnas.0802898105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 372PP
UT WOS:000260913800034
PM 18957542
ER
PT J
AU Chen, WZ
Zhu, ZY
Feng, Y
Dimitrov, DS
AF Chen, Weizao
Zhu, Zhongyu
Feng, Yang
Dimitrov, Dimiter S.
TI Human domain antibodies to conserved sterically restricted regions on
gp120 as exceptionally potent cross-reactive HIV-1 neutralizers
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE neutralization; therapeutic; epitope; steric restriction
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CORECEPTOR-BINDING-SITE; GLYCOPROTEIN;
EXPRESSION; LIBRARY; CORE; GP41
AB The antibody access to some conserved structures on the HIV-1 envelope glycoprotein (Env) is sterically restricted. We have hypothesized that the smallest independently folded antibody fragments (domains) could exhibit exceptionally potent and broadly cross-reactive neutralizing activity by targeting hidden conserved epitopes that are not accessible by larger antibodies. To test this hypothesis, we constructed a large (size 2.5 x 1010), highly diversified library of human antibody variable domains (domain antibodies) and used it for selection of binders to conserved Env structures by panning sequentially against Envs from different isolates. The highest affinity binder, m36, neutralized all tested HIV-1 isolates from clades A- D with an activity on average higher than that of C34, a peptide similar to the fusion inhibitor T20, which is in clinical use, and that of m9, which exhibits a neutralizing activity superior to known potent cross-reactive antibodies. Large-size fusion proteins of m36 exhibited diminished neutralizing activity but preincubation of virions with soluble CD4 restored it, suggesting that m36 epitope is sterically restricted and induced by CD4 (CD4i). M36 bound to gp120-CD4 complexes better than to gp120 alone and competed with CD4i antibodies. M36 is the only reported representative of a promising class of potent, broadly cross-reactive HIV-1 inhibitors based on human domain antibodies. It has potential for prevention and therapy and as an agent for exploration of the closely guarded conserved Env structures with implications for design of small molecule inhibitors and elucidation of mechanisms of virus entry and evasion of immune responses.
C1 [Chen, Weizao; Zhu, Zhongyu; Feng, Yang; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA.
[Zhu, Zhongyu] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, CCRNP, CCR,NIH, Bldg 469,Rm 150B, Frederick, MD 21702 USA.
EM dimitrov@ncifcrf.gov
FU National Institutes of Health (NIH); National Cancer Institute; Center
for Cancer Research; National Cancer Institute, NIH [N01-CO-12400];
Gates Foundation
FX We thank Christopher Broder, Gerald Quinnan, Dennis Burton, and Tim
Fouts for providing reagents and the members of our group John Owens,
Meiyun Zhang, and Xiadong Xiao for help. This project was supported by
the Intramural AIDS Targeted Antiviral Program of the National
Institutes of Health (NIH), by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research, by federal
funds from the National Cancer Institute, NIH, under contract
N01-CO-12400, and by the Gates Foundation (D.S.D.).
NR 20
TC 46
Z9 48
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 4
PY 2008
VL 105
IS 44
BP 17121
EP 17126
DI 10.1073/pnas.0805297105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 372PP
UT WOS:000260913800059
PM 18957538
ER
PT J
AU Castillo, CG
Mendoza-Trejo, S
Aguilar, MB
Freed, WJ
Giordano, M
AF Castillo, Claudia G.
Mendoza-Trejo, Soledad
Aguilar, Manuel B.
Freed, William J.
Giordano, Magda
TI Intranigral transplants of a GABAergic cell line produce long-term
alleviation of established motor seizures
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE neural transplantation; human glutamate decarboxylase-67; (GAD67);
gamma-aminobutyric acid (GABA); temporal lobe epilepsy; animal models;
substantia nigra pars reticulata; GABAergic cell line; kainic acid; high
performance liquid chromatography; status epilepticus
ID TEMPORAL-LOBE EPILEPSY; KAINATE-INDUCED EPILEPSY; RAT SUBSTANTIA-NIGRA;
LESIONED CA3 REGION; LARGE T-ANTIGEN; KINDLING EPILEPSY; ADULT
HIPPOCAMPUS; KAINIC ACID; NORADRENALINE RELEASE; BEHAVIORAL SEIZURES
AB We have previously shown that intranigral transplants of immortalized GABAergic cells decrease the number of kainic acid-induced seizures [Castillo CG, Mendoza S, Freed WJ, Giordano M. Intranigral transplants Of immortalized GABAergic cells decrease the expression of kainic acid-induced seizures in the rat. Behav Brain Res 2006; 171:409-15] in an animal model. In the present Study, recurrent spontaneous behavioral seizures were established by repeated systemic injections of this excitotoxin into male Sprague-Dawley rats. After the seizures had been established, cells were transplanted into the substantia nigra. Animals with transplants of control cells (without hGAD67 expression) OF with sham transplants showed a death rate of more than 40% over the 12 weeks of observation, whereas in animals with M213-20 CL-4 transplants, the death rate was reduced to less than 20%. The M213-20 CL-4 transplants significantly reduced the percentage of animals showing behavioral seizures; animals with these transplants also showed a lower occurrence of stage V seizures than animals in the other groups. In vivo and in vitro analyses provided evidence that the GABAergic cells show sustained expression of both GAD67 and hGAD67 cDNA, as well as increased gamma-aminobutyric acid (GABA) levels in the ventral mesencephalon of transplanted animals. Therefore, transplantation of GABA-producing cells can produce long-term alleviation of behavioral seizures in an animal model. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Castillo, Claudia G.; Mendoza-Trejo, Soledad; Giordano, Magda] Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Conductual & Cognit, Queretaro 76230, Qto, Mexico.
[Aguilar, Manuel B.] Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Celular & Mol, Queretaro 76230, Qto, Mexico.
[Freed, William J.] Natl Inst Drug Abuse, NIH, DHHS, Baltimore, MD 21224 USA.
RP Giordano, M (reprint author), Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Conductual & Cognit, Blvd Juriquilla 3001, Queretaro 76230, Qto, Mexico.
EM cgcastillo@cbm.uam.es; solecito75@yahoo.com; maguilar@servidor.unam.mx;
WFREED@intra.nida.nih.gov; giordano@servidor.unam.mx
OI Giordano, Magda/0000-0002-4335-7953
FU CONACyT [IN225305, 46161-M, 41477-Q, 153810]; NIDA; NIH; DHHS; DGEP-UNAM
FX The authors acknowledge the technical assistance of J. Mejia, A.
Marquez, A. Falcon, L. Gonzalez, L. Lara, and E. N. Hernandez; Leonor
Casanova executive coordinator of graduate Studies: M. Garcia head of
the Animal Care Facility; Dr. Michael C. Jeziorski, Dr. Aurea Orozco,
and M.C. Patricia Villalobos for advice on detection of the transgene;
and Dr. D. Pless for editing of the manuscript. This work was supported
by grants IN225305 from PAPIIT-DGAPA, 46161-M and 41477-Q from CONACyT,
and in part by the NIDA Intramural program, NIH, DHHS. C.G. Castillo was
supported by a fellowship from CONACyT (153810) and DGEP-UNAM.
NR 47
TC 22
Z9 24
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
EI 1872-7549
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD NOV 3
PY 2008
VL 193
IS 1
BP 17
EP 27
DI 10.1016/j.bbr.2008.04.023
PG 11
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 341TQ
UT WOS:000258738400002
PM 18571743
ER
PT J
AU Iyer, LM
Burroughs, AM
Aravind, L
AF Iyer, Lakshminarayan M.
Burroughs, A. M.
Aravind, L.
TI Unraveling the biochemistry and provenance of pupylation: a prokaryotic
analog of ubiquitination
SO BIOLOGY DIRECT
LA English
DT Article
ID STRUCTURE PREDICTION; ALIGNMENT ALGORITHM; CRYSTAL-STRUCTURE;
GAMMA-GLUTAMYL; IDENTIFICATION; PROTEASOME; DATABASE; COMPLEX; KINASE;
SERVER
AB Recently Mycobacterium tuberculosis was shown to possess a novel protein modification, in which a small protein Pup is conjugated to the epsilon-amino groups of lysines in target proteins. Analogous to ubiquitin modification in eukaryotes, this remarkable modification recruits proteins for degradation via archaeal-type proteasomes found in mycobacteria and allied actinobacteria. While a mycobacterial protein named PafA was found to be required for this conjugation reaction, its biochemical mechanism has not been elucidated. Using sensitive sequence profile comparison methods we establish that the PafA family proteins are related to the gamma-glutamyl-cysteine synthetase and glutamine synthetase. Hence, we predict that PafA is the Pup ligase, which catalyzes the ATP-dependent ligation of the terminal gamma-carboxylate of glutamate to lysines, similar to the above enzymes. We further discovered that an ortholog of the eukaryotic PAC2 (e.g. cg2106) is often present in the vicinity of the actinobacterial Pup-proteasome gene neighborhoods and is likely to represent the ancestral proteasomal chaperone. Pup-conjugation is sporadically present outside the actinobacteria in certain lineages, such as verrucomicrobia, nitrospirae, deltaproteobacteria and planctomycetes, and in the latter two lineages it might modify membrane proteins.
Reviewers: This article was reviewed by M. Madan Babu and Andrei Osterman
C1 [Iyer, Lakshminarayan M.; Aravind, L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Burroughs, A. M.] RIKEN, Yokohama Inst, OSC, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM lakshmin@mail.nih.gov; burrough@gsc.riken.jp; aravind@mail.nih.gov
FU National Library of Medicine at the National Institutes of Health, USA
FX Work by LMI and LA is supported by the intramural funds of the National
Library of Medicine at the National Institutes of Health, USA.
NR 21
TC 53
Z9 55
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD NOV 3
PY 2008
VL 3
AR 45
DI 10.1186/1745-6150-3-45
PG 7
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 381AX
UT WOS:000261508300001
PM 18980670
ER
PT J
AU Kaur, S
Samant, GV
Pramanik, K
Loscombe, PW
Pendrak, ML
Roberts, DD
Ramchandran, R
AF Kaur, Sukhbir
Samant, Ganesh V.
Pramanik, Kallal
Loscombe, Philip W.
Pendrak, Michael L.
Roberts, David D.
Ramchandran, Ramani
TI Silencing of directional migration in roundabout4 knockdown endothelial
cells
SO BMC CELL BIOLOGY
LA English
DT Article
ID REPULSIVE AXON GUIDANCE; TUMOR ANGIOGENESIS; SLIT-ROBO; MAGIC
ROUNDABOUT; RECEPTORS; EXPRESSION; ZEBRAFISH; COMPLEX; CHEMOTAXIS;
REPELLENT
AB Background: Roundabouts are axon guidance molecules that have recently been identified to play a role in vascular guidance as well. In this study, we have investigated gene knockdown analysis of endothelial Robos, in particular roundabout 4 (robo4), the predominant Robo in endothelial cells using small interfering RNA technology in vitro.
Results: Robo1 and Robo4 knockdown cells display distinct activity in endothelial cell migration assay. The knockdown of robo4 abrogated the chemotactic response of endothelial cells to serum but enhanced a chemokinetic response to Slit2, while robo1 knockdown cells do not display chemotactic response to serum or VEGF. Robo4 knockdown endothelial cells unexpectedly show up regulation of Rho GTPases. Zebrafish Robo4 rescues both Rho GTPase homeostasis and serum reduced chemotaxis in robo4 knockdown cells. Robo1 and Robo4 interact and share molecules such as Slit2, Mena and Vilse, a Cdc42-GAP. In addition, this study mechanistically implicates IRSp53 in the signaling nexus between activated Cdc42 and Mena, both of which have previously been shown to be involved with Robo4 signaling in endothelial cells.
Conclusion: This study identifies specific components of the Robo signaling apparatus that work together to guide directional migration of endothelial cells.
C1 [Samant, Ganesh V.; Pramanik, Kallal; Ramchandran, Ramani] Med Coll Wisconsin, Dept Pediat, Childrens Res Inst, Milwaukee, WI 53226 USA.
[Kaur, Sukhbir] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Loscombe, Philip W.] Univ Scranton, Dept Biol, Scranton, PA 18510 USA.
[Pendrak, Michael L.; Roberts, David D.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Ramchandran, R (reprint author), Med Coll Wisconsin, Dept Pediat, Childrens Res Inst, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM kaurs@mail.nih.gov; samant@mcw.edu; kpramani@mcw.edu;
ploscombe@gmail.com; mpendrak@helix.nih.gov; droberts@helix.nih.gov;
rramchan@mcw.edu
RI Roberts, David/A-9699-2008; Xiao, Yang/B-5668-2012
OI Roberts, David/0000-0002-2481-2981;
FU NCI CRTA; State of Wisconsin Breast Cancer Research Post-doctoral
Fellowship; NIH; NCI; Center of Cancer Research
FX We thank Jessica Baer and James Cherry of Gene Expression Laboratory,
NCI, Frederick, MD for assistance with real time PCR analysis. S. K. is
a recipient of NCI CRTA fellowship award; R. R. is a recipient of NCI
Scholar grant. G. V. S. is a recipient of a State of Wisconsin Breast
Cancer Research Post-doctoral Fellowship award. D. D. R. was supported
by the Intramural Research Program of the NIH, NCI, Center of Cancer
Research. The authors have no conflicting financial interests.
NR 36
TC 26
Z9 30
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2121
J9 BMC CELL BIOL
JI BMC Cell Biol.
PD NOV 3
PY 2008
VL 9
AR 61
DI 10.1186/1471-2121-9-61
PG 12
WC Cell Biology
SC Cell Biology
GA 390QQ
UT WOS:000262179200001
PM 18980679
ER
PT J
AU Parthasarathy, N
Saksena, R
Kovac, P
DeShazer, D
Peacock, SJ
Wuthiekanun, V
Heine, HS
Friedlander, AM
Cote, CK
Welkos, SL
Adamovicz, JJ
Bavari, S
Waag, DM
AF Parthasarathy, N.
Saksena, R.
Kovac, P.
DeShazer, D.
Peacock, S. J.
Wuthiekanun, V.
Heine, H. S.
Friedlander, A. M.
Cote, C. K.
Welkos, S. L.
Adamovicz, J. J.
Bavari, S.
Waag, D. M.
TI Application of carbohydrate microarray technology for the detection of
Burkholderia pseudomallei, Bacillus anthracis and Francisella tularensis
antibodies
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE Carbohydrate microarray; Burkholderia pseudomallei (melioidosis);
Bacillus anthracis (anthrax); Francisella tularensis (tularemia); Serum
antibodies
ID GLYCAN ARRAYS; O-ANTIGEN; EXOSPORIUM; LIPOPOLYSACCHARIDE; MELIOIDOSIS;
BCLA; OLIGOSACCHARIDE; GLYCOMICS; IDENTIFICATION; GLYCOPROTEIN
AB We developed a microarray platform by immobilizing bacterial 'signature' carbohydrates onto epoxide modified glass slides. The carbohydrate microarray platform was probed with sera from non-melioidosis and melioidosis (Burkholderia pseudomallei) individuals. The platform was also probed with sera from rabbits vaccinated with Bacillus anthracis spores and Francisella tularensis bacteria. By employing this microarray platform, we were able to detect and differentiate B. pseudomallei, B. anthracis and F. tularensis antibodies in infected patients, and infected or vaccinated animals. These antibodies were absent in the sera of naive test subjects. The advantages of the carbohydrate microarray technology over the traditional indirect hemagglutination and microagglutination tests for the serodiagnosis of melioidosis and tularemia are discussed. Furthermore, this array is a multiplex carbohydrate microarray for the detection of all three biothreat bacterial infections including melioidosis, anthrax and tularemia with one, multivalent device. The implication is that this technology could be expanded to include a wide array of infectious and biothreat agents. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Parthasarathy, N.; DeShazer, D.; Heine, H. S.; Cote, C. K.; Welkos, S. L.; Adamovicz, J. J.; Bavari, S.; Waag, D. M.] USA, Med Res Inst Infect Dis, Bacteriol Div, Frederick, MD 21702 USA.
[Saksena, R.; Kovac, P.] NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
[Peacock, S. J.; Wuthiekanun, V.] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand.
RP Parthasarathy, N (reprint author), USA, Med Res Inst Infect Dis, Bacteriol Div, Frederick, MD 21702 USA.
EM Narayanan.Parthasarathy@us.army.mil
FU US Army Medical Research and Materiel Command [2.10018_06 _RD-B,
2.10019_07_RD-B, 5.10023_08_RD-B]; Welcome Trust Career Development
fellowship in Clinical Tropical Medicine; Human Use Committee [FY 06-36,
HP-06-36]
FX The research described herein was sponsored by the US Army Medical
Research and Materiel Command under projects 2.10018_06 _RD-B,
2.10019_07_RD-B and 5.10023_08_RD-B. The authors thank Sarah L. Norris
for statistical analysis. The authors also thank Dr. Sharan VedBrat
(KamTek Inc., Gaithersburg, MD) for carbohydrate printing. The support
of staff at Sappasithiprasong Hospital, Ubon Ratchathani, and the
Mahidol Oxford Tropical Medicine Research Unit, particularly Dr. Direk
Limmathurotsakul and Dr. Allen Chang, is gratefully acknowledged. S.P.
is funded by a Welcome Trust Career Development fellowship in Clinical
Tropical Medicine. The use of human serum samples was approved by the
Human Use Committee (FY 06-36, HP-06-36). Research was conducted in
compliance with the Animal Welfare Act and other federal statutes and
regulations relating to animals and experiments involving animals and
adheres to principles stated in the Guide for the Care and Use of
Laboratory Animals, National Research Council, 1996. The facility where
this research was conducted is fully accredited by the Association for
Assessment and Accreditation of Laboratory Animal Care International.
Opinions, interpretations, conclusions and recommendations are those of
the authors and not endorsed by the US Army.
NR 38
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U1 1
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0008-6215
J9 CARBOHYD RES
JI Carbohydr. Res.
PD NOV 3
PY 2008
VL 343
IS 16
BP 2783
EP 2788
DI 10.1016/j.carres.2008.05.021
PG 6
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 370AU
UT WOS:000260735900010
PM 18558401
ER
PT J
AU Rojas, R
van Vlijmen, T
Mardones, GA
Prabhu, Y
Rojas, AL
Mohammed, S
Heck, AJR
Raposo, G
van der Sluijs, P
Bonifacino, JS
AF Rojas, Raul
van Vlijmen, Thijs
Mardones, Gonzalo A.
Prabhu, Yogikala
Rojas, Adriana L.
Mohammed, Shabaz
Heck, Albert J. R.
Raposo, Graca
van der Sluijs, Peter
Bonifacino, Juan S.
TI Regulation of retromer recruitment to endosomes by sequential action of
Rab5 and Rab7
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID MANNOSE 6-PHOSPHATE RECEPTOR; GROWTH-FACTOR RECEPTOR; TRANS-GOLGI
NETWORK; TO-TGN TRANSPORT; SORTING NEXIN-1; RETROGRADE TRANSPORT;
ADAPTER PROTEIN; ENDOCYTIC COMPARTMENTS; MEMBRANE-PROTEINS; CARGO
PROTEINS
AB The retromer complex mediates retrograde transport of transmembrane cargo from endosomes to the trans-Golgi network (TGN). Mammalian retromer is composed of a sorting nexin (SNX) dimer that binds to phosphatidylinositol 3-phosphate-enriched endosomal membranes and a vacuolar protein sorting (Vps) 26/29/35 trimer that participates in cargo recognition. The mammalian SNX dimer is necessary but not sufficient for recruitment of the Vps26/29/35 trimer to membranes. In this study, we demonstrate that the guanosine triphosphatase Rab7 contributes to this recruitment. The Vps26/29/35 trimer specifically binds to Rab7-guanosine triphosphate (GTP) and localizes to Rab7-containing endosomal domains. Interference with Rab7 function causes dissociation of the Vps26/29/35 trimer but not the SNX dimer from membranes. This blocks retrieval of mannose 6-phosphate receptors to the TGN and impairs cathepsin D sorting. Rab5-GTP does not bind to the Vps26/29/35 trimer, but perturbation of Rab5 function causes dissociation of both the SNX and Vps26/29/35 components from membranes through inhibition of a pathway involving phosphatidylinositol 3-kinase. These findings demonstrate that Rab5 and Rab7 act in concert to regulate retromer recruitment to endosomes.
C1 [van Vlijmen, Thijs; van der Sluijs, Peter] Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands.
[Rojas, Raul; Mardones, Gonzalo A.; Prabhu, Yogikala; Bonifacino, Juan S.] Eunice Kennedy Shriver NICHHD, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
[Rojas, Adriana L.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Mohammed, Shabaz; Heck, Albert J. R.] Univ Med Ctr Utrecht, Dept Biomol Mass Spectrometry, NL-3584 CX Utrecht, Netherlands.
[Raposo, Graca] CNRS, Inst Curie, UMR 144, F-75248 Paris, France.
RP van der Sluijs, P (reprint author), Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands.
EM p.vandersluijs@umcutrecht.nl; juan@helix.nih.gov
RI van Vlijmen, Thijs/B-4069-2009; Heck, Albert/D-7098-2011; Mohammed,
Shabaz/D-1042-2010; Rojas, Adriana/G-2403-2011;
OI van Vlijmen, Thijs/0000-0002-5882-6660; Heck,
Albert/0000-0002-2405-4404; Mohammed, Shabaz/0000-0003-2640-9560; Rojas,
Adriana/0000-0002-7358-3505; Bonifacino, Juan S./0000-0002-5673-6370
FU National Institute of Child Health and Human Development; Netherlands
Proteomics Center
FX This work was supported by the Intramural Program of the National
Institute of Child Health and Human Development, the National Institutes
of Health (J.S. Bonifacino), and the Netherlands Proteomics Center (P.
van der Sluijs and A. J. R. Heck).
NR 63
TC 177
Z9 179
U1 4
U2 12
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD NOV 3
PY 2008
VL 183
IS 3
BP 513
EP 526
DI 10.1083/jcb.200804048
PG 14
WC Cell Biology
SC Cell Biology
GA 374RA
UT WOS:000261060200017
PM 18981234
ER
PT J
AU Luo, WM
Yu, QS
Tweedie, D
Deschamps, J
Parrish, D
Holloway, HW
Li, YZ
Brossi, A
Greig, NH
AF Luo, Weiming
Yu, Qian-Sheng
Tweedie, David
Deschamps, Jeffery
Parrish, Damon
Holloway, Harold W.
Li, Yazhou
Brossi, Arnold
Greig, Nigel H.
TI Syntheses of Aromatic Substituted 6 '-Thiothalidomides
SO SYNTHESIS-STUTTGART
LA English
DT Article
DE 6 '-thiothalidomides; TNF-alpha; thionation; regioselectivity; HMBC
ID ERYTHEMA-NODOSUM LEPROSUM; ORGANOPHOSPHORUS COMPOUNDS; ALPHA PRODUCTION;
THALIDOMIDE; DERIVATIVES; ANALOGS; INHIBITION; ACIDS
AB A resurgence of interest in thalidomide has occurred as a consequence of its diverse immunomodulatory and anticancer actions. which has fuelled interest in synthetic analogues with higher potencies or less undesirable side effect profiles. Several novel aromatic substituted 6'-thiothalidomides were synthesized whose synthetic route and strategy were developed on the basis of an analysis of reaction mechanisms. The regioselectivity of mono-thionation of aromatic substituted thalidomides with Lawesson's reagent is described, and the chemoselectivity of hydrogenation between the nitro group and 6'-thiocarbonyl group is discussed. Full characterization of eight substituted 6'-thiothalidomides is reported.
C1 [Luo, Weiming; Yu, Qian-Sheng; Tweedie, David; Holloway, Harold W.; Li, Yazhou; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Deschamps, Jeffery; Parrish, Damon] USN, Res Lab, Dept Navy, Struct Matter Lab, Washington, DC 20375 USA.
[Brossi, Arnold] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA.
RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM Greign@grc.nia.nih.gov
OI Deschamps, Jeffrey/0000-0001-5845-0010
FU National Institute on Aging; National Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health. The
authors are indebted to the Intramural Research Program of the National
Institute on Drug Abuse, NIH, for use of NMR equipment.
NR 19
TC 10
Z9 10
U1 0
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0039-7881
J9 SYNTHESIS-STUTTGART
JI Synthesis
PD NOV 3
PY 2008
IS 21
BP 3415
EP 3422
DI 10.1055/s-0028-1083179
PG 8
WC Chemistry, Organic
SC Chemistry
GA 375MO
UT WOS:000261118200009
ER
PT J
AU Schuckit, MA
Smith, TL
Trim, R
Heron, J
Horwood, J
Davis, JM
Hibbeln, JR
AF Schuckit, Marc A.
Smith, Tom L.
Trim, Ryan
Heron, Jon
Horwood, Jeremy
Davis, John M.
Hibbeln, Joseph R.
CA ALSPAC Study Team
TI The performance of elements of a 'level of response to alcohol'-based
model of drinking behaviors in 13-year-olds
SO ADDICTION
LA English
DT Article
DE Alcohol; environment; genetics; structural equation models; response to
alcohol; young adolescents
ID USE DISORDERS; RISK; QUESTIONNAIRE; ADOLESCENTS; CONSUMPTION;
POPULATION; PREDICTORS; DEPENDENCE; MODERATOR; CHILDREN
AB Aim The goals of this paper are to evaluate whether drinking practices among peers mediates the relationship between a low level of response (LR) to alcohol and a person's heavier drinking and alcohol-related problems in 12-14-year-olds. Design Correlations and structural equation models (SEM) were used to test a hypothesized model of the relationships among key variables in adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC), a longitudinal birth cohort study in Bristol, England. Participants These included 688 boys (40.4%) and girls who were offspring of the pregnant women who had been selected as ALSPAC participants in 1991 and 1992. The offspring were interviewed at about age 13 years, and those who had ever consumed a full drink completed the Self-Report of the Effects of Alcohol (SRE) questionnaire indicating the number of drinks required for up to four effects early in their drinking histories. A higher number of drinks required for effects indicated a low LR per drink consumed. Findings The SEM explained 58% of the variance of the alcohol pattern, and had good fit characteristics. A low LR was related to heavier drinking and more alcohol problems both directly and as mediated partially by drinking in peers. The model performed well across the narrow age range, and applied equally well in boys and girls. Conclusions The perceived drinking practices of peers is a potentially important mediator of how a low LR to alcohol relates to drinking practices during early adolescence. The findings may be useful in developing approaches to prevent heavier drinking in this young group.
C1 [Schuckit, Marc A.; Smith, Tom L.; Trim, Ryan] VA San Diego Healthcare Syst, San Diego, CA USA.
[Heron, Jon] ALSPAC, Dept Social Med, Bristol, Avon, England.
[Horwood, Jeremy] Univ Bristol, Dept Social Med, MRC Hlth Serv Res Collaborat, Bristol, Avon, England.
[Davis, John M.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
[Hibbeln, Joseph R.] NIAAA, LMBB, Bethesda, MD USA.
[ALSPAC Study Team] Univ Bristol, ALSPAC, Bristol, Avon, England.
[Schuckit, Marc A.; Smith, Tom L.; Trim, Ryan] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92161 USA.
RP Schuckit, MA (reprint author), Univ Calif San Diego, Dept Psychiat 116A, 3350 La Jolla Village Dr, San Diego, CA 92161 USA.
EM mschuckit@ucsd.edu
RI Heron, Jon/D-5884-2011
OI Heron, Jon/0000-0001-6199-5644
FU UK Medical Research Council; Wellcome Trust; University of Bristol;
University of California, San Francisco; NIAAA [2R01 AA05526]
FX We are extremely grateful to all the families who took part in this
study, the midwives for their help in recruiting them and the whole
ALSPAC team, which includes interviewers, computer and laboratory
technicians, clerical workers, research scientists, volunteers,
managers, receptionists and nurses. The UK Medical Research Council, the
Wellcome Trust and the University of Bristol provide core support for
ALSPAC. This publication is the work of the authors, who also serve as
guarantors for the contents of this paper. This work was supported by
the Veterans Affairs Research Service with funds provided by the State
of California for medical research on alcohol and substance abuse
through the University of California, San Francisco; and by NIAAA Grant
2R01 AA05526.
NR 49
TC 13
Z9 13
U1 5
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD NOV
PY 2008
VL 103
IS 11
BP 1786
EP 1792
DI 10.1111/j.1360-0443.2008.02325.x
PG 7
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 361MD
UT WOS:000260130900005
PM 18778389
ER
PT J
AU Grossman, C
Hadley, W
Brown, LK
Houck, CD
Peters, A
Tolou-Shams, M
AF Grossman, Cynthia
Hadley, Wendy
Brown, Larry K.
Houck, Christopher D.
Peters, April
Tolou-Shams, Marina
CA Project SHIELD Study Grp
TI Adolescent Sexual Risk: Factors Predicting Condom Use Across the Stages
of Change
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Adolescent; Sexual risk behavior; Stages of change; Condom use
ID TRANSTHEORETICAL MODEL; PSYCHOSOCIAL FACTORS; SELF-EFFICACY; DECISIONAL
BALANCE; BEHAVIORAL-CHANGE; HIV PREVENTION; TRANSITIONS; INTERCOURSE;
INTERVENTION; ADOPTION
AB This study examined factors associated with high-risk adolescents' movement toward or away from adopting consistent condom use behavior using the Transtheoretical Model Stages of Change. Participants drawn from the inactive comparison condition of a randomized HIV prevention trial (Project SHIELD) responded to items assessing pros and cons of condom use, peer norms, condom communication, and perceived invulnerability to HIV. Participants were categorized based on their condom use behavior using the Transtheoretical Model. Multiple logistic regressions found that progression to consistent condom use was predicted by continuing to perceive more advantages to condom use, reporting greater condom use communication with partners, and less perceived invulnerability to HIV. Movement away from adopting consistent condom use was predicted by a decrease in perceived advantages to condom use, increased perceived condom disadvantages, and fewer condom discussions. Future interventions may be tailored to enhance these factors that were found to change over time.
C1 [Grossman, Cynthia] NIMH, Bethesda, MD 20892 USA.
[Hadley, Wendy; Brown, Larry K.; Houck, Christopher D.; Peters, April; Tolou-Shams, Marina] Rhode Isl Hosp, Brown Med Sch, Providence, RI USA.
Project SHIELD Study Grp, Providence, RI USA.
RP Grossman, C (reprint author), NIMH, 6001 Execut Blvd,Rm 6201, Bethesda, MD 20892 USA.
EM grossmanc@mail.nih.gov
FU PHS HHS [U10 SMS2073]
NR 33
TC 19
Z9 19
U1 4
U2 15
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS behav.
PD NOV
PY 2008
VL 12
IS 6
BP 913
EP 922
DI 10.1007/s10461-008-9396-y
PG 10
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 359CC
UT WOS:000259962800010
PM 18427971
ER
PT J
AU Johnson, MO
Dilworth, SE
Neilands, TB
Chesney, MA
Rotheram-Borus, MJ
Remien, RH
Weinhardt, L
Ehrhardt, AA
Morin, SF
AF Johnson, Mallory O.
Dilworth, Samantha E.
Neilands, Torsten B.
Chesney, Margaret A.
Rotheram-Borus, Mary Jane
Remien, Robert H.
Weinhardt, Lance
Ehrhardt, Anke A.
Morin, Stephen F.
CA NIMH HLP Team
TI Predictors of Attrition Among High Risk HIV-Infected Participants
Enrolled in a Multi-Site Prevention Trial
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Clinical trials; Prevention; Retention; Depression
ID PROGRAM; DEPRESSION; MORTALITY
AB Retaining high-risk individuals is critical for HIV prevention trials. The current analyses examined predictors of trial dropout among HIV-infected men and women in a multi-site HIV prevention trial. Results indicated that dropouts (n = 74) were more likely to be younger, depressed, and not taking antiretroviral therapy (ART) than those who continued (n = 815). No other background, substance use, or transmission risk differences were found, suggesting no direct evidence of dropout bias on key outcomes. Efforts may be warranted for early detection and treatment of depression and for improving retention of younger participants and those not on ART.
C1 [Johnson, Mallory O.; Dilworth, Samantha E.; Neilands, Torsten B.; Chesney, Margaret A.; Rotheram-Borus, Mary Jane; Morin, Stephen F.] Univ Calif San Francisco, San Francisco, CA 94105 USA.
[Chesney, Margaret A.] NIH, Natl Ctr Complementary & Alternat Med, Los Angeles, CA USA.
[Weinhardt, Lance] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
NIMH HLP Team, Rockville, MD USA.
RP Johnson, MO (reprint author), Univ Calif San Francisco, 50 Beale St,Suite 1300, San Francisco, CA 94105 USA.
EM Mallory.Johnson@ucsf.edu
FU NIMH NIH HHS [P30 MH043520, U10 MH057616, U10 MH057616-07]
NR 12
TC 8
Z9 8
U1 1
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS behav.
PD NOV
PY 2008
VL 12
IS 6
BP 974
EP 977
DI 10.1007/s10461-007-9356-y
PG 4
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 359CC
UT WOS:000259962800017
PM 18202908
ER
PT J
AU Marsden, MD
Xu, J
Hamer, D
Zack, JA
AF Marsden, Matthew D.
Xu, Jie
Hamer, Dean
Zack, Jerome A.
TI Short Communication Activating Stimuli Enhance Immunotoxin-Mediated
Killing of HIV-Infected Macrophages
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY;
GREEN-FLUORESCENT PROTEIN; CD4(+) T-CELLS; IN-VIVO; MONONUCLEAR
PHAGOCYTES; REPLICATION-COMPETENT; COMBINATION THERAPY; LATENT
RESERVOIR; BRAIN-TISSUE
AB Strategies for purging persistent reservoirs in human immunodeficiency virus (HIV)-infected individuals may be enhanced by including agents that specifically kill virus-expressing cells. Anti-HIV envelope immunotoxins (ITs) represent one class of candidate molecules that could fulfill this function. We have previously utilized an anti-gp120 IT in conjunction with various stimulants to kill latently infected T cells ex vivo. Here we show that primary macrophages expressing HIV Env are relatively refractory to killing by IT when used alone. However, including stimulants such as prostratin or granulocyte-macrophage colony-stimulating factor to increase HIV gene expression in infected macrophages enhanced IT-mediated killing. Therefore, "activation-elimination" strategies similar to those proposed for purging the latent HIV reservoir may prove useful in clearing chronically infected macrophages in vivo.
C1 [Marsden, Matthew D.; Xu, Jie; Zack, Jerome A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Marsden, Matthew D.; Zack, Jerome A.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA AIDS Inst, Los Angeles, CA 90095 USA.
[Xu, Jie; Zack, Jerome A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA.
[Hamer, Dean] NCI, NIH, Vaccine Branch, Bethesda, MD 20892 USA.
RP Zack, JA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, 615 Charles E Young Dr,S BSRB 173, Los Angeles, CA 90095 USA.
EM jzack@ucla.edu
FU NIH [AI70010, AI036059]
FX This work was supported by NIH Grants AI70010, AI036059, and the UCLA
CFAR.
NR 53
TC 9
Z9 10
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV
PY 2008
VL 24
IS 11
BP 1399
EP 1404
DI 10.1089/aid.2008.0082
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 380UT
UT WOS:000261491600008
PM 19000022
ER
PT J
AU Schuckit, MA
Smith, TL
Trim, RS
Heron, J
Horwood, J
Davis, J
Hibbeln, J
AF Schuckit, Marc A.
Smith, Tom L.
Trim, Ryan S.
Heron, Jon
Horwood, Jeremy
Davis, John
Hibbeln, Joseph
CA ALSPAC Study Team
TI The Self-Rating of the Effects of Alcohol Questionnaire as a Predictor
of Alcohol-Related Outcomes in 12-Year-Old Subjects
SO ALCOHOL AND ALCOHOLISM
LA English
DT Article
ID LOW-LEVEL; USE DISORDERS; ADOLESCENTS; SENSITIVITY; DEPENDENCE; RISK;
CHALLENGE; RESPONSES; CHILDREN; DRINKING
AB Aims: A low level of response (LR), or low sensitivity, to alcohol as established by alcohol challenges has been shown to predict future heavier drinking, alcohol-related problems and alcohol use disorders. To date, only one study has evaluated the predictive validity of a second measure of LR as determined by the Self-Report of the Effects of Alcohol (SRE) Questionnaire. The current analyses evaluate the ability of SRE scores as determined at age 12 to predict heavier drinking and alcohol-related problems 2 years later in a sample from the United Kingdom. Methods: The subjects were 156 boys (54.5%) and girls from the Avon Longitudinal Study of Parents and Children (ALSPAC) who had reported consuming one or more standard drinks by age 12 and who were followed up 2 years later. Results: The age 12 SRE scores correlated with the number of drinks per week, maximum drinks and the number of alcohol problems both at baseline and at age 14 follow-ups. In these evaluations, a larger number of drinks required for effects on the SRE (i.e. a lower LR per drink consumed) related to heavier intake and alcohol-related difficulties. Simultaneous entry multiple regression analyses revealed that the age 12 SRE score maintained a significant relationship with age 14 higher number of drinks per week and the number of alcohol problems even when the age 12 values for alcohol intake and problems were used as covariates. Conclusion: The SRE scores appear to have value in predicting future heavier drinking and alcohol problems in 12-year olds that go beyond the information offered by the earlier drinking pattern alone.
C1 [Schuckit, Marc A.] Univ Calif San Diego, VA San Diego Healthcare Syst, San Diego, CA 92103 USA.
[Heron, Jon] Univ Bristol, Avon Longitudinal Study Parents & Children ALSPAC, Bristol BS8 1TH, Avon, England.
[Davis, John] Univ Illinois, Chicago, IL USA.
[Hibbeln, Joseph] NIAAA, NIH, Bethesda, MD USA.
RP Schuckit, MA (reprint author), Univ Calif San Diego, VA San Diego Healthcare Syst, San Diego, CA 92103 USA.
EM mschuckit@ucsd.edu
RI Heron, Jon/D-5884-2011
OI Heron, Jon/0000-0001-6199-5644
FU Veterans Affairs Research Service; NIAAA [2R01 AA05526]; State of
California for medical research on alcohol and substance abuse through
the University of California, San Francisco
FX We are extremely grateful to all the families who took part in this
study, the midwives for their help in recruiting them and the whole
ALSPAC team, which includes interviewers, computer and laboratory
technicians, clerical workers, research scientists, volunteers,
managers, receptionists and nurses. TheUKMedical Research Council, the
Wellcome Trust and the University of Bristol provide core support for
ALSPAC. This publication is the work of the authors who also serve as
guarantors for the contents of this paper. This work was supported by
the Veterans Affairs Research Service, NIAAA Grant 2R01 AA05526 and
funds were provided by the State of California for medical research on
alcohol and substance abuse through the University of California, San
Francisco.
NR 40
TC 20
Z9 20
U1 3
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0735-0414
J9 ALCOHOL ALCOHOLISM
JI Alcohol Alcohol.
PD NOV-DEC
PY 2008
VL 43
IS 6
BP 641
EP 646
DI 10.1093/alcalc/agn077
PG 6
WC Substance Abuse
SC Substance Abuse
GA 365BN
UT WOS:000260381000007
PM 18845530
ER
PT J
AU Signore, C
Aros, S
Morrow, JD
Troendle, J
Conley, MR
Flanigan, EY
Cassorla, F
Mills, JL
AF Signore, Caroline
Aros, Sofia
Morrow, Jason D.
Troendle, James
Conley, Mary R.
Flanigan, Elizabeth Y.
Cassorla, Fernando
Mills, James L.
TI Markers of Oxidative Stress and Systemic Vasoconstriction in Pregnant
Women Drinking >= 48 g of Alcohol per Day
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol; Pregnancy; Isoprostanes; Prostacyclin; Thromboxane; Fetal
Alcohol Spectrum Disorders
ID CHROMATOGRAPHY MASS-SPECTROMETRY; LIPID-PEROXIDATION; OXIDANT STRESS;
IN-VIVO; 8-ISO-PROSTAGLANDIN F2-ALPHA; MATERNAL THROMBOXANE; BIOACTIVE
PRODUCTS; BIOLOGICAL-FLUIDS; HUMAN PLACENTA; BLOOD-FLOW
AB Background: The precise pathway by which alcohol causes the characteristic features of fetal alcohol spectrum disorders is unknown. Proposed mechanisms for fetal injury from maternal alcohol use include cellular damage from oxidative stress and impaired fetal oxygenation related to maternal systemic vasoconstriction. Our objective was to compare the levels of urinary markers of oxidative stress and systemic vasoconstriction between women consuming large amounts of alcohol during pregnancy and women who did not drink alcohol during pregnancy. Methods: Pregnant women consuming >= 48 g alcohol per day (n = 29) on average and pregnant women who abstained from alcohol use (n = 39) were identified using detailed interviews and home visits. Random maternal urine specimens were collected. Urinary levels of the oxidative stress marker, 8-isoprostane F2 alpha, and of the vasoactive prostaglandin metabolites, 2,3-dinor-6-keto-prostaglandin F1 alpha (a vasodilator) and 11-dehydro-thromboxane B2 (a vasoconstrictor), were measured using mass spectrometric methods. All analyte levels were corrected for urinary creatinine.
Results: In crude analyses, there was no significant difference in 8-isoprostane F2 alpha between pregnant drinkers and nondrinkers (2.16 vs. 2.08 ng/mg creatinine, respectively, p = 0.87). There were no significant differences between the drinking and nondrinking groups in levels of 2,3-dinor-6-keto-prostaglandin F1 alpha (1.03 vs. 1.17 ng/mg creatinine, repectively, p = 0.50), 11-dehydro-thromboxane B2 (0.72 vs. 0.59 ng/mg creatinine, respectively, p = 0.21), or the ratio of vasodilatory metabolite to vasoconstrictive metabolite (1.73 vs. 2.72, respectively, p = 0.14). Adjusting for maternal age, marital status, smoking, and gestational age at sampling did not substantially alter the results.
Conclusion: Our results show no difference in levels of urinary eicosanoid markers of oxidative stress and systemic vasoconstriction between pregnant women who drink heavily and pregnant women who abstain. These findings speak against a role for maternal oxidative stress or systemic vasoconstriction in the pathogenesis of alcohol damage to the fetus.
C1 [Mills, James L.] NICHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res,NIH,US Dept Hlth, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Aros, Sofia] Univ Chile, San Borja Arriaran Clin Hosp, Sch Med, Dept Pediat, Santiago, Chile.
[Morrow, Jason D.] Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Dept Med, Nashville, TN 37212 USA.
[Morrow, Jason D.] Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Dept Pharmacol, Nashville, TN 37212 USA.
[Troendle, James] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH,US Dept Hlth & Human Serv, Bethesda, MD USA.
[Flanigan, Elizabeth Y.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Washington, DC USA.
[Flanigan, Elizabeth Y.] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Cassorla, Fernando] Univ Chile, Inst Maternal & Child Res, Dept Pediat, Div Pediat Endocrinol, Santiago, Chile.
RP Mills, JL (reprint author), NICHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res,NIH,US Dept Hlth, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
EM MillsJ@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institutes of Health [GM15431, DK48831, ES13125]
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development and by National Institutes of Health grants GM15431, DK48831
and ES13125.
NR 47
TC 8
Z9 9
U1 2
U2 6
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD NOV
PY 2008
VL 32
IS 11
BP 1893
EP 1898
DI 10.1111/j.1530-0277.2008.00773.x
PG 6
WC Substance Abuse
SC Substance Abuse
GA 362FK
UT WOS:000260183400005
PM 18715278
ER
PT J
AU Bain, LJ
Jedrziewski, K
Morrison-Bogorad, M
Albert, M
Cotman, C
Hendrie, H
Trojanowski, JQ
AF Bain, Lisa J.
Jedrziewski, Kathy
Morrison-Bogorad, Marcelle
Albert, Marilyn
Cotman, Carl
Hendrie, Hugh
Trojanowski, John Q.
TI Healthy brain aging: A meeting report from the Sylvan M. Cohen Annual
Retreat of the University of Pennsylvania Institute on Aging
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
ID ALZHEIMER-DISEASE; UNITED-STATES; DEMENTIA; EXERCISE; MEMORY; OLDER;
RISK
C1 [Bain, Lisa J.; Jedrziewski, Kathy; Trojanowski, John Q.] Univ Penn, Sch Med, Inst Aging, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA.
[Bain, Lisa J.; Jedrziewski, Kathy; Trojanowski, John Q.] Univ Penn, Sch Med, Dept Pathol & Lab, Philadelphia, PA 19104 USA.
[Morrison-Bogorad, Marcelle] NIA, NIH, Bethesda, MD 20892 USA.
[Albert, Marilyn] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Cotman, Carl] Univ Calif Irvine, Irvine, CA USA.
[Hendrie, Hugh] Indiana Univ, Sch Med, Indianapolis, IN USA.
RP Trojanowski, JQ (reprint author), Univ Penn, Sch Med, Inst Aging, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA.
EM trojanow@mail.med.upenn.edu
FU NIA NIH HHS [P30 AG010124, P30 AG010124-18]
NR 20
TC 10
Z9 10
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD NOV
PY 2008
VL 4
IS 6
BP 443
EP 446
DI 10.1016/j.jalz.2008.08.006
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 374PS
UT WOS:000261056800011
PM 18945646
ER
PT J
AU Keaney, JF
Lipinska, I
Larson, MG
Dupuis, J
Freedman, JE
Hamburg, NM
Massaro, JM
Rong, J
Sutherland, P
Vita, JA
Vasan, RS
Benjamin, EJ
AF Keaney, John F., Jr.
Lipinska, Izabella
Larson, Martin G.
Dupuis, Josee
Freedman, Jane E.
Hamburg, Naomi M.
Massaro, Joseph M.
Rong, Jian
Sutherland, Patrice
Vita, Joseph A.
Vasan, Ramachandran S.
Benjamin, Emelia J.
TI Clinical correlates, heritability, and genetic linkage of circulating
CD40 ligand in the Framingham Offspring Study
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ACUTE CORONARY SYNDROMES; SOLUBLE CD40L; ENDOTHELIAL-CELLS;
CARDIOVASCULAR RISK; ADHESION MOLECULE; HYPER-IGM; ATHEROSCLEROSIS;
EXPRESSION; PLASMA; INFLAMMATION
AB Background The CD40 receptor and its ligand (CD40L) are known to modulate both inflammation and thrombosis-2 processes important for the development and clinical expression of atherosclerosis. Circulating soluble CD40L (sCD40L) concentration predicts cardiovascular risk in selected patient samples. The purpose of this study was to determine the predictors of sCD40L in a large, community-based sample.
Methods We determined both serum and plasma sCD40L concentration in 3,259 participants (54% women) from the Framingham Offspring Study.
Results In multivariable models, advancing age was the only consistent (inverse) correlate of both serum and plasma sCD40L concentration. Overall, the variability explained by clinical covariates was very low for both measurements of sCD40L; with values of only 1.4% and 2.7% for serum and plasma, respectively. We observed that genetic factors accounted for a modest (12% serum; 14% plasma) amount of the adjusted variability in sCD40L.
Conclusions Circulating sCD40L concentration was poorly associated with known cardiovascular disease (CVD) risk factors and was modestly heritable. Determining if either serum or plasma sCD40L are predictive of CVD risk in the community will require longitudinal follow-up. (Am Heart J 2008;156:1003-9.)
C1 [Keaney, John F., Jr.; Freedman, Jane E.; Hamburg, Naomi M.; Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Mem Dept Med, Boston, MA 02118 USA.
[Keaney, John F., Jr.; Lipinska, Izabella; Freedman, Jane E.; Hamburg, Naomi M.; Vita, Joseph A.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Larson, Martin G.; Rong, Jian; Sutherland, Patrice; Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, NIH, Bethesda, MD 20892 USA.
[Dupuis, Josee; Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Massaro, Joseph M.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA.
RP Keaney, JF (reprint author), UMASS Med Sch, Div Cardiovasc Med, 55 Lake Ave N,S3-855, Worcester, MA 01655 USA.
EM john.keaney@umassmed.edu
OI Ramachandran, Vasan/0000-0001-7357-5970; Dupuis,
Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336;
Hamburg, Naomi/0000-0001-5504-5589; Vita, Joseph/0000-0001-5607-1797;
Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]; National Institutes of Health's Framingham Heart Study
[N01-HC-25195, HL076784, HL64753, NS17950, HL04334, AG027081, HL68758]
FX This work was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (contract no. N01-HC-25195). This
work was supported by the National Institutes of Health's Framingham
Heart Study N01-HC-25195, HL076784, and HL64753 (E.J.B.), NS17950 and
HL04334 (R.S.V.), and AG027081 and HL68758 (J.F.K.).
NR 39
TC 9
Z9 9
U1 1
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD NOV
PY 2008
VL 156
IS 5
BP 1003
EP 1009
DI 10.1016/j.ahj.2008.06.041
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 369NB
UT WOS:000260700100033
PM 19061720
ER
PT J
AU Aronow, HD
Lincoff, AM
Quinn, MJ
Mcrae, AT
Gurm, HS
Houghtaling, PL
Granger, CB
Harrington, RA
de Werf, FV
Topol, EJ
Lauer, MS
AF Aronow, Herbert D.
Lincoff, A. Michael
Quinn, Martin J.
McRae, A. Thomas
Gurm, Hitinder S.
Houghtaling, Penny L.
Granger, Christopher B.
Harrington, Robert A.
de Werf, Franz Van
Topol, Eric J.
Lauer, Michael S.
CA Gusto Ilb
TI Relation Between Previous Lipid-Lowering Therapy and Infaret Size
(Creatine Kinase-MB Level) in Patients Presenting With Acute Myocardial
Infarction
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID ACUTE CORONARY SYNDROMES; STATIN THERAPY; HEART-DISEASE; NITRIC-OXIDE;
SECONDARY PREVENTION; PROPENSITY SCORES; CHOLESTEROL; INJURY;
WITHDRAWAL; ROSUVASTATIN
AB Animal experimental data have shown that lipid-lowering agents reduce myocardial infarct size. This association has not been well studied in humans. We compared infarct size in 10,548 patients in the GUSTO IIb and PURSUIT trials who were (n = 1,028) or were not (n = 9,520) on lipid-lowering therapy before an enrolling myocardial infarction (MI). Patients using lipid-lowering agents before their index MI had smaller infarcts than those who were not using these agents (median peak creatine kinase [CK]-MB 4.2 vs 5.2 times the upper limit of normal [ULN]; p <0.0001). Similarly, in an unadjusted model, patients on previous lipid-lowering therapy were less likely to have a peak CK-MB >3 times the ULN (620 of 1,028 [60.3%] vs 6,486 of 9,520 patients [68.1%]; p <0.001; relative risk 0.88, 95% confidence interval 0.84 to 0.93, p <0.0001). In a covariate- and propensity-adjusted multivariable model, the association between pretreatment with lipid-lowering agents and smaller infarct size persisted (relative risk for CK-MB >3 times the ULN 0.94, 95% confidence interval 0.88 to 0.99, p = 0.04). In conclusion, patients on lipid-lowering agents before an MI had significantly smaller infarcts. These findings suggest that lipid-lowering therapy may exert additional salutary effects in the setting of acute coronary syndromes. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1119-1124)
C1 [Aronow, Herbert D.] St Joseph Mercy Hosp, Michigan Heart & Vasc Inst, Clin Scholars Program, Ann Arbor, MI 48104 USA.
[Lincoff, A. Michael; Houghtaling, Penny L.] Cleveland Clin, Cleveland, OH 44106 USA.
[Quinn, Martin J.] St Vincents Univ Hosp, Dublin 4, Ireland.
[McRae, A. Thomas] Centennial Heart Cardiovasc Consultants, Nashville, TN USA.
[Gurm, Hitinder S.] Univ Michigan, Sch Med, Div Cardiovasc Med, Ann Arbor, MI USA.
[Granger, Christopher B.; Harrington, Robert A.] Duke Clin Res Inst, Durham, NC USA.
[de Werf, Franz Van] Univ Hosp Gasthuisberg, Dept Cardiol, B-3000 Louvain, Belgium.
[Topol, Eric J.] Scripps Clin, Div Cardiovasc Dis, La Jolla, CA 92037 USA.
[Lauer, Michael S.] NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Aronow, HD (reprint author), St Joseph Mercy Hosp, Michigan Heart & Vasc Inst, Clin Scholars Program, Ann Arbor, MI 48104 USA.
EM haronow@michiganheart.com
RI Lauer, Michael/L-9656-2013; Granger, Christopher/D-3458-2014
OI Lauer, Michael/0000-0002-9217-8177; Granger,
Christopher/0000-0002-0045-3291
FU COR Therapeutics, Inc., San Francisco, California, and Schering-Plough
Research Institute, Kenilworth, New Jersey; Ciba-Geigy, Inc.. Summit,
New Jersey Boehringer-Mannheim. Indianapolis, Indiana; Guidant Corp.,
Redwood City, California
FX Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression
Using Integrilin Therapy (PURSUIT) was supported by COR Therapeutics,
Inc., San Francisco, California, and Schering-Plough Research Institute,
Kenilworth, New Jersey; and Global Use of Streptokinase or t-PA for
Occluded Coronary Arteries IIb (GUSTO IIb) was supported by Ciba-Geigy,
Inc.. Summit, New Jersey Boehringer-Mannheim. Indianapolis, Indiana: and
Guidant Corp., Redwood City. California.
NR 29
TC 4
Z9 4
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD NOV 1
PY 2008
VL 102
IS 9
BP 1119
EP 1124
DI 10.1016/j.amjcard.2008.06.032
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 373XT
UT WOS:000261007500001
PM 18940276
ER
PT J
AU Hoffmann, U
Massaro, JM
Fox, CS
Manders, E
O'Donnell, CJ
AF Hoffmann, Udo
Massaro, Joseph M.
Fox, Caroline S.
Manders, Emily
O'Donnell, Christopher J.
TI Defining Normal Distributions of Coronary Artery Calcium in Women and
Men (from the Framingham Heart Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID COMPUTED-TOMOGRAPHY; RISK-ASSESSMENT; CT; REPRODUCIBILITY;
QUANTIFICATION; GENDER; COHORT; MESA; AGE
AB Coronary artery calcium (CAC) may improve risk stratification for patients with coronary heart disease (CRD) beyond traditional risk factors. Subjects from the Framingham Heart Study Offspring and Third Generation cohorts (48% women; mean age 53 years) underwent noncontrast electrocardiographically triggered cardiac multidetector computed tomography. The prevalence of absolute CAC (Agatston score [AS] >0, >100, and >400) and relative age- and gender-specific strata (25th, 50th, 75th, 90th, and 95th percentiles) were determined in a healthy subset free of clinically apparent cardiovascular disease or CHD risk factors (n = 1,586), the overall sample at risk (n = 3,238), and subjects at intermediate Framingham risk score (FRS; 6% to 20% 10-year CHD event risk; n = 1,177). Absolute AS and relative cutoffs for CAC increased with age and FRS, were higher in men compared with women in each of the 3 cohorts, and increased from the healthy subset to the overall cohort to subjects at intermediate risk. However, in subjects with CAC, there was substantial disagreement between absolute and relative cut-off values for labeling subjects as having increased CAC. In general, more subjects were considered to have increased CAC using relative cut-off values, especially in women and younger subjects. Fewer subjects at intermediate FRS had increased CAC using comparable absolute versus relative cutoffs (men 32% at AS > 100 vs 36% at > 75th percentile; women 24% at AS > 100 vs 34% at >75th percentile). In conclusion, we provided distributions of CAC in a healthy subset, the overall cohort, and subjects at intermediate risk from the Framingham Heart Study for both absolute and relative cut-off values for CAC. Absolute cutoffs underestimated the proportion of subjects with increased CAC, specifically in women, younger persons, and persons at intermediate CHD risk. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Cardiac MR PET CT Program, Boston, MA 02115 USA.
[Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Fox, Caroline S.; Manders, Emily; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA.
[Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[O'Donnell, Christopher J.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiol Div, Boston, MA USA.
RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Cardiac MR PET CT Program, Boston, MA 02115 USA.
EM uhoffmann@partners.org
OI Massaro, Joseph/0000-0002-2682-4812
FU National Heart. Lung, and Blood Institute (NHLBI) Framingham Heart Study
[N01-HC-25195]
FX This work was supported by the National Heart. Lung, and Blood Institute
(NHLBI) Framingham Heart Study (National Institutes Of Health/NHLBI
Contract N01-HC-25195. Bethesda. maryland), Framingham, Massachusetts.
NR 13
TC 58
Z9 63
U1 0
U2 1
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD NOV 1
PY 2008
VL 102
IS 9
BP 1136
EP 1141
DI 10.1016/j.amjcard.2008.06.038
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 373XT
UT WOS:000261007500004
PM 18940279
ER
PT J
AU Parikh, NI
Hwang, SJ
Yang, Q
Larson, MG
Guo, CY
Robins, SJ
Sutherland, P
Benjamin, EJ
Levy, D
Fox, CS
AF Parikh, Nisha I.
Hwang, Shih-Jen
Yang, Qiong
Larson, Martin G.
Guo, Chao-Yu
Robins, Sander J.
Sutherland, Patrice
Benjamin, Emelia J.
Levy, Daniel
Fox, Caroline S.
TI Clinical Correlates and Heritability of Cystatin C (from the Framingham
Offspring Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; SERUM CREATININE;
ARTERIAL STIFFNESS; ELDERLY PERSONS; HEALTH; RISK; DYSFUNCTION;
COMMUNITY; OUTCOMES
AB Cystatin C (CysC) is associated with cardiovascular disease (CVD) and chronic kidney disease (CKD). We examined the clinical correlates and heritability of CysC and determined if associations between CVD risk factors and CysC differed by CKD status. Among Framingham Heart Study offspring (examined from 1998-2001, n = 3,241, mean age 61 years, 54% women), the 95(th) percentile cut-point was developed for CysC in a healthy subset (n = 779) after excluding participants with diabetes, hypertension, low high-density lipoproteins, obesity, smoking, high triglycerides, prevalent CVD, and CKD (as defined by glomerular filtration rate <60 mL/min per 1.73 m(2)). Multivariable logistic regression was used to evaluate the association between CVD risk factors and high CysC (CysC >= 95(th) percentile cut-point). In a family-based subset (n = 1,188), we estimated CysC heritability using the variance-components method. The cut-point for high CysC was 1.07 mg/L. Age, hypertension treatment, low diastolic blood pressure, body mass index, low high-density lipoprotein cholesterol, and smoking were associated with high CysC in multivariable models. These factors and estimated glomerular filtration rate (egFR) explained 39.2% of CysC variability (R(2)). Excluding CKD did not materially change associations. Multivariable-adjusted heritability for CysC was 0.35 (p <0.001). In conclusion, high CysC is associated with CVD risk factors even in the absence of CKD. The strong associations between CysC and CVD risk factors may partially explain why CysC is a strong predictor of incident CVD. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1194-1198)
C1 [Parikh, Nisha I.; Hwang, Shih-Jen; Larson, Martin G.; Robins, Sander J.; Sutherland, Patrice; Benjamin, Emelia J.; Levy, Daniel; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA.
[Yang, Qiong; Guo, Chao-Yu] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA.
[Hwang, Shih-Jen; Levy, Daniel; Fox, Caroline S.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Hwang, Shih-Jen; Levy, Daniel; Fox, Caroline S.] Ctr Populat Studies, Bethesda, MD USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
RI Yang, Qiong/G-5438-2014;
OI Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336
FU National Heart. Lung and Blood Institute [N01-HC-25195]
FX The Framingham Heart Study was supported by Grant N01-HC-25195 from the
National Heart. Lung and Blood Institute.
NR 27
TC 26
Z9 29
U1 0
U2 1
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD NOV 1
PY 2008
VL 102
IS 9
BP 1194
EP 1198
DI 10.1016/j.amjcard.2008.06.039
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 373XT
UT WOS:000261007500015
PM 18940290
ER
PT J
AU Craft, LL
Guralnik, JM
Ferrucci, L
Liu, K
Tian, L
Criqui, MH
Tan, J
McDermott, MM
AF Craft, Lynette L.
Guralnik, Jack M.
Ferrucci, Luigi
Liu, Kiang
Tian, Lu
Criqui, Michael H.
Tan, Jin
McDermott, Mary M.
TI Physical Activity During Daily Life and Circulating Biomarker Levels in
Patients With Peripheral Arterial Disease
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; ANKLE BRACHIAL INDEX; C-REACTIVE
PROTEIN; RISK-FACTORS; MUSCLE CHARACTERISTICS; D-DIMER; INFLAMMATION;
RESTENOSIS; MORTALITY; CLAUDICATION
AB Higher levels of inflammation are associated with adverse outcomes in patients with lower extremity peripheral arterial disease (PAD). This study evaluated associations of physical activity during daily life with levels of inflammatory biomarkers, D-dimer, and homocysteine in patients with PAD. Participants were 244 men and women (mean age 74.4 +/- 8.2 years) with PAD (ankle brachial index < 0.90). C-reactive protein, interleukin-6, soluble intracellular adhesion molecule-1, soluble vascular cellular adhesion molecule-1, D-dimer, and homocysteine were assessed at study entry. Physical activity was objectively assessed with a vertical accelerometer, which participants wore continuously for 7 days. After adjusting for age, gender, race, body mass index, smoking, co-morbidities, ankle brachial index, and other potential confounders, higher physical activity levels were associated linearly and significantly with lower levels of all measured circulating biomarkers: soluble vascular cellular adhesion molecule-1 (p trend = 0.001), D-dimer (p trend = 0.005), homocysteine (p trend = 0.006), interleukin-6 (p trend = 0.010), C-reactive protein (p trend = 0.028), and soluble intracellular adhesion molecule-1 (p trend = 0.033). In conclusion, higher levels of physical activity were associated independently with lower levels of inflammatory markers, homocysteine, and D-dimer in patients with PAD. 0 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1263-268)
C1 [Craft, Lynette L.; Liu, Kiang; Tian, Lu; Tan, Jin; McDermott, Mary M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Guralnik, Jack M.; Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA.
[Criqui, Michael H.] Univ Calif San Diego, San Diego, CA 92103 USA.
RP Craft, LL (reprint author), Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
EM lynette-craft@northwestern.edu
FU National Heart Lung and Blood Institute, Bethesda, Maryland
[R01-HL58099, R01-HL64739, R01-HL71223, R01-HL076298]; National Center
for Research Resources, [RR-00048]; National Institutes of Health,
Bethesda, Maryland; Intramural Research Program; National Institute on
Aging; National Institutes of Health
FX This study was supported by Grants R01-HL58099, R01-HL64739,
R01-HL71223, and R01-HL076298 from the National Heart Lung and Blood
Institute, Bethesda, Maryland; by Grant RR-00048 from the National
Center for Research Resources, National Institutes of Health, Bethesda,
Maryland: and in part by the Intramural Research Program, National
Institute on Aging, National Institutes of Health.
NR 24
TC 14
Z9 18
U1 1
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD NOV 1
PY 2008
VL 102
IS 9
BP 1263
EP 1268
DI 10.1016/j.amjcard.2008.06.051
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 373XT
UT WOS:000261007500029
PM 18940304
ER
PT J
AU Koster, A
Leitzmann, MF
Schatzkin, A
Adams, KF
van Eijk, JTM
Hollenbeck, AR
Harris, TB
AF Koster, Annemarie
Leitzmann, Michael F.
Schatzkin, Arthur
Adams, Kenneth F.
van Eijk, Jacques T. M.
Hollenbeck, Albert R.
Harris, Tamara B.
TI The combined relations of adiposity and smoking on mortality
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID BODY-MASS INDEX; WAIST CIRCUMFERENCE; CIGARETTE-SMOKING; PROSPECTIVE
COHORT; UNITED-STATES; RISK-FACTORS; HEALTH-RISK; US ADULTS; OBESITY;
WEIGHT
AB Background: Smoking and high adiposity are strong independent health risk factors but are also interrelated. Smoking is related to a lower body mass index (BMI) but not necessarily with a smaller waist circumference. Smoking cessation is associated with increased body weight and a substantial increase in waist circumference. How this affects mortality risk is unknown.
Objective: This study examined the combined relations of smoking status with BMI and waist circumference and smoking status to all-cause mortality.
Design: Data were from 149 502 men and 88 184 women aged 51-72 y participating in the National Institutes of Health-AARP Diet and Health Study. All-cause mortality was assessed over 10 y of follow-up from 1996 to 2006.
Results: Current smokers with a BMI (in kg/m(2)) < 18.5 or >= 35 had a mortality risk 6-8 times that of persons within the normal BMI range who never smoked. Current smokers with a large waist circumference had a mortality risk about 5 times that of never smokers with a waist circumference in the second quintile.
Conclusion: Both smoking and adiposity are independent predictors of mortality, but the combination of current or recent smoking with a BMI >= 35 or a large waist circumference is related to an especially high mortality risk. Am J Clin Nutr 2008; 88: 1206-12.
C1 [Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Koster, Annemarie; van Eijk, Jacques T. M.] Univ Maastricht, Fac Hlth Med & Life Sci, Maastricht, Netherlands.
[Leitzmann, Michael F.; Schatzkin, Arthur; Adams, Kenneth F.] Natl Canc Inst, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Koster, A (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA.
EM kostera@mail.nih.gov
RI Koster, Annemarie/E-7438-2010
FU NIH, National Cancer Institute; NIH, National Institute on Aging
FX Supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, and the Intramural Research Program of the
NIH, National Institute on Aging.
NR 37
TC 39
Z9 39
U1 0
U2 4
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 NOV 1
PY 2008
VL 88
IS 5
BP 1206
EP 1212
DI 10.3945/ajcn.2008.26298
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 370OD
UT WOS:000260770600006
PM 18996854
ER
PT J
AU Sieri, S
Krogh, V
Ferrari, P
Berrino, F
Pala, V
Thiebaut, ACM
Tjonneland, A
Olsen, A
Overvad, K
Jakobsen, MU
Clavel-Chapelon, F
Chajes, V
Boutron-Ruault, MC
Kaaks, R
Linseisen, J
Boeing, H
Nothlings, U
Trichopoulou, A
Naska, A
Lagiou, P
Panico, S
Palli, D
Vineis, P
Tumino, R
Lund, E
Kumle, M
Skeie, G
Gonzalez, CA
Ardanaz, E
Amiano, P
Tormo, MJ
Martinez-Garcia, C
Quiros, JR
Berglund, G
Gullberg, B
Hallmans, G
Lenner, P
Bueno-de-Mesquita, HB
van Duijnhoven, FJB
Peeters, PHM
van Gils, CH
Key, TJ
Crowe, FL
Bingham, S
Khaw, KT
Rinaldi, S
Slimani, N
Jenab, M
Norat, T
Riboli, E
AF Sieri, Sabina
Krogh, Vittorio
Ferrari, Pietro
Berrino, Franco
Pala, Valeria
Thiebaut, Anne C. M.
Tjonneland, Anne
Olsen, Anja
Overvad, Kim
Jakobsen, Marianne Uhre
Clavel-Chapelon, Francoise
Chajes, Veronique
Boutron-Ruault, Marie-Christine
Kaaks, Rudolf
Linseisen, Jakob
Boeing, Heiner
Noethlings, Ute
Trichopoulou, Antonia
Naska, Androniki
Lagiou, Pagona
Panico, Salvatore
Palli, Domenico
Vineis, Paolo
Tumino, Rosario
Lund, Eiliv
Kumle, Merethe
Skeie, Guri
Gonzalez, Carlos A.
Ardanaz, Eva
Amiano, Pilar
Tormo, Maria Jose
Martinez-Garcia, Carmen
Quiros, Jose R.
Berglund, Goeran
Gullberg, Bo
Hallmans, Goeran
Lenner, Per
Bueno-de-Mesquita, H. Bas
van Duijnhoven, Fraenzel J. B.
Peeters, Petra H. M.
van Gils, Carla H.
Key, Timothy J.
Crowe, Francesca L.
Bingham, Sheila
Khaw, Kay Tee
Rinaldi, Sabina
Slimani, Nadia
Jenab, Mazda
Norat, Teresa
Riboli, Elio
TI Dietary fat and breast cancer risk in the European Prospective
Investigation into Cancer and Nutrition
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID FOOD-FREQUENCY QUESTIONNAIRE; HORMONE-REPLACEMENT THERAPY; RELATIVE
VALIDITY; FOLLOW-UP; POSTMENOPAUSAL WOMEN; PROSPECTIVE COHORT;
MEASUREMENT ERROR; EPIC PROJECT; HEALTH; REPRODUCIBILITY
AB Background: Epidemiologic studies have produced conflicting results with respect to an association of dietary fat with breast cancer.
Objective: We aimed to investigate the association between fat consumption and breast cancer.
Design: We prospectively investigated fat consumption in a large (n = 319 826), geographically and culturally heterogeneous cohort of European women enrolled in the European Prospective Investigation into Cancer and Nutrition who completed a dietary questionnaire. After a mean of 8.8 y of follow-up, 7119 women developed breast cancer. Cox proportional hazard models, stratified by age and center and adjusted for energy intake and confounders, were used to estimate hazard ratios (HRs) for breast cancer.
Results: An association between high saturated fat intake and greater breast cancer risk was found [HR = 1.13 (95% CI: 1.00, 1.27; P for trend = 0.038) for the highest quintile of saturated fat intake compared with the lowest quintile: 1.02 (1.00, 1.04) for a 20% increase in saturated fat consumption (continuous variable)]. No significant association of breast cancer with total, monounsaturated, or polyunsaturated fat was found, although trends were for a direct association of risk with monounsaturated fat and an inverse association with polyunsaturated fat. In menopausal women, the positive association with saturated fat was confined to nonusers of hormone therapy at baseline [1.21 (0.99, 1.48) for the highest quintile compared with the lowest quintile; P for trend = 0.044; and 1.03 (1.00, 1.07) for a 20% increase in saturated fat as a continuous variable].
Conclusions: Evidence indicates a weak positive association between saturated fat intake and breast cancer risk. This association was more pronounced for postmenopausal women who never used hormone therapy. Am J Clin Nutr 2008; 88: 1304-12.
C1 [Sieri, Sabina; Krogh, Vittorio; Pala, Valeria] Ist Nazl Tumori, Fdn IRCCS, Nutr Epidemiol Unit, I-20133 Milan, Italy.
[Ferrari, Pietro; Rinaldi, Sabina; Slimani, Nadia; Jenab, Mazda] WHO, IARC, Lyon, France.
[Berrino, Franco] Ist Nazl Tumori, Fdn IRCCS, Etiol & Prevent Epidemiol Unit, I-20133 Milan, Italy.
[Thiebaut, Anne C. M.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, NIH,DHHS, Bethesda, MD 20892 USA.
[Tjonneland, Anne; Olsen, Anja] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Overvad, Kim; Jakobsen, Marianne Uhre] Aarhus Univ Hosp, Dept Clin Epidemiol, Aalborg, Denmark.
[Clavel-Chapelon, Francoise; Boutron-Ruault, Marie-Christine] Inst Gustave Roussy, INSERM, ERI 20, Villejuif, France.
[Chajes, Veronique] Inst Gustave Roussy, CNRS, FRE 2939, Villejuif, France.
[Kaaks, Rudolf; Linseisen, Jakob] German Canc Res Ctr, Div Clin Epidemiol, D-6900 Heidelberg, Germany.
[Boeing, Heiner; Noethlings, Ute] German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany.
[Trichopoulou, Antonia; Naska, Androniki; Lagiou, Pagona] Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-11527 Athens, Greece.
[Panico, Salvatore] Univ Naples Federico 2, Dept Clin & Expt Med, Naples, Italy.
[Palli, Domenico] Sci Inst Tuscany, CSPO, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Vineis, Paolo] Univ Turin, Turin, Italy.
[Tumino, Rosario] MP Arezzo Civ Hosp, Canc Registry, Ragusa, Italy.
[Lund, Eiliv; Kumle, Merethe; Skeie, Guri] Univ Tromso, Inst Community Med, Tromso, Norway.
[Gonzalez, Carlos A.] Catalan Inst Oncol, Dept Epidemiol, Barcelona, Spain.
[Ardanaz, Eva] Publ Hlth Inst Navarra, Pamplona, Spain.
[Ardanaz, Eva] CIBERESP, Pamplona, Spain.
[Amiano, Pilar] Publ Hlth Div Gipuzkoa, Donostia San Sebastian, Spain.
[Tormo, Maria Jose] Murcia Hlth Council, Dept Epidemiol, Murcia, Spain.
[Tormo, Maria Jose] CIBERESP, Murcia, Spain.
[Martinez-Garcia, Carmen] Andalusian Sch Publ Hlth, Granada, Spain.
[Martinez-Garcia, Carmen] CIBERESP, Granada, Spain.
[Quiros, Jose R.] Publ Hlth & Hlth Planning Directorate, Hlth Informat Unit, Asturias, Spain.
[Berglund, Goeran; Gullberg, Bo] Lund Univ, Dept Clin Sci, Malmo, Sweden.
[Hallmans, Goeran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Lenner, Per] Umea Univ, Dept Radiat Sci, Oncol Unit, Umea, Sweden.
[Bueno-de-Mesquita, H. Bas; van Duijnhoven, Fraenzel J. B.] Natl Inst Publ Hlth & Environm, Ctr Nutr & Hlth, NL-3720 BA Bilthoven, Netherlands.
[Peeters, Petra H. M.; van Gils, Carla H.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Crowe, Francesca L.] Univ Oxford, Canc Res UK Epidemiol Unit, Oxford, England.
[Bingham, Sheila; Khaw, Kay Tee] MRC, Dunn Human Nutr Unit, Cambridge, England.
[Norat, Teresa; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England.
RP Krogh, V (reprint author), Ist Nazl Tumori, Fdn IRCCS, Nutr Epidemiol Unit, Via Venezian 1, I-20133 Milan, Italy.
EM vittorio.krogh@istitutotumori.mi.it
RI Nothlings, Ute/B-2713-2010; Boutron Ruault, Marie-Christine/G-3705-2013;
Boutron, Marie-Christine/K-8168-2013; Linseisen, Jakob/B-5353-2014;
Clavel-Chapelon, Francoise/G-6733-2014; Gonzalez, Carlos A/O-4651-2014;
Boutron-Ruault, Marie-Christine/H-3936-2014; Krogh,
Vittorio/K-2628-2016; Sieri, Sabina/K-4667-2016; Panico,
Salvatore/K-6506-2016
OI PALLI, Domenico/0000-0002-5558-2437; Skeie, Guri/0000-0003-2476-4251;
Linseisen, Jakob/0000-0002-9386-382X; Gonzalez, Carlos
A/0000-0003-2822-9715; Krogh, Vittorio/0000-0003-0122-8624; Sieri,
Sabina/0000-0001-5201-172X; Panico, Salvatore/0000-0002-5498-8312
FU European Commission; Deutsche Krebshilfe; German Cancer Research Center;
German Federal Ministry of Education and Research; Danish Cancer
Society; Spanish Ministry of Health [CIBERESP, RETIC-RD06/0020]; Spanish
Institute of Health Carlos III; Catalan Institute of Oncology; Cancer
Research UK; Medical Research Council, United Kingdom; Stroke
Association, United Kingdom; British Heart Foundation; Department of
Health, United Kingdom; Food Standards Agency, United Kingdom; Wellcome
Trust, United Kingdom; Greek Ministry of Health and Social Solidarity;
Hellenic Health Foundation; Italian Association for Research on Cancer;
Dutch Ministry of Public Health, Welfare and Sports; National Cancer
Registry; World Cancer Research Fund; Swedish Cancer Society; Swedish
Scientific Council; Norwegian Research Council; University of Tromso
FX Supported by the Public Health and Consumer Protection Directorate
1993-2004 and the Research Directorate-General 2005 of the European
Commission; Deutsche Krebshilfe; the German Cancer Research Center; the
German Federal Ministry of Education and Research; the Danish Cancer
Society; the Health Research Fund of the Spanish Ministry of Health
(CIBERESP and RETIC-RD06/0020); the Spanish Institute of Health Carlos
III; the regional governments of Andalusia, Asturias, Basque Country,
Murcia, and Navarra in Spain; the Catalan Institute of Oncology; Cancer
Research UK; the Medical Research Council, United Kingdom; the Stroke
Association, United Kingdom; the British Heart Foundation; the
Department of Health, United Kingdom; the Food Standards Agency, United
Kingdom; the Wellcome Trust, United Kingdom; the Greek Ministry of
Health and Social Solidarity and the Hellenic Health Foundation; the
Italian Association for Research on Cancer; the Dutch Ministry of Public
Health, Welfare and Sports; the National Cancer Registry and the
regional cancer registries of Amsterdam, East, and Maastricht in the
Netherlands; the World Cancer Research Fund; the Swedish Cancer Society;
the Swedish Scientific Council; the regional government of Skane,
Sweden; and the Norwegian Research Council and the University of Tromso.
NR 63
TC 69
Z9 70
U1 3
U2 16
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 NOV 1
PY 2008
VL 88
IS 5
BP 1304
EP 1312
DI 10.3945/ajcn.2008.26090
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 370OD
UT WOS:000260770600019
PM 18996867
ER
PT J
AU Sattler, FR
Rajicic, N
Mulligan, K
Yarasheski, KE
Koletar, SL
Zolopa, A
Alston, B
Zackin, SR
Bistrian, B
AF Sattler, Fred R.
Rajicic, Natasa
Mulligan, Kathleen
Yarasheski, Kevin E.
Koletar, Susan L.
Zolopa, Andrew
Alston, Beverly
Zackin, Smith Robert
Bistrian, Bruce
CA ACTG 392 Study Team
TI Evaluation of high-protein supplementation in weight-stable HIV-positive
subjects with a history of weight loss: a randomized, double-blind,
multicenter trial
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; BODY CELL MASS; ACTIVE ANTIRETROVIRAL
THERAPY; INCREASING NITROGEN INTAKE; TOTAL PARENTERAL-NUTRITION;
INFECTED PATIENTS; AIDS PATIENTS; WASTING SYNDROME; WHEY PROTEINS;
DISEASE RISK
AB Background: HIV patients with wasting are at increased risk of opportunistic complications and fatality.
Objective: We hypothesized that augmenting dietary intake with high-biologic-value protein would enhance weight and lean tissue in weight-stable subjects with a prior unintentional weight loss of >3%.
Design: Fifty-nine subjects with HIV RNA concentrations <5000 copies/mL were randomly assigned to receive a 280-kcal supplement containing 40 g whey protein or a matched isocaloric control supplement without added protein twice daily for 12 wk.
Results: Before the study, intake of total energy and protein exceeded estimated requirements (44.3 +/- 12.6 kcal . kg(-1) . d(-1) and 1.69 +/- 0.55 g . kg(-1) . d(-1), respectively). Both supplements failed to increase total energy intake because of decreases in self-selected food intake. Changes in weight (0.8 +/- 2.4 and 0.7 +/- 2.4 kg) and lean body mass (0.3 +/- 1.4 and 0.3 +/- 1.5 kg) did not differ significantly between the whey protein and control groups, respectively. Waist-to-hip ratio improved more with whey protein (-0.02 +/- 0.05) than with the control (0.01 +/- 0.03; P = 0.025) at week 6 but not at week 12. Fasting triacylglycerol increased by 39 +/- 98 mg/dL with the control supplement and decreased by 16 +/- 62 mg/dL with whey protein at week 12 (P = 0.03). CD4 lymphocytes increased by 31 +/- 84 cells/mm3 with whey protein and decreased by 5 +/- 124 cells/mm(3) with the control supplement at 12 wk (P = 0.03). Gastrointestinal symptoms occurred more often with whey protein.
Conclusions: A whey protein supplement did not increase weight or lean body mass in HIV-positive subjects who were eating adequately, but it did increase CD4 cell counts. The control supplement with rapidly assimilable carbohydrate substituted for protein increased cardiovascular disease risk factors. Careful dietary and weight history should be obtained before starting nutritional supplements in subjects with stable weight loss and good viral control. Am J Clin Nutr 2008; 88: 1313-21.
C1 [Sattler, Fred R.] Univ So Calif, Keck Sch Med, LAC USC Med Ctr, Los Angeles, CA 90033 USA.
[Rajicic, Natasa; Zackin, Smith Robert] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Mulligan, Kathleen] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Mulligan, Kathleen] San Francisco Gen Hosp, San Francisco, CA 94110 USA.
[Yarasheski, Kevin E.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO USA.
[Koletar, Susan L.] Ohio State Univ, Div Infect Dis, Columbus, OH 43210 USA.
[Zolopa, Andrew] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Alston, Beverly] NIAID, Div Aids, Bethesda, MD 20892 USA.
[Zackin, Smith Robert] Harvard Univ, Sch Publ Hlth, Dept Med, Boston, MA 02115 USA.
[Bistrian, Bruce] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA.
RP Sattler, FR (reprint author), Univ So Calif, Keck Sch Med, LAC USC Med Ctr, Room 6442,1200 N State St, Los Angeles, CA 90033 USA.
EM fsattler@usc.edu
RI Yarasheski, Kevin/A-3025-2008;
OI Yarasheski, Kevin/0000-0001-5436-2451
FU National Institute of Allergy and Infectious Diseases through the Adult
AIDS Clinical Trials Group U01 [AI20766, AI69474, AI27663, AI25903,
AI27673, AI46386, AI34853, AI27668, AI27658, AI25897, AI34832, AI32770];
General Clinical Research Programs, NCRR, M01 [RR00070, RR00034,
RR00043, RR00083, RR00052, RR00044, RR00051]
FX Supported by the National Institute of Allergy and Infectious Diseases
through the Adult AIDS Clinical Trials Group U01 grants (AI20766,
AI69474, AI27663, AI25903, AI27673, AI46386, AI34853, AI27668, AI27658,
AI25897, AI34832, and AI32770) and the General Clinical Research
Programs, NCRR, M01 grants (RR00070, RR00034, RR00043, RR00083, RR00052,
RR00044, and RR00051). Biomune Systems, Inc, provided the whey protein
and control supplements.
NR 53
TC 16
Z9 17
U1 0
U2 2
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD NOV 1
PY 2008
VL 88
IS 5
BP 1313
EP 1321
DI 10.3945/ajcn.2006.23583
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 370OD
UT WOS:000260770600020
PM 18996868
ER
PT J
AU Wright, ME
Park, Y
Subar, AF
Freedman, ND
Albanes, D
Hollenbeck, A
Leitzmann, MF
Schatzkin, A
AF Wright, Margaret E.
Park, Yikyung
Subar, Amy F.
Freedman, Neal D.
Albanes, Demetrius
Hollenbeck, Albert
Leitzmann, Michael F.
Schatzkin, Arthur
TI Intakes of Fruit, Vegetables, and Specific Botanical Groups in Relation
to Lung Cancer Risk in the NIH-AARP Diet and Health Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cohort studies; fruit; lung neoplasms; vegetables
ID RETIRED-PERSONS DIET; BETA-CAROTENE; VITAMIN-C; AMERICAN-ASSOCIATION;
NATIONAL-INSTITUTES; CONSUMPTION; PREVENTION; COHORT; NUTRITION; SMOKERS
AB Increased fruit and vegetable consumption may protect against lung cancer, although epidemiologic findings are inconclusive. The authors prospectively examined associations between lung cancer risk and intakes of fruit, vegetables, and botanical subgroups in 472,081 participants aged 50-71 years in the National Institutes of Health (NIH)-AARP Diet and Health Study. Diet was assessed at baseline (1995-1996) with a 124-item dietary questionnaire. A total of 6,035 incident lung cancer cases were identified between 1995 and 2003. Total fruit and vegetable intake was unrelated to lung cancer risk in both men and women. Higher consumption of several botanical subgroups, however, was significantly inversely associated with risk, but only in men. For example, the relative risks of lung cancer among men in the highest versus lowest quintiles of intake of rosaceae, convolvulaceae, and umbelliferae were 0.82 (95% confidence interval (CI): 0.73, 0.91), 0.86 (95% CI: 0.75, 0.96), and 0.86 (95% CI: 0.78, 0.96), respectively; corresponding relative risks in women were 0.97 (95% CI: 0.85, 1.12), 0.95 (95% CI: 0.83, 1.09), and 0.92 (95% CI: 0.80, 1.06). These results provide support for a protective role of specific botanical subgroups of fruits and vegetables in lung cancer prevention in men, although the findings could also be due to residual confounding by smoking or chance.
C1 [Wright, Margaret E.] Univ Illinois, Coll Med, Dept Pathol, Chicago, IL 60612 USA.
[Wright, Margaret E.; Park, Yikyung; Freedman, Neal D.; Albanes, Demetrius; Leitzmann, Michael F.; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Subar, Amy F.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Freedman, Neal D.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
RP Wright, ME (reprint author), Univ Illinois, Coll Med, Dept Pathol MC 847, 840 S Wood St,Room 130, Chicago, IL 60612 USA.
EM mewright@uic.edu
RI Albanes, Demetrius/B-9749-2015; Freedman, Neal/B-9741-2015;
OI Freedman, Neal/0000-0003-0074-1098; Park, Yikyung/0000-0002-6281-489X
FU Intramural NIH HHS [Z99 CA999999]
NR 43
TC 42
Z9 43
U1 0
U2 6
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 NOV 1
PY 2008
VL 168
IS 9
BP 1024
EP 1034
DI 10.1093/aje/kwn212
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 365BM
UT WOS:000260380900008
PM 18791192
ER
PT J
AU Stolzenberg-Solomon, RZ
Weinstein, S
Pollak, M
Tao, YZ
Taylor, PR
Virtamo, J
Albanes, D
AF Stolzenberg-Solomon, Rachael Z.
Weinstein, Stephanie
Pollak, Michael
Tao, Yuzhen
Taylor, Philip R.
Virtamo, Jarmo
Albanes, Demetrius
TI Prediagnostic Adiponectin Concentrations and Pancreatic Cancer Risk in
Male Smokers
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE adenocarcinoma; adiponectin; biological markers; case-control studies;
diabetes mellitus; pancreatic neoplasms
ID BODY-FAT DISTRIBUTION; PLASMA ADIPONECTIN; INSULIN-RESISTANCE;
PHYSICAL-ACTIVITY; CIGARETTE-SMOKING; MASS INDEX; KOREAN MEN; OBESITY;
COHORT; GLUCOSE
AB Adiponectin, a hormone secreted by adipocytes, has insulin-sensitizing, antidiabetic, antiinflammatory, and antiangiogenic properties. The authors conducted a nested case-control study in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort, a cohort of male Finnish smokers aged 50-69 years at baseline, to test whether prediagnostic adiponectin concentrations are associated with pancreatic cancer. Between January 1985 and October 2004, 311 incident exocrine pancreatic cancer cases were diagnosed among cohort participants with serum samples. Controls (n = 510) were alive and free of cancer at the time the case was diagnosed and were matched to the cases by age and date of blood drawing. The authors used conditional logistic regression adjusted for smoking, blood pressure, and C-peptide level to calculate odds ratios and 95% confidence intervals for pancreatic cancer. Higher adiponectin concentrations were inversely associated with pancreatic cancer (for highest quintile (> 9.8 mu g/mL) vs. lowest (<= 4.6 mu g/mL), odds ratio = 0.65, 95% confidence interval: 0.39, 1.07; P-trend = 0.04). The inverse association was significant among cases diagnosed 5 or more years after blood collection (n = 238) (for highest quintile vs. lowest, odds ratio = 0.55, 95% confidence interval: 0.31, 0.98; P-trend = 0.03). These results support the hypothesis that higher adiponectin concentrations may be inversely associated with the development of pancreatic cancer.
C1 [Stolzenberg-Solomon, Rachael Z.; Weinstein, Stephanie; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Pollak, Michael; Tao, Yuzhen] Jewish Gen Hosp, Canc Prevent Program, Montreal, PQ, Canada.
[Pollak, Michael; Tao, Yuzhen] McGill Univ, Montreal, PQ, Canada.
[Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland.
RP Stolzenberg-Solomon, RZ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320, Rockville, MD 20852 USA.
EM rs221z@nih.gov
RI Pollak, Michael/G-9094-2011; Albanes, Demetrius/B-9749-2015
OI Pollak, Michael/0000-0003-3047-0604;
FU Intramural Research Program of the National Institutes of Health;
Division of Cancer Epidemiology and Genetics; National Cancer Institute;
US Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, and by US Public Health Service
contracts N01-CN-45165, N01-RC-45035, and N01-RC-37004 from the National
Cancer Institute.
NR 57
TC 34
Z9 38
U1 0
U2 6
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 NOV 1
PY 2008
VL 168
IS 9
BP 1047
EP 1055
DI 10.1093/aje/kwn221
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 365BM
UT WOS:000260380900010
PM 18801887
ER
PT J
AU Sharma, P
Wani, S
Romero, Y
Johnson, D
Hamilton, F
AF Sharma, Prateek
Wani, Sachin
Romero, Yvonne
Johnson, David
Hamilton, Frank
TI Racial and Geographic Issues in Gastroesophageal Reflux Disease
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID HELICOBACTER-PYLORI INFECTION; BODY-MASS INDEX; PROTON-PUMP INHIBITORS;
BARRETTS-ESOPHAGUS; CLINICAL SPECTRUM; RISK-FACTORS; ENDOSCOPIC
ESOPHAGITIS; GENERAL-POPULATION; ESOPHAGOGASTRIC JUNCTION; SWEDISH
POPULATION
AB Gastroesophageal reflux disease (GERD) is a common chronic disorder that is associated with a huge economic burden in the western countries and significantly decreased quality of life. This review focuses on the various multicultural issues in the epidemiology, pathophysiology, diagnosis, and treatment of GERD. The prevalence of GERD appears to be highest in North America and Europe, whereas epidemiologic data from the Indian subcontinent, Africa, South America, and the Middle East are sparse. A limited number of studies have elucidated ethnic differences in GERD in multiracial populations. African Americans and Asians appear to be at a lower risk for the development of complicated GERD including Barrett's esophagus (BE). Whether the pathophysiology of GERD differs among different populations remains to be answered satisfactorily. It appears that most of the factors involved in the pathogenesis of GERD, as described in western populations, are present in Asians but at a lower scale. The current recommendations for the management of GERD by the American College of Gastroenterology may not meet the need for different ethnic groups or for different geographic regions. Recognition of language barriers in understanding the common terms used to describe reflux symptoms should be borne in mind while treating GERD patients with different ethnic backgrounds. In addition, a universally accepted definition for treatment success in GERD patients is lacking. Given the negative impact on health-related quality of life, significant cost ramifications, and increased risk for BE and esophageal adenocarcinoma, the study of multicultural issues in GERD should be considered.
C1 [Sharma, Prateek] Vet Affairs Med Ctr, Dept Gastroenterol 111, Kansas City, MO 64128 USA.
[Sharma, Prateek; Wani, Sachin] Univ Kansas, Sch Med, Kansas City, MO USA.
[Romero, Yvonne] Mayo Clin, Rochester, MN USA.
[Johnson, David] Eastern Virginia Med Sch, Norfolk, VA 23501 USA.
[Hamilton, Frank] Natl Inst Hlth, Bethesda, MD USA.
RP Sharma, P (reprint author), Vet Affairs Med Ctr, Dept Gastroenterol 111, 4801 E Linwood Blvd, Kansas City, MO 64128 USA.
NR 110
TC 41
Z9 42
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 NOV
PY 2008
VL 103
IS 11
BP 2669
EP 2680
DI 10.1111/j.1572-0241.2008.02089.x
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 367HU
UT WOS:000260543900001
PM 19032462
ER
PT J
AU Tsai, CJ
Leitzmann, MF
Willett, WC
Giovannucci, EL
AF Tsai, Chung-Jyi
Leitzmann, Michael F.
Willett, Walter C.
Giovannucci, Edward L.
TI Macronutrients and Insulin Resistance in Cholesterol Gallstone Disease
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Review
ID TRANS-FATTY-ACIDS; BILIARY LIPID SECRETION; DEPENDENT DIABETES-MELLITUS;
MODERATE ALCOHOL INTAKE; DIETARY GLYCEMIC INDEX; HIGH-CARBOHYDRATE DIET;
GALL STONE DISEASE; METABOLIC SYNDROME; GALLBLADDER-DISEASE; FISH-OIL
AB Cholelithiasis is a major source of digestive morbidity worldwide. Cholesterol stones account for the majority of gallstones in the United States and other Western countries. The pathogenesis of cholesterol gallstone disease is multifactorial with key factors including cholesterol supersaturation of bile, altered biliary motility, and nucleation and growth of cholesterol crystals. Increasing evidence suggests that many, but not all, causative factors of cholesterol gallstones are related to insulin resistance which, in association with obesity, has reached an epidemic level worldwide. Experimental studies show that hyperinsulinemia, a key feature of insulin resistance, may cause increased hepatic cholesterol secretion and cholesterol supersaturation of bile and gallbladder dysmotility, and thereby may enhance gallstone formation. Insulin resistance syndrome can be modified by environmental factors, including dietary factors. The impact of diet on insulin sensitivity is mediated by both dietary composition and its energy content. The contribution of specific dietary elements to the prevalence and incidence of cholesterol gallstone disease has been explored in animal and human studies. There is considerable evidence to suggest that different types of fatty acids, independent of the total amount of fat consumption, affect insulin sensitivity and cholesterol gallstone disease differently. The effects of salt intake, consumption of protein and carbohydrates, and alcohol drinking on insulin resistance are controversial. Additional intervention trials and controlled experimental feeding studies are needed to further clarify these relationships and to provide useful prophylactic and therapeutic strategies.
C1 [Tsai, Chung-Jyi] Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY 40536 USA.
[Willett, Walter C.; Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA.
[Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Leitzmann, Michael F.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Tsai, CJ (reprint author), Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, 800 Rose St, Lexington, KY 40536 USA.
FU National Institute of Health [CA55075, DK46200]
FX Research grants (CA55075 and DK46200) from the National Institute of
Health.
NR 122
TC 25
Z9 26
U1 1
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 NOV
PY 2008
VL 103
IS 11
BP 2932
EP 2939
DI 10.1111/j.1572-0241.2008.02189.x
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 367HU
UT WOS:000260543900033
PM 18853969
ER
PT J
AU Anderson, RD
Sizemore, BC
Barrow, GM
Johnson, BD
Merz, CNB
Sopko, G
von Mering, GO
Handberg, EM
Nichols, WW
Pepine, CJ
AF Anderson, R. David
Sizemore, B. Clay
Barrow, Genevieve M.
Johnson, B. Delia
Merz, C. Noel Bairey
Sopko, George
von Mering, Gregory O.
Handberg, Eileen M.
Nichols, Wilmeer W.
Pepine, Carl J.
TI Pulse Pressure and Adverse Outcomes in Women: A Report From the Women's
Ischemia Syndrome Evaluation (WISE)
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
ID CONVERTING-ENZYME-INHIBITION; LEFT-VENTRICULAR HYPERTROPHY;
BLOOD-PRESSURE; HYPERTENSIVE PATIENTS; ARTERIAL STIFFNESS;
CARDIOVASCULAR RISK; AORTIC STIFFNESS; SYSTOLIC HYPERTENSION; WAVE
REFLECTIONS; CONTROLLED-TRIAL
AB BACKGROUND
Recent data suggest that brachia I pulse pressure (PP) maybe a better predictor of outcome than systolic or diastolic blood pressure (SBP/DBP). We sought to investigate the relative contributions of these indices to risk for adverse outcomes in women with suspected coronary artery disease (CAD) and myocardial ischemia.
METHODS
Among 857 women referred for angiography for suspected myocardial ischemia, baseline evaluations were performed, and the women were followed for clinical outcome. Relationships between baseline characteristics, blood pressure components, and outcomes were evaluated. Separate multivariate stepwise Cox regression models for PP and SBP (expressed in 10 mm Hg increments) were constructed and included covariates significantly associated with adverse outcomes.
RESULTS
After 5.2 years (mean), univariate testing identified higher PP associated with higher risk for cardiovascular (CV) mortality and adverse CV outcomes than SBP, DBP, or mean arterial pressure (MAP). Multivariate modeling identified both PP and SBP associated with adverse CV outcomes, but only PP was significantly associated with higher CV mortality. When both PP and SBP were included in the model, only PP remained an independent predictor of adverse outcomes for CV events.
CONCLUSIONS
In women with suspected CAD and myocardial ischemia, PP is a stronger predictor of adverse outcomes than SBP, DBP, or MAP with an 18% excess mortality risk for every 10 mm Hg increase in PP. Further investigations into pathophysiologic mechanisms and specific pharmacologic approaches to modifying this novel target are warranted. Am J Hypertens 2008; 21:1224-1230 (C) 2008 American Journal of Hypertension, Ltd.
C1 [Anderson, R. David; Sizemore, B. Clay; von Mering, Gregory O.; Handberg, Eileen M.; Nichols, Wilmeer W.; Pepine, Carl J.] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32611 USA.
[Barrow, Genevieve M.; Johnson, B. Delia] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Med & Clin Psychol, Pittsburgh, PA USA.
[Merz, C. Noel Bairey] Cedars Sinai Med Ctr, Prevent & Rehabil Cardiac Ctr, Los Angeles, CA 90048 USA.
[Sopko, George] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Pepine, CJ (reprint author), Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32611 USA.
EM pepincj@medicine.ufl.edu
FU NHLBI NIH HHS [N01 HV068163]
NR 46
TC 5
Z9 7
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0895-7061
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD NOV
PY 2008
VL 21
IS 11
BP 1224
EP 1230
DI 10.1038/ajh.2008.268
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 364BV
UT WOS:000260312100012
PM 18802432
ER
PT J
AU Foster, MC
Keyes, MJ
Larson, MG
Vita, JA
Mitchell, GF
Meigs, JB
Vasan, RS
Benjamin, EJ
Fox, CS
AF Foster, Meredith C.
Keyes, Michelle J.
Larson, Martin G.
Vita, Joseph A.
Mitchell, Gary F.
Meigs, James B.
Vasan, Ramachandran S.
Benjamin, Emelia J.
Fox, Caroline S.
TI Relations of Measures of Endothelial Function and Kidney Disease: The
Framingham Heart Study
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Chronic kidney disease; brachial reactivity; cystatin C; Framingham
Heart Study
ID FLOW-MEDIATED DILATION; CHRONIC-RENAL-FAILURE; CARDIOVASCULAR
RISK-FACTORS; GLOMERULAR-FILTRATION-RATE; HEMODIALYSIS-PATIENTS; SERUM
CREATININE; DEPENDENT DILATION; REACTIVE HYPEREMIA; BRACHIAL-ARTERY;
FAMILY-HISTORY
AB Background: Endothelial dysfunction is prevalent in individuals with end-stage renal disease. Whether endothelial dysfunction is present in patients with moderate chronic kidney disease (CKD) is uncertain.
Study Design: Cross-sectional study.
Settings & Participants: Brachial reactivity measurements were obtained during the seventh examination cycle in 2,818 (diameter measurements) and 2,256 (flow measurements) Framingham Heart Study Offspring cohort participants (53% women; mean age, 61 +/- 9 years).
Predictor: Estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) derived from creatinine-and cystatin C-based estimating equations; microalbuminuria status.
Outcome: Brachial reactivity measurements (baseline brachial diameter, flow-mediated dilation, baseline and hyperemic mean flow).
Measurements: Linear regression models were used to model brachial measures as a function of CKD and microalbuminuria status.
Results: Overall, 7.3% (n = 206) of participants had CKD, and of 2,301 with urinary measurements, 10.0% (n = 230) had microalbuminuria. Brachial reactivity measures did not differ significantly by CKD status in either creatinine- or cystatin C-based equations in either age- and sex- or multivariable-adjusted models. In age- and sex-adjusted models, microalbuminuria was associated with decreased hyperemic mean flow (47.2 +/- 1.4 versus 51.4 +/- 0.5 mg/g; P = 0.005), but the association was not significant after multivariable adjustment (P = 0.09).
Limitations: Predominantly white ambulatory cohort; results may not be generalizable to other ethnic groups or individuals with severe CKD.
Conclusions: Endothelial dysfunction was not a major correlate of CKD in our sample. Am J Kidney Dis 52:859-867. (C) 2008 by the National Kidney Foundation, Inc.
C1 [Foster, Meredith C.; Keyes, Michelle J.; Larson, Martin G.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Foster, Meredith C.; Fox, Caroline S.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Cardiol Sect, Boston, MA 02215 USA.
[Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Mitchell, Gary F.] Cardiovasc Engn Inc, Waltham, MA USA.
[Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Vasan, Ramachandran S.] Boston Univ, Prevent Med Sect, Boston, MA 02215 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254;
Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
Emelia/0000-0003-4076-2336
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC-25195, RO1s HL70100, HL60040, HL076784, AG028321]; National
Heart, Lung and Blood Institute, National Institutes of Health
[2K24HL04334]; American Diabetes Association Career Development Award;
National Center for Research Resources (NCRR) General Clinical Research
Centers (GCRC) [M01-RR-01066]
FX This work was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (N01-HC-25195) and RO1s HL70100,
HL60040, HL076784, AG028321 (E.J.B.). Dr Vasan is supported in part by
grant 2K24HL04334 from the National Heart, Lung and Blood Institute,
National Institutes of Health; American Diabetes Association Career
Development Award; and the National Center for Research Resources (NCRR)
General Clinical Research Centers (GCRC) grant M01-RR-01066 (J.B.M.).
NR 52
TC 13
Z9 13
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD NOV
PY 2008
VL 52
IS 5
BP 859
EP 867
DI 10.1053/j.ajkd.2008.04.027
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 367ML
UT WOS:000260556000008
PM 18617305
ER
PT J
AU Kottgen, A
Hsu, CC
Coresh, J
Shuldiner, AR
Berthier-Schaad, Y
Gambhir, TR
Smith, MW
Boerwinkle, E
Kao, WHL
AF Koettgen, Anna
Hsu, Charles C.
Coresh, Josef
Shuldiner, Alan R.
Berthier-Schaad, Yvette
Gambhir, Tejal Rami
Smith, Michael W.
Boerwinkle, Eric
Kao, W. H. Linda
TI The Association of Podocin R229Q Polymorphism With Increased Albuminuria
or Reduced Estimated GFR in a Large Population-Based Sample of US Adults
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article; Proceedings Paper
CT 47th Annual Conference on Cardiovascular Disease Epidemiology and
Prevention
CY FEB 28-MAR 03, 2007
CL Orlando, FL
SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst
DE NPHS2; podocin; albuminuria; association study; functional variant;
population-based sample
ID FOCAL-SEGMENTAL GLOMERULOSCLEROSIS; RESISTANT NEPHROTIC SYNDROME;
GLOMERULAR-FILTRATION-RATE; GENOME-WIDE ASSOCIATION; SERUM CREATININE;
NPHS2 MUTATION; DISEASE; RISK; SPECTRUM; KIDNEY
AB Background: Rare mutations in nephrosis 2 (NPHS2), encoding podocin, are found in patients with familial and sporadic steroid-resistant nephrotic syndrome and focal segmental glomerular sclerosis. The objective of this study is to assess the contribution of the commonly reported functional podocin polymorphism R229Q to kidney disease in the population at large and replicate a prior study of an association of R229Q and albuminuria in the general population.
Study Design: Large sample of the Atherosclerosis Risk in Communities (ARIC) Study, a population-ased prospective study.
Setting & Participants: 4,424 white and 3,746 black middle-aged adults.
Predictor: Genotype at the R229Q polymorphism in podocin.
Outcomes: Urinary albumin-creatinine ratio (ACR) and decreased estimated glomerular filtration rate (eGFR) as measures of kidney damage/dysfunction.
Measurements: Crude and multivariable adjusted linear and logistic regression models.
Results: R229Q allele frequencies were 3.7% in 4,424 white and 0.6% in 3,746 black individuals. No significant association of R229Q with increased ACR or decreased eGFR was observed (adjusted odds ratio of ACR >= 3 mg/g in RQ/QQ versus RR carriers, 1.18; 95% confidence interval, 0.76 to 1.84; adjusted odds ratio of eGFR < 60 mL/min/1.73 m(2) in RQ/QQ versus RR carriers, 1.18; 95% confidence interval, 0.76 to 1.83). As expected, the established kidney disease risk factors hypertension and diabetes mellitus were associated strongly with measures of kidney damage/dysfunction, but the R229Q polymorphism was not associated with an additional increase in kidney disease measures.
Limitations: Single measurement of ACR, subsample of all ARIC participants.
Conclusion: No significant association of the relatively rare R229Q variant and ACR or eGFR was found in either white or black individuals. The phenotypic effect of a variant as R229Q would have to be of great magnitude to meaningfully contribute to the risk of kidney disease on a population level. The importance of such variants in the general population, as well as replication studies, can be evaluated best in large community-based studies that allow for accounting of established disease risk factors. Am J Kidney Dis 52:868-875. (C) 2008 by the National Kidney Foundation, Inc.
C1 [Koettgen, Anna; Hsu, Charles C.; Coresh, Josef; Berthier-Schaad, Yvette; Gambhir, Tejal Rami; Kao, W. H. Linda] Johns Hopkins Univ, Baltimore, MD USA.
[Shuldiner, Alan R.] Univ Maryland, Baltimore, MD 21201 USA.
[Berthier-Schaad, Yvette; Smith, Michael W.] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
[Smith, Michael W.] NCI, Basic Res Program, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA.
[Boerwinkle, Eric] Univ Texas Houston, Houston, TX USA.
RP Kao, WHL (reprint author), 615 N Wolfe St,Rm W6513, Baltimore, MD 21205 USA.
EM wkao@jhsph.edu
RI Smith, Michael/B-5341-2012; Kottgen, Anna/D-2920-2012
FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NHLBI NIH
HHS [N01HC55019, N01 HC055016, N01 HC055018, N01 HC055019, N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, N01HC55015, N01HC55016, N01HC55018, N01HC55020,
N01HC55021, N01HC55022]; NIDDK NIH HHS [K01 DK067207, K01-DK-067207, R21
DK073482, R21 DK073482-02]
NR 29
TC 15
Z9 17
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 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD NOV
PY 2008
VL 52
IS 5
BP 868
EP 875
DI 10.1053/j.ajkd.2008.02.306
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 367ML
UT WOS:000260556000009
PM 18499321
ER
PT J
AU Denny, CC
Wilfond, BS
Peters, JA
Giri, N
Alter, BP
AF Denny, Colleen C.
Wilfond, Benjamin S.
Peters, June A.
Giri, Neelam
Alter, Blanche P.
TI All in the Family: Disclosure of "Unwanted" Information to an Adolescent
to Benefit a Relative
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE ethics; genetic disclosure; minor children; dyskeratosis congenita;
research results
ID DYSKERATOSIS-CONGENITA; CHILDREN; MEDICINE; CANCER; ANEMIA; DONORS;
HEALTH
AB Ethical assessments of clinical decisions are typically based on the preferences and interests of the individual patient. However, some clinical interventions, Such as genetic testing or organ donation, may involve multiple family members. in these cases, one family member may have the potential to benefit, while another family member is exposed to potential physical or psychological risk. in the research setting, the balancing of benefits and risks between family members may be further complicated by uncertainty about their magnitude and likelihood. in addition, when the individual facing these apparently uncompensated risks is a child, the situation becomes particularly ethically complicated, as we appreciated in a recent case. Investigators at the National Cancer Institute were faced with a decision about whether it would be appropriate to disclose apparently "unwanted" research test results (length of telomeres in leukocyte subsets) to an adolescent about risk Of future disease (dyskeratosis congenita), possibly causing psychological harm and an ethical wrong. These issues were not expected at the outset of the fan-lily'S Study participation but rather emerged with new data about the research tests. Disclosure of the research finding was an important consideration in order to avoid using the adolescent as a stem-cell donor for his sister. Disclosure to the adolescent Could not be justified by merely considering the immediate interests and preferences of the adolescent. However, an expanded ethical analysis that considers the adolescent's familial context offers a more complete picture of the adolescent's interests and preferences which provides justification for disclosure. Published 2008 Wiley-Liss, Inc.
C1 [Denny, Colleen C.; Wilfond, Benjamin S.] Natl Inst Hlth Clin Ctr, Dept Bioeth, Bethesda, MD USA.
[Wilfond, Benjamin S.] Univ Washington, Seattle Childrens Hosp, Treuman Katz Ctr Bioeth, Seattle, WA 98195 USA.
[Wilfond, Benjamin S.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Peters, June A.; Giri, Neelam; Alter, Blanche P.] Natl Canc Inst, Div Canc Epidemiol & Genet, Clin Genet Branch, Bethesda, MD USA.
RP Wilfond, BS (reprint author), Metropolitan Pk W,M-S,MPW 8-2,1100 Olive Way,Room, Seattle, WA 98101 USA.
EM benjamin.wilfond@seattlechildrens.org
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute
FX Grant sponsor: Intramural Research Program of the National Institutes of
Health; Grant sponsor: National Cancer Institute.
NR 18
TC 5
Z9 5
U1 1
U2 1
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 NOV 1
PY 2008
VL 146A
IS 21
BP 2719
EP 2724
DI 10.1002/ajmg.a.32362
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 373PW
UT WOS:000260985400002
PM 18831063
ER
PT J
AU Obafemi, AA
Bulas, DI
Troendle, J
Marini, JC
AF Obafemi, Abimbola A.
Bulas, Dorothy I.
Troendle, James
Marini, Joan C.
TI Popcorn Calcification in Osteogenesis Imperfecta: Incidence,
Progression, and Molecular Correlation
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE autosomal dominant osteogenesis imperfect; osteogenesis imperfect;
popcorn calcification; calcification; collagen mutations
ID PROLYL 3-HYDROXYLATION; GENETIC-HETEROGENEITY; DEFICIENCY; MUTATIONS;
COLLAGEN; CHILDREN
AB Osteogenesis imperfecta (OI) is a heritable disorder characterized by osteoporosis and increased susceptibility to fracture. All children with severe 01 have extreme short statute and some have "popcorn" calcifications, areas of disorganized hyperdense lines in the metaphysis and epiphysis around the growth plate on lower limb radiographs. Popcorn calcifications were noted on radiographs of two children with non-lethal type VIII 01, a recessive form caused by P3H1 deficiency. To determine the incidence, progression, and molecular correlations of popcorn calcifications, we retrospectively examined serial lower limb radiographs of 45 children with type III or IV OI and known dominant mutations in type I collagen. Popcorn calcifications were present in 13 of 25 type III (52%), but only 2 of 20 type IV (10%), OI children. The mean age of onset was 7.0 years, with a range of 4-14 years. All children with popcorn calcifications had this finding in their distal femora, and most also had calcifications in proximal tibiae. While unilateral popcorn calcification contributes to femoral growth deficiency and leg length discrepancy, severe linear growth deficiency, and metaphyseal flare do not differ significantly between type III OI patients with and without popcorn calcifications. The type I collagen Mutations associated with popcorn calcifications Occur equally in both COL1A1 and COL1A2, and have no preferential location along the chains. These data demonstrate that popcorn calcifications are a frequent feature of severe OI, but do not distinguish cases with defects in collagen structure (primarily dominant type III OI) or modification (recessive type VIII OI). Published 2008 Wiley-Liss, Inc.
C1 [Obafemi, Abimbola A.; Marini, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bone & Extracellular Mat Branch, Bethesda, MD 20892 USA.
[Obafemi, Abimbola A.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA.
[Bulas, Dorothy I.] Childrens Natl Med Ctr, Dept Diagnost Imaging & Radiol, Washington, DC 20010 USA.
[Troendle, James] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Biometry & Math Stat Branch DESPR, Bethesda, MD USA.
RP Marini, JC (reprint author), NICHHD, NIH, Bone & Extracellular Mat Branch, Bldg 10,Rm 10N260,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM oidoc@helix.nih.gov
FU NICHD Intramural Funds; NIH; Pfizer, Inc
FX Grant sponsor: NICHD Intramural Funds; Grant sponsor: NIH; Grant
sponsor: Pfizer, Inc.
NR 19
TC 15
Z9 15
U1 0
U2 2
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 NOV 1
PY 2008
VL 146A
IS 21
BP 2725
EP 2732
DI 10.1002/ajmg.a.32508
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 373PW
UT WOS:000260985400003
PM 18798308
ER
PT J
AU Kazi, S
Boroumand, S
AF Kazi, Shazia
Boroumand, Shahdokht
TI Assessing Quality of Primary Care Provided to the HIV-Infected Ryan
White Population in the Baltimore Eligible Metropolitan Area
SO AMERICAN JOURNAL OF MEDICAL QUALITY
LA English
DT Article
DE Ryan White; HIV/AIDS; quality; primary care
ID ANCILLARY SERVICES; ACT
AB The Baltimore Eligible Metropolitan Area (EAU) receives Ryan White (RW) funds each year because of its high AIDS case rate. This study assessed the quality of primary care services provided to HIV-infected clients in the Baltimore EMA. Medical charts of 384 randomly selected clients served in 2004 were reviewed. A survey instrument was designed to assess the minimum requirements satisfied for CD4 and viral load count, highly active antiretroviral treatment, pneumocystitis carinii pneumonia and mycobacterium avium complex prophylaxis, tuberculosis, syphilis, hepatitis B and C screening and safe sex education. A numeric index of quality was developed for each client in the form of a total score. The clients were categorized into high, medium and low quality groups depending on their total scores. Only 32% of clients were in the high-quality category. Number of primary care visits per year (P <= .0001) was found to be significantly associated with quality of care. Proactive efforts are needed at the provider level to keep or reengage HIV clients in care. (Am J Med Qual 2008;23:484-491)
C1 [Kazi, Shazia] City Baltimore Hlth Dept, Baltimore, MD USA.
[Boroumand, Shahdokht] NIH, Bethesda, MD 20892 USA.
RP Kazi, S (reprint author), 1001 E Fayette St, Baltimore, MD 21202 USA.
EM shazia.kazi@baltimorecity.gov
FU Baltimore City Health Department
FX The authors are grateful to Baltimore City Health Department for
supporting this study.
NR 20
TC 4
Z9 5
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1062-8606
J9 AM J MED QUAL
JI Am. J. Med. Qual.
PD NOV-DEC
PY 2008
VL 23
IS 6
BP 484
EP 491
DI 10.1177/1062860608324174
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 374JB
UT WOS:000261038500009
PM 19001104
ER
PT J
AU Alleyne, M
Horne, MK
Miller, JL
AF Alleyne, Michael
Horne, McDonald K.
Miller, Jeffery L.
TI Individualized Treatment for Iron-deficiency Anemia in Adults
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Review
DE Anemia; Dosing cycles; Hepcidin; Iron
ID DIFFERENTIAL-DIAGNOSIS; MANAGEMENT
AB Iron deficiency is one of the most common disorders affecting humans, and iron-deficiency anemia continues to represent a major public health problem worldwide. It is especially common among women of childbearing age because of pregnancy and menstrual blood loss. Additional patient groups include those with other sources of blood loss, malnutrition, or gut malabsorption. Iron-deficiency anemia remains prevalent despite the widespread ability to diagnose the disease and availability of medicinal iron preparations. Therefore, new approaches are needed to effectively manage these patient populations. In this review, the diagnosis and treatment of iron-deficiency anemia are discussed with emphasis placed on consideration of patient-specific features. It is proposed that all patients participate in their own care by helping their physician to identify a tolerable daily iron dose, formulation, and schedule. Dosing cycles are recommended for iron replacement based on the tolerated daily dose and the total iron deficit. Each cycle consists of 5000 mg of oral elemental iron ingested over at least 1 month with appropriate follow-up. This approach should assist physicians and their patients with the implementation of individualized treatment strategies for patients with iron-deficiency anemia. Published by Elsevier Inc.
C1 [Miller, Jeffery L.] NIDDK, Sect Mol Genom & Therapeut, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
[Alleyne, Michael] NCI, Bethesda, MD 20892 USA.
[Horne, McDonald K.] WG Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD USA.
[Horne, McDonald K.] WG Magnuson Clin Ctr, Hematol Serv, Bethesda, MD USA.
RP Miller, JL (reprint author), NIDDK, Sect Mol Genom & Therapeut, Mol Med Branch, NIH, Bldg 10,Room 9N311,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jm7f@nih.gov
FU National Institutes of Health; National Institute of Diabetes and
Digestive and Kidney Diseases
FX Funding: This research was supported by the Intramural Research Program
of the National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 23
TC 50
Z9 58
U1 1
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD NOV
PY 2008
VL 121
IS 11
BP 943
EP 948
DI 10.1016/j.amjmed.2008.07.012
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 364XV
UT WOS:000260369900004
PM 18954837
ER
PT J
AU Klebanoff, MA
Meis, PJ
Dombrowski, MP
Zhao, Y
Moawad, AH
Northen, A
Sibai, BM
Iams, JD
Varner, MW
Caritis, SN
O'Sullivan, MJ
Leveno, KJ
Miodovnik, M
Conway, D
Wapner, RJ
Carpenter, M
Mercer, BM
Ramin, SM
Thorp, JM
Peaceman, AM
AF Klebanoff, Mark A.
Meis, Paul J.
Dombrowski, Mitchell P.
Zhao, Yuan
Moawad, Atef H.
Northen, Allison
Sibai, Baha M.
Iams, Jay D.
Varner, Michael W.
Caritis, Steve N.
O'Sullivan, Mary J.
Leveno, Kenneth J.
Miodovnik, Menachem
Conway, Deborah
Wapner, Ronald J.
Carpenter, Marshall
Mercer, Brian M.
Ramin, Susan M.
Thorp, John M.
Peaceman, Alan M.
CA Natl Inst Child Hlth Human Dev
TI Salivary progesterone and estriol among pregnant women treated with
17-alpha-hydroxyprogesterone caproate or placebo
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT 20th Annual Meeting of the
Society-for-Pediatric-and-Perinatal-Epidemiologic-Research
CY JUN 18-19, 2007
CL Boston, MA
SP Soc Pediat & Perinatal Epidemiol Res
DE 17-alpha-hydroxyprogesterone caproate; longitudinal studies; preterm
birth; salivary estriol; salivary progesterone
ID RECURRENT PRETERM DELIVERY; FETAL MEMBRANES; INCREASED RISK; LABOR;
TERM; ESTRADIOL; BIRTH; RATIO; PREMATURITY; PARTURITION
AB OBJECTIVE: The objectives of the study was to determine whether salivary progesterone (P) or estriol (E3) concentration at 16-20 weeks' gestation predicts preterm birth or the response to 17 alpha-hydroxyprogesterone caproate (17OHPC) and whether 17OHPC treatment affected the trajectory of salivary P and E3 as pregnancy progressed.
STUDY DESIGN: This was a secondary analysis of a clinical trial of 17OHPC to prevent preterm birth. Baseline saliva was assayed for P and E3. Weekly salivary samples were obtained from 40 women who received 17OHPC and 40 who received placebo in a multicenter randomized trial of 17OHPC to prevent recurrent preterm delivery.
RESULTS: Both low and high baseline saliva P and E3 were associated with a slightly increased risk of preterm birth. However, 17OHPC prevented preterm birth comparably, regardless of baseline salivary hormone concentrations. 17OHPC did not alter the trajectory of salivary P over pregnancy, but it significantly blunted the rise in salivary E3 as well as the rise in the E3/P ratio.
CONCLUSION: 17OHPC flattened the trajectory of E3 in the second half of pregnancy, suggesting that the drug influences the fetoplacental unit.
C1 [Klebanoff, Mark A.] NICHHD, Bethesda, MD 20892 USA.
[Zhao, Yuan] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Meis, Paul J.] Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA.
[Dombrowski, Mitchell P.] Wayne State Univ, Detroit, MI USA.
[Moawad, Atef H.] Univ Chicago, Chicago, IL 60637 USA.
[Northen, Allison] Univ Alabama, Birmingham, AL USA.
[Sibai, Baha M.] Univ Cincinnati, Cincinnati, OH USA.
[Sibai, Baha M.] Univ Tennessee, Memphis, TN USA.
[Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA.
[Varner, Michael W.] Univ Utah, Salt Lake City, UT USA.
[Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
[O'Sullivan, Mary J.] Univ Miami, Miami, FL USA.
[Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Miodovnik, Menachem; Wapner, Ronald J.] Columbia Univ, New York, NY USA.
[Miodovnik, Menachem] Washington Hosp Ctr, Washington, DC 20010 USA.
[Conway, Deborah] Univ Texas San Antonio, San Antonio, TX USA.
[Wapner, Ronald J.] Drexel Univ, Philadelphia, PA 19104 USA.
[Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA.
[Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Ramin, Susan M.] Univ Texas Houston, Houston, TX USA.
[Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA.
[Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA.
RP Klebanoff, MA (reprint author), NICHHD, Bethesda, MD 20892 USA.
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973
FU Intramural NIH HHS [NIH0010045861]; NICHD NIH HHS [HD21410, HD21414,
HD27860, HD27861, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208,
HD34210, HD36801, HD40500, HD40512, HD40544, HD40560, U01 HD036801, U10
HD021410, U10 HD027860, U10 HD027860-09, U10 HD027869, U10 HD027905, U10
HD027915, U10 HD027917, U10 HD034116, U10 HD034122, U10 HD034136, U10
HD034208, U10 HD036801, U10 HD040485, U10 HD040500, U10 HD040512, U10
HD040544, U10 HD040560, UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1
HD034208, UG1 HD040500, UG1 HD040512, UG1 HD040544, UG1 HD040560]; PHS
HHS [NIH0010045861]
NR 28
TC 0
Z9 0
U1 0
U2 4
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 NOV
PY 2008
VL 199
IS 5
AR 506.e1
DI 10.1016/j.ajog.2008.03.003
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 367XL
UT WOS:000260585800023
PM 18456237
ER
PT J
AU Lynch, CD
Klebanoff, MA
Louis, GMB
AF Lynch, Courtney D.
Klebanoff, Mark A.
Louis, Germaine M. B.
TI Is caffeine use during pregnancy really unsafe?
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Letter
C1 [Lynch, Courtney D.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA.
[Klebanoff, Mark A.; Louis, Germaine M. B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Rockville, MD USA.
RP Lynch, CD (reprint author), Ohio State Univ, Coll Publ Hlth, Div Epidemiol, B218 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA.
EM clynch@cph.osu.edu
OI Buck Louis, Germaine/0000-0002-1774-4490
FU Intramural NIH HHS [Z01 HD008770-04]
NR 4
TC 2
Z9 2
U1 0
U2 2
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 NOV
PY 2008
VL 199
IS 5
AR e16
DI 10.1016/j.ajog.2008.05.035
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 367XL
UT WOS:000260585800060
PM 18691688
ER
PT J
AU Christodoulou, MI
Kapsogeorgou, EK
Moutsopoulos, NM
Moutsopoulos, HM
AF Christodoulou, Maria I.
Kapsogeorgou, Efstathia K.
Moutsopoulos, Niki M.
Moutsopoulos, Haralampos M.
TI Foxp3(+) T-Regulatory Cells in Sjogren's Syndrome Correlation with the
Grade of the Autoimmune Lesion and Certain Adverse Prognostic Factors
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID TRANSCRIPTION FACTOR FOXP3; GLAND EPITHELIAL-CELLS;
RHEUMATOID-ARTHRITIS; PERIPHERAL-BLOOD; DENDRITIC CELLS; SYNOVIAL-FLUID;
EXPRESSION; DISEASE; LYMPHOMA; CLASSIFICATION
AB Sjogren's syndrome (SS) is a chronic autoimmune exocrinopathy associated with variable lymphocytic infiltration of the affected organs (primarily salivary and lacrimal glands) and broad clinical manifestations, including lymphoma development. To investigate the potential implication of Foxp3(+) T-regulatory cells in the regulation of SS inflammatory responses, we studied their incidence in the minor salivary glands (MSGs) and their relationship with histopathological and clinical disease parameters. Similar percentages of infiltrating Foxp3(+) cells were observed in the MSG lesions of all SS patients (n = 30) and non-SS sialadenitis controls (n = 7). Foxp3(+) cells were not detected in sicca-complaining controls with negative biopsy (n = 6). In SS patients, Foxp3+ cell frequency varied according to lesion severity, with the highest and lowest frequencies obtained in intermediate and mild MSG lesions, respectively. In the peripheral blood of these patients, reverse distribution of Foxp3+ cells was observed. Furthermore, the frequency of Foxp3+ cells in the MSG lesions and peripheral blood was negatively associated (r = -0.6679, P = 0.0065). MSG-infiltrating Foxp3(+) cells were found to positively correlate with biopsy focus score (P = 0.05), infiltrating mononuclear cells, dendritic cells, and macrophages; (P <= 0.024 each), and serum C4 levels (P = 0.0328), whereas lower Foxp3(+) cell incidence correlated with adverse predictors for lymphoma development, such as the presence of C4 hypocomplementemia (P = 0.012) and SG enlargement (tendency, P = 0.067). our findings; suggest that the Foxp3(+) T-regulatory cell frequency in the MSG lesions of SS patients correlates with inflammation grade and certain risk factors for lymphoma development. (Am J Pathol 2008, 173:1389-1396; DOI: 10.2353/ajpath.2008.080246)
C1 [Christodoulou, Maria I.; Kapsogeorgou, Efstathia K.; Moutsopoulos, Haralampos M.] Natl Univ Athens, Sch Med, Dept Pathophysiol, Immunol Lab, Athens 11527, Greece.
[Moutsopoulos, Niki M.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA.
RP Moutsopoulos, HM (reprint author), Natl Univ Athens, Sch Med, Dept Pathophysiol, Immunol Lab, 75 Mikras Asias St, Athens 11527, Greece.
EM hmoutsop@med.uoa.gr
FU Hellenic Secretariat for Research and Technology; Lilian Voudouri
Foundation
FX Supported by the Hellenic Secretariat for Research and Technology and
the Lilian Voudouri Foundation.
NR 41
TC 60
Z9 62
U1 0
U2 1
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD NOV
PY 2008
VL 173
IS 5
BP 1389
EP 1396
DI 10.2353/ajpath.2008.080246
PG 8
WC Pathology
SC Pathology
GA 369XE
UT WOS:000260726400014
PM 18818377
ER
PT J
AU Deshpande, N
Ferrucci, L
Metter, J
Faulkner, KA
Strotmeyer, E
Satterfield, S
Schwartz, A
Simonsick, E
AF Deshpande, Nandini
Ferrucci, Luigi
Metter, Jeffrey
Faulkner, Kimberly A.
Strotmeyer, Elsa
Satterfield, Suzanne
Schwartz, Ann
Simonsick, Eleanor
TI Association of Lower Limb Cutaneous Sensitivity with Gait Speed in the
Elderly The Health ABC Study
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article; Proceedings Paper
CT 60th Annual Meeting of the Gerontological-Society-of-America
CY NOV, 2007
CL San Francisco, CA
SP Gerontol Soc Amer
DE Aging; Gait Speed; Cutaneous Vibration Sensitivity; Monofilament
Sensitivity
ID PERIPHERAL NEUROPATHY; OLDER-ADULTS; WALKING; FOOT; WOMEN; MUSCLES;
PEOPLE; RISK; AGE; STIMULATION
AB Objective: To examine the association of fast-adapting receptor-mediated vibrotactile sensitivity and slow-adapting receptor-mediated pressure sensitivity with self-selected usual gait speed and gait speed over a challenging narrow (20 cm wide) course.
Design: Participants from the population-based older cohort of the Health ABC study were included (n = 1721; age: 76.4 +/- 2.8 yrs). Usual gait speed over 6 m and, gait speed over a 6-m narrow course were measured. Vibration perception threshold (100 Hz) was measured on the plantar surface, and monofilament testing (1.4 and 10 g) was performed on the dorsum of the great toe. Covariates including knee extensor torque, standing balance, visual acuity and contrast sensitivity, knee pain, depressive symptoms, high fasting glucose levels, and peripheral arterial disease were evaluated.
Results: Vibrotactile and monofilament sensitivity were significantly worse in slower gait speed groups in both walking conditions (P < 0.001 to P = 0.015). Adjusting for covariates, vibrotactile (P < 0.001) but not monofilament sensitivity (P = 0.655) was independently associated with self-selected normal gait speed. Neither sensory function was associated with narrow-base gait speed.
Conclusions: In the elderly, poor lower limb vibrotactile sensitivity measured on the plantar surface of the great toe, but not the pressure sensitivity as measured by monofilament testing on the dorsum of the great toe, is independently associated with slower self-selected normal gait speed. Narrow-based walking seems to depend on other neuromuscular mechanisms.
C1 [Deshpande, Nandini] Univ Kansas, Med Ctr, Dept Phys Therapy & Rehabil Sci, Kansas City, KS 66160 USA.
[Deshpande, Nandini; Ferrucci, Luigi; Metter, Jeffrey; Strotmeyer, Elsa] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
[Faulkner, Kimberly A.; Strotmeyer, Elsa] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Schwartz, Ann] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Deshpande, N (reprint author), Univ Kansas, Med Ctr, Dept Phys Therapy & Rehabil Sci, MS 2002,3901 Rainbow Blvd, Kansas City, KS 66160 USA.
RI Strotmeyer, Elsa/F-3015-2014;
OI Strotmeyer, Elsa/0000-0002-4093-6036
FU NIA NIH HHS [N01 AG062101, N01 AG062103, N01 AG062106, N01-AG-2103,
N01-AG-2106, N01-AG-6-2101, R01 AG028050]
NR 30
TC 14
Z9 15
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-9115
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD NOV
PY 2008
VL 87
IS 11
BP 921
EP 928
DI 10.1097/PHM.0b013e31818a5556
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 364MX
UT WOS:000260340900007
PM 18936557
ER
PT J
AU Eisenhofer, G
Huynh, TT
Elkahloun, A
Morris, JC
Bratslavsky, G
Linehan, WM
Zhuang, Z
Balgley, BM
Lee, CS
Mannelli, M
Lenders, JWM
Bornstein, SR
Pacak, K
AF Eisenhofer, Graeme
Huynh, Thanh-Truc
Elkahloun, Abdel
Morris, John C.
Bratslavsky, Gennady
Linehan, W. Marston
Zhuang, Zhengping
Balgley, Brian M.
Lee, Cheng S.
Mannelli, Massimo
Lenders, Jacques W. M.
Bornstein, Stefan R.
Pacak, Karel
TI Differential expression of the regulated catecholamine secretory pathway
in different hereditary forms of pheochromocytoma
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE secretion; exocytosis; von Hippel-Lindau; multiple endocrine neoplasia
type 2
ID HIPPEL-LINDAU-SYNDROME; ENDOCRINE NEOPLASIA TYPE-2; TRANSCRIPTIONAL
REPRESSOR REST; PC12 CELLS; CHROMAFFIN CELLS; ADRENAL-MEDULLA; GENE;
NOREPINEPHRINE; EPINEPHRINE; EXOCYTOSIS
AB Eisenhofer G, Huynh TT, Elkahloun A, Morris JC, Bratslavsky G, Linehan WM, Zhuang Z, Balgley BM, Lee CS, Mannelli M, Lenders JW, Bornstein SR, Pacak K. Differential expression of the regulated catecholamine secretory pathway in different hereditary forms of pheochromocytoma. Am J Physiol Endocrinol Metab 295: E1223-E1233, 2008; doi:10.1152/ajpendo.90591.2008. - Pheochromocytomas in patients with von Hippel-Lindau (VHL) syndrome and multiple endocrine neoplasia type 2 (MEN 2) differ in the types and amounts of catecholamines produced and the resulting signs and symptoms. We hypothesized the presence of different processes of catecholamine release reflecting differential expression of components of the regulated secretory pathway among the two types of hereditary tumors. Differences in catecholamine secretion from tumors in patients with VHL syndrome (n = 47) and MEN 2 (n = 32) were examined using measurements of catecholamines in tumor tissue, urine, and plasma, the last of which was under baseline conditions in all subjects and in a subgroup of patients who received intravenous glucagon to provoke catecholamine release. Microarray and proteomics analyses, quantitative PCR, and Western blotting were used to assess expression of tumor tissue secretory pathway components. The rate constant for baseline catecholamine secretion was 20-fold higher in VHL than in MEN 2 tumors (0.359 +/- 0.094 vs. 0.018 +/- 0.009 day(-1)), but catecholamine release was responsive only to glucagon in MEN 2 tumors. Compared with tumors from MEN 2 patients, those from VHL patients were characterized by reduced expression of numerous components of the regulated secretory pathway (e. g., SNAP25, syntaxin, rabphilin 3A, annexin A7, calcium-dependent secretion activator). The mutation-dependent differences in expression of secretory pathway components indicate a more mature regulated secretory pathway in MEN 2 than VHL tumors. These data provide a unique mechanistic link to explain how variations in the molecular machinery governing exocytosis may contribute to clinical differences in the secretion of neurotransmitters or hormones and the subsequent presentation of a disease.
C1 [Eisenhofer, Graeme] Univ Dresden, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany.
[Eisenhofer, Graeme; Bornstein, Stefan R.] Univ Dresden, Dept Med, D-01307 Dresden, Germany.
[Huynh, Thanh-Truc; Pacak, Karel] NICHHD, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA.
[Elkahloun, Abdel] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Morris, John C.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Bratslavsky, Gennady; Linehan, W. Marston] NCI, Urol Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
[Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Balgley, Brian M.; Lee, Cheng S.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
[Mannelli, Massimo] Univ Florence, Dept Clin Pathophysiol, Florence, Italy.
[Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands.
RP Eisenhofer, G (reprint author), Univ Dresden, Inst Clin Chem & Lab Med, Fetscherstr 74, D-01307 Dresden, Germany.
EM Graeme.Eisenhofer@uniklinikum-dresden.de
RI Lenders, J.W.M./L-4487-2015;
OI Balgley, Brian/0000-0002-3509-4567; Mannelli,
Massimo/0000-0002-8001-9857
FU National Institute of Child Health and Human Development; Center for
Cancer Research; National Cancer Institute; National Human Genome
Research Institute; National Institute of Neurological Disorders and
Stroke; National Institutes of Health, Bethesda, Maryland
FX This work was supported by the intramural programs of the National
Institute of Child Health and Human Development, the Center for Cancer
Research, the National Cancer Institute, the National Human Genome
Research Institute, and the National Institute of Neurological Disorders
and Stroke at the National Institutes of Health, Bethesda, Maryland.
NR 41
TC 25
Z9 25
U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
EI 1522-1555
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD NOV
PY 2008
VL 295
IS 5
BP E1223
EP E1233
DI 10.1152/ajpendo.90591.2008
PG 11
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 370OA
UT WOS:000260770300027
PM 18854424
ER
PT J
AU Csiszar, A
Labinskyy, N
Perez, V
Recchia, FA
Podlutsky, A
Mukhopadhyay, P
Losonczy, G
Pacher, P
Austad, SN
Bartke, A
Ungvari, Z
AF Csiszar, Anna
Labinskyy, Nazar
Perez, Viviana
Recchia, Fabio A.
Podlutsky, Andrej
Mukhopadhyay, Partha
Losonczy, Gyorgy
Pacher, Pal
Austad, Steven N.
Bartke, Andrzej
Ungvari, Zoltan
TI Endothelial function and vascular oxidative stress in long-lived
GH/IGF-deficient Ames dwarf mice
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE senescence; vascular disease; atherosclerosis; Prop1(df/df) mice
ID GROWTH-FACTOR-I; MITOCHONDRIAL SUPEROXIDE-PRODUCTION; CARDIAC-SPECIFIC
OVEREXPRESSION; HORMONE RECEPTOR KNOCKOUT; NAKED MOLE-RAT; CONTRACTILE
DYSFUNCTION; NITRIC-OXIDE; LIFE-SPAN; VENTRICULAR MYOCYTES; CALORIC
RESTRICTION
AB Csiszar A, Labinskyy N, Perez V, Recchia FA, Podlutsky A, Mukhopadhyay P, Losonczy G, Pacher P, Austad SN, Bartke A, Ungvari Z. Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice. Am J Physiol Heart Circ Physiol 295: H1882-H1894, 2008. First published August 29, 2008; doi:10.1152/ajpheart.412.2008. - Hypopituitary Ames dwarf mice have low circulating growth hormone (GH)/IGF-I levels, and they have extended longevity and exhibit many symptoms of delayed aging. To elucidate the vascular consequences of Ames dwarfism we compared endothelial O-2(center dot-) and H2O2 production, mitochondrial reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and nitric oxide (NO) production in aortas of Ames dwarf and wild-type control mice. In Ames dwarf aortas endothelial O-2(center dot-) and H2O2 production and ROS generation by mitochondria were enhanced compared with those in vessels of wild-type mice. In Ames dwarf aortas there was a less abundant expression of Mn-SOD, Cu, Zn-SOD, glutathione peroxidase (GPx)-1, and endothelial nitric oxide synthase (eNOS). NO production and acetylcholine-induced relaxation were also decreased in aortas of Ames dwarf mice. In cultured wild-type mouse aortas and in human coronary arterial endothelial cells treatment with GH and IGF significantly reduced cellular O-2(center dot-) and H2O2 production and ROS generation by mitochondria and upregulated expression of Mn-SOD, Cu, Zn-SOD, GPx-1, and eNOS. Thus GH and IGF-I promote antioxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress.
C1 [Csiszar, Anna; Labinskyy, Nazar; Recchia, Fabio A.; Ungvari, Zoltan] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA.
[Perez, Viviana; Podlutsky, Andrej; Austad, Steven N.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Recchia, Fabio A.] Scuola Super Sant Anna, Sector Med, Pisa, Italy.
[Mukhopadhyay, Partha; Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA.
[Losonczy, Gyorgy; Ungvari, Zoltan] Semmelweis Univ, Dept Pulmonol, H-1085 Budapest, Hungary.
[Bartke, Andrzej] So Illinois Univ, Sch Med, Dept Internal Med, Springfield, IL USA.
[Bartke, Andrzej] So Illinois Univ, Sch Med, Dept Physiol, Springfield, IL USA.
RP Ungvari, Z (reprint author), New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA.
EM zoltan_ungvari@nymc.edu
RI Recchia, Fabio/F-2315-2010; MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher,
Pal/B-6378-2008; Podlutsky, Andrej/F-5421-2015; Bartke,
Andzej/D-6640-2017
OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher,
Pal/0000-0001-7036-8108; Bartke, Andzej/0000-0002-2569-557X
FU American Heart Association [0430108N, 0435140N]; American Diabetes
Association; Philip Morris USA Inc; Philip Morris International;
American Federation for Aging Research; Hungarian Scientific Research
Fund [OTKA-K68758]; San Antonio Area Foundation; National Institutes of
Health [HL-077256, HL-43023, AG-019899, U-19-AG-023122, PO1-HL-74237,
AG-022873, K07-AG-025063]; National Institute on Alcohol Abuse and
Alcoholism
FX This work was supported by grants from the American Heart Association
(0430108N and 0435140N), the American Diabetes Association (to Z.
Ungvari), Philip Morris USA Inc. and Philip Morris International (to Z.
Ungvari), the American Federation for Aging Research (to A. Csiszar),
the Hungarian Scientific Research Fund (OTKA-K68758), the San Antonio
Area Foundation (to A. Podlutsky), and the National Institutes of Health
(HL-077256 and HL-43023 to Z. Ungvari; AG-019899 and U-19-AG-023122 to
A. Bartke; PO1-HL-74237 to F. A. Recchia; AG-022873 and K07-AG-025063 to
S. Austad) and funded by the Intramural Research Program of the National
Institute on Alcohol Abuse and Alcoholism (to P. Pacher). F. A. Recchia
is an established investigator of the American Heart Association.
NR 56
TC 78
Z9 78
U1 0
U2 1
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 NOV
PY 2008
VL 295
IS 5
BP H1882
EP H1894
DI 10.1152/ajpheart.412.2008
PG 13
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 369VS
UT WOS:000260722600007
PM 18757483
ER
PT J
AU Nayeem, MA
Poloyac, SM
Falck, JR
Zeldin, DC
Ledent, C
Ponnoth, DS
Ansari, HR
Mustafa, SJ
AF Nayeem, Mohammed A.
Poloyac, Samuel M.
Falck, John R.
Zeldin, Darryl C.
Ledent, Catherine
Ponnoth, Dovenia S.
Ansari, Habib R.
Mustafa, S. Jamal
TI Role of CYP epoxygenases in A(2A)AR-mediated relaxation using
A(2A)AR-null and wild-type mice
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE epoxyeicosatrienoic acids; dihydroxyeicosatrienoic acids; vasodilation;
vasoconstriction; adenosine; cytochrome P-450s
ID SMOOTH-MUSCLE-CELLS; BOVINE CORONARY-ARTERIES; P450-DERIVED ARACHIDONATE
METABOLITES; RAT PREGLOMERULAR MICROVESSELS; RECEPTOR-MEDIATED
RELAXATION; PROTEIN-KINASE-C; K-ATP CHANNELS; EPOXYEICOSATRIENOIC ACIDS;
ADENOSINE RECEPTOR; HYPERPOLARIZING FACTOR
AB Nayeem MA, Poloyac SM, Falck JR, Zeldin DC, Ledent C, Ponnoth DS, Ansari HR, Mustafa SJ. Role of CYP epoxygenases in A(2A)AR-mediated relaxation using A(2A)AR-null and wild-type mice. Am J Physiol Heart Circ Physiol 295: H2068-H2078, 2008. First published September 19, 2008; doi: 10.1152/ajpheart.01333.2007.-We hypothesized that A(2A) adenosine receptor (A(2A)AR) activation causes vasorelaxation through cytochrome P-450 (CYP) epoxygenases and endothelium-derived hyperpolarizing factors, whereas lack of A(2A)AR activation promotes vasoconstriction through Cyp4a in the mouse aorta. Adenosine 5'-N-ethylcarboxamide (NECA; 10(-6) M), an adenosine analog, caused relaxation in wild-type A(2A)AR (A(2A)AR(+/+); + 33.99 +/- 4.70%, P < 0.05) versus contraction in A(2A)AR knockout (A(2A)AR(+/+); + 27.52 +/- 4.11%) mouse aortae. An A(2A)AR-specific antagonist (SCH-58261; 1 mu M) changed the NECA (10(-6) M) relaxation response to contraction (-35.82 +/- 4.69%, P < 0.05) in A(2A)AR(+/+) aortae, whereas no effect was noted in A(2A)AR(-/-) aortae. Significant contraction was seen in the absence of the endothelium in A(2A)AR(+/+) (-2.58 +/- 2.25%) aortae compared with endothelium intact aortae. An endothelial nitric oxide synthase inhibitor (N-nitroL-arginine methyl ester; 100 mu M) and a cyclooxygenase inhibitor (indomethacin; 10 mu M) failed to block NECA-induced relaxation in A(2A)AR(-/-) aortae. A selective inhibitor of CYP epoxygenases (methylsulfonyl-propargyloxyphenylhexanamide; 10(-6) M) changed NECA-mediated relaxation (-22.74 +/- 5.11% at 10(-6) M) and CGS-21680 mediated relaxation (-18.54 +/- 6.06% at 10 - 6 M) to contraction in A(2A)AR(+/+) aortae, whereas no response was noted in A(2A)AR(-/-) aortae. Furthermore, an epoxyeicosatrienoic acid (EET) antagonist [14,15-epoxyeicosa-5(Z)-enoic acid; 10 mu M] was able to block NECAinduced relaxation in A(2A)AR(+/+) aortae, whereas omega-hydroxylase inhibitors (10 mu M dibromo-dodecenyl-methylsulfimide and 10 mu M HET-0016) changed contraction into relaxation in A(2A)AR (-/-) aorta. Cyp2c29 protein was upregulated in A(2A)AR(+/+) aortae, whereas Cyp4a was upregulated in A(2A)AR(-/-) aortae. Higher levels of dihydroxyeicosatrienoic acids (DHETs; 14,15-DHET, 11,12-DHET, and 8,9-DHET, P < 0.05) were found in A(2A)AR(+/+) versus A(2A)AR(-/-) aortae. EET levels were not significantly different between A(2A)AR(+/+) and A(2A)AR(-/-) aortae. It is concluded that CYP epoxygenases play an important role in A(2A)AR-mediated relaxation, and the deletion of the A(2A)AR leads to contraction through Cyp4a.
C1 [Mustafa, S. Jamal] W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Ctr Interdisciplinary Res Cardiovasc Sci, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA.
[Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
[Ledent, Catherine] Univ Libre Bruxelles, Brussels, Belgium.
[Poloyac, Samuel M.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA.
[Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Mustafa, SJ (reprint author), W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Ctr Interdisciplinary Res Cardiovasc Sci, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA.
EM smustafa@hsc.wvu.edu
RI Nayeem, Mohammed/A-3949-2017;
OI Nayeem, Mohammed/0000-0002-7827-4760; Falck, John/0000-0002-9219-7845
FU National Institutes of Health [HL027339, HL-094447, GM-31278,
RO1-NS-052315, S10-RR-023461]; Intramural Research Program of the
National Institute of Environmental Health Sciences
FX This work was supported by National Institutes of Health Grants
HL027339, HL-094447, GM-31278, RO1-NS-052315, S10-RR-023461, and
RO1-NS-052315 and by the Intramural Research Program of the National
Institute of Environmental Health Sciences.
NR 69
TC 23
Z9 24
U1 0
U2 1
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 NOV
PY 2008
VL 295
IS 5
BP H2068
EP H2078
DI 10.1152/ajpheart.01333.2007
PG 11
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 369VS
UT WOS:000260722600028
PM 18805895
ER
PT J
AU Smirnov, MS
Kiyatkin, EA
AF Smirnov, Michael S.
Kiyatkin, Eugene A.
TI Fluctuations in central and peripheral temperatures associated with
feeding behavior in rats
SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE
PHYSIOLOGY
LA English
DT Article
DE eating; food seeking; deprivation; motivation; metabolic brain
activation; peripheral vasoconstriction
ID BRAIN TEMPERATURE; BLOOD-FLOW; SOMATOSENSORY STIMULATION; PATHOLOGICAL
CONDITIONS; HYPERTHERMIA; SKIN; COCAINE; MONKEY
AB We examined the pattern of temperature fluctuations in the nucleus accumbens (NAcc), temporal muscle, and skin, along with locomotion in food-deprived and nondeprived rats following the presentation of an open or closed food container and during subsequent eating or food-seeking behavior without eating. Although rats in food-deprived, quiet resting conditions had more than twofold lower spontaneous locomotion and lower temperature values than in nondeprived conditions, after presentation of a container, they consistently displayed food-seeking behavior, showing much larger and longer temperature changes. When the container was open, rats rapidly retrieved food and consumed it. Food consumption was preceded and accompanied by gradual increases in brain and muscle temperatures (similar to 1.5 degrees C) and a weaker, delayed increase in skin temperature (similar to 0.8 degrees C). All temperatures began to rapidly fall immediately after eating was completed, but NAcc and muscle temperatures returned to baseline after similar to 35 min. When the container was closed and rats were unable to obtain food, they continued food-seeking activity during the entire period of presentation. Similar to eating, this activity was preceded and accompanied by gradual temperature increases in the brain and muscle, which were somewhat smaller than those during eating (similar to 1.2 degrees C), with no changes in skin temperature. In contrast to trials with eating, NAcc and muscle temperatures continued to increase for similar to 10 min after the container was removed from the cage and the rat continued food-seeking behavior, with a return to baselines after similar to 50 min. These temperature fluctuations are discussed with respect to alterations in metabolic brain activity associated with feeding behavior, depending upon deprivation state and food availability.
C1 [Kiyatkin, Eugene A.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA.
RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM ekiyatki@intra.nida.nih.gov
OI Smirnov, Michael/0000-0003-2248-8863
FU National Institutes of Health; National Institute on Drug Abuse
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Drug Abuse.
NR 43
TC 6
Z9 7
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6119
J9 AM J PHYSIOL-REG I
JI Am. J. Physiol.-Regul. Integr. Comp. Physiol.
PD NOV
PY 2008
VL 295
IS 5
BP R1415
EP R1424
DI 10.1152/ajpregu.90636.2008
PG 10
WC Physiology
SC Physiology
GA 368DB
UT WOS:000260600400007
PM 18799633
ER
PT J
AU Paukner, A
Suomi, SJ
AF Paukner, Annika
Suomi, Stephen J.
TI The Effects of Fur Rubbing on the Social Behavior of Tufted Capuchin
Monkeys
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Article
DE Cebus apella; affiliation; aggression; group cohesion; proximity
ID CEBUS-CAPUCINUS; APELLA; PLANTS
AB Fur rubbing has often been attributed as a social as well as a medicinal function in capuchin monkeys, yet to date there have been no studies investigating the effects of fur rubbing on subsequent group dynamics. Here, we report for the first time how social group cohesion is affected by fur rubbing in tufted capuchin monkeys. Fifteen captive capuchins were each observed six times for 45 min, three times following the provision of materials typically used for fur rubbing (onion) and three times following control food items (apple). When compared with the apple condition, monkeys significantly increased proximity to one another in the first 15 min of the onion condition, which is when most fur rubbing took place. Moreover, monkeys were more likely to spend time in groups when fur rubbing but less likely to spend time in groups when manipulating the onion in other ways. In subsequent periods monkeys were less likely to be in proximity to one another in the onion condition compared with the apple condition. Aggression between group members was elevated whereas affiliation was decreased throughout the onion condition. In short, capuchins spent more time further apart and engaged in more aggressive acts and shorter affiliative acts following fur-rubbing bouts. It is possible that these differences in behavior could be owing to differences in how the monkeys competed for and interacted with the items presented in each condition rather than due to fur rubbing as such. Alternatively, fur rubbing with pungent materials might interfere with olfactory cues used to regulate social interactions within a group and thereby cause increased levels of aggression. Am. J. Primatol. 70:1007-1012, 2008. (c) 2008 Wiley-Liss, Inc.
C1 [Paukner, Annika; Suomi, Stephen J.] NIH, Anim Ctr, Poolesville, MD 20837 USA.
RP Paukner, A (reprint author), NIH, Anim Ctr, POB 529, Poolesville, MD 20837 USA.
EM pauknera@mail.nih.gov
FU Division of Intramural Research; NICHD
FX Contract grant sponsor: Division of Intramural Research, NICHD.
NR 10
TC 5
Z9 5
U1 0
U2 6
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD NOV
PY 2008
VL 70
IS 11
BP 1007
EP 1012
DI 10.1002/ajp.20595
PG 6
WC Zoology
SC Zoology
GA 360NN
UT WOS:000260064300001
PM 18626908
ER
PT J
AU Lutsey, PL
Roux, AVD
Jacobs, DR
Burke, GL
Harman, J
Shea, S
Folsom, AR
AF Lutsey, Pamela L.
Roux, Ana V. Diez
Jacobs, David R., Jr.
Burke, Gregory L.
Harman, Jane
Shea, Steven
Folsom, Aaron R.
TI Associations of Acculturation and Socioeconomic Status With Subclinical
Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; ARTERY RISK DEVELOPMENT;
CAROTID ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; GENERAL-POPULATION;
ADOLESCENT HEALTH; NATIONAL SAMPLE; YOUNG-ADULTS; NHANES-III
AB Objectives. We assessed whether markers of acculturation (birthplace and number of US generations) and socioeconomic status (SES) are associated with markers of subclinical cardiovascular disease-carotid artery plaque, internal carotid intima-media thickness, and albuminuria-in 4 racial/ethnic groups.
Methods. With data from the Multi-Ethnic Study of Atherosclerosis (n =6716 participants aged 45-84years) and race-specific binomial regression models, we computed prevalence ratios adjusted for demographics and traditional cardiovascular risk factors.
Results. The adjusted US-to foreign-born prevalence ratio for carotid plaque was 1.20 (99% confidence interval [CI]=0.97, 1.39) among Whites, 1.91 (99% CI=0.94, 2.94) among Chinese, 1.62 (99% CI=1.28, 2.06) among Blacks, and 1.23 (99% CI=1.15, 1.31) among Hispanics. Greater carotid plaque prevalence was found among Whites, Blacks, and Hispanics with a greater number of generations with US residence (P<.001) and among Whites with less education and among Blacks with lower incomes. Similar associations were observed with intima-media thickness. There was also evidence of an inverse association between albuminuria and SES among Whites and Hispanics.
Conclusions. Greater US acculturation and lower SES were associated with a higher prevalence of carotid plaque and greater intima-media thickness but not with albuminuria. Maintenance of healthful habits among recent immigrants should be encouraged. (Am J Public Health. 2008;98:1963-1970. doi:10.2105/AJPH.2007.123844)
C1 [Lutsey, Pamela L.; Jacobs, David R., Jr.; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
[Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, Oslo, Norway.
[Roux, Ana V. Diez] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Burke, Gregory L.] Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Harman, Jane] NHLBI, Bethesda, MD 20892 USA.
[Shea, Steven] Columbia Univ, Dept Med & Epidemiol, New York, NY USA.
RP Folsom, AR (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55455 USA.
EM folsom@epi.umn.edu
FU National Heart Lung, and Blood Institute [N01-HC-95159, N01-HC-95165,
N01-HC-95169]
FX This research was supported by the National Heart Lung, and Blood
Institute (contracts N01-HC-95159 through N01-HC-95165 and
N01-HC-95169). P.L. Lutsey was supported by the National Heart Lung, and
Blood Institute as a predoctoral fellow on a training grant (T32
HL07779).; The authors thank the other investigators, the staff, and the
participants of the Multi-Ethnic Study of Atherosclorosis (MESA) study
for their valuable contributions. A full list of participating MESA
investigators and institutions can be found at http://www.mesanhlbi.org.
NR 49
TC 48
Z9 49
U1 1
U2 6
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 NOV
PY 2008
VL 98
IS 11
BP 1963
EP 1970
DI 10.2105/AJPH.2007.123844
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 368LP
UT WOS:000260622900016
PM 18511718
ER
PT J
AU Garantziotis, S
Zudaire, E
Trempus, CS
Hollingsworth, JW
Jiang, DH
Lancaster, LH
Richardson, E
Zhu, LS
Cuttitta, F
Brown, KK
Noble, PW
Kimata, K
Schwartz, DA
AF Garantziotis, Stavros
Zudaire, Enrique
Trempus, Carol S.
Hollingsworth, John W.
Jiang, Dianhua
Lancaster, Lisa H.
Richardson, Elizabeth
Zhu, Lisheng
Cuttitta, Frank
Brown, Kevin K.
Noble, Paul W.
Kimata, Koji
Schwartz, David A.
TI Serum Inter-alpha-Trypsin Inhibitor and Matrix Hyaluronan Promote
Angiogenesis in Fibrotic Lung Injury
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE inter-alpha-trypsin inhibitor; hyaluronan; angiogenesis; pulmonary
fibrosis
ID IDIOPATHIC PULMONARY-FIBROSIS; INTERSTITIAL PNEUMONIA; LEUKOCYTE
ADHESION; GENE-EXPRESSION; CD44; ACID; MICE; DEPOSITION; RETICULUM;
CHEMOKINE
AB Rationale. The etiology and pathogenesis of angiogenesis in idiopathic pulmonary fibrosis (IPF) is poorly understood. Inter-alpha-trypsin inhibitor (IaI) is a serum protein that can bind to hyaluronan (HA) and may contribute to the angiogenic response to tissue injury.
Objectives: To determine whether IaI promotes HA-mediated angiogenesis in tissue injury.
Methods: An examination was undertaken of angiogenesis in IaI sufficient and -deficient mice in the bleomycin model of pulmonary fibrosis and in angiogenesis assays in vivo and in vitro. IaI and HA in patients with IPF were examined.
Measurements and Main Results: IaI significantly enhances the angiogenic response to short-fragment HA in vivo and in vitro. IaI deficiency leads to decreased angiogenesis in the matrigel model, and decreases lung angiogenesis after bleomycin exposure in mice. IaI is found in fibroblastic foci in IPF, where it colocalizes with HA. The colocalization is particularly strong in vascular areas around fibroblastic foci. Serum levels of IaI and HA are significantly elevated in patients with IPF compared with control subjects. High serum IaI and HA levels are associated with decreased lung diffusing capacity, but not FVC.
Conclusions: Our findings indicate that serum IaI interacts with HA, and promotes angiogenesis in lung injury. IaI appears to contribute to the vascular response to lung injury and may lead to aberrant angiogenesis.
C1 [Garantziotis, Stavros] NIEHS, Clin Res Unit, Res Triangle Pk, NC 27709 USA.
[Zudaire, Enrique; Cuttitta, Frank] NCI, Angiogenesis Core Facil, Gaithersburg, MD USA.
[Hollingsworth, John W.; Jiang, Dianhua; Noble, Paul W.] Duke Univ, Med Ctr, Durham, NC USA.
[Lancaster, Lisa H.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Zhu, Lisheng; Kimata, Koji] Aichi Med Univ, Inst Mol Sci Med, Aichi, Japan.
[Brown, Kevin K.] Natl Jewish Med & Res Ctr, Denver, CO USA.
[Schwartz, David A.] NHLBI, Bethesda, MD 20892 USA.
RP Garantziotis, S (reprint author), NIEHS, Clin Res Unit, POB 12233, Res Triangle Pk, NC 27709 USA.
EM garantziotis@niehs.nih.gov
RI Garantziotis, Stavros/A-6903-2009; Jiang, Dianhua/B-1421-2009; Cuttitta,
Frank/B-4758-2016
OI Garantziotis, Stavros/0000-0003-4007-375X; Jiang,
Dianhua/0000-0002-4508-3829;
FU National Institute of Environmental Health Services [ES11961]; National
Heart, Lung, and Blood Institute [HL91335]; National Institutes of
Health; National Institute of Environmental Health Sciences; National
Cancer Institute; National Heart, Lung, and Blood Institute
FX Supported in part by grants from National Institute of Environmental
Health Services (ES11961) and National Heart, Lung, and Blood Institute
(HL91335), and by the Intramural Research Program of the National
Institutes of Health, the National Institute of Environmental Health
Sciences, the National Cancer Institute, and the National Heart, Lung,
and Blood Institute.
NR 48
TC 20
Z9 22
U1 0
U2 1
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD NOV 1
PY 2008
VL 178
IS 9
BP 939
EP 947
DI 10.1164/rccm.200803-386OC
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 368HG
UT WOS:000260611600011
PM 18703791
ER
PT J
AU Brass, DM
Hollingsworth, JW
Cinque, M
Li, ZW
Potts, E
Toloza, E
Foster, WM
Schwartz, DA
AF Brass, David M.
Hollingsworth, John W.
Cinque, Mark
Li, Zhouwei
Potts, Erin
Toloza, Eric
Foster, William M.
Schwartz, David A.
TI Chronic LPS Inhalation Causes Emphysema-Like Changes in Mouse Lung that
Are Associated with Apoptosis
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; COTTON DUST; INTRATRACHEAL INSTILLATION;
EXPERIMENTAL CARDROOM; PROTEINASE-INHIBITOR; NEUTROPHIL ELASTASE;
AIRWAY-OBSTRUCTION; INHALED ENDOTOXIN; TEXTILE WORKERS; UP-REGULATION
AB Lipopolysaccharide (LPS) is ubiquitous in the environment. Recent epidemiologic data suggest that occupational exposure to inhaled LIPS can contribute to the progression of chronic obstructive pulmonary disease. To address the hypothesis that inhaled LIPS can cause emphysema-like changes in mouse pulmonary parenchyma, we exposed C57BL/6 mice to aerosolized LIPS daily for 4 weeks. By 3 days after the end of the 4-week exposure, LPS-exposed mice developed enlarged airspaces that persisted in the 4-week recovered mice. These architectural alterations in the lung are associated with enhanced type I, III, and IV procollagen mRNA as well as elevated levels of matrix metalloproteinase (MMP)-9 mRNA, all of which have been previously associated with human emphysema. Interestingly, MMP-9-deficient mice were not protected from the development of LPS-induced emphysema. However, we demonstrate that LPS-induced airspace enlargement was associated with apoptosis within the lung parenchyma, as shown by prominent TUNEL staining and elevated cleaved caspase 3 immunoreactivity. Antineutrophil antiserum-treated mice were partially protected from the lung destruction caused by chronic inhalation of LPS. Taken together, these findings demonstrate that inhaled LIPS can cause neutrophil-dependent emphysematous changes in lung architecture that are associated with apoptosis and that these changes may be occurring through mechanisms different than those induced by cigarette smoke.
C1 [Brass, David M.; Cinque, Mark; Schwartz, David A.] NIEHS, NHLBI, Lab Resp Biol, Environm Lung Dis Res Grp, Res Triangle Pk, NC 27709 USA.
[Hollingsworth, John W.; Li, Zhouwei; Potts, Erin; Foster, William M.] Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC USA.
[Toloza, Eric] Duke Univ, Med Ctr, Div Thorac Surg, Durham, NC USA.
RP Brass, DM (reprint author), Duke Univ, Med Ctr, Dept Pediat, Neonatal Perinatal Res Inst, 403 Alex R Sands Lab Bldg,DUMC Box 3373, Durham, NC 27710 USA.
EM david.brass@duke.edu
FU NIEHS; NHLBI; Department of Veterans Affairs (Merit Review) [ES11375,
ES7498, ES9607, ES11961, A158161, HL91335]
FX This work was funded by the intramural research programs at NIEHS and
NHLBI and by the Department of Veterans Affairs (Merit Review),
extramural grants (ES11375 [D.A.S.], ES7498 [D.A.S.], ES9607 [D.A.S.],
ES11961 [J.W.H., W.M.F.], A158161 [J.W.H.], and HL91335 [J.W.H.]).
NR 54
TC 45
Z9 50
U1 0
U2 4
PU AMER THORACIC SOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD NOV
PY 2008
VL 39
IS 5
BP 584
EP 590
DI 10.1165/rcmb.2007-0448OC
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 366WM
UT WOS:000260514300014
PM 18539952
ER
PT J
AU Van Uitert, RL
Summers, RM
White, JM
Deshpande, KK
Choi, JR
Pickhardt, PJ
AF Van Uitert, Robert L.
Summers, Ronald M.
White, Jacob M.
Deshpande, Keshav K.
Choi, J. Richard
Pickhardt, Perry J.
TI Temporal and Multiinstitutional Quality Assessment of CT Colonography
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE colon; colonography; CT; quality; virtual colonoscopy
ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; OPTIMIZING COLONIC DISTENSION;
COLORECTAL NEOPLASIA; VIRTUAL COLONOSCOPY; CARBON-DIOXIDE; RESIDUAL
FLUID; INSUFFLATION; VALIDATION; EXPERIENCE
AB OBJECTIVE. The purpose of this study was to investigate the variability of CT colonography (CTC) scan quality obtained within and between institutions by using previously validated automated quality assessment (QA) software that assesses colonic distention and surface area obscured by residual fluid.
MATERIALS AND METHODS. The CTC scans of 120 patients were retrospectively selected, 30 from each of four institutions. The bowel preparation included oral contrast material for fecal and fluid tagging. Patients at one institution (institution 4) drank half the amount of oral contrast material compared with the patients at the other three institutions. Fifteen of the CTC scans were from the beginning of the protocol studied at each institution and 15 scans were from the same protocol acquired approximately 1 year later in the study. We used previously validated QA software to automatically measure the mean distention and residual fluid of each of five colonic segments (ascending, transverse, descending, sigmoid, and rectum). Adequate distention was defined as a colonic diameter of at least 2 cm. Residual fluid was determined by the percentage of colonic surface area covered by fluid. We compared how the quality varied across multiple institutions and over time within the same institution.
RESULTS. No significant difference in the amount of colonic distention among the four institutions was found (p = 0.19). However, the distention in the prone position was significantly greater than the distention in the supine position (p < 0.001). Patients at institution 4 had about half the amount of residual colonic fluid compared with patients at the other three institutions (p < 0.01). The sigmoid and descending colons were the least distended segments, and the transverse and descending colons contained the most fluid on the prone and supine scans, respectively. More recently acquired studies had greater distention and less residual fluid, but the differences were not statistically significant (p = 0.30 and p = 0.96, respectively).
CONCLUSION. Across institutions, a significant difference can exist in bowel preparation quality for CTC. This study reaffirms the need for standardized bowel preparation and quality monitoring of CTC examinations to reduce poor CTC performance.
C1 [Van Uitert, Robert L.; Summers, Ronald M.; White, Jacob M.; Deshpande, Keshav K.] Natl Inst Hlth Clin Ctr, Bethesda, MD 20892 USA.
[Choi, J. Richard] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA.
[Choi, J. Richard] Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA.
[Pickhardt, Perry J.] Univ Wisconsin, Sch Med, Dept Radiol, Madison, WI USA.
RP Summers, RM (reprint author), Natl Inst Hlth Clin Ctr, Bldg 10,Rm 1C368X MSC 1182, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU National Institutes of Health Clinical Center
FX This study was supported by the Intramural Research Program of the
National Institutes of Health Clinical Center.
NR 25
TC 6
Z9 6
U1 0
U2 1
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD NOV
PY 2008
VL 191
IS 5
BP 1503
EP 1508
DI 10.2214/AJR.07.3591
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 363DQ
UT WOS:000260246700034
PM 18941092
ER
PT J
AU Yang, WJ
Gu, DF
Chen, J
Jaquish, CE
Rao, DC
Wu, XG
Hixson, JE
Duan, XF
Kelly, TN
Hamm, LL
Whelton, PK
He, J
AF Yang, Wenjie
Gu, Dongfeng
Chen, Jing
Jaquish, Cashell E.
Rao, D. C.
Wu, Xigui
Hixson, James E.
Duan, Xiufang
Kelly, Tanika N.
Hamm, L. Lee
Whelton, Paul K.
He, Jiang
CA GenSalt Collaborative Res Grp
TI Agreement of Blood Pressure Measurements Between Random-Zero and
Standard Mercury Sphygmomanometers
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article
DE Blood pressure measurements; Random-zero sphygmomanometer; Standard
mercury sphygmomanometer; Agreement
ID SOCIETY-OF-HYPERTENSION; EUROPEAN-SOCIETY; ANEROID SPHYGMOMANOMETERS;
INTERNATIONAL PROTOCOL; MONITOR; CALIBRATION; VALIDATION; INACCURACY;
BURDEN
AB The random-zero sphygmomanometer has been widely used in observational studies and clinical trials for blood pressure measurement. We examined the agreement of blood pressure measurements between random-zero and standard mercury sphygmomanometers among 2007 Chinese study participants aged 15 to 60 years. Three blood pressure readings were obtained by trained observers using random-zero and standard mercury sphygmomanometers, respectively, in a random order. Overall, blood pressure readings obtained using the random-zero device were significantly lower than those obtained with the standard mercury sphygmomanometer, with a mean difference ranging from -3.0 to -2.7 mm Hg for systolic and -1.4 to -0.9 mm Hg for diastolic blood pressure (all P < 0.01). Correlation coefficients between mean blood pressure measurements obtained using the random-zero and standard mercury sphygmomanometers were high (0.90 for systolic and 0.85 for diastolic blood pressure, both P < 0.0001). In conclusion, our study indicated that there was strong agreement between blood pressure measurements obtained using the random-zero and standard mercury sphygmomanometers although blood pressure values were on average lower with the random-zero sphygmomanometer.
C1 [Yang, Wenjie; Chen, Jing; Hixson, James E.; Kelly, Tanika N.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA.
[Chen, Jing; Hamm, L. Lee; He, Jiang] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
[Gu, Dongfeng; Wu, Xigui; Duan, Xiufang] Chinese Acad Med Sci, Fuwai Hosp, Beijing 100037, Peoples R China.
[Gu, Dongfeng; Wu, Xigui; Duan, Xiufang] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100037, Peoples R China.
Peking Union Med Coll, Beijing 100021, Peoples R China.
Chinese Natl Ctr Cardiovasc Dis Control & Res, Beijing, Peoples R China.
[Jaquish, Cashell E.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Rao, D. C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Hixson, James E.] Univ Texas Houston, Sch Publ Hlth, Dept Epidemiol, Houston, TX USA.
[Whelton, Paul K.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
RP He, J (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1430 Tulane Ave SL18, New Orleans, LA 70112 USA.
EM jhe@tulane.edu
FU National Institutes of Health, Bethesda, Maryland [U01HL072507]
FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is
supported by a cooperative agreement project grant (U01HL072507) from
the National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland.
NR 34
TC 7
Z9 7
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-9629
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD NOV
PY 2008
VL 336
IS 5
BP 373
EP 378
DI 10.1097/MAJ.0b013e31816956ac
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 375NY
UT WOS:000261121800001
PM 19011391
ER
PT J
AU McArthur, JH
Durbin, AP
Marron, JA
Wanionek, KA
Thumar, B
Pierro, DJ
Schmidt, AC
Blaney, JE
Murphy, BR
Whitehead, SS
AF McArthur, Julie H.
Durbin, Anna P.
Marron, Jennifer A.
Wanionek, Kimberli A.
Thumar, Bhavin
Pierro, Dennis J.
Schmidt, Alexander C.
Blaney, Joseph E., Jr.
Murphy, Brian R.
Whitehead, Stephen S.
TI Phase I Clinical Evaluation of rDEN4 Delta 30-200,201: A Live Attenuated
Dengue 4 Vaccine Candidate Designed for Decreased Hepatotoxicity
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID VIRUS-VACCINE; HEMORRHAGIC-FEVER; VOLUNTEERS; IMMUNOGENICITY;
INFECTIONS; HUMANS; STRAIN; SAFE
AB The rDEN4A/30-200,201 is a live attenuated DENV-4 vaccine candidate specifically designed to further attenuate the rDEN4 Delta 30 parent virus. In the present study, 28 healthy adult volunteers were randomized to receive either 105 plaque-forming unit (PFU) of vaccine (20) or placebo (8) as a single subcutaneous injection. Volunteers were evaluated for safety every other day for 16 days. Serum neutralizing antibody titer against DEN4 was determined at study day 28, 42, and 180. The vaccine infected all vaccinees and was well tolerated without inducing alanine aminotransferase (ALT) elevations. Although virus was not recovered from the serum of any vaccinee, moderate levels of neutralizing antibody were induced in all volunteers. Thus the restricted replication of rDEN4 Delta 30-200,201 previously documented in animal models was confirmed in humans. The rDEN4 Delta 30-200,201 is a promising candidate and can be considered for inclusion in a tetravalent dengue virus (DENV) vaccine.
C1 [Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, Baltimore, MD 21205 USA.
[Pierro, Dennis J.; Schmidt, Alexander C.; Blaney, Joseph E., Jr.; Murphy, Brian R.] 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, 624 N Broadway,Room 251, Baltimore, MD 21205 USA.
EM jmcarthu@jhsph.edu; adurbin@jhsph.edu; jmarron@jhsph.edu;
kwanione@jhsph.edu; bthumar@jhsph.edu; pierrod@mail.nih.gov;
as337y@nih.gov; jblaney@niaid.nih.gov; bmurphy@niaid.nih.gov;
swhitehead@niaid.nih.gov
FU NIAID; National Institutes of Health
FX This research was supported by the Intramural Research Program of the
NIAID, National Institutes of Health.
NR 27
TC 47
Z9 48
U1 0
U2 1
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 NOV
PY 2008
VL 79
IS 5
BP 678
EP 684
PG 7
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 373BD
UT WOS:000260945100010
PM 18981503
ER
PT J
AU Hu, CAA
Phang, JM
Valle, D
AF Hu, Chien-an A.
Phang, James M.
Valle, David
TI Proline metabolism in health and disease
SO AMINO ACIDS
LA English
DT Editorial Material
C1 [Hu, Chien-an A.] Univ New Mexico, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA.
[Phang, James M.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Valle, David] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA.
RP Hu, CAA (reprint author), Univ New Mexico, Dept Biochem & Mol Biol, MSC08 4670,BMSB-258,915 Camino Salud, Albuquerque, NM 87131 USA.
EM ahu@salud.unm.edu
FU NCI NIH HHS [R01 CA106644-04, R01 CA106644, R01 CA106644-03]; NCRR NIH
HHS [P20 RR016480, P20 RR016480-086585]
NR 0
TC 14
Z9 14
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD NOV
PY 2008
VL 35
IS 4
BP 651
EP 652
DI 10.1007/s00726-008-0102-1
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 355NE
UT WOS:000259714800001
PM 18504525
ER
PT J
AU Phang, JM
AF Phang, James M.
TI Introduction to second proline symposium
SO AMINO ACIDS
LA English
DT Editorial Material
C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA.
RP Phang, JM (reprint author), NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA.
EM phang@ncifcrf.gov
FU Intramural NIH HHS [Z01 BC010743-02]
NR 0
TC 4
Z9 4
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD NOV
PY 2008
VL 35
IS 4
BP 653
EP 654
DI 10.1007/s00726-008-0103-0
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 355NE
UT WOS:000259714800002
PM 18491029
ER
PT J
AU Phang, JM
Donald, SP
Pandhare, J
Liu, YM
AF Phang, James M.
Donald, Steven P.
Pandhare, Jui
Liu, Yongmin
TI The metabolism of proline, a stress substrate, modulates carcinogenic
pathways
SO AMINO ACIDS
LA English
DT Article; Proceedings Paper
CT 2nd International Symposium on Proline Metabolism in Health and Disease
CY SEP 10-11, 2007
CL Frederick, MD
DE proline oxidase; proline dehydrogenase; mTOR; PPAR gamma; apoptosis;
bioenergetics
ID ACTIVATED-RECEPTOR-GAMMA; MATRIX METALLOPROTEINASES; COLORECTAL-CANCER;
LUNG-CANCER; PPAR-GAMMA; OXIDASE; APOPTOSIS; CELLS; GENE; COLLAGEN
AB The resurgence of interest in tumor metabolism has led investigators to emphasize the metabolism of proline as a "stress substrate" and to suggest this pathway as a potential anti-tumor target. Proline oxidase, a.k.a. proline dehydrogenase (POX/PRODH), catalyzes the first step in proline degradation and uses proline to generate ATP for survival or reactive oxygen species for programmed cell death. POX/PRODH is induced by p53 under genotoxic stress and initiates apoptosis by both mitochondrial and death receptor pathways. Furthermore, POX/PRODH is induced by PPAR gamma and its pharmacologic ligands, the thiazolidinediones. The anti-tumor effects of PPAR gamma may be critically dependent on POX/PRODH. In addition, it is upregulated by nutrient stress through the mTOR pathway to maintain ATP levels. We propose that proline is made available as a stress substrate by the degradation of collagen in the microenvironmental extracellular matrix by matrix metalloproteinases. In a manner analogous to autophagy, this proline-dependent process for bioenergetics from collagen in extracellular matrix can be designated "ecophagy".
C1 [Phang, James M.; Donald, Steven P.; Pandhare, Jui] NCI, Ctr Canc Res, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
[Liu, Yongmin] NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA.
RP Phang, JM (reprint author), NCI, Ctr Canc Res, Comparat Carcinogenesis Lab, Bldg 538,Room 115, Frederick, MD 21702 USA.
EM phang@mail.ncifcrf.gov
FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]
NR 64
TC 100
Z9 106
U1 1
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD NOV
PY 2008
VL 35
IS 4
BP 681
EP 690
DI 10.1007/s00726-008-0063-4
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 355NE
UT WOS:000259714800006
PM 18401543
ER
PT J
AU Surazynski, A
Miltyk, W
Palka, J
Phang, JM
AF Surazynski, A.
Miltyk, W.
Palka, J.
Phang, J. M.
TI Prolidase-dependent regulation of collagen biosynthesis
SO AMINO ACIDS
LA English
DT Article; Proceedings Paper
CT 2nd International Symposium on Proline Metabolism in Health and Disease
CY SEP 10-11, 2007
CL Frederick, MD
DE prolidase; collagen metabolism; beta(1)-integrin signaling
ID HUMAN SKIN FIBROBLASTS; HUMAN-ERYTHROCYTE PROLIDASE; HUMAN DERMAL
FIBROBLASTS; EXTRACELLULAR-MATRIX; L-PROLINE; GENE-TRANSCRIPTION;
CLINICAL SYMPTOMS; MOLECULAR-CLONING; ACTIVE-SITE; PEPTIDASE-D
AB Prolidase [EC.3.4.13.9] is a cytosolic imidodipeptidase, which specifically splits imidodipeptides with C-terminal proline or hydroxyproline. The enzyme plays an important role in the recycling of proline from imidodipeptides (mostly derived from degradation products of collagen) for resynthesis of collagen and other proline-containing proteins. The enzyme activity is up-regulated by beta(1)-integrin receptor stimulation. The increase in the enzyme activity is due to its phosphorylation on serine/threonine residues. Collagen is not only structural component of extracellular matrix. It has been recognized as a ligand for integrin receptors, which play an important role in signaling that regulate ion transport, lipid metabolism, kinase activation and gene expression. Therefore, changes in the quantity, structure and distribution of collagens in tissues may affect cell signaling, metabolism and function. Several line of evidence suggests that prolidase activity may be a step-limiting factor in the regulation of collagen biosynthesis. It has been shown in different physiologic and pathologic conditions. It is of great importance during wound healing, inflammation, aging, tissue fibrosis and possibly skeletal abnormalities seen in Osteogenesis Imperfecta. The mechanism of prolidase-dependent regulation of collagen biosynthesis was found at both transcriptional and post-transcriptional levels. In this study, we provide evidence for prolidase-dependent transcriptional regulation of collagen biosynthesis. The mechanism was found at the level of NF-kB, known inhibitor of type I collagen gene expression. Modulation of integrin-dependent signaling by stimulatory (i.e. thrombin) or inhibitory (i.e. echistatin) beta(1)-integrin ligands or by nitric oxide donors (i.e. DETA/NO) affect prolidase at post-transcriptional level. All those factors may represent novel approach to pharmacotherapy of connective tissue disorders.
C1 [Surazynski, A.; Miltyk, W.; Palka, J.] Med Univ Bialystok, Dept Med Chem, PL-15089 Bialystok, Poland.
[Phang, J. M.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21701 USA.
RP Palka, J (reprint author), Med Univ Bialystok, Dept Med Chem, Ul Kilinskiego 1, PL-15089 Bialystok, Poland.
EM pal@amb.edu.pl
NR 74
TC 63
Z9 67
U1 2
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD NOV
PY 2008
VL 35
IS 4
BP 731
EP 738
DI 10.1007/s00726-008-0051-8
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 355NE
UT WOS:000259714800011
PM 18320291
ER
PT J
AU Liao, XH
Majithia, A
Huang, XL
Kimmel, AR
AF Liao, Xin-Hua
Majithia, Amit
Huang, Xiuli
Kimmel, Alan R.
TI Growth control via TOR kinase signaling, an intracellular sensor of
amino acid and energy availability, with crosstalk potential to proline
metabolism
SO AMINO ACIDS
LA English
DT Article; Proceedings Paper
CT 2nd International Symposium on Proline Metabolism in Health and Disease
CY SEP 10-11, 2007
CL Frederick, MD
DE TORC1; rapamycin; Raptor; FKBP12; S6K; 4E-BP
ID CAP-DEPENDENT TRANSLATION; MESSENGER-RNA TRANSLATION; RICTOR-MTOR
COMPLEX; P70 S6 KINASE; SACCHAROMYCES-CEREVISIAE; CELL-GROWTH; MAMMALIAN
TARGET; NUCLEAR-LOCALIZATION; BINDING PARTNER; GENE-EXPRESSION
AB The TOR (Target of Rapamycin) protein kinase pathway plays a central role in sensing and responding to nutrients, stress, and intracellular energy state. TOR complex 1 (TORC1) is comprised of TOR, Raptor, and Lst8 and its activity is sensitive to inhibition by the macrolide antibiotic rapamycin. TORC1 regulates protein synthesis, ribosome biogenesis, autophagy, and ultimately cell growth through the phosphorylation of S6 K, 4E-BP, and other substrates. As TORC1 activity is positively or negatively modulated in response to upstream regulators, cellular growth rate is, respectively, enhanced or suppressed. A separate multiprotein TOR complex, TORC2, is insensitive to direct inhibition by rapamycin and does not regulate growth patterns directly; TORC2 can, however, impact certain aspects of TORC1 signaling and cell survival. TOR signaling is an ancient pathway, conserved among the yeasts, Dictyostelium, C. elegans, Drosophila, mammals, and Arabidopsis. This review will focus on the regulation of TORC1 in mammalian cells in the context of amino acid sensing/regulation and intracellular ATP homeostasis, but will also include comparisons among other organisms.
C1 [Liao, Xin-Hua; Majithia, Amit; Huang, Xiuli; Kimmel, Alan R.] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
[Majithia, Amit] Howard Hughes Med Inst, Natl Inst Hlth Res Scholar, Bethesda, MD 20817 USA.
RP Kimmel, AR (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
EM ark1@helix.nih.gov
FU Intramural NIH HHS
NR 68
TC 58
Z9 62
U1 3
U2 19
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD NOV
PY 2008
VL 35
IS 4
BP 761
EP 770
DI 10.1007/s00726-008-0100-3
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 355NE
UT WOS:000259714800014
PM 18651095
ER
PT J
AU Kempf, L
AF Kempf, Lucas
TI POX imaging genetics: Proline oxidase's impact on brain structure and
function
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Kempf, Lucas] NIMH, NIH, Bethesda, MD 20892 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 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD NOV
PY 2008
VL 35
IS 4
BP 773
EP 773
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 355NE
UT WOS:000259714800021
ER
PT J
AU Drgonova, J
Liu, QR
Hall, FS
Uhl, GR
AF Drgonova, Jana
Liu, Qing-Rong
Hall, F. Scott
Uhl, George R.
TI Deletion of v7-3 (SLC6A15) transporter improves motor performance in
aging female mice
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Drgonova, Jana; Liu, Qing-Rong; Hall, F. Scott; Uhl, George R.] NIDA, Mol Neurobiol Branch, NIH, Intramural Res Program,DHHS, Baltimore, MD 21224 USA.
RI Drgonova, Jana/B-2903-2008; Liu, Qing-Rong/A-3059-2012; Hall,
Frank/C-3036-2013
OI Liu, Qing-Rong/0000-0001-8477-6452; Hall, Frank/0000-0002-0822-4063
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 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD NOV
PY 2008
VL 35
IS 4
BP 774
EP 774
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 355NE
UT WOS:000259714800025
ER
PT J
AU Sun, XB
Li, Q
Veeramani, S
Wan, GH
Phang, J
Lin, MF
Hu, CAA
AF Sun, Xiaobo
Li, Qian
Veeramani, Suresh
Wan, Guanghua
Phang, James
Lin, Ming-Fong
Hu, Chien-an A.
TI Interactive role of POX and p66(Shc) in oxidative stress-induced cell
death in cancer cells
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Sun, Xiaobo; Li, Qian; Wan, Guanghua; Hu, Chien-an A.] Univ New Mexico, Sch Med, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA.
[Veeramani, Suresh; Lin, Ming-Fong] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA.
[Phang, James] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD NOV
PY 2008
VL 35
IS 4
BP 774
EP 774
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 355NE
UT WOS:000259714800024
ER
PT J
AU Alvord, WG
Roayaei, JA
Reinhold, WC
Quinones, OA
Weinstein, JN
AF Alvord, W. Gregory
Roayaei, Jean A.
Reinhold, William C.
Quinones, Octavio A.
Weinstein, John N.
TI A microarray analysis for differential gene expression for two cancer
cell lines, DU145 non-drug resistant and RC.01 drug-resistant using R &
bioconductor
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Alvord, W. Gregory; Roayaei, Jean A.; Quinones, Octavio A.] NCI, DMS Inc, Frederick, MD 21701 USA.
[Reinhold, William C.; Weinstein, John N.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 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 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD NOV
PY 2008
VL 35
IS 4
BP 775
EP 776
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 355NE
UT WOS:000259714800030
ER
PT J
AU Velazquez, C
Knaus, E
Chen, QH
Citro, M
Keefer, L
AF Velazquez, Carlos
Knaus, Edward
Chen, Quiao-Hong
Citro, Michael
Keefer, Larry
TI NONO-NSAIDS possessing a PROLI/NO moiety: The new anti-inflammatory,
analgesic, and potentially chemopreventive prodrugs
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Velazquez, Carlos; Keefer, Larry] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA.
[Knaus, Edward; Chen, Quiao-Hong] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada.
[Citro, Michael] NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21701 USA.
RI Velazquez, Carlos/C-4224-2008
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD NOV
PY 2008
VL 35
IS 4
BP 776
EP 776
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 355NE
UT WOS:000259714800031
ER
PT J
AU Kacinko, SL
Concheiro-Guisan, M
Shakleya, DM
Huestis, MA
AF Kacinko, Sherri L.
Concheiro-Guisan, Marta
Shakleya, Diaa M.
Huestis, Marilyn A.
TI Development and validation of a liquid chromatography-tandem mass
spectrometry assay for the simultaneous quantification of buprenorphine,
norbuprenorphine, and metabolites in human urine
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article; Proceedings Paper
CT 41st Annual Meeting of the German-Society-for-Mass-Spectrometry
CY MAR 02-05, 2008
CL Giessen, GERMANY
SP German Soc Mass Spectrometry
DE Buprenorphine; Norbuprenorphine; Buprenorphine glucuronide;
Norbuprenorphine glucuronide; Urine; Liquid chromatography-tandem mass
spectrometry
ID SAMPLES; HAIR; PLASMA; MISUSE; BLOOD; MS
AB A liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and norbuprenorphine glucuronide (NBUP-Gluc) in human urine was developed and fully validated. Extensive endogenous and exogenous interferences were evaluated and limits of quantification were identified empirically. Analytical ranges were 5-1,000 ng/mL for BUP and BUP-Gluc and 25-1,000 ng/mL for NBUP and NBUP-Gluc. Intra-assay and interassay imprecision were less than 17% and recovery was 93-116%. Analytes were stable at room temperature, at 4 degrees C, and for three freeze-thaw cycles. This accurate and precise assay has sufficient sensitivity and specificity for urine analysis of specimens collected from individuals treated with BUP for opioid dependence.
C1 [Kacinko, Sherri L.; Concheiro-Guisan, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, Suite 200,Room 05A-721,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural NIH HHS [Z01 DA000412-10]
NR 23
TC 13
Z9 14
U1 1
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD NOV
PY 2008
VL 392
IS 5
BP 903
EP 911
DI 10.1007/s00216-008-2326-z
PG 9
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 362SV
UT WOS:000260218300017
PM 18758763
ER
PT J
AU Brooks, BD
Albertson, AE
Jones, JA
Speare, JO
Lewis, RV
AF Brooks, Benjamin D.
Albertson, Amy E.
Jones, Justin A.
Speare, Jonathan O.
Lewis, Randolph V.
TI Efficient screening of high-signal and low-background antibody pairs in
the bio-bar code assay using prion protein as the target
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
ID DISEASE
AB The bio-bar code assay is an assay for ultrasensitive detection of proteins. The main technical hurdle in bio-bar code assay development is achieving a dose-dependent, reproducible signal with low background. We report on a magnetic bead ELISA screening mechanism for characterizing antibody pairs that are effective for use in the bio-bar code assay. The normal isoform of prion protein was utilized as the target protein as dozens of antibodies have been developed against it. The development of an ultrasensitive assay for the detection of the various isoforms of PrP has the potential to enable significant advances in the diagnosis and understanding of transmissible spongiform encephalopathies, including transmission mechanisms, disease pathology, and potential therapeutics. With prion protein as the target, the magnetic bead ELISA identified pairs with high background and low signal in the bio-bar code assay. The magnetic bead ELISA was effective as a screening mechanism because it reduced assay time and cost and allowed for understanding of pair characteristics such as development times and signal-to-noise ratios. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Brooks, Benjamin D.; Albertson, Amy E.; Jones, Justin A.; Lewis, Randolph V.] Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA.
[Speare, Jonathan O.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Brooks, BD (reprint author), Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA.
EM bbrooks@uwyo.edu
FU Department of Defense and a US Department of Agriculture CSREES
FX The authors acknowledge Phil Lefebvre, Paul Bao, Uwe Mueller, and
Liangxiu He from Nanosphere, Inc., for technical training, reagents, and
advice. The authors also acknowledge Jan Langeveld of the Central
Institute for Animal Disease Control in the Netherlands, Kathryn
O'Rourke of the USDA, Greg Raymond of the NIH Rocky Mountain Labs, and
Man-Sun Sy of Case University, who provided antibodies and excellent
advice during the study. The authors also acknowledge Amanda Brooks,
Holly Steinkraus, and Erin Shefferly for their technical support. This
research was funded by the Department of Defense and a US Department of
Agriculture CSREES nanotechnology grant.
NR 10
TC 7
Z9 7
U1 1
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD NOV 1
PY 2008
VL 382
IS 1
BP 60
EP 62
DI 10.1016/j.ab.2008.07.009
PG 3
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 409OZ
UT WOS:000263517000010
PM 18694717
ER
PT J
AU Mussolino, ME
Gillum, RF
AF Mussolino, Michael E.
Gillum, R. F.
TI Low Bone Mineral Density and Mortality in Men and Women: The Third
National Health and Nutrition Examination Survey Linked Mortality File
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Bone Density; Follow-up Studies; Longitudinal Studies; Mortality;
Proportional Hazards Models; Men; Women
ID ELDERLY-WOMEN; FRACTURES; STROKE
AB PURPOSE: The aim of this study is to determine the association of bone mineral density and mortality over a median follow-up of 9 years.
METHODS: The baseline data used are from the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative sample of non-institutionalized civilians. A cohort of 5,769 non-Hispanic whites, non-Hispanic blacks, and Mexican Americans aged 50 years and older at baseline (1988-1994) was followed through 2000 for overall mortality using the restricted-Use NHANES III Linked Mortality File (1,741 deaths). Total proximal femoral bone mineral density was measured by dual-energy x-ray absorptiometry and categorized into quartiles. Cox proportional hazards models were used to estimate the relative risk of death after adjusting for multiple risk factors.
RESULTS: Compared with subjects in the highest quartile of bone mineral density, those in the lowest quartile had greater risk of death (relative risk, 1.53; 95% confidence interval: 1.08-2.18; P 0.02). There was no significant interaction of bone mineral density with race or ethnicity.
CONCLUSION: Low bone mineral density was associated with increased risk of death.
C1 [Mussolino, Michael E.; Gillum, R. F.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
RP Mussolino, ME (reprint author), NHLBI, Div Prevent & Populat Sci, NIH, 6701 Rockledge Dr,Suite 10018, Bethesda, MD 20892 USA.
EM mussolinom@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 15
TC 20
Z9 21
U1 0
U2 1
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 NOV
PY 2008
VL 18
IS 11
BP 847
EP 850
DI 10.1016/j.annepidem.2008.07.003
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 369PG
UT WOS:000260705800004
PM 18809342
ER
PT J
AU Gail, MH
Pfeiffer, RM
Wheeler, W
Pee, D
AF Gail, M. H.
Pfeiffer, R. M.
Wheeler, W.
Pee, D.
TI Probability that a Two-Stage Genome-Wide Association Study will Detect a
Disease-Associated SNP and Implications for Multistage Designs
SO ANNALS OF HUMAN GENETICS
LA English
DT Article
DE case-control association study; detection probability; power; proportion
positive; ranking and selection; SNP chip
ID SAMPLE-SIZE; GENE; GENOTYPES; SCANS
AB Large two-stage genome-wide association studies (GWASs) have been shown to reduce required genotyping with little loss of power, compared to a one-stage design, provided a substantial fraction of cases and controls, pi(sample), is included in stage 1. However, a number of recent GWASs have used pi(sample) < 0.2. Moreover, standard power calculations are not applicable because SNPs are selected in stage 1 by ranking their p-values, rather than comparing each SNP's statistic to a fixed critical value. We define the detection probability (DP) of a two-stage design as the probability that a given disease-associated SNP will have a p-value among the lowest ranks of p-values at stage 1, and, among those SNPs selected at stage 1, at stage 2. For 8000 cases and 8000 controls available for study and for odds ratios per allele in the range 1.1-1.3, we show that DP is substantially reduced for designs with pi(sample) <= 0.25, and that DP cannot be appreciably increased by analyzing the stage 1 and stage 2 data jointly. These results suggest that multistage designs with small first stages (e.g. pi(sample) <= 0.25) should be avoided, and that additional genotyping in earlier studies with small first stages will yield previously unselected disease-associated SNPs.
C1 [Gail, M. H.; Pfeiffer, R. M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wheeler, W.; Pee, D.] Informat Management Serv Inc, Rockville, MD 20852 USA.
RP Gail, MH (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 8032, Bethesda, MD 20892 USA.
EM gailm@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011
FU Intramural NIH HHS [Z01 CP010181-05]
NR 17
TC 12
Z9 12
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0003-4800
J9 ANN HUM GENET
JI Ann. Hum. Genet.
PD NOV
PY 2008
VL 72
BP 812
EP 820
DI 10.1111/j.1469-1809.2008.00467.x
PN 6
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 358SB
UT WOS:000259936700011
PM 18652601
ER
PT J
AU Zheng, G
AF Zheng, Gang
TI Can the Allelic Test be Retired from Analysis of Case-Control
Association Studies?
SO ANNALS OF HUMAN GENETICS
LA English
DT Article
DE Allele-based test; trend test; disequilibrium coefficient; genetic
model; robust tests
ID HARDY-WEINBERG EQUILIBRIUM; SAMPLE-SIZE
AB It has been stated that, when Hardy-Weinberg equilibrium (HWE) holds in the combined case-control samples, the allelic test is asymptotically equivalent to the trend test (for the additive model) for testing genetic association, and hence the allelic test should not be used. A recent publication shows that the allelic test and the trend test are asymptotically equivalent when HWE holds in the population. It is known that, when HWE does not hold, the trend test can still be used while the allelic test is no longer valid. Therefore, the allelic test is either not valid or is asymptotically equivalent to the trend test. It appears that the allelic test is a nuisance test. Can it be retired from the analysis of case-control association studies ? It all depends on data and model assumptions. We give conditions under which the allelic test and the trend test are asymptotically equivalent under both null and alternative hypotheses.
C1 NHLBI, Off Biostat Res, DPPS, Bethesda, MD 20892 USA.
RP Zheng, G (reprint author), NHLBI, Off Biostat Res, DPPS, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM zhengg@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 16
TC 7
Z9 7
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0003-4800
J9 ANN HUM GENET
JI Ann. Hum. Genet.
PD NOV
PY 2008
VL 72
BP 848
EP 851
DI 10.1111/j.1469-1809.2008.00466.x
PN 6
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 358SB
UT WOS:000259936700014
PM 18652599
ER
PT J
AU Ay, H
Arsava, EM
Gungor, L
Greer, D
Singhal, AB
Furie, KL
Koroshetz, WJ
Sorensen, AG
AF Ay, Hakan
Arsava, Ethem Murat
Gungor, Levent
Greer, David
Singhal, Aneesh B.
Furie, Karen L.
Koroshetz, Walter J.
Sorensen, A. Gregory
TI Admission International Normalized Ratio and Acute Infarct Volume in
Ischemic Stroke
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID ATRIAL-FIBRILLATION; ENDOTHELIAL FUNCTION; ANTICOAGULATION; TRIAL;
THROMBOLYSIS; ASSOCIATION; PREVENTION; REGRESSION; SEVERITY; THROMBUS
AB Objective: The level of anticoagulation at the time of stroke onset may influence the size, composition, and dissolution rate of the occlusive clot. We explored the relation between admission international normalized ratio (INR) and acute infarct volume in patients with ischemic stroke.
Methods: We studied 93 consecutive patients with preadmission warfarin use who had INR measurement and diffusion-weighted imaging performed within 24 hours of stroke onset. Ninety-three etiologic stroke subtype-matched patients without prior warfarin use served as control patients. Linear regression analysis was used to test for independence of INR as a predictor of infarct volume.
Results: In patients with preadmission warfarin use, admission INR was inversely correlated with lesion volume oil diffusion-weighted imaging (r = -0-38). This relation was retained after adjustment for potential covariates (p = 0.014). INR less than 2.0 was associated with 3.5-fold (95% confidence interval, 2.9-4.2) greater lesion volume on diffusion-weighted imaging as compared with INR of 2.0 or more. Patients who were on therapeutic INR ( :2.0) had smaller infarcts compared with patients without preadmission warfarin use (p = 0.001). Admission INR was inversely correlated with acute perfusion defect (r = -0.33), chronic infarct volume (r = -0.42), National Institutes of Health Stroke Scale score at admission (r = -0.27), and modified Rankin score at discharge (r = -0.28).
Interpretation: These results suggest that preadmission warfarin use associated with therapeutic level of anticoagulation can offer a benefit in limiting the extent of ischemic injury in an event of acute stroke.
C1 [Ay, Hakan; Greer, David; Singhal, Aneesh B.; Furie, Karen L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Boston, MA USA.
[Ay, Hakan; Arsava, Ethem Murat; Gungor, Levent; Sorensen, A. Gregory] Harvard Univ, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol,Sch Med, Boston, MA USA.
[Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
RP Ay, H (reprint author), Harvard Univ, Sch Med, AA Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA.
EM hay@partners.org
RI Arsava, Ethem Murat/I-9197-2013
OI Arsava, Ethem Murat/0000-0002-6527-4139
FU NIH (National Institute of Neurological Disorders and Stroke)
[R01-NS038477, R01NS051412, P50-NS051343]
FX This work was Supported by NIH (National Institute of Neurological
Disorders and Stroke) grants R01-NS038477 (AGS), R01NS051412 (ABS) and
P50-NS051343 (KLF).
NR 27
TC 37
Z9 39
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD NOV
PY 2008
VL 64
IS 5
BP 499
EP 506
DI 10.1002/ana.21456
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 383BS
UT WOS:000261649700009
PM 18661516
ER
PT J
AU Cushman, M
Cantrell, RA
McClure, LA
Howard, G
Prineas, RJ
Moy, CS
Temple, EM
Howard, VJ
AF Cushman, Mary
Cantrell, Ronald A.
McClure, Leslie A.
Howard, George
Prineas, Ronald J.
Moy, Claudia S.
Temple, Ella M.
Howard, Virginia J.
TI Estimated 10-Year Stroke Risk by Region and Race in the United States:
Geographic and Racial Differences in Stroke Risk
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; BLACK-WHITE DIFFERENCES; LEFT-VENTRICULAR
MASS; FOLLOW-UP; ATHEROSCLEROSIS RISK; NATIONAL-HEALTH; HYPERTENSION;
MORTALITY; COMMUNITIES; DISPARITIES
AB Objective: Black individuals younger than 75 years have more than twice the risk for stroke death than whites in the United States. Regardless of race, stroke death is approximately 50% greater in the "stroke belt" and "stroke buckle" states of the Southeastern United States. We assessed geographic and racial differences in estimated 10-year stroke risk.
Methods: The Reasons for Geographic and Racial Differences in Stroke study is a population-based cohort of men and women 45 years or older, recruited February 2003 to September 2007 at this report, with oversampling of stroke belt/buckle residents and blacks. Racial and regional differences in the Framingham Stroke Risk Score were Studied in 23,940 participants without previous stroke or transient ischemic attack.
Results: The mean age-, race-, and sex-adjusted 10-year predicted stroke probability differed slightly across regions: 10.7% in the belt, 10.4% in the buckle, and 10.1% elsewhere (p < 0.001). Geographic differences were largest for the score components of diabetes and use of antihypertensive therapy. Blacks had a greater age- and sex-adjusted mean 10-year predicted stroke probabilicy than whites: 12.0 versus 9.2%, respectively (p < 0.001). Race differences were largest for the score components of hypertension, systolic blood pressure, diabetes, smoking, and left ventricular hypertrophy.
Interpretation. Although blacks had a greater predicted stroke probability than whites, regional differences were small. Results suggest that interventions to reduce racial disparities in stroke risk factors hold promise to reduce the racial disparity in stroke mortality. The same may not be true regarding geographic disparities in stroke mortality.
C1 [Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA.
[Cantrell, Ronald A.; Howard, Virginia J.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA.
[McClure, Leslie A.; Howard, George; Temple, Ella M.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA.
[Prineas, Ronald J.] Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Moy, Claudia S.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
RP Cushman, M (reprint author), Univ Vermont, Dept Med, 208 S Pk Dr,Suite 2, Colchester, VT 05446 USA.
EM mary.cushman@uvm.edu
RI McClure, Leslie/P-2929-2015
FU NINDS NIH HHS [U01 NS041588-03, R01 NS041588, R01 NS041588-01, U01
NS041588, U01 NS041588-02, U01 NS041588-04, U01 NS041588-05, U01
NS041588-06, U01 NS041588-08]
NR 31
TC 60
Z9 61
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD NOV
PY 2008
VL 64
IS 5
BP 507
EP 513
DI 10.1002/ana.21493
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 383BS
UT WOS:000261649700010
PM 19067365
ER
PT J
AU Schiffmann, R
Fitzgibbon, EJ
Harris, C
DeVile, C
Davies, EH
Abel, L
van Schaik, IN
Benko, W
Timmons, M
Ries, M
Vellodi, A
AF Schiffmann, Raphael
Fitzgibbon, Edmond J.
Harris, Chris
DeVile, Catherine
Davies, Elin H.
Abel, Larry
van Schaik, Ivo N.
Benko, William
Timmons, Margaret
Ries, Markus
Vellodi, Ashok
TI Randomized, Controlled Trial of Miglustat in Gaucher's Disease Type 3
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID ENZYME REPLACEMENT THERAPY; N-BUTYLDEOXYNOJIRIMYCIN; INVOLVEMENT;
IDENTIFICATION; BIOSYNTHESIS; INHIBITOR; EFFICACY; OGT-918
AB Objective: To evaluate the efficacy and safety of miglustat, concomitant with enzyme replacement therapy (ERT), in patients with Gaucher's disease type 3 (GD3).
Methods: This 24-month, phase II, open-label clinical trial of miglustat in GD3 was conducted in two phases. During the initial 12 months, patients were randomized 2:1 to receive miglustat or "no miglustat treatment." The randomized phase was followed by an optional 12-month extension phase in which all patients received miglustat. All patients received ERT during the 24-month period. The primary efficacy end points were change from baseline to months 12 and 24 in vertical saccadic eye movement velocity as determined by the peak amplitude versus amplitude regression line slope. Secondary end points included changes in neurological and neuropsychological assessments, pulmonary function tests, liver and spleen organ volumes, hematological and clinical laboratory assessments, and safety evaluations.
Results: Thirty patients were enrolled, of whom 21 were randomized to miglustat and 9 to "no miglustat treatment." Twenty-eight patients entered the 12-month extension phase. No significant between-group differences in vertical saccadic eye movement velocity or in the other neurological or neuropsychological evaluations were observed. Organ volumes and hematological parameters remained stable in both treatment groups, but improvement in pulmonary function and decrease of chitotriosidase levels were observed with miglustat compared with patients receiving ERT alone.
Interpretation: Miglustat does not appear to have significant benefits on the neurological manifestations of GD3. However, miglustar may have positive effects on systemic disease (pulmonary function and chitotriosidase activity) in addition to ERT in patients with GD3.
C1 [Schiffmann, Raphael; Benko, William; Timmons, Margaret; Ries, Markus] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, Bethesda, MD USA.
[Fitzgibbon, Edmond J.] NEI, NIH, Bethesda, MD 20892 USA.
[Harris, Chris] Univ Plymouth, Ctr Theoret & Computat Neurosci, Plymouth PL4 8AA, Devon, England.
[DeVile, Catherine; Davies, Elin H.; Vellodi, Ashok] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[Abel, Larry] Univ Melbourne, Dept Optometry & Vis Sci, Melbourne, Vic, Australia.
[van Schaik, Ivo N.] Univ Amsterdam, Acad Med Ctr, Dept Neurol & Clin Neurophysiol, NL-1105 AZ Amsterdam, Netherlands.
RP Schiffmann, R (reprint author), Baylor Inst Metab Dis, 3812 Elm St, Dallas, TX 75226 USA.
EM raphael.schiffmann@baylorhealth.edu
RI Abel, Larry/D-9915-2012;
OI Abel, Larry/0000-0002-2393-0644; Ries, Markus/0000-0002-5054-5741
FU Intramural NIH HHS [Z01 NS002984-09, Z99 NS999999]
NR 27
TC 82
Z9 82
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD NOV
PY 2008
VL 64
IS 5
BP 514
EP 522
DI 10.1002/ana.21491
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 383BS
UT WOS:000261649700011
PM 19067373
ER
PT J
AU Mortiboys, H
Thomas, KJ
Koopman, WJH
Klaffke, S
Abou-Sleiman, P
Olpin, S
Wood, NW
Willems, PHGM
Smeitink, JAM
Cookson, MR
Bandmann, O
AF Mortiboys, Heather
Thomas, Kelly Jean
Koopman, Werner J. H.
Klaffke, Stefanie
Abou-Sleiman, Patrick
Olpin, Simon
Wood, Nicholas W.
Willems, Peter H. G. M.
Smeitink, Jan A. M.
Cookson, Mark R.
Bandmann, Oliver
TI Mitochondrial Function and Morphology Are Impaired in parkin-Mutant
Fibroblasts
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID COMPLEX-I DEFICIENCY; SKIN FIBROBLASTS; DISEASE; MUTATIONS; PATHOLOGY;
MUSCLE; PINK1; CELLS; DEGENERATION; ASSOCIATION
AB Objective: There are marked mitochondrial abnormalities in parkin-knock-out Drosophila and other model systems. The aim of Our Study was to determine mitochondrial function and morphology in parkin-mutant patients. We also investigated whether pharmacological rescue of impaired mitochondrial function may be possible in parkin-mutant human tissue.
Methods: We used three sets of techniques, namely, biochemical measurements of mitochondrial function, quantitative morphology, and live cell imaging of functional connectivity to assess the mitochondrial respiratory chain, the outer shape and connectivity of the mitochondria, and their functional inner connectivity in fibroblasts from patients with homozygous or compound heterozygous parkin Mutations.
Results. Parkin-mutant cells had lower mitochondrial complex I activity and complex I-linked adenosine triphosphate production, which correlated with a greater degree of mitochondrial branching, suggesting that the functional and morphological effects of Parkin are related. Knockdown of parkin in control fibroblasts confirmed chat Parkin deficiency is sufficient to explain these mitochondrial effects. In contrast, 50% knockdown of parkin, mimicking haploinsufficiency in human patient tissue, did not result in impaired mitochondrial function or morphology. Fluorescence recovery after photobleaching assays demonstrated a lower level of functional connectivity of the mitochondrial matrix, which further worsened after rotenone exposure. Treatment with experimental neuroprotective compounds resulted in a rescue of the mitochondrial membrane potential.
Interpretation: Our Study demonstrates marked abnormalities of mitochondrial function and morphology in parkin-mutant patients and provides proof-of-principle data for the potential usefulness of this new model system as a tool to screen for disease-modifying compounds in genetically homogenous parkinsonian disorders.
C1 [Mortiboys, Heather; Klaffke, Stefanie; Bandmann, Oliver] Univ Sheffield, Sch Med, Acad Neurol Unit, Sheffield S10 2RX, S Yorkshire, England.
[Thomas, Kelly Jean; Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Koopman, Werner J. H.; Willems, Peter H. G. M.] Radboud Univ Nijmegen, Ctr Med, Dept Biochem, Nijmegen Cencre Mol Life Sci, Nijmegen, Netherlands.
[Abou-Sleiman, Patrick; Wood, Nicholas W.] Inst Neurol, London WC1N 3BG, England.
[Olpin, Simon] Sheffield Childrens Hosp, Sheffield S10 2TH, S Yorkshire, England.
[Smeitink, Jan A. M.] Radboud Univ Nijmegen, Dept Pediat, Nijmegen Ctr Mitochondrial Disorders, Nijmegen, Netherlands.
RP Bandmann, O (reprint author), Univ Sheffield, Sch Med, Acad Neurol Unit, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England.
EM o.bandmann@sheffield.ac.uk
RI Smeitink, Jan/D-6064-2011; Smeitink, Jan/C-1351-2013; Koopman,
Werner/N-3586-2014; Mortiboys, Heather/E-8838-2010; Wood,
Nicholas/C-2505-2009; Koopman, Werner/D-3592-2009; Willems,
P.H.G.M./L-4759-2015;
OI Wood, Nicholas/0000-0002-9500-3348; Koopman, Werner/0000-0002-5340-6747;
Willems, P.H.G.M./0000-0002-0915-1599; olpin, simon/0000-0001-9018-5173
FU Parkinson's Disease Society (UK) [G-0715]; University of Sheffield; NIH;
National Institute on Aging [Z01 AG000953-07]
FX This work was supported by the Parkinson's Disease Society (UK) (G-0715,
H.M., O.B.), the Sheila McKenzie Fund of the University of Sheffield
(H.M., O.B.), the Intramural Research Program of the NIH (National
Institute on Aging, Z01 AG000953-07, K.J.T., M.R.C.), and an Innovative
Research Projects (IOP)-genomics project entitled "New tools for the
identification of nutritional modulators of mitochondrial activity:
small molecules that promote health and combat disease" (IGE05003,
W.J.H.K., P.H.G.M.W., J.A.M.S.).
NR 33
TC 170
Z9 172
U1 1
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
EI 1531-8249
J9 ANN NEUROL
JI Ann. Neurol.
PD NOV
PY 2008
VL 64
IS 5
BP 555
EP 565
DI 10.1002/ana.21492
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 383BS
UT WOS:000261649700015
PM 19067348
ER
PT J
AU Pierson, TM
Bonnemann, CG
Finkel, RS
Bunin, N
Tennekoon, GI
AF Pierson, Tyler Mark
Bonnemann, Carsten G.
Finkel, Richard S.
Bunin, Nancy
Tennekoon, Gihan I.
TI Umbilical Cord Blood Transplantation for Juvenile Metachromatic
Leukodystrophy
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; CELL TRANSPLANTATION; METABOLIC DISEASES;
NERVE-CONDUCTION; LYSOSOMAL-ENZYME; GENETICS; OUTCOMES; CHILDREN; HURLER
AB Three siblings with metachromatic leukodystrophy underwent umbilical cord blood transplantation at different stages of disease. Neuroimaging, nerve conduction studies, neurological examinations, and neuropsychological examinations were used to measure Outcome over 2 years. After transplant, the oldest sibling experienced disease progression. His two siblings had near or total resolution of signal abnormalities on neuroimaging. Their neuropsychological testing remained stable, and nerve conduction studies have shown improvement. These results indicate pretransplantation neurological examinations may be the most significant predictor of outcome after transplant. To our knowledge, this report is the first to document neurological outcome of metachromatic leukodystrophy treated by umbilical cord blood transplantation.
C1 [Pierson, Tyler Mark; Bonnemann, Carsten G.; Finkel, Richard S.; Tennekoon, Gihan I.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA.
[Bunin, Nancy] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
RP Pierson, TM (reprint author), NINDS, Nenrogenet Branch, Porter Neurosci Res Ctr, Bldg 35,Room 2A-1000,35 Convent Dr,MSC 3705, Bethesda, MD 20892 USA.
EM piersonty@ninds.nih.gov
FU NIH [T32-HD043021-04]
FX This work was supported by, the NIH (T32-HD043021-04, T. M. P.).
NR 23
TC 24
Z9 24
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD NOV
PY 2008
VL 64
IS 5
BP 583
EP 587
DI 10.1002/ana.21522
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 383BS
UT WOS:000261649700018
PM 19067349
ER
PT J
AU Villalona-Calero, MA
Otterson, GA
Wientjes, MG
Weber, F
Bekaii-Saab, T
Young, D
Murgo, AJ
Jensen, R
Yeh, TK
Wei, Y
Zhang, Y
Eng, C
Grever, M
Au, JLS
AF Villalona-Calero, M. A.
Otterson, G. A.
Wientjes, M. G.
Weber, F.
Bekaii-Saab, T.
Young, D.
Murgo, A. J.
Jensen, R.
Yeh, T. -K.
Wei, Y.
Zhang, Y.
Eng, C.
Grever, M.
Au, J. L. -S.
TI Noncytotoxic suramin as a chemosensitizer in patients with advanced
non-small-cell lung cancer: a phase II study
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE chemosensitization; drug resistance; FGF; lung cancer; suramin
ID FIBROBLAST-GROWTH-FACTOR; FACTOR RECEPTOR-BINDING; HUMAN BREAST-CANCER;
PROGNOSTIC-SIGNIFICANCE; PLUS CARBOPLATIN; POTENT INHIBITOR; ENHANCE
ACTIVITY; FACTOR BFGF; PACLITAXEL; GEFITINIB
AB Background: The purpose of this study was to evaluate the potential of noncytotoxic doses of suramin to reverse chemotherapy resistance in advanced chemonaive and chemoresistant non-small-cell lung cancer patients.
Patients and methods: Patients received paclitaxel (Taxol) (200 mg/m(2)) and carboplatin (area under the concentration-time curve 6 mg/ml/min) every 3 weeks. The total suramin per cycle dose was calculated using a nomogram derived from the preceding phase I trial to obtain the desirable plasma concentration range of 10-50 mu M.
Results: Thirty-nine response-assessable chemonaive patients (arm A) received 213 cycles. Thirty-eight cycles were administered to 15 patients with demonstrated resistance to paclitaxel and carboplatin (arm B). The pattern/frequency of toxic effects was similar to those expected for paclitaxel/carboplatin, and pharmacokinetic analyses (199 cycles) showed suramin plasma concentrations maintained between 10 and 50 mu M in 94% of cycles. In arm A, response evaluation criteria in solid tumors (RECIST) response rate was 36% (95% confidence interval 22% to 54%; two complete, 12 partial); 15 patients (38%) had disease stabilization for >= 4 months; median progression-free survival (intention to treat) was 6.4 months; median overall survival (OS) 10.4 months and 1-year survival rate 38%. In arm B, no RECIST responses occurred; four patients had disease stabilization for >= 4 months; median OS was 132 days and 1-year survival rate 7%. Plasma basic fibroblast growth factor levels were higher in chemopretreated/refractory patients compared with chemonaive patients (P = 0.05). Sequence analysis of the EGFR tyrosine kinase domain in a long-term disease-free survivor revealed an ATP-binding pocket mutation (T790M).
Conclusions: Noncytotoxic suramin did not increase paclitaxel/carboplatin's toxicity and the suramin dose was predicted from clinical parameters. No clinically significant reversal of primary resistance was documented, but a modulatory effect in chemotherapy-naive patients cannot be excluded. Controlled randomization is planned for further evaluation of this treatment strategy.
C1 [Villalona-Calero, M. A.; Otterson, G. A.; Wientjes, M. G.; Bekaii-Saab, T.; Young, D.; Murgo, A. J.; Jensen, R.; Yeh, T. -K.; Wei, Y.; Zhang, Y.; Grever, M.; Au, J. L. -S.] Ohio State Univ, Dept Med, Arthur G James Canc Hosp, Columbus, OH 43210 USA.
[Villalona-Calero, M. A.; Otterson, G. A.; Wientjes, M. G.; Bekaii-Saab, T.; Young, D.; Murgo, A. J.; Jensen, R.; Yeh, T. -K.; Wei, Y.; Zhang, Y.; Grever, M.; Au, J. L. -S.] Ohio State Univ, Coll Pharm, Arthur G James Canc Hosp, Columbus, OH 43210 USA.
[Villalona-Calero, M. A.; Otterson, G. A.; Wientjes, M. G.; Bekaii-Saab, T.; Young, D.; Murgo, A. J.; Jensen, R.; Yeh, T. -K.; Wei, Y.; Zhang, Y.; Grever, M.; Au, J. L. -S.] Richard J Solove Res Inst, Columbus, OH USA.
[Villalona-Calero, M. A.; Otterson, G. A.; Wientjes, M. G.; Bekaii-Saab, T.; Young, D.; Murgo, A. J.; Jensen, R.; Yeh, T. -K.; Wei, Y.; Zhang, Y.; Grever, M.; Au, J. L. -S.] NCI, Bethesda, MD 20892 USA.
[Weber, F.; Eng, C.] Cleveland Clin Fdn, Genom Med Inst, Lerner Res Inst, Cleveland, OH 44195 USA.
[Weber, F.; Eng, C.] Cleveland Clin Fdn, Taussig Canc Ctr, Cleveland, OH 44195 USA.
RP Villalona-Calero, MA (reprint author), Ohio State Univ, B406 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA.
EM miguel.villalona@osumc.edu
RI Weber, Frank/A-1883-2012; Bekaii-Saab, Tanios/E-2733-2011;
OI Weber, Frank/0000-0002-0995-667X; Eng, Charis/0000-0002-3693-5145
FU National Cancer Institute, DHHS [R37CA49816, R21CA91547, R01CA97067,
U01CA76576]; NCI Merit Award; Doris Duke Distinguished Clinical
Scientist Award
FX R37CA49816 (JLSA), R21CA91547 (JLSA), R01CA97067 (JLSA), and U01CA76576
(MG) from the National Cancer Institute, DHHS; NCI Merit Award to JLSA;
Doris Duke Distinguished Clinical Scientist Award to CE.
NR 57
TC 20
Z9 20
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD NOV
PY 2008
VL 19
IS 11
BP 1903
EP 1909
DI 10.1093/annonc/mdn412
PG 7
WC Oncology
SC Oncology
GA 365BO
UT WOS:000260381100013
PM 18632723
ER
PT J
AU Bishop, MR
Dean, RM
Steinberg, SM
Odom, J
Pavletic, SZ
Chow, C
Pittaluga, S
Sportes, C
Hardy, NM
Gea-Banacloche, J
Kolstad, A
Gress, RE
Fowler, DH
AF Bishop, M. R.
Dean, R. M.
Steinberg, S. M.
Odom, J.
Pavletic, S. Z.
Chow, C.
Pittaluga, S.
Sportes, C.
Hardy, N. M.
Gea-Banacloche, J.
Kolstad, A.
Gress, R. E.
Fowler, D. H.
TI Clinical evidence of a graft-versus-lymphoma effect against relapsed
diffuse large B-cell lymphoma after allogeneic hematopoietic stem-cell
transplantation
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE allogeneic; diffuse large B-cell lymphoma; graft-versus-lymphoma
ID NON-HODGKINS-LYMPHOMA; BONE-MARROW-TRANSPLANTATION; AUTOLOGOUS
TRANSPLANTATION; EUROPEAN GROUP; CHEMOTHERAPY; LEUKEMIA; BLOOD;
EFFICACY; REGISTRY; DISEASE
AB Background: A graft-versus-lymphoma effect against diffuse large B-cell lymphoma (DLBCL) is inferred by sustained relapse-free survival after allogeneic stem-cell transplantation; however, there are limited data on a direct graft-versus-lymphoma effect against DLBCL following immunotherapeutic intervention by either withdrawal of immunosuppression or donor lymphocyte infusion (DLI).
Materials and methods: An analysis was carried out to determine whether a direct graft-versus-lymphoma effect exists against DLBCL. The analysis was restricted to patients with DLBCL, who were either not in complete remission at day +100 after allogeneic stem-cell transplantation or subsequently relapsed beyond this time point.
Results: Fifteen patients were identified as either not in complete remission (n = 13) at their day +100 evaluation or subsequently relapsed (n = 2) and were assessed for subsequent responses after withdrawal of immunosuppression or DLI. Eleven patients were treated with either withdrawal of immunosuppression (n = 10) or a DLI (n = 1) alone; four patients received chemotherapy with DLI to reduce tumor bulk. Nine (60%) patients subsequently responded (complete = 8, partial = 1). Six responses occurred after withdrawal of immunosuppression alone. Six patients are alive (range 42-83+ months) in complete remission without further treatment.
Conclusion: The demonstration of sustained complete remission following immunotherapeutic intervention provides direct evidence of a graft-versus-lymphoma effect against DLBCL.
C1 [Bishop, M. R.; Dean, R. M.; Odom, J.; Pavletic, S. Z.; Sportes, C.; Hardy, N. M.; Gea-Banacloche, J.; Gress, R. E.; Fowler, D. H.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Dean, R. M.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Steinberg, S. M.] Natl Canc Inst, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD USA.
[Chow, C.] NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA.
[Pittaluga, S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kolstad, A.] Norwegian Radium Hosp, Oslo, Norway.
RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bldg 10,CRC Room 4-3152,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mbishop@mail.nih.gov
FU The Center for Cancer Research, National Cancer Institute.
FX The Center for Cancer Research, National Cancer Institute.
NR 31
TC 38
Z9 41
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD NOV
PY 2008
VL 19
IS 11
BP 1935
EP 1940
DI 10.1093/annonc/mdn404
PG 6
WC Oncology
SC Oncology
GA 365BO
UT WOS:000260381100018
PM 18684698
ER
PT J
AU Hoffer, LJ
Levine, M
Assouline, S
Melnychuk, D
Padayatty, SJ
Rosadiuk, K
Rousseau, C
Robitaille, L
Miller, WH
AF Hoffer, L. J.
Levine, M.
Assouline, S.
Melnychuk, D.
Padayatty, S. J.
Rosadiuk, K.
Rousseau, C.
Robitaille, L.
Miller, W. H., Jr.
TI Phase I clinical trial of i.v. ascorbic acid in advanced malignancy
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE antioxidants; vitamin C
ID VITAMIN-C; DEHYDROASCORBIC ACID; HYDROGEN-PEROXIDE; OXIDATIVE STRESS;
CANCER-THERAPY; LUNG-CANCER; CELLS; INHIBITION; CHEMOTHERAPY; TOXICITY
AB Background: Ascorbic acid is a widely used and controversial alternative cancer treatment. In millimolar concentrations, it is selectively cytotoxic to many cancer cell lines and has in vivo anticancer activity when administered alone or together with other agents. We carried out a dose-finding phase I and pharmacokinetic study of i.v. ascorbic acid in patients with advanced malignancies.
Patients and methods: Patients with advanced cancer or hematologic malignancy were assigned to sequential cohorts infused with 0.4, 0.6, 0.9 and 1.5 g ascorbic acid/kg body weight three times weekly.
Results: Adverse events and toxicity were minimal at all dose levels. No patient had an objective anticancer response.
Conclusions: High-dose i.v. ascorbic acid was well tolerated but failed to demonstrate anticancer activity when administered to patients with previously treated advanced malignancies. The promise of this approach may lie in combination with cytotoxic or other redox-active molecules.
C1 [Levine, M.; Padayatty, S. J.] NIDDKD, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
[Hoffer, L. J.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal Ctr Expt Therapeut Canc, Montreal, PQ H3T 1E2, Canada.
RP Hoffer, LJ (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal Ctr Expt Therapeut Canc, 3755 Cote Ste Catherine Rd, ANNALS ONCO Montreal, PQ H3T 1E2, Canada.
EM l.hoffer@mcgill.ca
RI Padayatty, Sebastian/A-8581-2012
OI Padayatty, Sebastian/0000-0001-8758-3170
FU Lotte and John Hecht Memorial Foundation
FX Lotte and John Hecht Memorial Foundation.
NR 33
TC 110
Z9 112
U1 1
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD NOV
PY 2008
VL 19
IS 11
BP 1969
EP 1974
DI 10.1093/annonc/mdn377
PG 6
WC Oncology
SC Oncology
GA 365BO
UT WOS:000260381100023
PM 18544557
ER
PT J
AU Shanti, RM
Janjanin, S
Li, WJ
Nesti, LJ
Mueller, MB
Tzeng, MB
Tuan, RS
AF Shanti, Rabie M.
Janjanin, Sasa
Li, Wan-Ju
Nesti, Leon J.
Mueller, Michael B.
Tzeng, Megan B.
Tuan, Rocky S.
TI In Vitro Adipose Tissue Engineering Using an Electrospun Nanofibrous
Scaffold
SO ANNALS OF PLASTIC SURGERY
LA English
DT Article
DE adipose tissue engineering; electrospinning; nanofibers; mesechymal stem
cells; tissue engineering
ID MESENCHYMAL STEM-CELLS; COLLAGEN IMPLANT; AUGMENTATION; VIVO;
PREADIPOCYTES; MATRIX; DIFFERENTIATION; TRANSPLANTATION; PROLIFERATION;
LIPOSUCTION
AB Electrospun 3-dimensional nanofibrous scaffolds share morphologic similarities to collagen fibrils, and promote favorable biologic responses of seeded cells. In this Study, we have fabricated a 3-dimensional nanofibrous scaffold made of poly L-lactic acid, and examined its ability to support and maintain the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells in vitro. After a 21-day incubation, on red O staining of constructs treated with adipogenic supplements revealed positive adipose-like staining, compared with lack of staining in untreated cultures. Semi-quantitative RT-PCR analysis of human bone marrow-derived mesenchymal stern Cells Cultured in adipogenic medium revealed highly elevated levels of adipogenesis-associated genes (1797-fold for lipoprotein lipase, and 5.6-fold for peroxisome proliferator-activated receptor gamma). Immunofluorescence staining of cellular constructs in adipogenic culture media showed the presence of lipoprotein lipase vesicles, a characteristic feature of adipose tissue. These results suggest that the poly L-lactic acid-based nanofibrous scaffold is a promising candidate for adult stern cell-based engineering of adipose tissue.
C1 [Shanti, Rabie M.; Janjanin, Sasa; Li, Wan-Ju; Mueller, Michael B.; Tzeng, Megan B.; Tuan, Rocky S.] NIAMSD, Dept Hlth & Human Serv, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA.
[Shanti, Rabie M.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
[Nesti, Leon J.] Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, Washington, DC 20307 USA.
RP Tuan, RS (reprint author), NIAMSD, Dept Hlth & Human Serv, Cartilage Biol & Orthopaed Branch, NIH, Bldg 50,Room 1523,MSC 8022, Bethesda, MD 20892 USA.
EM shanti.rabie@gmail.com
FU Intramural Research Program of NIAMS [NIH Z01 AR 41131]
FX The authors thank the Light Imaging Section of the Intramural Research
National Institute of Arthritis and Musculoskeletal and Skin Diseases,
and Dr. James A. Cooper for aid in confocal laser scanning microscopy
and scanning electron microscopy, respectively. This work is supported
by the Intramural Research Program of NIAMS (NIH Z01 AR 41131).
NR 43
TC 23
Z9 25
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-7043
J9 ANN PLAS SURG
JI Ann. Plast. Surg.
PD NOV
PY 2008
VL 61
IS 5
BP 566
EP 571
DI 10.1097/SAP.0b013e31816d9579
PG 6
WC Surgery
SC Surgery
GA 364VP
UT WOS:000260363800022
PM 18948788
ER
PT J
AU Zeitoun, G
Mourra, N
Blanche-Koch, H
Thomas, G
Olschwang, S
AF Zeitoun, Guy
Mourra, Najat
Blanche-Koch, Helene
Thomas, Gilles
Olschwang, Sylviane
TI Genomic Profile of Colon Cancer Metastases
SO ANTICANCER RESEARCH
LA English
DT Article
DE Colon cancer; metastasis; genomic profiling; dormancy; clonal expansion;
microsatellite stability
ID COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; DORMANCY; APC; MUTATIONS;
SURVIVAL; CELLS; SEED
AB Background: In colon cancer, the occurrence of metastases is associated with microsatellite stability. As metastatic cells derive from a clonal expansion of primary tumor cells, specific genomic alterations are expected in addition to the common genomic profile. Patients and Methods: Genome-wide allelotyping was performed on 75 liver metastases samples from sporadic colon cancer. Results: No microsatellite instability was observed. Allelic loss on 5q in metastases was significantly different from that of non metastatic primary tumors (16/58 vs. 43/75, p=0.0008). Four additional chromosomes, 4, 7, 8 and 19, were more frequently lost in liver metastases, but statistical significance was reached only for 19q (14/63 versus 2/68 in primary tumors; p=0.033 after Dunn-Sidak adjustment). Conclusion: This study, confirms that liver metastasis is rather restricted to patients with microsatellite stable colon cancer and these retain the 5q arm with high frequency. In addition, it suggests that loss of 19q may be critical for one of the steps involved in the development of liver metastases.
C1 [Olschwang, Sylviane] Inst J Paoli I Calmettes, CRCM, INSERM, U891, F-13009 Marseille, France.
[Zeitoun, Guy] Gen Hosp, Dept Surg, F-78000 Mantes La Jolie, France.
[Mourra, Najat] Hop St Antoine, Dept Pathol, F-75012 Paris, France.
[Blanche-Koch, Helene] Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France.
[Olschwang, Sylviane] Inst J Paoli I Calmettes, F-13009 Marseille, France.
[Olschwang, Sylviane] Univ Aix Marseille 2, F-13007 Marseille, France.
[Thomas, Gilles] NCI, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA.
RP Olschwang, S (reprint author), Inst J Paoli I Calmettes, CRCM, INSERM, U891, 232 Blvd St Marguerite, F-13009 Marseille, France.
EM sylviane.olschwang@inserm.f2r
RI Olschwang, Sylviane/G-2716-2013
FU Ligue Nationale Contre le Cancer and Association pour la Recherche
contre le Cancer
FX This work was supported by grants from Ligue Nationale Contre le Cancer
and Association pour la Recherche contre le Cancer. The French
Association for Surgical Research is gratefully acknowledged for its
collaboration with patient recruitment.
NR 22
TC 6
Z9 7
U1 0
U2 0
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD NOV-DEC
PY 2008
VL 28
IS 6A
BP 3609
EP 3612
PG 4
WC Oncology
SC Oncology
GA 388VW
UT WOS:000262049100007
PM 19189641
ER
PT J
AU Petraitiene, R
Petraitis, V
Hope, WW
Mickiene, D
Kelaher, AM
Murray, HA
Mya-San, C
Hughes, JE
Cotton, MP
Bacher, J
Walsh, TJ
AF Petraitiene, Ruta
Petraitis, Vidmantas
Hope, William W.
Mickiene, Diana
Kelaher, Amy M.
Murray, Heidi A.
Mya-San, Christine
Hughes, Johanna E.
Cotton, Margaret P.
Bacher, John
Walsh, Thomas J.
TI Cerebrospinal Fluid and Plasma (1 -> 3)-beta-D-Glucan as Surrogate
Markers for Detection and Monitoring of Therapeutic Response in
Experimental Hematogenous Candida Meningoencephalitis
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; BIRTH-WEIGHT INFANTS; BETA-D-GLUCAN;
AMPHOTERICIN-B; INVASIVE CANDIDIASIS; FUNGAL-INFECTIONS; MICAFUNGIN
FK463; BLOOD CULTURES; RISK-FACTORS; ANTIFUNGAL
AB The treatment, diagnosis and therapeutic monitoring of hematogenous Candida meningoencephalitis (HCME) are not well understood. We therefore studied the expression of (1 -> 3)-beta-D-glucan (beta-glucan) in cerebrospinal fluid (CSF) and plasma in a nonneutropenic rabbit model of experimental HCME treated with micafungin and amphotericin B. Groups studied consisted of micafungin (0.5 to 32 mg/kg) and amphotericin B (1 mg/kg) treatment groups and the untreated controls (UC). Despite well-established infection in the cerebrum, cerebellum, choroid, vitreous humor (10(2) to 10(3) CFU/ml), spinal cord, and meninges (10 to 10(2) CFU/g), only 8.1% of UC CSF cultures were positive. By comparison, all 25 UC CSF samples tested for beta-glucan were positive (755 to 7,750 pg/ml) (P < 0.001). The therapeutic response in CNS tissue was site dependent, with significant decreases of the fungal burden in the cerebrum and cerebellum starting at 8 mg/kg, in the meninges at 2 mg/kg, and in the vitreous humor at 4 mg/kg. A dosage of 24 mg/kg was required to achieve a significant effect in the spinal cord and choroid. Clearance of Candida albicans from blood cultures was not predictive of eradication of organisms from the CNS; conversely, beta-glucan levels in CSF were predictive of the therapeutic response. A significant decrease of beta-glucan concentrations in CSF, in comparison to that for UC, started at 0.5 mg/kg (P < 0.001). Levels of plasma beta-glucan were lower than levels in simultaneously obtained CSF (P < 0.05). CSF beta-glucan levels correlated in a dose-dependent pattern with therapeutic responses and with Candida infection in cerebral tissue (r = 0.842). Micafungin demonstrated dose-dependent and site-dependent activity against HCME. CSF beta-glucan may be a useful biomarker for detection and monitoring of therapeutic response in HCME.
C1 [Petraitiene, Ruta; Petraitis, Vidmantas; Hope, William W.; Mickiene, Diana; Kelaher, Amy M.; Murray, Heidi A.; Mya-San, Christine; Hughes, Johanna E.; Cotton, Margaret P.; Walsh, Thomas J.] Natl Canc Inst, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Petraitiene, Ruta; Petraitis, Vidmantas; Mickiene, Diana] SAIC Frederick Inc, Lab Anim Sci Program, Frederick, MD USA.
[Bacher, John] Off Res Serv, Surg Serv, Div Vet Resources, Bethesda, MD USA.
RP Walsh, TJ (reprint author), Natl Canc Inst, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,CRC,Rm 1W-5740,10 Ctr Dr, Bethesda, MD 20892 USA.
EM walsht@mail.nih.gov
NR 35
TC 28
Z9 29
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD NOV
PY 2008
VL 52
IS 11
BP 4121
EP 4129
DI 10.1128/AAC.00674-08
PG 9
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 363ZI
UT WOS:000260305600041
PM 18779361
ER
PT J
AU Ostrosky-Zeichner, L
Rex, JH
Pfaller, MA
Diekema, DJ
Alexander, BD
Andes, D
Brown, SD
Chaturvedi, V
Ghannoum, MA
Knapp, CC
Sheehan, DJ
Walsh, TJ
AF Ostrosky-Zeichner, Luis
Rex, John H.
Pfaller, Michael A.
Diekema, Daniel J.
Alexander, Barbara D.
Andes, David
Brown, Steven D.
Chaturvedi, Vishnu
Ghannoum, Mahmoud A.
Knapp, Cindy C.
Sheehan, Daniel J.
Walsh, Thomas J.
TI Rationale for Reading Fluconazole MICs at 24 Hours Rather than 48 Hours
When Testing Candida spp. by the CLSI M27-A2 Standard Method
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID COLORIMETRIC ANTIFUNGAL PANEL; INTERPRETIVE BREAKPOINTS; EMPIRIC
TREATMENT; AMPHOTERICIN-B; ITRACONAZOLE; MORTALITY; COMMITTEE; ALBICANS;
THERAPY
AB We investigated if CLSI M27-A2 Candida species breakpoints for fluconazole MIC are valid when read at 24 h. Analysis of a data set showed good correlation between 48- and 24-h MICs, as well as similar outcomes and pharmacodynamic efficacy parameters, except for isolates in the susceptible dose-dependent category, such as Candida glabrata.
C1 [Ostrosky-Zeichner, Luis; Rex, John H.] Univ Texas Houston, Sch Med, Houston, TX 77030 USA.
[Rex, John H.] AstraZeneca, Macclesfield, Cheshire, England.
[Pfaller, Michael A.; Diekema, Daniel J.] Univ Iowa, Iowa City, IA USA.
[Alexander, Barbara D.] Duke Univ, Durham, NC USA.
[Andes, David] Univ Wisconsin, Madison, WI USA.
[Brown, Steven D.] Inst Clin Microbiol, Wilsonville, OR USA.
[Chaturvedi, Vishnu] New York State Dept Hlth, Albany, NY USA.
[Ghannoum, Mahmoud A.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Knapp, Cindy C.] TREK Diagnost Syst, Cleveland, OH USA.
[Sheehan, Daniel J.] Pfizer Inc, New York, NY USA.
[Walsh, Thomas J.] NCI, Bethesda, MD 20892 USA.
RP Ostrosky-Zeichner, L (reprint author), Univ Texas Houston, Sch Med, 6431 Fannin,MSB 2-112, Houston, TX 77030 USA.
EM Luis.Ostrosky-Zeichner@uth.tmc.edu
OI Diekema, Daniel/0000-0003-1273-0724
NR 17
TC 19
Z9 20
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 NOV
PY 2008
VL 52
IS 11
BP 4175
EP 4177
DI 10.1128/AAC.00420-08
PG 3
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 363ZI
UT WOS:000260305600053
PM 18809944
ER
PT J
AU Baker, R
Peacock, S
AF Baker, Robert
Peacock, Susan
TI BEI Resources: Supporting antiviral research
SO ANTIVIRAL RESEARCH
LA English
DT Article
DE Biodefense; Emerging infectious disease; Repository; Reagents; Culture
collection; Antiviral therapy
AB The Biodefense and Emerging Infections Research Resources Repository (BEI Resources) provides unique, quality-assured reagents to the scientific community for use in basic research and product development involving biodefense and emerging infectious diseases. These include microorganisms (up to Biosafety Level-3) on the National Institute of Allergy and Infectious Diseases (NIAID)and Centers for Disease Control and Prevention (CDC) lists of Category A, B and C priority pathogens. In addition to live microorganisms, related products such as polyclonal antisera, monoclonal antibodies, isolated nucleic acid preparations, overlapping peptide arrays, purified proteins, and assay kits are also available. Many of these materials have direct or indirect applications in antiviral research. These reagents are available free of charge to all registered investigators, regardless of funding source or affiliation. Acquisition of new reagents for the repository is one of the critically necessary and challenging tasks for BEI Resources. Therefore, investigators are encouraged to deposit relevant items, so as to provide access to materials, relief from the burden of distribution, protection of intellectual property rights, and secure storage. In addition, BEI Resources has the capability of contracting for the preparation of specific reagents. If there is a resource needed to advance a specific research area, contact an NIAID program officer or use the "suggest a reagent" option on the BEI Resources homepage, www.beiresources.org. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Peacock, Susan] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
[Baker, Robert] BEI Resources, Amer Type Culture Collect, Manassas, VA USA.
RP Peacock, S (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
EM peacocksusan@niaid.nih.gov
FU NIAID NIH HHS [N01 AI030067]
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
J9 ANTIVIR RES
JI Antiviral Res.
PD NOV
PY 2008
VL 80
IS 2
BP 102
EP 106
DI 10.1016/j.antiviral.2008.07.003
PG 5
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA 371FX
UT WOS:000260818300003
PM 18675849
ER
PT J
AU Silverman, JEY
Ciustea, M
Shudofsky, AMD
Bender, F
Shoemaker, RH
Ricciardi, RP
AF Silverman, Janice Elaine Y.
Ciustea, Mihai
Shudofsky, Abigail M. Druck
Bender, Florent
Shoemaker, Robert H.
Ricciardi, Robert P.
TI Identification of polymerase and processivity inhibitors of vaccinia DNA
synthesis using a stepwise screening approach
SO ANTIVIRAL RESEARCH
LA English
DT Article
DE Poxvirus; Vaccinia virus; DNA polymerase; Processivity factor; Antiviral
inhibitors; High-throughput screening; Rapid plate assay; Smallpox
ID ANTIBACTERIAL AGENT FENTICHLOR; ANTIPOXVIRUS COMPOUND ST-246;
TRITYL-L-CYSTEINE; STAPHYLOCOCCUS-AUREUS; SMALLPOX VACCINATION;
ESCHERICHIA-COLI; PROTEIN INTERACTIONS; ANTI-MICROBIALS; SLIDING CLAMPS;
UNITED-STATES
AB Nearly all DNA polymerases require processivity factors to ensure continuous incorporation of nucleotides. Processivity factors are specific for their cognate DNA polymerases. For this reason, the vaccinia DNA polymerase (E9) and the proteins associated with processivity (A20 and D4) are excellent therapeutic targets. In this study, we show the utility of stepwise rapid plate assays that (i) screen for compounds that block vaccinia DNA synthesis, (ii) eliminate trivial inhibitors, e.g. DNA intercalators, and (iii) distinguish whether inhibitors are specific for blocking DNA polymerase activity or processivity. The sequential plate screening of 2222 compounds from the NO Diversity Set library yielded a DNA polymerase inhibitor (NSC 55636) and a processivity inhibitor (NSC 123526) that were capable of reducing vaccinia viral plaques with minimal cellular cytotoxicity. These compounds are predicted to block cellular infection by the smallpox virus, variola, based on the very high sequence identity between A20, D4 and E9 of vaccinia and the corresponding proteins of variola. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Silverman, Janice Elaine Y.; Ciustea, Mihai; Bender, Florent; Ricciardi, Robert P.] Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA.
[Shudofsky, Abigail M. Druck] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
[Shoemaker, Robert H.] NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21701 USA.
[Ricciardi, Robert P.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
RP Ricciardi, RP (reprint author), Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA.
EM ricciardi@biochem.dental.upenn.edu
FU NIH [EID T32]; NIAID [U54-AI057168 MARCE]
FX The authors thank Dr. G.H. Cohen and Dr. R.J. Eisenberg (University of
Pennsylvania) for kindly providing the viral stocks and HSV antibodies,
Dr. S.N. Isaac (University of Pennsylvania) for helpful advice on the
plaque assay and Dr. M.J. Currens (NCI) for helping to obtain compounds
from the NCI Diversity Set library. A.M.D.S.was supported by an NIH EID
T32 training grant. This study was supported by NIAID U54-AI057168 MARCE
grant.
NR 66
TC 9
Z9 9
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
J9 ANTIVIR RES
JI Antiviral Res.
PD NOV
PY 2008
VL 80
IS 2
BP 114
EP 123
DI 10.1016/j.antiviral.2008.05.010
PG 10
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA 371FX
UT WOS:000260818300005
PM 18621425
ER
PT J
AU Krajewski, P
Ammann, M
Bartuskova, M
Duffa, C
Filistovic, V
Homma, T
Kanyar, B
Malatova, I
Nedveckaite, T
Simon, S
Vlasov, O
Webbe-Wood, D
Zvonova, I
AF Krajewski, P.
Ammann, M.
Bartuskova, M.
Duffa, C.
Filistovic, V.
Homma, T.
Kanyar, B.
Malatova, I.
Nedveckaite, T.
Simon, S.
Vlasov, O.
Webbe-Wood, D.
Zvonova, I.
TI Validation of environmental transfer models and assessment of the
effectiveness of countermeasures using data on I-131 releases from
Chernobyl
SO APPLIED RADIATION AND ISOTOPES
LA English
DT Article; Proceedings Paper
CT International Conference on Environmental Radioactivity - From
Measurements and Assessments to Regulation
CY APR 23-27, 2007
CL Vienna, AUSTRIA
SP IAEA, Dept Nucl Sci & Applicat, Dept Nucl Safety & Secur
DE environmental assessment modelling; iodine-131; Chernobyl releases;
thyroid doses; dose reconstruction; effectiveness of countermeasures
ID THYROID-CANCER; RECONSTRUCTION; ACCIDENT; BYELARUS; POPULATION; FALLOUT;
RUSSIA
AB The studies undertaken by the I-131 Working Group, part of the International Atomic Energy Agency's EMRAS (Environmental Modelling for Radiation Safety) programme, were focused primarily on evaluating the predictive capability of environmental models. Particular emphasis was placed on applying models to evaluate the effectiveness of countermeasures. (C) 2008 IAEA. Published by Elsevier Ltd. All rights reserved.
C1 [Krajewski, P.] Cent Lab Radiol Protect, Warsaw, Poland.
[Ammann, M.; Homma, T.] Radiat & Nucl Safety Author STUK, Helsinki, Finland.
[Bartuskova, M.] Natl Radiat Protect Inst SURO, Ostrava, Czech Republic.
[Duffa, C.] IRSN, Fontenay Aux Roses, France.
[Filistovic, V.; Nedveckaite, T.] Lithuania Acad Sci, Inst Phys, LT-232600 Vilnius, Lithuania.
[Kanyar, B.] Univ Pannonia, Veszprem, Hungary.
[Malatova, I.] Natl Radiat Protect Inst SURO, Prague, Czech Republic.
[Simon, S.] NCI, Bethesda, MD 20892 USA.
[Vlasov, O.] RAMS, MRRC, Obninsk, Russia.
[Webbe-Wood, D.] FSA, London, England.
[Zvonova, I.] Minist Publ Hlth, Inst Radiat Hyg, St Petersburg, Russia.
RP Krajewski, P (reprint author), Cent Lab Radiol Protect, Warsaw, Poland.
EM krajewski@clor.waw.pl
FU PHS HHS [263-MQ-408981]
NR 14
TC 2
Z9 3
U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0969-8043
J9 APPL RADIAT ISOTOPES
JI Appl. Radiat. Isot.
PD NOV
PY 2008
VL 66
IS 11
BP 1730
EP 1735
DI 10.1016/j.apradiso.2007.11.022
PG 6
WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology,
Nuclear Medicine & Medical Imaging
SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 357GK
UT WOS:000259834100044
PM 18541435
ER
PT J
AU Schultz, ZD
Stranick, SJ
Levin, IW
AF Schultz, Zachary D.
Stranick, Stephan J.
Levin, Ira W.
TI Tip-Enhanced Raman Spectroscopy and Imaging: An Apical Illumination
Geometry
SO APPLIED SPECTROSCOPY
LA English
DT Article
DE Tip-enhanced Raman spectroscopy; TERS; Raman spectroscopy; Near field;
Microscopy; Imaging; Vibrational spectroscopy; Radial polarization
ID FIELD; MICROSCOPY; SURFACE; SCATTERING; NANOSCALE; AU(111); PROBES;
BEAMS
AB Results are presented illustrating the use of tip-enhanced Raman spectroscopy (TERS) and imaging in a top-illumination geometry. A radially polarized beam is used to generate an electric field component in the direction of beam propagation, normal to the surface, resulting in a 5X increased enhancement compared to a linearly polarized beam. This multiplicative enhancement facilitates a discrimination of tile near-field signal from the far-field Raman background. The top illumination configuration facilitates the application of TERS for investigating molecules on a variety of surfaces, such as All, glass, and Si. The near-field Raman spectra of Si(100), rhodamine B, brilliant cresyl blue, and single wall carbon nanotubes are presented. Sufficient enhancement is obtained to permit a sub-diffraction-limited resolution Raman imaging of the surface distribution of large bundles of carbon nanotubes of various diameters.
C1 [Schultz, Zachary D.; Levin, Ira W.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Stranick, Stephan J.] Natl Inst Stand & Technol, Surface & Microanal Sci Div, Gaithersburg, MD 20899 USA.
RP Levin, IW (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM iwl@helix.nih.gov
RI Schultz, Zachary/L-5724-2013
OI Schultz, Zachary/0000-0003-1741-8801
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institutes of Health
FX We acknowledge support from the intramural program of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health.
NR 28
TC 15
Z9 15
U1 2
U2 20
PU SOC APPLIED SPECTROSCOPY
PI FREDERICK
PA 201B BROADWAY ST, FREDERICK, MD 21701 USA
SN 0003-7028
J9 APPL SPECTROSC
JI Appl. Spectrosc.
PD NOV
PY 2008
VL 62
IS 11
BP 1173
EP 1179
PG 7
WC Instruments & Instrumentation; Spectroscopy
SC Instruments & Instrumentation; Spectroscopy
GA 376QO
UT WOS:000261198300003
PM 19007457
ER
PT J
AU Guyer, AE
Lau, JYF
McClure-Tone, EB
Parrish, J
Shiffrin, ND
Reynolds, RC
Chen, G
Blair, RJR
Leibenluft, E
Fox, NA
Ernst, M
Pine, DS
Nelson, EE
AF Guyer, Amanda E.
Lau, Jennifer Y. F.
McClure-Tone, Erin B.
Parrish, Jessica
Shiffrin, Nina D.
Reynolds, Richard C.
Chen, Gang
Blair, R. J. R.
Leibenluft, Ellen
Fox, Nathan A.
Ernst, Monique
Pine, Daniel S.
Nelson, Eric E.
TI Amygdala and Ventrolateral Prefrontal Cortex Function During Anticipated
Peer Evaluation in Pediatric Social Anxiety
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID MASKED ANGRY FACES; FACIAL EXPRESSIONS; DISORDERS; PHOBIA; ADOLESCENTS;
ACTIVATION; BEHAVIOR; CHILDREN; HUMANS; FMRI
AB Context: Amygdala and ventrolateral prefrontal cortex (vlPFC) dysfunction manifests in adolescents with anxiety disorders when they view negatively valenced stimuli in threatening contexts. Such fear-circuitry dysfunction may also manifest when anticipated social evaluation leads socially anxious adolescents to misperceive peers as threatening.
Objective: To determine whether photographs of negatively evaluated smiling peers viewed during anticipated social evaluation engage the amygdala and vlPFC differentially in adolescents with and without social anxiety.
Design: Case-control study.
Setting: Government clinical research institute.
Participants: Fourteen adolescents with anxiety disorders associated with marked concerns of social evaluation and 14 adolescents without a psychiatric diagnosis matched on sex, age, intelligence quotient, and socioeconomic status.
Main Outcome Measures: Blood oxygenation level dependent signal measured with event-related functional magnetic resonance imaging. Before and during neuroimaging scans, participants anticipating social evaluation completed peer- and self-appraisals. Event-related analyses were tailored to participants' ratings of specific peers.
Results: Participants classified 40 pictures of same-age peers as ones with whom they did or did not want to engage in a social interaction. Anxious adolescents showed greater amygdala activation than healthy adolescents when anticipating evaluation from peers previously rated as undesired for an interaction. Psychophysiological interaction connectivity analyses also revealed a significant positive association between amygdala and vlPFC activation in anxious vs healthy adolescents in response to these stimuli.
Conclusions: Anticipating social evaluation from negatively perceived peers modulates amygdala and vlPFC engagement differentially in anxious and healthy adolescents. Amygdala and vlPFC dysfunction manifests in adolescent anxiety disorders in specific contexts of anticipated peer evaluation.
C1 [Guyer, Amanda E.; Lau, Jennifer Y. F.; Shiffrin, Nina D.; Blair, R. J. R.; Leibenluft, Ellen; Ernst, Monique; Pine, Daniel S.; Nelson, Eric E.] NIMH, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA.
[McClure-Tone, Erin B.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA.
[Parrish, Jessica] Catholic Univ, Dept Psychol, Washington, DC USA.
[Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
RP Guyer, AE (reprint author), NIMH, Mood & Anxiety Program, NIH, 15K N Dr,Room 208, Bethesda, MD 20892 USA.
EM amandaguyer@mail.nih.gov
RI Nelson, Eric/B-8980-2008
OI Nelson, Eric/0000-0002-3376-2453
FU Intramural NIH HHS [Z01 MH002781-06]; NIMH NIH HHS [R29 MH057503-03, K99
MH080076, R00 MH080076, R29 MH057503-04]
NR 49
TC 151
Z9 154
U1 15
U2 41
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-990X
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD NOV
PY 2008
VL 65
IS 11
BP 1303
EP 1312
DI 10.1001/archpsyc.65.11.1303
PG 10
WC Psychiatry
SC Psychiatry
GA 368DA
UT WOS:000260600300008
PM 18981342
ER
PT J
AU Murphy, AJ
Woollard, KJ
Hoang, A
Mukhamedova, N
Stirzaker, RA
McCormick, SPA
Remaley, AT
Sviridov, D
Chin-Dusting, J
AF Murphy, Andrew J.
Woollard, Kevin J.
Hoang, Anh
Mukhamedova, Nigora
Stirzaker, Roslynn A.
McCormick, Sally P. A.
Remaley, Alan T.
Sviridov, Dmitri
Chin-Dusting, Jaye
TI High-Density Lipoprotein Reduces the Human Monocyte Inflammatory
Response
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE apolipoprotein A-I; CD11b; monocyte; ABCA1; Tangier
ID APOLIPOPROTEIN-A-I; HUMAN ENDOTHELIAL-CELLS; CASSETTE TRANSPORTER A1;
CORONARY HEART-DISEASE; C-REACTIVE PROTEIN; CHOLESTEROL EFFLUX; ADHESION
MOLECULES; HELICAL PEPTIDES; LIPID EFFLUX; ICAM-1 CD54
AB Objective-Whereas the anti-inflammatory effects of high-density lipoprotein (HDL) on endothelial cells are well described, such effects on monocytes are less studied.
Methods and Results-Human monocytes were isolated from whole blood followed by assessment of CD11b activation/expression and cell adhesion under shear-flow. HDL caused a dose-dependent reduction in the activation of CD11b induced by PMA or receptor-dependent agonists. The constituent of HDL responsible for the antiinflammatory effects on CD11b activation was found to be apolipoprotein A-I (apoA-I). Cyclodextrin, but not cyclodextrin/cholesterol complex, also inhibited PMA-induced CD11b activation implicating cholesterol efflux as the main mechanism. This was further confirmed with the demonstration that cholesterol content of lipid rafts diminished after treatment with the cholesterol acceptors. Blocking ABCA1 with an anti-ABCA1 antibody abolished the effect of apoA-I. Furthermore, monocytes derived from a Tangier disease patient definitively confirmed the requirement of ABCA1 in apoA-I mediated CD11b inhibition. The antiinflammatory effects of apoA-I were also observed in functional models including cell adhesion to an endothelial cell monolayer, monocytic spreading under shear flow, and transmigration.
Conclusions-HDL and apoA-I exhibit an antiinflammatory effect on human monocytes by inhibiting activation of CD11b. ApoA-I acts through ABCA1, whereas HDL may act through several receptors. (Arterioscler Thromb Vasc Biol. 2008; 28: 2071-2077)
C1 [Murphy, Andrew J.; Woollard, Kevin J.; Chin-Dusting, Jaye] Baker Heart Res Inst, Labs Vasc Pharmacol, Melbourne, Vic 8008, Australia.
[Hoang, Anh; Mukhamedova, Nigora; Sviridov, Dmitri] Baker Heart Res Inst, Lab Lipoprot & Atherosclerosis, Melbourne, Vic 8008, Australia.
[Stirzaker, Roslynn A.] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia.
[McCormick, Sally P. A.] Univ Otago, Dept Biochem, Dunedin, Otago, New Zealand.
[Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Chin-Dusting, J (reprint author), Baker Heart Res Inst, Labs Vasc Pharmacol, POB 6492, Melbourne, Vic 8008, Australia.
EM jaye.chin-dusting@baker.edu.au
RI Sviridov, Dmitri/E-7943-2010;
OI Woollard, Kevin/0000-0002-9839-5463
FU Actelion Ltd, Sydney; Australian National Heart Foundation Research
Fellow; Australian National Health; Medical Research Council
FX A.J.M. is supported by an industry scholarship form Actelion Ltd,
Sydney. K.J.W. is an Australian National Heart Foundation Research
Fellow. D. S. and J.C.-D. are Senior Research Fellows of the Australian
National Health and Medical Research Council.
NR 51
TC 167
Z9 174
U1 1
U2 11
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 NOV
PY 2008
VL 28
IS 11
BP 2071
EP U313
DI 10.1161/ATVBAHA.108.168690
PG 23
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 363NK
UT WOS:000260273800030
PM 18617650
ER
PT J
AU Fujimura, Y
Hwang, PM
Trout, H
Kozloff, L
Imaizumi, M
Innis, RB
Fujita, M
AF Fujimura, Yota
Hwang, Paul M.
Trout, Hugh, III
Kozloff, Louis
Imaizumi, Masao
Innis, Robert B.
Fujita, Masahiro
TI Increased peripheral benzodiazepine receptors in arterial plaque of
patients with atherosclerosis: An autoradiographic study with [(3)H]PK
11195
SO ATHEROSCLEROSIS
LA English
DT Article
DE Atherosclerosis; Macrophage; Peripheral benzodiazepine receptor;
[(3)H]PK 11195; Imaging; Nuclear medicine; CD68
ID BRAIN; MACROPHAGES; INFLAMMATION; BINDING
AB Inflammation in atherosclerotic plaques makes them unstable and can cause thrombosis. Therefore, it is important to detect macrophage activity for clinical management of atherosclerosis. Peripheral benzodiazepine receptor (PBR) is expressed in various tissue and organs including macrophages. In this study, we tested whether inflammation characterized by macrophage infiltration can be detected by PBR binding. Six patients diagnosed as carotid atherosclerosis underwent endarterectomy. Using the fresh frozen sections, presence of PBRs and macrophages was examined by in vitro autoradiography using [(3)H]PK 11195 and immunohistochemical staining of CD68, respectively. All sections showed specific binding of [(3)H]PK 11195, and the staining with CD68 indicating macrophage infiltration. Density and distribution of PBR detected by [(3)H]PK 11195 autoradiography were consistent with those of the immunohistochemical staining.
In conclusion, this Study demonstrated that macrophage and inflammatory activity in atherosclerotic plaque can be imaged specifically by the binding of PBR indicating future application of PET imaging for PBR. Published by Elsevier Ireland Ltd.
C1 [Fujimura, Yota; Imaizumi, Masao; Innis, Robert B.; Fujita, Masahiro] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Hwang, Paul M.] NHLBI, Cardiol Branch, Bethesda, MD 20892 USA.
[Trout, Hugh, III; Kozloff, Louis] Suburban Hosp, Bethesda, MD USA.
RP Fujimura, Y (reprint author), NIMH, Mol Imaging Branch, Bldg 31,Room B2-B37,31 Ctr Dr, Bethesda, MD 20892 USA.
EM fujimuray@mail.nih.gov
FU NIMH [Z01-MH-002852-03]
FX This research was supported by the Intramural Program of NIMH (project #
Z01-MH-002852-03). We thank David Mozley, MD (Merck Research Laboratory)
for suggesting the potential utility of PBR imaging as a marker of
inflammation in vulnerable plaque.
NR 16
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U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD NOV
PY 2008
VL 201
IS 1
BP 108
EP 111
DI 10.1016/j.atherosclerosis.2008.02.032
PG 4
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 377QN
UT WOS:000261265800013
PM 18433754
ER
PT J
AU Levitzky, YS
Guo, CY
Rong, J
Larson, MG
Walter, RE
Keaney, JF
Sutherland, PA
Vasan, A
Lipinska, I
Evans, JC
Benjamin, EJ
AF Levitzky, Yamini S.
Guo, Chao-Yu
Rong, Jian
Larson, Martin G.
Walter, Robert E.
Keaney, John F., Jr.
Sutherland, Patrice A.
Vasan, Aditi
Lipinska, Izabella
Evans, Jane C.
Benjamin, Emelia J.
TI Relation of smoking status to a panel of inflammatory markers: The
Framingham offspring
SO ATHEROSCLEROSIS
LA English
DT Article
DE Smoking; Inflammation; Cardiovascular disease; Epidemiology
ID CARDIOVASCULAR-DISEASE RISK; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN;
CIGARETTE-SMOKING; OXIDATIVE STRESS; EXPOSURE; ATHEROSCLEROSIS;
POLYMORPHISMS; ASSOCIATIONS; INEQUALITIES
AB Aims: We sought to investigate the hypothesis that smoking is accompanied by systemic inflammation.
Methods and results: We examined the relation of smoking to 11 systemic inflammatory markers in Framingham Study participants (n = 2944) mean age 60 years, 55% women, 12% ethnic minorities) examined from 1998-2001. The cohort was divided into never (n = 1149), former (n = 1424), and current smokers with last cigarette >6 h (n = 134) or <= 6 h (n = 237) prior to phlebotomy. In multivariable-adjusted models there were significant overall between-smoking group differences (defined as p < 0.0045 to account for multiple testing) for every inflammatory 9 C marker tested, except for serum CD40 ligand (CD40L), myeloperoxidase (MPO) and tumor necrosis factor receptor-2 (TNFR2). With multivariable-adjustment, pair-wise comparisons with never smokers revealed that former smokers had significantly lower concentrations of plasma CD40L (p < 0.0001) and higher concentrations of (CRP) C-reactive protein (p = 0.002).
Conclusions: As opposed to never smokers, those with acute cigarette smoke exposure (<= 6h) had significantly higher concentrations of all markers p < 0.0001) except serum CD40L, MPO, and TNFR2; plasma CD40L were significantly lower. Compared with never smokers, cigarette snickers have significantly elevated concentrations of most circulating inflammatory markers, consistent with the hypothesis that smoking is associated with a systemic inflammatory state. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Benjamin, Emelia J.] Boston Univ, NHLBI, Framingham Heart Study, Sch Med, Framingham, MA 01702 USA.
[Guo, Chao-Yu; Larson, Martin G.; Evans, Jane C.] Boston Univ, Sch Med, Dept Math Stat & Consulting, Boston, MA 02118 USA.
[Keaney, John F., Jr.; Lipinska, Izabella; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Keaney, John F., Jr.; Benjamin, Emelia J.] Boston Med Ctr, Div Cardiol, Boston, MA USA.
[Walter, Robert E.] Boston Med Ctr, Div Pulm & Crit Care, Boston, MA USA.
[Levitzky, Yamini S.] Case Western Reserve Univ, Heart & Vasc Ctr, Cleveland, OH 44106 USA.
RP Benjamin, EJ (reprint author), Boston Univ, NHLBI, Framingham Heart Study, Sch Med, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM emelia@bu.edu
OI Larson, Martin/0000-0002-9631-1254; Walter, Robert/0000-0003-4931-5049;
Benjamin, Emelia/0000-0003-4076-2336
FU National Heart, Lung, and Blood Institute's Framingham Heart [N01-HC
25195, RO1 HL076784, RO1 HL064753, RO1 AG028321]; Flight Attendants
Medical Research Institute's Young Clinical Scientist Award
FX This work was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study N01-HC 25195; RO1 HL076784; RO1
HL064753, RO1 AG028321; and the Flight Attendants Medical Research
Institute's Young Clinical Scientist Award (Dr. Walter).
NR 43
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Z9 44
U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD NOV
PY 2008
VL 201
IS 1
BP 217
EP 224
DI 10.1016/j.atherosclerosis.2007.12.058
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 377QN
UT WOS:000261265800029
PM 18289552
ER
PT J
AU Evrony, HK
Ganiban, JM
Ulbricht, J
Haddad, SK
Lichtenstein, P
Spotts, EL
Reiss, D
Neiderhiser, JM
AF Evrony, Hilah K.
Ganiban, Jody M.
Ulbricht, J.
Haddad, Suzanne K.
Lichtenstein, Paul
Spotts, Erica L.
Reiss, David
Neiderhiser, Jenae M.
TI Retrospective Perceptions of Parenting and Marital Satisfaction: Genetic
and Environmental Influences
SO BEHAVIOR GENETICS
LA English
DT Meeting Abstract
CT 38th Annual Meeting of the Behavior-Genetics-Association
CY JUN 28, 2008
CL Louisville, KY
SP Behav Genet Assoc
C1 [Evrony, Hilah K.; Ganiban, Jody M.; Ulbricht, J.; Haddad, Suzanne K.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA.
[Lichtenstein, Paul] Karolinska Inst, Stockholm, Sweden.
[Spotts, Erica L.] NIA, Bethesda, MD 20892 USA.
[Neiderhiser, Jenae M.] Penn State Univ, Dept Psychol, College Stn, TX USA.
[Reiss, David] Yale Univ, New Haven, CT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-8244
J9 BEHAV GENET
JI Behav. Genet.
PD NOV
PY 2008
VL 38
IS 6
BP 625
EP 626
PG 2
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA 367FX
UT WOS:000260539000058
ER
PT J
AU Ganiban, JM
Jacobs, T
Spotts, EL
Lichtenstein, P
Reiss, D
Neiderhiser, J
AF Ganiban, Jody M.
Jacobs, Tova
Spotts, Erica L.
Lichtenstein, Paul
Reiss, David
Neiderhiser, Jenae
TI Family Influences on Personality
SO BEHAVIOR GENETICS
LA English
DT Meeting Abstract
CT 38th Annual Meeting of the Behavior-Genetics-Association
CY JUN 28, 2008
CL Louisville, KY
SP Behav Genet Assoc
C1 [Ganiban, Jody M.; Jacobs, Tova] George Washington Univ, Dept Psychol, Washington, DC 20052 USA.
[Spotts, Erica L.] NIA, Behav & Social Sci Res Program, Bethesda, MD 20892 USA.
[Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Stat, Stockholm, Sweden.
[Reiss, David] Yale Univ, New Haven, CT USA.
[Neiderhiser, Jenae] Penn State Univ, Dept Psychol, State Coll, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-8244
J9 BEHAV GENET
JI Behav. Genet.
PD NOV
PY 2008
VL 38
IS 6
BP 628
EP 628
PG 1
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA 367FX
UT WOS:000260539000066
ER
PT J
AU Grassmann, R
Jeang, KT
AF Grassmann, Ralph
Jeang, Kuan-Teh
TI The roles of microRNAs in mammalian virus infection
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE MicroRNA; Virus replication; Innate immunity; Post-transcriptional
regulation; Viral gene expression; Virus-host interaction
ID SARCOMA-ASSOCIATED HERPESVIRUS; EPSTEIN-BARR-VIRUS; SMALL INTERFERING
RNAS; VIRAL GENE-EXPRESSION; HIV-1 TAR ELEMENT; ANTIVIRAL DEFENSE;
ENCODED MICRORNAS; ANTISENSE TRANSCRIPTS; CELLULAR MICRORNAS; SILENCING
PATHWAY
AB MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that are important for the control of a multitude of critical processes in mammalian cells. Increasing evidence supports that miRNAs also have important functions in viral replication and may be used by host cells to control viral infection. Expression of miRNAs has been reported for various groups of viruses including herpesviruses, small DNA viruses and retroviruses. The recent identification of target genes regulated by some of these viral miRNAs suggests that they may function in the control of lytic and latent viral replication, in the limitation of antiviral responses, in the inhibition of apoptosis, and in the stimulation of cellular growth. In this review, we summarize in brief recent findings on the antiviral activities of cellular miRNAs and the viral counter-responses to the cell's RNAi restriction. Published by Elsevier B.V.
C1 [Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Grassmann, Ralph] Univ Erlangen Nurnberg, Inst Clin & Mol Virol, D-91054 Erlangen, Germany.
RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM grassmann@viro.med.uni-erlangen.de; kj7e@nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU EU; INCA [LSHC-CF-2005-018704]; Deutsche Forschungsgemeinschaft
[DFG-GRK1071, GR 1224/3-1]; MAID; NIH; Intramural AIDS Targeted
Antiviral Program
FX Work in RG's laboratory is supported by grants from Wilhelm
Sander-Stiftung, EU (INCA, LSHC-CF-2005-018704) and by Deutsche
Forschungsgemeinschaft (DFG-GRK1071, GR 1224/3-1). Work in KTj's
laboratory is supported by intramural funding from MAID, NIH; and by the
Intramural AIDS Targeted Antiviral Program from the Office of the
Director, NIH.
NR 100
TC 76
Z9 80
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD NOV
PY 2008
VL 1779
IS 11
BP 706
EP 711
DI 10.1016/j.bbagrm.2008.05.005
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 377UF
UT WOS:000261275500010
PM 18549828
ER
PT J
AU Voss, TC
Hager, GL
AF Voss, Ty C.
Hager, Gordon L.
TI Visualizing chromatin dynamics in intact cells
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Review
DE Chromatin Nuclear receptor; Dynamics; Living cells; Hit-and-run;
Transcription
ID MAMMARY-TUMOR VIRUS; ESTROGEN-RECEPTOR-ALPHA; RNA-POLYMERASE-II; GREEN
FLUORESCENT PROTEIN; LIGAND-SPECIFIC DYNAMICS; INTERACTIONS IN-VIVO;
GLUCOCORTICOID-RECEPTOR; LIVING CELLS; MOLECULAR CHAPERONES; NUCLEAR
RECEPTORS
AB Chromatin and associated regulatory proteins regulate gene expression in the natural environment of the intact cell nucleus. Specific combinations of DNA-binding transcription factors and recruited coregulatory proteins alter the conformation of chromatin at promoters and enhancers of target genes to stimulate or repress transcription. The dynamic nature of the regulatory proteins active in these processes allows the cell to modulate gene expression very rapidly, an important feature in many physiological processes. Live cell imaging and photobleaching studies of fluorescently-tagged proteins reveal that many transcription factors and other chromatin-associated proteins rapidly move through the nucleoplasm. Transcription factors also transiently interact with specific regulatory sequences in chromatin, suggesting that gene activation does not require the formation of stable long-lived regulatory complexes on the chromatin. In this review we discuss how dynamic interactions allow transcriptional regulatory proteins find their targets within the nucleus, alter target chromatin structure, and modulate physiological gene expression. Published by Elsevier B.V.
C1 [Voss, Ty C.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602,41 Lib Dr, Bethesda, MD 20892 USA.
EM hagerg@exchange.nih.gov
FU NIH; National Cancer Institute; 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. We
would like to acknowledge the assistance of Tatiana Karpova, manager of
the LRBGE Fluorescence Imaging Facility.
NR 77
TC 18
Z9 18
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD NOV
PY 2008
VL 1783
IS 11
SI SI
BP 2044
EP 2051
DI 10.1016/j.bbamcr.2008.06.022
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 372PD
UT WOS:000260912600002
PM 18675855
ER
PT J
AU Dowd, TL
Li, L
Gundberg, CM
AF Dowd, T. L.
Li, L.
Gundberg, C. M.
TI The H-1 NMR structure of bovine Pb2+-osteocalcin and implications for
lead toxicity
SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
LA English
DT Article
DE Osteocalcin; NMR; Pb2+; Lead toxicity
ID GAMMA-CARBOXYGLUTAMIC ACID; OSTEOCALCIN-DEFICIENT MICE; OSTEOBLASTIC
BONE-CELLS; X-RAY-FLUORESCENCE; BINDING-PROPERTIES; CRYSTAL-STRUCTURE;
CHEMICAL-SHIFT; ELDERLY-MEN; NMR-SPECTRA; PROTEIN
AB Structural information on the effect of Pb2+ on proteins under physiologically relevant conditions is largely unknown. We have previously shown that low levels of lead increased the amount of osteocalcin bound to hydroxyapatite (BBA 1535:153). This suggested that lead induced a more compact structure in the protein. We have determined the 3D structure of Pb2+-osteocalcin (49 amino acids), a bone protein from a target tissue, using H-1 2D NMR techniques. Lead, at a stoichiometry of only 1:1, induced a similar fold in the protein as that induced by Ca2+ at a stoichiometry of 3:1. The structure consisted of an unstructured N-terminus and an ordered C-terminal consisting of a hydrophobic core (residues 16-49). The genetic algorithm-molecular dynamics simulation predicted the lead ion was coordinated by the Gla 24 and Gla 21 residues. It is proposed that mineral binding occurs via uncoordinated Gla oxygen ions binding to calcium in hydroxyapatite. A comparison of Pb2+- and Ca2+-osteocalcin suggests Pb2+, at a lower stoichiometry, may induce similar conformational changes in proteins and subsequent molecular processes normally controlled by calcium alone. This may contribute to a molecular mechanism of lead toxicity for calcium binding proteins. Lead exposure may alter the amount of mineral bound osteocalcin and contribute to abnormal bone remodeling. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Dowd, T. L.] CUNY Brooklyn Coll, Dept Chem, Brooklyn, NY 11210 USA.
[Li, L.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Gundberg, C. M.] Yale Univ, Sch Med, Dept Orthoped, New Haven, CT USA.
RP Dowd, TL (reprint author), CUNY Brooklyn Coll, Dept Chem, Room 359 NE,2900 Bedford Ave, Brooklyn, NY 11210 USA.
EM TDowd@brooklyn.cuny.edu
FU NIH [ES-9032, AR-38460]
FX The authors would like to thank Drs. Mark Girvin, Sean Cahill and John
Rosen for their technical advice and helpful discussions. Support for
this project was provided by NIH grant ES-9032 to T.D., and NIH grant
AR-38460 to C.G. The authors would also like to thank the Analytical
Ultracentrifugation Facility of the Albert Einstein College of Medicine
for conducting the sedimentation equilibrium experiments.
NR 70
TC 5
Z9 5
U1 5
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-9639
J9 BBA-PROTEINS PROTEOM
JI BBA-Proteins Proteomics
PD NOV
PY 2008
VL 1784
IS 11
BP 1534
EP 1545
DI 10.1016/j.bbapap.2008.08.010
PG 12
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 374CC
UT WOS:000261019000007
PM 18793762
ER
PT J
AU Roy, SW
Irimia, M
AF Roy, Scott William
Irimia, Manuel
TI Comment on "When good transcripts go bad: artifactual RT-PCR 'splicing'
and genome analysis" response
SO BIOESSAYS
LA English
DT Letter
ID INTRON GAIN
C1 [Roy, Scott William] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Irimia, Manuel] Univ Barcelona, Fac Biol, Dept Genet, Barcelona, Spain.
RP Roy, SW (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA.
EM scottwroy@gmail.com; mirimia@gmail.com
RI Irimia, Manuel/E-3040-2010
NR 10
TC 0
Z9 0
U1 0
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0265-9247
J9 BIOESSAYS
JI Bioessays
PD NOV-DEC
PY 2008
VL 30
IS 11-12
BP 1257
EP 1258
DI 10.1002/bies.20841
PG 2
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 372PF
UT WOS:000260912800026
ER
PT J
AU de Souza, RF
Anantharaman, V
de Souza, SJ
Aravind, L
Gueiros, FJ
AF de Souza, Robson Francisco
Anantharaman, Vivek
de Souza, Sandro Jose
Aravind, L.
Gueiros-Filho, Frederico J.
TI AMIN domains have a predicted role in localization of diverse
periplasmic protein complexes
SO BIOINFORMATICS
LA English
DT Article
ID MULTIPLE SEQUENCE ALIGNMENT; ESCHERICHIA-COLI; ARCHITECTURE; SECRETIN;
KALIGN; FTSN
AB We describe AMIN (Amidase N-terminal domain), a novel protein domain found specifically in bacterial periplasmic proteins. AMIN domains are widely distributed among peptidoglycan hydrolases and transporter protein families. Based on experimental data, contextual information and phyletic profiles, we suggest that AMIN domains mediate the targeting of periplasmic or extracellular proteins to specific regions of the bacterial envelope.
C1 [de Souza, Robson Francisco; Gueiros-Filho, Frederico J.] Univ Sao Paulo, Dept Bioquim, Sao Paulo, Brazil.
[de Souza, Robson Francisco; de Souza, Sandro Jose] Ludwig Inst Canc Res, Sao Paulo Branch, Sao Paulo, Brazil.
[Anantharaman, Vivek; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Gueiros, FJ (reprint author), Univ Sao Paulo, Dept Bioquim, Sao Paulo, Brazil.
RI Gueiros-Filho, Frederico/D-2160-2013;
OI Gueiros-Filho, Frederico/0000-0001-5425-2439; Anantharaman,
Vivek/0000-0001-8395-0009
FU FAPESP [02/10616-4]; National Library of Medicine; CNPq (Brazil)
FX FAPESP 02/10616-4 (to F. J. G.-F.); National Library of Medicine
[Intramural funds. National Institutes of Health (to V. A. and L. A.)].
R. F. de. S. was a recipient of a doctoral fellowship from CNPq
(Brazil).
NR 19
TC 6
Z9 6
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 NOV 1
PY 2008
VL 24
IS 21
BP 2423
EP 2426
DI 10.1093/bioinformatics/btn449
PG 4
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 365BP
UT WOS:000260381200001
PM 18723522
ER
PT J
AU La Camera, G
Giugliano, M
Senn, W
Fusi, S
AF La Camera, Giancarlo
Giugliano, Michele
Senn, Walter
Fusi, Stefano
TI The response of cortical neurons to in vivo-like input current: theory
and experiment
SO BIOLOGICAL CYBERNETICS
LA English
DT Review
DE Integrate-and-fire; Mean field; Population density; Collective dynamics;
Attractor; Pyramidal; Fast spiking
ID INTEGRATE-AND-FIRE; SPIKE-FREQUENCY ADAPTATION; NEOCORTICAL PYRAMIDAL
NEURONS; PRIMATE TEMPORAL CORTEX; MULTIPLE TIME SCALES; WORKING-MEMORY;
IN-VIVO; SYNAPTIC INPUT; PERSISTENT ACTIVITY; PREFRONTAL CORTEX
AB The study of several aspects of the collective dynamics of interacting neurons can be highly simplified if one assumes that the statistics of the synaptic input is the same for a large population of similarly behaving neurons (mean field approach). In particular, under such an assumption, it is possible to determine and study all the equilibrium points of the network dynamics when the neuronal response to noisy, in vivo-like, synaptic currents is known. The response function can be computed analytically for simple integrate-and-fire neuron models and it can be measured directly in experiments in vitro. Here we review theoretical and experimental results about the neural response to noisy inputs with stationary statistics. These response functions are important to characterize the collective neural dynamics that are proposed to be the neural substrate of working memory, decision making and other cognitive functions. Applications to the case of time-varying inputs are reviewed in a companion paper (Giugliano et al. in Biol Cybern, 2008). We conclude that modified integrate-and-fire neuron models are good enough to reproduce faithfully many of the relevant dynamical aspects of the neuronal response measured in experiments on real neurons in vitro.
C1 [La Camera, Giancarlo] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Giugliano, Michele] Ecole Polytech Fed Lausanne, Lab Neural Microcircuitry, Lausanne, Switzerland.
[Giugliano, Michele] Univ Antwerp, Antwerp, Belgium.
[Senn, Walter] Univ Bern, Inst Physiol, Bern, Switzerland.
[Fusi, Stefano] Columbia Univ Coll Phys & Surg, Ctr Theoret Neurosci, New York, NY 10032 USA.
[Fusi, Stefano] Univ Zurich, ETH, Inst Neuroinformat, Zurich, Switzerland.
RP La Camera, G (reprint author), NIMH, Neuropsychol Lab, NIH, 49 Convent Dr,Rm 1B80, Bethesda, MD 20892 USA.
EM lacamerag@gmail.com
RI Giugliano, Michele/A-5666-2012; Senn, Walter/D-6308-2014; Fusi,
Stefano/E-9109-2011
OI Giugliano, Michele/0000-0003-2626-594X; Senn,
Walter/0000-0003-3622-0497; Fusi, Stefano/0000-0002-3035-6652
FU National Institute of Mental Health; European Commission
[FP6-2004-IST-FETPI-015879, LSHM-CT-2005-019055]; Swiss National Science
Foundation [3152A0-105966, PP00A-106556]
FX G. La Camera is supported by the Intramural Research Program of the
National Institute of Mental Health. M. Giugliano is supported by the
European Commission (FACETS Project FP6-2004-IST-FETPI-015879, EUSynapse
Project LSHM-CT-2005-019055). W. Senn is supported by the Swiss National
Science Foundation, grant No. 3152A0-105966. S. Fusi is supported by the
Swiss National Science Foundation, grant PP00A-106556. The views
expressed in this article do not necessarily represent the views of the
NIMH, NIH, or the US Government.
NR 155
TC 18
Z9 18
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-1200
J9 BIOL CYBERN
JI Biol. Cybern.
PD NOV
PY 2008
VL 99
IS 4-5
BP 279
EP 301
DI 10.1007/s00422-008-0272-7
PG 23
WC Computer Science, Cybernetics; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA 372YL
UT WOS:000260938100005
PM 18985378
ER
PT J
AU Giugliano, M
La Camera, G
Fusi, S
Senn, W
AF Giugliano, Michele
La Camera, Giancarlo
Fusi, Stefano
Senn, Walter
TI The response of cortical neurons to in vivo-like input current: theory
and experiment: II. Time-varying and spatially distributed inputs
SO BIOLOGICAL CYBERNETICS
LA English
DT Review
DE Populations of spiking neurons; Dynamics; Integrate-and-fire model;
Patch clamp; Calcium spikes
ID SPIKE-FREQUENCY ADAPTATION; POPULATION-DENSITY APPROACH; PRIMARY
VISUAL-CORTEX; PYRAMIDAL NEURONS; NEOCORTICAL NEURONS; FIRE NEURONS;
SHUNTING INHIBITION; SENSORY ADAPTATION; GAIN MODULATION;
NEURAL-NETWORKS
AB The response of a population of neurons to time-varying synaptic inputs can show a rich phenomenology, hardly predictable from the dynamical properties of the membrane's inherent time constants. For example, a network of neurons in a state of spontaneous activity can respond significantly more rapidly than each single neuron taken individually. Under the assumption that the statistics of the synaptic input is the same for a population of similarly behaving neurons (mean field approximation), it is possible to greatly simplify the study of neural circuits, both in the case in which the statistics of the input are stationary (reviewed in La Camera et al. in Biol Cybern, 2008) and in the case in which they are time varying and unevenly distributed over the dendritic tree. Here, we review theoretical and experimental results on the single-neuron properties that are relevant for the dynamical collective behavior of a population of neurons. We focus on the response of integrate-and-fire neurons and real cortical neurons to long-lasting, noisy, in vivo-like stationary inputs and show how the theory can predict the observed rhythmic activity of cultures of neurons. We then show how cortical neurons adapt on multiple time scales in response to input with stationary statistics in vitro. Next, we review how it is possible to study the general response properties of a neural circuit to time-varying inputs by estimating the response of single neurons to noisy sinusoidal currents. Finally, we address the dendrite-soma interactions in cortical neurons leading to gain modulation and spike bursts, and show how these effects can be captured by a two-compartment integrate-and-fire neuron. Most of the experimental results reviewed in this article have been successfully reproduced by simple integrate-and-fire model neurons.
C1 [Giugliano, Michele] Ecole Polytech Fed Lausanne, Lab Neural Microcircuitry, CH-1015 Lausanne, Switzerland.
[Giugliano, Michele] Univ Antwerp, Antwerp, Belgium.
[La Camera, Giancarlo] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Fusi, Stefano] Columbia Univ Coll Phys & Surg, Ctr Theoret Neurosci, New York, NY 10032 USA.
[Fusi, Stefano] Univ Zurich, ETH, Inst Neuroinformat, Zurich, Switzerland.
[Senn, Walter] Univ Bern, Dept Physiol, CH-3012 Bern, Switzerland.
RP Giugliano, M (reprint author), Ecole Polytech Fed Lausanne, Lab Neural Microcircuitry, Stn 15, CH-1015 Lausanne, Switzerland.
EM michele.giugliano@epfl.ch; michele.giugliano@ua.ac.be
RI Giugliano, Michele/A-5666-2012; Senn, Walter/D-6308-2014; Fusi,
Stefano/E-9109-2011
OI Giugliano, Michele/0000-0003-2626-594X; Senn,
Walter/0000-0003-3622-0497; Fusi, Stefano/0000-0002-3035-6652
FU European Commission; Intramural Research Program; NIMH; Swiss National
Science Foundation [PP00A-106556, 3152A0-105966]
FX M. Giugliano acknowledges support from the European Commission (FACETS
and EUSynapse Project). G. La Camera is supported by the Intramural
Research Program, NIMH. S. Fusi is supported by the Swiss National
Science Foundation, grant PPP00A-106556. W. Senn is supported by the
Swiss National Science Foundation, grant no. 3152A0-105966. The views
expressed in this article do not necessarily repesent the views of the
NIMH, NIH, or the United States Government.
NR 93
TC 9
Z9 9
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-1200
J9 BIOL CYBERN
JI Biol. Cybern.
PD NOV
PY 2008
VL 99
IS 4-5
BP 303
EP 318
DI 10.1007/s00422-008-0270-9
PG 16
WC Computer Science, Cybernetics; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA 372YL
UT WOS:000260938100006
PM 19011920
ER
PT J
AU Ceaser, AE
Goldberg, TE
Egan, MF
McMahon, RP
Weinberger, DR
Gold, JM
AF Ceaser, Alan E.
Goldberg, Terry E.
Egan, Michael F.
McMahon, Robert P.
Weinberger, Daniel R.
Gold, James M.
TI Set-Shifting Ability and Schizophrenia: A Marker of Clinical Illness or
an Intermediate Phenotype?
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE CANTAB; cognition; executive function; intermediate phenotype;
schizophrenia; set-shifting; working memory
ID EXECUTIVE FUNCTION; 1ST-EPISODE SCHIZOPHRENIA; PREPULSE INHIBITION;
PARKINSONS-DISEASE; COGNITIVE DEFICITS; HEALTHY-VOLUNTEERS;
WORKING-MEMORY; LIFE-SPAN; PERFORMANCE; RELATIVES
AB Background: Impairments of executive functioning, such as set-shifting ability, are seen as core deficits of schizophrenia and are of interest as candidate intermediate phenotype markers. The lntradimensional/Extradimensional (ID/ED) shift task offers a differentiated assessment of shifting from previously reinforced stimuli as well as shifting from previously reinforced features and has proven to be sensitive to the impairment seen in patients with schizophrenia.
Methods: We examined ID/ED performance in 147 patients with schizophrenia, 131 of their healthy siblings, and 303 healthy control subjects. Participants were recruited from local and national sources as volunteers for the Clinical Brain Disorders Branch/National Institute of Mental Health "sibling study".
Results: Nearly all control subjects (87%) finished the task successfully, as did 80% of siblings. In contrast only 54% of patients with schizophrenia were able to complete the task. Despite the apparent similarity of performance across the sibling and healthy comparison group, the two groups differed significantly in terms of the number of stages until failure. This difference, however, was not present at any particular stage or any other measure of performance.
Conclusions: Patients demonstrated robust ID/ED deficits. However, their siblings were minimally impaired, and this impairment did not seem to run in families. These results suggest that impairments on attentional set shifting assessed by ID/ED task are strongly associated with clinical illness, but these impairments are not a promising intermediate phenotype.
C1 [Ceaser, Alan E.; Goldberg, Terry E.; Egan, Michael F.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
[McMahon, Robert P.; Gold, James M.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
RP Weinberger, DR (reprint author), 10 Ctr Dr,MSC 1379,CRC Bldg,10 Bethesda, Bethesda, MD 20892 USA.
EM weinberd@mail.nih.gov
RI McMahon, Robert/C-5462-2009;
OI Ceaser, Alan/0000-0002-1554-6693
FU Intramural NIH HHS [Z01 MH002712-13]
NR 41
TC 46
Z9 46
U1 3
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD NOV 1
PY 2008
VL 64
IS 9
BP 782
EP 788
DI 10.1016/j.biopsych.2008.05.009
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 364WD
UT WOS:000260365300007
PM 18597738
ER
PT J
AU Karlsson, RM
Tanaka, K
Heilig, M
Holmes, A
AF Karlsson, Rose-Marie
Tanaka, Kohichi
Heilig, Markus
Holmes, Andrew
TI Loss of Glial Glutamate and Aspartate Transporter (Excitatory Amino Acid
Transporter 1) Causes Locomotor Hyperactivity and Exaggerated Responses
to Psychotomimetics: Rescue by Haloperidol and Metabotropic Glutamate
2/3 Agonist
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE GLAST; glutamate; mGlu2/3; NMDA; schizophrenia
ID PREFRONTAL CORTEX; RECEPTOR AGONIST; SCHIZOPHRENIA; KETAMINE; MICE;
PHENCYCLIDINE; TRANSMISSION; EXPRESSION; RAT
AB Background: Recent data suggest that excessive glutamatergic signaling in the prefrontal cortex may contribute to the pathophysiology of schizophrenia and that promoting presynaptic glutamate modulation via group II metabotropic glutamate 2/3 (mGlu2/3) receptor activation can exert antipsychotic efficacy. The glial glutamate and aspartate transporter (GLAST) (excitatory amino acid transporter 1 [EAAT1]) regulates extracellular glutamate levels via uptake into glia, but the consequences of GLAST dysfunction for schizophrenia are largely unknown.
Methods: We examined GLAST knockout mice (KO) for behaviors thought to model positive symptoms in schizophrenia (locomotor hyperactivity to novelty, exaggerated locomotor response to N-methyl-D-aspartate receptor [NMDAR] antagonism) and the ability of haloperidol and the mGlu2/3 agonist LY379268 to normalize novelty-induced hyperactivity.
Results: Glial glutamate and aspartate transporter KO consistently showed locomotor hyperactivity to a novel but not familiar environment, relative to wild-type (WT) mice. The locomotor hyperactivity-inducing effects of the NMDAR antagonist MK-801 was exaggerated in GLAST KO relative to WT. Treatment with haloperidol or LY379268 normalized novelty-induced locomotor hyperactivity in GLAST KO.
Conclusions: Schizophrenia-related abnormalities in GLAST KO raise the possibility that loss of GLAST-mediated glutamate clearance could be a pathophysiological risk factor for the disease. Our findings provide novel support for the hypothesis that glutamate dysregulation contributes to the pathophysiology of schizophrenia and for the antipsychotic potential of mGlu2/3 agonists.
C1 [Karlsson, Rose-Marie; Heilig, Markus] Natl Inst Alcohol Abuse & Alcoholism, Lab Clin & Translat Studies, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Tanaka, Kohichi] Tokyo Med & Dent Univ, Lab Mol Neurosci, Sch Biomed Sci, Bunkyo Ku, Tokyo, Japan.
[Tanaka, Kohichi] Tokyo Med & Dent Univ, Med Res Inst, Bunkyo Ku, Tokyo, Japan.
[Holmes, Andrew] Natl Inst Alcoholism & Alcohol Abuse, NIH, Lab Integrat Neurosci, Sect Behav Sci & Genet, Rockville, MD USA.
RP Karlsson, RM (reprint author), Natl Inst Alcohol Abuse & Alcoholism, Lab Clin & Translat Studies, Natl Inst Hlth, 10 Ctr Dr,Bldg 10,Room 1-5330, Bethesda, MD 20892 USA.
EM karlssonr@mail.nih.gov
OI Heilig, Markus/0000-0003-2706-2482
FU National Institute on Alcohol Abuse and Alcoholism (AMAA)-Intramural
Research Program (IRP); The Novartis Foundation (Japan); The Tokyo
Biochemical Research Foundation; Research Foundation of Opto-Science and
Technology; Ministry of Education, Culture, Sports, Science, and
Technology of Japan [20022013, 18053006]
FX This work was supported by the National Institute on Alcohol Abuse and
Alcoholism (AMAA)-Intramural Research Program (IRP). Tanaka was
supported by The Novartis Foundation (Japan) for the Promotion of
Science, Takeda Science Foundation, The Tokyo Biochemical Research
Foundation, Research Foundation of Opto-Science and Technology, and
Grants-in-Aids for Scientific Research on Prioriy Area (20022013 and
18053006) provided by the Ministry of Education, Culture, Sports,
Science, and Technology of Japan.
NR 23
TC 50
Z9 52
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD NOV 1
PY 2008
VL 64
IS 9
BP 810
EP 814
DI 10.1016/j.biopsych.2008.05.001
PG 5
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 364WD
UT WOS:000260365300011
PM 18550032
ER
PT J
AU Petricciani, J
Sheets, R
AF Petricciani, John
Sheets, Rebecca
TI An overview of animal cell substrates for biological products
SO BIOLOGICALS
LA English
DT Article
DE Cell substrates; Vaccines; Biological products
AB The issue of which cells to use as substrates for the production of biological products, and especially vaccines, has been with us in one form or another ever since the development of cell cultures in the 1950s.
The major cell substrate events that occurred over the past 50 years are reviewed briefly. Although numerous conferences were held during that period, incomplete resolution of some cell substrate issues has remained. Specifically, the potential oncogenicity of cellular DNA derived from continuous cell lines, and the tests that are used to rule out the presence of adventitious agents have been recognized as areas that could benefit greatly from studies using state-of-the-art techniques.
A collaborative effort involving WHO, NIAID, and IABS resulted from consensus recommendations of a 2004 conference, and the prospects for revised guidance in the near future on the characterization and use of animal cell substrates are bright. (C) 2008 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.
C1 [Petricciani, John] John Wayne Canc Inst, Santa Monica, CA 90404 USA.
[Sheets, Rebecca] NIAID, US PHS, NIH, Bethesda, MD 20892 USA.
RP Petricciani, J (reprint author), John Wayne Canc Inst, 2200 Santa Monica Blvd, Santa Monica, CA 90404 USA.
EM jpmdpsca@aol.com
NR 8
TC 14
Z9 15
U1 2
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1045-1056
J9 BIOLOGICALS
JI Biologicals
PD NOV
PY 2008
VL 36
IS 6
BP 359
EP 362
DI 10.1016/j.biologicals.2008.06.004
PG 4
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
GA 389BY
UT WOS:000262066300005
PM 18674929
ER
PT J
AU Lee, SJ
Astigarraga, CC
Eapen, M
Artz, AS
Davies, SM
Champlin, R
Jagasia, M
Kernan, NA
Loberiza, FR
Bevans, M
Soiffer, RJ
Joffe, S
AF Lee, Stephanie J.
Astigarraga, Claudia C.
Eapen, Mary
Artz, Andrew S.
Davies, Stella M.
Champlin, Richard
Jagasia, Madan
Kernan, Nancy A.
Loberiza, Fausto R., Jr.
Bevans, Margaret
Soiffer, Robert J.
Joffe, Steven
TI Variation in Supportive Care Practices in Hematopoietic Cell
Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Practice variation; Supportive care; Autologous stem cell
transplantation; Allogeneic stem cell transplantation
ID BONE-MARROW-TRANSPLANTATION; HEPATIC VENOOCCLUSIVE DISEASE; RANDOMIZED
CONTROLLED-TRIALS; URSODEOXYCHOLIC ACID; PROTECTIVE ISOLATION;
INFORMED-CONSENT; CLINICAL-TRIALS; EUROPEAN-GROUP; ACUTE GVHD; BLOOD
AB Hematopoietic cell transplantation is an elective procedure that results in prolonged immune suppression and high treatment-related morbidity and mortality. Transplant centers and physicians use a variety of prophylaxis and monitoring strategies to prevent or minimize complications. Little is known about the variability in these practices. We conducted an international Internet-based survey of 526 physicians to describe the spectrum of supportive care practices employed. Consistency in pretransplant cardiac (96%) and pulmonary (95%) screening, informed consent documentation (93%), and use of antifungal prophylaxis (92%) was observed. Greater heterogeneity was seen in use of myelogenous growth factors, empiric antibiotic therapy, protective isolation procedures, posttransplant monitoring, and environmental and social restrictions. Although some practice differences were associated with physician characteristics and transplant type, most practice variation remained unexplained. These results suggest a need for well-designed observational and interventional studies to provide data about which supportive care practices improve outcomes. For practices proved to be beneficial, publication of guidelines and incorporation of monitoring into quality improvement initiatives may help standardize practices.
C1 [Lee, Stephanie J.; Astigarraga, Claudia C.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Artz, Andrew S.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Davies, Stella M.] Cincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH USA.
[Champlin, Richard] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
[Jagasia, Madan] Vanderbilt Univ, Ctr Med, Div Hematol Oncol, Nashville, TN 37232 USA.
[Kernan, Nancy A.] Mem Sloan Kettering Canc Ctr, Pediat Bone Marrow Transplantat Serv, New York, NY 10021 USA.
[Loberiza, Fausto R., Jr.] Univ Nebraska, Dept Med, Omaha, NE 68182 USA.
[Bevans, Margaret] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Soiffer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Joffe, Steven] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA.
[Joffe, Steven] Childrens Hosp, Dept Med, Boston, MA 02115 USA.
RP Lee, SJ (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-290, Seattle, WA 98109 USA.
EM sjlee@fhcrc.org
OI Kernan, Nancy/0000-0003-1417-1823; Joffe, Steven/0000-0002-0667-7384
FU Intramural NIH HHS [Z99 CL999999]; NCI NIH HHS [U24 CA076518]
NR 34
TC 21
Z9 22
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD NOV
PY 2008
VL 14
IS 11
BP 1231
EP 1238
DI 10.1016/j.bbmt.2008.08.008
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 367DY
UT WOS:000260533900005
PM 18940677
ER
PT J
AU Allen, D
Herbert, DC
McMahan, CA
Rotrekl, V
Sobol, RW
Wilson, SH
Walter, CA
AF Allen, Diwi
Herbert, Damon C.
McMahan, C. Alex
Rotrekl, Vladimir
Sobol, Robert W.
Wilson, Samuel H.
Walter, Christi A.
TI Mutagenesis Is Elevated in Male Germ Cells Obtained from DNA
Polymerase-beta Heterozygous Mice
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE base excision repair; DNA repair; gamete biology; gametogenesis; lacl;
mutagenesis; POLB; spermatogenesis; spermatogenic cells
ID BASE EXCISION-REPAIR; LIGASE-III; NUCLEAR EXTRACTS; MAMMALIAN-CELLS;
POLY(ADP-RIBOSE) POLYMERASE; MEIOTIC RECOMBINATION; SPERMATOGENIC CELLS;
MUTATION FREQUENCY; BINDING ACTIVITY; TRANSGENIC MICE
AB Gametes carry the DNA that will direct the development of the next generation. By compromising genetic integrity, DNA damage and mutagenesis threaten the ability of gametes to fulfill their biological function. DNA repair pathways function in germ cells and serve to ameliorate much DNA damage and prevent mutagenesis. High base excision repair (BER) activity is documented for spermatogenic cells. DNA polymerase-beta (POLB) is required for the short-patch BER pathway. Because mice homozygous null for the Polb gene die soon after birth, mice heterozygous for Polb were used to examine the extent to which POLB contributes to maintaining spermatogenic genomic integrity in vivo. POLB protein levels were reduced only in mixed spermatogenic cells. In vitro short-patch BER activity assays revealed that spermatogenic cell nuclear extracts obtained from Polb heterozygous mice had one third the BER activity of age-matched control mice. Polb heterozygosity had no effect on the BER activities of somatic tissues tested. The Polb heterozygous mouse line was crossed with the lacl transgenic Big Blue mouse line to assess mutant frequency. The spontaneous mutant frequency for mixed spermatogenic cells prepared from Polb heterozygous mice was 2-fold greater than that of wild-type controls, but no significant effect was found among the somatic tissues tested. These results demonstrate that normal POLB abundance is necessary for normal BER activity, which is critical in maintaining a low germline mutant frequency. Notably, spermatogenic cells respond differently than somatic cells to Polb haploinsufficiency.
C1 [Allen, Diwi; Herbert, Damon C.; Rotrekl, Vladimir; Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[McMahan, C. Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
[Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78229 USA.
[Sobol, Robert W.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA.
[Sobol, Robert W.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA.
[Wilson, Samuel H.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
[Walter, Christi A.] Audie Murphy Mem Vet Affairs Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
RP Walter, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Mail Code 7762, San Antonio, TX 78229 USA.
EM walter@uthscsa.edu
RI Sobol, Robert/E-4125-2013
OI Sobol, Robert/0000-0001-7385-3563
FU Elsa U. Pardee Foundation [P20 CA103730]; National Institutes of Health
[1 R01 AG24364-01, AG21163]; National Institute of Environmental Health
Sciences
FX Supported by grant P20 CA103730 from the Elsa U. Pardee Foundation and
the National Institutes of Health to R.W.S. and by grants 1 R01
AG24364-01 and AG21163 from the National Institutes of Health to C.A.W.
This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute of
Environmental Health Sciences. The contents are solely the
responsibility of the authors and do not necessarily reflect the views
of the funding agencies.
NR 73
TC 15
Z9 17
U1 0
U2 8
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
EI 1529-7268
J9 BIOL REPROD
JI Biol. Reprod.
PD NOV
PY 2008
VL 79
IS 5
BP 824
EP 831
DI 10.1095/biolreprod.108.069104
PG 8
WC Reproductive Biology
SC Reproductive Biology
GA 364FJ
UT WOS:000260321300005
PM 18650495
ER
PT J
AU Han, YM
Romero, R
Kim, JS
Tarca, AL
Kim, SK
Draghici, S
Kusanovic, JP
Gotsch, F
Mittal, P
Hassan, SS
Kim, CJ
AF Han, Yu Mi
Romero, Roberto
Kim, Jung-Sun
Tarca, Adi L.
Kim, Sun Kwon
Draghici, Sorin
Kusanovic, Juan Pedro
Gotsch, Francesca
Mittal, Pooja
Hassan, Sonia S.
Kim, Chong Jai
TI Region-Specific Gene Expression Profiling: Novel Evidence for Biological
Heterogeneity of the Human Amnion
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE IL1B; lipopolysaccharide; microarray; parturition; placenta; pregnancy
ID OCULAR SURFACE RECONSTRUCTION; HUMAN GESTATIONAL TISSUES; FETAL
MEMBRANES; PREMATURE RUPTURE; HLA-G; SPONTANEOUS LABOR;
EPITHELIAL-CELLS; HUMAN PLACENTA; TERM; PRETERM
AB The amnion plays an important role during pregnancy and parturition. Though referred to as a single structure, this fetal tissue is regionally divided into placental amnion, reflected amnion, and umbilical amnion. Histological differences between placental amnion and reflected amnion led us to hypothesize that the amnion is biologically heterogeneous. The gene expression profiles of placental amnion and reflected amnion were compared in patients at term with no labor (TNL; n = 10) and in labor (TIL; n = 10). Real-time quantitative RTPCR revealed a higher expression of IL1B mRNA in reflected amnion than in placental amnion in TNL cases but not in TIL cases. Extended screening using microarrays showed differential expression of 17 genes in labor, regardless of the region. Interestingly, 839 genes were differentially expressed between placental amnion and reflected amnion. Pathway analysis identified 19 signaling pathways, such as mitogen-activated protein kinase and transforming growth factor beta pathways, associated with region. Lipopolysaccharide (LPS) treatment of the amnion explants showed more robust activation of mitogen-activated protein kinase 3/1 (extracellular signal-regulated kinase 1/2) in placental amnion of TNL but not in TIL cases. Placental amnion from TNL and TIL cases showed a significant difference in the amplitude of IL1B mRNA induction by LPS. We report that the anatomical region has a substantial impact on the transcriptional program and the biological properties of the amnion. Labor-associated switching to a proinflammatory signature is a feature particular to placental amnion. The novel observations herein strongly suggest that the seemingly homogeneous amnion is biologically heterogeneous and compartmentalized, with implications for the physiology of pregnancy and parturition.
C1 [Han, Yu Mi; Romero, Roberto; Kim, Jung-Sun; Kim, Sun Kwon; Kusanovic, Juan Pedro; Gotsch, Francesca; Mittal, Pooja; Hassan, Sonia S.; Kim, Chong Jai] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Han, Yu Mi; Romero, Roberto; Kim, Jung-Sun; Tarca, Adi L.; Kim, Sun Kwon; Kusanovic, Juan Pedro; Gotsch, Francesca; Mittal, Pooja; Hassan, Sonia S.; Kim, Chong Jai] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI 48201 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Tarca, Adi L.; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI 48201 USA.
[Kim, Jung-Sun; Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
[Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,4th Floor, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu; cjkim@med.wayne.edu
RI Draghici, Sorin/B-3074-2013
OI Draghici, Sorin/0000-0002-0786-8377
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; NIH; DHHS
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH,
DHHS.
NR 36
TC 29
Z9 30
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1603 MONROE ST, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD NOV
PY 2008
VL 79
IS 5
BP 954
EP 961
DI 10.1095/biolreprod.108.069260
PG 8
WC Reproductive Biology
SC Reproductive Biology
GA 364FJ
UT WOS:000260321300020
PM 18685129
ER
PT J
AU Kuznetsov, SA
Huang, KE
Marshall, GW
Robey, PG
Mankani, MH
AF Kuznetsov, Sergei A.
Huang, Katherine E.
Marshall, Grayson W.
Robey, Pamela G.
Mankani, Mahesh H.
TI Long-term stable canine mandibular augmentation using autologous bone
marrow stromal cells and hydroxyapatite/tricalcium phosphate
SO BIOMATERIALS
LA English
DT Article
DE Autologous cell; Bone tissue engineering; Hydroxyapatite composite; Stem
cell; Transplantation
ID TISSUE-ENGINEERED BONE; MESENCHYMAL STEM-CELLS; TRICALCIUM PHOSPHATE;
IN-VIVO; RECONSTRUCTION; DEFECTS; REGENERATION; REPAIR
AB Transplants of culture-expanded bone marrow stromal cells (BMSCs) combined with hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds successfully form cortico-cancellous bone to reconstruct the dog craniofacial skeleton. Yet, these transplants' long-term stability in large animal models has not been evaluated. This study's purpose was the evaluation of long-term BMSC transplant stability when used to augment the mandible. Here, autologous BMSC-HA/TCP transplants were introduced onto the unilateral dog mandible as onlay grafts, while contralateral control mandibles received HA/TCP onlays alone. Quantitative CT (qCT) scans were obtained both early and late after transplantation. Transplants were harvested up to 19 months later for histologic and mechanical analyses. In all dogs, BMSC transplants formed significantly greater amounts of bone over their control counterparts. The new bone formed an extensive union with the underlying mandible. BMSC transplants retained the majority of their initial volume, while control (HA/TCP only) transplants were nearly completely resorbed. By qCT, the extent of newly formed bone could be determined non-invasively. In summary, HA/TCP particles alone undergo a high degree of resorption, while autologous cultured BMSC-HA/TCP transplants provide long-term bony augmentation of the mandible. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Huang, Katherine E.; Mankani, Mahesh H.] Univ Calif San Francisco, Dept Surg, Div Plast Surg, San Francisco, CA 94143 USA.
[Kuznetsov, Sergei A.; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
RP Mankani, MH (reprint author), Univ Calif San Francisco, Dept Surg, Div Plast Surg, 1001 Potrero Ave,Box 0807, San Francisco, CA 94143 USA.
EM mahesh.mankani@ucsf.edu
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
FU University of California- San Francisco Research Evaluation and
Allocation Committee; National Institute of Dental and Craniofacial
Research, NIH, DHHS
FX The authors are indebted to Zimmer (Warsaw, IN) for its gift of HA/TCP,
to Mindways Software (San Francisco, CA) and Dr. Chris Cann for
technical assistance, and to Dr. Nilo Avila, Mr. Dennis Johnson, Mr.
David Williams, and Mr. Ronald Norman (Department of Radiology, Clinical
Center, National Institutes of Health, Bethesda, MD) for assistance with
the imaging. Mr. Kent Yamaguchi Jr. provided additional technical
assistance. This research was supported in part by the University of
California- San Francisco Research Evaluation and Allocation Committee
and in part by the Intramural Research Program of the National Institute
of Dental and Craniofacial Research, NIH, DHHS.
NR 12
TC 23
Z9 23
U1 0
U2 9
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
J9 BIOMATERIALS
JI Biomaterials
PD NOV
PY 2008
VL 29
IS 31
BP 4211
EP 4216
DI 10.1016/j.biomaterials.2008.07.013
PG 6
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 359BG
UT WOS:000259960600009
PM 18687465
ER
PT J
AU Thomas, JD
Hofer, T
Rader, C
Burke, TR
AF Thomas, Joshua D.
Hofer, Thomas
Rader, Christoph
Burke, Terrence R., Jr.
TI Application of a trifunctional reactive linker for the construction of
antibody-drug hybrid conjugates
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE LLP2A; Immunoconjugate; Fc; IgG1; Peptidomimetic; Integrin
ID ALPHA(4)BETA(1) INTEGRIN; CANCER-THERAPY; SOLID-PHASE
AB A flexible, trifunctional poly(ethylene glycol)-succinamide-Lysine-Lysine-maleimide (PEG-SU-Lys-Lysmal) linker was employed to simultaneously allow biotin tagging and cell-surface targeting through an integrin alpha(4)beta(1)-binding peptidomimetic that was regiospecifically conjugated to an IgG1-derived Fc fragment with an engineered C-terminal selenocysteine residue. The resulting antibody derivative mediates Fc receptor binding by virtue of the Fc protein and selectively targets cancer cells expressing human integrin alpha(4)beta(1). The PEG-SU-Lys-Lys-mal linker may have general utility as an organic tether for the construction of antibody-drug conjugates. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Thomas, Joshua D.; Burke, Terrence R., Jr.] NCI, NIH, Med Chem Lab, CCR, Frederick, MD 21702 USA.
[Hofer, Thomas; Rader, Christoph] NCI, NIH, Expt Transplantat & Immunol Branch, CCR, Bethesda, MD 20892 USA.
RP Burke, TR (reprint author), NCI, NIH, Med Chem Lab, CCR, Frederick, MD 21702 USA.
EM tburke@helix.nih.gov
RI Burke, Terrence/N-2601-2014
FU Intramural Research Program of the Center for Cancer Research;
NCI-Frederick; NCI; NIH
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, NCI-Frederick and NCI, NIH.
NR 17
TC 7
Z9 7
U1 2
U2 15
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 NOV 1
PY 2008
VL 18
IS 21
BP 5785
EP 5788
DI 10.1016/j.bmcl.2008.09.078
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 362WH
UT WOS:000260227400019
PM 18922692
ER
PT J
AU Chong, HS
Lim, S
Baidoo, KE
Milenic, DE
Ma, X
Jia, F
Song, HA
Brechbiel, MW
Lewis, MR
AF Chong, Hyun-Soon
Lim, Sooyoun
Baidoo, Kwamena E.
Milenic, Diane E.
Ma, Xiang
Jia, Fang
Song, Hyun A.
Brechbiel, Martin W.
Lewis, Michael R.
TI Synthesis and biological evaluation of a novel decadentate ligand DEPA
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Radioimmunotherapy; DEPA; (177)Lu; (212)Bi; (213)Bi; Bimodal ligand
ID AGENTS; RADIOIMMUNOTHERAPY; RADIONUCLIDES; CHELATORS; COMPLEXES; COPPER;
ACID
AB An efficient and short synthetic route to a novel decadentate ligand 7-[2-(bis-carboxymethyl-amino)-ethyl]-4,10-bis-carboxymethyl-1,4,7,10-tetraaza-cyclododec-1-yl-acetic acid (DEPA) with both macrocyclic and acyclic binding moieties is reported. A reproducible and scalable synthetic method to a precursor molecule of DEPA, 1,4,7-tris(tert-butoxycarbonylmethyl) tetraazacyclododecane was developed. DEPA was evaluated as a chelator of (177)Lu, (212)Bi, and (213)Bi for potential use in an antibody-targeted cancer therapy, radioimmunotherapy (RIT) using Arsenazo III based spectroscopic complexation kinetics, in vitro serum stability, and in vivo biodistribution studies. (C) 2008 Published by Elsevier Ltd.
C1 [Chong, Hyun-Soon; Lim, Sooyoun; Ma, Xiang; Song, Hyun A.] IIT, Div Chem, Biol Chem & Phys Sci Dept, Chicago, IL 60616 USA.
[Baidoo, Kwamena E.; Milenic, Diane E.; Brechbiel, Martin W.] NCI, NIH, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch,Ctr Canc Res, Bethesda, MD 20892 USA.
[Jia, Fang; Lewis, Michael R.] Univ Missouri, Nucl Sci & Engn Inst, Dept Radiol, Dept Vet Med & Surg, Columbia, MO USA.
RP Chong, HS (reprint author), IIT, Div Chem, Biol Chem & Phys Sci Dept, 3101 S Dearborn St,LS 182, Chicago, IL 60616 USA.
EM Chong@iit.edu
FU National Institutes of Health [R01CA112503-01A2]; Intramural Research
Program of the NIH; National Cancer Institute; Center for Cancer
Research; Office of Research and Development (Medical Research Service);
Department of Veterans Affairs
FX This research is supported by the National Institutes of Health
(R01CA112503-01A2 to C. H. S.). This material is in part based upon work
supported by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research (M. W. B.) and by the Office of
Research and Development (Medical Research Service), Department of
Veterans Affairs, through a Merit Review Type I Award (M. R. L.).
NR 18
TC 11
Z9 11
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD NOV 1
PY 2008
VL 18
IS 21
BP 5792
EP 5795
DI 10.1016/j.bmcl.2008.09.063
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 362WH
UT WOS:000260227400021
PM 18845437
ER
PT J
AU Damjanovic, A
Wu, XW
Garcia-Moreno, B
Brooks, BR
AF Damjanovic, Ana
Wu, Xiongwu
Garcia-Moreno E., Bertrand
Brooks, Bernard R.
TI Backbone Relaxation Coupled to the Ionization of Internal Groups in
Proteins: A Self-Guided Langevin Dynamics Study
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID PH MOLECULAR-DYNAMICS; SECONDARY STRUCTURE ASSIGNMENT; PHOTOACTIVE
YELLOW PROTEIN; CONSTANT-PH; STAPHYLOCOCCAL NUCLEASE; WATER PENETRATION;
FREE-ENERGY; CONFORMATIONAL-CHANGES; STRUCTURAL-CHANGES;
HYDROGEN-EXCHANGE
AB Pathways of structural relaxation triggered by ionization of internal groups in staphylococcal nuclease ( SNase) were studied through multiple self-guided Langevin dynamics ( SGLD) simulations. Circular dichroism, steady-state Trp fluorescence, and nuclear magnetic resonance spectroscopy have shown previously that variants of SNase with internal Glu, Asp, and Lys at positions 66 or 92, and Arg at position 66, exhibit local reorganization or global unfolding when the internal ionizable group is charged. Except for Arg-66, these internal ionizable groups have unusual pK(a) values and are neutral at physiological pH. The structural trends observed in the simulations are in general agreement with experimental observations. The I92D variant, which unfolds globally upon ionization of Asp-92, in simulations often exhibits extensive hydration of the protein core, and sometimes also significant perturbations of the beta-barrel. In the crystal structure of the V66R variant, the beta 1 strand from the beta-barrel is domain-swapped; in the simulations, the beta 1 strand is sometimes partially released. The V66K variant, which in solutions shows reorganization of six residues at the C-terminus of helix alpha 1 and perturbations in the beta-barrel structure, exhibits fraying of three residues of helix a1 in one simulation, and perturbations and partial unfolding of three beta-strands in a few other simulations. In sharp contrast, very small structural changes were observed in simulations of the wild-type protein. The simulations indicate that charging of internal groups frequently triggers penetration of water into the protein interior. The pK(a) values of Asp-92 and Arg-66 calculated with continuum methods on SGLD-relaxed structures reached the normal values in most simulations. Detailed analysis of accuracy and performance of SGLD demonstrates that SGLD outperforms LD in sampling of alternative protein conformations without loss of the accuracy and level of detail characteristic of regular LD.
C1 [Damjanovic, Ana; Garcia-Moreno E., Bertrand] Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21205 USA.
[Damjanovic, Ana; Wu, Xiongwu; Brooks, Bernard R.] NHLBI, NIH, Lab Computat Biol, Bethesda, MD 20892 USA.
RP Damjanovic, A (reprint author), Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21205 USA.
EM ad@jhu.edu
FU National Institutes of Health [R01 GM061597]; National Heart, Lung, and
Blood Institute
FX This work was supported by a National Institutes of Health grant (No.
R01 GM061597) to B. G. M. E. This research was supported in part by the
Intramural Research Program of the National Institutes of Health,
National Heart, Lung, and Blood Institute.
NR 60
TC 36
Z9 36
U1 1
U2 10
PU BIOPHYSICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD NOV 1
PY 2008
VL 95
IS 9
BP 4091
EP 4101
DI 10.1529/biophysj.108.130906
PG 11
WC Biophysics
SC Biophysics
GA 360QO
UT WOS:000260072600003
PM 18641078
ER
PT J
AU Low, C
Weininger, U
Lee, H
Schweimer, K
Neundorf, I
Beck-Sickinger, AG
Pastor, RW
Balbach, J
AF Low, Christian
Weininger, Ulrich
Lee, Hwankyu
Schweimer, Kristian
Neundorf, Ines
Beck-Sickinger, Annette G.
Pastor, Richard W.
Balbach, Jochen
TI Structure and Dynamics of Helix-0 of the N-BAR Domain in Lipid Micelles
and Bilayers
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID CLATHRIN-MEDIATED ENDOCYTOSIS; MEMBRANE CURVATURE; MOLECULAR-DYNAMICS;
AMPHIPHYSIN-2 BIN1; VESICLE; NMR; SIMULATIONS; PROTEINS; ENVIRONMENTS;
RECOGNITION
AB Bin/Amphiphysin/Rvs-homology (BAR) domains generate and sense membrane curvature by binding the negatively charged membrane to their positively charged concave surfaces. N-BAR domains contain an N-terminal extension (helix-0) predicted to form an amphipathic helix upon membrane binding. We determined the NMR structure and nano-to-picosecond dynamics of helix-0 of the human Bin1/Amphiphysin II BAR domain in sodium dodecyl sulfate and dodecylphosphocholine micelles. Molecular dynamics simulations of this 34-amino acid peptide revealed electrostatic and hydrophobic interactions with the detergent molecules that induce helical structure formation from residues 8-10 toward the C-terminus. The orientation in the micelles was experimentally confirmed by backbone amide proton exchange. The simulation and the experiment indicated that the N-terminal region is disordered, and the peptide curves to adopted the micelle shape. Deletion of helix-0 reduced tubulation of liposomes by the BAR domain, whereas the helix-0 peptide itself was fusogenic. These findings support models for membrane curving by BAR domains in which helix-0 increases the binding affinity to the membrane and enhances curvature generation.
C1 [Balbach, Jochen] Univ Halle Wittenberg, Fachgrp Biophys, Inst Phys, D-06120 Halle, Saale, Germany.
[Lee, Hwankyu] NHLBI, NIH, Lab Computat Biol, Bethesda, MD 20892 USA.
[Schweimer, Kristian; Pastor, Richard W.] Univ Bayreuth, Lehrstuhl Biopolymere, D-95447 Bayreuth, Germany.
[Neundorf, Ines; Beck-Sickinger, Annette G.] Univ Leipzig, Fak Biowissensch Pharm & Psychol, Inst Biochem, D-04103 Leipzig, Germany.
[Balbach, Jochen] Univ Halle Wittenberg, Mitteldeutsch Zentrum Struktur & Dynam Prot MZP, D-4010 Halle, Germany.
RP Balbach, J (reprint author), Univ Halle Wittenberg, Fachgrp Biophys, Inst Phys, D-06120 Halle, Saale, Germany.
EM jochen.balbach@physik.uni-halle.de
OI Weininger, Ulrich/0000-0003-0841-8332
FU Deutsche Forschungsgemeinschaft [Ba 1821/3-1, GRK 1026]; Excellence
Initiative of the State Sachsen-Anhalt; National Institutes of Health
(NIH); National Heart, Lung and Blood Institute; CIT [Biowulf/LoBoS3]
FX This research was supported in part by a grant from the Deutsche
Forschungsgemeinschaft (Ba 1821/3-1 and GRK 1026); the Excellence
Initiative of the State Sachsen-Anhalt; the Intramural Research Program
of the National Institutes of Health (NIH), National Heart, Lung and
Blood Institute; and the CIT Biowulf/LoBoS3 cluster at the NIH for use
of the high-performance computational capabilities.
NR 52
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Z9 31
U1 0
U2 14
PU BIOPHYSICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD NOV 1
PY 2008
VL 95
IS 9
BP 4315
EP 4323
DI 10.1529/biophysj.108.134155
PG 9
WC Biophysics
SC Biophysics
GA 360QO
UT WOS:000260072600024
PM 18658220
ER
PT J
AU Phue, JN
Lee, SJ
Trinh, L
Shiloach, J
AF Phue, Je-Nie
Lee, Sang Jun
Trinh, Loc
Shiloach, Joseph
TI Modified Escherichia coli B (BL21), a Superior Producer of Plasmid DNA
Compared With Escherichia coli K (DH5 alpha)
SO BIOTECHNOLOGY AND BIOENGINEERING
LA English
DT Article
DE pDNA: E. coli B; high density
ID DIRECT GENE-TRANSFER; VACCINE; IMMUNOGENICITY; FERMENTATION; PROTECTION;
INVIVO; GROWTH; SAFETY
AB Plasmid DNA (pDNA) is an emerging experimental vaccine, Produced in E. coli, initially targeted for viral diseases. Unlike traditional protein vaccines whose average dose is micrograms, the average dose of pDNA is on the scale of milligrams. Production yields are, therefore, important for the future development of this vaccine. The E. coli strains currently used for pDNA production, JM109 and DH5 alpha, are both suitable for production of stable pDNA due to the deletion of recA and endA, however, these two E. coli K strains are sensitive to growth conditions such as high glucose concentration. On the other hand E. coli BL21 is less sensitive to growth conditions than E. coli JM109 or DH5a, this strain grows to higher densities and due to its active glyoxylate shunt and anaplerotic pathways is not sensitive to high glucose concentration. This strain is used for recombinant protein production but not for pDNA production because of its inability to produce stable pDNA. To adapt E. coli BL21 for stable pDNA production, the strain was mutated by deleting both recA and endA, and a proper growth and production strategy was developed. Production values, reaching 2 g/L were obtained using glucose as a carbon source. The produced plasmid, which was constructed for HIV clinical study, was found to halve identical properties to the plasmid currently produced by E. coli DH5u.
C1 [Phue, Je-Nie; Trinh, Loc; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
[Lee, Sang Jun] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bldg 14A Room 173, Bethesda, MD 20892 USA.
EM yossi@nih.gov
FU NIDDK; NIH
FX Funding was provided by the intramural program at the NIDDK, NIH.
NR 26
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Z9 38
U1 1
U2 19
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-3592
J9 BIOTECHNOL BIOENG
JI Biotechnol. Bioeng.
PD NOV 1
PY 2008
VL 101
IS 4
BP 831
EP 836
DI 10.1002/bit.21973
PG 6
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 360AY
UT WOS:000260030600018
PM 18814292
ER
PT J
AU Holmes, MK
Erickson, K
Luckenbaugh, DA
Drevets, WC
Bain, EE
Cannon, DM
Snow, J
Sahakian, BJ
Manji, HK
Zarate, CA
AF Holmes, M. Kathleen
Erickson, Kristine
Luckenbaugh, David A.
Drevets, Wayne C.
Bain, Earle E.
Cannon, Dara M.
Snow, Joseph
Sahakian, Barbara J.
Manji, Husseini K.
Zarate, Carlos A., Jr.
TI A comparison of cognitive functioning in medicated and unmedicated
subjects with bipolar depression
SO BIPOLAR DISORDERS
LA English
DT Article
DE bipolar disorder; cognition; depression; lithium; valproate
ID SUSTAINED ATTENTION-DEFICIT; AFFECTIVE-DISORDER; EUTHYMIC PATIENTS; MOOD
DISORDERS; DOUBLE-BLIND; IMPAIRMENT; MEMORY; LITHIUM; UNIPOLAR; MANIA
AB Objective: Neuropsychological studies of bipolar disorder reveal deficits in a variety of domains, including affective processing, memory, and sustained attention. These. findings are difficult to interpret due to the potential confounding effects of mood-stabilizing medications. The present study aims to compare the cognitive performance of medicated and unmedicated subjects with bipolar depression to healthy control subjects.
Method: Unmedicated subjects with bipolar depression (UBD, n = 32), subjects with bipolar depression on therapeutic doses of lithium or valproic acid (MBD, n = 33), and healthy control subjects (HC, n = 52) performed neuropsychological tasks measuring affective processing, visual memory, and sustained attention. Performance measures were covaried with age and mood ratings, where applicable.
Results: With regard to affective processing, the MBD group exhibited greater response latency than the UBD and HC groups. For the same task, the MBD group made more omission errors during the happy condition than in the sad condition. On a task of sustained attention, the MBD group made more errors than the HC group. There were no significant group differences on measures of visual memory.
Conclusions: Deficits in affective processing were found in the medicated group, while unmedicated subjects appear to be unaffected. In particular, the MBD group made more errors during happy conditions, indicating a potential attentional bias in subjects with bipolar depression on mood-stabilizing medications. The present study also implicates impairment in sustained attention for medicated subjects with bipolar disorder, particularly those with the type II variety.
C1 [Holmes, M. Kathleen; Erickson, Kristine; Luckenbaugh, David A.; Drevets, Wayne C.; Bain, Earle E.; Cannon, Dara M.; Snow, Joseph; Manji, Husseini K.; Zarate, Carlos A., Jr.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Sahakian, Barbara J.] Univ Cambridge, Dept Psychiat, Cambridge, England.
RP Zarate, CA (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 10 Ctr Dr,Mark O Hatfield CRC,Unit 7 SE,Rm 7-3445, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
RI Cannon, Dara/C-1323-2009
OI Cannon, Dara/0000-0001-7378-3411
FU Stanley Medical Research Institute; NARSAD
FX This study was completed within the Intramural Research Program at the
National Institutes of Health, Bethesda, MD, USA. We thank the
participating subjects, their families, and the nursing and research
staff.. We also acknowledge the support of the Stanley Medical Research
Institute and NARSAD.
NR 43
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U1 3
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD NOV
PY 2008
VL 10
IS 7
BP 806
EP 815
DI 10.1111/j.1399-5618.2008.00628.x
PG 10
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 394TZ
UT WOS:000262472900006
PM 19032712
ER
PT J
AU Deep-Soboslay, A
Iglesias, B
Hyde, TM
Bigelow, LB
Imamovic, V
Herman, MM
Kleinman, JE
AF Deep-Soboslay, Amy
Iglesias, Bianca
Hyde, Thomas M.
Bigelow, Llewelyn B.
Imamovic, Vesna
Herman, Mary M.
Kleinman, Joel E.
TI Evaluation of tissue collection for postmortem studies of bipolar
disorder
SO BIPOLAR DISORDERS
LA English
DT Article
DE bipolar disorder; brain; Harvard Brain Tissue Resource Center; NIMH
Brain Collection; postmortem; Stanley Array Collection; Stanley
Foundation Neuropathology Consortium
ID FOUNDATION BRAIN COLLECTION; GENE-EXPRESSION; MENTAL-ILLNESS;
SCHIZOPHRENIA; CORTEX; NEUROPATHOLOGY; COMORBIDITY
AB Objectives: Postmortem human brain is a valuable resource for studying the neuropathology, neurochemistry, and molecular pathways of genes associated with bipolar disorder (BPD), yet available, well-characterized BPD brain tissue appears scarce. We set out to evaluate BPD postmortem brain collections in order to identify both successful methods as well as barriers to collection.
Methods: We conducted a literature review of postmortem studies of BPD over the past 30 years, compared and contrasted characteristics of established BPD collections, and identified possible barriers specific to BPD brain collection based on our experience at the NIMH Brain Collection.
Results: Currently, 80% of postmortem BPD studies were derived from just two brain repositories worldwide: the Stanley Brain Collection (69%) and Harvard Brain Tissue Resource Center (HBTRC) (11%) (combined subjects n = 72). The NIMH Brain Collection collected BPD cases four times less frequently than cases with schizophrenia, despite similar prevalence rates for these disorders. Only 53% of cases referred to the NIMH collection as BPD met DSM-IV criteria, with inadequate documentation and comorbid substance abuse as primary confounds for diagnosis in the remaining 47% of cases.
Conclusions: Accurate identification and diagnosis of BPD is a central obstacle to BPD brain collection. Comorbid substance abuse and manner of death are two of many critical factors to consider in BPD postmortem studies. Difficulties in BPD brain collection, coupled with the cessation of brain collection by the Stanley Brain Collection, make the need for alternative BPD brain sources imperative. Recommendations for future BPD tissue collection are offered.
C1 [Deep-Soboslay, Amy; Iglesias, Bianca; Hyde, Thomas M.; Bigelow, Llewelyn B.; Imamovic, Vesna; Herman, Mary M.; Kleinman, Joel E.] NIMH, Sect Neuropathol, CBDB, Div Intramural Res Programs,NIH, Bethesda, MD 20892 USA.
RP Kleinman, JE (reprint author), NIMH, Sect Neuropathol, CBDB, Div Intramural Res Programs,NIH, 10 Ctr Dr,MSC 1385, Bethesda, MD 20892 USA.
EM joel.kleinman@mail.nih.gov
FU NIMH Intramural Research Programs; National Institutes of Health
FX This research was supported by the NIMH Intramural Research Programs,
National Institutes of Health. We thank the families of the individuals
who generously donated tissue for this research. We acknowledge the
Offices of the Chief Medical Examiner of the District of Columbia and
Northern Virginia, USA, for their collaboration. We also thank Yeva
Snitkovsky and Jewell King for their efforts in tissue collection and
processing, and John Meyers and Tianzhang Ye for data management.
NR 35
TC 9
Z9 9
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD NOV
PY 2008
VL 10
IS 7
BP 822
EP 828
DI 10.1111/j.1399-5618.2008.00607.x
PG 7
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 394TZ
UT WOS:000262472900008
PM 19032714
ER
PT J
AU Kristinsson, SY
Fears, TR
Gridley, G
Turesson, I
Mellqvist, UH
Bjorkholm, M
Landgren, O
AF Kristinsson, Sigurdur Y.
Fears, Thomas R.
Gridley, Gloria
Turesson, Ingemar
Mellqvist, Ulf-Henrik
Bjoerkholm, Magnus
Landgren, Ola
TI Deep vein thrombosis after monoclonal gammopathy of undetermined
significance and multiple myeloma
SO BLOOD
LA English
DT Article
ID PROTHROMBOTIC COAGULATION ABNORMALITIES; PULMONARY-EMBOLISM; VENOUS
THROMBOSIS; INCREASED RISK; THALIDOMIDE; THROMBOEMBOLISM; CANCER;
POPULATION; THERAPY; DISEASE
AB Patients with multiple myeloma ( MM) have an increased risk of deep venous thrombosis (DVT), particularly when treated with immunomodulatory drugs. Recently, 2 small hospital-based studies observed persons with the MM precursor condition, monoclonal gammopathy of undetermined significance (MGUS), to be at increased risk of developing DVT. Among 4 196 197 veterans hospitalized at least once at US Veterans Affairs hospitals, we identified a total of 2374 cases of MGUS, and 39 272 persons were diagnosed with DVT ( crude incidence 0.9 per 1000 person-years). A total of 31 and 151 DVTs occurred among MGUS and MM patients, respectively ( crude incidence 3.1 and 8.7 per 1000 person-years, respectively; P <.01). Compared with the entire study population, the relative risk (RR) of DVT after a diagnosis of MGUS and MM was 3.3 (95% confidence interval [CI], 2.3-4.7) and 9.2 ( 95% CI, 7.9-10.8), respectively. The most prominent excess risk of DVT was found during the first year after diagnosis of MGUS ( RR = 8.4; 95% CI, 5.7-12.2) and MM ( RR = 11.6; 95% CI, 9.2-14.5). Among 229 MGUS cases (9.5%) that progressed to MM, only one person had a DVT diagnosis before transformation. Our findings suggest the operation of shared underlying mechanisms causing coagulation abnormalities among patients with MGUS and MM. (Blood. 2008; 112: 3582-3586)
C1 [Landgren, Ola] NCI, DCEG, GEB, US Dept HHS,NIH, Bethesda, MD 20892 USA.
[Kristinsson, Sigurdur Y.; Bjoerkholm, Magnus] Karolinska Univ Hosp & Inst, Div Hematol, Dept Med, Stockholm, Sweden.
[Turesson, Ingemar] Lund Univ, Malmo Univ Hosp, Dept Med, Sect Hematol, Malmo, Sweden.
[Mellqvist, Ulf-Henrik] Sahlgrens Univ Hosp, Sect Hematol & Coagulat, Dept Med, Gothenburg, Sweden.
RP Landgren, O (reprint author), NCI, DCEG, GEB, US Dept HHS,NIH, 6120 Execut Blvd,Bldg EPS,Rm 7110, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
FU National Institutes of Health; National Cancer Institute; Division of
Cancer Epidemiology and Genetics (DCEG); Swedish Cancer Society;
Stockholm County Council; Karolinska Institutet Foundations
FX We thank the Medical Administration Service of the Veterans Health
Services and Research Administration, which provided the data on which
this study is based, and Ms Heather Morris of Information Management
Services (Silver Spring, MD) for computer programming support.; This
work was supported by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Division of Cancer
Epidemiology and Genetics (DCEG) and by grants from the Swedish Cancer
Society, Stockholm County Council, and Karolinska Institutet
Foundations.
NR 33
TC 68
Z9 69
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD NOV 1
PY 2008
VL 112
IS 9
BP 3582
EP 3586
DI 10.1182/blood-2008-04-151076
PG 5
WC Hematology
SC Hematology
GA 363XW
UT WOS:000260301800016
PM 18559977
ER
PT J
AU Yu, CI
Gallegos, M
Marches, F
Zurawski, G
Ramilo, O
Garcia-Sastre, A
Banchereau, J
Palucka, AK
AF Yu, Chun I.
Gallegos, Michael
Marches, Florentina
Zurawski, Gerard
Ramilo, Octavio
Garcia-Sastre, Adolfo
Banchereau, Jacques
Palucka, A. Karolina
TI Broad influenza-specific CD8(+) T-cell responses in humanized mice
vaccinated with influenza virus vaccines
SO BLOOD
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; DENDRITIC CELLS; IN-VIVO; SMALLPOX
VACCINATION; IMMUNE PROTECTION; DNA VACCINES; SUBSETS; IMMUNOLOGY;
ANTIGEN; IMMUNODEFICIENCY
AB The development of novel human vaccines would be greatly facilitated by the development of in vivo models that permit preclinical analysis of human immune responses. Here, we show that nonobese diabetic severe combined immunodeficiency (NOD/SCID) beta(2) microglobulin(-/-) mice, engrafted with human CD34(+) hematopoietic progenitors and further reconstituted with T cells, can mount specific immune responses against influenza virus vaccines. Live attenuated trivalent influenza virus vaccine induces expansion of CD8(+) T cells specific to influenza matrix protein (FluM1) and nonstructural protein 1 in blood, spleen, and lungs. On ex vivo exposure to influenza antigens, antigen-specific CD8(+) T cells produce IFN-gamma and express cell-surface CD107a. FluM1-specific CD8(+) T cells can be also expanded in mice vaccinated with inactivated trivalent influenza virus vaccine. Expansion of antigen-specific CD8(+) T cells is dependent on reconstitution of the human myeloid compartment. Thus, this humanized mouse model permits preclinical testing of vaccines designed to induce cellular immunity, including those against influenza virus. Furthermore, this work sets the stage for systematic analysis of the in vivo functions of human DCs. This, in turn, will allow a new approach to the rational design and preclinical testing of vaccines that cannot be tested in human volunteers. (Blood. 2008; 112: 3671-3678)
C1 [Yu, Chun I.; Gallegos, Michael; Marches, Florentina; Zurawski, Gerard; Ramilo, Octavio; Banchereau, Jacques; Palucka, A. Karolina] Baylor Inst Immunol Res, Baylor Natl Inst Allergy & Infect Dis NIAID, Cooperat Ctr Translat Res Human Immunol, INSERM,U899, Dallas, TX 75204 USA.
[Yu, Chun I.] Baylor Univ, Waco, TX 76798 USA.
[Ramilo, Octavio] Univ Texas SW, Dallas, TX USA.
[Garcia-Sastre, Adolfo] Emerging Pathogens Inst, Dept Microbiol, New York, NY USA.
[Garcia-Sastre, Adolfo] Mt Sinai Sch Med, NIAID, Ctr Investigating Virus Immun & Antagonism, New York, NY USA.
RP Palucka, AK (reprint author), Baylor Inst Immunol Res, Baylor Natl Inst Allergy & Infect Dis NIAID, Cooperat Ctr Translat Res Human Immunol, INSERM,U899, 3434 Live Oak St, Dallas, TX 75204 USA.
EM karolinp@baylorhealth.edu
FU BHCS Foundation; DANA Foundation; National Institutes of Health [U19
AI057234, U19 AI062623, AIO56001, CA78846]
FX The authors thank volunteers for participation in our studies; Dr Joseph
Fay and the clinical group as well as Lynette Walters and the personnel
at Cell and Tissue Procurement core at Baylor Institute for Immunology
Research; Albert Barnes and the personnel at Bioscience Center at BRI;
Flow cytometry and Luminex Core at Baylor Institute for Immunology
Research; Anne-Laure Flamar, Dr Xiao-Hua Li, Sandra Zurawski, and Dr
Gouchen He for FLT3 Ligand; Dr SangKon Oh and Dr Hideki Ueno for
discussion; Cindy Samuelsen, Dr Carson Harrod, and Nicolas Taquet for
administrative and facility support; and Dr Michael Ramsay and Dr
William Duncan for continuous support.; This work was supported by BHCS
Foundation, DANA Foundation, and National Institutes of Health (U19
AI057234, U19 AI062623, AIO56001, and CA78846). J.B. holds the Caruth
Chair for Transplant Immunology Research. A. K. P. holds the Ramsay
Chair for Cancer Immunology Research.
NR 38
TC 26
Z9 27
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD NOV 1
PY 2008
VL 112
IS 9
BP 3671
EP 3678
DI 10.1182/blood-2008-05-157016
PG 8
WC Hematology
SC Hematology
GA 363XW
UT WOS:000260301800026
PM 18713944
ER
PT J
AU Jeker, LT
Barthlott, T
Keller, MP
Zuklys, S
Hauri-Hohl, M
Deng, CX
Hollander, GA
AF Jeker, Lukas T.
Barthlott, Thomas
Keller, Marcel P.
Zuklys, Saulius
Hauri-Hohl, Mathias
Deng, Chu-Xia
Hollaender, Georg A.
TI Maintenance of a normal thymic microenvironment and T-cell homeostasis
require Smad4-mediated signaling in thymic epithelial cells
SO BLOOD
LA English
DT Article
ID EARLY THYMOCYTE DEVELOPMENT; TGF-BETA SUPERFAMILY; TRANSCRIPTION
FACTORS; LINEAGE COMMITMENT; C-KIT; DIFFERENTIATION; PROGENITORS;
SMAD4/DPC4; RECEPTOR; RECRUITMENT
AB Signals mediated by the transforming growth factor-beta superfamily of growth factors have been implicated in thymic epithelial cell (TEC) differentiation, homeostasis, and function, but a direct reliance on these signals has not been established. Here we demonstrate that a block in canonical transforming growth factor-beta signaling by the loss of Smad4 expression in TECs leads to qualitative changes in TEC function and a progressively disorganized thymic microenvironment. Moreover, the number of thymus resident early T-lineage progenitors is severely reduced in the absence of Smad4 expression in TECs and directly correlates with extensive thymic and peripheral lymphopenia. Our observations hence place Smad4 within the signaling events in TECs that determine total thymus cellularity by controlling the number of early T-lineage progenitors. (Blood. 2008; 112:3688-3695)
C1 [Jeker, Lukas T.; Barthlott, Thomas; Keller, Marcel P.; Zuklys, Saulius; Hauri-Hohl, Mathias; Hollaender, Georg A.] Univ Basel, Lab Pediat Immunol, Dept Biomed, CH-4058 Basel, Switzerland.
[Jeker, Lukas T.; Barthlott, Thomas; Keller, Marcel P.; Zuklys, Saulius; Hauri-Hohl, Mathias; Hollaender, Georg A.] Univ Childrens Hosp, Basel, Switzerland.
[Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA.
RP Hollander, GA (reprint author), Univ Basel, Lab Pediat Immunol, Dept Biomed, Mattenstr 28, CH-4058 Basel, Switzerland.
EM georg-a.hollaender@unibas.ch
RI deng, chuxia/N-6713-2016;
OI Jeker, Lukas/0000-0002-3359-8796
FU Swiss National Science Foundation [3100-68310.02, 3235062696.00];
European Community 6th Framework Programme Euro-Thymide Integrated
Project; National Institutes of Health [ROI-A105747701]; Roche Research
Foundation
FX The authors thank Thomas Boulay, Katrin Hafen, and Annick Peter for
expert technical help, Angelika Offinger and Rodrigo Recinos for
excellent animal care, and Ed Palmer, Willem van Ewijk, and Hamish Scott
for providing reagents.; This work was supported by the Swiss National
Science Foundation (grant 3100-68310.02, G. A. H.; and grant
3235062696.00, L. T. J.), the European Community 6th Framework Programme
Euro-Thymide Integrated Project (G. A. H.), the National Institutes of
Health (Besthesda, MD; grant ROI-A105747701, G. A. H.), and the Roche
Research Foundation (M. H.-H.).
NR 50
TC 10
Z9 10
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD NOV 1
PY 2008
VL 112
IS 9
BP 3688
EP 3695
DI 10.1182/blood-2008-04-150532
PG 8
WC Hematology
SC Hematology
GA 363XW
UT WOS:000260301800028
PM 18695001
ER
PT J
AU Calvo, KR
Dabir, B
Kovach, A
Devor, C
Bandle, R
Bond, A
Shih, JH
Jaffe, ES
AF Calvo, Katherine R.
Dabir, Bhavana
Kovach, Alexandra
Devor, Christopher
Bandle, Russell
Bond, Amelia
Shih, Joanna H.
Jaffe, Elaine S.
TI IL-4 protein expression and basal activation of Erk in vivo in
follicular lymphoma
SO BLOOD
LA English
DT Article
ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; GENE-EXPRESSION;
TUMOR-DEVELOPMENT; GERMINAL CENTER; T-CELLS; INTERLEUKIN-4-INDUCED
TRANSCRIPTION; MEK INHIBITORS; KINASE CASCADE; STAT6
AB Follicular lymphoma (FL) is characterized by constitutive expression of Bcl-2 as a consequence of t(14;18). Evidence suggests factors in the lymph node microenvironment, related to intratumoral T cells, macrophages, and dendritic cells, play a role in the disease process. We generated proteomic cytokine profiles of FL (N=50) and follicular hyperplasia (FH; N=23). A total of 10 cytokines were assayed using ultrasensitive multiplex enzyme-linked immunosorbent assays: IL-1 beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-13, IL-12p70, tumor necrosis factor-alpha, and interferon-gamma. Each cytokine showed overall lower protein concentrations in FL, with the exception of IL-4, which was nearly 5 times higher in FL than FH (P= .005). Using reverse-phase protein microarrays (RPMAs), we evaluated the activation state of several intracellular signaling proteins downstream of cytokine receptors. Basal Erk phosphorylation was approximately 4 times greater in FL than FH (P <.001), with similar findings for Mek; Stat-6 showed weak basal phosphorylation that was approximately twice as high in FL than in FH (P=.012). In conclusion, the FL microenvironment contains increased levels of IL-4, with prominent tumor basal phosphorylation of Erk. These findings suggest IL-4, Erk, and possibly Stat-6 may play a role in the biology of FL and may serve as targets for future therapies. (Blood. 2008; 112:3818-3826)
C1 [Calvo, Katherine R.] NCI, NIH, Ctr Clin, Dept Lab Med,Hematopathol Sect,Lab Pathol, Bethesda, MD 20892 USA.
[Devor, Christopher; Bandle, Russell; Bond, Amelia] NCI, NIH, Clin Prote Core Lab, LP, Bethesda, MD 20892 USA.
[Shih, Joanna H.] NCI, NIH, Div Canc Treatment, Bethesda, MD 20892 USA.
[Shih, Joanna H.] NCI, NIH, Diag Biometr Res Branch, Bethesda, MD 20892 USA.
RP Calvo, KR (reprint author), NCI, NIH, Ctr Clin, Dept Lab Med,Hematopathol Sect,Lab Pathol, 10 Ctr Dr,Bldg 10-2C306, Bethesda, MD 20892 USA.
EM calvok@mail.nih.gov
RI Calvo, Katherine/A-8109-2009;
OI Calvo, Katherine/0000-0002-0771-4191
FU NIH, National Cancer Institute
FX We thank Dr Liang Cao for use of the SECTOR Imager 6000, Adnan Siddiqui
for assistance in lysate preparation, and Dr David Levens and Dr
Hye-Jung Chung for invaluable discussions.; This research was supported
by the Intramural Research Program of the NIH, National Cancer
Institute.
NR 60
TC 29
Z9 31
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD NOV 1
PY 2008
VL 112
IS 9
BP 3818
EP 3826
DI 10.1182/blood-2008-02-138933
PG 9
WC Hematology
SC Hematology
GA 363XW
UT WOS:000260301800042
PM 18682601
ER
PT J
AU Zoueva, OP
Garrett, LJ
Bodine, D
Rodgers, GP
AF Zoueva, Olga P.
Garrett, Lisa J.
Bodine, David
Rodgers, Griffin P.
TI BP1 motif in the human beta-globin promoter affects beta-globin
expression during embryonic/fetal erythropoiesis in transgenic mice
bearing the human beta-globin gene
SO BLOOD CELLS MOLECULES AND DISEASES
LA English
DT Article
DE Human beta-globin promoter; BP1 binding site; Human beta-globin
expression; Transcription factor; Transgenic mice
ID REGULATORY ELEMENTS
AB The binding of the transcription factor BP1 (beta protein 1) to its site on the promoter of the adult beta-globin gene has a silencing effect on beta-globin transcription in vitro. To better understand the mechanism of BP1's negative regulation of p-globin expression, we developed transgenic mice bearing a human beta-globin locus-containing cosmid. Specifically, we introduced a mutated BP1 binding site (mtBP1) into the promoter of the beta-globin gene sequence of this cosmid construct. In the mtBP1 mice, we detected a more than a 20-fold increase in human beta-globin expression in the yolk sac-derived blood at E10.5, a 3-fold increase in fetal livers at E13.5, and an approximately 1.4-fold increase in adult reticulocytes compared with control mice bearing the human beta-globin gene with the wild-type BP1 binding site sequence (wtBP1). Our in vivo observations support the contention that the BP1 binding site of the beta-globin promoter plays an important role in the regulation of transcription of the adult beta-globin gene. Published by Elsevier Inc.
C1 [Zoueva, Olga P.; Rodgers, Griffin P.] NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Garrett, Lisa J.; Bodine, David] Natl Human Genome Res Inst, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Rodgers, GP (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, 9000 Rockville Pike,Bldg 31,Room 9A52, Bethesda, MD 20892 USA.
EM gprod@helix.nih.gov
FU Intramural NIH HHS [Z01 DK027008-10]
NR 12
TC 2
Z9 3
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1079-9796
J9 BLOOD CELL MOL DIS
JI Blood Cells Mol. Dis.
PD NOV-DEC
PY 2008
VL 41
IS 3
BP 244
EP 251
DI 10.1016/j.bcmd.2008.05.008
PG 8
WC Hematology
SC Hematology
GA 361TT
UT WOS:000260150700002
PM 18656399
ER
PT J
AU Yang, H
Dixit, VD
Patel, K
Vandanmagsar, B
Collins, G
Sun, YX
Smith, RG
Taub, DD
AF Yang, Hyunwon
Dixit, Vishwa D.
Patel, Kalpesh
Vandanmagsar, Bolormaa
Collins, Gary
Sun, Yuxiang
Smith, Roy G.
Taub, Dennis D.
TI Reduction in hypophyseal growth hormone and prolactin expression due to
deficiency in ghrelin receptor signaling is associated with Pit-1
suppression: Relevance to the immune system
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Ghrelin; GHS-R; Aging; Pituitary; GH; IGF-1; Prolactin; Pit-1; Thymus
ID GH SECRETAGOGUE MK-677; SOMATOSTATIN SECRETION; PITUITARY; STIMULATION;
RELEASE; MICE
AB In mice and in rats, reduced levels of the growth hormone secretagogue receptor (GHS-R1a) results in reduced body weight and lower levels of serum insulin-like growth factor I (IGF-1). However, the mechanism leading to these impairments has not been elucidated. Studies in primary cultures of pituitary cells from very young mice have shown that GHS-R1a agonists, including ghrelin, increase expression of the pituitary-specific transcription factor (Pit-1) that is critical for differentiation of pituitary cells into somatotrophs, lactotrophs, and thyrotrophs. Hence, we hypothesized that ablation of Ghsr would reduce Pit-1 expression and as a consequence reduce growth hormone (GH) production explaining the lower body weight of Ghsr-/- mice. Here, we now show that Pit-1 mRNA levels are significantly lower in the pituitary gland of Ghsr-/- mice compared to wild-type littermates and also with advancing age. This Pit-1 loss is associated with reduced GH mRNA and fewer GH producing cells. To determine whether reduced GH is caused by reduced expression of Pit-1 in Ghsr-/- mice, we also measured prolactin (PRL) expression in the pituitary gland and in the circulation. PRL mRNA was significantly reduced in Ghsr-/- mice compared to wild-type littermates and fewer cells expressed PRL. The reduction in expression of both GH and PRL is consistent with a Pit-1 regulated pathway and demonstrates that the GHS-R has an important role in the pituitary gland as a modulator of Pit-1 expression and provides a possible mechanism to explain the lower plasma IGF-1 and modestly reduced body weight exhibited by Ghsr-/ - mice. We also believe that lower systemic and lymphoid hormone expression may also account, in part, for the enhanced thymic involution and reduced thymic output in Ghsr-/- mice. Published by Elsevier Inc.
C1 [Yang, Hyunwon; Dixit, Vishwa D.; Patel, Kalpesh; Vandanmagsar, Bolormaa; Collins, Gary; Taub, Dennis D.] NIA, Immunol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Sun, Yuxiang; Smith, Roy G.] Baylor Coll Med, Huffington Ctr Aging, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Sun, Yuxiang; Smith, Roy G.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
RP Taub, DD (reprint author), NIA, Immunol Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM rsmith@bcm.edu; taubd@grc.nia.nih.gov
RI Patel, Kalpesh/G-6685-2012
OI Patel, Kalpesh/0000-0002-2952-6773
FU Intramural Research Program of the National Institute on Aging; National
Institutes of Health [R01 AG19230-01, R01 AG18895-02]; NIH
FX We thank the staff of the Comparative Medicine Section of the NIA animal
facility for their support in maintaining and monitoring our animals. We
would also like to thank Drs. Dan L. Longo, Mark Mattson, and Arya
Biragyn for reviewing this manuscript and Mrs. Dawn Tripp for her
administrative assistance with the manuscript. This research was
supported in part by the Intramural Research Program of the National
Institute on Aging, National Institutes of Health and R01 AG19230-01 and
R01 AG18895-02 NIH grants to R.G.S.
NR 24
TC 13
Z9 14
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
EI 1090-2139
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD NOV
PY 2008
VL 22
IS 8
BP 1138
EP 1145
DI 10.1016/j.bbi.2008.06.003
PG 8
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 360UM
UT WOS:000260083400004
PM 18602461
ER
PT J
AU Wayne, SJ
Neuhouser, ML
Ulrich, CM
Koprowski, C
Baumgartner, KB
Baumgartner, RN
McTiernan, A
Bernstein, L
Ballard-Barbash, R
AF Wayne, Sharon J.
Neuhouser, Marian L.
Ulrich, Cornelia M.
Koprowski, Carol
Baumgartner, Kathy B.
Baumgartner, Richard N.
McTiernan, Anne
Bernstein, Leslie
Ballard-Barbash, Rachel
TI Dietary fiber is associated with serum sex hormones and insulin-related
peptides in postmenopausal breast cancer survivors
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE breast cancer outcomes; dietary fiber; serum hormones; serum peptides
ID CARDIOVASCULAR-DISEASE RISK; PHYSICAL-ACTIVITY LEVELS; GROWTH-FACTOR-I;
PREMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; C-PEPTIDE; ESTROGEN
CONCENTRATIONS; PLASMA-INSULIN; WEIGHT-GAIN; WHEAT BRAN
AB Objective To measure the association between dietary fiber intake and eleven hormones and peptides in postmenopausal breast cancer survivors. Methods Intake of fiber from food and supplements was measured two to three years after breast cancer diagnosis in 493 postmenopausal women from three western states. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), leptin, C-peptide, insulin-like growth factor-1 (IGF1), and IGF-binding protein-3. Adjusted means of these hormones and peptides were calculated for categories of fiber intake. Results High intake of dietary fiber was significantly (P <= 0.05) associated with low serum levels of estradiol and free estradiol and with high serum levels of IGF1. The combination of high dietary fiber intake and use of fiber supplements was additionally associated with low serum levels of C-peptide. The magnitude of the difference in hormone/peptide values, comparing high fiber intake to low fiber intake, varied from 16 to 28%, and the associations were independent of multiple confounding variables. Conclusion High fiber diets may be beneficial to postmenopausal breast cancer survivors due to fiber's favorable influence on sex hormones and peptides known to affect breast cancer prognosis.
C1 [Wayne, Sharon J.] 1 Univ New Mexico, New Mexico Tumor Registry, Albuquerque, NM 87131 USA.
[Neuhouser, Marian L.; Ulrich, Cornelia M.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Koprowski, Carol] Univ So Calif, Inst Hlth Promot & Dis Prevent, Alhambra, CA 91803 USA.
[Baumgartner, Kathy B.; Baumgartner, Richard N.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40202 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Ballard-Barbash, Rachel] NCI, Appl Res Program, Bethesda, MD 20892 USA.
RP Wayne, SJ (reprint author), 1 Univ New Mexico, New Mexico Tumor Registry, MSC 11 620, Albuquerque, NM 87131 USA.
EM swayne@salud.unm.edu
RI Perez , Claudio Alejandro/F-8310-2010
OI Perez , Claudio Alejandro/0000-0001-9688-184X
FU National Cancer Institute [N01-CN-75036-20, N01-CN-05228,
N01-PC-67010/N01PC-35139, N01-PC-67007/N01-PC-35138,
N01-PC-67009/N01PC-35142, T32 CA09661]; NIH [M01-RR-00037]; National
Institute of Child Health and Human Development [N01-HD-3-3175];
California Department of Health Services [050Q-8709-S1528]
FX National Cancer Institute contracts N01-CN-75036-20, N01-CN-05228,
N01-PC-67010/N01PC-35139, N01-PC-67007/N01-PC-35138 and
N01-PC-67009/N01PC-35142, and training grant T32 CA09661. A portion of
this work was conducted through the Clinical Research Center at the
University of Washington and supported by the NIH grant M01-RR-00037.
Data collection for the Women's Contraceptive and Reproductive
Experiences Study at the University of Southern California was supported
by the National Institute of Child Health and Human Development contract
N01-HD-3-3175. Patient identification was supported in part by the
California Department of Health Services grant 050Q-8709-S1528.
NR 48
TC 5
Z9 5
U1 0
U2 8
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 NOV
PY 2008
VL 112
IS 1
BP 149
EP 158
DI 10.1007/s10549-007-9834-y
PG 10
WC Oncology
SC Oncology
GA 355GD
UT WOS:000259696500018
PM 18058020
ER
PT J
AU Pro, B
Leber, B
Smith, M
Fayad, L
Romaguera, J
Hagemeister, F
Rodriguez, A
McLaughlin, P
Samaniego, F
Zwiebel, J
Lopez, A
Kwak, L
Younes, A
AF Pro, Barbara
Leber, Brian
Smith, Mitchell
Fayad, Luis
Romaguera, Jorge
Hagemeister, Fredrick
Rodriguez, Alma
McLaughlin, Peter
Samaniego, Felipe
Zwiebel, James
Lopez, Adriana
Kwak, Larry
Younes, Anas
TI Phase II multicenter study of oblimersen sodium, a Bcl-2 antisense
oligonucleotide, in combination with rituximab in patients with
recurrent B-cell non-Hodgkin lymphoma
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE non-Hodgkin lymphoma; oblimersen sodium; rituximab; recurrent B-cell NHL
ID ANTI-CD20 MONOCLONAL-ANTIBODY; CHRONIC LYMPHOCYTIC-LEUKEMIA;
PROGNOSTIC-SIGNIFICANCE; PROTEIN EXPRESSION; THERAPY; CYCLOPHOSPHAMIDE;
APOPTOSIS; EFFICACY
AB Oblimersen sodium plus rituximab was evaluated in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) patients. Oblimersen was administered as a continuous intravenous infusion at a daily dose of 3 mg/kg/d for 7 d on alternate weeks for 3 weeks. Rituximab was given at a weekly dose of 375 mg/m(2) for six doses. Patients with stable disease or objective response were allowed to receive a second course of treatment. The overall response rate (ORR) was 42% with 10 complete responses (CR) and eight partial responses (PR). Twelve (28%) patients achieved a minimal response or stable disease. Among the 20 patients with follicular lymphoma the ORR was 60% (eight CR, four PR). Three of the responders were refractory to prior treatment with rituximab, and two of the responses occurred in patients who had failed an autologous stem cell transplant. Median duration of response was 12 months. Most toxicities were low grade and reversible. In conclusion, oblimersen sodium can be safely combined with rituximab. The combination appears to be most beneficial in patients with indolent NHL and warrants further investigation in a large randomized trial.
C1 [Pro, Barbara] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Unit 429, Houston, TX 77030 USA.
[Leber, Brian] McMaster Univ, Hamilton, ON, Canada.
[Smith, Mitchell] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Zwiebel, James] Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA.
[Lopez, Adriana] Univ Texas MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA.
RP Pro, B (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Unit 429, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM bpro@mdanderson.org
OI Smith, Mitchell/0000-0003-1428-8765
FU National Cancer Institute [01/CM17003]
FX This study was supported by the National Cancer Institute Grant No
01/CM17003.
NR 14
TC 65
Z9 66
U1 0
U2 1
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 NOV
PY 2008
VL 143
IS 3
BP 355
EP 360
DI 10.1111/j.1365-2141.2008.07353.x
PG 6
WC Hematology
SC Hematology
GA 361HC
UT WOS:000260117300005
PM 18764869
ER
PT J
AU Chin, KL
Aerbajinai, WL
Zhu, JQ
Drew, L
Chen, L
Liu, WL
Rodgers, GP
AF Chin, Kyung L.
Aerbajinai, Wulin
Zhu, Jiangqiong
Drew, LaShawn
Chen, Ling
Liu, Wenli
Rodgers, Griffin P.
TI The regulation of OLFM4 expression in myeloid precursor cells relies on
NF-kappa B transcription factor
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE olfactomedin 4 gene; human G-CSF-stimulated clone-1; NF-kappa B;
activator protein 1; GW112
ID SIGNAL-TRANSDUCTION; REDOX-REGULATION; TYROSINE PHOSPHORYLATION;
GENE-EXPRESSION; RECEPTOR; PROTEIN; GROWTH; PROLIFERATION; ANTIOXIDANT;
TRANSITION
AB The human olfactomedin 4 gene (OLFM4, also known as hGC-1, GW112) is thought to be a useful marker for early myeloid development. To understand the molecular mechanisms underlying granulocyte colony-stimulating factor (G-CSF)-stimulated OLFM4 expression, we characterized the promoter region of OLFM4. The 35-bp region (-101 to -66) of the proximal promoter regulated reporter gene expression, and mutation of the nuclear factor (NF)-kappa B binding site within the promoter abolished the binding of the transcription factor and the ability to regulate OLFM4 expression. G-CSF increased reactive oxygen species (ROS) production in human CD34(+) cells, which was abrogated by inhibition of phosphatidylinositol 3-kinase (PI3K) or NADPH oxidase. Phosphorylation of ERK1/2 mitogen-activated protein kinase (MAPK) induced by G-CSF inhibited by the antioxidant N-acetyl-L-cysteine (NAC), ERK1/2 inhibitor PD98059, or U0126. However, phosphorylation of signal transducer and activator of transcription (STAT)3 was only partially inhibited by NAC, but not by PD98059 or U0126. Inhibition of the ERK pathway remarkably decreased OLFM4 expression and this inhibition required NF-kappa B transcription factor. Inhibition of ROS or the ERK pathway remarkably decreased G-CSF-induced OLFM4 expression. Our results suggest that G-CSF-induced expression of OLFM4 is regulated by the transcription factor NF-kappa B, and that this induction is mediated by the ERK1/2 MAPK signaling pathway through PI3K-driven ROS production.
C1 [Chin, Kyung L.; Aerbajinai, Wulin; Zhu, Jiangqiong; Drew, LaShawn; Chen, Ling; Liu, Wenli; Rodgers, Griffin P.] NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Rodgers, GP (reprint author), NIDDKD, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N115,10 Ctr Dr, Bethesda, MD 20892 USA.
EM gprod@helix.nih.gov
NR 30
TC 24
Z9 24
U1 0
U2 3
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 NOV
PY 2008
VL 143
IS 3
BP 421
EP 432
DI 10.1111/j.1365-2141.2008.07368.x
PG 12
WC Hematology
SC Hematology
GA 361HC
UT WOS:000260117300015
PM 18764868
ER
PT J
AU Latimer, AE
Rench, TA
Rivers, SE
Katulak, NA
Materese, SA
Cadmus, L
Hicks, A
Hodorowski, JK
Salovey, P
AF Latimer, Amy E.
Rench, Tara A.
Rivers, Susan E.
Katulak, Nicole A.
Materese, Stephanie A.
Cadmus, Lisa
Hicks, Althea
Hodorowski, Julie Keany
Salovey, Peter
TI Promoting participation in physical activity using framed messages: An
application of prospect theory
SO BRITISH JOURNAL OF HEALTH PSYCHOLOGY
LA English
DT Article
ID MASS-MEDIA CAMPAIGNS; PLANNED BEHAVIOR; SELF-EFFICACY; ACTIVITY
QUESTIONNAIRE; SOURCE CREDIBILITY; HEALTHY BEHAVIOR; LOW-INCOME; FAT
INTAKE; INTERVENTION; PERCEPTIONS
AB Objectives. Messages designed to motivate participation in physical activity usually emphasize the benefits of physical activity (gain-framed) as well as the costs of inactivity (loss-framed). The framing implications of prospect theory suggest that the effectiveness of these messages could be enhanced by providing gain-framed information only. We compared the effectiveness of gain-, loss-, and mixed-framed messages for promoting moderate to vigorous physical activity.
Design. Randomized trial.
Method. Sedentary, healthy callers to the US National Cancer Institute's Cancer Information Service (N = 322) received gain-, loss-, or mixed-framed messages on three occasions (baseline, Week 1, and Week 5). Social cognitive variables and self-reported physical activity were assessed at baseline, Week 2, and Week 9. Separate regression analyses were conducted to examine message effects at each assessment point.
Results. At Week 2, gain-and mixed-framed messages resulted in stronger intentions and greater self-efficacy than loss-framed messages. At Week 9, gain-framed messages resulted in greater physical activity participation than loss-or mixed-framed messages. Social cognitive variables at Week 2 did not mediate the Week 9 framing effects on physical activity participation.
Conclusions. Using gain-framed messages exclusively may be a means of increasing the efficacy of physical activity materials.
C1 [Latimer, Amy E.; Rench, Tara A.; Rivers, Susan E.; Katulak, Nicole A.; Cadmus, Lisa; Salovey, Peter] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[Materese, Stephanie A.; Cadmus, Lisa] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
[Hicks, Althea; Hodorowski, Julie Keany] Mem Sloan Kettering Canc Ctr, Natl Canc Inst, Canc Informat Serv, New York, NY 10021 USA.
RP Latimer, AE (reprint author), Queens Univ, Sch Kinesiol & Hlth Studies, 69 Union St, Kingston, ON K7L 3N6, Canada.
EM amy.latimer@queensu.ca
OI Hodorowski, Julie/0000-0003-3587-2135
FU NCI NIH HHS [R01-CA68427, N02-CO-51101, R01 CA068427]; PHS HHS
[HHSN261200511001C]
NR 56
TC 43
Z9 43
U1 2
U2 15
PU BRITISH PSYCHOLOGICAL SOC
PI LEICESTER
PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND
SN 1359-107X
J9 BRIT J HEALTH PSYCH
JI Br. J. Health Psychol.
PD NOV
PY 2008
VL 13
BP 659
EP 681
DI 10.1348/135910707X246186
PN 4
PG 23
WC Psychology, Clinical
SC Psychology
GA 366DG
UT WOS:000260460200006
PM 17925060
ER
PT J
AU McLaren, GD
McLaren, CE
Adams, PC
Barton, JC
Reboussin, DM
Gordeuk, VR
Acton, RT
Harris, EL
Speechley, MR
Sholinsky, P
Dawkins, FW
Snively, BM
Vogt, TM
Eckfeldt, JH
AF McLaren, Gordon D.
McLaren, Christine E.
Adams, Paul C.
Barton, James C.
Reboussin, David M.
Gordeuk, Victor R.
Acton, Ronald T.
Harris, Emily L.
Speechley, Mark R.
Sholinsky, Phyliss
Dawkins, Fitzroy W.
Snively, Beverly M.
Vogt, Thomas M.
Eckfeldt, John H.
CA HEIRC Study Res Invest
TI Clinical manifestations of hemochromatosis in HFE C282Y homozygotes
identified by screening
SO CANADIAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
DE Complications; Cross-sectional study; Hemochromatosis; FIFE; Iron
overload; Prevalence
ID PRIMARY-CARE PATIENTS; HEREDITARY HEMOCHROMATOSIS; IRON-OVERLOAD;
GENETIC HEMOCHROMATOSIS; TRANSFERRIN SATURATION; GENERAL-POPULATION;
AMERICAN-COLLEGE; LIVER-DISEASES; SERUM FERRITIN; PREVALENCE
AB BACKGROUND: Patients with hemochromatosis may suffer organ damage from iron overload, often with serious clinical consequences.
OBJECTIVE: To assess prevalences of self-reported symptoms and clinical signs and conditions in persons homozygous for the hemochromatosis gene (HFE) mutation (C282Y) identified by screening.
METHODS: Participants were adults 25 years of age or older enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. C282Y homozygotes (n=282) were compared with control participants without the HFE C282Y or H63D alleles (ie, wild type/wild type; n=364).
RESULTS: Previously diagnosed C282Y homozygotes and newly diagnosed homozygotes with elevated serum ferritin levels had higher prevalences of certain symptoms such as chronic fatigue (OR 2.8; 95% CI 1.34 to 5.95, and OR 2.0; 95% CI 1.07 to 3.75, respectively), and had more hyperpigmentation on physical examination (OR 4.7; 95% CI 1.50 to 15.06, and OR 3.7; 95% CI 1.10 to 12.16, respectively) and swelling or tenderness of the second and third metacarpophalangeal joints (OR 4.2; 95% CI 1.37 to 13.03, and OR 3.3; 95% CI 1.17 to 9.49, respectively) than control subjects. Joint stiffness was also more common among newly diagnosed C282Y homozygotes with elevated serum ferritin than among control subjects (OR 2.7; 95% CI 1.38 to 5.30). However, the sex- and age-adjusted prevalences of self-reported symptoms and signs of liver disease, heart disease, diabetes and most other major clinical manifestations of hemochromatosis were similar in C282Y homozygotes and control subjects.
CONCLUSIONS: Some symptoms and conditions associated with hemochromatosis were more prevalent among C282Y homozygotes identified by screening than among control subjects, but prevalences of most outcomes were similar in C282Y homozygotes and controls in this primary care-based study.
C1 [McLaren, Gordon D.] Dept Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA.
[McLaren, Gordon D.] Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92717 USA.
[McLaren, Christine E.] Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA.
[Adams, Paul C.] London Hlth Sci Ctr, Dept Med, London, ON, Canada.
[Barton, James C.] So Iron Disorders Ctr, Birmingham, AL USA.
[Reboussin, David M.; Snively, Beverly M.] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA.
[Gordeuk, Victor R.] Howard Univ, Dept Med, Washington, DC 20059 USA.
[Acton, Ronald T.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[Acton, Ronald T.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Acton, Ronald T.] Univ Alabama, Dept Genet & Epidemiol, Birmingham, AL USA.
[Acton, Ronald T.] Univ Alabama, Dept Int Hlth, Birmingham, AL USA.
[Harris, Emily L.] Kaiser Permanente Ctr Hlth Res, Honolulu, HI USA.
[Speechley, Mark R.] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada.
[Sholinsky, Phyliss] NHLBI, Epidemiol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Vogt, Thomas M.] Kaiser Permanente Ctr Hlth Res, Honolulu, HI USA.
[Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
RP McLaren, GD (reprint author), VA Long Beach Healthcare Syst, Hematol Oncol Sect, 11-111-H,5901 E 7th St, Long Beach, CA 90822 USA.
EM gordon.mclaren@va.gov
FU NHLBI,; NHGRI; University of Minnesota [N01-HC-05185]; Howard University
[NO1-HC-05186]; University of Alabama at Birmingham [NO1-HC-05188];
Kaiser Permanente Centre for Health Research [N01-HC-05189]; University
of California, Irvine [N01-HC-05190]; London Health Sciences Centre
[N01-HC-05191]; Wake Forest University [N01-HC-05192]; General Clinical
Research Center, School of Medicine, University of California, Irvine;
National Center for Research Resources [5M01RR 00827-29]; U.S. Public
Health Service; GCRC [M01-RR00032]; Howard University General Clinical
Research Center (GCRC) [M01-RR10284]; NHLBI and the Office of Minority
Health [UH1-HL03679-05]
FX The HEIRS study was initiated and funded by NHLBI, in conjunction with
NHGRI. The study was supported by contracts N01-HC-05185 (University of
Minnesota), NO1-HC-05186 (Howard University), NO1-HC-05188 (University
of Alabama at Birmingham), N01-HC-05189 (Kaiser Permanente Centre for
Health Research), N01-HC-05190 (University of California, Irvine),
N01-HC-05191 (London Health Sciences Centre), and N01-HC-05192 (Wake
Forest University). Additional support was provided by the General
Clinical Research Center, School of Medicine, University of California,
Irvine, with funds provided by the National Center for Research
Resources, 5M01RR 00827-29, U.S. Public Health Service; GCRC grant
#M01-RR00032 (University of Alabama at Birmingham); and the Howard
University General Clinical Research Center (GCRC) grant, M01-RR10284
and from the NHLBI and the Office of Minority Health UH1-HL03679-05. The
work was independent of the funding.
NR 52
TC 30
Z9 31
U1 1
U2 1
PU PULSUS GROUP INC
PI OAKVILLE
PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA
SN 0835-7900
J9 CAN J GASTROENTEROL
JI Can. J. Gastroenterol.
PD NOV
PY 2008
VL 22
IS 11
BP 923
EP 930
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 378XX
UT WOS:000261359500008
PM 19018338
ER
PT J
AU Figueroa, JD
Sakoda, LC
Graubard, BI
Chanock, S
Rubertone, MV
Erickson, RL
McGlynn, KA
AF Figueroa, Jonine D.
Sakoda, Lori C.
Graubard, Barry I.
Chanock, Stephen
Rubertone, Mark V.
Erickson, R. Loren
McGlynn, Katherine A.
TI Genetic variation in hormone metabolizing genes and risk of testicular
germ cell tumors
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE testicular cancer; hormone metabolism; genetic polymorphisms
ID BREAST-CANCER RISK; POLYCHLORINATED-BIPHENYLS; ANDROGEN RECEPTOR; CYP1A1
POLYMORPHISMS; CYTOCHROME-P450 1A1; HSD17B1 GENE; IN-UTERO; ESTROGEN;
WOMEN; EXPOSURE
AB Testicular germ cell tumors (TGCT) that arise in young men are composed of two histologic types, seminomas and nonseminomas. Risk patterns for the two types appear to be similar and may be related to either endogenous or exogenous hormonal exposures in utero. Why similar risk patterns would result in different histologic types is unclear, but could be related to varying genetic susceptibility profiles. Genetic variation in hormone metabolizing genes could potentially modify hormonal exposures, and thereby affect which histologic type a man develops. To examine this hypothesis, 33 single nucleotide polymorphisms (SNPs) in four hormone metabolism candidate genes (CYP1A1, CYP17A1, HSD17B1, HSD17B4) and the androgen receptor gene (AR) were genotyped. Associations with TGCT were evaluated among 577 TGCT cases (254 seminoma, 323 nonseminoma) and 707 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study. There were no significant associations with TGCT overall based on a test using an additive model. However, compared to homozygotes of the most common allele, two nonredundant SNPs in CYP1A1 were inversely associated with nonseminoma: CYP1A1 promoter SNP rs4886605 OR = 0.75 (95% CI = 0.54-1.04) among the heterozygotes and OR = 0.37, 95% CI = 0.12-1.11 among the homozygotes with a p-value for trend = 0.02; rs2606345 intron 1 SNP, OR = 0.69 (95% CI = 0.51-0.93) among heterozygotes and OR = 0.70 (95% CI = 0.42-1.17) among homozygotes, with a p-value for trend = 0.02. Caution in interpretation is warranted until findings are replicated in other studies; however, the results suggest that genetic variation in CYP1A1 may be associated with nonseminoma.
C1 [Figueroa, Jonine D.; Graubard, Barry I.; Chanock, Stephen; McGlynn, Katherine A.] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Figueroa, Jonine D.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA.
[Sakoda, Lori C.] Univ Washington, Dept Epidemiol, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA.
[Chanock, Stephen] NCI, Dept Hlth & Human Serv, Core Genotyping Facil, Adv Technol Ctr, Bethesda, MD 20892 USA.
[Rubertone, Mark V.] USA, Ctr Hlth Promot & Prevent Med, Silver Spring, MD USA.
[Erickson, R. Loren] Walter Reed Army Inst Res, Global Emerging Infect Syst, Silver Spring, MD USA.
RP Figueroa, JD (reprint author), NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM figueroaj@mail.nih.gov
FU NCI Cancer Prevention Fellowship program
FX The authors wish to thank Emily Steplowski of IMS for her contributions
to data management and Sabah Quraishi for her contributions to data
analysis. In addition, Jonine Figueroa would like to thank Victoria Chia
and Michael Cook for discussions about data presentation and the NCI
Cancer Prevention Fellowship program for their support. The opinions or
assertions contained herein are the private views of the authors and are
not to be construed as official or as reflecting the views of the
Department of the Army or the Department of Defense.
NR 60
TC 20
Z9 23
U1 1
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD NOV
PY 2008
VL 19
IS 9
BP 917
EP 929
DI 10.1007/s10552-008-9153-6
PG 13
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 351WR
UT WOS:000259457100003
PM 18415690
ER
PT J
AU Howard, RA
Freedman, DM
Park, Y
Hollenbeck, A
Schatzkin, A
Leitzmann, MF
AF Howard, Regan A.
Freedman, D. Michal
Park, Yikyung
Hollenbeck, Albert
Schatzkin, Arthur
Leitzmann, Michael F.
TI Physical activity, sedentary behavior, and the risk of colon and rectal
cancer in the NIH-AARP Diet and Health Study
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE colon cancer; rectal cancer; physical activity; cohort studies
ID MIDDLE-AGED MEN; COLORECTAL-CANCER; LEISURE-TIME; UNITED-STATES;
FOLLOW-UP; ACTIVITY PATTERNS; WOMEN; COHORT; NUTRITION; OBESITY
AB Objective: In order to prospectively investigate physical activity at varying intensities and sedentary behavior in relation to colorectal cancer.
Methods: We considered 488,720 participants of the NIH-AARP Diet and Health Study who were aged 50-71 years at baseline in 1995-1996. Through 31 December, 2003, we identified 3,240 and 1,482 colorectal cancers among men and women, respectively. We estimated multivariable relative risks (RR) and 95% confidence intervals (CI) of colorectal cancer using Cox regression.
Results: Engaging in exercise/sports five or more times per week compared to never or rarely exercising was associated with a reduced risk of colon cancer among men (p = 0.001; RR = 0.79, 95% CI = 0.68-0.91) and a suggestive decrease in risk among women (p = 0.376; RR = 0.85, 95% CI = 0.70-1.04). Engaging in exercise/sports was also associated with a decreased risk of rectal cancer in men (P = 0.074; RR comparing extreme categories = 0.76, 95% CI = 0.61-0.94). In men, we observed inverse relations of both low intensity (p = 0.017; RR = 0.81, 95% CI = 0.65-1.00 for >= 7 h/week) and moderate to vigorous intensity activity (p = 0.037; RR = 0.82, 95% CI = 0.67-0.99 for >= 7 h/week) to colon cancer risk. In contrast, sedentary behavior (time spent watching television/videos) was positively associated with colon cancer (p < 0.001; RR = 1.61, 95% CI = 1.14-2.27 for >= 9 h/day) among men. Similar, but less pronounced relations were observed in women.
Conclusion: Engaging in physical activity of any intensity is associated with reductions in colon and rectal cancer risk. Conversely, time spent sedentary is associated with increased colon cancer risk.
C1 [Howard, Regan A.; Freedman, D. Michal] NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, NIH,DHHS, Bethesda, MD 20892 USA.
[Park, Yikyung; Schatzkin, Arthur; Leitzmann, Michael F.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
RP Howard, RA (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, NIH,DHHS, Execut Plaza S,Suite 7091, Bethesda, MD 20892 USA.
EM reganho@mail.nih.gov
OI Park, Yikyung/0000-0002-6281-489X
FU Intramural NIH HHS [Z01 CP010196-01]
NR 55
TC 73
Z9 75
U1 1
U2 19
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD NOV
PY 2008
VL 19
IS 9
BP 939
EP 953
DI 10.1007/s10552-008-9159-0
PG 15
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 351WR
UT WOS:000259457100005
PM 18437512
ER
PT J
AU Liang, XJ
Yin, JJ
Taylor, B
Winkovitch, SM
Garfield, SH
Shen, DW
Gottesman, MM
Aszalos, A
AF Liang, Xing-Jie
Yin, Jun-Jie
Taylor, Barbara
Winkovitch, Stephen M.
Garfield, Susan H.
Shen, Ding-Wu
Gottesman, Michael M.
Aszalos, Adorjan
TI Disruption of microfilaments by cytochalasin B decreases accumulation of
cisplatin in human epidermal carcinoma and liver carcinoma cell lines
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE cisplatin; electron spin resonance; cytochalasin B; carcinoma cell
lines; microfilaments
ID RESISTANT CELLS; PLEIOTROPIC DEFECT; CROSS-RESISTANCE; PLASMA-MEMBRANES;
CANCER-CELLS; ACTIN; PROTEINS; MICROTUBULES; ENDOCYTOSIS; METALS
AB Background Although cisplatin is a frequently used cancer chemotherapeutic drug, its effectiveness is hindered by the development of resistance in cancer cells. In order to understand the reason(s) for this resistance, the mechanism of uptake of cisplatin into cells must be characterized. While several previous studies showed structural differences between cisplatin-sensitive and resistant cells, the influence of microfilaments, known to affect transport of molecules into cells, and the influence of certain biophysical characteristics of the plasma membrane needed clarification.
Results We show that resistant human epidermal carcinoma (KB-CP20) and liver carcinoma (BEL-7404-CP20) cells become relatively more resistant if their already weak microfilaments are degraded by cytochalasin B treatment (.5-2 mu M). The sensitive counterparts of these cells with intact microfilaments are not significantly affected by this treatment. We also show that the "fluidity" of the plasma membrane and the membrane potential of the sensitive and resistant cells studied do not appear to influence the uptake of cisplatin into the cells.
Conclusion Our results suggest that the status of the microfilament system influences the mechanism of uptake of cisplatin into cells.
C1 [Liang, Xing-Jie; Shen, Ding-Wu; Gottesman, Michael M.; Aszalos, Adorjan] Natl Canc Inst, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Yin, Jun-Jie] US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Taylor, Barbara] NIH, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Winkovitch, Stephen M.; Garfield, Susan H.] NIH, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA.
RP Aszalos, A (reprint author), Natl Canc Inst, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM aszalosa@nih.gov
RI Yin, Jun Jie /E-5619-2014
FU Intramural Research Program of the NIH; Center for Cancer Research,
National Cancer Institute
FX We would like to thank George Leiman for his assistance with the text
and figures. This research was funded by the Intramural Research Program
of the NIH, Center for Cancer Research, National Cancer Institute.
NR 25
TC 6
Z9 6
U1 2
U2 10
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 NOV
PY 2008
VL 62
IS 6
BP 977
EP 984
DI 10.1007/s00280-008-0687-9
PG 8
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 348CR
UT WOS:000259189100006
PM 18274748
ER
PT J
AU White, DB
Bonham, VL
Jenkins, J
Stevens, N
McBride, CM
AF White, Della Brown
Bonham, Vence L.
Jenkins, Jean
Stevens, Nancy
McBride, Colleen M.
TI Too Many Referrals of Low-Risk Women for BRCA1/2 Genetic Services by
Family Physicians
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID OVARIAN-CANCER SUSCEPTIBILITY; RANDOMIZED CONTROLLED-TRIAL; MANAGED CARE
ORGANIZATION; BREAST-CANCER; INFORMATION-SERVICE; PUBLIC-HEALTH;
TASK-FORCE; KNOWLEDGE; IMPACT; GUIDELINES
AB The increasing availability and public awareness of BRCA1/2 genetic testing will increase women's self-referrals to genetic services. The objective of this study was to examine whether patient characteristics influence the referral decisions of family physicians when a patient requests BRCA1/2 genetic testing. Family physicians (n = 284) completed a Web-based survey in 2006 to assess their attitudes and practices related to the use of genetics in their clinical practice. Using a 2 x 2 x 2 factorial design, we tested the effects of a hypothetical patient's race, level of worry, and insurance status on the decisions of family physicians to refer her for BRCA1/2 testing. The patient was not appropriate for referral based on U.S. Preventive Services Task Force guidelines. No patient characteristics were associated with the family physicians' referral decisions. Although referral was not indicated, only 8% did not refer to genetic services; 92% referred for genetic services, and 50% referred to genetic counseling. Family physicians regarded it unlikely that the patient carried a mutation, but 65% of family physicians believed that if they refused to refer for genetic services it would harm their relationship with the patient. Despite scarce and costly genetic services, family physicians were likely to inappropriately refer a low-risk patient who requested BRCA1/2 testing. The implications of this inappropriate referral on women's screening behavior, genetic services, and health care costs are unknown. Clinicians and patients could benefit from education about the appropriate use of genetic services so that both are more comfortable with a decision against referral. (Cancer Epidemiol Biomarkers Prev 2008;17(11):2980-6)
C1 [White, Della Brown; Bonham, Vence L.; McBride, Colleen M.] NHGRI, NIH, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[Jenkins, Jean] NHGRI, NIH, Off Director, Bethesda, MD 20892 USA.
[Stevens, Nancy] Univ Washington, Sch Med, Seattle, WA 98195 USA.
RP White, DB (reprint author), NHGRI, NIH, Social & Behav Res Branch, 31 Ctr Dr,Bldg 31,Room B1B54G, Bethesda, MD 20892 USA.
EM whitede@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute, NIH
FX Grant support: Intramural Research Program of the National Human Genome
Research Institute, NIH.
NR 41
TC 25
Z9 25
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD NOV
PY 2008
VL 17
IS 11
BP 2980
EP 2986
DI 10.1158/1055-9965.EPI-07-2879
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 372IY
UT WOS:000260896500012
PM 18990739
ER
PT J
AU Fatima, N
Yi, M
Ajaz, S
Stephens, RM
Stauffer, S
Greenwald, P
Munroe, DJ
Ali, IU
AF Fatima, Naheed
Yi, Ming
Ajaz, Sadia
Stephens, Robert M.
Stauffer, Stacey
Greenwald, Peter
Munroe, David J.
Ali, Iqbal Unnisa
TI Altered Gene Expression Profiles Define Pathways in Colorectal Cancer
Cell Lines Affected by Celecoxib
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID INHIBITOR CELECOXIB; DNA-DAMAGE; COX-2; SUPPRESSION; APOPTOSIS;
CARCINOMA; PROTEIN; TARGET; GROWTH; TRANSCRIPTION
AB It is well established that celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) and a tested chemopreventive agent, has several COX-2-independent activities. In an attempt to better understand COX-2-independent molecular mechanisms underlying the chemopreventive activity of celecoxib, we did global transcription profiling of celecoxib-treated COX-2-positive and COX-2-deficient colorectal cancer cell lines. Celecoxib treatment resulted in significantly altered expression levels of over 1,000 to 3,000 transcripts in these cell lines, respectively. A pathway/functional analysis of celecoxib-affected transcripts, using Gene Ontology and Biocarta Pathways and exploring biological association networks, revealed that celecoxib modulates expression of numerous genes involved in a variety of cellular processes, including metabolism, cell proliferation, apoptotic signaling, cell cycle check points, lymphocyte activation, and signaling pathways. Among these processes, cell proliferation and apoptotic signaling consistently ranked as the highest-scoring Gene Ontology terms and Biocarta Pathways in both COX-2 expresser and nonexpresser cell lines. Altered expression of many of the genes by celecoxib was confirmed by quantitative PCR and at the protein level by Western blotting. Many novel genes emerged from our analysis of global transcription patterns that were not previously reported to be affected by celecoxib. In the future, in-depth work on selected genes will determine if these genes may serve as potential molecular targets for more effective chemopreventive strategies. (Cancer Epidemiol Biomarkers Prev 2008; 17(11):3051-61)
C1 [Fatima, Naheed; Stauffer, Stacey; Greenwald, Peter; Ali, Iqbal Unnisa] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Yi, Ming; Stephens, Robert M.] Sci Applicat Int Corp Inc, Adv Biomed Comput Ctr, Frederick, MD USA.
[Fatima, Naheed] Sci Applicat Int Corp Inc, Basic Res Program, Frederick, MD USA.
[Munroe, David J.] Sci Applicat Int Corp Inc, Lab Mol Technol, Frederick, MD USA.
[Ajaz, Sadia] Univ Karachi, Panjwani Ctr Mol Med, Karachi 75270, Pakistan.
RP Ali, IU (reprint author), Univ Karachi, Int Ctr Chem Biol Sci, Panjwani Ctr Mol Med & Drug Res, Mol Oncol Program, Karachi 75270, Pakistan.
EM iuali@cyber.net.pk
OI Ajaz, Sadia/0000-0003-3940-1269
FU National Cancer Institute, NIH [N01-C0-12400]
FX Grant support: National Cancer Institute, NIH, under contract
N01-C0-12400.
NR 42
TC 7
Z9 8
U1 0
U2 0
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 NOV
PY 2008
VL 17
IS 11
BP 3051
EP 3061
DI 10.1158/1055-9965.EPI-08-0261
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 372IY
UT WOS:000260896500021
PM 18957522
ER
PT J
AU Abnet, CC
Kamangar, F
Islami, F
Nasrollahzadeh, D
Brennan, P
Aghcheli, K
Merat, S
Pourshams, A
Marjani, HA
Ebadati, A
Sotoudeh, M
Boffetta, P
Malekzadeh, R
Dawsey, SM
AF Abnet, Christian C.
Kamangar, Farin
Islami, Farhad
Nasrollahzadeh, Dariush
Brennan, Paul
Aghcheli, Karim
Merat, Shahin
Pourshams, Akram
Marjani, Haj Amin
Ebadati, Abdolhakim
Sotoudeh, Masoud
Boffetta, Paolo
Malekzadeh, Reza
Dawsey, Sanford M.
TI Tooth Loss and Lack of Regular Oral Hygiene Are Associated with Higher
Risk of Esophageal Squamous Cell Carcinoma
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID MALE HEALTH-PROFESSIONALS; NORTHEASTERN IRAN; GASTROINTESTINAL-TRACT;
PERIODONTAL-DISEASE; PANCREATIC-CANCER; GOLESTAN COHORT; GASTRIC
CANCERS; POPULATION; CHINA; RELIABILITY
AB We tested the association between tooth loss and oral hygiene and the risk of esophageal squamous cell carcinoma (ESCC) in people living in a high-risk area of Iran. We used a case-control study of pathologically confirmed ESCC cases (n = 283) and controls (n = 560) matched on sex, age, and neighborhood. Subjects with ESCC had significantly more decayed, missing, or filled teeth (DMFT) with a median (interquartile range) of 31 (23-32) compared with controls 28 (16-32; P = 0.0045). Subjects with ESCC were significantly more likely than controls to fail to practice regular oral hygiene (78% versus 58%). In multivariate-adjusted conditional logistic regression models, having 32 DMFT compared with <= 15 conferred an odds ratio (95% confidence interval) of 2.10 (1.19-3.70). Compared with daily tooth brushing, practicing no regular oral hygiene conferred an odds ratio (95% confidence interval) of 2.37 (1.42-3.97). Restricting the analysis to subjects that had never smoked tobacco did not materially alter these results. We found significant associations between two markers of poor oral hygiene, a larger number of DMFT and lack of daily tooth brushing, and risk of ESCC in a population at high risk for ESCC where many cases occur in never smokers. Our results are consistent with several previous analyses in other high-risk populations. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3062-8)
C1 [Abnet, Christian C.; Kamangar, Farin; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Rockville, MD 20852 USA.
[Islami, Farhad; Aghcheli, Karim; Merat, Shahin; Pourshams, Akram; Marjani, Haj Amin; Ebadati, Abdolhakim; Sotoudeh, Masoud; Malekzadeh, Reza] IARC, Lyon, France.
[Islami, Farhad; Nasrollahzadeh, Dariush; Brennan, Paul; Boffetta, Paolo] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran.
RP Abnet, CC (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Execut Plaza S,Room 320,6120 Execut Blvd,MSC 7232, Rockville, MD 20852 USA.
EM abnetc@mail.nih.gov
RI Abnet, Christian/C-4111-2015;
OI Abnet, Christian/0000-0002-3008-7843; Malekzadeh,
Reza/0000-0003-1043-3814
FU Digestive Disease Research Center of Tehran University of Medical
Sciences [82-603]; National Cancer Institute, NIH intramural funds
FX Grant support: Digestive Disease Research Center of Tehran University of
Medical Sciences grant 82-603 and National Cancer Institute, NIH
intramural funds.
NR 31
TC 65
Z9 66
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD NOV
PY 2008
VL 17
IS 11
BP 3062
EP 3068
DI 10.1158/1055-9965.EPI-08-0558
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 372IY
UT WOS:000260896500022
PM 18990747
ER
PT J
AU Anderson, LA
Pfeiffer, R
Warren, JL
Landgren, O
Gadalla, S
Berndt, SI
Ricker, W
Parsons, R
Wheeler, W
Engels, EA
AF Anderson, Lesley A.
Pfeiffer, Ruth
Warren, Joan L.
Landgren, Ola
Gadalla, Shahinaz
Berndt, Sonja I.
Ricker, Winnie
Parsons, Ruth
Wheeler, William
Engels, Eric A.
TI Hematopoietic Malignancies Associated with Viral and Alcoholic Hepatitis
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; C-VIRUS-INFECTION; B-VIRUS; UNITED-STATES;
EPIDEMIOLOGY CONSORTIUM; CYTOTOXIC THERAPY; BURKITTS-LYMPHOMA; RISK;
PREVALENCE; CONSUMPTION
AB Hepatitis C virus (HCV) and hepatitis B virus (HBV) have been associated with hematopoietic malignancies, but data for many subtypes are limited. From the U.S. Surveillance, Epidemiology, and End Results-Medicare database, we selected 61,464 cases ( >= 67 years) with hematopoietic malignancies and 122,531 population-based controls, frequency-matched by gender, age, and year (1993-2002). Logistic regression was used to compare the prevalence of HCV, HBV, and alcoholic hepatitis in cases and controls, adjusted for matching factors, race, duration of Medicare coverage, and number of physician claims. HCV, HBV, and alcoholic hepatitis were reported in 195 (0.3%), 111 (0.2%), and 404 (0.7%) cases and 264 (0.2%), 242 (0.2%), and 798 (0.7%) controls, respectively. HCV was associated with increased risk of diffuse large B-cell lymphoma [odds ratio (OR) 1.52,95% confidence interval (95% CI) 1.05-2.18], Burkitt lymphoma (OR 5.21, 95% CI 1.62-16.8), follicular lymphoma (OR 1.88, 95% CI 1.17-3.02), marginal zone lymphoma (OR 2.20, 95% Cl 1.22-3.95), and acute myeloid leukemia (OR 1.54, 95% Cl 1.00-2.37). In contrast, HBV was unrelated to any hematopoietic malignancies. Alcoholic hepatitis was associated with decreased risk of non-Hodgkin lymphoma overall, but increased risk of Burkitt lymphoma. In summary, HCV, but not other causes of hepatitis, was associated with the elevated risk of non-Hodgkin lymphoma and acute myeloid leukemia. HCV may induce lymphoproliferative malignancies through chronic immune stimulation. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3069-75)
C1 [Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA.
[Warren, Joan L.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Anderson, Lesley A.] Queens Univ Belfast, Ctr Clin & Populat Sci, Belfast, Antrim, North Ireland.
[Ricker, Winnie; Parsons, Ruth; Wheeler, William] Informat Management Serv Inc, Rockville, MD USA.
RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, 6120 Execut Blvd,EPS 7076, Bethesda, MD 20892 USA.
EM engelse@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011;
OI Anderson, Lesley/0000-0002-1000-3649
FU National Cancer Institute; Research and Development Office, Northern
Ireland
FX The costs of publication of this article were defrayed in part by the
payment of page charges. This article must therefore be hereby marked
advertisement in accordance with 18 U.S.C. Section 1734 solely to
indicate this fact.; This study used the linked SEER-Medicare database.
The interpretation and reporting of these data are the sole
responsiblity of the authors. The authors acknowledge the effort of the
Applied Research Program, National Cancer Institute (NCI); the Office of
research, Development, and Information, Centres for Medicare and
Medicaid Services; Information Management Services (IMS), Inc; and the
Surveillance, Epidemiology, and End Result (SEER) Program tumour
registries in the creation of the SEER-Medicare database. This research
was supported by the Intramural Research Program of the National Cancer
Institute. The Research and Development Office, Northern Ireland, funded
Dr. Lesley Anderson to participate in the Cancer Prevention Felllowship
Program, Office of Preventive Oncology, NCI.
NR 49
TC 49
Z9 52
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD NOV
PY 2008
VL 17
IS 11
BP 3069
EP 3075
DI 10.1158/1055-9965.EPI-08-0408
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 372IY
UT WOS:000260896500023
PM 18957521
ER
PT J
AU Hung, RJ
Christiani, DC
Risch, A
Popanda, O
Haugen, A
Zienolddiny, S
Benhamou, S
Bouchardy, C
Lan, Q
Spitz, MR
Wichmann, HE
LeMarchand, L
Vineis, P
Matullo, G
Kiyohara, C
Zhang, ZF
Pezeshki, B
Harris, C
Mechanic, L
Seow, A
Ng, DPK
Szeszenia-Dabrowska, N
Zaridze, D
Lissowska, J
Rudnai, P
Fabianova, E
Mates, D
Foretova, L
Janout, V
Bencko, V
Caporaso, N
Chen, C
Duell, EJ
Goodman, G
Field, JK
Houlston, RS
Hong, YC
Landi, MT
Lazarus, P
Muscat, J
McLaughlin, J
Schwartz, AG
Shen, H
Stucker, I
Tajima, K
Matsuo, K
Thun, M
Yang, P
Wiencke, J
Andrew, AS
Monnier, S
Boffetta, P
Brennan, P
AF Hung, Rayjean J.
Christiani, David C.
Risch, Angela
Popanda, Odilia
Haugen, Aage
Zienolddiny, Shan
Benhamou, Simone
Bouchardy, Christine
Lan, Qing
Spitz, Margaret R.
Wichmann, H. -Erich
LeMarchand, Loic
Vineis, Paolo
Matullo, Giuseppe
Kiyohara, Chikako
Zhang, Zuo-Feng
Pezeshki, Benhnaz
Harris, Curtis
Mechanic, Leah
Seow, Adeline
Ng, Daniel P. K.
Szeszenia-Dabrowska, Neonila
Zaridze, David
Lissowska, Jolanta
Rudnai, Peter
Fabianova, Eleonora
Mates, Dana
Foretova, Lenka
Janout, Vladimir
Bencko, Vladimir
Caporaso, Neil
Chen, Chu
Duell, Eric J.
Goodman, Gary
Field, John K.
Houlston, Richard S.
Hong, Yun-Chul
Landi, Maria Teresa
Lazarus, Philip
Muscat, Joshua
McLaughlin, John
Schwartz, Ann G.
Shen, Hongbing
Stucker, Isabelle
Tajima, Kazuo
Matsuo, Keitaro
Thun, Michael
Yang, Ping
Wiencke, John
Andrew, Angeline S.
Monnier, Stephanie
Boffetta, Paolo
Brennan, Paul
TI International Lung Cancer Consortium: Pooled Analysis of Sequence
Variants in DNA Repair and Cell Cycle Pathways
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; SUSCEPTIBILITY LOCUS; RISK;
METAANALYSIS; XRCC3; ASSOCIATION; SMOKING; GENES; P53; EPIDEMIOLOGY
AB Background: The International Lung Cancer Consortium was established in 2004. To clarify the role of DNA repair genes in lung cancer susceptibility, we conducted a pooled analysis of genetic variants in DNA repair pathways, whose associations have been investigated by at least 3 individual studies.
Methods: Data from 14 studies were pooled for 18 sequence variants in 12 DNA repair genes, including APEX1, OGG1, XRCC1, XRCC2, XRCC3, ERCC1, XPD, XPF, XPG, XPA, MGMT, and TP53. The total number of subjects included in the analysis for each variant ranged from 2,073 to 13,955 subjects.
Results: Four of the variants were found to be weakly associated with lung cancer risk with borderline significance: these were XRCC3 T241M [heterozygote odds ratio (OR), 0.89; 95% confidence interval (95% CI), 0.79-0.99 and homozygote OR, 0.84; 95% Cl, 0.71-1.00] based on 3,467 cases and 5,021 controls from 8 studies, XPD K751Q (heterozygote OR, 0.99; 95% Cl, 0.89-1.10 and homozygote OR, 1.19; 95% CI, 1.02-1.39) based on 6,463 cases and 6,603 controls from 9 studies, and TP53 R72P (heterozygote OR, 1.14; 95% Cl, 1.00-1.29 and homozygote OR, 1.20; 95% CI, 1.02-1.42) based on 3,610 cases and 5,293 controls from 6 studies. OGG1 S326C homozygote was suggested to be associated with lung cancer risk in Caucasians (homozygote OR, 1.34; 95% CI, 1.01-1.79) based on 2,569 cases and 4,178 controls from 4 studies but not in Asians. The other 14 variants did not exhibit main effects on lung cancer risk.
Discussion: In addition to data pooling, future priorities of International Lung Cancer Consortium include coordinated genotyping and multistage validation for ongoing genome-wide association studies. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3081-9)
C1 [Hung, Rayjean J.; Duell, Eric J.; Monnier, Stephanie; Boffetta, Paolo; Brennan, Paul] IARC, F-69008 Lyon, France.
[McLaughlin, John] Canc Care Ontario, Toronto, ON, Canada.
[Christiani, David C.] Harvard Univ, Boston, MA 02115 USA.
[Risch, Angela; Popanda, Odilia] German Canc Res Ctr, D-6900 Heidelberg, Germany.
[Haugen, Aage; Zienolddiny, Shan] Natl Inst Occupat Hlth, Oslo, Norway.
[Benhamou, Simone] Fdn Jean Dausset CEPH, INSERM U794, Paris, France.
[Benhamou, Simone] Inst Gustave Roussy, CNRS FRE2939, Villejuif, France.
[Bouchardy, Christine] Canc Registry, Geneva, Switzerland.
[Lan, Qing; Harris, Curtis; Mechanic, Leah; Caporaso, Neil; Landi, Maria Teresa] NCI, Rockville, MD USA.
[Spitz, Margaret R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Wichmann, H. -Erich] GSF Natl Res Ctr Environm & Hlth, Neuherberg, Germany.
[Wichmann, H. -Erich] Univ Munich, IBE, D-80539 Munich, Germany.
[LeMarchand, Loic] Univ Hawaii, Honolulu, HI 96822 USA.
[Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, London, England.
[Matullo, Giuseppe] Univ Turin, Turin, Italy.
[Kiyohara, Chikako] Kyushu Univ, Fukuoka 812, Japan.
[Zhang, Zuo-Feng; Pezeshki, Benhnaz] Univ Calif Los Angeles, Los Angeles, CA USA.
[Seow, Adeline; Ng, Daniel P. K.] Natl Univ Singapore, Singapore 117548, Singapore.
[Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Dept Epidemiol, Lodz, Poland.
[Zaridze, David] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Rudnai, Peter] Fodor Jozsef Natl Ctr Publ Hlth, Natl Inst Environm Hlth, Budapest, Hungary.
[Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia.
[Mates, Dana] Inst Publ Hlth, Bucharest, Romania.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Janout, Vladimir] Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic.
[Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Chen, Chu; Goodman, Gary] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Field, John K.] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Programme, Liverpool L69 3BX, Merseyside, England.
[Houlston, Richard S.] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England.
[Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Seoul, South Korea.
[Lazarus, Philip; Muscat, Joshua] Penn State Coll Med, Hershey, PA USA.
[Schwartz, Ann G.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA.
[Shen, Hongbing] Nanjing Med Univ, Sch Publ Hlth, Nanjing, Peoples R China.
[Stucker, Isabelle] INSERM U754, Villejuif, France.
[Stucker, Isabelle] UMR S754, Villejuif, France.
[Tajima, Kazuo; Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Aichi, Japan.
[Thun, Michael] Amer Canc Soc, Atlanta, GA 30329 USA.
[Yang, Ping] Mayo Clin, Ctr Canc, Rochester, MI USA.
[Wiencke, John] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Andrew, Angeline S.] Dartmouth Med Sch, Lebanon, NH USA.
RP Boffetta, P (reprint author), IARC, 150 Cours Albert Thomas, F-69008 Lyon, France.
EM boffetta@iarc.fr
RI Hong, Yun-Chul/J-5725-2012; Hung, Rayjean/A-7439-2013; McLaughlin,
John/E-4577-2013; Zaridze, David/K-5605-2013; Janout,
Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010;
Zienolddiny, Shanbeh/O-7392-2015; Benhamou, Simone/K-6554-2015; Matullo,
Giuseppe/K-6383-2016; Risch, Angela/H-2669-2013;
OI Field, John/0000-0003-3951-6365; Matsuo, Keitaro/0000-0003-1761-6314;
Houlston, Richard/0000-0002-5268-0242; mates, dana/0000-0002-6219-9807;
Lissowska, Jolanta/0000-0003-2695-5799; Risch,
Angela/0000-0002-8026-5505; Duell, Eric J/0000-0001-5256-0163; MATULLO,
Giuseppe/0000-0003-0674-7757
FU National Cancer Institute [CA119704]
FX Grant support: National Cancer Institute R03 grant CA119704.
NR 36
TC 58
Z9 68
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 NOV
PY 2008
VL 17
IS 11
BP 3081
EP 3089
DI 10.1158/1055-9965.EPI-08-0411
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 372IY
UT WOS:000260896500025
PM 18990748
ER
PT J
AU Brinton, LA
Richesson, D
Leitzmann, MF
Gierach, GL
Schatzkin, A
Mouw, T
Hollenbeck, AR
Lacey, JV
AF Brinton, Louise A.
Richesson, Douglas
Leitzmann, Michael F.
Gierach, Gretchen L.
Schatzkin, Arthur
Mouw, Traci
Hollenbeck, Albert R.
Lacey, James V., Jr.
TI Menopausal Hormone Therapy and Breast Cancer Risk in the NIH-AARP Diet
and Health Study Cohort
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID PROGESTIN-REPLACEMENT THERAPY; ESTROGEN PLUS PROGESTIN; CONJUGATED
EQUINE ESTROGENS; RANDOMIZED CONTROLLED-TRIAL; WOMENS HEALTH;
POSTMENOPAUSAL WOMEN; UNITED-STATES; DIFFERENT REGIMENS;
PROGNOSTIC-FACTORS; RECEPTOR STATUS
AB Background: Results from the Women's Health Initiative trial raise new questions regarding the effects of estrogen therapy (ET) and estrogen plus progestin therapy (EPT) on breast cancer risk.
Methods: We analyzed data from 126,638 females, ages 50 to 71 years at baseline, who completed two questionnaires (1995-1996 and 1996-1997) as part of the NIH-AARP Diet and Health Cohort Study and in whom 3,657 incident breast cancers were identified through June 30, 2002. Hormone-associated relative risks (RR) and 95% confidence intervals (CI) of breast cancer were estimated via multivariable regression models.
Results: Among thin women (body mass index <25 kg/m(2)), ET use was associated with a significant 60% excess risk after 10 years of use. EPT was associated with a significantly increased risk among women with intact uteri, with the highest risk among current, long-term (>= 10 years) users (RR, 2.44; 95% Cl, 2.13-2.79). These risks were slightly higher when progestins were prescribed continuously than sequentially (<15 days/mo; respective RRs of 2.76 versus 2.01). EPT associations were strongest in thin women, but elevated risks persisted among heavy women. EPT use was strongly related to estrogen receptor (ER)-positive tumors, requiring consideration of this variable when assessing relationships according to other clinical features. For instance, ER- ductal tumors were unaffected by EPT use, but all histologic subgroups of ER+ tumors were increased, especially low-grade and mixed ductal-lobular tumors.
Conclusions: Both ET and EPT were associated with breast cancer risks with the magnitude of increase varying according to body mass and clinical characteristics of the tumors. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3150-60)
C1 [Brinton, Louise A.; Richesson, Douglas; Gierach, Gretchen L.; Lacey, James V., Jr.] NCI, Hormonal & Reprod Epidemiol Branch, Washington, DC USA.
[Leitzmann, Michael F.; Schatzkin, Arthur; Mouw, Traci] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Washington, DC USA.
[Hollenbeck, Albert R.] AARP, Org & Tracking Res Dept, Washington, DC USA.
RP Brinton, LA (reprint author), 6120 Execut Blvd,Suite 550,Room 5018, Rockville, MD 20852 USA.
EM brinton@nih.gov
RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016
OI Brinton, Louise/0000-0003-3853-8562; Gierach,
Gretchen/0000-0002-0165-5522
FU NIH, National Cancer Institute; Department of Health; Louisiana by the
Louisiana Tumor Registry; Louisiana State University Medical Center; New
Orleans; New Jersey by the New Jersey State Cancer Registry; Cancer
Epidemiology Services; New Jersey State Department of Health and Senior
Services; North Carolina by the North Carolina Central Cancer Registry;
Pennsylvania by the Division of Health Statistics and Research;
Pennsylvania Department of Health, Harrisburg, PA
FX Intramural Research Program of the NIH, National Cancer Institute.
Cancer incidence data were collected for the Atlanta metropolitan area
by the Georgia Center for Cancer Statistics, Department of Epidemiology,
Rollins School of Public Health, Emory University; for California by the
California Department of Health Services, Cancer Surveillance Section;
for the Detroit metropolitan area by the Michigan Cancer Surveillance
Program, Community Health Administration, State of Michigan; for Florida
by the Florida Cancer Data Svstem under contract to the Department of
Health; for Louisiana by the Louisiana Tumor Registry, Louisiana State
University Medical Center, New Orleans; for New Jersey by the New Jersey
State Cancer Registry, Cancer Epidemiology Services, New Jersey State
Department of Health and Senior Services; for North Carolina by the
North Carolina Central Cancer Registry; and for Pennsylvania by the
Division of Health Statistics and Research, Pennsylvania Department of
Health, Harrisburg, PA.
NR 56
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U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD NOV
PY 2008
VL 17
IS 11
BP 3150
EP 3160
DI 10.1158/1055-9965.EPI-08-0435
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 372IY
UT WOS:000260896500034
PM 18990757
ER
PT J
AU Wayne, S
Neuhouser, ML
Ulrich, CM
Koprowski, C
Wiggins, C
Baumgartner, KB
Bernstein, L
Baumgartner, RN
Gilliland, F
McTiernan, A
Ballard-Barbash, R
AF Wayne, Sharon
Neuhouser, Marian L.
Ulrich, Cornelia M.
Koprowski, Carol
Wiggins, Charles
Baumgartner, Kathy B.
Bernstein, Leslie
Baumgartner, Richard N.
Gilliland, Frank
McTiernan, Anne
Ballard-Barbash, Rachel
TI Association between Alcohol Intake and Serum Sex Hormones and Peptides
Differs by Tamoxifen Use in Breast Cancer Survivors
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID PHYSICAL-ACTIVITY LEVELS; GROWTH-FACTOR-I; POSTMENOPAUSAL WOMEN;
DEHYDROEPIANDROSTERONE-SULFATE; INSULIN-RESISTANCE; MESSENGER-RNA;
LEPTIN LEVELS; DHEA SULFATE; RISK; CONSUMPTION
AB Objective: To measure the association between alcohol intake and 11 hormones and peptides in postmenopausal breast cancer survivors and to evaluate whether this association differs by tamoxifen use.
Methods: Self-reported alcohol intake was assessed via food frequency questionnaire on average 30 months post-breast cancer diagnosis in 490 postmenopausal women from three western states. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, C-peptide, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3. Adjusted means of these hormones and peptides were calculated for categories of alcohol intake, overall and stratified by tamoxifen use.
Results: The association between alcohol intake and serum hormone and peptide levels differed by tamoxifen use. We found statistically significant inverse associations between alcohol intake and both leptin and SHBG values but only among tamoxifen users. In women not using tamoxifen, we found a positive association between alcohol intake and DHEAS but no association in tamoxifen users.
Conclusion: Tamoxifen may modify the association between alcohol intake and serum hormones and peptides. The significant associations found for DHEAS and SHBG are in a direction considered unfavorable for breast cancer prognosis. Postmenopausal breast cancer survivors may benefit from decreasing their alcohol intake. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3224-32)
C1 [Wayne, Sharon; Wiggins, Charles] Univ New Mexico, New Mexico Tumor Registry, Albuquerque, NM 87131 USA.
[Neuhouser, Marian L.; Ulrich, Cornelia M.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
[Koprowski, Carol; Gilliland, Frank] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Baumgartner, Kathy B.; Baumgartner, Richard N.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Ballard-Barbash, Rachel] NCI, Appl Res Program, Bethesda, MD 20892 USA.
RP Wayne, S (reprint author), Univ New Mexico, New Mexico Tumor Registry, MSC 11 6020, Albuquerque, NM 87131 USA.
EM swayne@salud.unm.edu
RI Perez , Claudio Alejandro/F-8310-2010
OI Perez , Claudio Alejandro/0000-0001-9688-184X
FU National Cancer Institute [N01-CN-75036-20, N01-CN-05228, N01-PC-67010,
N01-PC-35139, N01-PC-67007, N01-PC-35138, N01-PC-67009, N01-PC-35142,
T32 CA09661]; University of Washington; NIH [M01-RR-00037]; National
Institute of Child Health and Human Development [N01-HD-3-3175];
California Department of Health Services [050Q-8709-S1528]; University
of New Mexico Cancer Center; National Cancer Institute cancer
[P30-CA118100]
FX National Cancer Institute contracts N01-CN-75036-20, N01-CN-05228,
N01-PC-67010/N01-PC-35139, N01-PC-67007/N01-PC-35138, and
N01-PC-67009/N01-PC-35142 and training grant T32 CA09661. A portion of
this work was conducted through the Clinical Research Center at the
University of Washington and supported by the NIH grant M01-RR-00037.
Data collection for the Women's Contraceptive and Reproductive
Experiences Study at the University of Southern California was supported
by the National Institute of Child Health and Human Development contract
N01-HD-3-3175. Patient identification was supported in part by the
California Department of Health Services grant 050Q-8709-Sl528.
Preparation of this article was supported, in part, by the University of
New Mexico Cancer Center, a recipient of National Cancer Institute
cancer support grant P30-CA118100.
NR 55
TC 5
Z9 5
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD NOV
PY 2008
VL 17
IS 11
BP 3224
EP 3232
DI 10.1158/1055-9965.EPI-08-0171
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 372IY
UT WOS:000260896500043
PM 18957523
ER
PT J
AU Weinstein, SJ
Albanes, D
Selhub, J
Graubard, B
Lim, U
Taylor, PR
Virtamo, J
Stolzenberg-Solomon, R
AF Weinstein, Stephanie J.
Albanes, Demetrius
Selhub, Jacob
Graubard, Barry
Lim, Unhee
Taylor, Philip R.
Virtamo, Jarmo
Stolzenberg-Solomon, Rachael
TI One-Carbon Metabolism Biomarkers and Risk of Colon and Rectal Cancers
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID NESTED CASE-CONTROL; COLORECTAL-CANCER; FOLATE LEVELS;
CELL-PROLIFERATION; TOTAL HOMOCYSTEINE; PLASMA FOLATE; FOLIC-ACID;
VITAMIN-B-6; COHORT; WOMEN
AB Background: Folate intake has been associated with reduced colorectal cancer risk; however, few studies have prospectively examined circulating folate or other related one-carbon biomarkers.
Methods: We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 50- to 69-year-old Finnish men to investigate associations between serum folate, vitamin B6, vitamin B12, riboflavin, and homocysteine and risk of colon and rectal cancers. Controls were alive and cancer-free at the time of case diagnosis and matched 1:1 on age and date of baseline fasting serum collection with cases (152 colon and 126 rectal cancers). Multivariate-adjusted odds ratios and 95% confidence intervals were calculated using conditional logistic regression.
Results: Serum vitamin B6 was inversely associated with colon cancer [odds ratio, 0.30 (95% confidence interval, 0.11-0.82) in the highest versus lowest quintile]. An increased risk of colon cancer was suggested for men in the middle quintile of serum folate, but without indication of a dose-response relationship. None of the other serum biomarkers were associated with colon or rectal cancer, and we observed no interactions with alcohol consumption or methionine or protein intake. A priori combinations of the five one-carbon serum biomarkers provided no clear evidence to support a collective influence on colorectal cancer risk.
Conclusions: Our results support the hypothesis that higher vitamin B6 status may play a role in inhibiting colon cancer carcinogenesis; however, folate and other one-carbon related biomarkers were not associated with colon or rectal cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3233-40)
C1 [Weinstein, Stephanie J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Ser, Bethesda, MD 20892 USA.
[Selhub, Jacob] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA.
[Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland.
RP Weinstein, SJ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Ser, Suite 320,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM weinstes@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015
FU NIH National Cancer Institute Intramural Research Program and Public
Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004]; National
Cancer Institute, Department of Health and Human Services
FX NIH National Cancer Institute Intramural Research Program and Public
Health Service contracts N01-CN-45165, N01-RC-45035, and N01-RC-37004
from the National Cancer Institute, Department of Health and Human
Services.
NR 50
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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 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD NOV
PY 2008
VL 17
IS 11
BP 3233
EP 3240
DI 10.1158/1055-9965.EPI-08-0459
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 372IY
UT WOS:000260896500044
PM 18990766
ER
PT J
AU Chu, LW
Zhu, Y
Yu, K
Zheng, TZ
Chokkalingam, AP
Stanczyk, FZ
Gao, YT
Hsing, AW
AF Chu, Lisa W.
Zhu, Yong
Yu, Kai
Zheng, Tongzhang
Chokkalingam, Anand P.
Stanczyk, Frank Z.
Gao, Yu-Tang
Hsing, Ann W.
TI Correlation between Circadian Gene Variants and Serum Levels of Sex
Steroids and Insulin-like Growth Factor-I
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID EXTREME DIURNAL PREFERENCE; FACTOR BINDING PROTEIN-3; FACTOR (IGF)-I;
PROSTATE-CANCER; BREAST-CANCER; ELDERLY MEN; IGF-II; HORMONE;
TESTOSTERONE; POLYMORPHISM
AB A variety of biological processes, including steroid hormone secretion, have circadian rhythms, which are influenced by nine known circadian genes. Previously, we reported that certain variants in circadian genes were associated with risk for prostate cancer. To provide some biological insight into these findings, we examined the relationship of five variants of circadian genes, including NPAS2 (rs2305160:G>A), PER1 (rs2585405:G>C), CSNK1E (rs1005473:A>C), PER3 (54-bp repeat length variant), and CRY2 (rs1401417:G>C), with serum levels of sex steroids and insulin-like growth factor (IGF)-I and IGF-binding protein 3 (IGFBP3) in 241 healthy elderly Chinese men (mean age of 71.5). Age-adjusted and waist-to-hip ratio-adjusted ANOVA followed by likelihood ratio tests (LRT) showed that the NPAS2 variant A allele was associated with lower free and bioavailable testosterone (P-LRT = 0.02 and 0.01, respectively) compared with the GG genotype. In addition, the PER1 variant was associated with higher serum levels of sex hormonebinding globulin levels (P-trend = 0.03), decreasing 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide levels (P-trend = 0.02), and decreasing IGFBP3 levels (P-trend = 0.05). Furthermore, the CSNK1E variant C allele was associated with higher testosterone to dihydrotestosterone ratios (P-LRT = 0-01) compared with the AA genotype, whereas the longer PER3 repeat was associated with higher serum levels of IGF-I (P-LRT = 0.03) and IGF-I to IGFBP3 ratios (P-LRT = 0.04). The CRY2 polymorphism was not associated with any biomarkers analyzed. Our findings, although in need of confirmation, suggest that variations in circadian genes are associated with serum hormone levels, providing biological support for the role of circadian genes in hormone-related cancers. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3268-73)
C1 [Chu, Lisa W.; Yu, Kai; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Chu, Lisa W.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA.
[Zhu, Yong; Zheng, Tongzhang] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Chokkalingam, Anand P.] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA.
[Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
RP Chu, LW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA.
EM chulisa@mail.nih.gov
NR 35
TC 22
Z9 23
U1 0
U2 0
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 NOV
PY 2008
VL 17
IS 11
BP 3268
EP 3273
DI 10.1158/1055-9965.EPI-08-0073
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 372IY
UT WOS:000260896500048
PM 18990770
ER
PT J
AU Berzofsky, JA
Terabe, M
AF Berzofsky, Jay A.
Terabe, Masaki
TI A novel immunoregulatory axis of NKT cell subsets regulating tumor
immunity
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article; Proceedings Paper
CT Progress in Vaccination Against Cancer 7 (PIVAC 7)
CY SEP 10-11, 2007
CL Stockholm, SWEDEN
DE tumor immunosurveillance; immunoregulation; NKT cells; tumor immunity
ID KILLER T-CELLS; ANTITUMOR IMMUNITY; IN-VIVO; IMMUNOSURVEILLANCE;
ACTIVATION; IL-13; AUTOIMMUNITY; RECOGNITION; SUFFICIENT; SULFATIDE
AB There are many mechanisms that regulate and dampen the immune response to cancers, including several types of regulatory T cells. Besides the T reg cell, we have identified another immunoregulatory circuit initiated by NKT cells that produce IL-13 in response to tumor growth and this IL-13 then induces myeloid cells to make TGF-beta that inhibits cytotoxic T cell-mediated tumor immunosurveillance in several mouse tumor models. This finding created a paradox in the role of NKT cells in tumor immunity, in that they can also contribute to protection. We resolve this paradox by the finding that the suppressive NKT cell is a type II NKT cell that lacks the canonical invariant T cell receptor, whereas the protective cell is a type I NKT cell that expresses the invariant receptor. Further, we see that these two subsets of NKT cells counter-regulate each other, defining a new immunoregulatory axis. The balance along this axis may determine the outcome of tumor immunosurveillance as well as influence the efficacy of anti-cancer vaccines and immunotherapy.
C1 [Berzofsky, Jay A.; Terabe, Masaki] Natl Canc Inst, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Berzofsky, JA (reprint author), Natl Canc Inst, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA.
EM berzofsk@helix.nih.gov; terabe@mail.nih.gov
NR 31
TC 35
Z9 38
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD NOV
PY 2008
VL 57
IS 11
BP 1679
EP 1683
DI 10.1007/s00262-008-0495-4
PG 5
WC Oncology; Immunology
SC Oncology; Immunology
GA 341MC
UT WOS:000258717600011
PM 18369622
ER
PT J
AU Rowland, JH
AF Rowland, Julia H.
TI What Are Cancer Survivors Telling Us?
SO CANCER JOURNAL
LA English
DT Article
DE cancer survivors; lessons learned; cancer survivorship research; quality
of care; cancer control
ID BREAST-CANCER; PHYSICAL-ACTIVITY; PSYCHOSOCIAL FACTORS; TEACHABLE
MOMENT; PEDIATRIC CANCER; DIAGNOSIS; HEALTH; CARE; MECHANISMS; CHALLENGE
AB Among the great medical success stories of the 20th century was our ability to turn cancer. once almost uniformily fatal into an illness that was curable for more people, and could be controlled in most. As a result of advances in screening and early detection, the development of effective treatments and the delivery of better supportive care, the population of those living long term with a history of cancer continues to grow. The field of cancer survivorship research, now entering its adolescence, has developed to help us better understand the human and social challenges of living long term after cancer. Estimated at approaching 12 million, cancer survivors have taught us a number of important lessons about what it means to live beyond a cancer diagnosis. In this article, 7 of these lessons will be discussed along with their implications for current clinical practice and future directions in cancer survivorship research.
C1 [Rowland, Julia H.] NCI, Off Canc Survivorship, NIH, DHHS, Bethesda, MD 20892 USA.
RP Rowland, JH (reprint author), 6116 Execut B,Blvd,Suite 404, Bethesda, MD 20892 USA.
EM rowland.j@mail.nih.gov
NR 56
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Z9 32
U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
J9 CANCER J
JI Cancer J.
PD NOV-DEC
PY 2008
VL 14
IS 6
BP 361
EP 368
DI 10.1097/PPO.0b013e31818ec48e
PG 8
WC Oncology
SC Oncology
GA 382IY
UT WOS:000261600700004
PM 19060600
ER
PT J
AU Fall-Dickson, JM
Mock, V
Berk, RA
Grimm, PM
Davidson, N
Gaston-Johansson, F
AF Fall-Dickson, Jane M.
Mock, Victoria
Berk, Ronald A.
Grimm, Patricia M.
Davidson, Nancy
Gaston-Johansson, Fannie
TI Stomatitis-Related Pain in Women With Breast Cancer Undergoing
Autologous Hematopoietic Stem Cell Transplant
SO CANCER NURSING
LA English
DT Article
DE Acute oral pain; Autologous hematopoietic stem cell transplantation;
Stomatitis
ID BONE-MARROW-TRANSPLANTATION; ORAL MUCOSITIS; DEPRESSION; COMPLICATIONS;
PATHOBIOLOGY; MANAGEMENT
AB The purpose of this cross-sectional, correlational study was to describe stomatitis-related pain in women with breast cancer undergoing autologous hematopoietic stem cell transplant. The hypotheses that significant, positive relationships would exist between oral pain and stomatitis, state anxiety, depression, and alteration in swallowing were tested. Stomatitis, sensory dimension of oral pain, and state anxiety were hypothesized to most accurately predict oral pain overall intensity. Thirty-two women were recruited at 2 East Coast comprehensive cancer centers. Data were collected on bone marrow transplantation day +7 +/- 24 hours using Painometer, Oral Mucositis Index-20, Oral Assessment Guide, State-Trait Anxiety Inventory, and Beck Depression Inventory. Data analysis included descriptive statistics, correlations, and stepwise multiple regression. All participants had stomatitis; 47% had oral pain, with a subset reporting continuous moderate to severe oral pain despite pain management algorithms. Significant, positive associations were seen between oral pain, stomatitis, and alteration in swallowing and between oral pain with swallowing and alteration in swallowing. Oral pain was not significantly correlated with state anxiety and depression. Oral sensory and affective pain Intensity most accurately predicted oral pain overall intensity. Future research needs to explore factors that affect perception and response to stomatitis-related oropharyngeal pain and individual patient response to opioid treatment.
C1 [Fall-Dickson, Jane M.] NINR, Symptom Management Branch, NIH, Bethesda, MD 20892 USA.
[Mock, Victoria] Johns Hopkins Univ, Ctr Nursing Res, Baltimore, MD USA.
[Berk, Ronald A.; Grimm, Patricia M.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA.
[Davidson, Nancy] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Gaston-Johansson, Fannie] Johns Hopkins Univ, Acute & Chron Care Dept, Baltimore, MD USA.
RP Fall-Dickson, JM (reprint author), NINR, Symptom Management Branch, NIH, CRC 2NE 1339,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dicksonj@mail.nih.gov
FU American Cancer Society Doctoral Scholarship in Cancer Nursing (Atlanta,
Georgia); Sigma Theta Tau; Nu Beta Chapter; Johns Hopkins University
School of Nursing; Nursing Research Award
FX This work was supported by an American Cancer Society Doctoral
Scholarship in Cancer Nursing (Atlanta, Georgia) and a Sigma Theta Tau,
Nu Beta Chapter, Johns Hopkins University School of Nursing, Nursing
Research Award for Outstanding Research Proposal.
NR 43
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0162-220X
J9 CANCER NURS
JI Cancer Nurs.
PD NOV-DEC
PY 2008
VL 31
IS 6
BP 452
EP 461
DI 10.1097/01.NCC.0000339244.58914.4a
PG 10
WC Oncology; Nursing
SC Oncology; Nursing
GA 371GU
UT WOS:000260820600006
PM 18987512
ER
PT J
AU Sigurdson, AJ
Bhatti, P
Preston, DL
Doody, MM
Karnpa, D
Alexander, BH
Petibone, D
Yong, LC
Edwards, AA
Ron, E
Tucker, JD
AF Sigurdson, Alice J.
Bhatti, Parveen
Preston, Dale L.
Doody, Michele Morin
Karnpa, Diane
Alexander, Bruce H.
Petibone, Dayton
Yong, Lee C.
Edwards, Alan A.
Ron, Elaine
Tucker, James D.
TI Routine Diagnostic X-ray Examinations and Increased Frequency of
Chromosome Translocations among US Radiologic Technologists
SO CANCER RESEARCH
LA English
DT Article
ID RADIATION-INDUCED TRANSLOCATIONS; SELLAFIELD NUCLEAR FACILITY;
BIOLOGICAL DOSIMETRY; CANCER INCIDENCE; UNITED-STATES; ABERRATION
ANALYSIS; MEDICAL RADIATION; SMOKING-HABITS; EXPOSURE; FISH
AB The U.S. population has nearly one radiographic examination per person per year, and concern about cancer risks associated with medical radiation has increased. Radiologic technologists were surveyed to determine whether their personal cumulative exposure to. diagnostic X-rays was associated with increased frequencies of chromosome translocations, an established radiation biomarker and possible intermediary suggesting increased cancer risk. Within a large cohort of U.S. radiologic technologists, 150 provided a blood sample for whole chromosome painting and,were interviewed about past X-ray examinations. The number and types of examinations reported were converted to a red bone marrow (RBM) dose score with units that approximated 1 mGy. The relationship between dose score and chromosome translocation frequency was assessed using Poisson regression. The estimated mean cumulative RBM radiation dose score was 49 (range, 0-303). After adjustment for age, translocation frequencies significantly increased with increasing RBM dose score with an estimate of 0.004 translocations per 100 cell equivalents per score unit (95% confidence interval, 0.002-0.007; P < 0.001). Removing extreme values or adjustment for gender, cigarette smoking, occupational radiation dose, allowing practice X-rays while training, work with radioisotopes, and radiotherapy for benign conditions did not affect the estimate. Cumulative radiation exposure from routine X-ray examinations was associated independently with increased chromosome damage, suggesting the possibility of elevated long-term health risks, including cancer. The slope estimate was consistent with expectation based on cytogenetic experience and atomic bomb survivor data. [Cancer lies 2008;68(21):8825-31]
C1 [Sigurdson, Alice J.; Bhatti, Parveen; Doody, Michele Morin; Ron, Elaine] Natl Canc Inst, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Preston, Dale L.] HiroSoft Int Corp, Seattle, WA USA.
[Karnpa, Diane; Alexander, Bruce H.] Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN USA.
[Petibone, Dayton; Tucker, James D.] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA.
[Yong, Lee C.] NIOSH, Cincinnati, OH 45226 USA.
[Edwards, Alan A.] Hlth Protect Agcy, Radiat Protect Div, Didcot, Oxon, England.
RP Sigurdson, AJ (reprint author), Natl Canc Inst, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7060,MSC 7238, Bethesda, MD 20892 USA.
EM sigurdsa@mail.nih.gov
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, the National Cancer Institute, NIH, Department Health and
Human Services,; National Institute for Occupational Safety and Health
[Y1-CP-9012]; National Institute for Occupational Safety and Health
FX Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, the National Cancer Institute, NIH, Department Health and
Human Services, and by all interagency agreement with the National
Institute for Occupational Safety and Health contract Y1-CP-9012. The
findings and Conclusions ill this report are those of the author(s) and
do not necessarily represent the views of the National Institute for
Occupational Safety and Health.
NR 45
TC 10
Z9 11
U1 1
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD NOV 1
PY 2008
VL 68
IS 21
BP 8825
EP 8831
DI 10.1158/0008-5472.CAN-08-1691
PG 7
WC Oncology
SC Oncology
GA 369MP
UT WOS:000260698900023
PM 18974125
ER
PT J
AU Yeung, ML
Yasunaga, JI
Bennasser, Y
Dusetti, N
Harris, D
Ahmad, N
Matsuoka, M
Jeang, KT
AF Yeung, Man Lung
Yasunaga, Jun-ichirou
Bennasser, Yamina
Dusetti, Nelson
Harris, David
Ahmad, Nafees
Matsuoka, Masao
Jeang, Kuan-Teh
TI Roles for MicroRNAs, miR-93 and miR-130b, and Tumor Protein 53-induced
Nuclear Protein 1 Tumor Suppressor in Cell Growth Dysregulation by Human
T-Cell Lymphotrophic Virus 1
SO CANCER RESEARCH
LA English
DT Article
ID P53-INDUCED NUCLEAR-PROTEIN-1; TRANSCRIPTION FACTOR; GENE-REGULATION;
TAX GENE; I TAX; EXPRESSION; CANCER; LEUKEMIA; RNA; TRANSFORMATION
AB A role for microRNAs (miRNA) in human T-cell leukemia virus 1 (HTLV-1)-mediated cellular transformation has not been described. Here, we profiled miRNA expression in HTLV-1-transformed human T-cell lines and primary peripheral blood mononuclear cells from adult T-cell leukemia patients. Analyses of I I different profiles revealed six miRNAs that were consistently up-regulated. Two of the up-regulated miRNAs (miR-93 and miR-130b) target the 3' untranslated region (3'UTR) of the mRNA for a tumor suppressor protein, tumor protein 53-induced nuclear protein 1 (TP53INP1). A low expression level of TP53INP1 protein was found in HTLV-1-transformed cells. Additionally, when antagomirs were used to knock down miR-93 and miR-130b in these cells, the expression of TP53INP1 was increased, suggesting that the latter is regulated inside cells by the former. A role for TP53INP1 in regulating cell growth was established by experiments that showed that enhanced TP53INP1 expression increased apoptosis. Collectively, the findings implicate a miR-93/miR-130b-TP53INP1 axis that affects the proliferation and survival of HTLV-1-infected/transformed cells. [Cancer Res 2008;68(21):8976-85]
C1 [Yeung, Man Lung; Yasunaga, Jun-ichirou; Bennasser, Yamina; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Yasunaga, Jun-ichirou; Matsuoka, Masao] Kyoto Univ, Inst Virus Res, Lab Virus Immunol, Sakyo Ku, Kyoto 606, Japan.
[Dusetti, Nelson] Univ Mediterrance, INSERM, IFR 137, Inst Cancerol & Immunol Marseille,U624, Marseille, France.
[Bennasser, Yamina] CNRS, Mol Virol Lab, Inst Genet Humaine, UPR 1142, Montpellier, France.
[Harris, David; Ahmad, Nafees] Univ Arizona, Dept Microbiol & Immunol, Hlth Sci Ctr, Tucson, AZ 85721 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;
OI Matsuoka, Masao/0000-0002-0473-754X; Yasunaga,
Jun-ichirou/0000-0002-7939-2080
FU National Institute of Allergy and Infectious Diseases/NIH; NIH
FX Work in K-T. Jeang's laboratory is supported by intramural National
Institute of Allergy and Infectious Diseases/NIH funds and funding from
the NIH IATAP program.
NR 49
TC 117
Z9 125
U1 2
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 NOV 1
PY 2008
VL 68
IS 21
BP 8976
EP 8985
DI 10.1158/0008-5472.CAN-08-0769
PG 10
WC Oncology
SC Oncology
GA 369MP
UT WOS:000260698900040
PM 18974142
ER
PT J
AU Neklason, DW
Kerber, RA
Nilson, DB
Anton-Culver, H
Schwartz, AG
Griffin, CA
Lowery, JT
Schildkraut, JM
Evans, JP
Tomlinson, GE
Strong, LC
Miller, AR
Stopfer, JE
Finkelstein, DM
Nadkarni, PM
Kasten, CH
Mineau, GP
Burt, RW
AF Neklason, Deborah W.
Kerber, Richard A.
Nilson, David B.
Anton-Culver, Hoda
Schwartz, Ann G.
Griffin, Constance A.
Lowery, Jan T.
Schildkraut, Joellen M.
Evans, James P.
Tomlinson, Gail E.
Strong, Louise C.
Miller, Alexander R.
Stopfer, Jill E.
Finkelstein, Dianne M.
Nadkarni, Prakash M.
Kasten, Carol H.
Mineau, Geraldine P.
Burt, Randall W.
TI Common Familial Colorectal Cancer Linked to Chromosome 7q31: A
Genome-Wide Analysis
SO CANCER RESEARCH
LA English
DT Article
ID SUSCEPTIBILITY LOCUS; ASSOCIATION SCAN; LINKAGE; GENES; KINDREDS; ERBB4;
TESTS; RISK; 8Q24; MAP
AB Present investigations suggest that similar to 30% of colorectal cancer cases arise on the basis of inherited factors. We hypothesize that the majority of inherited factors are moderately penetrant genes, common in the population. We use an affected sibling pair approach to identify genetic regions that are coinherited by siblings with colorectal cancer. Individuals from families with at least two siblings diagnosed with colorectal adenocarcinoma or high-grade dysplasia were enrolled. Known familial colorectal cancer syndromes were excluded. A genome-wide scan on 151 DNA samples from 70 kindreds was completed using deCODE 1100 short tandem repeat marker set at an average 4-cM density. Fine mapping on a total of 184 DNAs from 83 kindreds was done in regions suggesting linkage. Linkage analysis was accomplished with Merlin analysis package. Nonparametric linkage analysis revealed three genetic regions with logarithm of the odds (LOD) scores >= 2.0: Ch. 3q29, LOD 2.61 (P = 0.0003); Ch. 4q31.3, LOD 2.13 (P = 0.0009); and Ch. 7q31.31, LOD 3.08 (P = 0.00008). Affected siblings with increased sharing at the 7q31 locus have a 3.8-year (+/- 3.5) earlier age of colorectal cancer onset although this is not statistically significant (P = 0.11). No significant linkage was found near genes causing known syndromes or regions previously reported (8q24, 9q22, and 11q23). The chromosome 3q21-q24 region reported to be linked in colorectal cancer relative pairs is supported by our study, albeit a minor peak (LOD 0.9; P = 0.02). No known familial cancer genes reside in the 7q31 locus, and thus the identified region may contain a novel susceptibility gene responsible for common familial colorectal cancer. [Cancer Res 2008;68(21):8993-7]
C1 [Neklason, Deborah W.; Kerber, Richard A.; Nilson, David B.; Mineau, Geraldine P.; Burt, Randall W.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
[Anton-Culver, Hoda] Univ Calif Irvine, Irvine, CA USA.
[Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Griffin, Constance A.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Griffin, Constance A.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA.
[Lowery, Jan T.] Colorado Sch Publ Hlth, Denver, CO USA.
[Schildkraut, Joellen M.] Duke Univ, Durham, NC USA.
[Evans, James P.] Univ N Carolina, Chapel Hill, NC USA.
[Tomlinson, Gail E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Strong, Louise C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Miller, Alexander R.] Canc Therapy & Res Ctr S Texas, San Antonio, TX 78229 USA.
[Miller, Alexander R.] Univ Texas San Antonio, San Antonio, TX USA.
[Stopfer, Jill E.] Univ Penn, Philadelphia, PA 19104 USA.
[Finkelstein, Dianne M.] Massachusetts Gen Hosp, Stat Coordinating Ctr, Boston, MA 02114 USA.
[Nadkarni, Prakash M.] Yale Ctr Informat, New Haven, CT USA.
[Kasten, Carol H.] NCI, Rockville, MD USA.
RP Neklason, DW (reprint author), Univ Utah, Huntsman Canc Inst, 2000 Circle Hope, Salt Lake City, UT 84112 USA.
EM Deb.neklason@hci.utah.edu
RI Kerber, Richard/B-8038-2009
FU NIH [U24-CA78174, P01-CA073992, U24-CA78134, U01-CA78285, N01-PC35145,
U24-CA78148, CA74799, U24-CA78142, CA78157-05S1, U01-CA078284];
University of Utah General Clinical Research Center [M01-RR00064,
N01-PC-67000]; National Cancer Institute Surveillance, Epidemiology, and
End Results; Utah State Department of Health; University of Utah;
Huntsman Cancer Foundation
FX NIH grants U24-CA78174 (G.P. Mineau), P01-CA073992 (RAV. Burt),
U24-CA78134 (H. Anton-Culver), U01-CA78285 (H. Anton-Culver),
N01-PC35145 (A.G. Schwartz), U24-CA78148 (C.A. Griffin), CA74799 (J.T.
Lowery), U24-CA78142 (I-C. Strong), CA78157-05S1 (J.E. Stopfer), and
U01-CA078284 (D.M. Finkelstein); University of Utah General Clinical
Research Center grants M01-RR00064 and N01-PC-67000; Utah Cancer
Registry grant. N01-PC-35141 from the National Cancer Institute
Surveillance, Epidemiology, and End Results program; the Utah State
Department of Health; and the University of Utah, Huntsman Cancer
Foundation.
NR 26
TC 28
Z9 28
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD NOV 1
PY 2008
VL 68
IS 21
BP 8993
EP 8997
DI 10.1158/0008-5472.CAN-08-1376
PG 5
WC Oncology
SC Oncology
GA 369MP
UT WOS:000260698900042
PM 18974144
ER
PT J
AU Kim, HH
Yang, X
Kuwano, Y
Gorospe, M
AF Kim, Hyeon Ho
Yang, Xiaoling
Kuwano, Yuki
Gorospe, Myriam
TI Modification at HuR(S242) alters HuR localization and proliferative
influence
SO CELL CYCLE
LA English
DT Article
DE cell cycle; cyclins; RNA-binding protein; post-transcriptional gene
expression; ribonucleoprotein complex; mRNA turnover
ID RNA-BINDING PROTEIN; AU-RICH ELEMENT; MESSENGER-RNA; NUCLEAR IMPORT;
PHOSPHORYLATION; ALPHA; STABILIZATION; EXPRESSION; STABILITY;
TRANSLATION
AB HuR is predominantly nuclear but following exposure to stress and mitogens, it can translocate to the cytoplasm where it stabilizes target mRNAs and/or modulates their translation. Several phosphorylation sites in a central 'hinge' region of HuR have been reported to affect its nucleocytoplasmic shuttle: phosphorylation by PKC at serine (S) 221 and by Cdk1 at S202. Here, we investigated if there are additional putative phosphorylation sites within the HuR hinge region capable of influencing its cytoplasmic abundance. We systematically mutated all seven serine residues within the shuttling hinge domain to the nonphosphorylatable residue alanine (A), S197A, S202A, S221A, S229A, S232A, S241A and S242A. Using HeLa cells as the study system, we found that the HuR(S242A) mutant was more abundant in the cytoplasm in both untreated cells and in cells treated with short-wavelength ultraviolet light or with an inhibitor of Cdk1. Conversely, mutation of S242 to aspartic acid (D), rendered the phosphomimetic HuR(S242D) nuclear under all treatment conditions. S242 mutations did not influence HuR stability, but HuR(S242A) showed increased association with target cyclin A2 and cyclin B1 mRNAs. Accordingly, expression of HuR(S242A) led to increased cyclin mRNA stability and heightened cell proliferation rates. Our findings suggest that HuR phosphorylation at S242 hinders its cytoplasmic localization, its function as a posttranscriptional regulator, and its proliferative influence.
C1 [Kim, Hyeon Ho; Yang, Xiaoling; Kuwano, Yuki; Gorospe, Myriam] NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA.
RP Gorospe, M (reprint author), NIA, LCMB, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM myriam-gorospe@nih.gov
FU National Institute on Aging, National Institutes of Health
FX This work was supported entirely by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health.
NR 49
TC 39
Z9 40
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 NOV 1
PY 2008
VL 7
IS 21
BP 3371
EP 3377
PG 7
WC Cell Biology
SC Cell Biology
GA 368AS
UT WOS:000260594300019
PM 18948743
ER
PT J
AU Eiden, MV
AF Eiden, M. V.
TI Endogenous retroviruses - Aiding and abetting genomic plasticity
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Editorial Material
DE Endogenous retrovirus; exogenous retrovirus; retroelements; symbionts;
insertional mutagenesis; evolution; germ line
ID KOALA RETROVIRUS; VIRUS; SYNCYTIN; RECEPTOR; GENE
C1 NIH, Bethesda, MD 20892 USA.
RP Eiden, MV (reprint author), NIH, Bldg 49,MSC 4483, Bethesda, MD 20892 USA.
EM eidenm@mail.nih.gov
FU Intramural NIH HHS [Z01 MH002592-17, ZIA MH002592-19, ZIA MH002592-20]
NR 16
TC 3
Z9 3
U1 0
U2 3
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD NOV
PY 2008
VL 65
IS 21
BP 3327
EP 3328
DI 10.1007/s00018-008-8493-4
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 369HC
UT WOS:000260684200001
PM 18818876
ER
PT J
AU Stocking, C
Kozak, CA
AF Stocking, C.
Kozak, C. A.
TI Murine endogenous retroviruses
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Virus restriction factors; retroviral receptors; Env-receptor
interactions; murine ERV classification
ID MAMMARY-TUMOR VIRUS; LONG TERMINAL REPEAT; CELL-SURFACE RECEPTOR; MOUSE
LEUKEMIA VIRUS; WILD-DERIVED MICE; DNA-SEQUENCES; MUERV-L; MUS-MUSCULUS;
Y-CHROMOSOME; HOST-RANGE
AB Up to 10% of the mouse genome is comprised of endogenous retrovirus (ERV) sequences, and most represent the remains of ancient germ line infections. Our knowledge of the three distinct classes of ERVs is inversely correlated with their copy number, and their characterization has benefited from the availability of divergent wild mouse species and subspecies, and from ongoing analysis of the Mus genome sequence. In contrast to human ERVs, which are nearly all extinct, active mouse ERVs can still be found in all three ERV classes. The distribution and diversity of ERVs has been shaped by host-virus interactions over the course of evolution, but ERVs have also been pivotal in shaping the mouse genome by altering host genes through insertional mutagenesis, by adding novel regulatory and coding sequences, and by their co-option by host cells as retroviral resistance genes. We review mechanisms by which an adaptive coexistence has evolved. (Part of a Multiauthor Review).
C1 [Stocking, C.] Heinrich Pette Inst, D-20251 Hamburg, Germany.
[Kozak, C. A.] NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA.
RP Stocking, C (reprint author), Heinrich Pette Inst, Martinistr 52, D-20251 Hamburg, Germany.
EM stocking@hpi.uni-hamburg.de; ckozak@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000300-26, Z99 AI999999]
NR 150
TC 93
Z9 94
U1 3
U2 23
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
EI 1420-9071
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD NOV
PY 2008
VL 65
IS 21
BP 3383
EP 3398
DI 10.1007/s00018-008-8497-0
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 369HC
UT WOS:000260684200005
PM 18818872
ER
PT J
AU Luo, R
Jenkins, LMM
Randazzo, PA
Gruschus, J
AF Luo, Ruibai
Jenkins, Lisa M. Miller
Randazzo, Paul A.
Gruschus, James
TI Dynamic interaction between Arf GAP and PH domains of ASAP1 in the
regulation of GAP activity
SO CELLULAR SIGNALLING
LA English
DT Article
DE ADP-ribosylation factor; GTPase-activating protein; Pleckstrin homology
domain; Nuclear Magnetic Resonance spectrometry
ID GTPASE-ACTIVATING PROTEIN; ADP-RIBOSYLATION FACTOR; PLECKSTRIN HOMOLOGY
DOMAIN; ACTIN CYTOSKELETON; N-TERMINUS; COMPLEX; AGAP1; HYDROLYSIS;
ACID; PHOSPHOLIPIDS
AB ASAP family Arf GAPs induce the hydrolysis of GTP bound to the Ras superfamily protein Arf1, regulate cell adhesion and migration and have been implicated in carcinogenesis. The ASAP proteins have a core catalytic domain of PH, Arf GAP and Ank repeat domains. The PH domain is necessary for both biological and catalytic functions of ASAP1 and has been proposed to be integrally folded with the Arf GAP domain. Protection studies and analytical ultracentrifugation studies previously reported indicated that the domains are, at least partly, folded together. Here, using NMR spectroscopy and biochemical analysis, we have further tested this hypothesis and characterized the interdomain interaction. A comparison of NMR spectra of three recombinant proteins comprised of either the isolated PH domain of ASAP1, the Arf GAP and ankyrin repeat domain or all three domains indicated that the PH domain did interact with the Arf GAP and Ank repeat domains; however, we found a significant amount of dynamic independence between the PH and Arf GAP domains, consistent with the interactions being transient. In contrast, the Arf GAP and Ank repeat domains form a relatively rigid structure. The PH-Arf GAP domain interaction partially occluded the phosphomositide binding site in the soluble Protein, but binding studies indicated the PIP2 binding site was accessible in ASAP1 bound to a lipid bilayer Surface. Phosphomositide binding altered the conformation of the PH domain, but had little effect on the structure of the Arf GAP domain. Mutations in a loop of the PH domain that contacts the Arf GAP domain affected PIP2 binding and the K-m and k(cat) for converting Arf1.GTP to Arf1.GDP. Based on these results, we generated a homology model of a composite PH/Arf GAP/Ank repeat domain structure. We propose that the PH domain contributes to Arf GAP activity by either binding to or positioning Arf1.GTP that is simultaneously bound to the Arf GAP domain. Published by Elsevier Inc.
C1 [Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Jenkins, Lisa M. Miller] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Gruschus, James] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Randazzo, PA (reprint author), NCI, Cellular & Mol Biol Lab, NIH, Bldg 37,Room 2042, Bethesda, MD 20892 USA.
EM Randazzo@helix.nih.gov
FU Intramural Research Program of the National Cancer Institute; National
Heart, Lung and Blood Institute; National Institutes of Health,
Department of Health and Human Services
FX This work was supported by the Intramural Research Program of the
National Cancer Institute and the National Heart, Lung and Blood
Institute, National Institutes of Health, Department of Health and Human
Services.
NR 44
TC 10
Z9 10
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
J9 CELL SIGNAL
JI Cell. Signal.
PD NOV
PY 2008
VL 20
IS 11
BP 1968
EP 1977
DI 10.1016/j.cellsig.2008.07.007
PG 10
WC Cell Biology
SC Cell Biology
GA 368QL
UT WOS:000260637500007
PM 18675341
ER
PT J
AU Pamonsinlapatham, P
Gril, B
Dufour, S
Hadj-Slimane, R
Gigoux, V
Pethe, S
L'Hoste, S
Camonis, J
Garbay, C
Raynaud, F
Vidal, M
AF Pamonsinlapatham, Perayot
Gril, Brunilde
Dufour, Sylvie
Hadj-Slimane, Reda
Gigoux, Veronique
Pethe, Stephanie
L'Hoste, Sebastien
Camonis, Jacques
Garbay, Christiane
Raynaud, Francoise
Vidal, Michel
TI Capns1, a new binding partner of RasGAP-SH3 domain in K-Ras(V12)
oncogenic cells: Modulation of cell survival and migration
SO CELLULAR SIGNALLING
LA English
DT Article
DE Calpain; Migration; RasGAP; SH3 domain
ID GTPASE-ACTIVATING PROTEIN; UBIQUITOUS CALPAINS PROMOTE; SH3 DOMAIN;
RAS-GAP; PHOSPHORYLATION; APOPTOSIS; COMPLEX; GROWTH; SRC; DISRUPTION
AB Ras GTPase-activating protein (RasGAP) is hypothesized to be an effector of oncogenic Ras Stimulating numerous downstream cellular signaling cascades involved in survival, proliferation and motility. In this study, we identified calpain small subunit-1 (Capns1) as a new RasGAP-SH3 domain binding partner, using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation assay and was found specific to cells expressing oncogenic K-Ras. We used confocal microscopy to analyze our stably transfected cell model producing mutant Ras (PC3Ras(V12)). Staining for RasGAP-SH3/Capns1 co-localization was two-fold stronger in the protrusions of Ras(V12) cells than in PO cells. RasGAP or Capns1 knockdown in PC3Ras(V12) cells induced a two- to three-fold increase in apoptosis. Capns1 gene silencing reduced the speed and increased the persistence of movement in PC3Ras(V12) cells. In contrast, RasGAP knockdown in PC3Rasv 12 cells increased cell migration. Knockdown of both proteins altered the speed and directionality of cell Motility. Our findings Suggest that RasGAP and Capns1 interaction in oncogenic Ras cells is involved in regulating migration and cell survival. (c) 2008 Elsevier Inc. All rights reserved.
C1 [Pamonsinlapatham, Perayot; Gril, Brunilde; Hadj-Slimane, Reda; Gigoux, Veronique; Pethe, Stephanie; Garbay, Christiane; Raynaud, Francoise; Vidal, Michel] Univ Paris 05, Lab Pharmacochim Mol & Cellulaire, Unites Format & Rech Biomed, F-75270 Paris 06, France.
[Pamonsinlapatham, Perayot; Gril, Brunilde; Hadj-Slimane, Reda; Gigoux, Veronique; Pethe, Stephanie; Garbay, Christiane; Raynaud, Francoise; Vidal, Michel] INSERM U648, Lab Pharmacochim Mol & Cellulaire, Paris 06, France.
[Gril, Brunilde] NCI, NIH, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
[Dufour, Sylvie] CNRS, Inst Curie, UMR144, F-75005 Paris, France.
[Pethe, Stephanie; L'Hoste, Sebastien] INSERM U528, Inst Curie, Lab Transduc Signal & Oncogenese, F-75005 Paris, France.
RP Raynaud, F (reprint author), Univ Paris 05, Lab Pharmacochim Mol & Cellulaire, Unites Format & Rech Biomed, 45 Rue St Peres, F-75270 Paris 06, France.
EM francoise.raynaud@univ-paris5.fr; michel.vidal@univ-paris5.fr
FU La Ligue Nationale contre le Cancer; Ministere de la Technologie et de
la Recherche [02L0521]; Faculty of Pharmacy, Silpakorn University,
Thailand; Ministere de la Technologie et de la Recherche; Association
pour la Recherche contre le Cancer [3737]
FX This work received financial support from La Ligue Nationale contre le
Cancer, 2006 and from Ministere de la Technologie et de la Recherche,
ACI 2002 Molecules et cibles therapeutiques (number 02L0521). PP Was
Supported by a scholarship from the Faculty of Pharmacy, Silpakorn
University, Thailand. BG received a grant from the Ministere de la
Technologie et de la Recherche and SD received financial support from
the Association pour la Recherche contre le Cancer (grant 3737). The
authors acknowledge NIH for stylistic revision of this manuscript. They
also thank Pr Marie Agnes Sari, Yves Lepelletier, William Thomas and
Pierre Colas for critical reading of the manuscript, and Veronique
Lenoir for her technical assistance.
NR 40
TC 12
Z9 13
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
J9 CELL SIGNAL
JI Cell. Signal.
PD NOV
PY 2008
VL 20
IS 11
BP 2119
EP 2126
DI 10.1016/j.cellsig.2008.08.005
PG 8
WC Cell Biology
SC Cell Biology
GA 368QL
UT WOS:000260637500023
PM 18761085
ER
PT J
AU Wilson, PWF
Pencina, M
Jacques, P
Selhub, J
D'Agostino, R
O'Donnell, CJ
AF Wilson, Peter W. F.
Pencina, Michael
Jacques, Paul
Selhub, Jacob
D'Agostino, Ralph, Sr.
O'Donnell, Christopher J.
TI C-Reactive Protein and Reclassification of Cardiovascular Risk in the
Framingham Heart Study
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE epidemiology; inflammation; risk factors; statistics
AB Background-The relationship of circulating levels of high-sensitivity C-reactive protein (CRP) with cardiovascular disease (CVD) risk, particularly with consideration of effects at intermediate levels of risk, has not been fully assessed.
Methods and Results-Among 3006 offspring participants in the Framingham Heart Study free of CVD (mean age, 46 years at baseline), there were 129 hard coronary heart disease (CHD) events and 286 total CVD events during 12 years of follow-up. Cox regression, discrimination with area under the receiver operating characteristic curve, and net reclassification improvement were used to assess the role of CRP on vascular risk. In an age-adjusted model that included both sexes, the hazard ratios for new hard CHD and total CVD were significantly associated with higher CRP levels. Similar analyses according to increasing homocysteine level showed significant protective associations for hard CHD but not for total CVD. In multivariable analyses that included age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, diabetes mellitus, current smoking, hypertension treatment, and homocysteine, the log CRP level remained significantly related to development of hard CHD and total CVD and provided moderate improvement in the discrimination of events. The net reclassification improvement when CRP was added to traditional factors was 5.6% for total CVD (P=0.014) and 11.8% for hard CHD (P=0.009).
Conclusions-Circulating levels of CRP help to estimate risk for initial cardiovascular events and may be used most effectively in persons at intermediate risk for vascular events, offering moderate improvement in reclassification of risk. (Circ Cardiovasc Qual Outcomes. 2008;1:92-97.)
C1 [Wilson, Peter W. F.] Emory Univ, Sch Med, EPICORE, Atlanta, GA 30306 USA.
[Wilson, Peter W. F.] Atlanta VAMC Epidemiol & Genet Sect, Atlanta, GA USA.
[Pencina, Michael; D'Agostino, Ralph, Sr.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Pencina, Michael; D'Agostino, Ralph, Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Jacques, Paul; Selhub, Jacob] Tufts USDA Nutr Ctr, Boston, MA USA.
RP Wilson, PWF (reprint author), Emory Univ, Sch Med, EPICORE, Suite 1 N,1256 Briarcliff Rd, Atlanta, GA 30306 USA.
EM peter.wf.wilson@emory.edu
FU Framingham Heart Study of the National Heart, Lung, and Blood Institute
of the National Institutes of Health [R01 HL073272, N01 HC-25195];
Boston University School of Medicine
FX This study was supported by grant R01 HL073272 (to P. W. F. W.) 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. This work was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (contract N01 HC-25195).
NR 35
TC 147
Z9 152
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD NOV
PY 2008
VL 1
IS 2
BP 92
EP 97
DI 10.1161/CIRCOUTCOMES.108.831198
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V11AL
UT WOS:000207504400005
PM 20031795
ER
PT J
AU Go, AS
Magid, DJ
Wells, B
Sung, SH
Cassidy-Bushrow, AE
Greenlee, RT
Langer, RD
Lieu, TA
Margolis, KL
Masoudi, FA
McNeal, CJ
Murata, GH
Newton, KM
Novotny, R
Reynolds, K
Roblin, DW
Smith, DH
Vupputuri, S
White, RE
Olson, J
Rumsfeld, JS
Gurwitz, JH
AF Go, Alan S.
Magid, David J.
Wells, Barbara
Sung, Sue Hee
Cassidy-Bushrow, Andrea E.
Greenlee, Robert T.
Langer, Robert D.
Lieu, Tracy A.
Margolis, Karen L.
Masoudi, Frederick A.
McNeal, Catherine J.
Murata, Glen H.
Newton, Katherine M.
Novotny, Rachel
Reynolds, Kristi
Roblin, Douglas W.
Smith, David H.
Vupputuri, Suma
White, Robert E.
Olson, Jean
Rumsfeld, John S.
Gurwitz, Jerry H.
TI The Cardiovascular Research Network A New Paradigm for Cardiovascular
Quality and Outcomes Research
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE cardiovascular disease; risk factors; outcomes; epidemiology; quality of
care
ID ACUTE MYOCARDIAL-INFARCTION; BARE-METAL STENTS; SIROLIMUS-ELUTING
STENTS; ACUTE CORONARY SYNDROMES; CLINICAL-DATA STANDARDS; ASSOCIATION
TASK-FORCE; HMO-RESEARCH-NETWORK; KEY DATA ELEMENTS; NATIONAL REGISTRY;
HEART-FAILURE
AB Background-A clear need exists for a more systematic understanding of the epidemiology, diagnosis, and management of cardiovascular diseases. More robust data are also needed on how well clinical trials are translated into contemporary community practice and the associated resource use, costs, and outcomes.
Methods and Results-The National Heart, Lung, and Blood Institute recently established the Cardiovascular Research Network, which represents a new paradigm to evaluate the epidemiology, quality of care, and outcomes of cardiovascular disease and to conduct future clinical trials using a community-based model. The network includes 15 geographically distributed health plans with dedicated research centers, National Heart, Lung, and Blood Institute representatives, and an external collaboration and advisory committee. Cardiovascular research network sites bring complementary content and methodological expertise and a diverse population of approximate to 11 million individuals treated through various health care delivery models. Each site's rich electronic databases (eg, sociodemographic characteristics, inpatient and outpatient diagnoses and procedures, pharmacy, laboratory, and cost data) are being mapped to create a standardized virtual data warehouse to facilitate rapid and efficient large-scale research studies. Initial projects focus on (1) hypertension recognition and management, (2) quality and outcomes of warfarin therapy, and (3) use, outcomes, and costs of implantable cardioverter defibrillators.
Conclusions-The Cardiovascular Research Network represents a new paradigm in the approach to cardiovascular quality of care and outcomes research among community-based populations. Its unique ability to characterize longitudinally large, diverse populations will yield novel insights into contemporary disease and risk factor surveillance, management, outcomes, and costs. The Cardiovascular Research Network aims to become the national research partner of choice for efforts to improve the prevention, diagnosis, treatment, and outcomes of cardiovascular diseases. (Circ Cardiovasc Qual Outcomes. 2008;1:138-147.)
C1 [Go, Alan S.; Sung, Sue Hee] Univ Calif San Francisco, Kaiser Permanente No Calif, San Francisco, CA 94143 USA.
[Magid, David J.] Univ Colorado, Kaiser Permanente Colorado, Denver, CO 80202 USA.
[Wells, Barbara; Olson, Jean] NHLBI, Bethesda, MD 20892 USA.
[Cassidy-Bushrow, Andrea E.] Henry Ford Hlth Syst, Detroit, MI USA.
[Greenlee, Robert T.] Univ Wisconsin, Marshfield Clin Fdn Med Res & Educ, Madison, WI USA.
[Langer, Robert D.] Geisinger Hlth Syst, Danville, PA USA.
[Lieu, Tracy A.] Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA.
[Lieu, Tracy A.] Harvard Univ, Sch Med, Boston, MA USA.
[Margolis, Karen L.] Univ Minnesota, HealthPartners Res Fdn, Minneapolis, MN USA.
[Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA.
[McNeal, Catherine J.] Scott & White Mem Hosp & Clin, Temple, TX USA.
[McNeal, Catherine J.] Texas A&M Univ, Texas A&M Hlth Sci Ctr, College Stn, TX USA.
[Murata, Glen H.; White, Robert E.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Murata, Glen H.] New Mexico VA Hlth Care Syst, Albuquerque, NM USA.
[Newton, Katherine M.] Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA.
[Newton, Katherine M.; Smith, David H.] Univ Washington, Seattle, WA 98195 USA.
[Novotny, Rachel] Univ Hawaii, Kaiser Permanente Ctr Hlth Res Hawaii, Honolulu, HI 96822 USA.
[Reynolds, Kristi] Kaiser Permanente So Calif, Pasadena, CA USA.
[Roblin, Douglas W.; Vupputuri, Suma] Kaiser Permanente Georgia, Atlanta, GA USA.
[Roblin, Douglas W.] Emory Univ, Atlanta, GA 30322 USA.
[Smith, David H.] Kaiser Permanente NW, Portland, OR USA.
[Smith, David H.] Oregon State Univ, Corvallis, OR 97331 USA.
[White, Robert E.] Lovelace Clin Fdn, Albuquerque, NM USA.
[Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA.
[Gurwitz, Jerry H.] Meyers Primary Care Inst & Fallon Community Hlth, Worcester, MA USA.
[Gurwitz, Jerry H.] Univ Massachusetts, Amherst, MA 01003 USA.
RP Go, AS (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway St,3rd Floor, Oakland, CA 94612 USA.
EM Alan.S.Go@kp.org
OI Cassidy-Bushrow, Andrea/0000-0001-8272-4448
FU National Heart, Lung, and Blood Institute [U19 HL91179-01]
FX This work was supported by National Heart, Lung, and Blood Institute
cooperative agreement U19 HL91179-01.
NR 44
TC 49
Z9 49
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD NOV
PY 2008
VL 1
IS 2
BP 138
EP 147
DI 10.1161/CIRCOUTCOMES.108.801654
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V11AL
UT WOS:000207504400012
PM 20031802
ER
PT J
AU Engelhardt, KR
Woellner, C
Schaffer, AA
Gertz, EM
Hagena, T
Salzer, U
Pfeifer, D
Yeganeh, M
Ehl, S
Holland, SM
Hsu, V
Puck, JM
Plebani, A
Junker, A
Niehues, T
E'tzioni, A
Grimbacher, B
AF Engelhardt, K. R.
Woellner, C.
Schaffer, A. A.
Gertz, E. M.
Hagena, T.
Salzer, U.
Pfeifer, D.
Yeganeh, M.
Ehl, S.
Holland, S. M.
Hsu, V
Puck, J. M.
Plebani, A.
Junker, A.
Niehues, T.
E'tzioni, A.
Grimbacher, B.
TI Identification of genes mutated in autosomal-recessive hyper-IgE
syndrome
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 13th European-Soc-for-Immunodeficiencies/10th
Int-Patient-Org-for-Primary-Immunodeficiencies/8th
Int-Nursing-Group-for-Immunodeficiencies Meeting
CY OCT 16-19, 2008
CL Hertogenbosch, NETHERLANDS
SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies
C1 UCL, London, England.
NCBI, Computat Biol Branch, NIH, Bethesda, MD USA.
Univ Hosp Freiburg, Div Rheumatol & Clin Immunol, Freiburg, Germany.
Univ Sherbrooke, Div Immunol, Dept Pediat, Quebec City, PQ, Canada.
NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
Univ Brescia, Brescia, Italy.
Children & Womens Hlth Ctr, Vancouver, BC, Canada.
Univ Klinikum Dusseldorf, Dusseldorf, Germany.
Rappaport Sch Med, Haifa, Israel.
RI Plebani, Alessandro/C-8593-2011; Schaffer, Alejandro/F-2902-2012
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-9104
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD NOV
PY 2008
VL 154
BP 53
EP 53
PG 1
WC Immunology
SC Immunology
GA 398JD
UT WOS:000262727500100
ER
PT J
AU Lopez-Herrera, G
Detkova, D
Schaffer, AA
Salzer, U
Pfeifer, D
Gertz, M
Hagena, T
Kesel, A
Srugo, I
Etzioni, A
Grimbacher, B
AF Lopez-Herrera, G.
Detkova, D.
Schaffer, A. A.
Salzer, U.
Pfeifer, D.
Gertz, M.
Hagena, T.
Kesel, A.
Srugo, I
Etzioni, A.
Grimbacher, B.
TI Genetic linkage in autosomal recessive common variable immunodeficiency
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 13th European-Soc-for-Immunodeficiencies/10th
Int-Patient-Org-for-Primary-Immunodeficiencies/8th
Int-Nursing-Group-for-Immunodeficiencies Meeting
CY OCT 16-19, 2008
CL Hertogenbosch, NETHERLANDS
SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies
C1 [Lopez-Herrera, G.; Detkova, D.; Grimbacher, B.] Royal Free Hosp, London NW3 2QG, England.
[Lopez-Herrera, G.; Detkova, D.; Grimbacher, B.] UCL, London, England.
[Schaffer, A. A.] NIH, DHHS, Natl Ctr Biotechnol Infor, Bethesda, MD 20892 USA.
[Salzer, U.; Pfeifer, D.; Gertz, M.; Hagena, T.] Univ Hosp Freiburg, Freiburg, Germany.
[Kesel, A.; Srugo, I; Etzioni, A.] Rappaport Sch Med, Div Pediat, Haifa, Israel.
RI Schaffer, Alejandro/F-2902-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-9104
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD NOV
PY 2008
VL 154
BP 65
EP 65
PG 1
WC Immunology
SC Immunology
GA 398JD
UT WOS:000262727500124
ER
PT J
AU Woellner, C
Gertz, EM
Schaeffer, AA
Lagos, M
Perro, M
Pietrogrande, MC
Cossu, F
Franco, JL
Matamoros, N
Pietrucha, B
Heropolianska-Pliszka, E
Yeganeh, M
Espanol, T
Ehl, S
Gennery, AR
Abinun, M
Breborowicz, A
Niehues, T
Kilic, SS
Junker, A
Turvey, S
Plebani, A
Sanchez, B
Garty, BZ
Pignata, C
Cancrini, C
Litzman, J
Sanal, O
Baumann, U
Bacchetta, R
Hsu, A
Hammarstrom, L
Davies, EG
Eren, E
Arkwright, PD
Moilanen, JS
Viemann, D
Khan, S
Marodi, L
Cant, AM
Puck, JM
Holland, SM
Grimbacher, B
AF Woellner, C.
Gertz, E. M.
Schaeffer, A. A.
Lagos, M.
Perro, M.
Pietrogrande, M. C.
Cossu, F.
Franco, J. L.
Matamoros, N.
Pietrucha, B.
Heropolianska-Pliszka, E.
Yeganeh, M.
Espanol, T.
Ehl, S.
Gennery, A. R.
Abinun, M.
Breborowicz, A.
Niehues, T.
Kilic, S. S.
Junker, A.
Turvey, S.
Plebani, A.
Sanchez, B.
Garty, B. Z.
Pignata, C.
Cancrini, C.
Litzman, J.
Sanal, O.
Baumann, U.
Bacchetta, R.
Hsu, A.
Hammarstrom, L.
Davies, E. G.
Eren, E.
Arkwright, P. D.
Moilanen, J. S.
Viemann, D.
Khan, S.
Marodi, L.
Cant, A. M.
Puck, J. M.
Holland, S. M.
Grimbacher, B.
TI Diagnostic criteria for the hyper IgE recurrent infection syndrome/Job's
syndrome/STAT3 deficiency
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 13th European-Soc-for-Immunodeficiencies/10th
Int-Patient-Org-for-Primary-Immunodeficiencies/8th
Int-Nursing-Group-for-Immunodeficiencies Meeting
CY OCT 16-19, 2008
CL Hertogenbosch, NETHERLANDS
SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies
C1 [Woellner, C.; Perro, M.] UCL, Royal Free Hosp, Dept Immunol & Mol Pathol, London, England.
[Gertz, E. M.; Schaeffer, A. A.] NCBI, Computat Biol Branch, NIH, Bethesda, MD USA.
[Lagos, M.] Univ Valparaiso, Catedra Inmunol, Escuela Med, Valparaiso, Chile.
[Pietrogrande, M. C.] Univ Milan, Dept Paediat, Milan, Italy.
[Cossu, F.] Osped Microcitem, Bone Marrow Transplant Unit, Cagliari, Italy.
[Franco, J. L.] Univ Antioquia, Grp Primary Immunodeficiencies, Medellin, Colombia.
[Matamoros, N.] Hosp Son Dureta, Serv Inmunol, Palma de Mallorca, Spain.
[Pietrucha, B.; Heropolianska-Pliszka, E.] Childrens Mem Hlth Inst, Dept Immunol, Warsaw, Poland.
[Yeganeh, M.] Univ Sherbrooke, Dept Pediat, Div Immunol, Quebec City, PQ, Canada.
[Espanol, T.] CSI Univ, Immunol Unit, Barcelona, Spain.
[Ehl, S.] Univ Freiburg Klinikum, Zentrum Kinderheilkunde & Jugendme, Freiburg, Germany.
[Gennery, A. R.] Newcastle Univ, Childrens BMT Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Abinun, M.] Newcastle Gen Hosp, Dept Paediat, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England.
[Breborowicz, A.] Poznan Univ Med Sci, Dept Pediat Pulmonol, Poznan, Poland.
[Niehues, T.] Univ Dusseldorf, Zentrum Kinderheilkunde, Dusseldorf, Germany.
[Kilic, S. S.] Uludag Univ, Fac Med, Dept Pediat, Bursa, Turkey.
[Junker, A.] Children & Womens Hlth Ctr, Div Infect & Immunol, Vancouver, BC, Canada.
[Turvey, S.] BC Childrens Hosp & Child, Div Infect Dis & Immunol, Vancouver, BC, Canada.
[Turvey, S.] Family Res Inst, Vancouver, BC, Canada.
[Plebani, A.] Univ Brescia, Pediat Clin, Brescia, Italy.
[Sanchez, B.] Hosp Virgen Rocio, Seville, Spain.
[Garty, B. Z.] Schneider Childrens Med Ctr Israel, Dept Pediat B & Kipper In, Petah Tiqwa, Israel.
[Pignata, C.] Univ Naples Federico II, Dept Pediat, Naples, Italy.
[Cancrini, C.] Univ Rome, Dept Pediat, Rome, Italy.
[Litzman, J.] Dept Clin Immunol & Allergol, Brno, Czech Republic.
[Sanal, O.] Hacettepe Univ, Div Immunol, Ankara, Turkey.
[Baumann, U.] Hannover Med Sch, Abt Padiatr Pneunol & N, D-30623 Hannover, Germany.
[Bacchetta, R.] Hosp San Raffaele, San Raffaele Telethon Inst Gene, I-20132 Milan, Italy.
[Hsu, A.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Hammarstrom, L.] Karolinska Inst, Dept Lab Med, Stockholm, Sweden.
[Davies, E. G.] Hosp Childrens NHS Trust, Great Ormond St Children, Ctr Immunodeficiency, London, England.
[Eren, E.] Southampton Gen Hosp, Dept Immunol, Southampton SO9 4XY, Hants, England.
[Arkwright, P. D.] Univ Manchester, Dept Child Hlth, Manchester, Lancs, England.
[Moilanen, J. S.] Univ Tampere, IMT Bioinformat, FIN-33101 Tampere, Finland.
[Moilanen, J. S.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Viemann, D.] Univ Munster, Inst Expt Dermatol, D-4400 Munster, Germany.
[Khan, S.] Scunthorpe Gen Hosp, Scunthorpe, Humberside, England.
[Marodi, L.] Univ Debrecen, Dept Infect Pediat, H-4012 Debrecen, Hungary.
[Marodi, L.] Hlth Sci Ctr, Debrecen, Hungary.
[Cant, A. M.] Newcastle Gen Hosp, Childrens BMT Unit, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England.
[Puck, J. M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
RI Plebani, Alessandro/C-8593-2011; Moilanen, Jukka/G-2604-2012; Pignata,
Claudio/O-2466-2013; Litzman, Jiri/E-2746-2012
OI Moilanen, Jukka/0000-0002-8041-3205; Pignata,
Claudio/0000-0003-1568-9843;
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9104
EI 1365-2249
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD NOV
PY 2008
VL 154
SU 1
BP 154
EP 155
PG 2
WC Immunology
SC Immunology
GA 398JD
UT WOS:000262727500288
ER
PT J
AU Meyts, I
Renard, M
Uyttebroeck, A
De Vos, R
Freson, K
Holland, S
Van Geet, C
AF Meyts, I
Renard, M.
Uyttebroeck, A.
De Vos, R.
Freson, K.
Holland, S.
Van Geet, C.
TI Recurrent severe colitis in a boy with congenital neutropenia and
neutrophil dysfunction
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 13th European-Soc-for-Immunodeficiencies/10th
Int-Patient-Org-for-Primary-Immunodeficiencies/8th
Int-Nursing-Group-for-Immunodeficiencies Meeting
CY OCT 16-19, 2008
CL Hertogenbosch, NETHERLANDS
SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies
C1 [Meyts, I; Renard, M.; Uyttebroeck, A.; De Vos, R.; Freson, K.; Van Geet, C.] Univ Hosp Leuven, Dept Pediat, Louvain, Belgium.
[Holland, S.] Natl Inst Allergy & Infect, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-9104
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD NOV
PY 2008
VL 154
BP 168
EP 168
PG 1
WC Immunology
SC Immunology
GA 398JD
UT WOS:000262727500311
ER
PT J
AU Boztug, K
Appaswamy, G
Ashikov, A
Schaffer, AA
Salzer, U
Diestelhorst, J
Germeshausen, M
Brandes, G
Lee-Gossler, J
Noyan, F
Gatzke, AK
Minkov, M
Greil, J
Kratz, C
Petropoulou, T
Pellier, I
Bellanne-Chantelot, C
Rezaei, N
Monkemoller, K
Irani-Hakimeh, N
Bakker, H
Gerardy-Schahn, R
Zeidler, C
Grimbacher, B
Welte, K
Klein, C
AF Boztug, K.
Appaswamy, G.
Ashikov, A.
Schaeffer, A. A.
Salzer, U.
Diestelhorst, J.
Germeshausen, M.
Brandes, G.
Lee-Gossler, J.
Noyan, F.
Gatzke, A. K.
Minkov, M.
Greil, J.
Kratz, C.
Petropoulou, T.
Pellier, I
Bellanne-Chantelot, C.
Rezaei, N.
Moenkemoeller, K.
Irani-Hakimeh, N.
Bakker, H.
Gerardy-Schahn, R.
Zeidler, C.
Grimbacher, B.
Welte, K.
Klein, C.
TI A novel clinical syndrome associating severe congenital neutropenia and
complex developmental aberrations caused by deficiency of G6PC(3)
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 13th European-Soc-for-Immunodeficiencies/10th
Int-Patient-Org-for-Primary-Immunodeficiencies/8th
Int-Nursing-Group-for-Immunodeficiencies Meeting
CY OCT 16-19, 2008
CL Hertogenbosch, NETHERLANDS
SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies
C1 [Boztug, K.; Appaswamy, G.; Ashikov, A.; Diestelhorst, J.; Germeshausen, M.; Brandes, G.; Lee-Gossler, J.; Noyan, F.; Gatzke, A. K.; Bakker, H.; Gerardy-Schahn, R.; Zeidler, C.; Welte, K.; Klein, C.] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany.
[Schaeffer, A. A.] Natl Biotechnol Ctr, Natl Inst Hlth, Bethesda, MD USA.
[Salzer, U.; Kratz, C.] Freiburg Med Ctr, Dept Rheumatol Immunol, Freiburg, Germany.
[Minkov, M.] St Anna Childrens Hosp, Dept Pediat Hematol Oncol, A-1090 Vienna, Austria.
[Greil, J.] Univ Heidelberg, Dept Pediat Hematol Oncol, Heidelberg, Germany.
[Petropoulou, T.] Univ Athens, Sophia Childrens Hosp, Athens, Greece.
[Pellier, I] CHU Angers, Dept Pediat Hematol Oncol, Angers, France.
[Bellanne-Chantelot, C.] AP HP Pitie Salpetrere, Dept Genet, Paris, France.
[Rezaei, N.] Univ Tehran Med Sci, Immunol Asthma & Allergy Res Inst, Tehran, Iran.
[Moenkemoeller, K.] Childrens Hosp Amsterdamer Str, Cologne, Germany.
[Irani-Hakimeh, N.] St Georges Univ Hosp, Beirut, Lebanon.
[Grimbacher, B.] Royal Free Hosp, London NW3 2QG, England.
[Grimbacher, B.] UCL, London, England.
RI Rezaei, Nima/B-4245-2008; Schaffer, Alejandro/F-2902-2012; isabelle,
pellier/L-5683-2015; Ashikov, Angel/N-7714-2015
OI Rezaei, Nima/0000-0002-3836-1827; Ashikov, Angel/0000-0001-9679-7955
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 0009-9104
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD NOV
PY 2008
VL 154
SU 1
BP 206
EP 207
PG 2
WC Immunology
SC Immunology
GA 398JD
UT WOS:000262727500398
ER
PT J
AU Grimbacher, B
Hennigs, A
Nabavi, M
Glocker, EO
Schaffer, A
Woellner, C
Salzer, U
Pfeifer, D
Tahami, F
Plebani, A
Amirzagar, M
Rezaei, N
AF Grimbacher, B.
Hennigs, A.
Nabavi, M.
Glocker, E. O.
Schaffer, A.
Woellner, C.
Salzer, U.
Pfeifer, D.
Tahami, F.
Plebani, A.
Amirzagar, M.
Rezaei, N.
TI Chronic mucocutaneous candidiasis is associated with a homozygous
mutation in CARD9
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 13th European-Soc-for-Immunodeficiencies/10th
Int-Patient-Org-for-Primary-Immunodeficiencies/8th
Int-Nursing-Group-for-Immunodeficiencies Meeting
CY OCT 16-19, 2008
CL Hertogenbosch, NETHERLANDS
SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies
C1 [Grimbacher, B.; Glocker, E. O.; Woellner, C.; Tahami, F.] Royal Free Hosp, Dpt Immunol, London NW3 2QG, England.
[Grimbacher, B.; Glocker, E. O.; Woellner, C.] UCL, Dpt Immunol, London, England.
[Hennigs, A.] Univ Hosp Freiburg, Freiburg, Germany.
[Nabavi, M.] Semnan Med Univ, Amir Almomenin Hosp, Semnan, Iran.
[Schaffer, A.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Plebani, A.] Univ Brescia, Paediat Clin, Brescia, Italy.
[Amirzagar, M.; Rezaei, N.] Univ Tehran Med Sci, Immunogenet Lab, Tehran, Iran.
RI Plebani, Alessandro/C-8593-2011; Rezaei, Nima/B-4245-2008
OI Rezaei, Nima/0000-0002-3836-1827
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-9104
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD NOV
PY 2008
VL 154
BP 213
EP 213
PG 1
WC Immunology
SC Immunology
GA 398JD
UT WOS:000262727500412
ER
PT J
AU Franco, J
Moncada, MA
Velez-Ortega, AC
Gomez-Rodriguez, J
Dutra, AC
Munoz, S
Orrego, JC
Montoya, J
AF Franco, J.
Moncada, M. A.
Velez-Ortega, A. C.
Gomez-Rodriguez, J.
Dutra, A. C.
Munoz, S.
Orrego, J. C.
Montoya, J.
TI CD4 deficiency in a child with a congenital syndrome and recurrent
infections
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 13th European-Soc-for-Immunodeficiencies/10th
Int-Patient-Org-for-Primary-Immunodeficiencies/8th
Int-Nursing-Group-for-Immunodeficiencies Meeting
CY OCT 16-19, 2008
CL Hertogenbosch, NETHERLANDS
SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies
C1 [Franco, J.] Hosp A, Medellin, Colombia.
[Moncada, M. A.; Velez-Ortega, A. C.; Munoz, S.; Orrego, J. C.] Univ Antioquia, Medellin, Colombia.
[Gomez-Rodriguez, J.; Dutra, A. C.] NHGRI, Bethesda, MD 20892 USA.
[Montoya, J.] Hosp Univ San Vicente Paul, Medellin, Colombia.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-9104
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD NOV
PY 2008
VL 154
BP 216
EP 216
PG 1
WC Immunology
SC Immunology
GA 398JD
UT WOS:000262727500417
ER
PT J
AU Kinders, RJ
Hollingshead, M
Khin, S
Rubinstein, L
Tomaszewski, JE
Doroshow, JH
Parchment, RE
AF Kinders, Robert J.
Hollingshead, Melinda
Khin, Sonny
Rubinstein, Larry
Tomaszewski, Joseph E.
Doroshow, James H.
Parchment, Ralph E.
CA Natl Canc Inst Phase 0 Clinical Tr
TI Preclinical Modeling of a Phase 0 Clinical Trial: Qualification of a
Pharmacodynamic Assay of Poly (ADP-Ribose) Polymerase in Tumor Biopsies
of Mouse Xenografts
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID POLY(ADP-RIBOSE) POLYMERASE; CELL-DEATH; INHIBITION; REPAIR
AB Purpose: The National Cancer Institute has completed a first-in-human clinical pharmacodynamic trial of the targeted agent ABT-888, a poly (ADP-ribose) polymerase (PARP) inhibitor, under the auspices of the U.S. Food and Drug Administration's Exploratory Investigational New Drug Application. Performance of the study design, needle biopsy procedure, and validated pharmacodynamic assay were evaluated in human tumor xenograft models.
Experimental Design: A validated ELISA was used to quantify PAR, a product of the PARP 1/2 enzyme activity. Sampling variability from tumor heterogeneity was determined by comparing PAR content in multiple tumors, and in different areas of the same tumor in a particular animal, collected under anesthesia by needle biopsy or resection before and after administration of nontoxic doses of ABT-888. The degree of PARP inhibition following single-dose treatment was evaluated in the time frame anticipated for biopsy in humans.
Results: Sampling variability around the mean (similar to 50%) for untreated and vehicle-treated animals was random and due to specimen heterogeneity. PAR levels in initial and repeat tumor biopsies, separated by 1 week, were not altered by the stress induced by daily handling of the animals. A single ABT-888 dose (3 or 12.5 mg/kg) reduced intratumor PAR levels by >95%. ABT-888 (1.56-25 mg/kg) significantly decreased PAR levels at 2 h post-dosing.
Conclusion: The detailed methodologies developed for this study facilitated the design of a phase 0, first-in-human clinical trial of ABT-888 and could serve as a model for developing proof-of-principle clinical trials of molecularly targeted anticancer agents.
C1 [Kinders, Robert J.; Khin, Sonny; Parchment, Ralph E.] Natl Canc Inst Frederick, Sci Applicat Int Corp, Frederick Inc,Appl Dev Res Support Directorate, Lab Human Toxicol & Pharmacol, Frederick, MD 21702 USA.
[Hollingshead, Melinda] NCI, Dev Therapeut Program, Biol Testing Branch, Frederick, MD 21701 USA.
[Rubinstein, Larry] NCI, Biometr Res Branch, Frederick, MD 21701 USA.
[Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Frederick, MD 21701 USA.
[Doroshow, James H.] NCI, Mol Pharmacol Lab, Frederick, MD 21701 USA.
RP Kinders, RJ (reprint author), Natl Canc Inst Frederick, Sci Applicat Int Corp, Frederick Inc,Appl Dev Res Support Directorate, Lab Human Toxicol & Pharmacol, POB B, Frederick, MD 21702 USA.
EM kindersr@mail.nih.gov
FU National Cancer Institute; NIH [N01-CO-12400]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, NIH under contract N01-CO-12400.The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. 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
costs of publication of this article were defrayed in part by the
payment of page charges. This article must therefore be hereby marked
advertisement in accordance with 18 U.S.C. Section 1734 solely to
indicate this fact.
NR 19
TC 54
Z9 54
U1 1
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 NOV 1
PY 2008
VL 14
IS 21
BP 6877
EP 6885
DI 10.1158/1078-0432.CCR-08-0214
PG 9
WC Oncology
SC Oncology
GA 369ZK
UT WOS:000260732200021
PM 18980982
ER
PT J
AU Jacobs, SA
Swerdlow, SH
Kant, J
Foon, KA
Jankowitz, R
Land, SR
DeMonaco, N
Joyce, J
Osborn, JL
Evans, TL
Schaefer, PM
Luong, TM
AF Jacobs, Samuel A.
Swerdlow, Steven H.
Kant, Jeffrey
Foon, Kenneth A.
Jankowitz, Rachel
Land, Stephanie R.
DeMonaco, Nicholas
Joyce, Judith
Osborn, Jennifer L.
Evans, Terry L.
Schaefer, Patricia M.
Luong, The Minh
TI Phase II Trial of Short-Course CHOP-R Followed by Y-90-ibritumomab
Tiuxetan and Extended Rituximab in Previously Untreated Follicular
Lymphoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; POSITRON-EMISSION-TOMOGRAPHY; LOW-GRADE;
IBRITUMOMAB TIUXETAN; RESPONSE ASSESSMENT; 1ST-LINE TREATMENT; INDOLENT
LYMPHOMA; I-131 TOSITUMOMAB; INITIAL TREATMENT; FREE SURVIVAL
AB Purpose: Radioimmunotherapy has been approved for relapsed follicular lymphoma (FL), including rituximab-refractory FL. This study was designed to determine the CR rate with short-course chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP-R) followed by 90-Y ibritumomab tiuxetan (RIT) with extended rituximab as first-line treatment.
Experimental Design: Between March 2004 and February 2007, 60 patients with stage 11 to IV symptomatic or bulky FL from a single institution supported by a large community network entered this phase 11 trial. Patients received CHOP-R for three treatment cycles before RIT followed by four additional weekly treatments with rituximab. Response was determined using fusion [18 F] fluorodeoxyglucose-positron emission tomography (PET)-computed tomography (CT) imaging.
Results: Of the 60 patients entering this trial, 55 patients completed all protocol therapy. The median follow up was 19.7 months (range, 0.26-35.9 months). For intent-to-treat analysis, the complete response (CR) rate after CHOP-R, as assessed by CT and PET imaging, was 40% and 46%, respectively. After RIT, the CR rate improved, as assessed by CT and PET imaging, to 82% and 89%, respectively. Ten patients have progressed, including eight from best response of CR. Seven of 18 patients who were PET positive after CHOP-R progressed compared with 3 of 37 patients who were PET negative (P = 0.010).
Conclusions: In patients with previously untreated, symptomatic or bulky FL, short-course chemoimmunotherapy and consolidation RIT and extended rituximab resulted in a high CR rate. Failure to achieve an early PET CR after CHOP-R indicated high risk of relapse.
C1 [Jacobs, Samuel A.] Univ Pittsburgh, Med Ctr, Ctr Canc, Univ Pittsburgh Med Ctr Canc Pavil,Dept Med, Pittsburgh, PA 15232 USA.
[Swerdlow, Steven H.; Kant, Jeffrey] Univ Pittsburgh, Med Ctr, Ctr Canc, Dept Pathol, Pittsburgh, PA 15232 USA.
[Joyce, Judith] Univ Pittsburgh, Med Ctr, Ctr Canc, Dept Radiol, Pittsburgh, PA 15232 USA.
[Schaefer, Patricia M.] Univ Pittsburgh, Med Ctr, Ctr Canc, Clin Res Serv, Pittsburgh, PA 15232 USA.
[Land, Stephanie R.; Luong, The Minh] NSABP, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA USA.
[Land, Stephanie R.; Luong, The Minh] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Land, Stephanie R.; Luong, The Minh] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA.
[DeMonaco, Nicholas] Oncol Hematol Associates, Pittsburgh, PA USA.
RP Jacobs, SA (reprint author), Univ Pittsburgh, Med Ctr, Ctr Canc, Univ Pittsburgh Med Ctr Canc Pavil,Dept Med, 5150 Ctr Ave,Suite 510, Pittsburgh, PA 15232 USA.
EM jacobssa@upmc.edu
FU Biogenldec Pharmaceuticals and National Cancer Institute [CCSG/IRAT P30
CA 047904]
FX Biogenldec Pharmaceuticals and National Cancer Institute CCSG/IRAT P30
CA 047904. The trial is registered at http://www.clinicaltrials.gov
(identifier: NCT00177554.)
NR 36
TC 56
Z9 59
U1 0
U2 0
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 NOV 1
PY 2008
VL 14
IS 21
BP 7088
EP 7094
DI 10.1158/1078-0432.CCR-08-0529
PG 7
WC Oncology
SC Oncology
GA 369ZK
UT WOS:000260732200046
PM 18981007
ER
PT J
AU Odenike, OM
Alkan, S
Sher, D
Godwin, JE
Huo, D
Brandt, SJ
Green, M
Xie, J
Zhang, Y
Vesole, DH
Stiff, P
Wright, J
Larson, RA
Stock, W
AF Odenike, Olatoyosi M.
Alkan, Serhan
Sher, Dorie
Godwin, John E.
Huo, Dezheng
Brandt, Stephen J.
Green, Margaret
Xie, Jingping
Zhang, Yariming
Vesole, David H.
Stiff, Patrick
Wright, John
Larson, Richard A.
Stock, Wendy
TI Histone Deacetylase Inhibitor Romidepsin Has Differential Activity in
Core Binding Factor Acute Myeloid Leukemia
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID T(8/21) FUSION PROTEIN; TRANS-RETINOIC ACID; VALPROIC ACID; DEPSIPEPTIDE
FR901228; MYELODYSPLASTIC SYNDROME; GRANULOCYTIC MATURATION; DNA
METHYLTRANSFERASE; MYELOGENOUS LEUKEMIA; GENE-EXPRESSION;
DOWN-REGULATION
AB Purpose: Recruitment of histone deacetylases (HDAC) is a mechanism of transcriptional repression implicated in the differentiation block in acute myeloid leukemia (AML). We hypothesized that the HDAC inhibitor romidepsin could cause transcriptional derepression, up-regulation of specific target genes in AML, and differentiation of the leukemic clone. The primary objectives of the study were to evaluate the safety and efficacy of romidepsin in advanced AML.
Experimental Design: Twenty patients were stratified into cohort A or B based on the absence or presence of chromosomal abnormalities known to recruit HDACs, including those involving core binding factor (CBF). Romidepsin was administered i.v. at 13 mg/m(2)/d on days 1, 8, and 15 of a 28-day cycle. Pharmacodynamic endpoints were evaluated at serial time points.
Results: Common adverse effects noted were grade 1 to 2 nausea, anorexia, and fatigue. No objective evidence of antileukemic activity was seen in cohort A. In cohort B, although there were no clinical responses by standard criteria, antileukemic activity was observed in 5 of 7 patients. Two patients had clearance of bone marrow blasts and 3 patients had a >50% decrease in bone marrow blasts. Furthermore, in cohort B, at 24 h, there was a significant increase in MDR1 (P = 0.005), p15 (P = 0.01), and p14 (P < 0.0001) expression. In cohort A, although there was a trend toward up-regulation of MDR1, p15, and p14 expression, these changes were not statistically significant.
Conclusion: Romidepsin has differential antileukemic and molecular activity in CBF AML. Development of this agent in CBF AML should focus on combinations that target related mechanisms of gene silencing such as DNA methylation.
C1 [Odenike, Olatoyosi M.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Alkan, Serhan; Godwin, John E.; Stiff, Patrick] Loyola Univ, Maywood, IL 60153 USA.
[Brandt, Stephen J.; Xie, Jingping] Vanderbilt Univ, Nashville, IL USA.
[Vesole, David H.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Wright, John] NCI, Bethesda, MD 20892 USA.
RP Odenike, OM (reprint author), Univ Chicago, Med Ctr, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA.
EM todenike@medicine.bsd.uchicago.edu
OI Larson, Richard/0000-0001-9168-3203
FU National Cancer Institute/Cancer Therapy Evaluation Program
[N01-CM-62201]; American Society of Oncology Career Development Award;
American Cancer Society Institutional Grant; National Cancer Institute
Translational Research
FX National Cancer Institute/Cancer Therapy Evaluation Program contract
N01-CM-62201 in collaboration with Gloucester Pharmaceuticals, American
Society of Oncology Career Development Award (O.M. Odenike), American
Cancer Society Institutional Grant (O.M. Odenike), and National Cancer
Institute Translational Research funds (O.M. Odenike and S. Alkan).
NR 43
TC 49
Z9 50
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD NOV 1
PY 2008
VL 14
IS 21
BP 7095
EP 7101
DI 10.1158/1078-0432.CCR-08-1007
PG 7
WC Oncology
SC Oncology
GA 369ZK
UT WOS:000260732200047
PM 18981008
ER
PT J
AU Agrawal, Y
Koch, WM
Xiao, W
Westra, WH
Trivett, AL
Symer, DE
Gillison, ML
AF Agrawal, Yuri
Koch, Wayne M.
Xiao, Weihong
Westra, William H.
Trivett, Anna L.
Symer, David E.
Gillison, Maura L.
TI Oral Human Papillomavirus Infection Before and After Treatment for Human
Papillomavirus 16-Positive and Human Papillomavirus 16-Negative Head and
Neck Squamous Cell Carcinoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID UPPER AERODIGESTIVE TRACT; CERVICAL-CANCER PATIENTS; RISK-FACTOR; PCR;
ASSOCIATION; TONSILLAR; HUSBANDS; SAMPLES; ADULTS; DNA
AB Purpose: Oral human papillomavirus (HPV) infection is a risk factor for head and neck squamous cell carcinoma (HNSCC), and is a concern for patients with HPV-positive HNSCC and their partners. The prevalence of oral HPV infection before and after cancer therapy was investigated among patients with HPV16-positive and HPV16-negative HNSCC.
Experimental Design: Serial oral rinse samples (ORS) were collected from a cohort of 135 HNSCC cases as frequently as every 3 months for up to 3 years. Tumor HPV status was determined by HPV16 in situ hybridization. HPV was detected in ORS by consensus PCR and line blot hybridization. The HPV16 variants in positive oral rinse - tumor pairs were determined by sequencing. The odds of oral HPV infection among HPV16-positive and HPV16-negative cases were compared by use of generalized estimating equations.
Results: Patients were followed for a median of 21 months and provided a median of 4 samples. Forty-four of 135 patients had HPV16-positive tumors. HPV16-positive cases were more likely than HPV16-negative cases to have an oral HPV infection detected before (odds ratio, 8.6; 95% confidence interval, 3.5-21) and after therapy (OR, 2.9; 95% confidence interval, 1.1-7.4). Oral infections by HPV16 and other high-risk, but not low-risk, types were more common among HPV16-positive cases both before and after therapy. Most HPV16 variants in ORS were European, unique, and identical to that in the tumor. Persistence of a type-specific oral infection was demonstrable for as long as 5 years.
Conclusion: Oral high-risk HPV infections are more frequent among patients with HPV16-positive than HPV16-negative HNSCC, consistent with a behavioral and/or biological disposition to infection,
C1 [Agrawal, Yuri; Koch, Wayne M.] Johns Hopkins Univ Hosp, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA.
[Westra, William H.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA.
[Xiao, Weihong; Gillison, Maura L.] Johns Hopkins Kimmel Comprehens Canc Ctr, Div Viral Oncol, Baltimore, MD USA.
[Trivett, Anna L.; Symer, David E.] Natl Canc Inst, Basic Res Lab, Frederick, MD USA.
RP Gillison, ML (reprint author), Johns Hopkins Univ, Canc Res Bldg 1,Rm 351,1650 Orleans St, Baltimore, MD 21231 USA.
EM gillima@jhmi.edu
RI Symer, David/E-4173-2011
FU NIDCR [DE016631]; Oral Cancer Foundation; NIH [1 P50 CA96784-01];
Intramural Research Program of the Center for Cancer Research; National
Cancer Institute
FX NIDCR DE016631, Oral Cancer Foundation (M.L. Gillison) and NIH 1 P50
CA96784-01 (W. Koch). This research was supported in part by the
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, NIH (D. Symer). The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 27
TC 41
Z9 42
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD NOV 1
PY 2008
VL 14
IS 21
BP 7143
EP 7150
DI 10.1158/1078-0432.CCR-08-0498
PG 8
WC Oncology
SC Oncology
GA 369ZK
UT WOS:000260732200053
PM 18981014
ER
PT J
AU Goldstein, DS
Holmes, C
AF Goldstein, David S.
Holmes, Courtney
TI Neuronal Source of Plasma Dopamine
SO CLINICAL CHEMISTRY
LA English
DT Article
ID POSTURAL TACHYCARDIA SYNDROME; SYMPATHETIC-NERVE ACTIVITY; CHRONIC
ORTHOSTATIC INTOLERANCE; NEURALLY-MEDIATED SYNCOPE; NOREPINEPHRINE;
TYRAMINE; NORADRENALINE; RELEASE; HUMANS; CATECHOLS
AB BACKGROUND: Determinants of plasma norepinephrine (NE) and epinephrine concentrations are well known; those of the third endogenous catecholamine, dopamine (DA), remain poorly understood. We tested ill humans whether DA enters the plasma after corelease with NE during exocytosis from sympathetic noradrenergic nerves.
METHODS: We reviewed plasma catecholamine data from patients referred for autonomic testing and control subjects under the following experimental conditions: during Supine rest and in response to orthostasis; intravenous yohimbine (YOH), isoproterenol (ISO), or glucagon (GLU), which augment exocytotic release of NE from sympathetic nerves; intravenous trimethaphan (TRI) or pentolinium (PEN), which decrease exocytotic NE release; or intravenous tyramine (TYR), which releases NE by nonexocytotic means. We included groups of patients with pure autonomic failure (PAF), bilateral thoracic sympathectomises (SNS-x) or multiple system atrophy (MSA), since PAF and SNS-x are associated with noradrenergic denervation and MSA is not.
RESULTS: Orthostasis, YOH, ISO, and TYR increased and TR1/PEN decreased plasma DA concentrations. Individual Values for changes in plasma DA concentrations correlated positively with changes in NE in response to orthostasis (r = 0.72, P < 0.0001), YOH (r = 0.75, P < 0.0001), ISO (r = 0.71, P < 0.0001), GLU (r = 0.47, P = 0.01), and TYR (r = 0.67, P < 0.0001). PAF and SNS-x patients had low plasma DA concentrations. We estimated that DA constitutes 2%-4% of the catecholamine released by exocytosis from sympathetic nerves and that 50%-90% of plasma DA has a sympathoneural Source.
CONCLUSIONS: Plasma DA is derived Substantially from sympathetic noradrenergic nerves. (C) 2008 American Association for Clinical Chemistry
C1 [Goldstein, David S.; Holmes, Courtney] 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 6N252, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU NIH; National Institute of Neurological Disorders and Stroke
FX Research Funding: This research was supported by the Intramural Research
Program of the NIH, National Institute of Neurological Disorders and
Stroke.
NR 40
TC 23
Z9 23
U1 1
U2 3
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
EI 1530-8561
J9 CLIN CHEM
JI Clin. Chem.
PD NOV
PY 2008
VL 54
IS 11
BP 1864
EP 1871
DI 10.1373/clinchem.2008.107193
PG 8
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 366AO
UT WOS:000260452000016
PM 18801936
ER
PT J
AU Venditti, CP
AF Venditti, Charles P.
TI Increased C3-Carnitine in a Healthy Premature Infant Commentary
SO CLINICAL CHEMISTRY
LA English
DT Editorial Material
C1 NHGRI, Genet Dis Res Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Venditti, CP (reprint author), NHGRI, Genet Dis Res Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM venditti@mail.nih.gov
NR 3
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2008
VL 54
IS 11
BP 1917
EP 1918
DI 10.1373/clinchem.2008.113449
PG 2
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 366AO
UT WOS:000260452000023
ER
PT J
AU Gennari, M
Stratakis, CA
Hovarth, A
Pirazzoli, P
Cicognani, A
AF Gennari, Monia
Stratakis, Constantine A.
Hovarth, Anelia
Pirazzoli, Piero
Cicognani, Alessandro
TI A novel PRKAR1A mutation associated with hepatocellular carcinoma in a
young patient and a variable Carney complex phenotype in affected
subjects in older generations
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID PROTEIN-KINASE-A; TISSUE-SPECIFIC EXTINGUISHER; SUBUNIT TYPE 1A;
REGULATORY SUBUNIT; TSE1 ENCODES; ENDOCRINE; DISEASE; TUMORS; NEOPLASIA;
GENETICS
AB Context Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia syndrome (OMIM 160980). About 70% of cases are familiar; most have mutations of the PRKAR1A gene on chromosome 17q22-24. There is little phenotype-genotype correlation known to date.
Objective To study the genotype-phenotype correlation in a family with newly diagnosed CNC and three generations of subjects bearing the same PRKAR1A mutation. The proband was diagnosed with hepatocellular carcinoma, a tumour that appears to be associated with CNC.
Design The study consisted of clinical and genetic analysis of a total of 10 individuals belonging to a large Italian family.
Patients The index case was referred for PRKAR1A gene mutation analysis because he met the diagnostic criteria for a clinical diagnosis of CNC.
Results The PRKAR1A-inactivating mutation c.502 + 1G > A in the intron 5 splice-donor site was detected after bidirectional sequencing of germline DNA. The mutation causes a frameshift in the transcribed sequence and a nonsense mRNA that was shown to be degraded; this leads to PRKAR1A haploinsufficiency in all tissues. All available relatives were screened first by DNA testing and, if the latter was positive, by clinical, biochemical and imaging means.
Conclusions A novel PRKAR1A mutation with an apparently low penetrance and variable expression is reported; the same mutation is also associated with a hepatocellular carcinoma. This is the first time a PRKAR1A mutation is reported in individuals who were diagnosed with CNC after retrospective family screening and following the identification of a proband; the finding has implications for genetic counselling on PRKAR1A and/or CNC.
C1 [Gennari, Monia; Pirazzoli, Piero; Cicognani, Alessandro] Univ Bologna, S Orsola Hosp, I-40138 Bologna, Italy.
[Stratakis, Constantine A.; Hovarth, Anelia] NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NICHD,NIH, Bethesda, MD 20892 USA.
[Gennari, Monia; Stratakis, Constantine A.] NICHHD, Pediat Endocrinol Program, NICHD, NIH, Bethesda, MD 20892 USA.
RP Gennari, M (reprint author), Univ Bologna, S Orsola M Malpighi Hosp, Pad 13,Via Massarenti 11, I-40138 Bologna, Italy.
EM monia.gennari2@unibo.it
FU Department of Oncology; Hematology, Pathology Division; Felice Addarii'
Institute S. Orsola-Malpighi Hospital; University of Bologna
FX We thank Chiara Martini MD (General Medicine third Clinic-Hospital,
Padua) for collecting blood samples of the maternal grand father (I. 2),
maternal uncles (II. 1, II. 2) and their children (III. 1, III. 2, III.
3) to do genetic assay. We also thank Antonietta D'Errico MD and Barbara
Corti MD (Department of Oncology and Hematology, Pathology Division,
'Felice Addarii' Institute S. Orsola-Malpighi Hospital, University of
Bologna, Bologna) for liver DNA extraction.
NR 20
TC 14
Z9 16
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD NOV
PY 2008
VL 69
IS 5
BP 751
EP 755
DI 10.1111/j.1365-2265.2008.03286.x
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 361GZ
UT WOS:000260117000009
PM 18445140
ER
PT J
AU Fitzgerald, DP
Palmieri, D
Hua, E
Hargrave, E
Herring, JM
Qian, YZ
Vega-Valle, E
Weil, RJ
Stark, AM
Vortmeyer, AO
Steeg, PS
AF Fitzgerald, Daniel P.
Palmieri, Diane
Hua, Emily
Hargrave, Elizabeth
Herring, Jeanne M.
Qian, Yongzhen
Vega-Valle, Eleazar
Weil, Robert J.
Stark, Andreas M.
Vortmeyer, Alexander O.
Steeg, Patricia S.
TI Reactive glia are recruited by highly proliferative brain metastases of
breast cancer and promote tumor cell colonization
SO CLINICAL & EXPERIMENTAL METASTASIS
LA English
DT Article
DE brain metastasis; brain pathology; breast cancer; neuroinflammation;
reactive glia; xenograft
ID CENTRAL-NERVOUS-SYSTEM; EXTRACELLULAR-MATRIX; NUDE-MICE; ALTERED
EXPRESSION; IN-VIVO; INJURY; GROWTH; MICROENVIRONMENT; MICROGLIA; STROMA
AB Interactions between tumor cells and the microenvironment are crucial to tumor formation and metastasis. The central nervous system serves as a "sanctuary" site for metastasis, resulting in poor prognosis in diagnosed patients. The incidence of brain metastasis is increasing; however, little is known about interactions between the brain and metastatic cells. Brain pathology was examined in an experimental model system of brain metastasis, using a subline of MDA-MB-231 human breast cancer cells. The results were compared with an analysis of sixteen resected human brain metastases of breast cancer. Experimental metastases formed preferentially in specific brain regions, with a distribution similar to clinical cases. In both the 231-BR model, and in human specimens, Ki67 expression indicated that metastases were highly proliferative (similar to 50%). Little apoptosis was observed in either set of tumors. In the model system, metastases elicited a brain inflammatory response, with extensive reactive gliosis surrounding metastases. Similarly, large numbers of glial cells were found within the inner tumor mass of human brain metastases. In vitro co-cultures demonstrated that glia induced a similar to 5-fold increase in metastatic cell proliferation (P < 0.001), suggesting that brain tissue secretes factors conducive to tumor cell growth. Molecules used to signal between tumor cells and the surrounding glia could provide a new avenue of therapeutic targets for brain metastases.
C1 [Fitzgerald, Daniel P.; Palmieri, Diane; Hua, Emily; Hargrave, Elizabeth; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
[Herring, Jeanne M.; Qian, Yongzhen; Vega-Valle, Eleazar] NCI, Lab Anim Sci Program, Sci Applicat Int Corp, NIH, Frederick, MD 21701 USA.
[Weil, Robert J.] Cleveland Clin, Brain Tumor & Neurooncol Ctr, Dept Neurosurg, Cleveland, OH 44106 USA.
[Weil, Robert J.] Cleveland Clin, Brain Tumor & Neurooncol Ctr, Neurol Inst, Cleveland, OH 44106 USA.
[Stark, Andreas M.] Schleswig Holstein Univ, Dept Neurosurg, Med Ctr, Kiel, Germany.
[Vortmeyer, Alexander O.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Fitzgerald, DP (reprint author), NCI, Womens Canc Sect, Mol Pharmacol Lab, NIH, Bldg 37,Room 1126, Bethesda, MD 20892 USA.
EM fitzgeda@mail.nih.gov
RI Fitzgerald, Daniel/B-1633-2009; Palmieri, Diane/B-4258-2015
FU US Department of Defense Breast Cancer Research Program [W81
XWH-062-0033]; National Cancer Institute; CCR; NIH
FX We would like to thank Hong Wang (Developmental Neurobiology Section of
the NHLBI Division of Intramural Research, NIH) for providing mixed
glial cultures used in the soft agar experiments. This research was
supported by the US Department of Defense Breast Cancer Research
Program, grant number: W81 XWH-062-0033; and the Intramural Research
Program of the National Cancer Institute, CCR, NIH.
NR 52
TC 90
Z9 92
U1 3
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0262-0898
J9 CLIN EXP METASTAS
JI Clin. Exp. Metastasis
PD NOV
PY 2008
VL 25
IS 7
BP 799
EP 810
DI 10.1007/s10585-008-9193-z
PG 12
WC Oncology
SC Oncology
GA 355PG
UT WOS:000259720200010
PM 18649117
ER
PT J
AU Loomba, R
Wesley, R
Pucino, F
Liang, TJ
Kleiner, DE
Lavine, JE
AF Loomba, Rohit
Wesley, Robert
Pucino, Frank
Liang, T. Jake
Kleiner, David E.
Lavine, Joel E.
TI Placebo in Nonalcoholic Steatohepatitis: Insight Into Natural History
and Implications for Future Clinical Trials
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
ID FATTY LIVER-DISEASE; URSODEOXYCHOLIC ACID; METAANALYSIS; REMISSION;
RATES
AB Background & Aims: Changes in biochemical and histologic parameters related to nonalcoholic steatohepatitis (NASH) in placebo-treared patients may provide an insight into the natural history and help in defining treatment end points in NASH. The aim of our study was to assess the biochemical and histologic changes seen in the placebo arm of the randomized, placebo-controlled trials in adult patients with NASH. Methods: Medline was searched (through May 2008) for studies published in the English language. Randomized, placebo-controlled trials of at least 6 months' duration in patients with NASH that provided biochemical and/or histologic data of the placebo arm were included. One investigator performed the literature search and data extraction. Two investigators independently confirmed that the studies met prespecified criteria. Pooled estimates of biochemical and histologic parameters associated with NASH were calculated. Results: Five randomized controlled trials met the predefined criteria and included 162 placebo-treated and 189 active-treatment patients. The mean serum alanine and aspartate aminotransferase levels decreased on placebo. A 1-point improvement in steatosis, ballooning degeneration, lobular inflammation, NASH fibrosis, and combined inflammation scores was seen in 31% 15%, 33%, 22%, and 32% of patients, respectively. A 2-point improvement in NASH histologic scores is rarely seen. Conclusions: Serum alanine aminotransferase levels may decrease on placebo and is not a reliable measure of treatment response. Although a 1-point improvement is seen in a third of patients, a 2-point improvement in histologic parameters is rarely seen in the placebo arm and may be more reliable in assessing treatment response. These data may have important implications in designing future clinical trials in NASH.
C1 [Loomba, Rohit; Liang, T. Jake] Natl Inst Diabet & Digest Dis, Liver Dis Branch, Bethesda, MD USA.
[Wesley, Robert] Hosp Epidemiol, Bethesda, MD USA.
[Pucino, Frank] Ctr Clin, Dept Pharm, Bethesda, MD USA.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Loomba, Rohit] Univ Calif San Diego, Div Gastroenterol, Dept Med, La Jolla, CA 92093 USA.
[Lavine, Joel E.] Univ Calif San Diego, Dept Pediat, Div Pediat Gastroenterol, La Jolla, CA 92093 USA.
RP Loomba, R (reprint author), Univ Calif San Diego, Div Gastroenterol, Dept Med, UC 303,MC0063,9500 Gilman Dr, La Jolla, CA 92093 USA.
EM roloomba@ucsd.edu
OI Kleiner, David/0000-0003-3442-4453
FU National institute of Diabetes and Digestive and Kidney Diseases;
National Cancer Institute; National Institutes of Health.
FX This study was supported by the intramural research programs of the
National institute of Diabetes and Digestive and Kidney Diseases and the
National Cancer Institute, National Institutes of Health.; The authors
thank Dr Jay H. Hoofnagle for providing helpful comments at various
stages of the study.
NR 17
TC 24
Z9 24
U1 0
U2 0
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 NOV
PY 2008
VL 6
IS 11
BP 1243
EP 1248
DI 10.1016/j.cgh.2008.07.013
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 376VK
UT WOS:000261210900018
PM 18829391
ER
PT J
AU Biesecker, BB
Erby, L
AF Biesecker, B. B.
Erby, L.
TI Adaptation to living with a genetic condition or risk: a mini-review
SO CLINICAL GENETICS
LA English
DT Review
DE adaptation; living with a genetic condition; genetics services;
interventions
ID QUALITY-OF-LIFE; PSYCHOLOGICAL ADJUSTMENT; CYSTIC-FIBROSIS; CHRONIC
ILLNESS; SOCIAL SUPPORT; RHEUMATOID-ARTHRITIS; INTERVENTION; CANCER;
CHILDREN; HEALTH
AB One goal of genetic counseling is to facilitate client adaptation to a genetic condition or risk. Adaptation refers to both the process of coming to terms with the implications of the condition or risk and the observable outcomes of that process. This review summarizes existing studies on how well clients adapt to living with a common chronic disease, and more specifically, a genetic condition. Overall, it appears that about one-third of clients do not adjust well to the stress of living with a genetic condition or at risk. However, the data are limited by inconsistencies in the conceptualization of adaptation, a paucity of theoretical models, poor study design and inadequate outcome measures. Well-designed studies based upon multidimensional models are needed that focus on familial as well as individual adaptation. We conclude with a summary of studies that have explored the use of interventions to enhance adaptation and suggest improved client outcomes. Further research should result in evidence-based interventions to facilitate client adaptation that can be used effectively by genetic providers within the confines of their clinical work.
C1 [Biesecker, B. B.] Johns Hopkins Univ, NHGRI, Genet Counseling Program, Social & Behav Res Branch,NIH, Bethesda, MD 20892 USA.
[Erby, L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA.
RP Biesecker, BB (reprint author), Johns Hopkins Univ, NHGRI, Genet Counseling Program, Social & Behav Res Branch,NIH, Bldg 31,Room B1B36C,31 Ctr Dr,MSC 2073, Bethesda, MD 20892 USA.
EM barbarab@mail.nih.gov
FU National Human Genome Research Institute; National Institutes of Health
FX Part of the research for this manuscript was funded by the intramural
research program of the National Human Genome Research Institute,
National Institutes of Health.
NR 45
TC 29
Z9 29
U1 2
U2 7
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 NOV
PY 2008
VL 74
IS 5
BP 401
EP 407
DI 10.1111/j.1399-0004.2008.01088.x
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 359ST
UT WOS:000260009100001
PM 18823383
ER
PT J
AU Young, JA
Hwang, SJ
Sarnak, MJ
Hoffmann, U
Massaro, JM
Levy, D
Benjamin, EJ
Larson, MG
Vasan, RS
O'Donnell, CJ
Fox, CS
AF Young, Jill A.
Hwang, Shih-Jen
Sarnak, Mark J.
Hoffmann, Udo
Massaro, Joseph M.
Levy, Daniel
Benjamin, Emelia J.
Larson, Martin G.
Vasan, Ramachandran S.
O'Donnell, Christopher J.
Fox, Caroline S.
TI Association of Visceral and Subcutaneous Adiposity with Kidney Function
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID SERUM CYSTATIN-C; IMPAIRED GLUCOSE-TOLERANCE;
GLOMERULAR-FILTRATION-RATE; BODY-FAT DISTRIBUTION; METABOLIC SYNDROME;
TISSUE VOLUMES; RENAL-FUNCTION; UNITED-STATES; RISK-FACTORS; MASS INDEX
AB Background and objectives: Obesity is a risk factor for incident chronic kidney disease (CKD). Visceral (VAT) and subcutaneous adipose tissue (SAT) may confer differential metabolic risk profiles. The relations of VAT and SAT were analyzed with CKD as estimated by creatinine- and cystatin-based estimating equations.
Design, setting, participants, & measurements: Participants from the Framingham Offspring Study who underwent abdominal computed tomography for VAT and SAT quantification were included (n = 1299; 53% women; mean age 60 yr). CKD was defined as estimated GFR < 60 ml/min per 1.73 m(2), as estimated using creatinine (n = 89) in the Modification of Diet ill Renal Disease (MDRD) formula or by cystatin C (n = 136). Regression models evaluated the cross-sectional relations between VAT and SAT with CKD and cystatin C, with age and gender adjustment and cardiovascular risk factor adjustment.
Results: Neither VAT nor SAT was associated with CKD as estimated by the MDRD equation. In contrast, both VAT and SAT were associated with CKD when defined using cystatin-based equations. The estimated decrease in estimated GFR by cystatin C per 1-SD increase of VAT was 1.9 ml/min per 1.73 m(2) and for SAT was 2.6 ml/min per 1.73 m2 in a multivariable-adjusted model.
Conclusions: VAT and SAT were associated with CKD when defined using cystatin C estimating equations but not when using a creatinine-based estimating equation. Mechanisms linking adipose tissue to cystatin C warrant further research.
C1 [Young, Jill A.; Sarnak, Mark J.] Tufts Univ New England Med Ctr, Boston, MA USA.
[Hoffmann, Udo; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hoffmann, Udo; O'Donnell, Christopher J.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Brigham & Womens Hosp, Sch Publ Hlth, Boston, MA 02115 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol Hypertens & Metab, Boston, MA 02115 USA.
[Hwang, Shih-Jen; Massaro, Joseph M.; Levy, Daniel; Benjamin, Emelia J.; Larson, Martin G.; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA.
[Hwang, Shih-Jen; Levy, Daniel; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254;
Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
Emelia/0000-0003-4076-2336
FU National Heart, Lung, and Blood Institute/National Institutes of Health
[N01-HC-25195, 2K24HL04334]
FX This study was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (N01-HC-25195). R.S.V. is supported
in part by 2K24HL04334 (National Heart, Lung, and Blood
Institute/National Institutes of Health).
NR 37
TC 23
Z9 23
U1 0
U2 0
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD NOV
PY 2008
VL 3
IS 6
BP 1786
EP 1791
DI 10.2215/CJN.02490508
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 366TE
UT WOS:000260505500028
PM 18815239
ER
PT J
AU Morash, V
Bai, O
Furlani, S
Lin, P
Hallett, M
AF Morash, Valerie
Bai, Ou
Furlani, Stephen
Lin, Peter
Hallett, Mark
TI Classifying EEG signals preceding right hand, left hand, tongue, and
right foot movements and motor imageries
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Electroencephalography (EEG); Event-related (de)synchronization
(ERD/ERS); Brain-computer interface (BCI); Movement; Motor imagery
ID CONTINGENT NEGATIVE-VARIATION; EVENT-RELATED DESYNCHRONIZATION;
SINGLE-TRIAL EEG; BRAIN; POTENTIALS; HUMANS; CORTEX; AREA
AB Objective: To use the neural signals preceding movement and motor imagery to predict which of the four movements/motor imageries is about to occur, and to access this utility for brain-computer interface (BCI) applications.
Methods: Eight naive subjects performed or kinesthetically imagined four movements while electroencephalogram (EEG) was recorded from 29 channels over sensorimotor areas. The task was instructed with a specific stimulus (SI) and performed at a second stimulus (S2). A classifier was trained and tested off-line at differentiating the EEG signals from movement/imagery preparation (the 1.5-s preceding movement/imagery execution).
Results: Accuracy of movement/imagery preparation classification varied between subjects. The system preferentially selected event-related (de)synchronization (ERD/ERS) signals for classification, and high accuracies were associated with classifications that relied heavily on the ERD/ERS to discriminate movement/imagery planning.
Conclusions: The ERD/ERS preceding movement and motor imagery can be used to predict which of the four movements/imageries is about to Occur. Prediction accuracy depends on this signal's accessibility.
Significance: The ERD/ERS is the most specific pre-movement/imagery signal to the movement/imagery about to be performed. Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology.
C1 [Bai, Ou] Virginia Commonwealth Univ, Dept Biomed Engn, EEG & BCI Lab, Richmond, VA 23284 USA.
[Morash, Valerie; Bai, Ou; Furlani, Stephen; Lin, Peter; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Bai, O (reprint author), Virginia Commonwealth Univ, Dept Biomed Engn, EEG & BCI Lab, 401 W Main St Rm 1252,POB 843067, Richmond, VA 23284 USA.
EM obai@vcu.edu
FU NIH; National Institute of Neurological Disorders and Stroke; NINDS
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Neurological Disorders and Stroke. Ms. Morash
was also partly supported by NINDS Summer Intern Program. The authors
thank Ms. D.G. Schoenberg for skillful editing.
NR 23
TC 51
Z9 54
U1 0
U2 10
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 NOV
PY 2008
VL 119
IS 11
BP 2570
EP 2578
DI 10.1016/j.clinph.2008.08.013
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 377NM
UT WOS:000261257900021
PM 18845473
ER
PT J
AU Kubler, A
Birbaumer, N
AF Kuebler, A.
Birbaumer, N.
TI Brain-computer interfaces and communication in paralysis: Extinction of
goal directed thinking in completely paralysed patients?
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Brain-computer interfaces; Brain-computer communication; Locked-in
state; Consciousness; Complete locked-in state
ID AMYOTROPHIC-LATERAL-SCLEROSIS; SLOW CORTICAL POTENTIALS; VEGETATIVE
STATE; INFORMATION-TRANSFER; SELF-REGULATION; BCI OPERATION; EEG;
TETRAPLEGIA; DISORDERS; MOVEMENT
AB Objective: To investigate the relationship between physical impairment and brain-computer interface (BCI) performance.
Method: We present a meta-analysis of 29 patients with amyotrophic lateral sclerosis and six patients with other severe neurological diseases in different stages of physical impairment who were trained with a BCI In most cases voluntary regulation of slow cortical potentials has been Used as input signal for BCI-control. More recently sensorimotor rhythms and the P300 event-related brain potential were recorded.
Results: A strong correlation has been found between physical impairment and BCI performance, indicating that performance worsens as impairment increases. Seven patients were in the complete locked-in state (CLIS) with no communication possible. After removal of these patients from the analysis, the relationship between physical impairment and BCI performance disappeared. The lack of a relation between physical impairment and BCI performance was confirmed when adding BCI data of patients from other BCI research groups.
Conclusions: Basic communication (yes/no) was not restored in any of the CLIS patients with a BCI. Whether locked-in patients can transfer learned brain control to the CLIS remains an open empirical question.
Significance: Voluntary brain regulation for communication is possible in all stages of paralysis except the CLIS. (C) 2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Kuebler, A.] Roehampton Univ, Sch Human & Life Sci, Clin & Hlth Psychol Res Ctr, Whitelands Coll, London SW15 4JD, England.
[Kuebler, A.; Birbaumer, N.] Univ Tubingen, Inst Med Psychol & Behav Neurol, Tubingen, Germany.
[Birbaumer, N.] NINDS, NIH, Human Cort Physiol Sect, Bethesda, MD 20892 USA.
RP Kubler, A (reprint author), Roehampton Univ, Sch Human & Life Sci, Clin & Hlth Psychol Res Ctr, Whitelands Coll, Holybourne Ave, London SW15 4JD, England.
EM a.kuebler@roehampton.ac.uk
OI Kubler, Andrea/0000-0003-4876-0415
FU Deutsche Forschungsgemeinschaft [SFB 550/TB5]; National Institutes of
Health NIH [HD30146]; NIBIB/National Institute of Neurologic Disorders
and Stroke [EB00856]
FX We are greatly indebted to our patients, who made this research
possible. Particularly HPS allowed us deep insights in the psychological
state of a person in the locked-in state over the past 11 years. We
thank our colleagues Samuel Faran, Adrian Furdea, Sebastian Halder,
Slavica von Hartlieb, Thilo Hinterberger, Miguel Jordan, Ahmed el Karim,
Boris Kleber, Boris Kotchoubey, Seung-Soo Lee, Tamara Matuz, Jurgen
Mellinger, Ursula Mochty, Emily Mugler, Nicola Neumann, Femke Nijboer,
Ute Strehl, Tracy Trevorrow, and Barbara Wilhelm for their contribution.
This study is supported by the Deutsche Forschungsgemeinschaft (SFB
550/TB5) and the National Institutes of Health NIH (NICHD, HD30146) and
NIBIB/National Institute of Neurologic Disorders and Stroke (EB00856).
The authors have no conflicts of interest and no financial interest.
Both authors declare that they participated in data collection, data
analysis, writing of the manuscript and that they have seen and approved
the final version. Both authors had full access to all the data in the
study and had final responsibility for the decision to submit for
publication.
NR 49
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Z9 178
U1 1
U2 20
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 NOV
PY 2008
VL 119
IS 11
BP 2658
EP 2666
DI 10.1016/j.clinph.2008.06.019
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 377NM
UT WOS:000261257900031
PM 18824406
ER
PT J
AU Kacinko, SL
Jones, HE
Johnson, RE
Choo, RE
Huestis, MA
AF Kacinko, S. L.
Jones, H. E.
Johnson, R. E.
Choo, R. E.
Huestis, M. A.
TI Correlations of Maternal Buprenorphine Dose, Buprenorphine, and
Metabolite Concentrations in Meconium With Neonatal Outcomes
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID IN-VITRO METABOLISM; ABSTINENCE SYNDROME; HUMAN PLACENTA; DRUG-USE;
METHADONE; INFANTS; NEWBORN; NORBUPRENORPHINE; LOCALIZATION; GESTATION
AB For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS.
C1 [Kacinko, S. L.; Huestis, M. A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA.
[Jones, H. E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Johnson, R. E.] Reckitt Benckiser Pharmaceut, Richmond, VA USA.
[Choo, R. E.] Univ Pittsburgh, Dept Biol, Titusville, PA USA.
RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA.
EM mhuestis@intra.nida.nih.gov
FU National Institute on Drug Abuse [R01 12220, R01 DA015764, M01RR-02719];
General Clinical Research Centers Program; National Center of Research
Resources; National Institutes of Health
FX We thank the women who participated in this study. We also thank Paul
Wakim for statistical guidance and Rosemarie Rios from the United States
Drug Testing Laboratory for analyzing meconium samples for cocaine,
opiates, and benzodiazepines. We thank the research and clinical staff
of the Center for Addiction and Pregnancy. This study was supported by
National Institute on Drug Abuse grants R01 12220 and R01 DA015764, and
M01RR-02719 from the General Clinical Research Centers Program, National
Center of Research Resources, National Institutes of Health.
NR 39
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U1 1
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD NOV
PY 2008
VL 84
IS 5
BP 604
EP 612
DI 10.1038/clpt.2008.156
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 362PL
UT WOS:000260209500018
PM 18701886
ER
PT J
AU Giacoia, GP
Taylor-Zapata, P
Mattison, D
AF Giacoia, George P.
Taylor-Zapata, Perdita
Mattison, Donald
TI Eunice Kennedy Shriver National Institute of Child Health and Human
Development Pediatric Formulation Initiative: Selected Reports from
Working Groups
SO CLINICAL THERAPEUTICS
LA English
DT Article
DE National Institute of Child Health and Human Development; Pediatric
Formulation Initiative; pediatrics; extemporaneous; compounding
AB Background: The Pediatric Formulation Initiative (PFI) is a project of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The PFI was established to address the issue of the lack of appropriate formulations in children and to use this activity as a means to improve pediatric formulations, as mandated by the Best Pharmaceuticals for Children Act of 2002 and 2007. The PFI began in 2005 with the formation of 3 working groups-Scientific, Economics, and Taste and Flavor. These groups began the process of identifying issues, gathering needed information, and considering possible ways to overcome barriers to the development of pediatric drug formulations.
Objective: The purpose of this supplement was to provide details of the working groups' activities through presentation of full-length articles. Also presented is an article that discusses the 2007 European Union (EU) regulation on medicinal products for pediatric use.
Methods: Information for this article was gathered from the proceedings of a PFI workshop, sponsored by the NICHD, that was held in Bethesda, Maryland, on December 6 and 7, 2005, as well as postworkshop discussions of the different working groups.
Results: The increased awareness that the majority of medications used today have not been labeled for use in children, and have not been tested to define safety, efficacy, and appropriate dosing, has led to the passage of legislation in the United States and in the EU to create incentives to stimulate the testing of drugs in this special population. It is imperative that the problems associated with the compounding and use of extemporaneous formulations as described in this supplement be addressed. Regulatory barriers to the availability of commercially developed pediatric formulations in different countries will need to be minimized or removed. New drug delivery systems will need to be tested and made available to pediatric patients. Further research in the mediators of bitter taste and study of taste blockers, as well as newer methods for taste testing in pediatrics, should be encouraged. An overarching goal for the future is addressing the economic barriers to develop appropriate pediatric dosage forms for drugs with limited market penetration. The lack of appropriate formulations is part of a larger problem that includes limited development and manufacture of medicines tailored for pediatric patients (particularly those affected by neglected diseases), insufficient investment in drug trials, and limited research on drug disposition in various pediatric populations worldwide.
Conclusion: The solution to these issues will require alignment of vision and commitment as a global priority of policy makers, regulators, scientists, pharmaceutical sponsors, academic institutions, governments, and research foundations. (Clin Ther. 2008; 30:2097-2101) (C) 2008 Excerpta Medica Inc.
C1 [Giacoia, George P.; Taylor-Zapata, Perdita; Mattison, Donald] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH,Dept Hlth & Human Serv, Bethesda, MD 20847 USA.
RP Giacoia, GP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH,Dept Hlth & Human Serv, 6100 Execut Blvd,MSC 7510, Bethesda, MD 20847 USA.
EM giacoiag@exchange.nih.gov
RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013
OI Mattison, Donald/0000-0001-5623-0874
NR 7
TC 11
Z9 12
U1 1
U2 1
PU ELSEVIER
PI BRIDGEWATER
PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA
SN 0149-2918
J9 CLIN THER
JI Clin. Ther.
PD NOV
PY 2008
VL 30
IS 11
BP 2097
EP 2101
DI 10.1016/j.clinthera.2008.11.017
PG 5
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 385JX
UT WOS:000261811600014
PM 19108797
ER
PT J
AU Shippenberg, TS
LeFevour, A
Chefer, VI
AF Shippenberg, T. S.
LeFevour, A.
Chefer, V. I.
TI Targeting Endogenous Mu- and Delta-Opioid Receptor Systems for the
Treatment of Drug Addiction
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Review
DE Opioid receptors; drug self-administration; enkephalin; endorphin;
cocaine; ethanol; morphine
ID VENTRAL TEGMENTAL AREA; FREELY MOVING RATS; MEDIAL PREFRONTAL CORTEX;
NUCLEUS-ACCUMBENS SHELL; EXTRACELLULAR DOPAMINE LEVELS; COCAINE-INDUCED
REINSTATEMENT; CONDITIONED PLACE PREFERENCE; ANTERIOR CINGULATE CORTEX;
CENTRAL AMYGDALA NEURONS; BETA-ENDORPHIN
AB Drug addiction is a chronic, relapsing disorder that is characterized by a compulsion to take drug regardless of the adverse consequences that may ensue. Although the involvement of mesoaccumbal dopamine neurons in the initiation of drug abuse is well-established, neuroadaptations within the limbic cortical-striatopallidal circuit that occur as a consequence of repeated drug use are thought to lead to the behavioral dysregulation that characterizes addiction. Opioid receptors and their endogenous ligands are enriched in brain regions comprising this system and are, thus, strategically located to modulate neurotransmission therein. This article will review data suggesting an important role of mu-opioid receptor (MOPr) and delta opioid receptor (DOPr) systems in mediating the rewarding effects of several classes of abused drugs and that aberrant activity of these opioid systems may not only contribute to the behavioral dysregulation that characterizes addiction but to individual differences in addiction vulnerability.
C1 [Shippenberg, T. S.; LeFevour, A.; Chefer, V. I.] NIH NIDA Intramural Res Program, Integrat Neurosci Sect, Baltimore, MD 21224 USA.
RP Shippenberg, TS (reprint author), NIH NIDA Intramural Res Program, Integrat Neurosci Sect, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM tshippen@intra.nida.nih.gov
FU Intramural NIH HHS [Z99 DA999999, ZIA DA000538-04]
NR 195
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Z9 31
U1 2
U2 6
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5273
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PD NOV
PY 2008
VL 7
IS 5
BP 442
EP 453
PG 12
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 397HY
UT WOS:000262654700005
PM 19128202
ER
PT J
AU Scherma, M
Fadda, P
Le Foll, B
Forget, B
Fratta, W
Goldberg, SR
Tanda, G
AF Scherma, Maria
Fadda, Paola
Le Foll, Bernard
Forget, Benoit
Fratta, Walter
Goldberg, Steven R.
Tanda, Gianluigi
TI The Endocannabinoid System: A New Molecular Target for the Treatment of
Tobacco Addiction
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Review
DE Addiction; tobacco dependence; nicotine; endocannabinoid system; CB(1)
receptors
ID CANNABINOID CB1 RECEPTOR; VENTRAL TEGMENTAL AREA; ACID AMIDE HYDROLASE;
NICOTINIC ACETYLCHOLINE-RECEPTORS; CENTRAL-NERVOUS-SYSTEM;
N-ARACHIDONYLETHANOLAMINE ANANDAMIDE; CONDITIONED PLACE PREFERENCES;
FOOD-REINFORCED BEHAVIOR; NUCLEUS-ACCUMBENS; RAT-BRAIN
AB Tobacco addiction is one of the leading preventable causes of mortality in the world and nicotine appears to be the main critical psychoactive component in establishing and maintaining tobacco dependence. Several lines of evidence suggest that the rewarding effects of nicotine, which underlie its abuse potential, can be modulated by manipulating the endocannabinoid system. For example, pharmacological blockade or genetic deletion of cannabinoid CB(1) receptors reduces or eliminates many behavioral and neurochemical effects of nicotine that are related to its addictive potential.
This review will focus on the recently published literature about the role of the endocannabinoid system in nicotine addiction and on the endocannabinoid system as a novel molecular target for the discovery of medications for tobacco dependence.
C1 [Tanda, Gianluigi] Natl Inst Drug Abuse, NIH, Dept Hlth & Human Serv,Intramural Res Program, Psychobiol Sect,Medicat Discovery Res Branch, Baltimore, MD USA.
[Scherma, Maria; Goldberg, Steven R.] Natl Inst Drug Abuse, NIH, Dept Hlth & Human Serv,Intramural Res Program, Preclin Pharmacol Sect,Behav Neurosci Res Branch, Baltimore, MD USA.
[Fadda, Paola; Fratta, Walter] Univ Cagliari, Bb Brodie Dept Neurosci, I-09124 Cagliari, Italy.
[Le Foll, Bernard; Forget, Benoit] Ctr Addict & Mental Hlth, Translat Addict Res Lab, Toronto, ON, Canada.
[Le Foll, Bernard; Forget, Benoit] Univ Toronto, Toronto, ON, Canada.
RP Tanda, G (reprint author), Natl Inst Drug Abuse, NIH, Dept Hlth & Human Serv,Intramural Res Program, Psychobiol Sect,Medicat Discovery Res Branch, Baltimore, MD USA.
EM gtanda@intra.nida.nih.gov
RI Tanda, Gianluigi/B-3318-2009; Le Foll, Bernard/K-2952-2014;
OI Tanda, Gianluigi/0000-0001-9526-9878; Le Foll,
Bernard/0000-0002-6406-4973; FADDA, PAOLA/0000-0002-0642-6710
FU National Institute on Drug Abuse; National Institutes of Health; U.S.
Department of Health and Human Services
FX This research was supported in part by the Intramural Research Program
of the National Institute on Drug Abuse, National Institutes of Health,
U.S. Department of Health and Human Services.
NR 249
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U1 2
U2 6
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5273
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PD NOV
PY 2008
VL 7
IS 5
BP 468
EP 481
PG 14
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 397HY
UT WOS:000262654700007
PM 19128204
ER
PT J
AU Saltz, J
Kurc, T
Hastings, S
Langella, S
Oster, S
Ervin, D
Sharma, A
Pan, T
Gurcan, M
Permar, J
Ferreira, R
Payne, P
Catalyurek, U
Caserta, E
Leone, G
Ostrowski, MC
Madduri, R
Foster, I
Madhavan, S
Buetow, KH
Shanbhag, K
Siegel, E
AF Saltz, Joel
Kurc, Tahsin
Hastings, Shannon
Langella, Stephen
Oster, Scott
Ervin, David
Sharma, Ashish
Pan, Tony
Gurcan, Metin
Permar, Justin
Ferreira, Renato
Payne, Philip
Catalyurek, Umit
Caserta, Enrico
Leone, Gustavo
Ostrowski, Michael C.
Madduri, Ravi
Foster, Ian
Madhavan, Subhashree
Buetow, Kenneth H.
Shanbhag, Krishnakant
Siegel, Eliot
TI e-Science, caGrid, and Translational Biomedical Research
SO COMPUTER
LA English
DT Article
ID INFRASTRUCTURE
AB Researchers are harnessing dramatic advances in many biomedical technology areas to better understand the causes of disease and to direct disease treatment. The authors' work explores the critical role e-Science plays in enabling translational biomedical research-the process of developing and applying basic science knowledge and techniques to enable new ways of diagnosing and staging, treating, or preventing diseases, as well as the adoption of best practices in the community.
C1 [Saltz, Joel; Kurc, Tahsin] Emory Univ, Ctr Comprehens Informat, Atlanta, GA 30322 USA.
[Hastings, Shannon; Langella, Stephen; Oster, Scott; Ervin, David; Permar, Justin] Ohio State Univ, Software Res Inst, Columbus, OH 43210 USA.
[Sharma, Ashish; Pan, Tony; Gurcan, Metin; Payne, Philip; Catalyurek, Umit] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA.
[Leone, Gustavo] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Ostrowski, Michael C.] Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA.
[Ostrowski, Michael C.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Madduri, Ravi; Foster, Ian] Argonne Natl Lab, Argonne, IL 60439 USA.
[Buetow, Kenneth H.] NCI, Ctr Bioinformat, Bethesda, MD 20892 USA.
[Shanbhag, Krishnakant] NCI, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA.
[Siegel, Eliot] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
RP Saltz, J (reprint author), Emory Univ, Ctr Comprehens Informat, Atlanta, GA 30322 USA.
EM jhsaltz@emory.edu; tkurc@emory.edu; shannon.hastings@osumc.edu;
stephen.langella@osumc.edu; oster@bmi.osu.edu; ervin@bmi.osu.edu;
ashish@bmi.osu.edu; tpan@bmi.osu.edu; gurcan@bmi.osu.edu;
jpermar@bmi.osu.edu; renato@dcc.ufmg.br; philip.payne@osumc.edu;
umit@bmi.osu.edu; enrico.caserta@osumc.edu; gustavo.leone@osumc.edu;
michael.ostrowski@osumc.edu; madduri@mcs.anl.gov;
foster@ci.uchicago.edu; madhavas@mail.nih.gov; buetowk@mail.nih.gov;
shanbhak@mail.nih.gov; esiegel@umaryland.edu
RI Catalyurek, Umit/A-2454-2008; Ostrowski, Michael/H-3108-2011; Gurcan,
Metin/F-4536-2012; InWeb, Inct/J-9839-2013
OI Catalyurek, Umit/0000-0002-5625-3758; Ostrowski,
Michael/0000-0003-2948-6297;
FU NCI caGrid Developer grant [79077CBS10]; State of Ohio BRTT Program
[04-049, BRTT02-0003]; NHLBI [R24 HL085343]; NIH [U54 CA113001, R01
LM009239, N01-CO-12400]; NSF [CNS-0403342, CNS-0615155]; US Department
of Energy [DE-AC02-06CH11357]; Children's Neuroblastoma Cancer
Foundation
FX We thank Laura Esserman and Nola Hylton at the University of California,
San Francisco, the PIs for the I-SPY trial project; Howard Fine at the
NCI, the PI for the GMDI and Rembrandt projects; and Stephen Chanock,
NCI, the PI for the CGEMS (GWAS) project. Our work was supported in part
by the NCI caGrid Developer grant 79077CBS10, the State of Ohio BRTT
Program grants ODOD AGMT TECH 04-049 and BRTT02-0003, the NHLBI R24
HL085343 grant, the NIH U54 CA113001 and R01 LM009239 grants, and NSF
grants CNS-0403342 and CNS-0615155; by the NCI and NIH under contract
no. N01-CO-12400; by the US Department of Energy under contract
DE-AC02-06CH11357; and by Children's Neuroblastoma Cancer Foundation.
The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US government.
NR 12
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U1 1
U2 6
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
SN 0018-9162
EI 1558-0814
J9 COMPUTER
JI Computer
PD NOV
PY 2008
VL 41
IS 11
BP 58
EP +
DI 10.1109/MC.2008.459
PG 10
WC Computer Science, Hardware & Architecture; Computer Science, Software
Engineering
SC Computer Science
GA 369VT
UT WOS:000260722700014
PM 21311723
ER
PT J
AU Gadegbeku, CA
Stillman, PK
Huffman, MD
Jackson, JS
Kusek, JW
Jamerson, KA
AF Gadegbeku, Crystal A.
Stillman, Phyllis Kreger
Huffman, Mark D.
Jackson, James S.
Kusek, John W.
Jamerson, Kenneth A.
TI Factors associated with enrollment of African Americans into a clinical
trial: Results from the African American study of kidney disease and
hypertension
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE African Americans; Subject recruitment; Willingness to participate;
Clinical trials
ID HEALTH RESEARCH; PARTICIPATION; CANCER; RACE; WILLINGNESS; DETERMINANTS;
PERCEPTIONS; DISPARITIES; PREVENTION; MINORITIES
AB Recruitment of diverse populations into clinical trials remains challenging but is needed to fully understand disease processes and benefit the general public. Greater knowledge of key factors among ethnic and racial minority populations associated with the decision to participate in clinical research studies may facilitate recruitment and enhance the generalizibility of study results. Therefore, during the recruitment phase of the African American Study of Kidney Disease and Hypertension (AASK) trial, we conducted a telephone survey. using validated questions, to explore potential facilitators and barriers of research participation among eligible candidates residing in seven U.S. locations. Survey responses included a range of characteristics and perceptions among participants and non-participants and were compared using bivariate and step-wise logistic regression analyses.
One-hundred forty-one respondents in the one-hundred forty (70 trial participants and 71 nonparticipants) completed the Survey. Trial participants and non-participants were similar in multiple demographic characteristics and shared similar views on discrimination, physician mistrust. and research integrity. Key group differences were related to their perceptions of the impact of their research participation. Participants associated enrollment with personal and societal health benefits. while non-participants were influenced by the health risks. In a stepwise linear regression analysis, the most powerful significant positive predictors of participation were acknowledgement of health status as important in the enrollment decision (OR = 4.54, p = 0.006), employment (OR = 3.12, p = 0.05) and healthcare satisfaction (OR = 2.12, p < 0.01). Racially-based mistrust did not emerge as a negative predictor and subjects' decisions were not influenced by the race of the research staff.
In conclusion, these results suggest that health-related factors. and not psychosocial perceptions, have predominant influence on research participation among African Americans. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Gadegbeku, Crystal A.; Huffman, Mark D.; Jamerson, Kenneth A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Stillman, Phyllis Kreger; Jackson, James S.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[Kusek, John W.] NIDDK, NIH, Bethesda, MD USA.
RP Gadegbeku, CA (reprint author), Univ Michigan Hlth Syst, Dept Internal Med, Div Nephrol, 310 Simpson Mem Inst,102 Observ Rd, Ann Arbor, MI 48109 USA.
EM cgadegbe@umich.edu
OI Huffman, Mark/0000-0001-7412-2519
FU National Institute of Diabetes and Digestive and Kidney Diseases [U01
DK48682, DK45381, DK48659, DK65473, DK48669, DK48645, DK45386]; National
Center for Minority Health and Health Disparities and the Office of
Behavioral and Social Sciences Research; National Institutes of Health
FX Supported by cooperative agreements U01 DK48682 (University of
Michigan), DK45381 (Case Western Reserve), DK48659 (Medical University
of South Carolina), DK65473 (Meharry Medical College), DK48669
(University of Alabama, Birminghan), DK48645 (University of California,
San Diego), DK45386 (University of Texas, Southwestern) from the
National Institute of Diabetes and Digestive and Kidney Diseases.
Additional support is provided by the National Center for Minority
Health and Health Disparities and the Office of Behavioral and Social
Sciences Research, National Institutes of Health.
NR 33
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U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD NOV
PY 2008
VL 29
IS 6
BP 837
EP 842
DI 10.1016/j.cct.2008.06.001
PG 6
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 373RO
UT WOS:000260990300004
PM 18639652
ER
PT J
AU O'Grady, NP
Barie, PS
Carroll, K
AF O'Grady, Naomi P.
Barie, Philip S.
Carroll, Karen
TI Fever in critically ill patients Reply
SO CRITICAL CARE MEDICINE
LA English
DT Letter
ID PARKINSONS-DISEASE
C1 [O'Grady, Naomi P.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Barie, Philip S.] Weill Cornell Med Coll, New York, NY USA.
[Carroll, Karen] Johns Hopkins Sch Med, Baltimore, MD USA.
RP O'Grady, NP (reprint author), NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD NOV
PY 2008
VL 36
IS 11
BP 3130
EP 3130
DI 10.1097/CCM.0b013e31818c0f23
PG 1
WC Critical Care Medicine
SC General & Internal Medicine
GA 369KU
UT WOS:000260694200052
ER
PT J
AU Hayton, K
Su, XZ
AF Hayton, Karen
Su, Xin-zhuan
TI Drug resistance and genetic mapping in Plasmodium falciparum
SO CURRENT GENETICS
LA English
DT Review
DE Malaria; Genetics; Genomics; Antimalarial agents
ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; TRANSMEMBRANE
PROTEIN PFCRT; CHLOROQUINE-RESISTANCE; IN-VITRO; MALARIA PARASITES;
MEFLOQUINE RESISTANCE; MULTIDRUG-RESISTANCE; ANTIMALARIAL-DRUGS; QUININE
RESISTANCE
AB Drug resistance in malaria parasites is a serious public health burden, and resistance to most of the antimalarial drugs currently in use has been reported. A better understanding of the molecular mechanisms of drug resistance is urgently needed to slow or circumvent the spread of resistance, to allow local treatments to be deployed more effectively to prolong the life span of the current drugs, and to develop new drugs. Although mutations in genes determining resistance to drugs such as chloroquine and the antifolates have been identified, we still do not have a full understanding of the resistance mechanisms, and genes that contribute to resistance to many other drugs remain to be discovered. Genetic mapping is a powerful tool for the identification of mutations conferring drug resistance in malaria parasites because most drug-resistant phenotypes were selected within the past 60 years. High-throughput methods for genotyping large numbers of single nucleotide polymorphisms (SNPs) and microsatellites (MSs) are now available or are being developed, and genome-wide association studies for malaria traits will soon become a reality. Here we discuss strategies and issues related to mapping genes contributing to drug resistance in the human malaria parasite Plasmodium falciparum.
C1 [Su, Xin-zhuan] NIAID, Malaria Funct Genom Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Su, XZ (reprint author), NIAID, Malaria Funct Genom Sect, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM KHayton@niaid.nih.gov; xsu@niaid.nih.gov
OI Su, Xinzhuan/0000-0003-3246-3248
FU Intramural Research Program of the Division of Intramural Research;
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. We thank NIAID
intramural editor Brenda Rae Marshall for assistance. Because the
authors are government employees and this is a government work, the work
is in the public domain in the United States. Notwithstanding any other
agreements, the NIH reserves the right to provide the work to
PubMedCentral for display and use by the public, and PubMedCentral may
tag or modify the work consistent with its customary practices. You can
establish rights outside of the US subject to a government use license.
NR 184
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PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0172-8083
J9 CURR GENET
JI Curr. Genet.
PD NOV
PY 2008
VL 54
IS 5
BP 223
EP 239
DI 10.1007/s00294-008-0214-x
PG 17
WC Genetics & Heredity
SC Genetics & Heredity
GA 366GR
UT WOS:000260469100001
PM 18802698
ER
PT J
AU Mehta, RG
Naithani, R
Huma, L
Hawthorne, M
Moriarty, RM
McCormick, DL
Steele, VE
Kopelovich, L
AF Mehta, Rajendra G.
Naithani, Rajesh
Huma, Loredana
Hawthorne, Michael
Moriarty, Robert M.
McCormick, David L.
Steele, Vernon E.
Kopelovich, Levy
TI Efficacy of Chemopreventive Agents in Mouse Mammary Gland Organ Culture
(MMOC) Model: A Comprehensive Review
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE Mammary gland organ culture assay; MMOC; natural products; DMBA;
chemoprevention; carcinogenesis; mammary alveolar lesions (MAL)
ID CELL-CYCLE ARREST; CANCER CHEMOPREVENTION; BREAST-CANCER; VITAMIN-D;
HELICOBACTER-PYLORI; INHIBITORY ACTIVITY; QUINONE REDUCTASE; DRUG
DEVELOPMENT; CARCINOGENESIS; CONSTITUENTS
AB Currently, breast cancer is considered as one of the leading causes for death in women in the United States. Consumption of natural products has received considerable attention in recent years as a possible approach for cancer prevention in general population. There are numerous cancer preventive agents present in the natural products, which may contribute to their chemopreventive properties. During the past two decades, numerous chemopreventive agents have been isolated and/or synthesized and evaluated for their efficacy in a variety of biological assays. To this end, we have established and utilized mouse mammary gland organ culture model (MMOC) as a bioassay for identifying chemopreventive agents. Mammary glands respond to growth promoting hormones and the physiological differentiation can be reproduced in MMOC in chemically defined medium by altering hormonal milieu. Both estrogen and progesterone dependent (mammary ductal lesions, MDL) and independent (mammary alveolar lesions, MAL) precancerous lesions can be induced in response to a 24 hour exposure to DMBA in MMOC. Suppression of the incidence and multiplicity of these lesions by a possible chemopreventive agent can serve as a tool to evaluate efficacy of potential experimental agents. Using this approach, we have evaluated more than 200 synthetic and natural product-derived chemopreventive agents in this model as a part of the National Cancer Institute-supported projects. Many of these chemopreventive agents expressing significant activity have progressed to the in vivo experimental mammary carcinogenesis studies. Thus, this bioassay has proven to be a valuable tool for screening cancer chemopreventive agents for breast cancer prevention and for understanding molecular mechanism(s) of action of these agents. In this comprehensive review, we provide a complete list of chemopreventive agents evaluated for the efficacy against development of mammary alveolar lesions (MAL) in MMOC along with the recent developments in this area. The structure-activity relationships for many chemopreventive agents evaluated in the MMOC model have been discussed.
C1 [Mehta, Rajendra G.; Hawthorne, Michael; McCormick, David L.] IIT, Res Inst, Carcinogenesis & Chemoprevent Div, Chicago, IL 60616 USA.
[Mehta, Rajendra G.; Naithani, Rajesh; Huma, Loredana; Moriarty, Robert M.; McCormick, David L.] IIT, Res Inst, Drug Discovery Div, Chicago, IL 60616 USA.
[Moriarty, Robert M.] Univ Illinois, Dept Chem, Chicago, IL 60680 USA.
[Steele, Vernon E.; Kopelovich, Levy] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Mehta, RG (reprint author), IIT, Res Inst, Carcinogenesis & Chemoprevent Div, 10 W 35th St, Chicago, IL 60616 USA.
EM RMehta@iitri.org
FU NCI Research Contracts, Grants and a Program Project grant
FX The authors acknowledge outstanding contribution of numerous fellows,
students and research technicians who have helped with the MMOC assays
for the past 25 years. We are thankful to our collaborators for
providing chemopreventive agents for the MMOC assays and scientific
discussions over the past several years. Specifically, we would like to
thank Dr. Richard Moon, Dr. John Pezzuto and Dr. A. Douglas Kinghorn for
their continuous support, valuable discussions and help with various
projects. Dr. Mehta is indebted to Dr. S. Nandi and late Dr. Mihir
Banerjee for introducing him to mammary gland organ culture studies and
for their continuous encouragement. The work was supported by the NCI
Research Contracts, Grants and a Program Project grant.
NR 111
TC 8
Z9 8
U1 1
U2 2
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 NOV
PY 2008
VL 15
IS 27
BP 2785
EP 2825
DI 10.2174/092986708786242787
PG 41
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 386OF
UT WOS:000261891800002
PM 18991637
ER
PT J
AU Vichinsky, E
Rodgers, GP
Rachmilewitz, E
AF Vichinsky, Elliott
Rodgers, Griffin P.
Rachmilewitz, Eliezer
TI Hot Topic: Genetic Disorders of Hemoglobin: Sickle Cell Anemia and
Thalassemia
SO CURRENT MOLECULAR MEDICINE
LA English
DT Editorial Material
C1 [Vichinsky, Elliott] Childrens Hosp & Res Ctr Oakland, Dept Hematol Oncol, Oakland, CA 94609 USA.
[Rodgers, Griffin P.] Natl Inst Diabet Digest & Kidney Disorders, NIH, Bethesda, MD 20892 USA.
[Rachmilewitz, Eliezer] Edith Wolfson Med Ctr, Head Hematol Dept, Holon, Israel.
RP Vichinsky, E (reprint author), Childrens Hosp & Res Ctr Oakland, Dept Hematol Oncol, 747 52nd St, Oakland, CA 94609 USA.
EM evichinsky@mail.cho.org; griffinr@extra.niddk.nih.gov;
rachmilewitz@wolfson.health.gov.il
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1566-5240
J9 CURR MOL MED
JI Curr. Mol. Med.
PD NOV
PY 2008
VL 8
IS 7
BP 591
EP 591
DI 10.2174/156652408786241456
PG 1
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 386OM
UT WOS:000261892500001
PM 18991644
ER
PT J
AU Morris, CR
Gladwin, MT
Kato, GJ
AF Morris, Claudia R.
Gladwin, Mark T.
Kato, Gregory J.
TI Nitric Oxide and Arginine Dysregulation: A Novel Pathway to Pulmonary
Hypertension in Hemolytic Disorders
SO CURRENT MOLECULAR MEDICINE
LA English
DT Review
DE Pulmonary hypertension; sickle cell disease; thalassemia;
hemoglobinopathies; arginine; nitric oxide; arginase; hemolysis
ID SICKLE-CELL-DISEASE; ACUTE CHEST SYNDROME; RED-BLOOD-CELLS;
GLUTATHIONE-REDUCTASE ACTIVITY; CHRONIC HYPERCOAGULABLE STATE; LOWER
AIRWAY-OBSTRUCTION; BETA-THALASSEMIA MAJOR; AMINO-ACID TRANSPORTER;
ARTERIAL-HYPERTENSION; ARGINASE ACTIVITY
AB Secondary pulmonary hypertension (PH) is emerging as one of the leading causes of mortality and morbidity in patients with hemolytic anemias such as sickle cell disease (SCD) and thalassemia. Impaired nitric oxide (NO) bioavailability represents the central feature of endothelial dysfunction, and is a major factor in the pathophysiology of PH. Inactivation of NO correlates with hemolytic rate and is associated with the erythrocyte release of cell-free hemoglobin, which consumes NO directly, and the simultaneous release of the arginine-metabolizing enzyme arginase, which limits bioavailability of the NO synthase substrate arginine during the process of intravascular hemolysis. Rapid consumption of NO is accelerated by oxygen radicals that exists in both SCD and thalassemia. A dysregulation of arginine metabolism contributes to endothelial dysfunction and PH in SCD, and is strongly associated with prospective patient mortality. The central mechanism responsible for this metabolic disorder is enhanced arginine turnover, occurring secondary to enhanced plasma arginase activity. This is consistent with a growing appreciation of the role of excessive arginase activity in human diseases, including asthma and pulmonary arterial hypertension. New treatments aimed at improving arginine and NO bioavailability through arginase inhibition, suppression of hemolytic rate, oral arginine supplementation, or use of NO donors represent potential therapeutic strategies for this common pulmonary complication of hemolytic disorders.
C1 [Morris, Claudia R.] Childrens Hosp & Res Ctr Oakland, Dept Emergency Med, Oakland, CA 94609 USA.
[Gladwin, Mark T.] Univ Pittsburgh, Hemostasis & Vasc Biol Res Inst, Pittsburgh, PA 15213 USA.
[Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Kato, Gregory J.] NHLBI, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA.
RP Morris, CR (reprint author), Childrens Hosp & Res Ctr Oakland, Dept Emergency Med, 747 52nd St, Oakland, CA 94609 USA.
EM claudiamorris@comcast.net
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU National Institutes of Health (NIH) [UL1 RR024131]; INO Therapeutics,
Inc.
FX Authors declare no conflicts of interest. This study was supported in
part by the NIH CTSI grant UL1 RR024131 (to CRM). GJK and MTG receive
intramural support from the National Institutes of Health (NIH). MTG
holds a cooperative research and development agreement (CRADA) through
the NIH with INO Therapeutics, Inc.
NR 215
TC 45
Z9 46
U1 0
U2 7
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1566-5240
J9 CURR MOL MED
JI Curr. Mol. Med.
PD NOV
PY 2008
VL 8
IS 7
BP 620
EP 632
DI 10.2174/156652408786241447
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 386OM
UT WOS:000261892500005
PM 18991648
ER
PT J
AU Masdeu, JC
Pascual, B
AF Masdeu, Joseph C.
Pascual, Belen
TI Neuroimaging of Disorders Leading to Dementia
SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
LA English
DT Editorial Material
ID CEREBRAL AMYLOID ANGIOPATHY; MILD COGNITIVE IMPAIRMENT;
ALZHEIMERS-DISEASE; ATROPHY; MRI; PROGRESSION; DIAGNOSIS; LESIONS;
BURDEN; ONSET
C1 [Masdeu, Joseph C.] NIMH, Sect Integrat Neuroimaging, NIH, CBDB,Intramural Res Program, Bethesda, MD 20892 USA.
RP Masdeu, JC (reprint author), NIMH, Sect Integrat Neuroimaging, NIH, CBDB,Intramural Res Program, 9000 Rockville Pike,Bldg 10,Room 4C101, Bethesda, MD 20892 USA.
EM masdeu@nih.org
NR 20
TC 1
Z9 1
U1 2
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1528-4042
J9 CURR NEUROL NEUROSCI
JI Curr. Neurol. Neurosci. Rep.
PD NOV
PY 2008
VL 8
IS 6
BP 443
EP 444
DI 10.1007/s11910-008-0069-z
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 381UC
UT WOS:000261560400001
PM 18957178
ER
PT J
AU Bondy, CA
AF Bondy, Carolyn A.
TI Aortic dissection in Turner syndrome
SO CURRENT OPINION IN CARDIOLOGY
LA English
DT Review
DE adult congenital heart disease; aorta; bicuspid aortic valve;
coarctation; X chromosome
ID MARFANS-SYNDROME; RISK-FACTOR; DILATION; DILATATION; PREVALENCE; VALVE;
WOMEN; ABNORMALITIES; MORTALITY; DISEASE
AB Purpose of review
Turner syndrome is a relatively common disorder of female development with cardinal features of short stature and congenital cardiovascular defects (CHD). Turner syndrome is the most common established cause of aortic dissection in young women, but has received little attention outside pediatric literature. This review focuses on emerging knowledge of the characteristics of aortic disease in Turner syndrome in comparison with Marfan-like syndromes and isolated aortic valve disease.
Recent findings
The incidence of aortic dissection is significantly increased in individuals with Turner syndrome at all ages, highest during young adult years and in pregnancy. Pediatric patients with dissection have known congenital cardiovascular defects (CHD), but adults often have aortic valve and arch abnormalities detected only by screening cardiac magnetic resonance. Thoracic aortic dilation in Turner syndrome must be evaluated in relation to body surface area. Dilation is most prominent at the ascending aorta, similar to the pattern seen in nonsyndromic bicuspid aortic valve, is equally prevalent (20-30%) in children and adults, and does not seem to be rapidly progressive. Cardiovascular anomalies and risk for aortic dissection in Turner syndrome are strongly linked to a history of fetal lymphedema, evidenced by the presence of neck webbing and shield chest.
Summary
Risk for acute aortic dissection is increased by more than 100-fold in young and middle-aged women with Turner syndrome. Monitoring frequency and treatment modalities are decided on an individual basis until more information on outcomes becomes available.
C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, CRC 1-3330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bondyc@mail.nih.gov
FU Intramural NIH HHS [Z01 HD000628-18]
NR 29
TC 68
Z9 74
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0268-4705
J9 CURR OPIN CARDIOL
JI Curr. Opin. Cardiol.
PD NOV
PY 2008
VL 23
IS 6
BP 519
EP 526
DI 10.1097/HCO.0b013e3283129b89
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 365KR
UT WOS:000260405800001
PM 18839441
ER
PT J
AU Stenholm, S
Harris, TB
Rantanen, T
Visser, M
Kritchevsky, SB
Ferrucci, L
AF Stenholm, Sari
Harris, Tamara B.
Rantanen, Taina
Visser, Marjolein
Kritchevsky, Stephen B.
Ferrucci, Luigi
TI Sarcopenic obesity: definition, cause and consequences
SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
LA English
DT Review
DE adipose tissue; body composition; disability; muscle strength; obesity;
older people; sarcopenia
ID BODY-MASS INDEX; HUMAN SKELETAL-MUSCLE; CARDIOVASCULAR RISK-FACTORS;
LOWER-EXTREMITY PERFORMANCE; ADIPOSE-TISSUE DISTRIBUTION;
INSULIN-RESISTANCE; OLDER-ADULTS; PHYSICAL-ACTIVITY; FAT DISTRIBUTION;
ELDERLY-MEN
AB Purpose of review
Older obese persons with decreased muscle mass or strength are at special risk for adverse outcomes. We discuss potential pathways to muscle impairment in obese individuals and the consequences that joint obesity and muscle impairment may have on health and disability. Tantamount to this discussion is whether low muscle mass or, muscle weakness should be used for the definition.
Recent findings
Excess energy intake, physical inactivity, low-grade inflammation, insulin resistance and changes in hormonal milieu may lead to the development of so-called 'sarcopenic obesity'. It was originally believed that the culprit of age-related muscle weakness was a reduction in muscle mass, but it is now clear that changes in muscle composition and quality are predominant. We propose that the risk of adverse outcomes, such as functional limitation and mortality, is better estimated by considering jointly obesity and muscle strength rather than obesity and muscle mass and the term sarcopenic obesity' should be revisited.
Summary
Recognition of obese patients who have associated muscle problems is an essential goal for clinicians. Further research is needed to identify new target for prevention and cure of this important geriatric syndrome.
C1 [Stenholm, Sari; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21225 USA.
[Stenholm, Sari] Natl Publ Hlth Inst, Dept Hlth & Funct Capac, Turku, Finland.
[Harris, Tamara B.] NIA, Geriatr Interdisciplinary Studies Sect, Lab Epidemiol Demog & Biometry, Baltimore, MD 21225 USA.
[Rantanen, Taina] Univ Jyvaskyla, Dept Hlth Sci, Finnish Ctr Interdisciplinary Gerontol, Jyvaskyla, Finland.
[Visser, Marjolein] Vrije Univ Amsterdam, Fac Earth & Life Sci, Inst Hlth Sci, Amsterdam, Netherlands.
[Visser, Marjolein] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Amsterdam, Netherlands.
[Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med,J Paul Sticht Ctr Agi, Winston Salem, NC 27103 USA.
RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, 3001 S Hanover St, Baltimore, MD 21225 USA.
EM ferruccilu@grc.nia.nih.gov
RI Stenholm, Sari/G-6940-2011; Rantanen, Taina/O-6579-2016;
OI Rantanen, Taina/0000-0002-1604-1945; Kritchevsky,
Stephen/0000-0003-3336-6781
FU Intramural Research Program; National Institute on Aging, [263 MID 9164
13, 263 MD 821336]; NIH; Italian Ministry of Health [ICS 110.1/RS97.71];
US National Institute on Aging [N01-AG916413, N01-AG-821336]; Dutch
Ministry of Public Health, Welfare and Sports; Finnish Academy [125494]
FX The present research was partly supported by the Intramural Research
Program, National Institute on Aging, NIH. The Baltimore Longitudinal
Study of Aging was supported by the Intramural Research Program of the
NIH, National Institute on Aging. The InCHIANTI Study was supported as a
'targeted project' (ICS 110.1/RS97.71) by the Italian Ministry of
Health, and in part by the US National Institute on Aging (Contracts
N01-AG916413 and N01-AG-821336), and by the Intramural Research Program
of the NIH, National Institute on Aging (Contracts 263 MID 9164 13 and
263 MD 821336). The Longitudinal Aging Study Amsterdam is financially
supported by the Dutch Ministry of Public Health, Welfare and Sports.
This work was also supported by grant from the Finnish Academy (no.
125494). None of the sponsoring institutions interfered with the
collection, analysis, presentation, or interpretation of the data
reported here. Authors have no conflicts of interest.
NR 110
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U1 4
U2 37
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1363-1950
J9 CURR OPIN CLIN NUTR
JI Curr. Opin. Clin. Nutr. Metab. Care
PD NOV
PY 2008
VL 11
IS 6
BP 693
EP 700
DI 10.1097/MCO.0b013e328312c37d
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 368KI
UT WOS:000260619600003
PM 18827572
ER
PT J
AU Bernstein, WB
Dennis, PA
AF Bernstein, Wendy B.
Dennis, Phillip A.
TI Repositioning HIV protease inhibitors as cancer therapeutics
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Article
DE Akt; apoptosis; autophagy; endoplasmic reticulum stress; protease
inhibitors
AB Purpose of review
Although designed to target only the HIV protease, HIV protease inhibitors induce toxicities in patients such as insulin resistance and lipodystrophy that suggest that protease inhibitors have other targets in mammalian cells. Akt controls insulin signaling and is an important target in cancer, but no Akt inhibitors are approved as cancer therapeutics. These observations have prompted the study of HIV protease inhibitors as inhibitors of Akt and possible cancer therapeutics. This review will highlight the latest advances in repositioning HIV protease inhibitors as cancer therapeutics.
Recent findings
Although protease inhibitors can inhibit Akt activation and the proliferation of over 60 cancer cell lines, as well as improve sensitivity to radiation or chemotherapy, these effects do not always correlate with Akt inhibition. Other important processes, such as the induction of endoplasmic reticulum stress, appear critical to the biological activity of protease inhibitors. These impressive and surprising preclinical data have prompted clinical testing of nelfinavir as a lead HIV protease inhibitor in cancer patients.
Summary
Although mechanisms of action for the antitumor effects of HIV protease inhibitors are complex, their broad spectrum of activity, minimal toxicity, and wide availability make protease inhibitors ideal candidates for repositioning as cancer therapeutics.
C1 [Bernstein, Wendy B.; Dennis, Phillip A.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bernstein, Wendy B.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA.
RP Dennis, PA (reprint author), NCI Navy Med Oncol, Room 5101 Bldg 8,8901 Wisconsin Ave, Bethesda, MD 20899 USA.
EM dennisp@mail.nih.gov
FU NIH, Center for Cancer Research, National Cancer Institute
FX This research was supported by the Intramural Research Programme of the
NIH, Center for Cancer Research, National Cancer Institute. The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services or Department of Defense,
nor does mention of trade names, commercial products, or organization
imply endorsement by the United States Government.
NR 65
TC 38
Z9 38
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD NOV
PY 2008
VL 3
IS 6
BP 666
EP 675
DI 10.1097/COH.0b013e328313915d
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V24OC
UT WOS:000208418700011
PM 19373040
ER
PT J
AU Lee, MJ
Kim, YS
Kummar, S
Giaccone, G
Trepel, JB
AF Lee, Min-Jung
Kim, Yeong Sang
Kummar, Shivaani
Giaccone, Giuseppe
Trepel, Jane B.
TI Histone deacetylase inhibitors in cancer therapy
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE cancer therapy; clinical trial; combination therapy; histone deacetylase
inhibitors
ID SUBEROYLANILIDE HYDROXAMIC ACID; ADVANCED SOLID TUMORS; T-CELL LYMPHOMA;
ACUTE MYELOID-LEUKEMIA; ACTIVITY IN-VITRO; PHASE-I; VALPROIC ACID; HDAC
INHIBITORS; RETINOIC ACID; HEMATOLOGICAL MALIGNANCIES
AB Purpose of review
The purpose of this review is to provide an overview of recent advances in the development of histone deacetylase inhibitors (HDACi) for the treatment of cancer.
Recent findings
Recently, there has been a dramatic expansion of HDACi clinical investigation There are. now 11 HDACi in clinical trial, including inhibitors with a broad spectrum of HDAC isoform inhibitory activity as well as drugs with isoform selectivity. Over 70 combination therapy trials are in progress. Major areas of progress covered include the entry of new HDAC inhibitors into clinical development, recent progress in understanding of molecular mechanisms of HDACi anticancer activity, and a preclinical and clinical update on HDACi in combination.
Summary
In the period under review there have been advances in understanding of HDACi mechanisms of action, identification of rational combinations that address increased efficacy and overcoming resistance, and greatly expanded clinical development of pan-HDAC-inhibitory and isoform-selective inhibitors in monotherapy and combination therapy protocols.
C1 [Lee, Min-Jung; Kim, Yeong Sang; Kummar, Shivaani; Giaccone, Giuseppe; Trepel, Jane B.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Trepel, JB (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N230,10 Ctr Dr, Bethesda, MD 20892 USA.
EM trepel@helix.nih.gov
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU Bayer Schering Pharma AG; Syndax Pharmaceuticals; Intramural Research
Program; Center for Cancer Research; National Cancer Institute; National
Institutes of Health
FX Research funding supporting this work was received from Bayer Schering
Pharma AG, Syndax Pharmaceuticals, and the Intramural Research Program,
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 120
TC 82
Z9 83
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8746
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD NOV
PY 2008
VL 20
IS 6
BP 639
EP 649
DI 10.1097/CCO.0b013e3283127095
PG 11
WC Oncology
SC Oncology
GA 369ND
UT WOS:000260700300006
PM 18841045
ER
PT J
AU Weichel, ED
Colyer, MH
AF Weichel, Eric D.
Colyer, Marcus H.
TI Combat ocular trauma and systemic injury
SO CURRENT OPINION IN OPHTHALMOLOGY
LA English
DT Article
DE closed-globe injury; combat ocular trauma; enucleation; intraocular
foreign body; open-globe injury; traumatic brain injury
ID EYE INJURIES; WAR INJURIES; IRAQI FREEDOM; DESERT-SHIELD; PROTECTION;
MANAGEMENT; STORM
AB Purpose of review
To review the recent literature regarding combat ocular trauma during hostilities in Operations Iraqi Freedom and Enduring Freedom, describe the classification of combat ocular trauma, and offer strategies that may assist in the management of eye injuries.
Recent findings
Several recent publications have highlighted features of combat ocular trauma from Operation Iraqi Freedom. The most common cause of today's combat ocular injuries is unconventional fragmentary munitions causing significant blast injuries. These explosive munitions cause high rates of concomitant nonocular injuries such as traumatic brain injury, amputation, and other organ injuries. The most frequent ocular injuries include open-globe and adnexal lacerations. The extreme severity of combat-related open-globe injuries leads to high rates of primary enucleation and retained intraocular foreign bodies. Visual outcomes of intraocular foreign body injuries are similar to other series despite delayed removal, and no cases of endophthalmitis have occurred. Despite these advances, however, significant vision loss persists in cases of perforating globe injuries as well as open and closed-globe trauma involving the posterior segment.
Summary
This review summarizes the recent literature describing ocular and systemic injuries sustained during Operations Iraqi and Enduring Freedom. An emphasis on classification of ocular injuries as well as a discussion of main outcome measures and complications is discussed.
C1 [Weichel, Eric D.] Walter Reed Army Med Ctr, Ophthalmol Serv, Washington, DC 20307 USA.
[Weichel, Eric D.] NEI, NIH, Bethesda, MD 20892 USA.
RP Weichel, ED (reprint author), Walter Reed Army Med Ctr, Ophthalmol Serv, 6900 Georgia Ave, Washington, DC 20307 USA.
EM eweichel@hotmail.com
NR 39
TC 24
Z9 24
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8738
J9 CURR OPIN OPHTHALMOL
JI Curr. Opin. Ophthalmol.
PD NOV
PY 2008
VL 19
IS 6
BP 519
EP 525
DI 10.1097/ICU.0b013e3283140e98
PG 7
WC Ophthalmology
SC Ophthalmology
GA 367WA
UT WOS:000260582100011
PM 18854697
ER
PT J
AU Jiang, S
Li, Z
Ding, K
Roller, PP
AF Jiang, Sheng
Li, Zheng
Ding, Ke
Roller, Peter P.
TI Recent Progress of Synthetic Studies to Peptide and Peptidomimetic
Cyclization
SO CURRENT ORGANIC CHEMISTRY
LA English
DT Review
ID SOLID-PHASE SYNTHESIS; RING-CLOSING METATHESIS; NATIVE CHEMICAL
LIGATION; AZIDE-ALKYNE CYCLOADDITION; SNAR-BASED CYCLOETHERIFICATION;
BIFUNCTIONAL BUILDING-BLOCKS; TYROSINE-DERIVED METABOLITE; GRB2-SH2
DOMAIN ANTAGONISTS; INTRAMOLECULAR O-ARYLATION; EFFICIENT COUPLING
REAGENT
AB A large number of cyclic peptides, which exhibit a range of biological activities, have been found in nature. The reason of cyclic peptides that attracted world wide attention and made them extensively studied, is their enhanced metabolic stabilities, biological specificities, bioavailability, and conformational constrained structural feature, which make them important leads for drug discovery, and as actual drugs. Many cyclic peptides show very promising biological activities, including anticancer, antibacterial, antiviral, antifungal, anti-inflammatory, and anti-clotting or anti-atherogenic properties. Peptide cyclization becomes an effective and commonly employed strategy for peptide modifications. During the past several decades, great efforts have been made to develop more efficient methods for the synthesis of cyclic peptides and peptidomimetics. This review will be focused on the major progress of the novel recently developed peptide cyclization approaches and the profitable applications since 2002.
C1 [Jiang, Sheng; Ding, Ke] CAS, Guangzhou Inst Biomed & Hlth, Lab Regenerat Biol, Guangzhou 510663, Guangdong, Peoples R China.
[Li, Zheng] Methodist Hosp, Res Inst, Dept Radiol, Houston, TX 77030 USA.
[Roller, Peter P.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA.
RP Jiang, S (reprint author), CAS, Guangzhou Inst Biomed & Hlth, Lab Regenerat Biol, Guangzhou Int Business Incubator D-10,Guangzhou S, Guangzhou 510663, Guangdong, Peoples R China.
EM jiang_sheng@gibh.ac.cn
RI Ding, Ke/B-3257-2010;
OI ding, ke/0000-0001-8167-0476
NR 298
TC 34
Z9 34
U1 3
U2 43
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1385-2728
J9 CURR ORG CHEM
JI Curr. Org. Chem.
PD NOV
PY 2008
VL 12
IS 17
BP 1502
EP 1542
DI 10.2174/138527208786241501
PG 41
WC Chemistry, Organic
SC Chemistry
GA 386OS
UT WOS:000261893100005
ER
PT J
AU Appay, V
van Lier, RAW
Sallusto, F
Roederer, M
AF Appay, Victor
van Lier, Rene A. W.
Sallusto, Federica
Roederer, Mario
TI Phenotype and Function of Human T Lymphocyte Subsets: Consensus and
Issues
SO CYTOMETRY PART A
LA English
DT Review
DE phenotype; function; T cells; virus
ID CHEMOKINE RECEPTOR EXPRESSION; EX-VIVO; MEMORY CELLS; IN-VITRO;
ANTIGENIC-STIMULATION; DISTINCT POPULATIONS; EFFECTOR FUNCTIONS; VIRUS;
DIFFERENTIATION; CD4(+)
AB In recent years, a tremendous effort has been devoted to the detailed characterization of the phenotype and function of distinct T cell subpopulations in humans, as well as to their pathway(s) of differentiation and role in immune responses. But these studies seem to have generated more questions than definitive answers. To clarify issues related to the function and differentiation of T cell subsets, one session of the MASIR 2008 conference was dedicated to this topic. Several points of consensus and discord were highlighted in the work presented during this session. We provide here all account of these points, including the relative heterogeneity of T cell subpopulations during infections with distinct pathogens, the relationship between phenotypic and functional T cell attributes, and the pathway(s) of T cell differentiation. Finally, we discuss the problems which still limit general agreement. Published 2008 Wiley-Liss, Inc.(dagger)
C1 [Appay, Victor] Univ Paris 06, Hop La Pitie Salpetriere, INSERM,Cellular Immunol Lab, U543,Avenir Grp, F-75013 Paris, France.
[van Lier, Rene A. W.] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, NL-1105 AZ Amsterdam, Netherlands.
[Sallusto, Federica] Inst Res Biomed, CH-6500 Bellinzona, Switzerland.
[Roederer, Mario] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Appay, V (reprint author), Univ Paris 06, Hop La Pitie Salpetriere, INSERM,Cellular Immunol Lab, U543,Avenir Grp, F-75013 Paris, France.
EM appay@chups.jussieu.fr
OI van Lier, Rene/0000-0002-3201-7144
NR 69
TC 335
Z9 344
U1 4
U2 20
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD NOV
PY 2008
VL 73A
IS 11
BP 975
EP 983
DI 10.1002/cyto.a.20643
PG 9
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 368LJ
UT WOS:000260622300002
PM 18785267
ER
PT J
AU Chattopadhyay, PK
Melenhorst, JJ
Ladell, K
Gostick, E
Scheinberg, P
Barrett, AJ
Wooldridge, L
Roederer, M
Sewell, AK
Price, DA
AF Chattopadhyay, Pratip K.
Melenhorst, J. Joseph
Ladell, Kristin
Gostick, Emma
Scheinberg, Phillip
Barrett, A. John
Wooldridge, Linda
Roederer, Mario
Sewell, Andrew K.
Price, David A.
TI Techniques to Improve the Direct Ex Vivo Detection of Low Frequency
Antigen-Specific CD8(+) T Cells with Peptide-Major Histocompatibility
Complex Class I Tetramers
SO CYTOMETRY PART A
LA English
DT Review
DE CD8(+) T cell; peptide-major histocompatibility complex class I
tetramer; polychromatic flow cytometry
ID MHC CLASS-I; POLYCHROMATIC FLOW-CYTOMETRY; ALPHA-3 DOMAIN MUTANTS;
EFFECTOR FUNCTION; MEMORY SUBSETS; CD8+T CELLS; BINDING; RECEPTOR;
CORECEPTOR; CTL
AB The ability to quantify and characterize antigen-specific CD8(+) T cells irrespective of functional readouts using fluorochrome-conjugated peptide-major histocompatibility complex class I (pMHCI) tetramers in conjunction with flow cytometry has transformed our understanding of cellular immune responses over the past decade. In the case of prevalent CD8(+) T cell populations that engage cognate pMHCI tetramers with high avidities, direct ex vivo identification and subsequent data interpretation is relatively straightforward. However, the accurate identification of low frequency antigen-specific CD8(+) T cell populations can be complicated, especially in situations where T cell receptor-mediated tetramer binding occurs at low avidities. Here, we highlight a few simple techniques that can be employed to improve the Visual resolution, and hence the accurate quantification, of tetramer binding CD8(+) T cell populations by flow cytometry. These methodological modifications enhance signal intensity, especially in the case of specific CD8(+) T cell populations that bind cognate antigen with low avidities, minimize background noise, and enable improved discrimination of true pMHCI tetramer binding events from nonspecific uptake. (C) 2008 international Society for Advancement of cytometry
C1 [Chattopadhyay, Pratip K.; Roederer, Mario] NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Chattopadhyay, Pratip K.; Roederer, Mario] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Chattopadhyay, Pratip K.; Roederer, Mario] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff CF14 4XN, S Glam, Wales.
[Chattopadhyay, Pratip K.; Roederer, Mario] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Chattopadhyay, PK (reprint author), NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pchattop@mail.nih.gov; priced6@cardiff.ac.uk
RI Ladell, Kristin/K-2475-2013; Price, David/C-7876-2013; Chattopadhyay,
Pratip/B-9227-2008; Ladell, Kristin/C-8301-2013;
OI Price, David/0000-0001-9416-2737; Ladell, Kristin/0000-0002-9856-2938;
Sewell, Andrew/0000-0003-3194-3135; Scheinberg,
Phillip/0000-0002-9047-4538; Chattopadhyay, Pratip/0000-0002-5457-9666
FU National Institutes of Health; Vaccine Research Center, National
Institute of Allergy and Infectious Diseases; Medical Research Council
(UK)
FX This work was sponsored by the Intramural Research Program of the
National Institutes of Health; Vaccine Research Center, National
Institute of Allergy and Infectious Diseases, and by the Medical
Research Council (UK).
NR 49
TC 27
Z9 27
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD NOV
PY 2008
VL 73A
IS 11
BP 1001
EP 1009
DI 10.1002/cyto.a.20642
PG 9
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 368LJ
UT WOS:000260622300005
PM 18836993
ER
PT J
AU Precopio, ML
Butterfield, TR
Casazza, JP
Little, SJ
Richman, DD
Koup, RA
Roederer, M
AF Precopio, Melissa L.
Butterfield, Tiffany R.
Casazza, Joseph P.
Little, Susan J.
Richman, Douglas D.
Koup, Richard A.
Roederer, Mario
TI Optimizing Peptide Matrices for Identifying T-Cell Antigens
SO CYTOMETRY PART A
LA English
DT Article
DE epitopes; T lymphocyte; HIV; epitope mapping
ID HUMAN CYTOMEGALOVIRUS; HIV-1 INFECTION; FLOW-CYTOMETRY; VIRAL LOAD;
RESPONSES; INDIVIDUALS; EPITOPES; CD4(+)
AB Mapping T-cell epitopes for a pathogen or vaccine requires a complex method for screening hundreds to thousands of peptides with a limited amount of donor sample. We describe an optimized deconvolution process by which peptides are pooled in a matrix format to minimize the number of tests required to identify peptide epitopes. Four peptide pool matrices were constructed to deconvolute the HIV-specific T-cell response in three HIV-infected individuals. ELISpot assays were used to map peptide antigens. Many HIV peptides were mapped in all three individuals. However, there were several challenges and limitations associated with the deconvolution process. Peptides that induced low-frequency responses or were masked by peptide competition within a given pool were not identified, because they did not meet the threshold criteria for a positive response. Also, amino acid sequence variation limited the ability of this method to map autologous HIV peptides. Alternative analysis strategies and revisions to the original matrix optimizations are presented that address ways to increase peptide identification. This optimized deconvolution method allows for efficient mapping of T-cell peptide epitopes. It is rapid, powerful, efficient, and unrestricted by HLA type. Published 2008 Wiley-Liss, Inc.(dagger)
C1 [Precopio, Melissa L.; Butterfield, Tiffany R.; Casazza, Joseph P.; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Little, Susan J.; Richman, Douglas D.] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
[Little, Susan J.; Richman, Douglas D.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Little, Susan J.; Richman, Douglas D.] VA San Diego Healthcare Syst, San Diego, CA 92161 USA.
[Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Precopio, ML (reprint author), Idera Pharmaceut Inc, 167 Sidney St, Cambridge, MA 02139 USA.
EM mprecopio@iderapharma.com
FU UCSD Center for AIDS Research (National Institutes of Health) [AI
043638, AI 047745]
FX Grant sponsor: UCSD Center for AIDS Research (National Institutes of
Health); Grant numbers: AI 043638, AI 047745.
NR 19
TC 16
Z9 16
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD NOV
PY 2008
VL 73A
IS 11
BP 1071
EP 1078
DI 10.1002/cyto.a.20646
PG 8
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 368LJ
UT WOS:000260622300013
PM 18781655
ER
PT J
AU Walker, JL
Menko, AS
Khalil, S
Rebustini, I
Hofftnan, MP
Kreidberg, JA
Kukuruzinska, MA
AF Walker, Janice L.
Menko, A. Sue
Khalil, Sheede
Rebustini, Ivan
Hofftnan, Matthew P.
Kreidberg, Jordan A.
Kukuruzinska, Maria A.
TI Diverse Roles of E-Cadherin in the Morphogenesis of the Submandibular
Gland: Insights Into the Formation of Acinar and Ductal Structures
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE E-cadberin; submandibular gland; branching morphogenesis; acinar
precursors; presumptive ducts; cytodifferentiation; catenins; adherens
junctions
ID CELL-ADHESION MOLECULES; BRANCHING MORPHOGENESIS; SALIVARY-GLAND;
ALPHA-6 INTEGRIN; BASEMENT-MEMBRANE; EPITHELIAL-CELLS; MOUSE;
EXPRESSION; JUNCTIONS; CYTOSKELETON
AB The formation of acinar and ductal structures during epithelial tissue branching morphogenesis is not well understood. We report that in the mouse submandibular gland (SMG), acinar and ductal cell fates are determined early in embryonic morphogenesis with E-cadherin playing pivotal roles in development. We identified two morphologically distinct cell populations at the single bud stage, destined for different functions. The outer layer of columnar cells with organized E-cadherin junctions expressed the neonatal acinar marker B1 by E13.5, demonstrating their acinar fate. The interior cells initially lacked distinct E-cadherin junctions, but with morphogenesis formed cytokeratin 7 (K7)-positive ductal structures with organized E-cadherin junctions and F-actin filaments. Inhibition of E-cadherin function with either siRNA or function blocking antibody caused extensive apoptosis of ductal cells and aberrantly dilated lumens, providing the first evidence that E-cadherin regulates ductal lumen formation during branching morphogenesis of the salivary gland. Developmental Dynamics 237.3128-3141, 2008. (C) 2008 Wiley-Liss, Inc.
C1 [Kukuruzinska, Maria A.] Boston Univ, Med Ctr, Dept Mol & Cell Biol, Sch Dent Med, Boston, MA 02118 USA.
[Walker, Janice L.; Menko, A. Sue] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
[Rebustini, Ivan; Hofftnan, Matthew P.] Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Unit, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA.
[Kreidberg, Jordan A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Kukuruzinska, MA (reprint author), Boston Univ, Med Ctr, Dept Mol & Cell Biol, Sch Dent Med, 715 Albany St,E428, Boston, MA 02118 USA.
EM mkukuruz@bu.edu
FU NIH/NIDCR [DE14437, DE 10183, EY014798]
FX We thank Wellington Cardoso for helpful discussions and Mihai
Nita-Lazar, Donna Afshar, and Michele Leonard for a critical reading of
the manuscript. The authors also thank Ni Zhai for her technical
assistance with the confocal imaging. This work was supported by Grants
DE14437 and DE 10183 from the NIH/NIDCR to M.A.K. and EY014798 to A.S.M.
NR 51
TC 44
Z9 45
U1 2
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1058-8388
J9 DEV DYNAM
JI Dev. Dyn.
PD NOV
PY 2008
VL 237
IS 11
BP 3128
EP 3141
DI 10.1002/dvdy.21717
PG 14
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA 372VP
UT WOS:000260930400004
PM 18816447
ER
PT J
AU Wingert, JR
Burton, H
Sinclair, RJ
Brunstrom, JE
Damiano, DL
AF Wingert, Jason R.
Burton, Harold
Sinclair, Robert J.
Brunstrom, Janice E.
Damiano, Diane L.
TI Tactile sensory abilities in cerebral palsy: deficits in roughness and
object discrimination
SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
LA English
DT Article
ID 2-POINT DISCRIMINATION; SPASTIC HEMIPLEGIA; CHILDREN; HANDS;
SENSIBILITY; RELIABILITY; RECOGNITION; PREVALENCE; DISORDERS; VALIDITY
AB Motor deficits in cerebral palsy (CP) have been well documented; however, associated sensory impairment in CP remains poorly understood. We examined tactile object recognition in the hands using geometric shapes, common objects, and capital letters. Discrimination of tactile roughness was tested using paired horizontal gratings of varied groove widths passively translated across the index finger. We tested 17 individuals with hemiplegia (mean 13y 9mo [SD 5y 2mo]; 6 males, 11 females), 21 with diplegia (mean 14y 10mo [SD 7y]; 10 males, 11 females), and 21 without disabilities (mean 14y 10mo [SD 5y 1mo]; 11 males, 10 females). All participants with CP fell within level I or II of the Gross Motor Function Classification System and level I or II of the Manual Abilities Classification System. Individuals with CP were significantly less accurate compared with those without disabilities on all tactile object-recognition tasks using their non-dominant hand. Both groups of patients also had significantly higher thresholds for groove-width differences with both hands compared with those without disabilities. Within the group with diplegia, only roughness discrimination differed between hands, whereas within the group with hemiplegia, significant between-limb differences were present for all tasks. Despite mild motor deficits compared with the entire population of individuals with CP, this sample demonstrated ubiquitous tactile deficits.
C1 [Wingert, Jason R.] Univ N Carolina, Dept Hlth & Wellness, Asheville, NC 28804 USA.
[Burton, Harold; Sinclair, Robert J.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
[Burton, Harold] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Brunstrom, Janice E.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Brunstrom, Janice E.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Brunstrom, Janice E.] Washington Univ, Sch Med, Dept Cell Biol, St Louis, MO 63110 USA.
[Damiano, Diane L.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
RP Wingert, JR (reprint author), Univ N Carolina, Dept Hlth & Wellness, WHC CPO 2730,1 Univ Hts, Asheville, NC 28804 USA.
EM jwingert@unca.edu
RI Damiano, Diane/B-3338-2010; Wingert, Jason/B-1528-2012
OI Damiano, Diane/0000-0002-2770-5356;
FU United Cerebral Palsy; Foundation for Physical Therapy PODS Scholarship;
Ogle family; NIH [NS054413, NS31005]
FX This study was supported by grants from United Cerebral Palsy, the
Foundation for Physical Therapy PODS Scholarship, funds from the Ogle
family, and NIH NS054413 and NS31005.
NR 26
TC 30
Z9 30
U1 1
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0012-1622
J9 DEV MED CHILD NEUROL
JI Dev. Med. Child Neurol.
PD NOV
PY 2008
VL 50
IS 11
BP 832
EP 838
DI 10.1111/j.1469-8749.2008.03105.x
PG 7
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 375MU
UT WOS:000261118800010
PM 18811710
ER
PT J
AU Narusyte, J
Neiderhiser, JM
D'Onofrio, BM
Reiss, D
Spotts, EL
Ganiban, J
Lichtenstein, P
AF Narusyte, Jurgita
Neiderhiser, Jenae M.
D'Onofrio, Brian M.
Reiss, David
Spotts, Erica L.
Ganiban, Jody
Lichtenstein, Paul
TI Testing Different Types of Genotype-Environment Correlation: An Extended
Children-of-Twins Model
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
DE children-of-twins model; parenting; child adjustment;
genotype-environment correlation
ID ADOLESCENT ANTISOCIAL-BEHAVIOR; EXPRESSED EMOTION; GENETIC INFLUENCE;
FAMILY ENVIRONMENT; CHILDHOOD; PSYCHOPATHOLOGY; DEPRESSION; INTERPLAY;
SYMPTOMS; TRANSMISSION
AB This study presents an extended children-of-twins model, which allowed the authors to test the direction of the association between parenting and child adjustment. Three mechanisms were examined: direct phenotypic influence of parenting on child behavior (controlling for both parental and child genotype), passive genotype-environment correlation, and evocative genotype-environment correlation. This model was tested with Monte Carlo simulations. The authors generated data sets consisting of 1,000 twin parent pairs together with their children and 1,000 twin children pairs together with their parents. These simulated data sets were then used to estimate the model, and the procedure was repeated 1,000 times. The simulation results showed that this model recovered the true values of parameters with high precision. The model was also applied to an observed data set to analyze, as a first example, the association between maternal emotional overinvolvement and child internalizing problems. The results showed that this association was best explained by evocative genotype-environment correlation.
C1 [Narusyte, Jurgita; Lichtenstein, Paul] Karolinska Inst, Dept Epidemiol & Biostat, Stockholm 17177, Sweden.
[Neiderhiser, Jenae M.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA.
[D'Onofrio, Brian M.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA.
[Reiss, David] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
[Spotts, Erica L.] NIA, NIH, Bethesda, MD 20892 USA.
[Ganiban, Jody] George Washington Univ, Dept Psychol, Washington, DC 20052 USA.
RP Narusyte, J (reprint author), Karolinska Inst, Dept Epidemiol & Biostat, Box 281, Stockholm 17177, Sweden.
EM jurgita.narusyte@ki.se
OI lichtenstein, paul/0000-0003-3037-5287
FU NIMH NIH HHS [R01 MH054610-09, R01MH54610, R01 MH054610]
NR 63
TC 46
Z9 47
U1 5
U2 12
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0012-1649
J9 DEV PSYCHOL
JI Dev. Psychol.
PD NOV
PY 2008
VL 44
IS 6
BP 1591
EP 1603
DI 10.1037/a0013911
PG 13
WC Psychology, Developmental
SC Psychology
GA 372VO
UT WOS:000260930300006
PM 18999324
ER
PT J
AU Gaulton, KJ
Willer, CJ
Li, Y
Scott, LJ
Conneely, KN
Jackson, AU
Duren, WL
Chines, PS
Narisu, N
Bonnycastle, LL
Luo, JC
Tong, M
Sprau, AG
Pugh, EW
Doheny, KF
Valle, TT
Abecasis, GR
Tuomilehto, J
Bergman, RN
Collins, FS
Boehnke, M
Mohlkel, KL
AF Gaulton, Kyle J.
Willer, Cristen J.
Li, Yun
Scott, Laura J.
Conneely, Karen N.
Jackson, Anne U.
Duren, William L.
Chines, Peter S.
Narisu, Narisu
Bonnycastle, Lori L.
Luo, Jingchun
Tong, Maurine
Sprau, Andrew G.
Pugh, Elizabeth W.
Doheny, Kimberly F.
Valle, Timo T.
Abecasis, Goncalo R.
Tuomilehto, Jaakko
Bergman, Richard N.
Collins, Francis S.
Boehnke, Michael
Mohlkel, Karen L.
TI Comprehensive Association Study of Type 2 Diabetes and Related
Quantitative Traits With 222 Candidate Genes
SO DIABETES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISMS; COMMON
VARIANTS; RISK LOCI; SUSCEPTIBILITY; CALPAIN-10; IDENTIFICATION;
POPULATION; EXPRESSION; MELLITUS
AB OBJECTIVE-Type 2 diabetes is a common complex disorder with environmental and genetic components. We used a candidate gene-based approach to identify single nucleotide polymorphism (SNP) variants in 222 candidate genes that influence susceptibility to type 2 diabetes.
RESEARCH DESIGN AND METHODS-In a case-control study of 1,161 type 2 diabetic subjects and 1,174 control Finns who are normal glucose tolerant, we genotyped 3,531 tagSNPs and annotation-based SNPs and imputed an additional 7,498 SNPs, providing 99.9% coverage of common HapMap variants in the 222 candidate genes. Selected SNPs were genotyped in an additional 1,211 type 2 diabetic case subjects and 1,259 control subjects who are normal glucose tolerant, also from Finland.
RESULTS-Using SNP- and gene-based analysis methods, we replicated previously reported SNP-type 2 diabetes associations in PPARG, KCNJ11, and SLC2A2; identified significant SNPs in genes with previously reported associations (ENPP1 [rs2021966, P = 0.00026] and NRF1 [rs1882095, P = 0.00096]); and implicated novel genes, including RAPGEF1 (rs4740283, P = 0.00013) and TP53 (rs1042522, Arg72Pro, P = 0.00086), in type 2 diabetes susceptibility.
CONCLUSIONS-Our study provides an effective gene-based approach to association study design and analysis. One or more of the newly implicated genes may contribute to type 2 diabetes pathogenesis. Analysis of additional samples will be necessary to determine their effect on susceptibility. Diabetes 57:31363144,2008
C1 [Gaulton, Kyle J.; Mohlkel, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
[Willer, Cristen J.; Li, Yun; Scott, Laura J.; Conneely, Karen N.; Jackson, Anne U.; Duren, William L.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Willer, Cristen J.; Li, Yun; Scott, Laura J.; Conneely, Karen N.; Jackson, Anne U.; Duren, William L.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Chines, Peter S.; Narisu, Narisu; Bonnycastle, Lori L.; Tong, Maurine; Sprau, Andrew G.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
[Luo, Jingchun] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Pugh, Elizabeth W.; Doheny, Kimberly F.] Johns Hopkins Sch Med, Inst Med Genet, Ctr Inherited Dis Res, Baltimore, MD USA.
[Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.
[Valle, Timo T.; Tuomilehto, Jaakko] Natl Publ Hlth Inst, Diabet & Genet Epidemiol Unit, Dept Epidemiol & Hlth Promot, Helsinki, Finland.
[Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland.
RP Mohlkel, KL (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
EM mohlke@med.unc.edu
RI Abecasis, Goncalo/B-7840-2010;
OI Abecasis, Goncalo/0000-0003-1509-1825
FU National Institutes of Health (NIH) [DK072193, DK062370]; American
Diabetes Association; National Center for Integrative Biomedical
Informatics (NCIBI) at the University of Michigan [U54 DA021519]; CIDR
NIH [N01-HG-65403]; GRCF SNP Center
FX Support for this research was provided by National Institutes of Health
(NIH) Grants DK072193 (to K.L.M.) and DK062370 (to M.B.), a postdoctoral
fellowship award from the American Diabetes Association (to C.J.W.), and
the National Center for Integrative Biomedical Informatics (NCIBI) at
the University of Michigan (U54 DA021519). K.L.M. and G.R.A. are Pew
Scholars in the Biomedical Sciences. Genome-wide genotyping was
performed by the Johns Hopkins University Genetic Resources Core
Facility (GRCF) SNP Center at the Center for Inherited Disease Research
(CIDR), with support from CIDR NIH contract no. N01-HG-65403 and the
GRCF SNP Center.; We thank the Finnish citizens who generously
participated in this study, Michael Andre and Rachana Kshatriya of the
University of North Carolina Mammalian Genotyping Core for Illumina
GoldenGate genotyping, Amy Swift and Mario Morken of the NHGRI for stage
2 genotyping, and Kurt Hetrick, Michael Barnhart, Craig Bark, Janet
Goldstein, and Lee Watkins of the CIDR for expert technical work on
genome-wide Illumina Infinium genotyping.
NR 46
TC 54
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U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD NOV
PY 2008
VL 57
IS 11
BP 3136
EP 3144
DI 10.2337/db07-1731
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 367PR
UT WOS:000260564800035
PM 18678618
ER
PT J
AU Qi, L
Kang, K
Zhang, CL
van Dam, RM
Kraft, P
Hunter, D
Lee, CH
Hu, FB
AF Qi, Lu
Kang, Kihwa
Zhang, Cuilin
van Dam, Rob M.
Kraft, Peter
Hunter, David
Lee, Chih-Hao
Hu, Frank B.
TI Fat Mass- and Obesity-Associated (FTO) Gene Variant Is Associated With
Obesity Longitudinal Analyses in Two Cohort Studies and Functional Test
SO DIABETES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; TYPE-2 DIABETES-MELLITUS;
CORONARY-HEART-DISEASE; PHYSICAL-ACTIVITY; EXTREME OBESITY; ADULT
OBESITY; LIFE-STYLE; RISK; WOMEN; ADIPONECTIN
AB OBJECTIVE-To examine the longitudinal association of fat, mass- and obesity-associated (FTO) variant with obesity, circulating adipokine levels, and FTO expression in various materials from human and mouse.
RESEARCH DESIGN AND METHODS-We genotyped rs9939609 in 2,287 men and 3,520 women from two prospective cohorts. Plasma adiponectin and leptin were measured in a subset of diabetic men (n = 854) and women (n = 987). Expression of FTO was tested in adipocytes from db/db mice and mouse macrophages.
RESULTS-We observed a trend toward decreasing associations between rs9939609 and BMI at older age ( >= 65 years) in men, whereas the associations were constant across different age groups in women. In addition, the single nucleotide polymorphism (SNP) rs9939609 was associated with lower plasma adiponectin (log[e]- means, 1.82 +/- 0.04, 1.73 +/- 0.03, and 1.68 +/- 0.05 for TT, TA, and AA genotypes, respectively; P for trend 0.02) and leptin (log[e]- means, 3.56 +/- 0.04, 3.63 +/- 0.04, and 3.70 +/- 0.06; P for trend = 0.06) in diabetic women. Adjustment for BMI attenuated the associations. FTO gene was universally expressed in human and mice tissues, including adipocytes. In an ancillary study of adipocytes from db/db mice, FTO expression was similar to 50% lower than in those from wild-type mice.
CONCLUSIONS-The association between FTO SNP rs9939609 and obesity risk may decline at older age. The variant affects circulating adiponectin and leptin levels through the changes in BMI. In addition, the expression of FTO gene was reduced in adipocytes from db/db mice. Diabetes 57:3145-3151, 2008
C1 [Qi, Lu; van Dam, Rob M.; Hunter, David; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Qi, Lu; van Dam, Rob M.; Kraft, Peter; Hunter, David; Hu, Frank B.] Harvard Univ, Sch Med & Dent, Boston, MA 02115 USA.
[Qi, Lu; van Dam, Rob M.; Kraft, Peter; Hunter, David; Hu, Frank B.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Kang, Kihwa; Lee, Chih-Hao] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA.
[Zhang, Cuilin] NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Kraft, Peter; Hunter, David; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
EM nhlqi@channing.harvard.edu
RI van Dam, Rob/F-9674-2010
OI van Dam, Rob/0000-0002-7354-8734
FU American Heart Association; Boston Obesity Nutrition Research Center
[DK46200]; National Institutes of Health [DK-58845, CA-87969]
FX L.Q. has received an American Heart Association Scientist Development
Award and was supported by the Boston Obesity Nutrition Research Center
(DK46200). C.-H.L. has received an American Heart Association Scientist
Development Award. F.B.H. has received an American Heart Association
Established Investigator Award. This work has been supported by National
Institutes of Health Grants DK-58845 and CA-87969.
NR 46
TC 89
Z9 93
U1 0
U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD NOV
PY 2008
VL 57
IS 11
BP 3145
EP 3151
DI 10.2337/db08-0006
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 367PR
UT WOS:000260564800036
PM 18647953
ER
PT J
AU Ma, LJ
Hanson, RL
Que, LN
Guo, Y
Kobes, S
Bogardus, C
Baier, LJ
AF Ma, Lijun
Hanson, Robert L.
Que, Lorem N.
Guo, Yan
Kobes, Sayuko
Bogardus, Clifton
Baier, Leslie J.
TI PCLO Variants Are Nominally Associated With Early-Onset Type 2 Diabetes
and Insulin Resistance in Pima Indians
SO DIABETES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GRANULE EXOCYTOSIS; CA2+ SENSOR; RISK LOCI;
CAMP; REPLICATION; MELLITUS; CHANNEL; SIGNALS; ATP
AB OBJECTIVE-A prior genome-wide association (GWA) study in Pima Indians identified variants within PCLO that were associated with early-onset type 2 diabetes. PCLO encodes a presynaptic cytomatrix protein that functions as a Ca2+ sensor that may be involved in insulin secretion and/or insulin action. Therefore, PCLO was analyzed as a candidate gene for type 2 diabetes.
RESEARCH DESIGN AND METHODS-Sequencing of PCLO identified four nonsynonymous variants and a 10-amino acid insertion. These variants, together with 100 additional variants identified by sequencing or chosen from databases, were genotyped for association analysis in the same 895 subjects analyzed in the prior GWA study (300 case subjects with diabetes onset at aged <25 years, 334 nondiabetic control subjects aged >45 years, and 261 discordant siblings of the case or control subjects for within-family analyses), as well as 415 nondiabetic Pima Indians who had been metabolically phenotyped for predictors of diabetes. Selected variants were further genotyped in a population-based sample of 3,501 Pima Indians.
RESULTS-Four variants were modestly associated With early-onset type 2 diabetes in both general and within-family analyses (P = 0.004-0.04, recessive model), where the diabetes risk allele was also nominally associated with a lower insulin-mediated glucose disposal rate (P = 0.009-0.14, recessive model) in nondiabetic Pima Indians. However, their association with diabetes in the population-based sample was weaker (P = 0.02-0.20, recessive model).
CONCLUSIONS-Variation within PCLO may have a modest effect on early-onset type 2 diabetes, possibly as a result of reduced insulin action, but has minimal, if any, impact on population-based risk for type 2 diabetes. Diabetes 57:31563160,2008
C1 [Ma, Lijun; Hanson, Robert L.; Que, Lorem N.; Guo, Yan; Kobes, Sayuko; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Diabet Mol Genet Sect, Phoenix Epidemiol & Clin Res Branch, NIH,Dept Hlth & Human Serv, Phoenix, AZ USA.
RP Baier, LJ (reprint author), NIDDK, Diabet Mol Genet Sect, Phoenix Epidemiol & Clin Res Branch, NIH,Dept Hlth & Human Serv, Phoenix, AZ USA.
EM lbaier@phx.niddk.nih.gov
FU National Institute of Digestive and Kidney Diseases (NIDDK), National
Institutes of Health; American Diabetes Association
FX This study was supported by the intramural research program of National
Institute of Digestive and Kidney Diseases (NIDDK), National Institutes
of Health. L.M. and Y.G. are supported by a grant from the American
Diabetes Association.; We thank Drs. Michael Traurig and Yunhua L.
Muller for critical reading of the manuscript and the staff of the
Phoenix Epidemiology and Clinical Research Branch of the NIDDK for
contributions to this study. We also thank the investigators from WTCCC,
DGI, and DIAGRAM for making their genotypic data publicly available;
this is a tremendous resource that will benefit everyone in our goal to
understand the genetics of complex diseases.
NR 22
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U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD NOV
PY 2008
VL 57
IS 11
BP 3156
EP 3160
DI 10.2337/db07-1800
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 367PR
UT WOS:000260564800038
PM 18647954
ER
PT J
AU Pettitt, DJ
Lawrence, JM
Beyer, J
Hillier, TA
Liese, AD
Mayer-Davis, B
Loots, B
Imperatore, G
Liu, L
Dolan, LM
Linder, B
Dabelea, D
AF Pettitt, David J.
Lawrence, Jean M.
Beyer, Jennifer
Hillier, Teresa A.
Liese, Angela D.
Mayer-Davis, Beth
Loots, Beth
Imperatore, Giuseppina
Liu, Lenna
Dolan, Lawrence M.
Linder, Barbara
Dabelea, Dana
TI Association Between Maternal Diabetes in Utero and Age at Offspring's
Diagnosis of Type 2 Diabetes
SO DIABETES CARE
LA English
DT Article
ID RISK-FACTORS; BIRTH-ORDER; FETAL HYPERINSULINISM; CHILDHOOD; MELLITUS;
MOTHERS; OBESITY; ENVIRONMENT; YORKSHIRE; DELIVERY
AB OBJECTIVE - The purpose of this study was to examine age of diabetes diagnosis in youth who have a parent with diabetes by diabetes type and whether the parent's diabetes was diagnosed before or after the youth's birth.
RESEARCH DESIGN AND METHODS - The cohort comprised SEARCH for Diabetes in Youth Study participants (diabetes diagnosis 2001-2005) with a diabetic parent. SEARCH is a multicenter survey of youth with diabetes diagnosed before age 20 years.
RESULTS - Youth with type 2 diabetes were more likely to have a parent with either type I or type 2 diabetes (mother 39.3%; father 21.2%) than youth with type 1 diabetes (5.3 and 6.7%, respectively, P < 0.001 for each). Type 2 diabetes was diagnosed 1.68 years earlier among those exposed to diabetes in utero (n = 174) than among those whose mothers' diabetes was diagnosed later (P = 0.018, controlled for maternal diagnosis age, paternal diabetes, sex, and race/ethnicity). Age at diagnosis of type 1 diabetes for 269 youth with and without in utero exposure did not differ significantly (difference 0.96 year, P = 0.403 after adjustment). Controlled for the father's age of diagnosis, father's diabetes before the child's birth was not associated with age at diagnosis (P = 0.078 for type 1 diabetes; P = 0.140 for type 2 diabetes).
CONCLUSIONS - Type 2 diabetes was diagnosed at younger ages among those exposed to hyperglycemia in utero. Among youth with type I diabetes, the effect of the intrauterine exposure was not significant when controlled for mother's age of diagnosis. This study helps explain why other studies have found higher age-specific rates of type 2 diabetes among offspring of women with diabetes.
C1 [Pettitt, David J.] Sansum Diabet Res Inst, Santa Barbara, CA USA.
[Lawrence, Jean M.] Kaiser Permanente So Calif, Pasadena, CA USA.
[Beyer, Jennifer] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Hillier, Teresa A.] Kaiser Permanente, Ctr Hlth Res NW Hawaii, Honolulu, HI USA.
[Liese, Angela D.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
[Liese, Angela D.] Univ S Carolina, Arnold Sch Publ Hlth, Ctr Res Nutr & Hlth Dispar, Columbia, SC 29208 USA.
[Mayer-Davis, Beth] Univ N Carolina, Chapel Hill, NC USA.
[Loots, Beth] Seattle Childrens Hosp, Seattle, WA USA.
[Loots, Beth] Reg Med Ctr, Seattle, WA USA.
[Imperatore, Giuseppina] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Liu, Lenna] Univ Washington, Seattle, WA 98195 USA.
[Dolan, Lawrence M.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Linder, Barbara] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Dabelea, Dana] Univ Colorado, Denver, CO 80202 USA.
RP Pettitt, DJ (reprint author), Sansum Diabet Res Inst, Santa Barbara, CA USA.
EM dpettitt@sansum.org
FU Centers for Disease Control and Prevention [PA 00097, DP-05-069];
National Institute of Diabetes and Digestive and Kidney Diseases; Kaiser
Permanente Southern California [U01 DP000246]; University of Colorado
Health Science Center [U01 DP000247]; Pacific Health Research Institute
[U01 DP000245]; Children's Hospital Medical Center (Cincinnati) [U01
DP000248]; University of South Carolina [U01 DP000254]; University of
Washington School of Medicine [U01 DP000244]; Wake Forest University
School of Medicine [U01 DP000250]
FX SEARCH for Diabetes in Youth is funded by the Centers for Disease
Control and Prevention (PA 00097 and DP-05-069) and supported by the
National Institute of Diabetes and Digestive and Kidney Diseases. Center
Contract Numbers are as follows: Kaiser Permanente Southern California
(U01 DP000246), University of Colorado Health Science Center (U01
DP000247), Pacific Health Research Institute (U01 DP000245), Children's
Hospital Medical Center (Cincinnati) (U01 DP000248), University of South
Carolina (U01 DP000254), University of Washington School of Medicine
(U01 DP000244), and Wake Forest University School of Medicine (U01
DP000250).; The SEARCH for Diabetes in Youth Study is indebted to the
many youth and their families and their health care providers, whose
participation made this study possible.
NR 25
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U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD NOV
PY 2008
VL 31
IS 11
BP 2126
EP 2130
DI 10.2337/dc08-0769
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 367PT
UT WOS:000260565000012
PM 18694977
ER
PT J
AU Nansel, TR
Weisberg-Benchell, J
Wysocki, T
Laffel, L
Anderson, B
AF Nansel, T. R.
Weisberg-Benchell, J.
Wysocki, T.
Laffel, L.
Anderson, B.
CA Steering Comm Family Management Di
TI Quality of life in children with Type 1 diabetes: a comparison of
general and diabetes-specific measures and support for a unitary
diabetes quality-of-life construct
SO DIABETIC MEDICINE
LA English
DT Article
DE children; measurement; quality of life; Type 1 diabetes
ID INSULIN PUMP THERAPY; METABOLIC-CONTROL; SELF-MANAGEMENT; ADOLESCENTS;
PARENTS
AB Aims To assess the factor structure of the Pediatric Quality of Life Inventory (PedsQL) Diabetes Module and to compare the PedsQL general and diabetes-specific quality of life (QOL) measures regarding psychometric properties and relations to relevant outcomes.
Methods The instruments were completed by 447 children age 9 to 15.5 years with Type 1 diabetes > 1 year from four US paediatric diabetes clinics; parents completed the parallel parent-proxy measures. Principal components factor analysis was used to examine the factor structure of the PedsQL diabetes module. Analyses of the generic and diabetes QOL measures included psychometric properties, parent-child correlations and correlations with depression, adherence and glycated haemoglobin (HbA(1c)).
Results The factor structure of the PedsQL diabetes module did not support the original five subscales. Both one- and two-factor models were supported; however, parallel parent and child subscales did not emerge. While the generic and diabetes-specific measures of QOL were moderately to highly correlated with each other, the constructs were differentially associated with relevant diabetes outcomes. Generic QOL was more highly associated with depression than diabetes QOL. Conversely, diabetes QOL was more highly associated with adherence and HbA(1c), although this was seen to a greater extent for parent-proxy report than for child report.
Conclusions Factor analysis of the PedsQL diabetes module supports the use of a total diabetes QOL score. Findings regarding the associations of the generic and diabetes modules with diabetes outcomes underscore the unique contribution provided by both generic and diabetes QOL.
C1 [Nansel, T. R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, DESPR, NIH,DHHS, Bethesda, MD USA.
[Weisberg-Benchell, J.] Childrens Mem Hosp, Chicago, IL 60614 USA.
[Wysocki, T.] Nemours Childrens Hosp, Jacksonville, FL USA.
[Laffel, L.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Anderson, B.] Baylor Coll Med, Houston, TX 77030 USA.
RP Nansel, TR (reprint author), NICHD, DESPR, PRB, 6100 Execut Blvd,Rm 7B13R,MSC 7510, Bethesda, MD 20892 USA.
EM nanselt@mail.nih.gov
OI Nansel, Tonja/0000-0002-8298-7595
FU Intramural NIH HHS [Z01 HD008741-06]; NICHD NIH HHS [N01-HD-3-3360,
N01-HD-4-3361, N01-HD-4-3364]
NR 24
TC 32
Z9 33
U1 4
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0742-3071
J9 DIABETIC MED
JI Diabetic Med.
PD NOV
PY 2008
VL 25
IS 11
BP 1316
EP 1323
DI 10.1111/j.1464-5491.2008.02574.x
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 367BT
UT WOS:000260528200009
PM 19046222
ER
PT J
AU Tsai, HT
Wang, JT
Chen, CJ
Chang, SC
AF Tsai, Hue-Ting
Wang, Jann-Tay
Chen, Chien-Jen
Chang, Shan-Chwen
TI Association between antibiotic usage and subsequent colonization or
infection of extensive drug-resistant Acinetobacter baumannii: a matched
case-control study in intensive care units
SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
LA English
DT Article
DE Extensive drug-resistant Acinetobacter baumannii; Infection control;
Antibiotic
ID RISK-FACTORS; CARBAPENEM RESISTANCE; NOSOCOMIAL OUTBREAK; MOLECULAR
EPIDEMIOLOGY; NEW-YORK; ACQUISITION; EMERGENCE; SPREAD; PREVALENCE;
VANCOMYCIN
AB Nosocomial spreading of extensive drug-resistant Acinetobacter baumannii (EDRAB) is an emerging problem. To clarify the association between prior antibiotic usage and subsequent EDRAB acquisition, we conducted a one-to-one matched case-control study among patients in all intensive care units (ICUs) at the National Taiwan University Hospital, Taipei, Taiwan, during a 1-year period. A total of 113 pairs of patients were identified. We measured prior antibiotics exposure in 4 perspectives: usage, overall treatment duration, accumulated dosage, and treatment potency. We found positive associations between EDRAB acquisition and prior usage of imipenem and meropenem across 4 measures, especially in usage and average treatment potency (usage, odds ratio [OR](imipenem) = 3.7 with 95% confidence interval [CI] = 1.2-11.0, ORmeropenem = 5.4 with 95% CI = 1.2-20.0; average treatment potency, [OR](imipenem) = 5.3 with 95% CI = 1.3-22.0, ORmeropenem = 3.4 with 95% CI = 1.0-12.0). Ceftazidime use with stronger treatment potency was also strongly associated with subsequent nosocomial EDRAB acquisition (OR = 5.5, 95% CI = 1.5-21.0). The OR of EDRAB acquisition greatly increased in patients who had previously been exposed to any 1 (OR = 5.5, 95% CI = 2.3-13.2) or to any 2 or 3 (OR = 11.1, 95% CI = 2.7-46.4) of the abovementioned antibiotics. Based on these findings, we conclude that usage of imipenem, meropenem, and/or ceftazidime is associated with subsequent acquisition of EDRAB in critically ill patients in ICUs. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Wang, Jann-Tay; Chang, Shan-Chwen] Natl Taiwan Univ Hosp, Dept Internal Med, Div Infect Dis, Taipei 100, Taiwan.
[Tsai, Hue-Ting; Chen, Chien-Jen] Natl Taiwan Univ Hosp, Grad Inst Epidemiol, Coll Publ Hlth, Taipei 100, Taiwan.
[Tsai, Hue-Ting] NCI, Div Canc Genet & Epidemiol, NIH, Rockville, MD 20852 USA.
[Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan.
[Chang, Shan-Chwen] Natl Taiwan Univ Hosp, Coll Med, Grad Inst Clin Pharm, Taipei 100, Taiwan.
RP Chang, SC (reprint author), Natl Taiwan Univ Hosp, Dept Internal Med, Div Infect Dis, Taipei 100, Taiwan.
EM changsc@ntu.edu.tw
RI Chen, Chien-Jen/C-6976-2008;
OI CHANG, SHAN-CHWEN/0000-0001-6505-4139; WANG,
JANN-TAY/0000-0002-0924-3469
NR 33
TC 27
Z9 34
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0732-8893
J9 DIAGN MICR INFEC DIS
JI Diagn. Microbiol. Infect. Dis.
PD NOV
PY 2008
VL 62
IS 3
BP 298
EP 305
DI 10.1016/j.diagmicrobio.2008.06.017
PG 8
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 370BE
UT WOS:000260736900009
PM 18707839
ER
PT J
AU Sharif, S
Ramanathan, RK
Potter, D
Cieply, K
Krasinskas, AM
AF Sharif, Saima
Ramanathan, Ramesh K.
Potter, Douglas
Cieply, Kathleen
Krasinskas, Alyssa M.
TI HER2 Gene Amplification and Chromosome 17 Copy Number Do Not Predict
Survival of Patients with Resected Pancreatic Adenocarcinoma
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE HER2 gene; Pancreatic cancer; Fluorescence in situ hybridization; Gene
amplification; Survival rate
ID EPIDERMAL-GROWTH-FACTOR; IN-SITU HYBRIDIZATION; METASTATIC
BREAST-CANCER; HER-2/NEU EXPRESSION; IMMUNOHISTOCHEMICAL EVALUATION;
FACTOR RECEPTOR; SOLID TUMORS; OVEREXPRESSION; ONCOGENE; CHEMOTHERAPY
AB HER2 gene amplification is an established predictive and prognostic marker in breast cancer. Since there are conflicting reports as to the significance of HER2 gene amplification in pancreatic cancer, we undertook this study. We studied HER2 gene amplification, HER2 copy numbers, and chromosome 17 copy numbers using fluorescence in situ hybridization in 63 cases of resected pancreatic cancer. Sixteen tumors (25%) had HER2 gene amplification, 7 (11%) had increased HER2 copy numbers, and 11 (17%) had increased chromosome 17 copy numbers. No statistical significance was found between the genetic parameters and tumor characteristics, stage, or survival. To the best of our knowledge, this is the largest case series reporting HER2 gene amplification status and its association with tumor characteristics and survival in pancreatic cancer in the literature. Although a significant percentage (25%) of pancreatic cancers demonstrate amplification of the HER2 gene, we find no association of HER2 gene amplification or chromosome 17 hyperploidy with poorer survival.
C1 [Cieply, Kathleen; Krasinskas, Alyssa M.] Univ Pittsburgh, UPMC Presbyterian Hosp, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA.
[Sharif, Saima] Allegheny Canc Ctr, Pittsburgh, PA USA.
[Sharif, Saima] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
[Ramanathan, Ramesh K.] Translat Genom Res Inst, Phoenix, AZ USA.
[Potter, Douglas] Univ Pittsburgh, Biostat Facil, Inst Canc, Pittsburgh, PA 15213 USA.
[Potter, Douglas] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA.
RP Krasinskas, AM (reprint author), Univ Pittsburgh, UPMC Presbyterian Hosp, Sch Med, Dept Pathol, A610,200 Lothrop St, Pittsburgh, PA 15213 USA.
EM krasinskasam@upmc.edu
NR 40
TC 11
Z9 11
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD NOV
PY 2008
VL 53
IS 11
BP 3026
EP 3032
DI 10.1007/s10620-008-0267-1
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 363EG
UT WOS:000260250000028
PM 18463983
ER
PT J
AU Gore, AV
Lampugnani, MG
Dye, L
Dejana, E
Weinstein, BM
AF Gore, Aniket V.
Lampugnani, Maria Grazia
Dye, Louis
Dejana, Elisabetta
Weinstein, Brant M.
TI Combinatorial interaction between CCM pathway genes precipitates
hemorrhagic stroke
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
ID CEREBRAL CAVERNOUS MALFORMATIONS; TRUNCATING MUTATIONS; EXPRESSION
ANALYSIS; ZEBRAFISH; KRIT1; RAP1; HETEROGENEITY; GTPASE; FORM;
HAPLOINSUFFICIENCY
AB Intracranial hemorrhage (ICH) is a particularly severe form of stroke whose etiology remains poorly understood, with a highly variable appearance and onset of the disease (Felbor et al., 2006; Frizzell, 2005; Lucas et al., 2003). In humans, mutations in any one of three CCM genes causes an autosomal dominant genetic ICH disorder characterized by cerebral cavernous malformations (CCM). Recent evidence highlighting multiple interactions between the three CCM gene products and other proteins regulating endothelial junctional integrity suggests that minor deficits in these other proteins could potentially predispose to, or help to initiate, CCM, and that combinations of otherwise silent genetic deficits in both the CCM and interacting proteins might explain some of the variability in penetrance and expressivity of human ICH disorders. Here, we test this idea by combined knockdown of CCM pathway genes in zebrafish. Reducing the function of rap1b, which encodes a Ras GTPase effector protein for CCM1/Krit1, disrupts endothelial junctions in vivo and in vitro, showing it is a crucial player in the CCM pathway. Importantly, a minor reduction of Rap1b in combination with similar reductions in the products of other CCM pathway genes results in a high incidence of ICH. These findings support the idea that minor polygenic deficits in the CCM pathway can strongly synergize to initiate ICH.
C1 [Gore, Aniket V.; Weinstein, Brant M.] NICHHD, Mol Genet Lab, Program Genom Dev, NIH, Bethesda, MD 20892 USA.
[Lampugnani, Maria Grazia; Dejana, Elisabetta] IFOM FIRC Inst Mol Oncol Fdn, Lab Vasc Biol, I-20193 Milan, Italy.
[Lampugnani, Maria Grazia] Mario Negri Inst Pharmacol Res, I-20156 Milan, Italy.
[Dye, Louis] NICHHD, Microscopy & Imaging Ctr, NIH, Bethesda, MD 20892 USA.
RP Weinstein, BM (reprint author), NICHHD, Mol Genet Lab, Program Genom Dev, NIH, Bethesda, MD 20892 USA.
EM bw96w@nih.gov
OI Lampugnani, Maria Grazia/0000-0002-4802-7064
FU intramural program of National Institute of Child Health and Human
Development; Associazione Italiana per la Ricerca sul Cancro; European
Community (EUSTROKE consortium); Leducq Fondation
FX We thank Drs I. Dawid, E. Tournier-Lasserve and K. Sampath for comments
on the manuscript. We thank members of the Weinstein Lab for technical
assistance and critical suggestions. This work was supported by the
intramural program of National Institute of Child Health and Human
Development (B.M.W.), by the Associazione Italiana per la Ricerca sul
Cancro and European Community (EUSTROKE consortium; M.G.L., E.D.), and
by the Leducq Fondation (B.M.W., M.G.L., E.D.). Deposited in PMC for
immediate release.
NR 41
TC 52
Z9 53
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 1754-8403
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD NOV-DEC
PY 2008
VL 1
IS 4-5
BP 275
EP 281
DI 10.1242/dmm.000513
PG 7
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 474AK
UT WOS:000268254400016
PM 19093037
ER
PT J
AU Kedar, PS
Stefanick, DF
Horton, JK
Wilson, SH
AF Kedar, Padmini S.
Stefanick, Donna F.
Horton, Julie K.
Wilson, Samuel H.
TI Interaction between PARP-1 and ATR in mouse fibroblasts is blocked by
PARP inhibition
SO DNA REPAIR
LA English
DT Article
DE ATR; PARP-1; PARP inhibitor; Methylation damage
ID BASE-EXCISION-REPAIR; DNA-POLYMERASE-BETA; ADP-RIBOSE POLYMERASE;
CELL-CYCLE ARREST; POLY(ADP-RIBOSE) POLYMERASE; MAMMALIAN-CELLS;
DEFICIENT CELLS; STRAND BREAKS; S-PHASE; DAMAGE
AB Inhibition of PARP activity results in extreme sensitization to MMS-induced cell killingin cultured mouse fibroblasts. In these MMS-treated cells, PARP inhibition is accompanied by an accumulation of S-phase cells that requires signaling by the checkpoint kinase ATR [J.K. Horton, D.F. Stefanick, J.M. Naron, P.S. Kedar, S.H. Wilson, Poly(ADP-ribose) polymerase activity prevents signaling pathways for cell cycle arrest following DNA methylating agent exposure, J. Biol. Chem. 280 (2005) 15773-15785]. Here, we examined mouse fibroblast extracts for formation of a complex that may reflect association between the damage responsive proteins PARP-1 and ATR. Co-immunoprecipitation of PARP-1 and ATR was observed in extracts prepared from MMS-treated cells, but not under conditions of PARP inhibition. Further, our experiments demonstrated PAR-adduction of ATR in extracts from control and MMS-treated cells. An interaction between purified ATR and PARP-1 was similarly demonstrated, suggesting that the observed co-immunoprecipitation of ATR and PARP-1 from cell extracts may be due to a direct interaction between the two enzymes. In addition, purified recombinant ATR is a substrate for poly(ADP-ribosyl)ation by PARP-1, and poly(ADP-1-ribose) adduction of PARP-1 and ATR resulted in an increase in PARP-1 and ATR co-immunoprecipitation. (C) 2008 Published by Elsevier B.V.
C1 [Kedar, Padmini S.; Stefanick, Donna F.; Horton, Julie K.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU NIH/NIEHS [HHSN273200700046U]
FX We thank Dr. William A. Beard for help with figure preparation and
Jennifer Myers for editorial assistance. We thank Dr. Michael J.
Carrozza for critical reading of the manuscript. We also thank Dr.
Robert Petrovich for assistance with expression of Flag-tagged human ATR
in 293 cells. This research was supported by the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences.
Dr. Kedar's contribution was funded in whole with federal funds from
NIH/NIEHS, under delivery order HHSN273200700046U to Constella/SRA, LLC.
NR 37
TC 20
Z9 20
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD NOV 1
PY 2008
VL 7
IS 11
BP 1787
EP 1798
DI 10.1016/j.dnarep.2008.07.006
PG 12
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 373CQ
UT WOS:000260949000003
PM 18691676
ER
PT J
AU Cisneros, GA
Perera, L
Garcia-Diaz, M
Bebenek, K
Kunkel, TA
Pedersen, LG
AF Cisneros, G. Andres
Perera, Lalith
Garcia-Diaz, Miguel
Bebenek, Katarzyna
Kunkel, Thomas A.
Pedersen, Lee G.
TI Catalytic mechanism of human DNA polymerase lambda with Mg2+ and Mn2+
from ab initio quantum mechanical/molecular mechanical studies
SO DNA REPAIR
LA English
DT Article
DE DNA polymerase lambda; QM/MM; Molecular dynamics; Simulations;
Polymerase catalysis
ID MINIMUM-ENERGY PATHS; CHEMICAL-REACTIONS; ACTIVE-SITE; NUCLEOTIDYL
TRANSFER; ENZYME CATALYSIS; TRANSITION-STATE; PROTON-TRANSFER; BETA;
REPAIR; FIDELITY
AB DNA polymerases play a crucial role in the cell cycle due to their involvement in genome replication and repair. Understanding the reaction mechanism by which these polymerases carry out their function can provide insights into these processes, Recently, the crystal structures of human DNA polymerase lambda (Pol lambda) have been reported both for pre- and post-catalytic complexes [Garcia-Diaz et al., DNA Repair 3 (2007), 1333]. Here we employ the pre-catalytic complex as a starting structure for the determination of the catalytic mechanism of Pol lambda using ab initio quantum mechanical/molecular mechanical methods. The reaction path has been calculated using Mg2+ and Mn2+ as the catalytic metals. In both cases the reaction proceeds through a two-step mechanism where the 3'-OH of the primer sugar ring is deprotonated by one of the conserved Asp residues (D490) in the active site before the incorporation of the nucleotide to the nascent DNA chain. A significant charge transfer is observed between both metals and some residues in the active site as the reaction proceeds. The optimized reactant and product structures agree with the reported crystal structures. In addition, the calculated reaction barriers for both metals are close to experimentally estimated barriers. Energy decomposition analysis to explain individual residue contributions suggests that several amino acids surrounding the active site are important for catalysis. Some of these residues, including R420, R488 and E529, have been implicated in catalysis by previous mutagenesis experiments on the homologous residues on Pol beta. Furthermore, Pol lambda residues R420 and E529 found to be important from the energy decomposition analysis, are homologous to residues R183 and E295 in Pol beta, both of which are linked to cancer. In addition, residues R386, E391, K422 and K472 appear to have an important role in catalysis and could be a potential target for mutagenesis experiments. There is partial conservation of these residues across the Pol X family of DNA polymerases. Published by Elsevier B.V.
C1 [Cisneros, G. Andres; Perera, Lalith; Garcia-Diaz, Miguel; Bebenek, Katarzyna; Kunkel, Thomas A.; Pedersen, Lee G.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
[Garcia-Diaz, Miguel; Bebenek, Katarzyna; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
[Pedersen, Lee G.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
RP Cisneros, GA (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
EM cisnero1@niehs.nih.gov; pereral2@niehs.nih.gov
RI Cisneros, Gerardo/B-3128-2010; perera, Lalith/B-6879-2012; Pedersen,
Lee/E-3405-2013
OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861
FU NIH; NIEHS
FX This research was supported by the intramural research program of the
NIH and NIEHS. Computing time from the NIEHS and UNC computing
facilities are gratefully acknowledged. GAC would like to thank Drs.
S.K. Burger, Z. Lu and Prof. W. Yang at Duke University for the QSM code
and Prof. Y Zhang at NYU for enlightening discussions. We would like to
thank the reviewers as well as Drs. T Darden, B. Beard and G. Muller at
NIEHS for critical reading of this manuscript.
NR 72
TC 38
Z9 38
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD NOV 1
PY 2008
VL 7
IS 11
BP 1824
EP 1834
DI 10.1016/j.dnarep.2008.07.007
PG 11
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 373CQ
UT WOS:000260949000006
PM 18692600
ER
PT J
AU Yeung, EYH
Sueyoshi, T
Negishi, M
Chang, TKH
AF Yeung, Eugene Y. H.
Sueyoshi, Tatsuya
Negishi, Masahiko
Chang, Thomas K. H.
TI Identification of Ginkgo biloba as a Novel Activator of Pregnane X
Receptor
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Article
ID CONSTITUTIVE-ANDROSTANE RECEPTOR; CYP3A GENE-EXPRESSION; NUCLEAR
RECEPTORS; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; LIPID-METABOLISM;
MESSENGER-RNA; MOUSE-LIVER; EXTRACT; CAR
AB Pregnane X receptor (PXR; NR1/2) is a ligand-activated transcription factor that plays a role not only in drug metabolism and transport but also in various other biological processes. Ginkgo biloba is a herbal medicine commonly used to manage memory impairment. Treatment of primary cultures of rat hepatocytes with G. biloba extract increases the mRNA expression of CYP3A23, which is a target gene for rat PXR. The present study was conducted to test the hypothesis that G. biloba extract activates PXR. Treatment of mouse PXR (mPXR) or human PXR (hPXR)-transfected HepG2 cells with G. biloba extract at 200 mu g/ml increased mPXR and hPXR activation by 3.2- and 9.5-fold, respectively. Dose-response analysis showed a log-linear increase in hPXR activation by the extract over the range of 200 to 800 mu g/ml. To determine whether G. biloba extract induces hPXR target gene expression, cultured LS180 human colon adenocarcinoma cells were treated for 72 h with the extract. G. biloba extract at 200, 400, and 800 mu g/ml increased CYP3A4 mRNA expression by 1.7-, 2.4-, and 2.5-fold, respectively. The same concentrations of the extract increased CYP3A5 (1.3-3.6-fold) and P-glycoprotein (ABCB) 1 (2.7-6.4-fold) mRNA expression. At concentrations (5 and 10 mu M) that did not down-regulate PXR gene expression and were not cytotoxic, L-sulforaphane (an hPXR antagonist) decreased CYP3A4, CYP3A5, and ABCB1 gene expression in cells treated with G. biloba extract. In summary, G. biloba extract activated mPXR and hPXR in a cell-based reporter gene assay and induced CYP3A4, CYP3A5, and ABCB1 gene expression in hPXR-expressing LS180 cells.
C1 [Yeung, Eugene Y. H.; Chang, Thomas K. H.] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V6T 1Z3, Canada.
[Sueyoshi, Tatsuya; Negishi, Masahiko] Natl Inst Environm Hlth Sci, NIH, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA.
RP Chang, TKH (reprint author), Univ British Columbia, Fac Pharmaceut Sci, 2146 E Mall, Vancouver, BC V6T 1Z3, Canada.
EM tchang@interchange.ubc.ca
FU Canadian Institutes of Health Research [MOP-84581]; Dawson Endowment
Fund in Pharmaceutical Sciences; Intramural Research Program of the
National Institutes of Health; National Institute of Environmental
Health Sciences; Izaak Walton Killam Faculty Research Fellowship;
Michael Smith Foundation for Health Research
FX This study was supported by the Canadian Institutes of Health Research
(Grant MOP-84581 to T. K. H. C.), by the Dawson Endowment Fund in
Pharmaceutical Sciences (a major equipment grant to T. K. H. C.), and by
the Intramural Research Program of the National Institutes of Health and
the National Institute of Environmental Health Sciences (to T. S.,
M.N.). E.Y.H.Y. received a Kam Li Ma Scholarship in Pharmaceutical
Sciences from the University of British Columbia and a partial graduate
student traineeship in drug metabolism from Merck Research Laboratories
(United States). T. K. H. C. received an Izaak Walton Killam Faculty
Research Fellowship and a Senior Scholar Award from the Michael Smith
Foundation for Health Research.
NR 40
TC 41
Z9 45
U1 0
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD NOV
PY 2008
VL 36
IS 11
BP 2270
EP 2276
DI 10.1124/dmd.108.023499
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 361MP
UT WOS:000260132100015
PM 18725505
ER
PT J
AU Le Duc, JW
Anderson, K
Bloom, ME
Estep, JE
Feldmann, H
Geisbert, JB
Geisbert, TW
Hensley, L
Holbrook, M
Jahrling, PB
Ksiazek, TG
Korch, G
Patterson, J
Skvorak, JP
Weingartl, H
AF Le Duc, James W.
Anderson, Kevin
Bloom, Marshall E.
Estep, James E.
Feldmann, Heinz
Geisbert, Joan B.
Geisbert, Thomas W.
Hensley, Lisa
Holbrook, Michael
Jahrling, Peter B.
Ksiazek, Thomas G.
Korch, George
Patterson, Jean
Skvorak, John P.
Weingartl, Hana
TI Framework for Leadership and Training of Biosafety Level 4 Laboratory
Workers
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
AB Construction of several new Biosafety Level 4 (BSL-4) laboratories and expansion of existing operations have created an increased international demand for well-trained staff and facility leaders. Directors of most North American BSL-4 laboratories met and agreed upon a framework for leadership and training of biocontainment research and operations staff. They agreed on essential preparation and training that includes theoretical consideration of biocontainment principles, practical hands-on training, and mentored on-the-job experiences relevant to positional responsibilities as essential preparation before a person's independent access to a BSL-4 facility. They also agreed that the BSL-4 laboratory director is the key person most responsible for ensuring that staff members are appropriately prepared for BSL-4 operations. Although standardized certification of training does not formally exist, the directors agreed that facility-specific, time-limited documentation to recognize specific skills and experiences of trained persons is needed.
C1 [Le Duc, James W.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston Natl Lab, Galveston, TX 77555 USA.
[Anderson, Kevin; Estep, James E.] Natl Biodef Anal & Countermeasures Ctr, Frederick, MD USA.
[Bloom, Marshall E.] Natl Inst Hlth, Hamilton, MT USA.
[Feldmann, Heinz] Publ Hlth Agcy Canada, Winnipeg, MB, Canada.
[Geisbert, Joan B.; Geisbert, Thomas W.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Hensley, Lisa; Korch, George; Patterson, Jean] USA, Med Res Inst Infect Dis, Frederick, MD USA.
[Jahrling, Peter B.] NIH, Bethesda, MD 20892 USA.
[Ksiazek, Thomas G.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Patterson, Jean] SW Fdn Biomed Res, San Antonio, TX 78284 USA.
[Weingartl, Hana] Canadian Food Inspect Agcy, Winnipeg, MB, Canada.
RP Le Duc, JW (reprint author), Univ Texas Med Branch, Inst Human Infect & Immun, Galveston Natl Lab, 301 Univ Blvd, Galveston, TX 77555 USA.
EM jwleduc@utmb.edu
FU National Institute of Allergy and Infectious Diseases (NIAID)
[UC7-AI-070083]; National Institutes of Health; NIAID Division of
Intramural Research
FX This study was supported by grant UC7-AI-070083 from the National
Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health, and by the NIAID Division of Intramural Research.
NR 5
TC 10
Z9 10
U1 0
U2 2
PU CENTER DISEASE CONTROL
PI ATLANTA
PA ATLANTA, GA 30333 USA
SN 1080-6040
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD NOV
PY 2008
VL 14
IS 11
BP 1685
EP 1688
DI 10.3201/eid1411.080741
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 368JI
UT WOS:000260617000001
PM 18976549
ER
PT J
AU McCutchan, TF
Piper, RC
Malkler, MT
AF McCutchan, Thomas F.
Piper, Robert C.
Malkler, Michael T.
TI Use of Malaria Rapid Diagnostic Test to Identify Plasmodioum knowlesi
Infection
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
AB Reports of human infection with Plasmodium knowlesi, a monkey malaria, suggest that it and other nonhuman malaria species may be an emerging health problem. We report the use of a rapid test to supplement microscopic analysis in distinguishing the 5 malaria species that infect humans.
C1 [McCutchan, Thomas F.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20892 USA.
[Piper, Robert C.] Univ Iowa, Iowa City, IA USA.
[Malkler, Michael T.] Flow Inc, Portland, OR USA.
RP McCutchan, TF (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20892 USA.
EM tmccutchan@niaid.nih.gov
FU Division of Intramural Research; National Institute of Allergy and
Infectious Diseases (NIAID); National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health.
NR 15
TC 42
Z9 43
U1 0
U2 1
PU CENTER DISEASE CONTROL
PI ATLANTA
PA ATLANTA, GA 30333 USA
SN 1080-6040
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD NOV
PY 2008
VL 14
IS 11
BP 1750
EP 1752
DI 10.3201/eid1411.080840
PG 3
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 368JI
UT WOS:000260617000013
PM 18976561
ER
PT J
AU Briese, T
Palacios, G
Lipkin, WI
Renwick, N
Venter, M
Jarman, RG
Dominguez, SR
Holmes, KV
Holmes, EC
AF Briese, Thomas
Palacios, Gustavo
Lipkin, W. Ian
Renwick, Neil
Venter, Marietjie
Jarman, Richard G.
Dominguez, Samuel R.
Holmes, Kathryn V.
Holmes, Edward C.
TI Prior Evidence of Putative Novel Rhinovirus Species, Australia Response
SO EMERGING INFECTIOUS DISEASES
LA English
DT Letter
ID GENOTYPE; ILLNESS
C1 [Briese, Thomas; Palacios, Gustavo; Lipkin, W. Ian] Columbia Univ, New York, NY USA.
[Renwick, Neil] Rockefeller Univ, New York, NY 10021 USA.
[Venter, Marietjie] Univ Pretoria, ZA-0002 Pretoria, South Africa.
[Jarman, Richard G.] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand.
[Dominguez, Samuel R.; Holmes, Kathryn V.] Univ Colorado, Denver Sch Med, Aurora, CO USA.
[Holmes, Edward C.] Penn State Univ, University Pk, PA 16802 USA.
[Holmes, Edward C.] Fogarty Int Ctr, Bethesda, MD USA.
RP Briese, T (reprint author), Columbia Univ Epidemiol, Mailman Sch Publ Hlth, Ctr Infect & Immun, 722 W 168th St, New York, NY 10032 USA.
EM thomas.briese@columbia.edu
RI Venter, Marietjie/H-3032-2011; Venter, Marietjie/P-9604-2016
OI Venter, Marietjie/0000-0003-2696-824X
NR 5
TC 0
Z9 0
U1 0
U2 0
PU CENTER DISEASE CONTROL
PI ATLANTA
PA ATLANTA, GA 30333 USA
SN 1080-6040
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD NOV
PY 2008
VL 14
IS 11
BP 1824
EP 1825
DI 10.3201/eid1411.081088
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 368JI
UT WOS:000260617000040
ER
PT J
AU Wang, XD
Matsuda, H
Shi, YB
AF Wang, Xuedong
Matsuda, Hiroki
Shi, Yun-Bo
TI Developmental Regulation and Function of Thyroid Hormone Receptors and
9-cis Retinoic Acid Receptors during Xenopus tropicalis Metamorphosis
SO ENDOCRINOLOGY
LA English
DT Article
ID AMPHIBIAN METAMORPHOSIS; LAEVIS METAMORPHOSIS; GENE-EXPRESSION; IN-VIVO;
POSTEMBRYONIC DEVELOPMENT; COREPRESSOR COMPLEX; FROG METAMORPHOSIS;
MOLECULAR-BASIS; TADPOLE TAIL; BETA GENE
AB Amphibian metamorphosis serves as an excellent model to study T-3 function during postembryonic development in vertebrate due to its total dependence on T-3. Earlier molecular studies in the model species Xenopus laevis have led to a number of important in vivo findings on the function and mechanisms of T-3 receptor (TR) action during vertebrate development. However, the lack of genomic sequence information, its tetraploid genome, and lengthy developmental cycle hinder further analyses on TR functions. In this regard, the highly related species, Xenopus tropicalis, is much more advantageous. Toward developing X. tropicalis for genome-wide and genetic studies of TR function, we analyzed the expression profiles of TRs and their heterodimerization partners, retinoid X receptors (RXRs) or 9-cis retinoic acid receptors. We show that their expression correlates with transformations in different organs and that TR/RXR heterodimers are capable of repressing and activating gene expression in vivo in the absence and presence of T-3, respectively. We further demonstrate that TRs are bound to endogenous target genes in X. tropicalis tadpoles. Our results thus support a role of TRs in mediating the metamorphic effects of T-3 in X. tropicalis. More importantly, the similarities in the expression and function between X. tropicalis and X. laevis TRs and RXRs as demonstrated by our study also pave the way to take advantages of existing morphological, molecular, and cellular knowledge of X. laevis development and the genetic and sequence superiority of X. tropicalis to dissect the molecular pathways governing tissue/organ-specific transformations during vertebrate postembryonic development. (Endocrinology 149: 5610-5618, 2008)
C1 [Wang, Xuedong; Matsuda, Hiroki; Shi, Yun-Bo] NICHHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, Program Cell Regulat & Metab,NIH, Bethesda, MD 20892 USA.
RP Shi, YB (reprint author), NICHHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, Program Cell Regulat & Metab,NIH, Bldg 18 T,Room 106, Bethesda, MD 20892 USA.
EM shi@helix.nih.gov
FU National Institute of Child Health and Human Development; National
Institutes of Health
FX This work was supported by the Intramural Research Program of National
Institute of Child Health and Human Development, National Institutes of
Health.
NR 47
TC 36
Z9 36
U1 0
U2 4
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD NOV
PY 2008
VL 149
IS 11
BP 5610
EP 5618
DI 10.1210/en.2008-0751
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 362JM
UT WOS:000260194000032
PM 18635662
ER
PT J
AU Huff, J
Jacobson, MF
Davis, DL
AF Huff, James
Jacobson, Michael F.
Davis, Devra Lee
TI The Limits of Two-Year Bioassay Exposure Regimens for Identifying
Chemical Carcinogens
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE animal cancer tests; aspartame; bioassay designs; bisphenol A; cadmium;
carcinogenicity; chemical carcinogens; genistein; toluene; toxicology
ID NATIONAL TOXICOLOGY PROGRAM; SPRAGUE-DAWLEY RATS; BISPHENOL-A;
RAMAZZINI-FOUNDATION; BREAST-CANCER; ASPARTAME; DIETHYLSTILBESTROL;
ADENOCARCINOMA; CADMIUM; RISK
AB BACKGROUND: Chemical carcinogenesis bioassays in animals have long been recognized and accepted as valid predictors of potential cancer hazards to humans. Most rodent bioassays begin several weeks after birth and expose animals to chemicals or other substances, including workplace and environmental pollutants, for 2 years. New findings indicate the need to extend the timing and duration of exposures used in the rodent bioassay.
OBJECTIVES: In this Commentary,, we propose that the sensitivity of chemical carcinogenesis bioassays would be enhanced by exposing rodents beginning in utero and continuing for 30 months (130 weeks) or until their natural deaths at tip to about 3 years.
DISCUSSION: Studies of three chemicals of different structures and uses-aspartame, cadmium, and toluene-suggest that exposing experimental animals in utero and continuing exposure for 30 months or until their natural deaths increase the sensitivity of bioassays, avoid false-negative results, and strengthen the value and validity of results for regulatory agencies.
CONCLUSIONS: Government agencies, drug companies, and the chemical industry should conduct and compare the results of 2-year bioassays of known carcinogens or chemicals for which there is equivocal evidence of carcinogenicity, with longer-term studies, with and without in utero exposure. If studies longer than 2 years and/or with in utero exposure are found to better identify potential human carcinogens, then regulatory agencies should promptly revise their testing guidelines, which were established in the 1960s and early 1970s. Changing the timing and dosing of the animal bioassay would enhance protection of workers and consumers who are exposed to potentially dangerous workplace or home contaminants, pollutants, drugs, food additives, and other chemicals throughout their lives.
C1 [Jacobson, Michael F.] Ctr Sci Publ Interest, Washington, DC 20009 USA.
[Huff, James] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Davis, Devra Lee] Univ Pittsburgh, Pittsburgh Canc Inst, Dept Epidemiol, Grad Sch Publ Hlth,Ctr Environm Oncol, Pittsburgh, PA USA.
RP Jacobson, MF (reprint author), Ctr Sci Publ Interest, 1875 Connecticut Ave,Suite 300, Washington, DC 20009 USA.
EM mjacobson@cspinet.org
NR 52
TC 26
Z9 26
U1 0
U2 9
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV
PY 2008
VL 116
IS 11
BP 1439
EP 1442
DI 10.1289/ehp.10716
PG 4
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 366ZG
UT WOS:000260521500014
PM 19057693
ER
PT J
AU Kan, HD
Heiss, G
Rose, KM
Whitsel, EA
Lurmann, F
London, SJ
AF Kan, Haidong
Heiss, Gerardo
Rose, Kathryn M.
Whitsel, Eric A.
Lurmann, Fred
London, Stephanie J.
TI Prospective Analysis of Traffic Exposure as a Risk Factor for Incident
Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC)
Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE air pollution; coronary disease; traffic
ID PARTICULATE AIR-POLLUTION; LONG-TERM EXPOSURE; ACUTE
MYOCARDIAL-INFARCTION; ULTRAFINE PARTICLES; MAJOR HIGHWAY; MORTALITY;
ASSOCIATION; HYPERTENSION; POLLUTANTS; COHORT
AB BACKGROUND: For people living close to busy roads, traffic is a major source of air pollution. Few prospective data have been published on the effects of long-term exposure to traffic on the incidence of coronary heart disease (CHID).
OBJECTIVES: In this article, we examined the association between long-term traffic exposure and incidence of fatal and nonfatal CHID in a population-based prospective cohort study.
METHODS: We studied 13,309 middle-age men and women in the Atherosclerosis Risk in Communities study I without previous CHD at enrollment, front 1987 to 1989 in four U.S. communities. Geographic information system-mapped traffic density and distance to major roads served as measures of traffic exposure. We examined the association between traffic exposure and incident CHD using proportional hazards regression models, with adjustment for background air pollution and a wide range of individual cardiovascular risk factors.
RESULTS: Over an average of 13 years of follow-tip, 976 subjects developed CHD. Relative to those in the lowest quartile of traffic density, the adjusted hazard ratio (HR) in the highest quartile was 1.32 [95% confidence interval (CI), 1.06-1.65; p-value for trend across quartiles = 0.042]. When we treated traffic density as a continuous variable, the adjusted HR per one Unit increase of log-transformed density was 1.03 (95% CI, 1.01-1-05; p = 0.006). For residents living within 300 m of major roads compared with those living farther away, the adjusted HR was 1.12 (95% CI, 0.95-1-32; p = 0.189). We found little evidence of effect modification for sex, smoking status, obesity. low-density lipoprotein cholesterol level, hypertension, age, or education.
CONCLUSION Higher long-term exposure to traffic is associated with incidence of CHID, independent of other risk factors. These prospective data support an effect of traffic-related air pollution on the development of CHD in middle-age persons.
C1 [Kan, Haidong; London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Kan, Haidong] Fudan Univ, Sch Publ Hlth, Dept Environm Hlth, Shanghai 200433, Peoples R China.
[Heiss, Gerardo; Rose, Kathryn M.; Whitsel, Eric A.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Whitsel, Eric A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
[Lurmann, Fred] Sonoma Technol Inc, Petaluma, CA USA.
RP London, SJ (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
EM london2@niehs.nih.gov
OI London, Stephanie/0000-0003-4911-5290
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];
National Institute of Environmental Health Sciences [Z01 ES043012]
FX The Atherosclerosis Risk in Communities study is a collaborative study
supported by National Heart, Lung, and Blood Institute contracts
N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021, and N01-HC-55022. This work was also supported by Z01
ES043012 from the Intramural Research Program, National Institute of
Environmental Health Sciences.
NR 42
TC 53
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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 NOV
PY 2008
VL 116
IS 11
BP 1463
EP 1468
DI 10.1289/ehp.11290
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 366ZG
UT WOS:000260521500018
PM 19057697
ER
PT J
AU van Bemmel, DM
Visvanathan, K
Freeman, LEB
Coble, J
Hoppin, JA
Alavanja, MCR
AF van Bemmel, Dana M.
Visvanathan, Kala
Freeman, Laura E. Beane
Coble, Joseph
Hoppin, Jane A.
Alavanja, Michael C. R.
TI S-Ethyl-N,N-dipropylthiocarbamate Exposure and Cancer Incidence among
Male Pesticide Applicators in the Agricultural Health Study: A
Prospective Cohort
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE agriculture; cancer; EPTC; herbicide; neoplasms; occupational exposure;
pesticides; thiocarbamates
ID NON-HODGKINS-LYMPHOMA; NICOTINIC ACETYLCHOLINE-RECEPTORS; ALACHLOR
MANUFACTURING WORKERS; THIOCARBAMATE HERBICIDES; CARBAMATE PESTICIDES;
RISK-FACTORS; VICIA-FABA; FARMERS; EPTC; IOWA
AB BACKGROUND: The Agricultural Health Study, (AHS) is a prospective cohort study of licensed pesticide applicators from Iowa and North Carolina enrolled between 1993 and 1997. EPTC (S-ethyl-N,N-dipropylthiocarbamate) is a thiocarbamate herbicide used in ever), region of the United States. The U.S. Environmental Protection Agency reports that EPTC is most likely not a human carcinogen; however, the previous epidemiologic data on EPTC exposure and cancer risk were limited.
OBJECTIVES: The purpose of this study was to examine cancer incidence and EPTC use in 48,378 male pesticide applicators enrolled in he AHS.
METHODS: We estimated the rate ratio (RR) and 95% confidence intervals (CIs) for all cancers and selected cancer sites using Poisson regression. We assessed EPTC exposure using two quantitative metrics: lifetime exposure day's and intensity-weighted lifetime exposure days, a measure that accounts for application factors that modify personal exposure likelihood.
RESULTS: Among the 9,878 applicators exposed to EPTC, 470 incident cancer cases were diagnosed during the follow-up period ending December 2004 compared with the 1,824 cases among individuals reporting no use. Although EPTC was associated with colon cancer in the highest tertile of both lifetime exposure days and intensity-weighted lifetime days (RR = 2.09; 95% Cl, 1.26-3.47 and RR = 2.05; 95% CI, 1.34-3.14, respectively) and the trend test was < 0.01 for both, the pattern of RR was not monotonic with increasing use. There was a suggestion of an association with leukemia. No other associations were observed.
CONCLUSION: In this analysis, EPTC use appeared to be associated with colon cancer and leukemia. However, given the relatively small number of cases in the highest exposure tertile, results should be interpreted with caution, and further investigations are needed.
C1 [van Bemmel, Dana M.; Freeman, Laura E. Beane; Coble, Joseph; Alavanja, Michael C. R.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Visvanathan, Kala] Johns Hopkins Med Inst, Dept Epidemiol & Oncol, Baltimore, MD 21205 USA.
[Hoppin, Jane A.] NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Alavanja, MCR (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8000, Rockville, MD 20852 USA.
EM alavanjm@mail.nih.gov
RI Beane Freeman, Laura/C-4468-2015
OI Beane Freeman, Laura/0000-0003-1294-4124
FU National Cancer Institute; Cancer Prevention Fellowship Program; NIH;
National Cancer Institute Division of Cancer Epidemiol and Genetics;
National Institute of Environmental Health Sciences
FX D.v. B is supported by the National Cancer Institute, Cancer Prevention
Fellowship Program. This research was supported by the Intramural
Research Program of the NIH (National Cancer Institute Division of
Cancer Epidemiol and Genetics and the National Institute of
Environmental Health Sciences).
NR 43
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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 NOV
PY 2008
VL 116
IS 11
BP 1541
EP 1546
DI 10.1289/ehp.11371
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 366ZG
UT WOS:000260521500029
PM 19057708
ER
PT J
AU Rusiecki, JA
Baccarelli, A
Bollati, V
Tarantini, L
Moore, LE
Bonefeld-Jorgensen, EC
AF Rusiecki, Jennifer A.
Baccarelli, Andrea
Bollati, Valentina
Tarantini, Letizia
Moore, Lee E.
Bonefeld-Jorgensen, Eva C.
TI Global DNA Hypomethylation Is Associated with High Serum-Persistent
Organic Pollutants in Greenlandic Inuit
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE DNA methylation; global methylation; Greenland; hypomethylation; Inuit;
organochlorines; PCBs; persistent organic pollutants; pesticides;
polychlorinated biphenyls; PoPs; serum
ID ENDOCRINE-DISRUPTING CHEMICALS; NON-HODGKIN-LYMPHOMA; ORGANOCHLORINE
LEVELS; PANCREATIC-CANCER; ADIPOSE-TISSUE; POLYCHLORINATED-BIPHENYLS;
LIFE-STYLE; METHYLATION; DDT; NEUROTOXICITY
AB BACKGROUND: Persistent organic pollutants (POPS) may influence epigenetic mechanisms; therefore, they, could affect chromosomal stability and gene expression. DNA methylation, an epigenetic mechanism, has been associated with cancer initiation and progression. Greenlandic Inuit have some of the highest reported POP levels worldwide.
OBJECTIVE: Our aim in this study was to evaluate the relationship between plasma POPS concentrations and global DNA methylation (percent 5-methylcytosine) in DNA extracted from blood samples from 70 Greenlandic Inuit. Blood samples were collected under the Arctic Monitoring and Assessment Program and previously analyzed for a battery of POPS.
METHODS: We used pyrosequencing to estimate global DNA methylation via Alu and LINEA assays of bisulfite- treated DNA. We investigated correlations between plasma POP concentrations and global DNA methylation via correlation coefficients and linear regression analyses.
RESULTS: We found inverse correlations between percents methylcytosine and many of the 13011 concentrations measured. Linear regressions, adjusting for age and cigarette smoking, showed statistically, significant inverse linear relationships mainly, for the Alu assay for p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane; beta = -0.26), p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene; beta = -0.38), beta-hexachlorocyclohexane (beta = -0.48), oxychlordane (beta = -0.32), alpha-chlordane beta = -0.75), mirex (beta = -0.27), SLIM of polychlorinated biphenyls (beta = -0.56), and sum of all POPS beta = -0.48). Linear regressions for the LINE-1 assay showed beta estimates of similar magnitudes to those using the Alu assay, however, none was statistically significant.
CONCLUSIONS: This is the first study to investigate environmental exposure to POPS and DNA methylation levels in a human population. Global methylation levels were inversely associated with blood plasma levels for several POPS and merit further investigation.
C1 [Rusiecki, Jennifer A.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA.
[Baccarelli, Andrea; Bollati, Valentina; Tarantini, Letizia] Univ Milan, Dept Environm & Occupat Hlth, Milan, Italy.
[Baccarelli, Andrea; Bollati, Valentina; Tarantini, Letizia] Maggiore Hosp, IRCCS, Ctr Mol & Genet Epidemiol, Milan, Italy.
[Moore, Lee E.] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,Dept Health & Human Serv, Bethesda, MD 20892 USA.
[Bonefeld-Jorgensen, Eva C.] Univ Aarhus, Unit Cellular & Mol Toxicol, Ctr Arctic Environm Med, Inst Publ Hlth, Aarhus, Denmark.
RP Rusiecki, JA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, PMB Room A1039,4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM jrusiecki@usuhs.mil
RI Bonefeld-Jorgensen, Eva Cecilie/A-1682-2015;
OI Baccarelli, Andrea/0000-0002-3436-0640; Bollati,
Valentina/0000-0002-0370-9598
FU Uniformed Services University intramural start-up [RO87YT]
FX This research was supported by a Uniformed Services University
intramural start-up grant, RO87YT.
NR 51
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PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV
PY 2008
VL 116
IS 11
BP 1547
EP 1552
DI 10.1289/ehp.11338
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 366ZG
UT WOS:000260521500030
PM 19057709
ER
PT J
AU Kuniholm, MH
Lesi, OA
Mendy, M
Akano, AO
Sam, O
Hall, AJ
Whittle, H
Bah, E
Goederts, JJ
Hainaut, P
Kirk, GD
AF Kuniholm, Mark H.
Lesi, Olufunmilayo A.
Mendy, Maimuna
Akano, Aliu O.
Sam, Omar
Hall, Andrew J.
Whittle, Hilton
Bah, Ebrima
Goederts, James J.
Hainaut, Pierre
Kirk, Gregory D.
TI Aflatoxin Exposure and Viral Hepatitis in the Etiology of Liver
Cirrhosis in The Gambia, West Africa
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE aflatoxin; Africa; hepatitis B virus; liver cirrhosis; p53; The Gambia;
ultrasound
ID HEPATOCELLULAR-CARCINOMA PATIENTS; B-VIRUS-INFECTION; C VIRUS; P53
MUTATIONS; PLASMA DNA; DEVELOPING-COUNTRIES; ALCOHOL INTAKE; TP53
MUTATION; RISK-FACTORS; CANCER
AB BACKGROUND: Cirrhosis of the liver is thought to be a major cause of morbidity and mortality in sub-Saharan Africa, but few controlled studies on the etiology of cirrhosis have been conducted in this region.
OBJECTIVES: We aimed to elucidate the association between environmental and infectious exposures and cirrhosis in The Gambia.
METHODS: Ninety-seven individuals were diagnosed with cirrhosis using a validated ultrasound scoring system and were compared with 397 controls. Participants reported demographic and food frequency information. Blood samples were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis C virus (HCV) antibody, HCV RNA, and the aflatoxin-associated 249(ser) TP53 mutation.
RESULTS: HBsAg seropositivity was associated with a significant increase in risk of cirrhosis [odds ratio (OR) = 8.0; 95% confidence interval (Cl), 4.4-14.7] as was the presence of HBeAg (OR = 10.3; 95% CI, 2.0-53.9) and HCV infection (OR = 3.3; 95% CI, 1.2-9.5). We present novel data that exposure to aflatoxin, as assessed both by high lifetime groundnut (peanut) intake and by the presence of the 249(ser) TP53 mutation in plasma, is associated with a significant increase in the risk for cirrhosis (OR = 2.8; 95% CI, 1.1-7.7 and OR = 3.8; 95% CI, 1.5-9.6, respectively). Additionally, aflatoxin and hepatitis B virus exposure appeared to interact synergistically to substantially increase the risk of cirrhosis, although this was not statistically significant.
CONCLUSIONS: Our results suggest that the spectrum of morbidity associated with aflatoxin exposure could include cirrhosis.
C1 [Kuniholm, Mark H.; Kirk, Gregory D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Program Infect Dis, Baltimore, MD USA.
[Lesi, Olufunmilayo A.; Bah, Ebrima] Gambia Hepatitis Intervent Study, Int Agcy Res Canc, Banjul, Gambia.
[Lesi, Olufunmilayo A.] Univ Lagos, Teaching Hosp, Dept Med, Lagos, Nigeria.
[Mendy, Maimuna; Whittle, Hilton] MRC Labs, Banjul, Gambia.
[Akano, Aliu O.; Sam, Omar] Royal Victoria Teaching Hosp, Dept Med Serv, Banjul, Gambia.
[Akano, Aliu O.] Natl Hosp, Dept Radiodiag, Abuja, Nigeria.
[Hall, Andrew J.] London Sch Hyg & Trop Med, London WC1, England.
[Goederts, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
[Hainaut, Pierre] Gambia Hepatitis Intervent Study, Int Agcy Res Canc, Lyon, France.
RP Kirk, GD (reprint author), 615 N Wolfe St,E-6533, Baltimore, MD 21205 USA.
EM gkirk@jhsph.edu
RI Kirk, Gregory/A-8484-2009; Hainaut, Pierre /B-6018-2012
OI Hainaut, Pierre /0000-0002-1303-1610
FU National Cancer Institute; National Institutes of Health [N02-CP40521]
FX This work was supported by the National Cancer Institute, National
Institutes of Health, contract N02-CP40521.
NR 49
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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 NOV
PY 2008
VL 116
IS 11
BP 1553
EP 1557
DI 10.1289/ehp.11661
PG 5
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 366ZG
UT WOS:000260521500031
PM 19057710
ER
PT J
AU Woodruff, TJ
Zeise, L
Axelrad, DA
Guyton, KZ
Janssen, S
Miller, M
Miller, GG
Schwartz, JM
Alexeeff, G
Anderson, H
Birnbaum, L
Bois, F
Cogliano, VJ
Crofton, K
Euling, SY
Foster, PMD
Germolec, DR
Gray, E
Hattis, DB
Kyle, AD
Luebke, RW
Luster, MI
Portier, C
Rice, DC
Solomon, G
Vandenberg, J
Zoeller, RT
AF Woodruff, Tracey J.
Zeise, Lauren
Axelrad, Daniel A.
Guyton, Kathryn Z.
Janssen, Sarah
Miller, Mark
Miller, Gregory G.
Schwartz, Jackie M.
Alexeeff, George
Anderson, Henry
Birnbaum, Linda
Bois, Frederic
Cogliano, Vincent James
Crofton, Kevin
Euling, Susan Y.
Foster, Paul M. D.
Germolec, Dori R.
Gray, Earl
Hattis, Dale B.
Kyle, Amy D.
Luebke, Robert W.
Luster, Michael I.
Portier, Chris
Rice, Deborah C.
Solomon, Gina
Vandenberg, John
Zoeller, R. Thomas
TI Meeting Report: Moving Upstream-Evaluating Adverse Upstream End Points
for Improved Risk Assessment and Decision-Making
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE adverse health effects; androgen antagonists; hazard identification;
immunotoxicants; risk assessment; science policy; thyroid hormone;
toxicologic assessments
ID N-BUTYL PHTHALATE; CONGENITAL HYPOTHYROIDISM; POLYCHLORINATED-BIPHENYLS;
GENE-EXPRESSION; NATIONAL-HEALTH; DISRUPTING CHEMICALS; REFERENCE RANGE;
IMMUNE STATUS; EXPOSURE; POPULATION
AB BACKGROUND: Assessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links, between early biological disturbances and subsequent overt downstream effects. A workshop was held to consider how the resulting data inform consideration of an "adverse effect" in the context of hazard identification and risk assessment.
OBJECTIVES: Our objective here is to review what is known about the relationships between chemical exposure, early biological effects (Upstream events), and later overt effects (downstream events) through three case studies (thyroid hormone disruption, antiandrogen effects, immune system disruption) and to consider how to evaluate hazard and risk when early biological effect data are available.
DISCUSSION: Each case study presents data on the toxicity pathways linking early biological perturbations with downstream overt effects. Case studies also emphasize several factors that can influence risk of overt disease as a result from early biological perturbations, including background chemical exposures, underlying individual biological processes, and disease susceptibility. Certain effects resulting from exposure during periods of sensitivity may, be irreversible. A chemical can act through multiple modes of action, resulting in similar or different overt effects.
CONCLUSIONS: For certain classes of early perturbations, Sufficient information oil the disease process is known, so hazard and quantitative risk assessment can proceed using information on upstream biological perturbations. Upstream data will Support improved approaches for considering developmental stage, background exposures, disease status, and other factors important to assessing hazard and risk for the whole population.
C1 [Woodruff, Tracey J.; Schwartz, Jackie M.] Univ Calif San Francisco, Dept Obstet & Gynecol, Program Reprod Hlth & Environm, San Francisco, CA 94143 USA.
[Zeise, Lauren; Miller, Mark] Calif Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Oakland, CA USA.
[Axelrad, Daniel A.; Miller, Gregory G.] US EPA, Off Policy Econ & Innovat, Washington, DC 20460 USA.
[Guyton, Kathryn Z.; Euling, Susan Y.; Vandenberg, John] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA.
[Janssen, Sarah; Solomon, Gina] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Janssen, Sarah] Natl Resource Defense Council, San Francisco, CA USA.
[Miller, Mark] Univ San Francisco, Pediat Environm Hlth Specialty Unit, San Francisco, CA 94117 USA.
[Anderson, Henry] Wisconsin Div Publ Hlth, Madison, WI USA.
[Birnbaum, Linda; Crofton, Kevin; Gray, Earl; Luebke, Robert W.] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA.
[Bois, Frederic] Natl Inst Environm Ind & Risques, Verneuil En Halatte, France.
[Cogliano, Vincent James] Int Agcy Res Canc, F-69372 Lyon, France.
[Foster, Paul M. D.; Germolec, Dori R.; Portier, Chris] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Hattis, Dale B.] Clark Univ, George Perkins Marsh Inst, Worcester, MA 01610 USA.
[Kyle, Amy D.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Luster, Michael I.] NIOSH, Atlanta, GA USA.
[Rice, Deborah C.] Maine Ctr Dis Control & Prevent, Environm & Occupat Hlth Program, Augusta, ME USA.
[Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA.
RP Woodruff, TJ (reprint author), Univ Calif San Francisco, Suite 1100,1330 Broadway St, Oakland, CA 94612 USA.
EM woodrufft@obgyn.ucsf.edu
RI Portier, Christopher/A-3160-2010; Bois, Frederic/E-9241-2012; Crofton,
Kevin/J-4798-2015;
OI Portier, Christopher/0000-0002-0954-0279; Bois,
Frederic/0000-0002-4154-0391; Crofton, Kevin/0000-0003-1749-9971;
Vandenberg, John/0000-0003-2619-9460; Miller, Mark/0000-0002-9301-0093;
gray jr, leon earl/0000-0002-1111-4754
FU California Environmental Protection Agency; Office of Environmental and
Health Hazar Assessment [OEHHA-06-S3]; U. S. Environmental Protection
Agency; Office of Policy, Economics, and Innovation; National Center for
Environmental Economics; National Center for Environmental Assessment
[EP07H001060]; National Institute of Environmental Health Sciences
(NIEHS); National Institutes of Health (NIH); University of California,
Berkeley; NIEHS Superfund Program at Berkeley; NIH [P42 ES04705];
University of California, San Francisco
FX This work was supported by California Environmental Protection Agency,
Office of Environmental and Health Hazar Assessment, contract
OEHHA-06-S34; the U. S. Environmental Protection Agency, Office of
Policy, Economics, and Innovation, National Center for Environmental
Economics and National Center for Environmental Assessment, contract
EP07H001060; the Intramural Research Program of the National Institute
of Environmental Health Sciences (NIEHS), National Institutes of Health
(NIH); University of California, Berkeley, NIEHS Superfund Program at
Berkeley, NIH grant P42 ES04705; and University of California, San
Francisco.
NR 56
TC 31
Z9 31
U1 1
U2 9
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV
PY 2008
VL 116
IS 11
BP 1568
EP 1575
DI 10.1289/ehp.11516
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 366ZG
UT WOS:000260521500034
PM 19057713
ER
PT J
AU Hrynkow, SH
AF Hrynkow, Sharon H.
TI Climate Change and Health Research: Time for Teamwork
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
C1 Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
RP Hrynkow, SH (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
EM hrynkows@niehs.nih.gov
NR 2
TC 4
Z9 4
U1 1
U2 2
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV
PY 2008
VL 116
IS 11
BP A470
EP A470
DI 10.1289/ehp.11250
PG 1
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 366ZG
UT WOS:000260521500001
PM 19057678
ER
PT J
AU Mozzachio, AM
Rusiecki, JA
Hoppin, JA
Mahajan, R
Patel, R
Beane-Freeman, L
Alavanja, MCR
AF Mozzachio, Alicia M.
Rusiecki, Jennifer A.
Hoppin, Jane A.
Mahajan, Rajeev
Patel, Rahulkumar
Beane-Freeman, Laura
Alavanja, Michael C. R.
TI Chlorothalonil exposure and cancer incidence among pesticide applicator
participants in the agricultural health study
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Chlorothalonil; Pesticides; Fungicides; Cancer; Agriculture
AB Background: Chlorothalonil is a broad spectrum, non-systemic fungicide widely used to control diseases affecting over 50 fruit, vegetable, and agricultural crops. Despite its extensive use for over 30 years, little is known about the potential human carcinogenicity associated with the routine application of chlorothalonil. Rodent studies have shown evidence of renal tubular carcinomas and adenomas. We explored cancer incidence with chlorothalonil exposure using data from the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina.
Methods: Licensed private and commercial pesticide applicators were recruited into this study from 1993 to 1997. Detailed information regarding pesticide use was obtained via self-administered questionnaires. Cancer incidence was followed through December 31, 2004. Chlorothalonil exposure was classified by lifetime exposure days and intensity-weighted lifetime exposure days, and then categorized into tertiles. The intensity-weighted lifetime exposure days metric was calculated based on a complex algorithm which includes pesticide application methods among other factors. This may increase or decrease exposure.
Results: Of the 47,625 pesticide applicators included in this analysis, 3657 applicators reported using chlorothalonil with a median of 3.5 application days per year. Chlorothalonil was not associated with overall cancer incidence, nor did we find any association with colon, lung, and prostate cancers-the only cancers for which we had sufficient numbers to explore associations.
Conclusion: We did not find any strong evidence for an association between chlorothalonil and the cancers investigated. Although animal studies have suggested renal cancer may be associated with chlorothalonil, we had insufficient data to evaluate this cancer. Published by Elsevier Inc.
C1 [Mozzachio, Alicia M.; Rusiecki, Jennifer A.; Patel, Rahulkumar] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA.
[Hoppin, Jane A.] NIEHS, Dept Hlth & Human Serv, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Mahajan, Rajeev; Beane-Freeman, Laura; Alavanja, Michael C. R.] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Rusiecki, JA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd,PMB A1039, Bethesda, MD 20814 USA.
EM amozzachio@att.net; jrusiecki@usuhs.mil
RI Beane Freeman, Laura/C-4468-2015
OI Beane Freeman, Laura/0000-0003-1294-4124
FU National Institutes of Health; National Institute of Environmental
Health Sciences; National Cancer Institute
FX This work was supported by the intramural research program of the
National Institutes of Health, National Institute of Environmental
Health Sciences and National Cancer Institute.; IRB approvals: All
participants provided verbal informed consent prior to participation in
this study, and the protocol was approved by the institutional review
boards of the National Cancer Institute, Batelle, the University of
Iowa, and Westat. These approvals will be provided upon request.
NR 12
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U2 11
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 NOV
PY 2008
VL 108
IS 3
BP 400
EP 403
DI 10.1016/j.envres.2008.07.018
PG 4
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 368YR
UT WOS:000260660000019
PM 18801479
ER
PT J
AU Hoover, RN
AF Hoover, Robert N.
TI The Sound and the Fury Was It All Worth It?
SO EPIDEMIOLOGY
LA English
DT Editorial Material
ID ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL HORMONE-THERAPY; DISEASE; TRIAL;
WOMEN
AB The initial report of coronary heart disease (CHD) results from the trial of menopausal hormone therapy within the Women's Health Initiative precipitated substantial surprise and concern in the epidemiology research community over the apparent differences between the trial results and those of observational studies. What followed was 6 years of discussion and debate, frequently acrimonious, along with intense methodologic and substantive research attempting to reconcile or explain the apparent differences. The results have been an impressive improvement in methods to contrast and combine studies of differing designs, dramatic illustrations of some central epidemiologic principles, insights into likely mechanisms of CHD, and increasing clarity of the public health message about menopausal hormone therapy.
C1 Natl Canc Inst, Epidemiol & Biostat Program, Div Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Hoover, RN (reprint author), Natl Canc Inst, Epidemiol & Biostat Program, Div Epidemiol & Genet, 6120 Execut Blvd,EPS-8094, Bethesda, MD 20892 USA.
EM hooverr@mail.nih.gov
NR 17
TC 6
Z9 6
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP 780
EP 782
DI 10.1097/EDE.0b013e318188e21d
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IP
UT WOS:000260191700003
PM 18813016
ER
PT J
AU Jukic, AMZ
Weinberg, CR
Baird, DD
Hornsby, PP
Wilcox, AJ
AF Jukic, Anne Marie Zaura
Weinberg, Clarice R.
Baird, Donna D.
Hornsby, Paige P.
Wilcox, Allen J.
TI Measuring Menstrual Discomfort A Comparison of Interview and Diary Data
SO EPIDEMIOLOGY
LA English
DT Article
ID PREMENSTRUAL-SYNDROME; PROSTAGLANDIN F-2ALPHA; PRIMARY DYSMENORRHEA;
CYCLE SYMPTOMS; PAIN; RECALL; MEMORY; WOMEN; DISTRESS; BELIEFS
AB Background: Menstrual discomfort is common among women of reproductive age and can be debilitating. The accuracy of self-report of menstrual discomfort is unknown.
Methods: At enrollment into the DES Reproductive Health Study in 1990, premenopausal women classified their frequency of any menstrual discomfort as "always," "often," "sometimes," and "never." Subsequently, women provided daily diary information for up to 6 months regarding any menstrual discomfort and medication used for menstrual pain.
Results: A total of 324 women contributed data on 4 or more menstrual cycles in the prospective study. At enrollment, 10% had reported never having menstrual discomfort. Of these, 65% recorded at least I day of menstrual discomfort during follow-up. For the 27% who had reported always having discomfort, 88% recorded discomfort in all cycles. The enrollment statement of discomfort was more strongly correlated with the percentage of cycles in which women took medication for menstrual pain; respondents who said they never had menstrual discomfort reported use of pain medication in 3% of cycles; sometimes, 36%; often, 67%; and always, 92%. The average number of days per cycle with prospectively recorded menstrual discomfort was also correlated with the enrollment response.
Conclusions: A single question regarding frequency of menstrual discomfort was positively correlated with prospectively recorded menstrual discomfort and especially with pain requiring medication.
C1 [Jukic, Anne Marie Zaura; Baird, Donna D.; Wilcox, Allen J.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Weinberg, Clarice R.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Jukic, AMZ (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,MD A3-05, Res Triangle Pk, NC 27709 USA.
EM jukica@niehs.nih.gov
RI Baird, Donna/D-5214-2017;
OI Baird, Donna/0000-0002-5544-2653; Wilcox, Allen/0000-0002-3376-1311
FU Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences.
NR 28
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP 846
EP 850
DI 10.1097/EDE.0b013e318187ac9e
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IP
UT WOS:000260191700016
PM 18854711
ER
PT J
AU Adar, SD
Klein, R
Klein, B
Cotch, M
Wong, T
O'Neill, MS
Shrager, S
Siscovick, D
Daviglus, M
Kaufrnan, J
AF Adar, S. D.
Klein, R.
Klein, B.
Cotch, M.
Wong, T.
O'Neill, M. S.
Shrager, S.
Siscovick, D.
Daviglus, M.
Kaufrnan, J.
TI Long-Term Exposures to Air Pollution and Retinal Micro-Vascular Caliber:
The Multi-Ethnic Study of Atherosclerosis (MESA)
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Adar, S. D.; Shrager, S.; Siscovick, D.; Kaufrnan, J.] Univ Washington, Seattle, WA 98195 USA.
[Klein, R.] Univ Wisconsin, Madison, WI USA.
[Cotch, M.] NEI, Bethesda, MD 20892 USA.
[Wong, T.] Univ Melbourne, Melbourne, Vic, Australia.
[Daviglus, M.] Northwestern Univ, Chicago, IL 60611 USA.
RI Adar, Sara/L-2278-2016
OI Adar, Sara/0000-0001-8383-485X
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 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S337
EP S338
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191901405
ER
PT J
AU Alavanja, M
AF Alavanja, M.
TI Cancer Risk Associated with Pesticide Exposure in the Agricultural
Health Study: Introduction and Recent Findings
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Alavanja, M.] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S79
EP S79
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191900243
ER
PT J
AU Bell, EM
Ward, MH
Colt, JS
Nioshioka, MG
Gunier, RB
Riggs, PD
Buffer, PA
Nuckols, JR
AF Bell, E. M.
Ward, M. H.
Colt, J. S.
Nioshioka, M. G.
Gunier, R. B.
Riggs, P. D.
Buffer, P. A.
Nuckols, J. R.
TI Geographic-Based Prediction of Agricultural Pesticide Exposure and
Concentrations in Windowsill Dust
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Bell, E. M.] SUNY Albany, Rensselaer, NY USA.
[Ward, M. H.; Colt, J. S.] NCI, Rockville, MD USA.
[Nioshioka, M. G.] Battelle Mem Inst, Columbus, OH 43201 USA.
[Gunier, R. B.] No Calif Canc Ctr, Berkeley, CA USA.
[Riggs, P. D.; Nuckols, J. R.] Colorado State Univ, Ft Collins, CO 80523 USA.
[Buffer, P. A.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S345
EP S345
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191901425
ER
PT J
AU De Roos, AJ
Davis, S
Colt, JS
Blair, A
Airola, M
Severson, RK
Cozen, W
Cerhan, JR
Hartge, P
Nuckols, JR
Ward, MH
AF De Roos, A. J.
Davis, S.
Colt, J. S.
Blair, A.
Airola, M.
Severson, R. K.
Cozen, W.
Cerhan, J. R.
Hartge, P.
Nuckols, J. R.
Ward, M. H.
TI Residential Proximity to Industrial Facilities and Risk of Non-Hodgkin
Lymphoma
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [De Roos, A. J.; Davis, S.] Univ Washington, Seattle, WA 98195 USA.
[Colt, J. S.; Blair, A.; Airola, M.; Hartge, P.; Ward, M. H.] NCI, Rockville, MD USA.
[Severson, R. K.] Wayne State Univ, Detroit, MI USA.
[Cozen, W.] Univ So Calif, Los Angeles, CA USA.
[Cozen, W.] Mayo Clin, Coll Med, Rochester, MN USA.
[Cozen, W.] Colorado State Univ, Ft Collins, CO 80523 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S181
EP S181
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191900515
ER
PT J
AU Dellarco, M
Viet, S
AF Dellarco, M.
Viet, S.
TI Challenges and Strategies for Exposure Measurement in the National
Children's Study
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Dellarco, M.] NICHD, Natl Childrens Study, Bethesda, MD USA.
[Viet, S.] WESTAT Corp, Rockville, MD 20850 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S47
EP S47
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191900130
ER
PT J
AU Engel, LS
Andersen, A
Barr, DB
Cantor, KP
Chou, J
Hayes, RB
Lan, Q
Langseth, H
Needham, LL
Wacholder, S
Blair, A
Rothman, N
AF Engel, L. S.
Andersen, A.
Barr, D. B.
Cantor, K. P.
Chou, J.
Hayes, R. B.
Lan, Q.
Langseth, H.
Needham, L. L.
Wacholder, S.
Blair, A.
Rothman, N.
TI Serum Concentrations of Organochlorines and Risk of Melanoma: Results of
a Prospective Analysis
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Engel, L. S.; Chou, J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Andersen, A.; Langseth, H.] Canc Registry Norway, Oslo, Norway.
[Barr, D. B.; Needham, L. L.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA.
[Cantor, K. P.; Hayes, R. B.; Lan, Q.; Wacholder, S.; Blair, A.; Rothman, N.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
RI Needham, Larry/E-4930-2011; Barr, Dana/E-6369-2011; Barr,
Dana/E-2276-2013
NR 0
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S195
EP S196
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191901031
ER
PT J
AU Fenton, SE
Mendola, P
Sjodin, A
Patterson, DG
Needham, LL
Hines, EP
AF Fenton, S. E.
Mendola, P.
Sjodin, A.
Patterson, D. G.
Needham, L. L.
Hines, E. P.
TI Brominated Flame Retardant Levels in Human Milk and Serum from MAMA
Study Participants: Preliminary Findings from Correlations over Time and
Matrix, and with Questionnaire Results
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Fenton, S. E.; Hines, E. P.] US EPA, Res Triangle Pk, NC USA.
[Mendola, P.] NICHHD, CDC, Rockville, MD USA.
[Sjodin, A.; Patterson, D. G.; Needham, L. L.] NCEH, DLS, CDC, Atlanta, GA USA.
RI Needham, Larry/E-4930-2011; Sjodin, Andreas/F-2464-2010
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S330
EP S330
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191901385
ER
PT J
AU Fleischman, A
AF Fleischman, A.
TI Practical Considerations of Privacy and Confidentiality: The National
Childrens Study As A Case Study
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Fleischman, A.] NIH, Natl Childrens Study, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S22
EP S23
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191900043
ER
PT J
AU Gunier, RB
Riggs, P
Ward, MH
Reynolds, P
Rull, RP
Hertz, A
Colt, JS
Metayer, C
Nishioka, M
Buffler, PA
Nuckols, JR
AF Gunier, R. B.
Riggs, P.
Ward, M. H.
Reynolds, P.
Rull, R. P.
Hertz, A.
Colt, J. S.
Metayer, C.
Nishioka, M.
Buffler, P. A.
Nuckols, J. R.
TI Proximity to Agricultural Pesticide Use and Concentrations in Carpet
Dust
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Gunier, R. B.; Reynolds, P.; Rull, R. P.; Hertz, A.] No Calif Canc Ctr, Berkeley, CA USA.
[Riggs, P.; Nuckols, J. R.] Colorado State Univ, Ft Collins, CO 80523 USA.
[Ward, M. H.; Colt, J. S.] Natl Canc Inst, Bethesda, MD USA.
[Metayer, C.; Buffler, P. A.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Nishioka, M.] Battelle Mem Inst, Columbus, OH 43201 USA.
RI Rull, Rudolph/B-8121-2013
OI Rull, Rudolph/0000-0003-0989-3629
NR 0
TC 0
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S269
EP S270
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191901225
ER
PT J
AU Hoppin, JA
AF Hoppin, J. A.
TI AHS Exposure Assessment Strategies: Questionnaires, Intensity Metrics,
and Validation Studies
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Hoppin, J. A.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S79
EP S80
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191900244
ER
PT J
AU Kamel, F
AF Kamel, F.
TI Organophosphate Insecticides and Neurologic Dysfunction in the
Agricultural Health Study
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Kamel, F.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S80
EP S80
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191900245
ER
PT J
AU Kan, H
London, SJ
Chen, G
Zhang, Y
Song, G
Jiang, L
Zhao, N
Chen, B
AF Kan, H.
London, S. J.
Chen, G.
Zhang, Y.
Song, G.
Jiang, L.
Zhao, N.
Chen, B.
TI Season, Gender, Age, and Education as Modifiers of the Effects of
Outdoor Air Pollution on Daily Mortality in Shanghai, China: The Public
Health and Air Pollution in Asia (PAPA) Study
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Kan, H.; Zhang, Y.; Zhao, N.; Chen, B.] Fudan Univ, Shanghai 200433, Peoples R China.
[London, S. J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Chen, G.] Shanghai Environm Monitoring Ctr, Shanghai, Peoples R China.
[Song, G.; Jiang, L.] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S92
EP S92
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191900278
ER
PT J
AU Nuckols, JR
Riggs, PD
Gunier, RB
Roll, RP
Bell, EM
Nishioka, M
Hertz, A
Reynolds, P
Buffler, PA
Ward, MH
AF Nuckols, J. R.
Riggs, P. D.
Gunier, R. B.
Roll, R. P.
Bell, E. M.
Nishioka, M.
Hertz, A.
Reynolds, P.
Buffler, P. A.
Ward, M. H.
TI Geographic-Based Prediction of Agricultural Pesticides in Household
Carpet Dust in the Central Valley of California
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Nuckols, J. R.; Riggs, P. D.] Colorado State Univ, Ft Collins, CO 80523 USA.
[Gunier, R. B.; Roll, R. P.; Hertz, A.; Reynolds, P.] No Calif Canc Ctr, Berkeley, CA USA.
[Bell, E. M.] SUNY Albany, Rensselaer, NY USA.
[Nishioka, M.] Battelle Labs, Columbus, OH USA.
[Buffler, P. A.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Ward, M. H.] NCI, Rockville, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S320
EP S320
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191901360
ER
PT J
AU Nuckols, JR
Beane-Freeman, L
Baris, D
Lubin, JH
Ayotte, JDJ
Schwenn, M
Johnson, A
Karagas, M
Colt, J
Silverman, DT
Cantor, KP
AF Nuckols, J. R.
Beane-Freeman, L.
Baris, D.
Lubin, J. H.
Ayotte, J. D. J.
Schwenn, M.
Johnson, A.
Karagas, M.
Colt, J.
Silverman, D. T.
Cantor, K. P.
TI Arsenic Exposure Assessment in the New England Bladder Cancer Study
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Nuckols, J. R.; Beane-Freeman, L.; Baris, D.; Lubin, J. H.; Colt, J.; Silverman, D. T.; Cantor, K. P.] NCI, Bethesda, MD 20892 USA.
[Ayotte, J. D. J.] US Geol Survey, Pembroke, NH USA.
[Schwenn, M.] Maime Canc Registry, Augusta, GA USA.
[Johnson, A.] Vermont Canc Registry, Burlington, VT USA.
[Karagas, M.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA.
RI Beane Freeman, Laura/C-4468-2015
OI Beane Freeman, Laura/0000-0003-1294-4124
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S23
EP S24
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191900046
ER
PT J
AU Rull, RP
Gunier, RB
Reynolds, P
Colt, JS
Nishicka, M
Metayer, C
Buffer, PA
Ward, MH
AF Rull, R. P.
Gunier, R. B.
Reynolds, P.
Colt, J. S.
Nishicka, M.
Metayer, C.
Buffer, P. A.
Ward, M. H.
TI Residential Concentrations of Polycyclic Aromatic Hydrocarbons and
Childhood Leukemia Risk
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Rull, R. P.; Gunier, R. B.; Reynolds, P.] No Calif Canc Ctr, Berkeley, CA USA.
[Colt, J. S.; Ward, M. H.] NCI, Bethesda, MD 20892 USA.
[Nishicka, M.] Battelle Mem Inst, Columbus, OH 43201 USA.
[Metayer, C.; Buffer, P. A.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
RI Rull, Rudolph/B-8121-2013
OI Rull, Rudolph/0000-0003-0989-3629
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S275
EP S275
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191901239
ER
PT J
AU Sandler, DP
AF Sandler, D. P.
TI Remote Data Collection Devices for Exposure Measurement in Large Scale
Epidemiologic Studies
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Sandler, D. P.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S53
EP S53
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191900148
ER
PT J
AU Stefaniak, AB
Virji, M
Day, G
Schuler, C
Tinkle, S
AF Stefaniak, A. B.
Virji, M.
Day, G.
Schuler, C.
Tinkle, S.
TI A Simple Biologically-Based Dynamic Model for Beryllium Sensitization
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Stefaniak, A. B.; Virji, M.; Day, G.; Schuler, C.] NIOSH, Morgantown, WV USA.
[Tinkle, S.] NIEHS, Res Triangle Pk, NC 27709 USA.
RI Stefaniak, Aleksandr/I-3616-2012
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S104
EP S104
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191900310
ER
PT J
AU Von Ehrenstein, OS
Hines, EP
Kato, K
Kuklenyik, Z
Calafat, AM
Fenton, SE
AF Von Ehrenstein, O. S.
Hines, E. P.
Kato, K.
Kuklenyik, Z.
Calafat, A. M.
Fenton, S. E.
TI Perfluoroalkyl Acids in the Serum and Milk of Breastfeeding North
Carolina Women
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Von Ehrenstein, O. S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Hines, E. P.; Fenton, S. E.] US EPA, ORD, NHEERL, RTD, Res Triangle Pk, NC USA.
[Kato, K.; Kuklenyik, Z.; Calafat, A. M.] CDC, Atlanta, GA 30333 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S338
EP S339
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191901407
ER
PT J
AU von Ehrenstein, OS
Sundaram, R
Nansel, T
Gabhainn, SN
Lannotti, RJ
AF von Ehrenstein, O. S.
Sundaram, R.
Nansel, T.
Gabhainn, Nic S.
Lannotti, R. J.
TI Self-reported Child Hunger in Relation to Socioeconomic Status in the US
and Across 36 Countries in the Health Behavior in School-Children Study
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [von Ehrenstein, O. S.; Sundaram, R.; Nansel, T.; Lannotti, R. J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Gabhainn, Nic S.] Natl Univ Ireland, Dept Hlth Promot, Galway, Ireland.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S270
EP S271
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191901228
ER
PT J
AU Ward, MH
Colt, JS
Metayer, C
Gunier, RB
Lubin, J
Nishioka, MG
Reynolds, P
Buffler, PA
AF Ward, M. H.
Colt, J. S.
Metayer, C.
Gunier, R. B.
Lubin, J.
Nishioka, M. G.
Reynolds, P.
Buffler, P. A.
TI Residential Exposure to Polychlorinated Biphenyls and Organochlorine
Pesticides and Risk of Childhood Leukemia
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Ward, M. H.; Colt, J. S.; Lubin, J.] NCI, Bethesda, MD 20892 USA.
[Metayer, C.; Buffler, P. A.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Gunier, R. B.; Reynolds, P.] No Calif Canc Ctr, Berkeley, CA USA.
[Nishioka, M. G.] Battelle Mem Inst, Columbus, OH 43201 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S206
EP S206
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191901060
ER
PT J
AU Weyer, PJ
Kantamneni, JR
Lu, X
Ward, MH
Cerhan, JR
AF Weyer, P. J.
Kantamneni, J. R.
Lu, X.
Ward, M. H.
Cerhan, J. R.
TI Nitrate Ingestion from Drinking Water and Diet and Cancer Risk
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Weyer, P. J.; Kantamneni, J. R.; Lu, X.] Univ Iowa, Ctr Hlth Effects Environm Contaminat, Iowa City, IA USA.
[Ward, M. H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Cerhan, J. R.] Mayo Clin, Coll Med, Rochester, MN USA.
NR 0
TC 2
Z9 2
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S55
EP S55
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191900156
ER
PT J
AU Winseck, K
AF Winseck, K.
TI Community Outreach and Engagement for the National Children's Study
SO EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Conference of the
International-Society-for-Environmental-Epidemiology
CY OCT 12-16, 2008
CL Pasadena, CA
SP Int Soc Environm Epidemiol
C1 [Winseck, K.] NICHD, Natl Childrens Study, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2008
VL 19
IS 6
BP S46
EP S47
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 362IR
UT WOS:000260191900129
ER
PT J
AU Theodore, WH
Epstein, L
Gaillard, WD
Shinnar, S
Wainwright, MS
Jacobson, S
AF Theodore, William H.
Epstein, Leon
Gaillard, William D.
Shinnar, Shlomo
Wainwright, Mark S.
Jacobson, Steven
TI Human herpes virus 6B: A possible role in epilepsy ?
SO EPILEPSIA
LA English
DT Review
DE Human herpes virus; Temporal lobe; Mesial temporal sclerosis; Febrile
seizures; Epilepsy
ID TEMPORAL-LOBE EPILEPSY; HUMAN HERPESVIRUS-6 INFECTION;
CENTRAL-NERVOUS-SYSTEM; POLYMERASE-CHAIN-REACTION; INDUCED
HYPERSENSITIVITY SYNDROME; BONE-MARROW-TRANSPLANTATION;
MULTIPLE-SCLEROSIS PATIENTS; FEBRILE STATUS EPILEPTICUS; STEM-CELL
TRANSPLANTATION; CYTOKINE UP-REGULATION
AB Human herpes virus 6 (HHV6) infection is nearly ubiquitous in childhood and may include central nervous system invasion. There are two variants, HHV6A and HHV6B. Usually asymptomatic, it is associated with the common, self-limited childhood illness roseola infantum and rarely with more severe syndromes. In patients with immune compromise, subsequent reactivation of viral activity may lead to severe limbic encephalitis. HHV6 has been identified as a possible etiologic agent in multiple sclerosis, myocarditis, and encephalitis. A preponderance of evidence supports an association between HHV6 and febrile seizures. An ongoing multicenter study is investigating possible links between HHV6 infection, febrile status epilepticus, and development of mesial temporal sclerosis (MTS). Investigation of temporal lobectomy specimens showed evidence of active HHV6B but not HHV6A replication in hippocampal astrocytes in about two-thirds of patients with MTS but not other causes of epilepsy. It has been suggested that HHV6B may cause "excitotoxicity" by interfering with astrocyte excitatory amino acid transport. Although conventional inflammatory changes are not found in most MTS specimens, inflammatory modulators may play a role in neuronal injury leading to MTS as well. If the link between early viral infection, complex or prolonged febrile seizures, and later development of intractable temporal lobe epilepsy is confirmed, new therapeutic approaches to a common intractable epilepsy syndrome may be possible.
C1 [Theodore, William H.; Gaillard, William D.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
[Epstein, Leon; Wainwright, Mark S.] Northwestern Univ, Feinberg Sch Med, Div Child Neurol, Chicago, IL 60611 USA.
[Gaillard, William D.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Shinnar, Shlomo] Albert Einstein Coll Med, Dept Neurol, New York, NY USA.
[Jacobson, Steven] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD USA.
RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, NIH, Bldg 10,Room 5N-250, Bethesda, MD 20892 USA.
EM theodorw@ninds.nih.gov
FU NINDS [NS 43209]
FX This work was supported by the NINDS Division of Intramural Research (to
W. D. G., S. J., and W. H. T.) and NINDS NS 43209 (to L. E. and S. S.).
We thank Jenny Ahlqvist and the NINDS EM facility for Figure 2.
NR 115
TC 57
Z9 58
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD NOV
PY 2008
VL 49
IS 11
BP 1828
EP 1837
DI 10.1111/j.1528-1167.2008.01699.x
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA 370DZ
UT WOS:000260744200002
PM 18627418
ER
PT J
AU Mayer, AMS
Gustafson, KR
AF Mayer, Alejandro M. S.
Gustafson, Kirk R.
TI Marine pharmacology in 2005-2006: Antitumour and cytotoxic compounds
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Review
DE Marine; Antitumour; Drugs; Agents; Antineoplastic; Cancer; Chemotherapy;
Pharmacology; Review; Screening
ID ADVANCED SOLID TUMORS; NEW-GUINEA COLLECTION; MULTICENTER PHASE-II;
SOFT-TISSUE SARCOMAS; CYANOBACTERIUM LYNGBYA-MAJUSCULA; CUCUMBER
PENTACTA-QUADRANGULARIS; SULFATED TRITERPENE GLYCOSIDES;
ENDOPLASMIC-RETICULUM STRESS; SPONGE THEONELLA-SWINHOEI; ADVANCED
BREAST-CANCER
AB During 2005 and 2006, marine pharmacology research directed towards the discovery and development of novel antitumour agents was reported in 171 peer-reviewed articles. The purpose of this article is to present a structured review of the antitumour and cytotoxic properties of 136 marine natural products, many of which are novel compounds that belong to diverse structural classes, including polyketides, terpenes, steroids and peptides. The organisms yielding these bioactive marine compounds included invertebrate animals, algae, fungi and bacteria. Antitumour pharmacological studies were conducted with 42 structurally defined marine natural products in a number of experimental and clinical models which further defined their mechanisms of action. Particularly potent in vitro cytotoxicity data generated with murine and human tumour cell lines were reported for 94 novel marine chemicals with as yet undetermined mechanisms of action. Noteworthy is the fact that marine anticancer research was sustained by a global collaborative effort, involving researchers from Australia, Belgium, Benin, Brazil, Canada, China, Egypt, France, Germany, India, Indonesia, Italy, Japan, Mexico, the Netherlands, New Zealand, Panama, the Philippines, Slovenia, South Korea, Spain, Sweden, Taiwan, Thailand, United Kingdom (UK) and the United States of America (USA). Finally, this 2005-2006 overview of the marine pharmacology literature highlights the fact that the discovery of novel marine antitumour agents continued at the same active pace as during 1998-2004. (C) 2008 Elsevier Ltd. All rights reserved,
C1 [Mayer, Alejandro M. S.] Midwestern Univ, Chicago Coll Osteopath Med, Dept Pharmacol, Downers Grove, IL 60515 USA.
[Gustafson, Kirk R.] NCI Frederick, Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21702 USA.
RP Mayer, AMS (reprint author), Midwestern Univ, Chicago Coll Osteopath Med, Dept Pharmacol, 555 31st St, Downers Grove, IL 60515 USA.
EM amayer@midwestern.edu
OI Mayer, Alejandro /0000-0002-8358-4528
FU NIH; National Cancer Institute; Center for Cancer Research; Midwestern
University's office of Research and Sponsored Programs
FX This publication was supported in part by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research. Additional support to AMSM from Midwestern University's office
of Research and Sponsored Programs is gratefully acknowledged. The
excellent support for literature searches and article retrieval by
library staff members as well as medical and pharmacy students of
Midwestern University is most gratefully recognised. The authors wish to
specially thank Mrs. Victoria Sears and Ms. Mary Hall for careful and
dedicated assistance in the preparation of this manuscript.
NR 174
TC 69
Z9 72
U1 5
U2 31
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2008
VL 44
IS 16
BP 2357
EP 2387
DI 10.1016/j.ejca.2008.07.001
PG 31
WC Oncology
SC Oncology
GA 376ZM
UT WOS:000261221500011
PM 18701274
ER
PT J
AU Blumenthal, GM
Dennis, PA
AF Blumenthal, Gideon M.
Dennis, Phillip A.
TI PTEN hamartoma tumor syndromes
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID RILEY-RUVALCABA-SYNDROME; BANNAYAN-ZONANA-SYNDROME;
LHERMITTE-DUCLOS-DISEASE; SYNDROME PLEASE STAND; COWDEN-SYNDROME;
BREAST-CANCER; PROTEUS-SYNDROME; SUPPRESSOR PTEN; GERMLINE MUTATION;
PHOSPHOINOSITOL-3-KINASE/AKT PATHWAY
AB The PTEN hamartoma tumor syndromes (PHTS) are a collection of rare clinical syndromes characterized by germline mutations of the tumor suppressor PTEN. These syndromes are driven by cellular overgrowth, leading to benign hamartomas in virtually any organ. Cowden syndrome (CS), the prototypic PHTS syndrome, is associated with increased susceptibility to breast, thyroid, and endometrial cancer. PTEN is located on chromosome 10q22-23 and negatively regulates the prosurvival PI3K/Akt/mTOR pathway through its lipid phosphatase activity. Loss of PTEN activates this pathway and leads to increased cellular growth, migration, proliferation, and survival. Clinical management of patients with PHTS, particularly those with CS, should include early and frequent screening, surveillance, and preventive care for associated malignancies. Concomitant with improved understanding of the biology of PTEN and the PI3K/Akt/mTOR pathway, inhibitors of this pathway are being developed as anticancer agents. These medications could have applications for patients with PHTS, for whom no medical options currently exist.
C1 [Dennis, Phillip A.] NCI, Signal Transduct Sect, Navy Med Oncol, Med Oncol Branch,Ctr Canc Res, Bethesda, MD 20889 USA.
RP Dennis, PA (reprint author), NCI, Signal Transduct Sect, Navy Med Oncol, Med Oncol Branch,Ctr Canc Res, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA.
EM pdennis@nih.gov
NR 77
TC 99
Z9 102
U1 1
U2 5
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 NOV
PY 2008
VL 16
IS 11
BP 1289
EP 1300
DI 10.1038/ejhg.2008.162
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 363JL
UT WOS:000260263500001
PM 18781191
ER
PT J
AU Wolf, RC
Sambataro, F
Vasic, N
Schonfeldt-Lecuona, C
Ecker, D
Landwehrmeyer, B
AF Wolf, R. C.
Sambataro, F.
Vasic, N.
Schoenfeldt-Lecuona, C.
Ecker, D.
Landwehrmeyer, B.
TI Altered frontostriatal coupling in pre-manifest Huntington's disease:
effects of increasing cognitive load
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Article
DE cognition; Huntington's disease; prefrontal cortex; pre-symptomatic;
psychophysiological interactions
ID WORKING-MEMORY; BASAL GANGLIA; GLUCOSE CONSUMPTION; PREFRONTAL CORTEX;
BLOOD-FLOW; FMRI; DYSFUNCTION; PET; MORPHOMETRY; DEPRESSION
AB Background and purpose: Functional neuroimaging studies have suggested a dysfunction of prefrontal regions in clinically pre-symptomatic individuals with the Huntington's disease (HD) gene mutation (pre-HD) during cognitive processing. The objective of this study was to test the impact of cognitive demand on prefrontal connectivity in pre-HD individuals. Methods: Sixteen healthy controls and sixteen pre-HD subjects were studied using functional MRI and a verbal working memory task with increasing cognitive load. Load-dependent functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) was investigated by means of psychophysiological interactions. Results: In pre-HD subjects, aberrant functional connectivity of the left DLPFC was found at high working memory load levels only. Compared with healthy controls, pre-HD individuals exhibited lower connectivity strength in the left putamen, the right anterior cingulate and the left medial prefrontal cortex. Pre-HD individuals close to the onset of motor symptoms additionally exhibited lower connectivity strength in the right putamen and the left superior frontal cortex. The connectivity strength in the left putamen was associated with several clinical measures including CAG repeat length, Unified Huntington's Disease Rating Scale motor score and predicted years to manifest symptom onset. Conclusion: These findings suggest that early prefrontal connectivity abnormalities in pre-HD individuals are modulated by cognitive demand.
C1 [Wolf, R. C.; Vasic, N.; Schoenfeldt-Lecuona, C.] Univ Ulm, Dept Psychiat & Psychotherapy 3, D-89075 Ulm, Germany.
[Sambataro, F.] NIMH, Clin Brain Disorders Branch, Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Ecker, D.; Landwehrmeyer, B.] Univ Ulm, Dept Neurol, D-89075 Ulm, Germany.
RP Wolf, RC (reprint author), Univ Ulm, Dept Psychiat & Psychotherapy 3, Leimgrubenweg 12-14, D-89075 Ulm, Germany.
EM christian.wolf@uni-ulm.de
RI Sambataro, Fabio/E-3426-2010;
OI Sambataro, Fabio/0000-0003-2102-416X; Landwehrmeyer, Georg
Bernhard/0000-0003-3375-790X
FU Clinical Brain Disorders Branch, National Institute of Mental Health,
NIH, Bethesda, MD; European Huntington's Disease Network (EHDN)
FX The authors would like to thank Georg Gron ( Department of Psychiatry
III, Ulm) for valuable comments during data evaluation and Qiang Chen
(Clinical Brain Disorders Branch, National Institute of Mental Health,
NIH, Bethesda, MD) for technical support with the PPI analysis. We are
grateful to Beate Englet and Sebastian Satzinger for their assistance
with data collection. This study was supported by the European
Huntington's Disease Network (EHDN).
NR 51
TC 41
Z9 41
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1351-5101
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD NOV
PY 2008
VL 15
IS 11
BP 1180
EP 1190
DI 10.1111/j.1468-1331.2008.02253.x
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 357BR
UT WOS:000259821800012
PM 18754766
ER
PT J
AU Di Giorgio, A
Blasi, G
Sambataro, F
Rampino, A
Papazacharias, A
Gambi, F
Romano, R
Caforio, G
Rizzo, M
Latorre, V
Popolizio, T
Kolachana, B
Callicott, JH
Nardini, M
Weinberger, DR
Bertolino, A
AF Di Giorgio, Annabella
Blasi, Giuseppe
Sambataro, Fabio
Rampino, Antonio
Papazacharias, Apostolos
Gambi, Francesco
Romano, Raffaella
Caforio, Grazia
Rizzo, Miriam
Latorre, Valeria
Popolizio, Teresa
Kolachana, Bhaskar
Callicott, Joseph H.
Nardini, Marcello
Weinberger, Daniel R.
Bertolino, Alessandro
TI Association of the Ser(704)Cys DISC1 polymorphism with human hippocampal
formation gray matter and function during memory encoding
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE DISC1; fMRI; gray matter; hippocampus; memory encoding; phenotypic
variance
ID MEDIAL TEMPORAL-LOBE; PREFRONTAL CORTEX; NEURITE OUTGROWTH;
NUCLEUS-ACCUMBENS; CEREBRAL-CORTEX; RHESUS-MONKEY; ADULT RATS;
SCHIZOPHRENIA; DISRUPTED-IN-SCHIZOPHRENIA-1; BINDING
AB A common nonsynonymous single nucleotide polymorphism leading to a serine-to-cysteine substitution at amino acid 704 (Ser(704)Cys) in the DISC1 protein sequence has been recently associated with schizophrenia and with specific hippocampal abnormalities. Here, we used multimodal neuroimaging to investigate in a large sample of healthy subjects the putative association of the Ser(704)Cys DISC1 polymorphism with in vivo brain phenotypes including hippocampal formation (HF) gray matter volume and function (as assessed with functional MRI) as well as HF functional coupling with the neural network engaged during encoding of recognition memory. Individuals homozygous for DISC1 Ser allele relative to carriers of the Cys allele showed greater gray matter volume in the HF. Further, Ser/Ser subjects exhibited greater engagement of the HF together with greater HF-dorsolateral prefrontal cortex functional coupling during memory encoding, in spite of similar behavioral performance. These findings consistently support the notion that Ser(704)Cys DISC1 polymorphism is physiologically relevant. Moreover, they support the hypothesis that genetic variation in DISC1 may affect the risk for schizophrenia by modifying hippocampal gray matter and function.
C1 [Di Giorgio, Annabella; Blasi, Giuseppe; Sambataro, Fabio; Rampino, Antonio; Papazacharias, Apostolos; Gambi, Francesco; Romano, Raffaella; Caforio, Grazia; Rizzo, Miriam; Latorre, Valeria; Nardini, Marcello; Bertolino, Alessandro] Univ Bari, Psychiat Neurosci Grp, Sect Mental Disorders, Dept Neurol & Psychiat Sci, I-70124 Bari, Italy.
[Sambataro, Fabio; Kolachana, Bhaskar; Callicott, Joseph H.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Popolizio, Teresa; Bertolino, Alessandro] IRCCSS Casa Sollievo Sofferenza, Dept Neuroradiol, San Giovanni Rotondo, Italy.
RP Bertolino, A (reprint author), Univ Bari, Psychiat Neurosci Grp, Sect Mental Disorders, Dept Neurol & Psychiat Sci, Piazza Giulio Cesare 9, I-70124 Bari, Italy.
EM a.bertolino@psichiat.uniba.it
RI Sambataro, Fabio/E-3426-2010; Callicott, Joseph/C-9102-2009; Bertolino,
Alessandro/O-6352-2016; Rampino, Antonio/Q-4465-2016; Di Giorgio,
Annabella /D-7353-2017;
OI Sambataro, Fabio/0000-0003-2102-416X; Callicott,
Joseph/0000-0003-1298-3334; Bertolino, Alessandro/0000-0002-1251-1380;
Rampino, Antonio/0000-0002-9654-3266; Di Giorgio, Annabella
/0000-0001-7876-3495; Papazacharias, Apostolos/0000-0001-5470-1601
FU Intramural NIH HHS [Z01 MH002734-12]
NR 48
TC 54
Z9 54
U1 0
U2 2
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 NOV
PY 2008
VL 28
IS 10
BP 2129
EP 2136
DI 10.1111/j.1460-9568.2008.06482.x
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 371HQ
UT WOS:000260822800018
PM 19046394
ER
PT J
AU Fejzo, MS
Ingles, SA
Wilson, M
Wang, W
MacGibbon, K
Romero, R
Goodwin, TM
AF Fejzo, Marlena S.
Ingles, Sue Ann
Wilson, Melissa
Wang, Wei
MacGibbon, Kimber
Romero, Roberto
Goodwin, Thomas M.
TI High prevalence of severe nausea and vomiting of pregnancy and
hyperemesis gravidarum among relatives of affected individuals
SO EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY
LA English
DT Article
DE Hyperemesis gravidarum; Nausea; Vomiting; Pregnancy; Genetic
ID THYROTROPIN RECEPTOR; EPIDEMIOLOGY; POPULATION; EXPOSURE; OUTCOMES;
DISEASE; RISK
AB Objective: The goal of this study was to determine the prevalence of severe nausea and vomiting of pregnancy/hyperemesis gravidarum among relatives of affected individuals.
Study design: Family history data were obtained on 1224 self-reported cases of hyperemesis gravidarum. Cases completed an online survey administered by the Hyperemesis Education and Research Foundation between 2003 and 2006.
Results: Approximately 28% of cases reported their mother had severe nausea and vomiting or hyperemesis gravidarum while pregnant with them. Of the 721 sisters with a pregnancy history, 137 (19%) had hyperemesis gravidarum. Among the most severe cases, those requiring total parenteral nutrition or nasogastric feeding tube, the proportion of affected sisters was even higher, 49/198 (25%). Nine percent of cases reported having at least two affected relatives including sister(s), mother, grandmother, daughters, aunt(s), and cousin(s).
Conclusion: There is a high prevalence of severe nausea and vomiting of pregnancy/hyperemesis gravidarum among relatives of hyperemesis gravidarum cases in this study population. Because the incidence of hyperemesis gravidarum is most commonly reported to be 0.5%, this study provides strong but preliminary evidence for a genetic component to extreme nausea and vomiting of pregnancy. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Fejzo, Marlena S.; Wilson, Melissa; Wang, Wei; Goodwin, Thomas M.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
[Ingles, Sue Ann; Wilson, Melissa; Wang, Wei] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[MacGibbon, Kimber] Hyperemesis Educ & Res Fdn, Leesburg, VA USA.
[Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA.
RP Fejzo, MS (reprint author), 5535 MRL,675 Charles E Young Dr S, Los Angeles, CA 90095 USA.
EM mfejzo@mednet.ucla.edu
OI MacGibbon, Kimber/0000-0002-6534-3114
FU Intramural Research Program of the National Institute of Child Health
and Human Development; NIH; DHHS
FX We thank Dr. Frederic Paik Schoenberg, UCLA Department of Statistics,
for his valuable contribution to the creation and implementation of the
original survey instrument. This research was supported (in part) by the
Intramural Research Program of the National Institute of Child Health
and Human Development, NIH, DHHS.
NR 32
TC 27
Z9 28
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-2115
J9 EUR J OBSTET GYN R B
JI Eur. J. Obstet. Gynecol. Reprod. Biol.
PD NOV
PY 2008
VL 141
IS 1
BP 13
EP 17
DI 10.1016/j.ejogrb.2008.07.003
PG 5
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 378CD
UT WOS:000261297800004
PM 18752885
ER
PT J
AU Loeb, S
Kettermann, A
Ferrucci, L
Landis, P
Metter, EJ
Carter, HB
AF Loeb, Stacy
Kettermann, Anna
Ferrucci, Luigi
Landis, Patricia
Metter, E. Jeffrey
Carter, H. Ballentine
TI PSA Doubling Time Versus PSA Velocity to Predict High-Risk Prostate
Cancer: Data from the Baltimore Longitudinal Study of Aging
SO EUROPEAN UROLOGY
LA English
DT Article
DE PSA kinetics; PSA doubling time; PSA velocity; Prostate cancer;
Prognosis
ID RADICAL PROSTATECTOMY; BIOCHEMICAL RECURRENCE; RADIATION-THERAPY;
ANTIGEN VELOCITY; MORTALITY; DEATH; AREAS; MEN
AB Background: Our group has previously shown that prostate-specific antigen (PSA) velocity (PSAV) is associated with the presence of life-threatening prostate cancer. Less is known about the relative utility of pretreatment PSA doubling time (PSA DT) to predict tumor aggressiveness.
Objective: To compare the utility of PSAV and PSA DT for the prediction of life-threatening prostate cancer.
Design, setting, and participants: From the Baltimore Longitudinal Study of Aging, we identified 681 men with serial PSA measurements.
Measurements: Receiver operating characteristic analysis was used to evaluate the relationship between PSAV, PSA DT, and the presence of high-risk disease.
Results and limitations: Within the period of 5 yr prior to diagnosis, PSAV was significantly higher among men with high-risk or fatal prostate cancer than men without it. By contrast, PSA DT was not significantly associated with high-risk or fatal disease. On multivariate analysis, including age, date of diagnosis, and PSA, the addition of PSAV significantly improved the concordance index from 0.85 to 0.88 (p < 0.001), whereas PSA DT did not.
Conclusions: These data suggest that PSAV is more useful than PSA DT in the pretreatment setting to help identify those men with life-threatening disease. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.
C1 [Loeb, Stacy; Kettermann, Anna; Landis, Patricia; Carter, H. Ballentine] Johns Hopkins Univ, Sch Med, Dept Urol, James Buchanan Brady Urol Inst,Johns Hopkins Hosp, Baltimore, MD 21205 USA.
[Ferrucci, Luigi; Metter, E. Jeffrey] NIA, NIH, Clin Res Branch, Baltimore, MD 21224 USA.
RP Loeb, S (reprint author), Johns Hopkins Sch Med, Dept Urol, Marburg 100,600 N Wolfe St, Baltimore, MD 21287 USA.
EM stacyloeb@gmail.com
OI Loeb, Stacy/0000-0003-3933-9207
FU US National Institutes of Health; National institute on Aging
FX This research was supported by the Intramural Research Program of the US
National Institutes of Health, National institute on Aging.
NR 18
TC 32
Z9 33
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD NOV
PY 2008
VL 54
IS 5
BP 1073
EP 1080
DI 10.1016/j.eururo.2008.06.076
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 368YO
UT WOS:000260659600013
PM 18614274
ER
PT J
AU Di Lorenzo, G
Figg, WD
Fossa, SD
Mirone, V
Autorino, R
Longo, N
Imbimbo, C
Perdona, S
Giordano, A
Giuliano, M
Labianca, R
De Placido, S
AF Di Lorenzo, Giuseppe
Figg, William D.
Fossa, Sophie D.
Mirone, Vincenzo
Autorino, Riccardo
Longo, Nicola
Imbimbo, Ciro
Perdona, Sisto
Giordano, Antonio
Giuliano, Mario
Labianca, Roberto
De Placido, Sabino
TI Combination of Bevacizumab and Docetaxel in Docetaxel-Pretreated
Hormone-Refractory Prostate Cancer: A Phase 2 Study
SO EUROPEAN UROLOGY
LA English
DT Article
DE Bevacizumab; Chemotherapy; Docetaxel; Hormone-refractory; prostate
cancer
ID METASTATIC COLORECTAL-CANCER; ENDOTHELIAL GROWTH-FACTOR; II TRIAL;
CHEMOTHERAPY; MITOXANTRONE; THALIDOMIDE; PREDNISONE
AB Objective: Although the taxanes represent the most active agents for the first-line treatment of metastatic hormone-refractory prostate cancer (HRPC), most patients eventually progress while receiving taxane-based treatments. No agents are approved for second-line therapy in HRPC, but common standard practice for the oncologists is to treat patients also after docetaxel failure.
Methods: Twenty highly pretreated patients with HRPC received bevacizumab (10 mg/kg) and docetaxel (60 mg/m(2)) every 3 wk, All patients had bone metastases and eight had measurable lesions.
Results: Eleven patients (55%) had major prostate-specific antigen (PSA) responses, and 3 (37.5%) had objective responses. Seven major PSA responses were recorded in the same patients who had reported a >50% PSA decrease after first-line docetaxel. However, four major PSA responses were observed in patients previously nonresponsive to docetaxel alone. The treatment was well tolerated.
Conclusions: Our results show that the combination of bevacizumab and docetaxel is active and well tolerated. Continued investigation of bevacizumab with cytotoxic chemotherapy is warranted in HRPC. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.
C1 [Di Lorenzo, Giuseppe; Giordano, Antonio; Giuliano, Mario; De Placido, Sabino] Univ Naples Federico 2, Dept Clin & Mol Oncol, Naples, Italy.
[Figg, William D.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Fossa, Sophie D.] Univ Oslo, Rikshosp, Canc Clin, N-0316 Oslo, Norway.
[Mirone, Vincenzo; Longo, Nicola; Imbimbo, Ciro] Univ Naples Federico 2, Urol Clin, Naples, Italy.
[Autorino, Riccardo] Seconda Univ, Urol Clin, Naples, Italy.
[Perdona, Sisto] Fdn G Pascale IRCSS Napoli, Ist Nazl Tumori, UO Urol, Naples, Italy.
[Labianca, Roberto] Osped Riuniti Bergamo, Oncol Sect, I-24100 Bergamo, Italy.
RP Di Lorenzo, G (reprint author), Univ Naples Federico 2, Dept Clin & Mol Oncol, Naples, Italy.
EM giuseppedilorenzoncol@hotmail.com
RI Figg Sr, William/M-2411-2016; Labianca, Roberto/N-1847-2016;
OI Labianca, Roberto/0000-0001-7149-822X; MIRONE,
Vincenzo/0000-0002-7639-2560
NR 22
TC 88
Z9 88
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD NOV
PY 2008
VL 54
IS 5
BP 1089
EP 1096
DI 10.1016/j.eururo.2008.01.082
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 368YO
UT WOS:000260659600015
PM 18276061
ER
PT J
AU Yamaguchi, Y
Coelho, SG
Zmudzka, BZ
Takahashi, K
Beer, JZ
Hearing, VJ
Miller, SA
AF Yamaguchi, Yuji
Coelho, Sergio G.
Zmudzka, Barbara Z.
Takahashi, Kaoruko
Beer, Janusz Z.
Hearing, Vincent J.
Miller, Sharon A.
TI Cyclobutane pyrimidine dimer formation and p53 production in human skin
after repeated UV irradiation
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Article
DE apoptosis; p53; pigmentation; skin cancer; UV
ID DNA-DAMAGE; ULTRAVIOLET-RADIATION; TANNING DEVICES; MELANIN CONTENT;
HUMAN EPIDERMIS; BASAL-CELL; IN-VIVO; EXPOSURE; RISK; RESPONSES
AB Substantial differences in DNA damage caused by a single UV irradiation were found in our previous study on skin with different levels of constitutive pigmentation. In this study, we assessed whether facultative pigmentation induced by repeated UV irradiation is photoprotective. Three sites on the backs of 21 healthy subjects with type II-III skin were irradiated at 100-600 J/m(2) every 2-7 days over a 4- to 5-week period. The three sites received different cumulative doses of UV (1900, 2900 or 4200 J/m(2)) and were biopsied 1 day after the last irradiation. Biomarkers examined included pigment content assessed by Fontana-Masson staining, melanocyte function by expression of melanocyte-specific markers, DNA damage as cyclobutane pyrimidine dimers (CPD), nuclear accumulation of p53, apoptosis determined by TUNEL assay, and levels of p21 and Ser46-phosphorylated p53. Increases in melanocyte function and density, and in levels of apoptosis were similar among the 3 study sites irradiated with different cumulative UV doses. Levels of CPD decreased while the number of p53-positive cells increased as the cumulative dose of UV increased. These results suggest that pigmentation induced in skin by repeated UV irradiation protects against subsequent UV-induced DNA damage but not as effectively as constitutive pigmentation.
C1 [Yamaguchi, Yuji; Coelho, Sergio G.; Takahashi, Kaoruko; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Coelho, Sergio G.; Zmudzka, Barbara Z.; Beer, Janusz Z.; Miller, Sharon A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,room 2132,MSC 4256, Bethesda, MD 20892 USA.
EM hearingv@nih.gov
FU Office of Science and the Center for Devices and Radiological Health;
Food and Drug Administration (FDA); NIH; Ministry of Education, Culture,
Sports, and Technology of Japan; FDA Office of Women's Health
FX This research was supported by the Office of Science and the Center for
Devices and Radiological Health, Food and Drug Administration (FDA), by
the Intramural Research Program of the National Cancer Institute at NIH,
by a grant-in-aid from the Ministry of Education, Culture, Sports, and
Technology of Japan, and by the FDA Office of Women's Health. The
opinions and conclusions stated in this paper are those of the authors
and do not represent the official position of the U. S. Department of
Health and Human Services. The mention of commercial products, their
sources, or their use in connection with material reported herein is not
to be construed as either an actual or implied endorsement of such
products by the U. S. Department of Health and Human Services.
NR 41
TC 23
Z9 23
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD NOV
PY 2008
VL 17
IS 11
BP 916
EP 924
DI 10.1111/j.1600-0625.2008.00722.x
PG 9
WC Dermatology
SC Dermatology
GA 358RV
UT WOS:000259936100003
PM 18363705
ER
PT J
AU Klitten, LL
Rath, MF
Coon, SL
Kim, JS
Klein, DC
Moller, M
AF Klitten, Laura L.
Rath, Martin F.
Coon, Steven L.
Kim, Jong-So
Klein, David C.
Moller, Morten
TI Localization and regulation of dopamine receptor D4 expression in the
adult and developing rat retina
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE retina; diurnal rhythm; dopamine; Drd4; development; triiodothyronine
ID SEROTONIN N-ACETYLTRANSFERASE; MT1 MELATONIN RECEPTOR; PINEAL-GLAND;
CIRCADIAN CLOCK; PHOTORECEPTOR CELLS; CHICK RETINA; AMPHIBIAN RETINA;
MAMMALIAN RETINA; GENE-EXPRESSION; AMACRINE CELLS
AB Levels of dopamine and melatonin exhibit diurnal rhythms in the rat retina. Dopamine is high during daytime adapting the retina to light, whereas melatonin is high during nighttime participating in the adaptation of the retina to low light intensities. Dopamine inhibits the synthesis of melatonin in the photoreceptors via Drd4 receptors located on the cell membrane of these cells. In this study, we show by semiquantitative in situ hybridization a prominent day/night variation in Drd4 expression in the retina of the Sprague-Dawley rat with a peak during the nighttime. Drd4 expression is seen in all retinal layers but the nocturnal increase is confined to the photoreceptors. Retinal Drd4 expression is not affected by removal of the sympathetic input to the eye, but triiodothyronine treatment induces Drd4 expression in the photoreceptors. In a developmental series, we show that the expression of Drd4 is restricted to postnatal stages with a peak at postnatal day 12. The high Drd4 expression in the rat retinal photoreceptors during the night supports physiological and pharmacologic evidence that the Drd4 receptor is involved in the dopaminergic inhibition of melatonin synthesis upon light stimulation. The sharp increase of Drd4 expression at a specific postnatal time suggests that dopamine is involved in retinal development. (c) 2008 Elsevier Ltd. All rights reserved.
C1 [Klitten, Laura L.; Rath, Martin F.; Moller, Morten] Univ Copenhagen, Dept Neurosci & Pharmacol, Panum Inst, DK-2200 Copenhagen, Denmark.
[Coon, Steven L.; Kim, Jong-So; Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Moller, M (reprint author), Univ Copenhagen, Dept Neurosci & Pharmacol, Panum Inst 24 3 43, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
EM morm@sund.ku.dk
OI Rath, Martin/0000-0002-4047-6324
FU Lundbeck Foundation; Danish Medical Research Council [271-06-0754]; Novo
Nordisk Foundation; Carlsberg Foundation; Simon Fougner Hartmann's
Family Foundation; Division of Intramural Research of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development; NIH
FX This study was supported by the Lundbeck Foundation, the Danish Medical
Research Council (grant number 271-06-0754), the Novo Nordisk
Foundation, the Carlsberg Foundation, the Simon Fougner Hartmann's
Family Foundation, the Division of Intramural Research of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH. We wish to thank Mrs. Ursula Rentzmann for expert
histological assistance.
NR 59
TC 26
Z9 26
U1 1
U2 5
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2008
VL 87
IS 5
BP 471
EP 477
DI 10.1016/j.exer.2008.08.004
PG 7
WC Ophthalmology
SC Ophthalmology
GA 374CT
UT WOS:000261020700010
PM 18778704
ER
PT J
AU Huey, ED
Armstrong, N
Momeni, P
Grafman, J
AF Huey, Edward D.
Armstrong, Nicole
Momeni, Parastoo
Grafman, Jordan
TI Challenges and new opportunities in the investigation of new drug
therapies to treat frontotemporal dementia
SO EXPERT OPINION ON THERAPEUTIC TARGETS
LA English
DT Review
DE frontotemporal dementia; medication treatment; neurodegenerative
disorders; neuroprotection
ID AMYOTROPHIC-LATERAL-SCLEROSIS; PROGRANULIN MUTATION CARRIERS; PRIMARY
PROGRESSIVE APHASIA; LOBAR DEGENERATION; ALZHEIMERS-DISEASE; TAU GENE;
BEHAVIORAL-CHARACTERISTICS; FTDP-17 MUTATIONS; SEMANTIC DEMENTIA;
TEMPORAL VARIANT
AB Background: Frontotemporal dementia spectrum disorders are a set of neurodegenerative disorders affecting the frontal and anterior temporal lobes. They are often fatal, and currently no medications have been shown to slow their progression. Recent developments in understanding these disorders may aid in developing treatments. Objective: To discuss the development of drug therapies for frontotemporal dementia spectrum disorders, both those under current investigation and those that could be targets for future investigation. Methods: This review is divided into four sections: First, a brief review of frontotemporal dementia spectrum disorders; second, a discussion of the challenges in the development of drug therapies third, a review of the current clinical trials; and finally a discussion of some recent discoveries, which have sparked new areas of investigation. Conclusions: Hopefully, advances in understanding of frontotemporal dementia spectrum disorders and clinical trial design will aid the development of new treatments.
C1 [Huey, Edward D.; Armstrong, Nicole; Grafman, Jordan] NINDS, NIH, Cognit Neurosci Sect, Bethesda, MD 20892 USA.
[Huey, Edward D.; Armstrong, Nicole] Lirwin Zucker Ctr Res Alzheimers Dis, Manhasset, NY 11030 USA.
[Momeni, Parastoo] Texas Tech Univ, Hlth Sci Ctr, Dept Neurol, Lubbock, TX 79430 USA.
RP Huey, ED (reprint author), NINDS, NIH, Cognit Neurosci Sect, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA.
EM hueye@ninds.nih.gov
OI Grafman, Jordan H./0000-0001-8645-4457
FU National Institutes of Health/The National Institute of Neurological
Disorders and Stroke
FX This study was supported by the intramural program of The National
Institutes of Health/The National Institute of Neurological Disorders
and Stroke.
NR 110
TC 6
Z9 6
U1 1
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1472-8222
J9 EXPERT OPIN THER TAR
JI Expert Opin. Ther. Targets
PD NOV
PY 2008
VL 12
IS 11
BP 1367
EP 1376
DI 10.1517/14728220802482148
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 368JT
UT WOS:000260618100005
PM 18851693
ER
PT J
AU Archer, TK
AF Archer, Trevor K.
TI Chromatin-modifying enzymes as therapeutic targets - Part 2
SO EXPERT OPINION ON THERAPEUTIC TARGETS
LA English
DT Review
DE chromatin; chromatin-modifying enzymes; epigenetics; histones;
nucleosome remodelling; phosphorylation; ribosylation; SUMOylation;
ubiquitylation
ID MITOTIC CHROMOSOME CONDENSATION; HISTONE H3 PHOSPHORYLATION; PROTEIN
TRIPLE KINASE; EARLY GENE INDUCTION; AURORA KINASES; POLY(ADP-RIBOSE)
POLYMERASE; TRANSCRIPTIONAL ELONGATION; MOUSE FIBROBLASTS;
ADP-RIBOSYLATION; CANCER-THERAPY
AB Background: Part 1 of this review described the importance of histone acetylases, cleacetylases, methylases and demethylases in transcriptional control and their potential as therapeutic targets. However precise gene regulation requires the involvement of more than just the addition or removal of acetyl and methyl groups on histories. Histone phosphorylation, ubiquitylation, SUMOylation and poly-ADP-ribosylation, as well as ATP-dependent nucleosome remodeling complexes, play equally pivotal roles in the maintenance of transcriptional fidelity. Accordingly, the enzymes responsible for these modifications are also misregulated in various disease states. Objective: To review the complex roles of chromatin-modifying enzymes in gene regulation and to highlight their potential as therapeutic targets. Methods: This review is based on recent published literature and online resources. Results/conclusion: In this second and final part of the review, we discuss the importance of these other histone and nucleosome modifying enzymes in gene transcription as well as their therapeutic potential.
C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Archer, TK (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
NR 65
TC 0
Z9 0
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1472-8222
EI 1744-7631
J9 EXPERT OPIN THER TAR
JI Expert Opin. Ther. Targets
PD NOV
PY 2008
VL 12
IS 11
BP 1457
EP 1466
DI 10.1517/14728220802384047
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 368JT
UT WOS:000260618100012
ER
PT J
AU Szklarczyk, A
Ewaleifoh, O
Beique, JC
Wang, Y
Knorr, D
Haughey, N
Malpica, T
Mattson, MP
Huganir, R
Conant, K
AF Szklarczyk, Arek
Ewaleifoh, Osefame
Beique, Jean-Claude
Wang, Yue
Knorr, David
Haughey, Norman
Malpica, Tanya
Mattson, Mark P.
Huganir, Richard
Conant, Katherine
TI MMP-7 cleaves the NR1 NMDA receptor subunit and modifies NMDA receptor
function
SO FASEB JOURNAL
LA English
DT Article
DE matrilysin; glutamate; synapse; proteolysis
ID MATRIX-METALLOPROTEINASE ACTIVITY; AMYLOID PROTEIN-PRECURSOR; FOCAL
CEREBRAL-ISCHEMIA; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE;
SPINAL-CORD; CELL-DEATH; CALCIUM DYSREGULATION; HIPPOCAMPAL SYNAPSES;
SYNAPTIC PLASTICITY
AB Matrix metalloproteinases (MMPs) are zinc-dependent enzymes that play a role in the inflammatory response. These enzymes have been well studied in the context of cancer biology and inflammation. Recent studies, however, suggest that these enzymes also play roles in brain development and neurodegenerative disease. Select MMPs can target proteins critical to synaptic structure and neuronal survival, including integrins and cadherins. Here, we show that one member of the MMP family, MMP-7, which may be released from cells, including microglia, can target a protein critical to synaptic function. Through analysis of extracts from murine cortical slice preparations, we show that MMP-7 cleaves the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor to generate an N-terminal fragment of similar to 65 kDa. Moreover, studies with recombinant protein show that MMP-7-mediated cleavage of NR1 occurs at amino acid 517, which is extracellular and just distal to the first transmembrane domain. Data suggest that NR2A, which shares sequence homology with NR1, is also cleaved following treatment of slices with MMP-7, while select AMPA receptor subunits are not. Consistent with a potential effect of MMP-7 on ligand binding, additional experiments demonstrate that NMDA-mediated calcium flux is significantly diminished by MMP-7 pretreatment of cultures. In addition, the AMPA/NMDA ratio is increased by MMP-7 pretreatment. These data suggest that synaptic function may be altered in neurological conditions associated with increased levels of MMP-7.-Szklarczyk, A., Ewaleifoh, O., Beique, J.-C., Wang, Y., Knorr, D., Haughey, N., Malpica, T., Mattson, M. P., Huganir, R., Conant, K. MMP-7 cleaves the NR1 NMDA receptor subunit and modifies NMDA receptor function. FASEB J. 22, 3757-3767 (2008)
C1 [Conant, Katherine] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21287 USA.
[Beique, Jean-Claude; Mattson, Mark P.; Huganir, Richard] Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21287 USA.
[Beique, Jean-Claude; Huganir, Richard] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Wang, Yue; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Conant, K (reprint author), Johns Hopkins Univ, Dept Neurol, Sch Med, Pathol Bldg Rm 625,600 N Wolfe St, Baltimore, MD 21287 USA.
EM kconant@mail.jhmi.edu
RI Mattson, Mark/F-6038-2012
FU National Institutes of Health [NS052580, DA024447]; Alzheimer's
Association; Howard Hughes Medical Institute; NARSAD; National Institute
on Aging Intramural Research Program
FX We thank Jenny Ryu and Jackie Mann for expert technical assistance. We
also thank Dr. Yuri Kim and Kee Jun Kim for helpful comments. And we
thank Marc Mayer and Yongneng Yao for the NR1 S1/S2 construct. This work
was supported, in part, by the National Institutes of Health (NS052580
and DA024447 to K. C.), the Alzheimer's Association (K.C.), the Howard
Hughes Medical Institute (J.C.B. and R.H.), NARSAD (J.C.B.), and the
National Institute on Aging Intramural Research Program.
NR 66
TC 27
Z9 29
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD NOV
PY 2008
VL 22
IS 11
BP 3757
EP 3767
DI 10.1096/fj.07-101402
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 366SF
UT WOS:000260503000004
PM 18644839
ER
PT J
AU Klootwijk, RD
Savelkoul, PJM
Ciccone, C
Manoli, I
Caplen, NJ
Krasnewich, DM
Gahl, WA
Huizing, M
AF Klootwijk, Riko D.
Savelkoul, Paul J. M.
Ciccone, Carla
Manoli, Irini
Caplen, Natasha J.
Krasnewich, Donna M.
Gahl, William A.
Huizing, Marjan
TI Allele-specific silencing of the dominant disease allele in sialuria by
RNA interference
SO FASEB JOURNAL
LA English
DT Article
DE real-time PCR; feedback inhibition; sialic acid; UDP-GlcNAc
2-epimerase/ManNAc kinase; siRNA; allosteric site
ID N-ACETYLGLUCOSAMINE 2-EPIMERASE; AMYOTROPHIC-LATERAL-SCLEROSIS; IN-VIVO;
PHOSPHORIBOSYLPYROPHOSPHATE SYNTHETASE; REGULATORY MUTATIONS; MOUSE
MODEL; GENE; DELIVERY; SUPERACTIVITY; PURIFICATION
AB Dominant disease alleles are attractive therapeutic targets for allele-specific gene silencing by small interfering RNA ( siRNA). Sialuria is a dominant disorder caused by missense mutations in the allosteric site of GNE, coding for the rate-limiting enzyme of sialic acid biosynthesis, UDP-GlcNAc 2-epimerase/ManNAc kinase. The resultant loss of feedback inhibition of GNE-epimerase activity by CMP-sialic acid causes excessive production of free sialic acid. For this study we employed synthetic siRNAs specifically targeting the dominant GNE mutation c. 797G > A (p.R266Q) in sialuria fibroblasts. We demonstrated successful siRNA-mediated down-regulation of the mutant allele by allele-specific real-time PCR. Importantly, mutant allele-specific silencing resulted in a significant decrease of free sialic acid, to within the normal range. Feedback inhibition of GNE-epimerase activity by CMP-sialic acid recovered after silencing demonstrating specificity of this effect. These findings indicate that allele-specific silencing of a mutated allele is a viable therapeutic strategy for autosomal dominant diseases, including sialuria.-Klootwijk, R. D., Savelkoul, P. J. M., Ciccone, C., Manoli, I., Caplen, N. J., Krasnewich, D. M., Gahl, W. A., Huizing, M. Allele-specific silencing of the dominant disease allele in sialuria by RNA interference. FASEB J. 22, 3846-3852 (2008)
C1 [Klootwijk, Riko D.; Savelkoul, Paul J. M.; Ciccone, Carla; Manoli, Irini; Krasnewich, Donna M.; Gahl, William A.; Huizing, Marjan] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Caplen, Natasha J.] NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Gahl, William A.] NIH, Off Rare Dis, Intramural Program, Bethesda, MD 20892 USA.
RP Huizing, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA.
EM mhuizing@mail.nih.gov
RI Caplen, Natasha/H-2768-2016
OI Manoli, Irini/0000-0003-1543-2941; Caplen, Natasha/0000-0002-0001-9460
FU National Human Genome Research Institute; National Cancer Institute;
National Institutes of Health, Bethesda, MD, USA
FX This study was supported by the Intramural Research programs of the
National Human Genome Research Institute and the National Cancer
Institute, National Institutes of Health, Bethesda, MD, USA.
NR 43
TC 10
Z9 10
U1 0
U2 1
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 NOV
PY 2008
VL 22
IS 11
BP 3846
EP 3852
DI 10.1096/fj.08-110890
PG 7
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 366SF
UT WOS:000260503000013
PM 18653764
ER
PT J
AU Gatsos, X
Perry, AJ
Anwari, K
Dolezal, P
Wolynec, PP
Likic, VA
Purcell, AW
Buchanan, SK
Lithgow, T
AF Gatsos, Xenia
Perry, Andrew J.
Anwari, Khatira
Dolezal, Pavel
Wolynec, P. Peter
Likic, Vladimir A.
Purcell, Anthony W.
Buchanan, Susan K.
Lithgow, Trevor
TI Protein secretion and outer membrane assembly in Alphaproteobacteria
SO FEMS MICROBIOLOGY REVIEWS
LA English
DT Review
DE outer membrane assembly; membrane structure; Omp85; beta-barrel
proteins; Alphaproteobacteria; mitochondria
ID CARBOXY-TERMINAL PHENYLALANINE; GRAM-NEGATIVE BACTERIA; BETA-BARREL
PROTEINS; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; MOLECULAR CHAPERONE;
TREPONEMA-PALLIDUM; STRUCTURAL BASIS; EVOLUTIONARY CONSERVATION;
SACCHAROMYCES-CEREVISIAE
AB The assembly of beta-barrel proteins into membranes is a fundamental process that is essential in Gram-negative bacteria, mitochondria and plastids. Our understanding of the mechanism of beta-barrel assembly is progressing from studies carried out in Escherichia coli and Neisseria meningitidis. Comparative sequence analysis suggests that while many components mediating beta-barrel protein assembly are conserved in all groups of bacteria with outer membranes, some components are notably absent. The Alphaproteobacteria in particular seem prone to gene loss and show the presence or absence of specific components mediating the assembly of beta-barrels: some components of the pathway appear to be missing from whole groups of bacteria (e.g. Skp, YfgL and NlpB), other proteins are conserved but are missing characteristic domains (e.g. SurA). This comparative analysis is also revealing important structural signatures that are vague unless multiple members from a protein family are considered as a group (e.g. tetratricopeptide repeat (TPR) motifs in YfiO, beta-propeller signatures in YfgL). Given that the process of the beta-barrel assembly is conserved, analysis of outer membrane biogenesis in Alphaproteobacteria, the bacterial group that gave rise to mitochondria, also promises insight into the assembly of beta-barrel proteins in eukaryotes.
C1 [Gatsos, Xenia; Perry, Andrew J.; Anwari, Khatira; Dolezal, Pavel; Purcell, Anthony W.; Lithgow, Trevor] Univ Melbourne, Dept Biochem & Mol Biol, Melbourne, Vic, Australia.
[Gatsos, Xenia; Perry, Andrew J.; Anwari, Khatira; Dolezal, Pavel; Wolynec, P. Peter; Likic, Vladimir A.; Purcell, Anthony W.; Lithgow, Trevor] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic, Australia.
[Buchanan, Susan K.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Lithgow, T (reprint author), Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia.
EM t.lithgow@unimelb.edu.au
RI Perry, Andrew/E-5607-2010;
OI Perry, Andrew/0000-0001-9256-6068; Purcell, Anthony/0000-0003-0532-8331
FU Intramural NIH HHS
NR 139
TC 60
Z9 62
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0168-6445
EI 1574-6976
J9 FEMS MICROBIOL REV
JI Fems Microbiol. Rev.
PD NOV
PY 2008
VL 32
IS 6
BP 995
EP 1009
DI 10.1111/j.1574-6976.2008.00130.x
PG 15
WC Microbiology
SC Microbiology
GA 359AQ
UT WOS:000259959000006
PM 18759741
ER
PT J
AU Kalantaridou, SN
Vanderhoof, VH
Calis, KA
Corrigan, EC
Troendle, JF
Nelson, LM
AF Kalantaridou, Sophia N.
Vanderhoof, Vien H.
Calis, Karim A.
Corrigan, Emily C.
Troendle, James F.
Nelson, Lawrence M.
TI Sexual function in young women with spontaneous 46,XX primary ovarian
insufficiency
SO FERTILITY AND STERILITY
LA English
DT Article
DE Sexual function; primary ovarian insufficiency; premature ovarian
failure; premature menopause; primary hypogonadism; hypergonadotropic
hypogonadism; hypergonadotropic amenorrhea; hormone replacement therapy;
estrogen; testosterone
ID SURGICALLY MENOPAUSAL WOMEN; TESTOSTERONE PATCH; DESIRE DISORDER;
POSTMENOPAUSAL WOMEN; NATURAL MENOPAUSE; DYSFUNCTION; FAILURE;
ENDOCRINE; OOPHORECTOMY; HEALTH
AB Objective: To assess sexual function in women with spontaneous 46,XX primary ovarian insufficiency after at least 3 months of a standardized hormone replacement regimen.
Design: Cross-sectional cohort, controlled. Setting: National Institutes of Health Clinical Research Center.
Patient(s): Women with primary ovarian insufficiency (n = 143) and regularly menstruating controls (n = 70). Intervention(s): Self administered questionnaires, 100 mu g/day E-2 patch, oral medroxyprogesterone acetate 10 mg for 12 days each month for patients.
Main Outcome Measure(s): Derogatis Interview for Sexual Function Self-Report (DISF-SR).
Result(s): Women with primary ovarian insufficiency had significantly lower DISF-SR composite scores compared with control women. Their serum total testosterone levels were significantly correlated with DISF-SR composite score, although this accounted for only 4% of the variance in this measure. Patients with testosterone levels below normal tended to have lower DISF-SR composite scores. Of patients with primary ovarian insufficiency, 9 of 127 (7%) scored below the second percentile on the composite sexual function score, compared with 1of 49 control women (2%).
Conclusion(s): As assessed by the DISF-SR, sexual function is in the normal range for most young women with 46,XX spontaneous primary ovarian insufficiency who are receiving physiologic E-2 replacement. However, as a group, these young women score significantly lower on this sexual function scale than control women. (Fertil Steril((R)) 2008;90:4805-11. (c) 2008 by American Society for Reproductive Medicine.)
C1 [Nelson, Lawrence M.] NICHHD, Integrat Reprod Med Unit, Reprod Biol & Med Branch, Intramural Res Program,NIH,CRC, Bethesda, MD 20892 USA.
[Calis, Karim A.] Warren O Hatfield Clin Res Ctr, Dept Pharm, Bethesda, MD USA.
[Troendle, James F.] NICHHD, Biometry & Math Stat Branch, NIH, Bethesda, MD 20892 USA.
RP Nelson, LM (reprint author), NICHHD, Integrat Reprod Med Unit, Reprod Biol & Med Branch, Intramural Res Program,NIH,CRC, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA.
EM lawrence_nelson@nih.gov
FU Intramural Research Program; National Institute of Child Health and
Human Development; National Institutes of Health
FX Supported by the Intramural Research Program, National Institute of
Child Health and Human Development, National Institutes of Health. Vien
H. Vanderhoof and Lawrence M. Nelson are commissioned officers in the
United States Public Health Service.
NR 41
TC 9
Z9 9
U1 1
U2 3
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 NOV
PY 2008
VL 90
IS 5
BP 1805
EP 1811
DI 10.1016/j.fertnstert.2007.08.040
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 370GZ
UT WOS:000260752000036
PM 17961560
ER
PT J
AU Centlow, M
Carninci, P
Nemeth, K
Mezey, E
Brownstein, M
Hansson, SR
AF Centlow, Magnus
Carninci, Piero
Nemeth, Krisztian
Mezey, Eva
Brownstein, Michael
Hansson, Stefan R.
TI Placental expression profiling in preeclampsia: local overproduction of
hemoglobin may drive pathological changes
SO FERTILITY AND STERILITY
LA English
DT Article
DE Hematopoiesis; endothelial damage; hypoxia; inflammation
ID HEME OXYGENASE EXPRESSION; MATERNAL SUSCEPTIBILITY LOCUS; LENGTH CDNA
LIBRARIES; BLOOD-CELL COUNTS; TROPHOBLAST CELLS; CHORIONIC VILLI;
GENE-EXPRESSION; HYPOXIA; PREGNANCIES; RISK
AB Objective: To create a library enriched in cDNAs from preeclamptic placentas to print onto microarrays for placental profiting of preeclampsia (PE) and high risk pregnancies.
Design: Prospective study. Setting: University women's clinic and academic research laboratory.
Patient(S): Ten patients with PE, 5 with PE and bilateral notching, 5 with bilateral notching without PE, and 15 normotensive patients were recruited.
Intervention(s): Placenta and placenta bed biopsies were collected after delivery.
Main Outcome Measure(s): Subtracted libraries of PE transcripts were produced, and cDNAs from these libraries were used to make PE-specific cDNA arrays. Results were verified quantitatively using real-time polymerase chain reaction (PCR) and histologically using in situ hybridization and immunohistochemistry.
Result(s): Thirty genes were significantly altered in at least one group comparison. Differences in two candidate genes were confirmed using quantitative real-time PCR. Hemoglobin alpha 2 and gamma transcripts were significantly over-expressed in the PE placenta. Scattered cells in the placenta and placental blood vessels were shown to express genes encoding these hemoglobin chains.
Conclusion(s): We demonstrate increased hemoglobin production in the PE placenta. The hemoglobin may be released into the placenta blood vessel lumen. Free heme and hemoglobin are potent toxins that cause endothelial damage and inflammation. (Fertil Steril((R)) 2008;90:1834-43. (c) 2008 by American Society for Reproductive Medicine.)
C1 [Centlow, Magnus; Hansson, Stefan R.] Lund Univ, Dept Obstet & Gynecol, SE-22644 Lund, Sweden.
[Carninci, Piero] RIKEN, Genome Sci Lab, Wako, Saitama, Japan.
[Nemeth, Krisztian; Mezey, Eva] Natl Inst Dent & Craniofacial Res, NIH, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA.
[Brownstein, Michael] J Craig Venter Inst, Rockville, MD USA.
RP Centlow, M (reprint author), Lund Univ, Dept Obstet & Gynecol, BMC C14,Klinikgatan 28, SE-22644 Lund, Sweden.
EM magnus.centlow@med.lu.se
RI Brownstein, Michael/B-8609-2009; Carninci, Piero/K-1568-2014
OI Carninci, Piero/0000-0001-7202-7243
FU Swedish Research Council [5775]; Knut and Alice Wallenberg Foundation;
Anna Lisa & Sven Erik Lundgrens foundation for Medical Research;
Crawford Foundation; Magnus Bergvalls Foundation; Swedish Society for
Medical Research; Intramural Research Program; National Institute of
Dental and Craniofacial Research; National Institutes of Health; Swegene
DNA Microarray Resource Center in Lund
FX Supported by grants from the Swedish Research Council: 5775, Anna Lisa &
Sven Erik Lundgrens foundation for Medical Research, Crawford
Foundation, Magnus Bergvalls Foundation, Swedish Society for Medical
Research, and the Intramural Research Program of the National Institute
of Dental and Craniofacial Research, National Institutes of Health.
Microarrays and protocols were obtained from the Swegene DNA Microarray
Resource Center in Lund, supported by the Knut and Alice Wallenberg
Foundation through the Swegene consortium.
NR 50
TC 33
Z9 35
U1 1
U2 4
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 NOV
PY 2008
VL 90
IS 5
BP 1834
EP 1843
DI 10.1016/j.fertnstert.2007.09.030
PG 10
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 370GZ
UT WOS:000260752000040
PM 18166190
ER
PT J
AU Browne, H
McCarthy-Keith, D
Stegmann, B
Spies, J
Armstrong, A
AF Browne, Hyacinth
McCarthy-Keith, Desiree
Stegmann, Barbara
Spies, James
Armstrong, Alicia
TI Ovarian response in women undergoing ovarian stimulation after
myomectomy
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
DE Fibroids; myomectomy; ovarian reserve; assisted reproductive technology
ID UTERINE ARTERY EMBOLIZATION; IN-VITRO FERTILIZATION; RESERVE;
LEIOMYOMATA; HYSTERECTOMY
AB Objective: To examine ovarian response in infertile women undergoing ovarian stimulation after abdominal myomectomy.
Design: Case report.
Setting: Academic medical research center.
Patient(s): Four infertile women with known fibroids who had a failed assisted reproductive technology (ART) cycle followed by an abdominal myomectomy.
Intervention(s): Infertile women with known fibroids who had a failed ART cycle, from January 2000 to December 2006, followed by an abdominal myomectomy and a subsequent ART cycle.
Main Outcome Measure(s): Ovarian function before (baseline) and after myomectomy was assessed by age, day 3 and day 10 FSH levels, days of stimulation, total gonadotropins used, peak E(2) level, the number of oocytes retrieved and embryos obtained, the number of high-grade embryos, and pregnancy outcome.
Result(s): The mean age was 35 and 36 years before and after myomectomy, respectively. All subjects had uterine factor infertility. Two of these women also had tubal factor infertility, and one had endometriosis and male factor infertility. There was no difference in ovarian response before and after myomectomy.
Conclusion(s): As expected, abdominal myomectomy did not adversely affect ovarian response in infertile women undergoing ovarian stimulation after a failed ART cycle. Larger randomized prospective studies are needed to accurately assess whether myomectomy has a negative impact on ovarian response. (Fertil Steril (R) 2008; 90: 2004. e19-e21. (C)2008 by American Society for Reproductive Medicine.)
C1 [Browne, Hyacinth; McCarthy-Keith, Desiree; Stegmann, Barbara; Armstrong, Alicia] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Browne, Hyacinth; McCarthy-Keith, Desiree; Stegmann, Barbara; Armstrong, Alicia] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Spies, James] Georgetown Univ Hosp, Dept Radiol, Intervent Radiol Sect, Washington, DC 20007 USA.
RP Browne, H (reprint author), NICHD, Program Reprod & Adult Endocrinol, NIH, CRC 1 E Rm 1-E-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM brownehy@mail.nih.gov
FU National Institute of Child Health and Human Development, National
Institutes of Health
FX Carried out under Walter Reed Army Medical Center Department of Clinical
Investigations protocol WU #08-04-44018hEX(1) and supported in part by
the Program in Reproductive and Adult Endocrinology, National Institute
of Child Health and Human Development, National Institutes of Health.
NR 14
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD NOV
PY 2008
VL 90
IS 5
AR 2004.e19
DI 10.1016/j.fertnstert.2008.04.008
PG 3
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V13XQ
UT WOS:000207699900010
PM 18565518
ER
PT J
AU Chason, RJ
Levens, ED
Yauger, BJ
Payson, MD
Cho, K
Larsen, FW
AF Chason, Rebecca J.
Levens, Eric D.
Yauger, Belinda J.
Payson, Mark D.
Cho, Kenneth
Larsen, Frederick W.
TI Balloon fluoroscopy as treatment for intrauterine adhesions: a novel
approach
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
DE Asherman's syndrome; synechiae; intrauterine adhesions; balloon
dilation; cesarean section scar
ID CESAREAN-SECTION SCAR; SONOHYSTEROGRAPHY
AB Objective: To report a unique fluoroscopically guided approach to treat severe intrauterine adhesions and cervical stenosis using balloon hysteroplasty.
Design: Case report.
Setting: Military-based fertility center.
Patient(s): A 33-year-old woman undergoing assisted reproductive technology whose uterus could not be cannulated because of the development of intrauterine synechiae and cervical stenosis after a post-IUI infection that was further complicated by a prominent lower uterine segment-filling defect in the location of a prior cesarean delivery scar.
Intervention(s): Fluoroscopic cannulation and balloon uterine dilation.
Main Outcome Measure(s): Resolution of synechiae by hysterosalpingogram and successful uterine cannulation.
Result(s): A postprocedure hysterosalpingogram demonstrated a normalized uterine cavity with the exception of a persistent prominent lower uterine segment-filling defect from a prior cesarean delivery. A frozen ET cycle was performed successfully.
Conclusion(s): Hysteroplasty, using standard interventional radiographic techniques, may provide an alternative treatment modality for patients with intrauterine adhesions and lower uterine defects from prior cesarean deliveries in select cases. While treating intrauterine adhesions improves pregnancy outcome, the effect of lower uterine segment-filling defects from cesarean deliveries on pregnancy outcome in assisted reproductive technology cycles warrants further investigation. (Fertil Steril (R) 2008; 90: 2005. e15-e17. (C)2008 by American Society for Reproductive Medicine.)
C1 [Chason, Rebecca J.] NICHHD, Natl Naval Med Ctr, NIH, Bethesda, MD 20892 USA.
[Levens, Eric D.; Yauger, Belinda J.] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Yauger, Belinda J.; Payson, Mark D.; Cho, Kenneth; Larsen, Frederick W.] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
RP Chason, RJ (reprint author), Care of Cyoyle MP, Natl Naval Med Ctr, Bldg 1,Rm 2435,8901 Rockville Pike, Bethesda, MD 20889 USA.
EM rebecca.chason@amedd.army.mil
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, the National Institutes of Health, Bethesda, Maryland
FX This research was supported, in part, by the Program in Reproductive and
Adult Endocrinology of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, the National Institutes of Health,
Bethesda, Maryland.
NR 11
TC 2
Z9 2
U1 0
U2 6
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 NOV
PY 2008
VL 90
IS 5
AR 2005.e15
DI 10.1016/j.fertnstert.2008.07.1752
PG 3
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA V13XQ
UT WOS:000207699900016
PM 18793771
ER
PT J
AU Metz, DC
Jensen, RT
AF Metz, David C.
Jensen, Robert T.
TI Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors
SO GASTROENTEROLOGY
LA English
DT Review
ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN RECEPTOR SCINTIGRAPHY;
ISLET-CELL TUMORS; HIPPEL-LINDAU-DISEASE; GASTRIC-ACID HYPERSECRETION;
EPIDERMAL-GROWTH-FACTOR; FINE-NEEDLE-ASPIRATION; NECROLYTIC MIGRATORY
ERYTHEMA; NEOPLASIA TYPE-1 MEN1; INSTITUTES-OF-HEALTH
C1 [Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
[Metz, David C.] Univ Penn, Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA.
RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA.
EM RobertJ@bdg10.niddk.nih.gov
FU Intramural NIH HHS [Z01 DK053200-16, Z01 DK053215-01]
NR 308
TC 253
Z9 261
U1 0
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD NOV
PY 2008
VL 135
IS 5
BP 1469
EP 1492
DI 10.1053/j.gastro.2008.05.047
PG 24
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 371YL
UT WOS:000260868500016
PM 18703061
ER
PT J
AU Boirivant, M
Amendola, A
Butera, A
Sanchez, M
Xu, LL
Marinaro, M
Kitani, A
Di Giacinto, C
Strober, W
Fuss, IJ
AF Boirivant, Monica
Amendola, Antonello
Butera, Alessia
Sanchez, Massimo
Xu, Lili
Marinaro, Mariarosaria
Kitani, Atsushi
Di Giacinto, Claudia
Strober, Warren
Fuss, Ivan J.
TI A Transient Breach in the Epithelial Barrier Leads to Regulatory T-Cell
Generation and Resistance to Experimental Colitis
SO GASTROENTEROLOGY
LA English
DT Article
ID INFLAMMATION; MODULATION; DISEASE; ACID
AB Background & Aims: Previous studies have indicated that a defective epithelial barrier leads to inflammation of the underlying lamina propria. Nevertheless, it is likely that physiologic breaks in the barrier must occur for homeostatic regulatory T cells to develop. We determined the effect of agents that disrupt epithelial tight junctions (ethanol and AT1002, a Vibrio cholerae zonula occludens toxin hexapeptide) on regulatory T-cell induction and resistance to induction of colitis by trinitrobenzene sulfonic acid (TNBS). Methods: The effects of ethanol and AT1002 on. colon immune function were evaluated by their capacity to induce direct phenotypic or functional changes in effector and regulatory cell populations and their indirect effect on the development of TNBS-induced colitis. The basis of regulatory cell development was evaluated with in vitro studies of isolated dendritic cell populations. The role of innate immunity was evaluated by in vivo gene silencing studies utilizing Toll-like receptor (TLR)-2-specific small interfering RNA (siRNA). Results: Both ethanol and AT1002 induced persistent latency-associated peptide-positive CD4(+) regulatory T cells that, as shown in adoptive transfer studies, render mice resistant to the induction of TNBS colitis. The development of these cells requires the presence of an intact microflora and the activity of CD11c(+) dendritic cells. Their induction is also influenced by innate immune factors operating through TLR-2, because attenuation of TLR-2 signaling by in vivo TLR-2 siRNA administration prevents their development. Conclusions: A mild and/or transient breach in epithelial barrier function leads to dominant regulatory T-cell responses that protect the mucosa from inflammation.
C1 [Boirivant, Monica; Amendola, Antonello; Butera, Alessia; Marinaro, Mariarosaria; Di Giacinto, Claudia] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, Immune Mediated Dis Sect, I-00161 Rome, Italy.
[Sanchez, Massimo] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy.
[Xu, Lili; Kitani, Atsushi; Strober, Warren; Fuss, Ivan J.] NIAID, Mucosal Immun Sect, Host Def Lab, Bethesda, MD 20892 USA.
RP Boirivant, M (reprint author), Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, Immune Mediated Dis Sect, Viale R Elena 299, I-00161 Rome, Italy.
EM monica.boirivant@iss.it
RI BOIRIVANT, MONICA/B-9977-2016; AMENDOLA, ANTONELLO/B-9979-2016; Butera,
Alessia /I-3399-2014
OI Butera, Alessia /0000-0002-7659-4066
FU Italian Ministry of Health
FX Supported in part by ISS-NIH program 5303 and grant "ricerca Finalizzata
2005 Fasc 6ACF" from the Italian Ministry of Health.
NR 18
TC 45
Z9 46
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 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD NOV
PY 2008
VL 135
IS 5
BP 1612
EP 1623
DI 10.1053/j.gastro.2008.07.028
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 371YL
UT WOS:000260868500031
PM 18765239
ER
PT J
AU Geyer, CB
Eddy, EM
AF Geyer, Christopher B.
Eddy, Edward M.
TI Identification and characterization of Rhox13, a novel X-linked mouse
homeobox gene
SO GENE
LA English
DT Article
DE testis; ovary; spermatogenesis; transcription; X chromosome
ID HOMEODOMAIN PROTEINS; GERM-CELLS; CLUSTER; DNA; PLACENTA; TESTIS;
CLASSIFICATION; FAMILY; MEMBER; MOTIF
AB Homeobox genes encode transcription factors whose expression organizes programs of development. A number of homeobox genes expressed in reproductive tissues have been identified recently, including a colinear cluster on the X chromosome in mice. This has led to an increased interest in understanding the role (s) of homeobox genes in regulating development of reproductive tissues including the testis, ovary, and placenta. Here we report the identification and characterization of a novel homeobox gene of the paired-like class on the X chromosome distal to the reproductive homeobox (Rhox) cluster in mice. Transcripts are found in the testis and ovary as early as 13.5 days post coitum, (dpc). Transcription ceases in the ovary by 3 days post partum (dpp), but continues in the testis through adulthood. The Rhox13 gene encodes a 25.3 kDa protein expressed in the adult testis in germ cells at the basal aspect of the seminiferous epithelium. Published by Elsevier B.V.
C1 [Geyer, Christopher B.; Eddy, Edward M.] NIEHS, Gamete Biol Grp, Reprod & Dev Toxicol Lab, NIH,DHHS, Res Triangle Pk, NC 27709 USA.
RP Eddy, EM (reprint author), NIEHS, Gamete Biol Grp, Reprod & Dev Toxicol Lab, NIH,DHHS, 111 TW Alexander Dr,MD C4-01, Res Triangle Pk, NC 27709 USA.
EM eddy1@niehs.nih.gov
FU Intramural NIH HHS [Z01 ES070076-21]
NR 29
TC 18
Z9 19
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
J9 GENE
JI Gene
PD NOV 1
PY 2008
VL 423
IS 2
BP 194
EP 200
DI 10.1016/j.gene.2008.06.031
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 361XF
UT WOS:000260160300013
PM 18675325
ER
PT J
AU Yang, S
Cohen, CJ
Peng, PD
Zhao, Y
Cassard, L
Yu, Z
Zheng, Z
Jones, S
Restifo, NP
Rosenberg, SA
Morgan, RA
AF Yang, S.
Cohen, C. J.
Peng, P. D.
Zhao, Y.
Cassard, L.
Yu, Z.
Zheng, Z.
Jones, S.
Restifo, N. P.
Rosenberg, S. A.
Morgan, R. A.
TI Development of optimal bicistronic lentiviral vectors facilitates
high-level TCR gene expression and robust tumor cell recognition
SO GENE THERAPY
LA English
DT Article
DE T-cell receptor; adoptive immunotherapy; tumor immunity; lentivirus; 2A
peptide
ID ENHANCED ANTITUMOR-ACTIVITY; RECEPTOR RETROGENIC MICE; EMBRYONIC
STEM-CELLS; CD8(+) T-CELLS; IN-VIVO; HUMAN-LYMPHOCYTES; TRANSGENE
EXPRESSION; RETROVIRAL VECTOR; SELECTION PROCESS; 2A PEPTIDE
AB In human gene therapy applications, lentiviral vectors may have advantages over gamma-retroviral vectors in several areas, including the ability to transduce nondividing cells, resistance to gene silencing and a potentially safer integration site profile. However, unlike gamma-retroviral vectors it has been problematic to drive the expression of multiple genes efficiently and coordinately with approaches such as internal ribosome entry sites or dual promoters. Using different 2A peptides, lentiviral vectors expressing two-gene T-cell receptors directed against the melanoma differentiation antigens gp100 and MART-1 were constructed. We demonstrated that addition of amino-acid spacer sequences (GSG or SGSG) before the 2A sequence is a prerequisite for efficient synthesis of biologically active T-cell receptors and that addition of a furin cleavage site followed by a V5 peptide tag yielded optimal T-cell receptor gene expression. Furthermore, we determined that the furin cleavage site was recognized in lymphocytes and accounted for removal of residual 2A peptides at the post-translational level with an efficiency of 20-30%, which could not be increased by addition of multiple furin cleavage sites. The novel bicistronic lentiviral vector developed herein afforded robust anti-melanoma activities to engineered peripheral blood lymphocytes, including cytokine secretion, cell proliferation and lytic activity. Such optimal vectors may have immediate applications in cancer gene therapy. Gene Therapy (2008) 15, 1411-1423; doi:10.1038/gt.2008.90; published online 22 May 2008
C1 [Yang, S.; Cohen, C. J.; Peng, P. D.; Zhao, Y.; Cassard, L.; Yu, Z.; Zheng, Z.; Jones, S.; Restifo, N. P.; Rosenberg, S. A.; Morgan, R. A.] NCI, NIH, Ctr Canc Res, Surg Branch, Bethesda, MD 20892 USA.
RP Morgan, RA (reprint author), NCI, NIH, Ctr Canc Res, Surg Branch, 10 Ctr Dr,Bldg 10,CRC 3W-3864, Bethesda, MD 20892 USA.
EM rmorgan@mail.nih.gov
RI Restifo, Nicholas/A-5713-2008;
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Center for Cancer Research; National Cancer Institute; National
Institutes of Health
FX We thank FACS laboratory and TIL laboratory in Surgery Branch for
providing technical support and maintenance of tumor cells from
patients. This work is supported by the Intramural Research Program of
the Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 56
TC 89
Z9 92
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
J9 GENE THER
JI Gene Ther.
PD NOV
PY 2008
VL 15
IS 21
BP 1411
EP 1423
DI 10.1038/gt.2008.90
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 363DZ
UT WOS:000260248500001
PM 18496571
ER
PT J
AU Fegley, DB
Holmes, A
Riordan, T
Faber, CA
Weiss, JR
Ma, S
Batkai, S
Pacher, P
Dobolyi, A
Murphy, A
Sleeman, MW
Usdin, TB
AF Fegley, D. B.
Holmes, A.
Riordan, T.
Faber, C. A.
Weiss, J. R.
Ma, S.
Batkai, S.
Pacher, P.
Dobolyi, A.
Murphy, A.
Sleeman, M. W.
Usdin, T. B.
TI Increased fear- and stress-related anxiety-like behavior in mice lacking
tuberoinfundibular peptide of 39 residues
SO GENES BRAIN AND BEHAVIOR
LA English
DT Article
DE Anxiety; conditioned fear; mouse knockout; neuropeptide; stress
ID ELEVATED PLUS-MAZE; SEROTONIN TRANSPORTER; HORMONE RECEPTOR-2;
NEUROPEPTIDE-Y; DEFICIENT MICE; KNOCKOUT MICE; ANIMAL-MODEL; RESTRAINT
STRESS; RAT; DEPRESSION
AB Tuberoinfundibular peptide of 39 residues (TIP39) is synthesized by two groups of neurons, one in the subparafascicular area at the caudal end of the thalamus and the other in the medial paralemniscal nucleus within the lateral brainstem. The subparafascicular TIP39 neurons project to a number of brain regions involved in emotional responses, and these regions contain a matching distribution of a receptor for TIP39, the parathyroid hormone 2 receptor (PTH2-R). We have now evaluated the involvement of TIP39 in anxiety-related behaviors using mice with targeted null mutation of the TIP39 gene (Tifp39). Tifp39(-/-) mice (TIP39-KO) did not significantly differ from wild-type (WT) littermates in the open field, light/dark exploration and elevated plus-maze assays under standard test conditions. However, the TIP39-KO engaged in more active defensive burying in the shock-probe test. In addition, when tested under high illumination or after restraint, TIP39-KO displayed significantly greater anxiety-like behavior in the elevated plus-maze than WT. In a Pavlovian fear-conditioning paradigm, TIP39-KO froze more than WT during training and during tone and context recall but showed normal fear extinction. Disruption of TIP39 projections to the medial prefrontal cortex, lateral septum, bed nucleus of the stria terminalis, hypothalamus and amygdala likely account for the fear- and anxiety-related phenotype of TIP39-KO. Current data support the hypothesis that TIP39 modulates anxiety-related behaviors following environmental provocation.
C1 [Fegley, D. B.; Riordan, T.; Faber, C. A.; Weiss, J. R.; Ma, S.; Usdin, T. B.] NIMH, NIH, Bethesda, MD 20892 USA.
[Holmes, A.; Batkai, S.; Pacher, P.] NIAAA, NIH, Rockville, MD 20852 USA.
[Dobolyi, A.] Semmelweis Univ, Hungarian Acad Sci, Neuromorphol Lab, H-1085 Budapest, Hungary.
[Murphy, A.; Sleeman, M. W.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA.
RP Usdin, TB (reprint author), 35 Convent Dr MSC 3728, Bethesda, MD 20892 USA.
EM usdint@mail.nih.gov
RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai,
Sandor/H-7983-2014
OI Pacher, Pal/0000-0001-7036-8108;
FU NIH, National Institute of Mental Health
FX We thank Ildiko Racz and Sarah Irwin for help with preliminary
experiments, Jim Pickel and the NIMH transgenic mouse core facility for
help with generation of mice, and Heather Cameron and Jacqueline Crawley
for the use of behavior testing equipment. This research was supported
by the Intramural Program of the NIH, National Institute of Mental
Health. M. W. S. and A. M. are employees of Regeneron and own stock in
Regeneron. The authors declare that there are no potential conflicts of
interest.
NR 61
TC 18
Z9 18
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1601-1848
J9 GENES BRAIN BEHAV
JI Genes Brain Behav.
PD NOV
PY 2008
VL 7
IS 8
BP 933
EP 942
DI 10.1111/j.1601-183X.2008.00432.x
PG 10
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 376LK
UT WOS:000261184900012
PM 18700839
ER
PT J
AU Ohali, A
Avigad, S
Naumov, I
Goshen, Y
Ash, S
Yaniv, I
AF Ohali, Anat
Avigad, Smadar
Naumov, Inna
Goshen, Yacov
Ash, Shifra
Yaniv, Isaac
TI Different telomere maintenance mechanisms in alveolar and embryonal
rhabdomyosarcoma
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID MESSENGER-RNA EXPRESSION; SOFT-TISSUE SARCOMAS; CANCER; ASSOCIATION;
LENGTH; TUMORS; LIPOSARCOMAS; OSTEOSARCOMA; PROGRESSION; CELLS
AB The activation of a telomere maintenance mechanism (TMM) is crucial for the immortalization of tumor cells. Most human cancers apply telomerase-dependent TMM but some use a mechanism called alternative lengthening of telomeres (ALT). The latter was suggested to be mainly characterizing sarcomas with nonspecific complex karyotypes, whereas telomerase activation is typical of sarcomas generated by specific translocations. In this study, we investigated the TMM and its association with survival in rhabdomyosarcoma (RMS), which is characterized by two major subtypes: one that is harboring a specific translocation (alveolar) and one that has a nonspecific karyotype (embryonal). Telomerase activity (TA), using telomerase repeat amplification protocol (TRAP) assay, and telomere length (TRF), using Southern blotting, were analyzed in tumor samples from 31 patients (16 embryonal and IS alveolar). Alveolar RMS tumors exhibited no ALT phenotype and the majority presented TA. Some embryonal tumors exhibited an ALT or "ALT-like" phenotype which lacked TA, whereas others expressed telomerase-dependent TMM, and neither TA nor ALT correlated with outcome. The average TRIF length of the embryonal tumors was significantly higher than that of the alveolar tumors (10.8 vs. 7.2 kb, P = 0.003). Interestingly, some tumors of both subtypes presented no TMM. These observations suggest that alveolar RMS predominantly use telomerase-dependent TMM, whereas in embryonal tumors both telomerase and ALT may play a role. These findings have important implications for understanding the role of TMM in the development of RMS tumors, and for future designing adapted treatment strategies. (c) 2008 Wiley-Liss, Inc.
C1 [Ohali, Anat; Avigad, Smadar; Goshen, Yacov; Ash, Shifra; Yaniv, Isaac] Schneider Childrens Med Ctr Israel, IL-49202 Petah Tiqwa, Israel.
[Ohali, Anat; Avigad, Smadar; Naumov, Inna; Goshen, Yacov; Ash, Shifra; Yaniv, Isaac] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Ohali, Anat; Avigad, Smadar; Naumov, Inna; Yaniv, Isaac] Felsenstein Med Res Ctr, Petah Tiqwa, Israel.
[Ohali, Anat] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Avigad, S (reprint author), Schneider Childrens Med Ctr Israel, 14 Kaplan St, IL-49202 Petah Tiqwa, Israel.
EM savigad@post.tau.ac.il
FU Tamar Kravitz Funds
FX Supported by: Tamar Kravitz Funds.
NR 24
TC 8
Z9 8
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1045-2257
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD NOV
PY 2008
VL 47
IS 11
BP 965
EP 970
DI 10.1002/gcc.20600
PG 6
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 350MH
UT WOS:000259356100006
PM 18663749
ER
PT J
AU Ullah, Z
Kohn, MJ
Yagi, R
Vassilev, LT
DePamphilis, ML
AF Ullah, Zakir
Kohn, Matthew J.
Yagi, Rieko
Vassilev, Lyubomir T.
DePamphilis, Melvin L.
TI Differentiation of trophoblast stem cells into giant cells is triggered
by p57/Kip2 inhibition of CDK1 activity
SO GENES & DEVELOPMENT
LA English
DT Article
DE Endoreduplication; placentomegaly; trophoblast giant cell; p57; CDK1;
DNA replication
ID DROSOPHILA FOLLICLE CELLS; CYCLE PROGRESSION; DNA-REPLICATION;
RETINOBLASTOMA PROTEIN; MAMMALIAN DEVELOPMENT; G(2)/M CHECKPOINT; CDC2
MUTANT; S-PHASE; P57(KIP2); GEMININ
AB Genome endoreduplication during mammalian development is a rare event for which the mechanism is unknown. It first appears when fibroblast growth factor 4 (FGF4) deprivation induces differentiation of trophoblast stem (TS) cells into the nonproliferating trophoblast giant (TG) cells required for embryo implantation. Here we show that RO3306 inhibition of cyclin-dependent protein kinase 1 (CDK1), the enzyme required to enter mitosis, induced differentiation of TS cells into TG cells. In contrast, RO3306 induced abortive endoreduplication and apoptosis in embryonic stem cells, revealing that inactivation of CDK1 triggers endoreduplication only in cells programmed to differentiate into polyploid cells. Similarly, FGF4 deprivation resulted in CDK1 inhibition by overexpressing two CDK-specific inhibitors, p57/KIP2 and p21/CIP1. TS cell mutants revealed that p57 was required to trigger endoreduplication by inhibiting CDK1, while p21 suppressed expression of the checkpoint protein kinase CHK1, thereby preventing induction of apoptosis. Furthermore, Cdk2(-/-) TS cells revealed that CDK2 is required for endoreduplication when CDK1 is inhibited. Expression of p57 in TG cells was restricted to G-phase nuclei to allow CDK activation of S phase. Thus, endoreduplication in TS cells is triggered by p57 inhibition of CDK1 with concomitant suppression of the DNA damage response by p21.
C1 [Ullah, Zakir; Kohn, Matthew J.; DePamphilis, Melvin L.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Yagi, Rieko] Ajinomoto Inst Life Sci, Kawasaki, Kanagawa 2108681, Japan.
[Vassilev, Lyubomir T.] Hoffmann La Roche Inc, Roche Res Ctr, Dept Discovery Oncol, Nutley, NJ 07110 USA.
RP DePamphilis, ML (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA.
EM depamphm@mail.nih.gov
NR 61
TC 87
Z9 89
U1 0
U2 6
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD NOV 1
PY 2008
VL 22
IS 21
BP 3024
EP 3036
DI 10.1101/gad.1718108
PG 13
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 368DY
UT WOS:000260602700012
PM 18981479
ER
PT J
AU Mukherjee, B
Ahn, J
Gruber, SB
Rennert, G
Moren, V
Chatterjee, N
AF Mukherjee, Bhramar
Ahn, Jaeil
Gruber, Stephen B.
Rennert, Gad
Moren, Victor
Chatterjee, Nilanjan
TI Tests for Gene-Environment Interaction From Case-Control Data: A Novel
Study of Type I Error, Power and Designs
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE case-only designs; empirical Bayes; gene-environment interaction;
genome-wide scan; Molecular Epidemiology of Colorectal Cancer
ID COLORECTAL-CANCER; MAXIMUM-LIKELIHOOD; RISK; INDEPENDENCE; ASSOCIATIONS;
GENOTYPE; EXPOSURE; SMOKING; DIET
AB To evaluate the risk of a disease associated with the joint effects of genetic susceptibility and environmental exposures, epidemiologic researchers often test for non-multiplicative gene-environment effects from case-control studies. In this article, we present a comparative study of four alternative tests for interactions: (i) the standard case-control method; (ii) the case-only method, which requires an assumption of gene-environment independence for the underlying population; (iii) a two-step method that decides between the case-only and case-control estimators depending on a statistical test for the gene-environment independence assumption and (iv) a novel empirical-Bayes (EB) method that combines the case-control and case-only estimators depending on the sample size and strength of the gene-environment association in the data. We evaluate the methods in terms of integrated Type I error and power, averaged with respect to varying scenarios for gene-environment association that are likely to appear in practice. These unique studies suggest that the novel EB procedure overall is a promising approach for detection of gene-environment interactions from case-control studies. In particular, the EB procedure, unlike the case-only or two-step methods, can closely maintain a desired Type I error under realistic scenarios of gene-environment dependence and yet can be substantially more powerful than the traditional case-control analysis when the gene-environment independence assumption is satisfied, exactly or approximately. Our studies also reveal potential utility of some non-traditional case-control designs that samples controls at a smaller rate than the cases. Apart from the simulation studies, we also illustrate the different methods by analyzing interactions of two commonly studied genes, N-acetyl transferase type 2 and glutathione s-transferase M1, with smoking and dietary exposures, in a large case-control study of colorectal cancer. Genet. Epidemiol. 32:615-626, 2008. Published 2008 Wiley-Liss, Inc.(dagger)
C1 [Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
[Mukherjee, Bhramar; Ahn, Jaeil] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Gruber, Stephen B.] Univ Michigan, Dept Internal Med Epidemiol & Human Genet, Ann Arbor, MI 48109 USA.
[Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel.
[Rennert, Gad] Technion Israel Inst Technol, Fac Med, CHS Natl Israeli Canc Control Ctr, Haifa, Israel.
[Moren, Victor] Catalan Inst Oncol, IDIBELL, Barcelona, Spain.
RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
EM chattern@mail.nih.gov
OI Moreno, Victor/0000-0002-2818-5487
FU NSF [DMS 07-06935]; NIH [R03 CA130045-01, R01 CA81488]; Spanish
Secretaria de Estado de Universidades e Investigacion [PR2006-04743];
National Heart Lung and Blood Institute [R01 HL091172-01]; National
Cancer Institute
FX Contract grant sponsor: NSF; Contract grant number: DMS 07-06935;
Contract grant sponsor: NIH; Contract grant numbers: R03 CA130045-01,
R01 CA81488; Contract grant sponsor: Spanish Secretaria de Estado de
Universidades e Investigacion; Contract grant number: PR2006-04743;
Contract grant sponsor: National Heart Lung and Blood Institute;
Contract grant number: R01 HL091172-01; Contract grant sponsor: National
Cancer Institute.
NR 18
TC 38
Z9 38
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
BP 615
EP 626
DI 10.1002/gepi.20337
PG 12
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600004
PM 18473390
ER
PT J
AU Pfeiffer, RM
Pee, D
Landi, MT
AF Pfeiffer, Ruth M.
Pee, David
Landi, Maria T.
TI On Combining Family and Case-Control Studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE ascertainment; nested random effects model; marginal model; family
history; stratified sampling
ID MELANOMA; MC1R; RISK; REGRESSION; INFERENCE; MODELS
AB Studies to detect genetic association with disease can be family-based, often using families with multiple affected members, or population based, as in population-based case-control studies. If data on both study types are available from the same population, it is useful to combine them to improve power to detect genetic associations. Two aspects of the data need to be accommodated, the sampling scheme and potential residual correlations among family members. We propose two approaches for combining data from a case-control study and a family study that collected families with multiple cases. In the first approach, we view a family as the sampling unit and specify the joint likelihood for the family members using a two-level mixed effects model to account for random familial effects and for residual genetic correlations among family members. The ascertainment of the families is accommodated by conditioning on the ascertainment event. The individuals in the case-control study are treated as families of size one, and their unconditional likelihood is combined with the conditional likelihood for the families. This approach yields subject specific maximum likelihood estimates of covariate effects. In the second approach, we view an individual as the sampling unit. The sampling scheme is accommodated using two-phase sampling techniques, marginal covariate effects are estimated, and correlations among family members are accounted for in the variance calculations. The models are compared in simulations. Data from a case-control and a family study from north-eastern Italy on melanoma and a low-risk melanoma-susceptibility gene, MC1R, are used to illustrate the approaches. Genet, Epidemiol. 32:638-646, 2008. Published 2008 Wiley-Liss, Inc.(dagger)
C1 [Pfeiffer, Ruth M.; Landi, Maria T.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Pee, David] Informat Management Serv Inc, Rockville, MD USA.
RP Pfeiffer, RM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd EPS 8030, Bethesda, MD 20892 USA.
EM pfeiffer@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011
NR 20
TC 11
Z9 11
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
BP 638
EP 646
DI 10.1002/gepi.20338
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600006
PM 18454494
ER
PT J
AU Kraft, P
Wacholder, S
Cornelis, M
Hu, F
Hayes, RB
Hunter, DJ
Chanock, S
AF Kraft, P.
Wacholder, S.
Cornelis, M.
Hu, F.
Hayes, R. B.
Hunter, D. J.
Chanock, S.
TI Crystal Ball, Magic 8 Ball, or Both? Empirical examples of the promise
and limits of genetic risk prediction for prostate cancer and type 2
diabetes
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Kraft, P.; Hunter, D. J.] Harvard Univ, Sch Publ Hlth, Prog Mol & Gen Epi, Cambridge, MA 02138 USA.
[Wacholder, S.; Hayes, R. B.] NCI, Div Can Epi & Gen, Bethesda, MD 20892 USA.
[Chanock, S.] NCI, Core Geno Fac, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 12
BP 672
EP 672
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600021
ER
PT J
AU Daw, EW
Kammerer, C
Lee, JH
Feitosa, M
Zmuda, J
Borecki, I
Barral, S
Hadley, E
Christensen, K
Maveux, R
Province, M
AF Daw, E. W.
Kammerer, C.
Lee, J. H.
Feitosa, M.
Zmuda, J.
Borecki, I.
Barral, S.
Hadley, E.
Christensen, K.
Maveux, R.
Province, M.
TI Genetic contributions to Longevity
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Daw, E. W.; Feitosa, M.; Borecki, I.; Province, M.] Washington Univ, St Louis, MO USA.
[Kammerer, C.; Zmuda, J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Lee, J. H.; Barral, S.; Maveux, R.] Columbia Univ, New York, NY USA.
[Hadley, E.] NIA, Bethesda, MD 20892 USA.
RI Feitosa, Mary/K-8044-2012
OI Feitosa, Mary/0000-0002-0933-2410
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 58
BP 685
EP 686
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600067
ER
PT J
AU Duggal, P
Klein, A
Cheng, CY
Lee, K
Klein, R
Klein, B
Bailey-Wilson, JE
AF Duggal, Priya
Klein, Alison
Cheng, Ching-Yu
Lee, Kris
Klein, Ronald
Klein, Barbara
Bailey-Wilson, Joan E.
TI SNP Linkage Scan of Glaucoma Related Traits in the Beaver Dam Eye Study
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Duggal, Priya; Cheng, Ching-Yu; Bailey-Wilson, Joan E.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Klein, Alison] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Lee, Kris; Klein, Ronald; Klein, Barbara] Univ Wisconsin, Madison, WI 53706 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 62
BP 687
EP 687
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600071
ER
PT J
AU Goldin, LR
Kristinsson, SY
Caporaso, NE
Bjorkholm, M
Turesson, I
Landgren, O
AF Goldin, L. R.
Kristinsson, S. Y.
Caporaso, N. E.
Bjorkholm, M.
Turesson, I.
Landgren, O.
TI Increased risk of monoclonal gammopathy of undetermined significance
(MGUS) and lymphoid tumors among first-degree relatives of MGUS cases
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Goldin, L. R.; Caporaso, N. E.; Landgren, O.] NCI, Bethesda, MD 20892 USA.
[Turesson, I.] Malmo Univ Hosp, Malmo, Sweden.
[Kristinsson, S. Y.; Bjorkholm, M.] Karolinska Inst, Stockholm, Sweden.
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 76
BP 691
EP 691
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600085
ER
PT J
AU Gu, E
Bergen, A
Chatterjee, N
Sheng-Shih, J
Yu, K
Yeager, M
Hunter, DJ
Thomas, G
Jacobs, K
Landi, MT
Chinock, S
Chen, J
Ziegler, R
Caporaso, N
Kraft, P
AF Gu, E.
Bergen, A.
Chatterjee, N.
Sheng-Shih, J.
Yu, K.
Yeager, M.
Hunter, D. J.
Thomas, G.
Jacobs, K.
Landi, M. T.
Chinock, S.
Chen, J.
Ziegler, R.
Caporaso, N.
Kraft, P.
TI Combining two genome wide association scans for seven smoking related
phenotypes replicates published associations in the CHRNA3/5 region
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Gu, E.; Hunter, D. J.; Chen, J.; Kraft, P.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Cambridge, MA 02138 USA.
[Chatterjee, N.; Yu, K.; Landi, M. T.; Ziegler, R.; Caporaso, N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Yeager, M.; Thomas, G.; Jacobs, K.; Chinock, S.] NCI, Core Genotyping Facil, Bethesda, MD 20892 USA.
[Sheng-Shih, J.] Johns Hopkins Univ, Baltimore, MD 21218 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 83
BP 693
EP 693
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600092
ER
PT J
AU Hancock, DB
Martin, ER
Scott, W
AF Hancock, D. B.
Martin, E. R.
Scott, Wk.
TI Potential interactions among NOS genes in Parkinson disease
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Hancock, D. B.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Martin, E. R.; Scott, Wk.] Univ Miami, Inst Human Genom, Miami, FL USA.
RI Hancock, Dana/D-8577-2012
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 89
BP 695
EP 695
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600098
ER
PT J
AU Kim, Y
Sorant, AJM
Wilson, AF
AF Kim, Y.
Sorant, A. J. M.
Wilson, A. F.
TI Genetic heterogeneity and the power of population- and intra-familial
based tests of association for quantitative traits
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Kim, Y.; Sorant, A. J. M.; Wilson, A. F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 105
BP 699
EP 700
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600114
ER
PT J
AU Liang, X
Ng, D
McMaster, ML
Landgren, O
Ciporaso, N
Goldin, LR
AF Liang, X.
Ng, D.
McMaster, M. L.
Landgren, O.
Ciporaso, N.
Goldin, L. R.
TI Common Genetic Variants in Candidate Genes and Risk of Familial Lymphoma
(LP)
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Liang, X.; Ng, D.; McMaster, M. L.; Landgren, O.; Ciporaso, N.; Goldin, L. R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 118
BP 703
EP 704
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600127
ER
PT J
AU Mandal, DM
Ledet, EM
Bailey-Wilson, JE
AF Mandal, D. M.
Ledet, E. M.
Bailey-Wilson, J. E.
TI Identification of prostate cancer susceptible locus in high-risk
African-American families
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Mandal, D. M.; Ledet, E. M.] LSU Hlth Sci Ctr, Dept Genet, New Orleans, LA USA.
[Bailey-Wilson, J. E.] NHGRI, NIH, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 127
BP 706
EP 706
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600136
ER
PT J
AU Matteini, AM
Fallin, MD
Kammerer, CM
Schupf, N
Yashin, AI
Mayeux, R
Barr, RG
Arbeev, KG
Christensen, K
Hadley, EC
Newman, AB
Walston, JD
AF Matteini, A. M.
Fallin, M. D.
Kammerer, C. M.
Schupf, N.
Yashin, A. I.
Mayeux, R.
Barr, R. G.
Arbeev, K. G.
Christensen, K.
Hadley, E. C.
Newman, A. B.
Walston, J. D.
TI Heritability of Endophenotypes of Pulmonary & Physical Function in Long
Life Family Study
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Matteini, A. M.; Walston, J. D.] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Kammerer, C. M.; Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Schupf, N.; Mayeux, R.; Barr, R. G.] Columbia Univ, New York, NY 10027 USA.
[Yashin, A. I.; Arbeev, K. G.] Duke Univ, Durham, NC 27706 USA.
[Christensen, K.] Univ So Denmark, Odense, Denmark.
[Hadley, E. C.] NIA, Bethesda, MD 20892 USA.
RI Christensen, Kaare/C-2360-2009
OI Christensen, Kaare/0000-0002-5429-5292
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 129
BP 706
EP 707
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600138
ER
PT J
AU Sung, H
Herrera-Galeano, JE
Sorant, AJM
Mathias, RA
Wilson, AF
AF Sung, H.
Herrera-Galeano, J. E.
Sorant, A. J. M.
Mathias, R. A.
Wilson, A. F.
TI Lack of agreement among intra-familial tests of association for
quantitative traits with low heritabilities
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Sung, H.; Herrera-Galeano, J. E.; Sorant, A. J. M.; Mathias, R. A.; Wilson, A. F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
[Herrera-Galeano, J. E.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 160
BP 715
EP 716
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600169
ER
PT J
AU Tayo, BO
Luke, A
Zhu, X
Adeyemo, A
Cooper, RS
AF Tayo, B. O.
Luke, A.
Zhu, X.
Adeyemo, A.
Cooper, R. S.
TI Association of regions on chromosomes 6 and 7 with blood pressure in
Nigerian families
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Tayo, B. O.; Luke, A.; Cooper, R. S.] Loyola Univ, Chicago Stritch Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL USA.
[Zhu, X.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Adeyemo, A.] NIH, Intramural Ctr Genom & Hlth Dispar, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 164
BP 716
EP 717
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600173
ER
PT J
AU Wu, H
Romieu, I
Sienra-Monge, JJ
Li, H
del Rio-Navarro, BE
London, SJ
AF Wu, H.
Romieu, I.
Sienra-Monge, J. J.
Li, H.
del Rio-Navarro, B. E.
London, S. J.
TI Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and
childhood asthma
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society
CY SEP 14-16, 2008
CL St Louis, MO
SP Int Genet Epidimiol Soc
C1 [Romieu, I.] NIPH, Cuernavaca, Morelos, Mexico.
[Sienra-Monge, J. J.; del Rio-Navarro, B. E.] HIMFG, Mexico City, DF, Mexico.
[London, S. J.] NIEHS, EB, DIR, NIH,DHHS,RTP,NC, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2008
VL 32
IS 7
MA 178
BP 720
EP 721
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 371ZQ
UT WOS:000260871600187
ER
PT J
AU Brandt, SM
Jaramillo-Gutierrez, G
Kumar, S
Barillas-Mury, C
Schneider, DS
AF Brandt, Stephanie M.
Jaramillo-Gutierrez, Giovanna
Kumar, Sanjeev
Barillas-Mury, Carolina
Schneider, David S.
TI Use of a Drosophila Model to Identify Genes Regulating Plasmodium Growth
in the Mosquito
SO GENETICS
LA English
DT Article
ID ANOPHELES-GAMBIAE; LISTERIA-MONOCYTOGENES; BACTERIAL; INFECTION;
MELANOGASTER; BERGHEI
AB We performed a forward genetic screen, using Drosophila as a surrogate mosquito, to identify host factors required for the growth of the avian malaria parasite, Plasmodium gallinaceum. We identified 18 presumed loss-of-function mutants that reduced the growth of the parasite in flies. Presumptive Mutation sites were identified in 14 of the mutants on the basis of the insertion site of a transposable element. None of the identified genes have been previously implicated in innate immune responses or interactions with Plasmodium. The functions of five Anopheles gambiae homologs were tested by using RNAi to knock down gene function followed by measuring the growth of the rodent parasite, Plasmodium berghei. Loss of function of four of these genes in the mosquito affected Plasmodium growth, suggesting that Drosophila can be used effectively as a Surrogate mosquito to identify relevant lost factors in the mosquito.
C1 [Brandt, Stephanie M.; Schneider, David S.] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
[Jaramillo-Gutierrez, Giovanna; Kumar, Sanjeev; Barillas-Mury, Carolina] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20892 USA.
RP Schneider, DS (reprint author), Stanford Univ, Dept Microbiol & Immunol, D333 Fairchild Bldg,299 Campus Dr, Stanford, CA 94305 USA.
EM dschneider@stanford.edu
FU Ellison Medical Foundation; National Science Foundation
FX This work was supported by the Ellison Medical Foundation (D.S.S.) and
the National Science Foundation (S.M.B.).
NR 19
TC 21
Z9 22
U1 1
U2 1
PU GENETICS
PI BALTIMORE
PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD NOV
PY 2008
VL 180
IS 3
BP 1671
EP 1678
DI 10.1534/genetics.108.089748
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 374IE
UT WOS:000261036200034
PM 18791251
ER
PT J
AU Gerken, TA
Ten Hagen, KG
Jamison, O
AF Gerken, Thomas A.
Ten Hagen, Kelly G.
Jamison, Oliver
TI Conservation of peptide acceptor preferences between Drosophila and
mammalian polypeptide-GalNAc transferase ortholog pairs
SO GLYCOBIOLOGY
LA English
DT Article
DE evolution; mucin; O-glycosylation; sequence motifs;
UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase
ID ACETYL-D-GALACTOSAMINE; N-ACETYLGALACTOSAMINYLTRANSFERASE FAMILY;
NEIGHBORING RESIDUE GLYCOSYLATION; O-LINKED GLYCOSYLATION; UDP-GALNAC;
TOXOPLASMA-GONDII; LECTIN DOMAINS; CDNA CLONING;
FUNCTIONAL-CHARACTERIZATION; CAENORHABDITIS-ELEGANS
AB UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltrans- ferases (ppGalNAc Ts) comprise a large family of glycosyltransferases that initiate mucin-type protein O-glycosylation, transferring alpha-GalNAc to Thr and Ser residues of polypeptide acceptors. Families of ppGalNAc Ts are found across diverse eukaryotes with orthologs identifiable from mammals to single-cell organisms. The peptide substrate specificity and specific protein targets of the individual ppGalNAc T family members remain poorly understood. Previously, we reported a series of oriented random peptide substrate libraries for quantitatively determining the peptide substrate specificities of the mammalian ppGalNAc T1 and T2 (Gerken TA, Raman J, Fritz TA, Jamison O. 2006. Identification of common and unique peptide substrate preferences for the UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases T1 & T2 (ppGalNAc T1 & T2) derived from oriented random peptide substrates. J Biol Chem. 281:32403-32416). With these substrates, previously unknown features of the transferases were revealed. Utilizing these and a new lengthened set of random peptides, studies have now been performed on PGANT5 and PGANT2, the Drosophila orthologs of T1 and T2. The results from these studies suggest that the major peptide substrate determinants for these transferases are contained within 2 to 3 residues flanking the site of glycosylation. It is further found that the mammalian and fly T1 orthologs display very similar peptide substrate preferences, while the T2 orthologs are nearly indistinguishable, suggesting similar peptide preferences amongst orthologous pairs have been maintained across evolution. This conclusion is further supported by sequence homology comparisons of each of the transferase orthologs, showing that the peptide substrate and UDP binding site residues are more highly conserved between species relative to their remaining catalytic and lectin domain residues.
C1 [Gerken, Thomas A.] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA.
[Gerken, Thomas A.; Jamison, Oliver] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA.
[Ten Hagen, Kelly G.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
RP Gerken, TA (reprint author), Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA.
EM txg2@cwru.edu
FU National Institutes of Health [RO1-CA-78834]; National Institute of
Dental and Craniofacial Research
FX National Institutes of Health (Grant RO1-CA-78834 to T. A. G.); the
Intramural Research Program of the National Institute of Dental and
Craniofacial Research, National Institutes of Health (to K. G. T. H).
NR 49
TC 27
Z9 27
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2008
VL 18
IS 11
BP 861
EP 870
DI 10.1093/glycob/cwn073
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 361QE
UT WOS:000260141400004
PM 18669915
ER
PT J
AU Ten Hagen, KG
Zhang, Y
Zhang, LP
AF Ten Hagen, Kelly G.
Zhang, Ying
Zhang, Liping
TI The Role of O-Glycosylation in Cell Adhesion During Development
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 12-15, 2008
CL Ft Worth, TX
SP Soc Glycobiol
C1 [Ten Hagen, Kelly G.; Zhang, Ying; Zhang, Liping] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2008
VL 18
IS 11
MA 12
BP 942
EP 942
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 361QE
UT WOS:000260141400021
ER
PT J
AU Ishihara, M
Sonon, R
Chill, L
Trinh, L
Shiloach, J
Azadi, P
AF Ishihara, Mayumi
Sonon, Roberto
Chill, Liat
Trinh, Loc
Shiloach, Joseph
Azadi, Parastoo
TI Characterization of Glycan Structure and the Sites of Glycosylation on
the Recombinant Human alpha 1-Proteinase Inhibitor, alpha-1PI By Mass
Spectrometry
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 12-15, 2008
CL Ft Worth, TX
SP Soc Glycobiol
C1 [Ishihara, Mayumi; Sonon, Roberto; Azadi, Parastoo] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA.
[Chill, Liat; Trinh, Loc; Shiloach, Joseph] NIH, Biotechnol Core Lab, Bethesda, MD 20892 USA.
US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2008
VL 18
IS 11
MA 95
BP 963
EP 963
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 361QE
UT WOS:000260141400104
ER
PT J
AU Poling, JS
Manoli, I
Klootwijk, R
Kurland, D
Ciccone, C
Patzel, K
Darvish, D
Zerfas, P
Starost, M
Dorward, H
Gahl, WA
Huizing, M
AF Poling, Justin S.
Manoli, Irini
Klootwijk, Riko
Kurland, David
Ciccone, Carla
Patzel, Katherine
Darvish, Daniel
Zerfas, Patricia
Starost, Matthew
Dorward, Heidi
Gahl, William A.
Huizing, Marjan
TI Hyposialylation in Various Glomerulopathies and Possible Rescue by
N-Acetylmannosamine
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 12-15, 2008
CL Ft Worth, TX
SP Soc Glycobiol
C1 [Poling, Justin S.; Manoli, Irini; Kurland, David; Ciccone, Carla; Patzel, Katherine; Dorward, Heidi; Gahl, William A.; Huizing, Marjan] NHGRI, NIH, Bethesda, MD 20892 USA.
[Klootwijk, Riko] Univ Coll, London, England.
[Darvish, Daniel] HIBM Res Grp, Encino, CA USA.
[Zerfas, Patricia; Starost, Matthew] NIH Vet Resources, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2008
VL 18
IS 11
MA 97
BP 964
EP 964
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 361QE
UT WOS:000260141400106
ER
PT J
AU Hsu, KL
Gildersleeve, JC
Mahal, LK
AF Hsu, Ku-Lung
Gildersleeve, Jeffrey C.
Mahal, Lara K.
TI Advancing the Lectin Microarray
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 12-15, 2008
CL Ft Worth, TX
SP Soc Glycobiol
C1 [Hsu, Ku-Lung; Mahal, Lara K.] Univ Texas Austin, Austin, TX 78712 USA.
[Gildersleeve, Jeffrey C.] NCI, Frederick, MD 21701 USA.
RI Gildersleeve, Jeffrey/N-3392-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2008
VL 18
IS 11
MA 123
BP 970
EP 970
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 361QE
UT WOS:000260141400132
ER
PT J
AU Raman, J
Guan, Y
Fritz, TA
Tabak, LA
AF Raman, Jayalakshmi
Guan, Yu
Fritz, Timothy A.
Tabak, Lawrence A.
TI Expression Patterns and Substrate Specificities of 4 Novel Members of
the UDP-GalNAc:Polypeptide a-N-Acetlygalactosaminyltransferase Family
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 12-15, 2008
CL Ft Worth, TX
SP Soc Glycobiol
C1 [Raman, Jayalakshmi; Guan, Yu; Fritz, Timothy A.; Tabak, Lawrence A.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2008
VL 18
IS 11
MA 144
BP 975
EP 975
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 361QE
UT WOS:000260141400153
ER
PT J
AU Puntambekar, N
Kee, Y
Kramer, K
AF Puntambekar, Nisha
Kee, Yun
Kramer, Kenneth
TI Spatial and Temporal Expressions of Glypicans in Zebrafish Embryonic
Development
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 12-15, 2008
CL Ft Worth, TX
SP Soc Glycobiol
C1 [Puntambekar, Nisha; Kee, Yun; Kramer, Kenneth] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2008
VL 18
IS 11
MA 158
BP 979
EP 979
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 361QE
UT WOS:000260141400167
ER
PT J
AU Tian, E
Hoffman, M
Ten Hagen, KG
AF Tian, E.
Hoffman, Matthew
Ten Hagen, Kelly G.
TI Mucin-Type O-Glycosylation During Epithelial Tube Formation
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 12-15, 2008
CL Ft Worth, TX
SP Soc Glycobiol
C1 [Tian, E.; Hoffman, Matthew; Ten Hagen, Kelly G.] NIDCR, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2008
VL 18
IS 11
MA 157
BP 979
EP 979
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 361QE
UT WOS:000260141400166
ER
PT J
AU Oyelaran, O
Joseph, M
Gildersleeve, J
AF Oyelaran, Oyinda
Joseph, Manimala
Gildersleeve, Jeff
TI Profiling Antibodies with Carbohydrate Antigen Arrays
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 12-15, 2008
CL Ft Worth, TX
SP Soc Glycobiol
C1 [Oyelaran, Oyinda; Joseph, Manimala; Gildersleeve, Jeff] Natl Canc Inst, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2008
VL 18
IS 11
MA 175
BP 983
EP 983
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 361QE
UT WOS:000260141400183
ER
PT J
AU Houghton, A
Barchi, J
Sundgren, A
Morey, S
Rittenhouse-Olson, K
AF Houghton, Amy
Barchi, Joseph
Sundgren, Andreas
Morey, Susan
Rittenhouse-Olson, Kate
TI Novel Synthetic Carbohydrate Tumor Antigen Vaccine Strategies
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 12-15, 2008
CL Ft Worth, TX
SP Soc Glycobiol
C1 [Houghton, Amy; Morey, Susan; Rittenhouse-Olson, Kate] SUNY Buffalo, Buffalo, NY 14260 USA.
[Barchi, Joseph; Sundgren, Andreas] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2008
VL 18
IS 11
MA 185
BP 985
EP 986
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 361QE
UT WOS:000260141400194
ER
PT J
AU Boeggeman, EE
Ramakrishnan, B
Pasek, M
Waybright, TJ
Manzoni, MR
Qasba, PK
AF Boeggeman, Elizabeth E.
Ramakrishnan, Boopathy
Pasek, Marta
Waybright, Timothy J.
Manzoni, Maria R.
Qasba, Pradman K.
TI Applications of Galactosyltransferases in the Site-specific Conjugation
of Therapeutic Monoclonal Antibodies
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 12-15, 2008
CL Ft Worth, TX
SP Soc Glycobiol
C1 [Pasek, Marta; Manzoni, Maria R.; Qasba, Pradman K.] NCI, SGS, CCR NP, Frederick, MD 21701 USA.
[Boeggeman, Elizabeth E.; Ramakrishnan, Boopathy; Waybright, Timothy J.] SAIC Frederick Inc, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2008
VL 18
IS 11
MA 236
BP 998
EP 998
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 361QE
UT WOS:000260141400245
ER
PT J
AU Pasek, M
Ramakrishnan, B
Boeggeman, E
Manzoni, M
Qasba, P
AF Pasek, Marta
Ramakrishnan, Boopathy
Boeggeman, Elizabeth
Manzoni, Maria
Qasba, Pradman
TI Targeted Mutations of Bovine alpha 1,3 Galactosyltransferase (a1,3 GalT)
that Change it's Sugar Donor Specificity: Applications in Nanobiology
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology
CY NOV 12-15, 2008
CL Ft Worth, TX
SP Soc Glycobiol
C1 [Pasek, Marta; Manzoni, Maria; Qasba, Pradman] NCI Frederick, CCR, Struct Glycobiol Sect, Frederick, MD USA.
[Ramakrishnan, Boopathy; Boeggeman, Elizabeth] SAIC, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2008
VL 18
IS 11
MA 235
BP 998
EP 998
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 361QE
UT WOS:000260141400244
ER
PT J
AU Vgontzas, A
Cui, LH
Merikangas, KR
AF Vgontzas, Angeliki
Cui, Lihong
Merikangas, Kathleen R.
TI Are Sleep Difficulties Associated With Migraine Attributable to Anxiety
and Depression?
SO HEADACHE
LA English
DT Article
DE sleep; migraine; anxiety; depression
ID QUALITY-OF-LIFE; PSYCHIATRIC-DISORDERS; GENERAL-POPULATION;
UNITED-STATES; YOUNG-ADULTS; HEADACHE; PREVALENCE; CHILDREN;
COMORBIDITY; DISTURBANCES
AB (Headache 2008;48:1451-1459)
To examine whether sleep complaints reported by migraineurs can be attributed to comorbid anxiety and/or depression.
A consistent association between migraine and sleep complaints has been reported in community and clinical studies. However, anxiety and depression are often comorbid with migraine. Thus, it may be possible that the increased prevalence of sleep problems in migraineurs is attributable to comorbid anxiety and depression. To our knowledge, no previous studies have demonstrated that the associations are not solely attributed to comorbid anxiety and depression.
Controlled family study of anxiety disorders and substance use disorders in a community in New Haven County, CT. The sample included 221 probands (41 migraineurs) and their 261 directly interviewed first-degree relatives (39 migrainuers), including parents, siblings, and offspring over age 18. A lifetime history of migraine was obtained using the Diagnostic Interview for Headache Syndromes. A lifetime history of psychiatric disorders was obtained using the semi-structured Schedule for Affective Disorders and Schizophrenia which was modified to incorporate Diagnostic and Statistical Manual diagnostic criteria. Several sleep items on current and lifetime sleep complaints were included as a subset of the interview.
There was a significant association between migraine and the number of sleep problems as well as several specific sleep symptoms among probands and their adult relatives. Adults with migraine reported having significantly more lifetime sleep problems (OR [CI] = 2.3 [1.1-4.6]), and more current sleep difficulties, specifically, inadequate sleep (2.5 [1.2-5.0]), difficulty falling asleep (3.0 [1.5-6.3]), and persistent nightmares of childhood onset (4.3 [1.8-9.9]) than those without migraine. The associations between sleep problems and migraine persisted after controlling for both lifetime and current anxiety and mood disorders.
The association between sleep problems and migraine that is not solely explained by comorbid anxiety disorders or depression suggests that sleep problems should be evaluated among people with migraine.
C1 [Vgontzas, Angeliki; Cui, Lihong; Merikangas, Kathleen R.] NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA.
RP Merikangas, KR (reprint author), 35 Convent Dr,1A201,MSC 3720, Bethesda, MD 20814 USA.
FU Intramural NIH HHS [Z01 MH002804-05, Z01 MH002849-03]
NR 48
TC 37
Z9 39
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0017-8748
J9 HEADACHE
JI Headache
PD NOV-DEC
PY 2008
VL 48
IS 10
BP 1451
EP 1459
DI 10.1111/j.1526-4610.2008.01175.x
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 375OV
UT WOS:000261124100006
PM 18624714
ER
PT J
AU Bandettini, WP
Arai, AE
AF Bandettini, W. P.
Arai, A. E.
TI Advances in clinical applications of cardiovascular magnetic resonance
imaging
SO HEART
LA English
DT Review
ID CORONARY-ARTERY-DISEASE; ACUTE MYOCARDIAL-INFARCTION;
POSITRON-EMISSION-TOMOGRAPHY; WALL-MOTION ABNORMALITIES;
LEFT-VENTRICULAR FUNCTION; TARGETED CONTRAST AGENT;
ISCHEMIC-HEART-DISEASE; MESENCHYMAL STEM-CELLS; TIME CINE MRI;
DELAYED-ENHANCEMENT
AB Cardiovascular magnetic resonance (CMR) is an evolving technology with growing indications within the clinical cardiology setting. This review article summarises the current clinical applications of CMR. The focus is on the use of CMR in the diagnosis of coronary artery disease with summaries of validation literature in CMR viability, myocardial perfusion, and dobutamine CMR. Practical uses of CMR in non-coronary diseases are also discussed.
C1 [Bandettini, W. P.; Arai, A. E.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
RP Bandettini, WP (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Room BID416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA.
EM ingkanisorn@nih.gov
FU Intramural NIH HHS [Z01 HL004607-09, Z01 HL004607-10, ZID HL006140-01,
ZID HL006140-02]
NR 142
TC 22
Z9 22
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
J9 HEART
JI Heart
PD NOV
PY 2008
VL 94
IS 11
BP 1485
EP 1495
DI 10.1136/hrt.2007.119016
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 361VK
UT WOS:000260155100026
PM 18208827
ER
PT J
AU Morishima, C
Morgan, TR
Everhart, JE
Wright, EC
Apodaca, MC
Gretch, DR
Shiffman, ML
Everson, GT
Lindsay, KL
Lee, WM
Lok, ASF
Dienstag, JL
Ghany, MG
Curto, TM
AF Morishima, Chihiro
Morgan, Timothy R.
Everhart, James E.
Wright, Elizabeth C.
Apodaca, Minjun C.
Gretch, David R.
Shiffman, Mitchell L.
Everson, Gregory T.
Lindsay, Karen L.
Lee, William M.
Lok, Anna S. F.
Dienstag, Jules L.
Ghany, Marc G.
Curto, Teresa M.
CA HALT C Trial Grp
TI Interpretation of Positive Transcription-Mediated Amplification Test
Results from Polymerase Chain Reaction-Negative Samples Obtained After
Treatment of Chronic Hepatitis C
SO HEPATOLOGY
LA English
DT Article
ID INTERFERON-ALPHA THERAPY; RNA QUALITATIVE ASSAY; HCV RNA; VIRUS-RNA;
VIROLOGICAL RESPONSE; PEGINTERFERON ALPHA-2A; FOLLOW-UP; RIBAVIRIN;
TRIAL; TMA
AB The siemens VERSANT (R) transcription-mediated amplification (TMA) assay is extremely sensitive for the detection of hepatitis C virus (HCV) RNA in serum. Eleven of 180 subjects in the Hepatitis C Antiviral Long-term Treatment against cirrhosis (HALT-C) Trial who achieved polymerase chain reaction (PCR)-defined sustained virological response (SVR) at week 72 also had TMA-positive results from the same blood draw; six were positive on repeat testing. We report the follow-up on these 11 patients, and the reproducibility of TMA test results from PCR-negative samples in relationship to antiviral treatment outcome. Peginterferon and ribavirin treatment was initiated in 1145 prior interferon nonresponders with advanced hepatic fibrosis. Treatment was continued for 48 weeks if patients had undetectable HCV RNA by PCR at treatment week 20. Frozen serum samples from weeks 12, 20, 24,48, and 72 were subsequently tested by TMA. Nine of the I I patients returned for testing (median, 30 months after the week 72 visit), and all had undetectable HCV RNA by TMA and PCR. Among 759 PCR-negative samples obtained during treatment that were tested twice by TMA, 17% overall exhibited consistently positive results, and 21% exhibited inconsistently positive results. SVR was more likely if TMA was consistently negative than if consistently or inconsistently positive. With continued treatment, patients with inconsistently positive TMA results were more likely to become TMA-negative than TMA-positive (P < 0.0001). Conclusion; In PCR-negative samples, positive TMA results may indicate the presence of low levels of HCV RNA. However, because patients with positive TMA results may achieve SVR, management decisions during therapy should not be based on a single positive TMA test result. (HEPATOLOGY 2008;48:1412-1419.)
C1 [Morishima, Chihiro; Apodaca, Minjun C.; Gretch, David R.] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA.
[Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA.
[Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
[Wright, Elizabeth C.] NIDDKD, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Shiffman, Mitchell L.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA.
[Everson, Gregory T.] Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Denver, CO 80202 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. F.] Univ Michigan, Div Gastroenterol, Med Ctr, Ann Arbor, MI 48109 USA.
[Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Dienstag, Jules L.] Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA USA.
[Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA.
RP Morishima, C (reprint author), Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA.
RI Lok, Anna /B-8292-2009; Lopes Lera, Daniele/H-6081-2016; Acorsi,
Rayanne/H-6066-2016; Vieira Teixeira, Jorge Juarez/H-6495-2016; MOREIRA
NETO, LUIZ JORGE/H-6588-2016; OLIVEIRA, WELLINGTON/H-6591-2016; Borges
Padilha Ferreira, Fabiana/H-6597-2016; Beletini, Lucimara
Fatima/H-6083-2016; Cristina Ferreira, Erika /H-6607-2016;
OI MOREIRA NETO, LUIZ JORGE/0000-0002-7407-4120; Yang,
Shuman/0000-0002-9638-0890
FU National Institute of Diabetes & Digestive & Kidney Diseases
[N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321,
N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325,
N01-DK-9-2326, N01-DK-9-2327, N01-DK-9-2328]; National Institute of
Allergy and Infectious Diseases (NIAID); National Cancer Institute;
National Center for Minority Health and Health Disparities; National
Center for Research Resources; National Institutes of Health
[M01RR-06192, M01RR-01066, M01RR-00051, M01RR-00827, M01RR-00633,
M01RR-00043, M01RR-00042, M01RR-00065]; Hoffmann-La Roche, Inc; Bayer
Diagnostics
FX This study was supported by the National Institute of Diabetes &
Digestive & Kidney Diseases under contract numbers N01-DK-9-2318,
N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322,
N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2326,
N01-DK-9-2327 and N01-DK-9-2328, with supplemental funds from the
National Institute of Allergy and Infectious Diseases (NIAID), the
National Cancer Institute, the National Center for Minority Health and
Health Disparities and by General Clinical Research Center grants from
the National Center for Research Resources, National Institutes of
Health (grant numbers M01RR-06192, M01RR-01066, M01RR-00051,
M01RR-00827, M01RR-00633, M01RR-00043, M01RR-00042, and M01RR-00065).
Additional funding to conduct this study was supplied by Hoffmann-La
Roche, Inc. through a Cooperative Research and Development Agreement
(CRADA) with the National Institutes of Health. Financial support was
also provided by Bayer Diagnostics through a Clinical Trial Agreement
with the National Institutes of Health and a Research and Technology
Development Agreement with the University of Washington.
NR 19
TC 18
Z9 19
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD NOV
PY 2008
VL 48
IS 5
BP 1412
EP 1419
DI 10.1002/hep.22487
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 368BP
UT WOS:000260596600010
PM 18816437
ER
PT J
AU Schonhoff, CM
Thankey, K
Webster, CRL
Wakabayashi, Y
Wolkoff, AW
Anwer, MS
AF Schonhoff, Christopher M.
Thankey, Krishna
Webster, Cynthia R. L.
Wakabayashi, Yoshiyuki
Wolkoff, Allan W.
Anwer, M. Sawkat
TI Rab4 Facilitates Cyclic Adenosine Monophosphate-Stimulated Bile Acid
Uptake and Na+-Taurocholate Cotransporting Polypeptide Translocation
SO HEPATOLOGY
LA English
DT Article
ID RAT-LIVER; SIGNALING PATHWAY; NA+/TAUROCHOLATE COTRANSPORT; VESICLE
TRANSPORT; GLUCOSE-TRANSPORT; INSULIN; EXPRESSION; PROTEINS; ADIPOCYTES;
MEMBRANE
AB Cyclic adenosine monophosphate (cAMP) stimulates hepatic bile acid uptake by translocating sodium-taurocholate (TC) cotransporting polypeptide (Ntcp) from an endosomal compartment to the plasma membrane. Rab4 is associated with early endosomes and involved in vesicular trafficking. This study was designed to determine the role of Rab4 in cAMP-induced TC uptake and Ntcp translocation. HuH-Ntcp cells transiently transfected with empty vector, guanosine triphosphate (GTP) locked dominant active Rab4 (Rab4(GTP)), or guanosine diphosphate (GDP) locked dominant inactive Rab4 (Rab4(GDP)) were used to study the role of Rab4. Neither Rab4(GTP) nor Rab4(GDP) affected either basal TC uptake or plasma membrane Ntcp level. However, cAMP-induced increases in TC uptake and Ntcp translocation were enhanced by Rab4(GTP) and inhibited by Rab4(GDP). In addition, cAMP increased GTP binding to endogenous Rab4 in a time-dependent, but phosphoinositide-3-kinase-independent manner. Conclusion: Taken together, these results suggest that cAMP-mediated phosphoinositide-3-kinase-independent activation of Rab4 facilitates Ntcp translocation in HuH-Ntcp cells. (HEPATOLOGY 2008;48:1665-1670.)
C1 [Schonhoff, Christopher M.; Thankey, Krishna; Anwer, M. Sawkat] Tufts Cummings Sch Vet Med, Dept Biomed Sci, North Grafton, MA 01536 USA.
[Webster, Cynthia R. L.] Tufts Cummings Sch Vet Med, Dept Clin Sci, North Grafton, MA 01536 USA.
[Wakabayashi, Yoshiyuki] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Wolkoff, Allan W.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
RP Anwer, MS (reprint author), Tufts Cummings Sch Vet Med, Dept Biomed Sci, 200 Westboro Rd, North Grafton, MA 01536 USA.
EM SawkatAnwer@tufts.edu
FU NIH [DK-33436, DK-65975, DK-07635, RR-18267, DK23026]; Intramural
Program of Eunice Kennedy Shriver, NICHD, NIH
FX Supported in part by NIH grants DK-33436 (to M. S.A.), DK-65975 (to C.
R.L.W), DK-07635 and RR- 18267 (to K.T.), DK23026 (to A.W.W) and by the
Intramural Program of Eunice Kennedy Shriver, NICHD, NIH (to Y.W)
NR 33
TC 11
Z9 11
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 NOV
PY 2008
VL 48
IS 5
BP 1665
EP 1670
DI 10.1002/hep.22495
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 368BP
UT WOS:000260596600035
PM 18688880
ER
PT J
AU Laszlo, V
Dezso, K
Baghy, K
Papp, V
Kovalszky, I
Safrany, G
Thorgeirsson, SS
Nagy, P
Paku, S
AF Laszlo, Viktoria
Dezso, Katalin
Baghy, Kornelia
Papp, Veronika
Kovalszky, Ilona
Safrany, Geza
Thorgeirsson, Snorri S.
Nagy, Peter
Paku, Sandor
TI Triiodothyronine accelerates differentiation of rat liver progenitor
cells into hepatocytes
SO HISTOCHEMISTRY AND CELL BIOLOGY
LA English
DT Article
DE Oval cell; Maturation; Regeneration; Retroviral transduction; Primary
mitogen
ID HEPATIC OVAL CELLS; STEM-CELLS; IN-VITRO; PARTIAL-HEPATECTOMY;
REGENERATION; EXPRESSION; PROLIFERATION; INJURY; MODEL;
HEPATOCARCINOGENESIS
AB The 2-acetaminofluorene/partial hepatectomy (AAF/Phx) model is widely used to induce oval/progenitor cell proliferation in the rat liver. We have used this model to study the impact of a primary hepatocyte mitogen, triiodothyronine (T3) on the liver regenerating by the recruitment of oval/progenitor cells. Administration of T3 transiently accelerates the proliferation of the oval cells, which is followed by rapid differentiation into small hepatocytes. The oval cell origin of the small hepatocytes has been proven by tracing retrovirally transduced and BrdU marked oval cells. The differentiating oval cells become positive for hepatocyte nuclear factor-4 and start to express hepatocyte specific connexin 32, alpha 1 integrin, Prox1, cytochrom P450s, and form CD 26 positive bile canaliculi. At the same time oval cell specific OV-6 and alpha-fetoprotein expression is lost. The upregulation of hepatocyte specific mRNAs: albumin, tyrosine aminotransferase and tryptophan 2,3-dioxygenase detected by real-time PCR also proves hepatocytic maturation. The hepatocytic conversion of oval cells occurs on the seventh day after the Phx in this model while the first small hepatocytes appear 5 days later without T3 treatment. The administration of the primary hepatocyte mitogen T3 accelerates the differentiation of hepatic progenitor cells into hepatocytes in vivo, and that may have therapeutic potential.
C1 [Laszlo, Viktoria; Dezso, Katalin; Baghy, Kornelia; Papp, Veronika; Kovalszky, Ilona; Nagy, Peter; Paku, Sandor] Semmelweis Univ, Dept Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary.
[Safrany, Geza] Natl Res Inst Radiobiol & Radiohyg, Budapest, Hungary.
[Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Nagy, P (reprint author), Semmelweis Univ, Dept Pathol & Expt Canc Res 1, Ulloi Ut 26, H-1085 Budapest, Hungary.
EM nagy@korb1.sote.hu
NR 42
TC 18
Z9 18
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0948-6143
J9 HISTOCHEM CELL BIOL
JI Histochem. Cell Biol.
PD NOV
PY 2008
VL 130
IS 5
BP 1005
EP 1014
DI 10.1007/s00418-008-0482-z
PG 10
WC Cell Biology; Microscopy
SC Cell Biology; Microscopy
GA 359OR
UT WOS:000259997900016
PM 18663461
ER
PT J
AU Read, JS
Best, BM
Stek, A
Hu, C
Capparelli, EV
Holland, DT
Burchett, SK
Smith, ME
Sheeran, EC
Shearer, WT
Febo, I
Mirochnick, M
AF Read, J. S.
Best, B. M.
Stek, A. M.
Hu, C.
Capparelli, E. V.
Holland, D. T.
Burchett, S. K.
Smith, M. E.
Sheeran, E. C.
Shearer, W. T.
Febo, I.
Mirochnick, M.
TI Pharmacokinetics of new 625 mg nelfinavir formulation during pregnancy
and postpartum
SO HIV MEDICINE
LA English
DT Article
DE HIV; nelfinavir; pharmacokinetics; pregnancy
ID PROTEASE INHIBITORS; WOMEN; EXPOSURE
AB Objectives
Our objective was to evaluate the pharmacokinetics of nelfinavir (NFV) (625 mg tablets) 1250 mg twice daily during pregnancy and postpartum.
Methods
The participants were HIV-1-infected pregnant women enrolled in P1026s and receiving NFV (625 mg tablets) 1250 mg twice daily as part of routine clinical care. Intensive steady-state 12-h NFV pharmacokinetic profiles were performed during pregnancy and postpartum. The target NFV area under the plasma concentration-time curve (AUC(0-12)) was >= 10th percentile NFV AUC(0-12) in non-pregnant historical controls (18.5 mu g h/mL).
Results
Of 27 patients receiving NFV, pharmacokinetic data were available for four (second trimester), 27 (third trimester) and 22 (postpartum) patients. The NFV maximum concentration (C(max)), 12-h post-dose concentration (C(12)) and AUC(0-12) were significantly lower during the third trimester compared to postpartum (P <= 0.03). The metabolite hydroxyl-tert-butylamide (M8) AUC(0-12) and the M8/NFV AUC ratio were lower during the third trimester compared to postpartum (P < 0.01). The NFV AUC(0-12) exceeded the AUC(0-12) target for 15/27 (56%) and 21/22 (95%) of third trimester and postpartum patients, respectively. The minimum concentration (C(min)) was above the suggested minimum trough concentration (0.8 mu g/mL) in 15% (third trimester) and 18% (postpartum). The plasma viral load was < 400 HIV-1 RNA copies/mL in 81% of patients at delivery.
Conculsions
These results suggest that higher doses of NFV should be considered during pregnancy.
C1 [Read, J. S.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA.
[Best, B. M.; Capparelli, E. V.; Holland, D. T.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Stek, A. M.] Univ So Calif, Los Angeles, CA USA.
[Hu, C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Burchett, S. K.] Childrens Hosp, Boston, MA 02115 USA.
[Smith, M. E.] NIAID, Bethesda, MD 20892 USA.
[Sheeran, E. C.] Social & Sci Syst Inc, Silver Spring, MD USA.
[Shearer, W. T.] Baylor Coll Med, Houston, TX 77030 USA.
[Febo, I.] Univ Puerto Rico, San Juan, PR 00936 USA.
[Mirochnick, M.] Boston Univ, Boston, MA 02215 USA.
RP Read, JS (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Execut Bldg,Room 4B11C,6100 Execut Blvd MSC 7510, Bethesda, MD 20892 USA.
EM jennifer_read@nih.gov
RI Hu, Chengcheng/A-8391-2017
FU NCRR NIH HHS [5 M01 RR01271, M01 RR000533, M01 RR001271, M01 RR00533];
NIAID NIH HHS [U01 AI068632-03, U01 AI027560, U01 AI032907, U01
AI041089, U01 AI04189, U01 AI32907, U01 AI41089, UO1 AI27560-18]; NICHD
NIH HHS [N01-HD-3-3365, U01 HD031318, U01-HD-031318-11]
NR 18
TC 21
Z9 21
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1464-2662
J9 HIV MED
JI HIV Med.
PD NOV
PY 2008
VL 9
IS 10
BP 875
EP 882
DI 10.1111/j.1468-1293.2008.00640.x
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA 366QS
UT WOS:000260499100006
PM 18795962
ER
PT J
AU Theoret, MR
Cohen, CJ
Nahvi, AV
Ngo, LT
Suri, KB
Powell, DJ
Dudley, ME
Morgan, RA
Rosenberg, SA
AF Theoret, Marc R.
Cohen, Cyrille J.
Nahvi, Azam V.
Ngo, Lien T.
Suri, Kimberly B.
Powell, Daniel J., Jr.
Dudley, Mark E.
Morgan, Richard A.
Rosenberg, Steven A.
TI Relationship of p53 Overexpression on Cancers and Recognition by
Anti-p53 T Cell Receptor-Transduced T Cells
SO HUMAN GENE THERAPY
LA English
DT Article
ID WILD-TYPE P53; SEQUENCE P53(264-272) PEPTIDE; PERIPHERAL-BLOOD
LYMPHOCYTES; ADVANCED BREAST-CANCER; MESSENGER-RNA LEVELS;
LI-FRAUMENI-SYNDROME; DENDRITIC CELLS; TUMOR-ANTIGEN; LUNG-CANCER;
COLORECTAL-CANCER
AB Tumor suppressor p53 is reported to be an attractive immunotherapy target because it is mutated in approximately half of human cancers, resulting in inactivation and often an accumulation of the protein in the tumor cells. Only low amounts of protein are detectable in normal tissues. The differential display of antigen in normal versus tumor tissues has been reported to create an opportunity to target p53 by immunotherapy. We sought to determine the relationship between p53 expression and its recognition by cognate T cells in human tumors including common epithelial malignancies. Inasmuch as nonsense or missense p53 mutations may disrupt processing and presentation, we studied tumors with either identified wild-type or mutated p53, based on our gene-sequencing studies or published data. T cells transduced with a high-affinity, p53(264-272)-reactive T cell receptor (TCR) derived from HLA-A2.1 transgenic mice recognized a wide panel of human tumor lines. There was no significant correlation between p53 expression in tumors and recognition by the anti-p53 TCR-transduced T cells. This conclusion was based on the study of 48 cell lines and is in contrast to several prior studies that used only a limited number of selected cell lines. A panel of normal cells was evaluated for recognition, and some of these populations were capable of stimulating anti-p53 T cells, albeit at low levels. These studies raise doubts concerning the suitability of targeting p53 in the immunotherapy of cancer patients.
C1 [Theoret, Marc R.; Nahvi, Azam V.; Ngo, Lien T.; Suri, Kimberly B.; Dudley, Mark E.; Morgan, Richard A.; Rosenberg, Steven A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Theoret, Marc R.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Cohen, Cyrille J.] Bar Ilan Univ, Lab Tumor Immunol & Immunotherapy, IL-52900 Ramat Gan, Israel.
[Powell, Daniel J., Jr.] Univ Penn, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10-CRC,Room 3W3-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM sar@nih.gov
FU National Cancer Institute, National Institutes of Health
FX Funding to support this work was provided by the Intramural Research
Program, National Cancer Institute, National Institutes of Health. The
authors thank Dr. Scott Garrett, Dr. Donald Sens, and Dr. Hung Khong for
providing cell lines; Dr. Zhiya Yu for providing a melanoma-specific,
gp100154-162-specific T cell receptor; and Dr. John
Wunderlich, Dr. Bianca Heemskerk, Arnold Mixon, and Shawn Farid for help
and expertise.
NR 59
TC 16
Z9 17
U1 1
U2 3
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 NOV
PY 2008
VL 19
IS 11
BP 1219
EP 1231
DI 10.1089/hum.2008.083
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 380UW
UT WOS:000261492100001
PM 19848582
ER
PT J
AU Muftuoglu, M
Oshima, J
von Kobbe, C
Cheng, WH
Leistritz, DF
Bohr, VA
AF Muftuoglu, Meltem
Oshima, Junko
von Kobbe, Cayetano
Cheng, Wen-Hsing
Leistritz, Dru F.
Bohr, Vilhelm A.
TI The clinical characteristics of Werner syndrome: molecular and
biochemical diagnosis
SO HUMAN GENETICS
LA English
DT Review
ID SYNDROME ADULT PROGERIA; CENTRAL-NERVOUS-SYSTEM; SYNDROME GENE; HELICASE
EXPRESSION; SYNDROME PROTEIN; SYNDROME LOCUS; BREAST-CANCER; AGING
PROCESS; DNA-REPAIR; WRN GENE
AB Werner syndrome (WS) is an adult onset segmental progeroid syndrome caused by mutations in the WRN gene. The WRN gene encodes a 180 kDa nuclear protein that possesses helicase and exonuclease activities. The absence of WRN protein leads to abnormalities in various DNA metabolic pathways such as DNA repair, replication and telomere maintenance. Individuals with WS generally develop normally until the third decade of life, when premature aging phenotypes and a series of age-related disorders begin to manifest. In Japan, where a founder effect has been described, the frequency of Werner heterozygotes appears to be as high as 1/180 in the general population. Due to the relatively non-specific nature of the symptoms and the lack of awareness of the condition, this disease may be under-diagnosed in other parts of the world. Genetic counseling of WS patients follows the path of other autosomal recessive disorders, with special attention needed for cancer surveillance in relatives. Molecular diagnosis of WS is made by nucleotide sequencing and, in some cases, protein analysis. It is also of potential interest to measure WRN activities in WS patients. More than 50 different disease-causing mutations in the WRN gene have been identified in WS patients from all over the world. All but one of these cases has mutations that result in the premature termination of the protein. Here we describe the clinical, molecular and biochemical characteristics of WS for use by medical professionals in a health care setting. Additional information is available through the International Registry of WS.
C1 [Muftuoglu, Meltem; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Oshima, Junko; Leistritz, Dru F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[von Kobbe, Cayetano] Chimera Pharma Bionostra Grp, Canc Vaccines Grp, Madrid 28760, Spain.
[Cheng, Wen-Hsing] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
FU NIH, National Institute on Aging [CA78088]
FX This work was partially supported by the Intramural Research Program of
the NIH, National Institute on Aging, and by the NIH grant CA78088 ( to
J.O).
NR 44
TC 68
Z9 73
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD NOV
PY 2008
VL 124
IS 4
BP 369
EP 377
DI 10.1007/s00439-008-0562-0
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 370MU
UT WOS:000260767100004
PM 18810497
ER
PT J
AU Nyholt, DR
LaForge, KS
Kallela, M
Alakurtti, K
Anttila, V
Farkkila, M
Hamalainen, E
Kaprio, J
Kaunisto, MA
Heath, AC
Montgomery, GW
Gobel, H
Todt, U
Ferrari, MD
Launer, LJ
Frants, RR
Terwindt, GM
de Vries, B
Verschuren, WMM
Brand, J
Freilinger, T
Pfaffenrath, V
Straube, A
Ballinger, DG
Zhan, Y
Daly, MJ
Cox, DR
Dichgans, M
van den Maagdenberg, AMJM
Kubisch, C
Martin, NG
Wessman, M
Peltonen, L
Palotie, A
AF Nyholt, Dale R.
LaForge, K. Steven
Kallela, Mikko
Alakurtti, Kirsi
Anttila, Verneri
Farkkila, Markus
Hamalainen, Eija
Kaprio, Jaakko
Kaunisto, Mari A.
Heath, Andrew C.
Montgomery, Grant W.
Goebel, Hartmut
Todt, Unda
Ferrari, Michel D.
Launer, Lenore J.
Frants, Rune R.
Terwindt, Gisela M.
de Vries, Boukje
Verschuren, W. M. Monique
Brand, Jan
Freilinger, Tobias
Pfaffenrath, Volker
Straube, Andreas
Ballinger, Dennis G.
Zhan, Yiping
Daly, Mark J.
Cox, David R.
Dichgans, Martin
van den Maagdenberg, Arn M. J. M.
Kubisch, Christian
Martin, Nicholas G.
Wessman, Maija
Peltonen, Leena
Palotie, Aarno
TI A high-density association screen of 155 ion transport genes for
involvement with common migraine
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID FAMILIAL HEMIPLEGIC MIGRAINE; SINGLE-NUCLEOTIDE POLYMORPHISMS;
GENOME-WIDE ASSOCIATION; LINKAGE DISEQUILIBRIUM; POTASSIUM CHANNELS;
POPULATION; AURA; ATP1A2; SAMPLE; POWER
AB The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case -control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P 5 0.00002; global P 5 0.02) was observed in the Finnish case -control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out.
C1 [Nyholt, Dale R.; Martin, Nicholas G.] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4029, Australia.
[LaForge, K. Steven] Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10065 USA.
[LaForge, K. Steven; Alakurtti, Kirsi; Anttila, Verneri; Hamalainen, Eija; Wessman, Maija; Palotie, Aarno] Univ Helsinki, Cent Hosp, Biomed Helsinki, Res Program Mol Med, FIN-00014 Helsinki, Finland.
[LaForge, K. Steven; Alakurtti, Kirsi; Anttila, Verneri; Hamalainen, Eija; Kaunisto, Mari A.; Wessman, Maija; Palotie, Aarno] Univ Helsinki, Cent Hosp, Dept Clin Chem, FIN-00014 Helsinki, Finland.
[LaForge, K. Steven; Alakurtti, Kirsi; Anttila, Verneri; Hamalainen, Eija; Kaunisto, Mari A.; Wessman, Maija; Palotie, Aarno] Univ Helsinki, Cent Hosp, Dept Med Genet, FIN-00014 Helsinki, Finland.
[Kallela, Mikko; Farkkila, Markus] Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00014 Helsinki, Finland.
[Hamalainen, Eija; Kaunisto, Mari A.; Wessman, Maija] Univ Helsinki, Finnish Inst Mol Med, Finnish Genome Ctr, FIN-00014 Helsinki, Finland.
[Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland.
[Kaprio, Jaakko] Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, SF-00300 Helsinki, Finland.
[Kaunisto, Mari A.; Wessman, Maija; Palotie, Aarno] Folkhalsan Res Ctr, Helsinki 00014, Finland.
[Heath, Andrew C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Montgomery, Grant W.] Queensland Inst Med Res, Mol Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Goebel, Hartmut] Kiel Pain & Headache Ctr, D-24149 Kiel, Germany.
[Todt, Unda; Kubisch, Christian] Univ Cologne, Inst Human Genet, Inst Genet, D-50923 Cologne, Germany.
[Todt, Unda] Univ Cologne, Ctr Mol Med, D-50923 Cologne, Germany.
[Ferrari, Michel D.; Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Dept Neurol, Med Ctr, NL-2300 RC Leiden, Netherlands.
[Launer, Lenore J.] NIA, IRP, NIH, Bethesda, MD 20892 USA.
[Frants, Rune R.; de Vries, Boukje; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RC Leiden, Netherlands.
[Verschuren, W. M. Monique] Natl Inst Publ Hlth & Environm, Ctr Prevent & Hlth Serv Res, NL-3720 BA Bilthoven, Netherlands.
[Brand, Jan] Migrane & Kopfschmerz Klin Konigstein, D-61462 Konigstein, Germany.
[Freilinger, Tobias; Straube, Andreas; Dichgans, Martin] Univ Munich, Klinikum Grosshadern, Dept Neurol, D-81377 Munich, Germany.
[Pfaffenrath, Volker] Neurol Gemeinschaftspraxis Leopoldstr, D-81377 Munich, Germany.
[Ballinger, Dennis G.; Zhan, Yiping; Cox, David R.] Perlegen Sci Inc, Mountain View, CA 94043 USA.
[Daly, Mark J.; Peltonen, Leena; Palotie, Aarno] MIT, Broad Inst, Cambridge, MA 02141 USA.
[Daly, Mark J.; Peltonen, Leena; Palotie, Aarno] Harvard Univ, Cambridge, MA 02141 USA.
[Peltonen, Leena] Finnish Inst Mol Med, Natl Publ Hlth Inst, Dept Mol Med, Helsinki, Finland.
[Peltonen, Leena; Palotie, Aarno] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
RP Nyholt, DR (reprint author), Queensland Inst Med Res, Genet Epidemiol Lab, PO Royal Brisbane Hosp, Brisbane, Qld 4029, Australia.
EM dale.nyholt@qimr.edu.au
RI Kubisch, Christian/F-1893-2011; Kaprio, Jaakko/A-1820-2008; Nyholt,
Dale/C-8384-2013; Montgomery, Grant/B-7148-2008;
OI Kubisch, Christian/0000-0003-4220-0978; Montgomery,
Grant/0000-0002-4140-8139; Anttila, Verneri/0000-0002-0073-4675;
Kaunisto, Mari/0000-0002-6946-9195; Kaprio, Jaakko/0000-0002-3716-2455;
Martin, Nicholas/0000-0003-4069-8020
FU Sigrid Juselius Foundation; Academy of Finland [200923, 00213]; Helsinki
University Central Hospital; EuroHead [LSHM-CT-2004-504837]; GenomEUtwin
[QLG2-CT-2002-01254]; Oxnard Foundation; Helsinki Biomedical Graduate
School; Biomedicum Helsinki Foundation; Finnish Cultural Foundation;
Finnish Neurology Foundation and National Institutes of Health [RO1
NS37675]; National Institute on Alcohol Abuse and Alcoholism (United
States) [AA007535, AA013320, AA013326, AA014041, AA07728, AA10249,
AA11998]; Academy of Finland Center of Excellence in Complex Disease
Genetics; National Health and Medical Research Council (NHMRC) [941177,
951023, 241916, 442981]; NHMRC; Deutsche Forschungsgemeinschaft
[FOR423]; Bundesministerium fur Bildung und Forschung (BMBF); Koeln
Fortune Program/Faculty of Medicine; Netherlands Organization
[903-52-291, 918.56.602]; Migraine Trust; Centre for Medical Systems
Biology (CMSB)
FX The Helsinki component of this study was supported by the Sigrid
Juselius Foundation, the Academy of Finland (200923 to A. P.; 00213 to
M. W.), the Helsinki University Central Hospital, the EuroHead project
(LSHM-CT-2004-504837), the GenomEUtwin project (QLG2-CT-2002-01254 and
to V. A.), the Oxnard Foundation, the Helsinki Biomedical Graduate
School (to V. A.), the Biomedicum Helsinki Foundation, the Finnish
Cultural Foundation (to V. A.), the Finnish Neurology Foundation and
National Institutes of Health (RO1 NS37675 to A. P.), National Institute
on Alcohol Abuse and Alcoholism (United States) grants AA007535,
AA013320, AA013326, AA014041, AA07728, AA10249 and AA11998. Academy of
Finland Center of Excellence in Complex Disease Genetics (to L. P., A.
P. and J. K.). The Brisbane component was supported by National Health
and Medical Research Council (NHMRC) (Australia) grants 941177, 951023,
241916 and 442981. D. R. N. and G. W. M were supported by NHMRC R. D.
Wright and Senior Research Fellowships. The Cologne component was
supported by Deutsche Forschungsgemeinschaft (DFG, FOR423), National
Genome Network (NGFN) by the Bundesministerium fur Bildung und Forschung
(BMBF), Koeln Fortune Program/Faculty of Medicine, University of
Cologne. The Leiden component was supported by the Netherlands
Organization for Scientific Research (NWO) (903-52-291 to M. D. F, R. R.
F. and Vici 918.56.602 to M. D. F), the Migraine Trust (R. R. F., M. D.
F.), the EuroHead project (LSHM-CT-2004-504837) and the Centre for
Medical Systems Biology (CMSB) in the framework of the Netherlands
Genomics Initiative (NGI). The Munich component was supported by the
Deutsche Forschungsgemeinschaft (DFG D1 722/8-1 and DI 722/8-2).
NR 55
TC 49
Z9 50
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD NOV 1
PY 2008
VL 17
IS 21
BP 3318
EP 3331
DI 10.1093/hmg/ddn227
PG 14
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 359GI
UT WOS:000259974000006
PM 18676988
ER
PT J
AU Greenblatt, MS
Brody, LC
Foulkes, WD
Genuardi, M
Hofstra, RMW
Olivier, M
Plon, SE
Sijmons, RH
Sinilnikova, O
Spurdle, AB
AF Greenblatt, Marc S.
Brody, Lawrence C.
Foulkes, William D.
Genuardi, Maurizio
Hofstra, Robert M. W.
Olivier, Magali
Plon, Sharon E.
Sijmons, Rolf H.
Sinilnikova, Olga
Spurdle, Amanda B.
CA IARC Unclassified Genetic Variants
TI Locus-Specific Databases and Recommendations to Strengthen Their
Contribution to the Classification of Variants in Cancer Susceptibility
Genes
SO HUMAN MUTATION
LA English
DT Article
DE locus-specific databases; LSDBs; BIC; mismatch repair; cancer;
unclassified variant; variant of unknown significance; pathogenic
ID UNKNOWN CLINICAL-SIGNIFICANCE; DNA-SEQUENCE VARIANTS; MUTATION
DATABASES; BIALLELIC MUTATIONS; ALLELIC VARIANTS; BRCA1; P53;
PREDISPOSITION; MAMMOGRAMS; PHENOTYPE
AB Locus-specific databases (LSDBs) are curated collections of sequence variants in genes associated with disease. LSDBs of cancer-related genes often serve as a critical resource to researchers, diagnostic laboratories, clinicians, and others in the cancer genetics community. LSDBs are poised to play an important role in disseminating clinical classification of variants. The IARC Working Group on Unclassified Genetic Variants has proposed a new system of five classes of variants in cancer susceptibility genes. However, standards are lacking for reporting and analyzing the multiple data types that assist in classifying variants. By adhering to standards of transparency and consistency in the curation and annotation of data, LSDBs can be critical for organizing our understanding of how genetic variation relates to disease. In this article we discuss how LSDBs can accomplish these goals, using existing databases for BRCA1, BRCA2, MSH2, MLH1, TP53, and CDKN2A to illustrate the progress and remaining challenges in this field. We recommend that: 1) LSDBs should only report a conclusion related to pathogenicity if a consensus has been reached by an expert panel. 2) The system used to classify variants should be standardized. The Working Group encourages use of the five class system described in this issue by Plon and colleagues. 3) Evidence that supports a conclusion should be reported in the database, including sources and criteria used for assignment. 4) Variants should only be classified as pathogenic if more than one type of evidence has been considered. 5) All instances of all variants should be recorded. Hum Mutat 29(11), 1273-1281, 2008. Published 2008 Wiley-Liss, Inc.
C1 [Greenblatt, Marc S.] Univ Vermont, Coll Med, Vermont Canc Ctr, Burlington, VT 05405 USA.
[Greenblatt, Marc S.] Univ Vermont, Dept Med, Burlington, VT 05405 USA.
[Brody, Lawrence C.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Foulkes, William D.] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ, Canada.
[Foulkes, William D.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
[Genuardi, Maurizio] Univ Florence, Dept Clin Pathophysiol, Florence, Italy.
[Hofstra, Robert M. W.; Sijmons, Rolf H.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Olivier, Magali] Int Agcy Res Canc, F-69372 Lyon, France.
[Plon, Sharon E.] Baylor Coll Med, Houston, TX 77030 USA.
[Sinilnikova, Olga] Ctr Leon Berard, Hosp Civils Lyon, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France.
[Spurdle, Amanda B.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Genuardi, Maurizio] Fiorgen Fdn Pharmacogenom, Sesto Fiorentino, Italy.
[Sinilnikova, Olga] Univ Lyon 1, CNRS, Lab Genet Mol Signalisat & Canc, UMR5201, F-69365 Lyon, France.
RP Greenblatt, MS (reprint author), Univ Vermont, Coll Med, Vermont Canc Ctr, 89 Beaumont Ave,Given E214, Burlington, VT 05405 USA.
EM Marc.Greenblatt@vtmednet.org
RI Spurdle, Amanda/A-4978-2011; Olivier, Magali/G-3728-2010; Sijmons,
Rolf/E-5829-2012; Hoogerbrugge, Nicoline/O-1016-2013;
OI Spurdle, Amanda/0000-0003-1337-7897; Olivier,
Magali/0000-0002-8202-342X; Sijmons, Rolf/0000-0001-8446-2779; Hofstra,
Robert/0000-0001-7498-3829; foulkes, william/0000-0001-7427-4651
FU National Institutes Of Health [CA 96536, HG 004064]; Lake Champlain
Cancer Research Organization; National Human Genomic Research Institute;
Fonds de la Recherche en Sante du Quebec; Canadian Breast Cancer
Research Alliance; Elite Cassa di Risparmio di Firenze; Dutch Cancer
Society [RUG2002-2678]; European Community; Australian National Health
and Medical Research Council
FX Supported by grants from the National Institutes Of Health (CA 96536 to
M.S.G.; HG 004064 to S.E.P), the Lake Champlain Cancer Research
Organization (to M.S.G.), the Intramural Research Program Of the
National Human Genomic Research Institute (to L.C.B.), the Fonds de la
Recherche en Sante du Quebec and the Canadian Breast Cancer Research
Alliance (to WDF.), Elite Cassa di Risparmio di Firenze (to M.G.), the
Dutch Cancer Society (RUG2002-2678 to R.M.W.H.), the European Community
(to R.M.W.H.), the Australian National Health and Medical Research
Council (to A.B.S.). We appreciate the helpful discussions with many
colleagues, at the Human Variome Project Planning Meeting chaired by
Professor Richard Cotton in May 2008.
NR 40
TC 24
Z9 24
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD NOV
PY 2008
VL 29
IS 11
BP 1273
EP 1281
DI 10.1002/humu.20889
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 372JF
UT WOS:000260897200003
PM 18951438
ER
PT J
AU Tsai-Morris, CH
Koh, E
Dufau, ML
AF Tsai-Morris, Chon-Hwa
Koh, Eitetsu
Dufau, Maria L.
TI Differences in gonadotropin-regulated testicular helicase (GRTH/DDX25)
single nucleotide polymorphism between Japanese and Chinese populations
SO HUMAN REPRODUCTION
LA English
DT Letter
ID RNA HELICASE; SPERMATOGENESIS; GENE; TRANSLATION
C1 [Tsai-Morris, Chon-Hwa; Dufau, Maria L.] NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Program Dev Endocrinol & Genet,NIH, Bethesda, MD 20892 USA.
[Koh, Eitetsu] Kanazawa Univ, Sch Med, Dept Urol, Kanazawa, Ishikawa 920, Japan.
RP Tsai-Morris, CH (reprint author), NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Program Dev Endocrinol & Genet,NIH, Bethesda, MD 20892 USA.
EM morrisch@mail.nih.gov
NR 9
TC 3
Z9 3
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD NOV
PY 2008
VL 23
IS 11
BP 2611
EP 2613
DI 10.1093/humrep/den063
PG 5
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 361QT
UT WOS:000260142900031
PM 18487219
ER
PT J
AU Dessy, FJ
Giannini, SL
Bougelet, CA
Kemp, TJ
David, MPM
Poncelet, SM
Pinto, LA
Wettendroff, MA
AF Dessy, Francis J.
Giannini, Sandra L.
Bougelet, Catherine A.
Kemp, Troy J.
David, Marie-Pierre M.
Poncelet, Sylviane M.
Pinto, Ligia A.
Wettendroff, Martine A.
TI Correlation between direct ELISA, single epitope-based inhibition ELISA
and pseudovirion-based neutralization assay for measuring anti-HPV-16
and anti-HPV-18 antibody response after vaccination with the
AS04-adjuvanted HPV-16/18 cervical cancer vaccine
SO HUMAN VACCINES
LA English
DT Article
DE HPV-16; HPV-18; cervical cancer; vaccine; VLP; AS04 Adjuvant System;
immune response; ELISA; pseudovirion; neutralization assay
ID HUMAN-PAPILLOMAVIRUS TYPE-16; VIRUS-LIKE PARTICLES; COTTONTAIL RABBIT
PAPILLOMAVIRUS; RANDOMIZED CONTROLLED-TRIAL; YOUNG-WOMEN; HPV
PSEUDOVIRIONS; IMMUNE-RESPONSE; DOUBLE-BLIND; HUMAN SERA; L1
AB To monitor immune status during clinical trials and after vaccine registration, several assays have been developed to measure type-specific human papillomavirus (HPV) serum antibody levels. These include neutralization assays, single epitope-based inhibition immunoassays, and direct enzyme-linked immunosorbent assays (ELISAs). Neutralization assays based on multiple epitopes and independent of vaccine material are considered the 'gold standard' for unbiased assessment of the protective potential of vaccine-induced antibodies. However, their use in large clinical trials is challenging. Here, we compare both the direct ELISA and the single epitope-based inhibition ELISA with the pseudovirion-based neutralization assay (PBNA) for HPV-16/18 antibody responses in vaccinated women enrolled in trials of Cervarix (TM), GSK's cervical cancer vaccine. The direct ELISA, which is based on multiple epitopes, was shown to have a higher degree of sensitivity and correlation with the PBNA when compared with the single epitope-based inhibition ELISA. Among double-positive results, high correlations were observed between the PBNA and the direct ELISA (0.70-0.88 for HPV-16 and 0.82-0.94 for HPV-18) and also with the single epitope-based inhibition ELISA (0.60-0.89 for HPV-16 and 0.57-0.96 for HPV-18) in women aged 15-25 years. The correlation persisted up to 6.4 years after primary vaccination. Similar levels of correlation were observed for adolescents aged 10-14 years and women aged 46-55 years. Therefore, the direct ELISA appears to be an excellent surrogate for neutralizing activity and can be used to evaluate antibody response induced by L1 virus-like particle-based cervical cancer vaccines, regardless of time elapsed after vaccination (up to 6.4 years) and the age of the vaccine recipient.
C1 [Dessy, Francis J.; Giannini, Sandra L.; Bougelet, Catherine A.; David, Marie-Pierre M.; Poncelet, Sylviane M.; Wettendroff, Martine A.] GlaxoSmithKline Biol, Res & Dev, B-1330 Rixensart, Belgium.
[Kemp, Troy J.; Pinto, Ligia A.] NCI, HPV Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Dessy, FJ (reprint author), GlaxoSmithKline Biol, Res & Dev, Rue Inst 89, B-1330 Rixensart, Belgium.
EM francis.dessy@gskbio.com
FU National Cancer Institute (NCI) HPV Vaccine Trial in Costa Rica
[NCT00128661, HPV-009]; NCI; National Institutes of Health
[N01-CO-12400]
FX F. Dessy, S. Giannini, C. Bougelet, M.-P. David, S. Poncelet and M.
Wettendorff are employees of GlaxoSmithKline Biologicals.; Testing of
specimens from the National Cancer Institute (NCI) HPV Vaccine Trial in
Costa Rica (NCT00128661; HPV-009) within this project has been funded in
whole with Federal funds from the NCI, National Institutes of Health,
under contract (N01-CO-12400). The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U. S. Government.;
Cervarix is a trademark of the GlaxoSmithKline group of companies.
GlutaMAX and Fungizone are trademarks of Invitrogen Corporation.
MaxiSorp is a trademark of Nalge Nunc International. SoftMax and LMaxII
are trademarks of Molecular Devices.; The authors are thankful to Ulrike
Krause, Alberta Di Pasquale, Veerle Ronsse, Laurence De Moerlooze, Allan
Hildesheim and Meridian HealthComms Ltd., for assistance in the
preparation of this manuscript.
NR 49
TC 99
Z9 102
U1 0
U2 10
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1554-8619
J9 HUM VACCINES
JI Hum. Vaccines
PD NOV-DEC
PY 2008
VL 4
IS 6
BP 425
EP 434
PG 10
WC Biotechnology & Applied Microbiology; Immunology
SC Biotechnology & Applied Microbiology; Immunology
GA 373LA
UT WOS:000260971900006
PM 18948732
ER
PT J
AU Paoletti, LC
Guttormsen, HK
Christian, MS
Hoberman, AM
McInnes, P
AF Paoletti, Lawrence C.
Guttormsen, Hilde-Kari
Christian, Mildred S.
Hoberman, Alan M.
McInnes, Pamela
TI Neither antibody to a group B streptococcal conjugate vaccine nor the
vaccine itself is teratogenic in rabbits
SO HUMAN VACCINES
LA English
DT Article
DE group B streptococcus; glycoconjugate vaccines; serotype III;
developmental toxicity study
ID POLYSACCHARIDE CONJUGATE; PREGNANT-WOMEN; IMMUNOGENICITY; INFECTION;
IMMUNIZATION; EFFICACY; ANIMALS; MODEL
AB Group B Streptococcus (GBS) is a leading cause of human neonatal bacterial disease, resulting in pneumonia, sepsis, meningitis and sometimes, death. Supportive preclinical studies of GBS capsular polysaccharide (CPS)-protein conjugate vaccines have led to several phase 1 and phase 2 trials in healthy, non-pregnant adults, which demonstrated that the vaccines, produced at the Channing Laboratory, were safe and immunogenic. However, evaluation of the safety and immunogenicity of a GBS conjugate vaccine administered to pregnant women demanded that it be manufactured under current good manufacturing practices (cGMP) and that it undergo developmental toxicity evaluation. In this report, we describe a GBS type III CPS-tetanus toxoid (III-TT) vaccine lot 3-1-96 manufactured and vialed under cGMP and our evaluation of the effect of this vaccine and of GBS type III CPS-specific antibody on conception and early-and late-stage fetal development in rabbits. III-TT lot 3-1-96 was compositionally similar to prototype III-TT lot 91-1, produced under non-GMP, and was potent in a mouse maternal vaccination-neonatal pup challenge model of GBS disease. Four groups of 30 female rabbits each were randomized to receive III-TT lot 3-1-96 vaccine, saline-alum, or combinations of these treatments before and after insemination. The dose of conjugated CPS on a weight basis was 1 mu g/kg, mimicking the anticipated actual human dose. Based on the weight of the rabbits, this was 20- to 100-fold greater than the expected human dose. Does were pre-assigned to deliver litters naturally or have their kits delivered by Caesarean-section at gestation day 29, to assess late fetal development. Sera from does and kits were collected, and the presence of type III CPS-specific IgG was confirmed by quantitative ELISA. Based on all assessments, GBS type III-TT lot 3-1-96, nor antibody to it did not affect embryo-fetal viability, sex ratio, growth or cause malformations (i.e., it was non-teratogenic). In addition, that III-TT lot 3-1-96 was found to be safe and immunogenic in two clinical studies involving healthy non-pregnant adults supports a clinical evaluation of this vaccine in pregnant women.
C1 [Paoletti, Lawrence C.; Guttormsen, Hilde-Kari] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA.
[Christian, Mildred S.] Argus Int Inc, Horsham, PA USA.
[Hoberman, Alan M.] Preclin Serv PA, Charles River Labs, Horsham, PA USA.
[McInnes, Pamela] Natl Inst Dent & Craniofacial Res, Div Extramural Res, NIH, Bethesda, MD USA.
RP Paoletti, LC (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA.
EM lpaoletti@rics.bwh.harvard.edu
FU NIAID [AI-25152, AI-060603]
FX We thank John Barnett, Kristen Sherer and Joseph Lech for technical
assistance as well as Valerie Sharper, Cheryl Van, Terry Clemson and
Karen Parker for study coordination and report preparation at Argus. We
also thank Matthew Chapdelaine for technical assistance with the ELISAs
and Michael Wessels for discussion about study design. This study was
funded by NIAID contract AI-25152 and grant AI-060603 (L. C. P.).
NR 34
TC 7
Z9 7
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8600
EI 1554-8619
J9 HUM VACCINES
JI Hum. Vaccines
PD NOV-DEC
PY 2008
VL 4
IS 6
BP 435
EP 443
PG 9
WC Biotechnology & Applied Microbiology; Immunology
SC Biotechnology & Applied Microbiology; Immunology
GA 373LA
UT WOS:000260971900007
PM 18443428
ER
PT J
AU Cutler, JA
Sorlie, PD
Wolz, M
Thom, T
Fields, LE
Roccella, EJ
AF Cutler, Jeffrey A.
Sorlie, Paul D.
Wolz, Michael
Thom, Thomas
Fields, Larry E.
Roccella, Edward J.
TI Trends in Hypertension Prevalence, Awareness, Treatment, and Control
Rates in United States Adults Between 1988-1994 and 1999-2004
SO HYPERTENSION
LA English
DT Article
DE hypertension; surveillance; trends; blood pressure; obesity
ID NUTRITION EXAMINATION SURVEY; HIGH BLOOD-PRESSURE; NATIONAL-HEALTH; US
ADULTS; PRIMARY PREVENTION; EDUCATION-PROGRAM; OBESITY; OVERWEIGHT;
METAANALYSIS; POPULATION
AB This study assesses trends in hypertension prevalence, blood pressure distributions and mean levels, and hypertension awareness, treatment, and control among US adults, age >= 18 years, between the third National Health and Nutrition Examination Survey (1988-1994) and the 1999-2004 National Health and Nutrition Examination Survey, a period of approximate to 10 years. The age-standardized prevalence rate increased from 24.4% to 28.9% (P < 0.001), with the largest increases among non-Hispanic women. Depending on gender and race/ethnicity, from one fifth to four fifths of the increase could be accounted for by increasing body mass index. Among hypertensive persons, there were modest increases in awareness (P = 0.04), from 68.5% to 71.8%. The rate for men increased from 61.6% to 69.3% (P = 0.001), whereas the rate for women did not change significantly. Rates remained higher for women than for men, although the difference narrowed considerably. Improvements in treatment and control rates were larger: 53.1% to 61.4% and 26.1% to 35.1%, respectively (both P < 0.001). The greatest increases occurred among non-Hispanic white men and non-Hispanic black persons, especially men. Mexican American persons showed improvement in treatment and control rates, but these rates remained the lowest among race/ethnic subgroups (47.4% and 24.3%, respectively). Among all of the race/ethnic groups, women continued to have somewhat better awareness, treatment, and control, except for control rates among non-Hispanic white persons, which became higher in men. Differences between non-Hispanic black and white persons in awareness, treatment, and control were small. These divergent trends may translate into disparate trends in cardiovascular disease morbidity and mortality. (Hypertension. 2008;52:818-827.)
C1 [Cutler, Jeffrey A.; Sorlie, Paul D.; Wolz, Michael; Thom, Thomas; Roccella, Edward J.] NHLBI, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Fields, Larry E.] Pfizer Inc, New York, NY USA.
RP Sorlie, PD (reprint author), NHLBI, NIH, US Dept HHS, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA.
EM sorliep@mail.nih.gov
FU National Heart, Lung, and Blood Institute [Y1-HC-8135]
FX This work was funded in part by an interagency agreement with the
National Center for Health Statistics by the National Heart, Lung, and
Blood Institute (Y1-HC-8135).
NR 45
TC 484
Z9 507
U1 1
U2 21
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD NOV
PY 2008
VL 52
IS 5
BP 818
EP 827
DI 10.1161/HYPERTENSIONAHA.108.113357
PG 10
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 363MT
UT WOS:000260272100014
PM 18852389
ER
PT J
AU Leslie, DS
Dascher, CC
Cembrola, K
Townes, MA
Hava, DL
Hugendubler, LC
Mueller, E
Fox, L
Roura-Mir, C
Moody, DB
Vincent, MS
Gumperz, JE
Illarionov, PA
Besra, GS
Reynolds, CG
Brenner, MB
AF Leslie, David S.
Dascher, Christopher C.
Cembrola, Katherine
Townes, Maria A.
Hava, David L.
Hugendubler, Lynne C.
Mueller, Elisabetta
Fox, Lisa
Roura-Mir, Carme
Moody, D. Branch
Vincent, Michael S.
Gumperz, Jenny E.
Illarionov, Petr A.
Besra, Gurdyal S.
Reynolds, Carol G.
Brenner, Michael B.
TI Serum lipids regulate dendritic cell CD1 expression and function
SO IMMUNOLOGY
LA English
DT Article
DE cell surface molecules; dendritic cells; human; lipid mediators; T cells
ID PROLIFERATOR-ACTIVATED RECEPTORS; PPAR-GAMMA; ANTIGEN PRESENTATION;
T-CELLS; MOLECULAR-MECHANISMS; LYMPHOCYTES-T; RECOGNITION; MATURATION;
RESTRICTS; PATHWAYS
AB Dendritic cells (DCs) are highly potent antigen-presenting cells (APCs) and play a vital role in stimulating naive T cells. Treatment of human blood monocytes with the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 stimulates them to develop into immature dendritic cells (iDCs) in vitro. DCs generated by this pathway have a high capacity to prime and activate resting T cells and prominently express CD1 antigen-presenting molecules on the cell surface. The presence of human serum during the differentiation of iDCs from monocytes inhibits the expression of CD1a, CD1b and CD1c, but not CD1d. Correspondingly, T cells that are restricted by CD1c showed poor responses to DCs that were generated in the presence of human serum, while the responses of CD1d-restricted T cells were enhanced. We chemically fractionated human serum to isolate the bioactive factors that modulate surface expression of CD1 proteins during monocyte to DC differentiation. The human serum components that affected CD1 expression partitioned with polar organic soluble fractions. Lysophosphatidic acid and cardiolipin were identified as lipids present in normal human serum that potently modulate CD1 expression. Control of CD1 expression was mediated at the level of gene transcription and correlated with activation of the peroxisome proliferator-activated receptor (PPAR) nuclear hormone receptors. These findings indicate that the ability of human DCs to present lipid antigens to T cells through expression of CD1 molecules is sensitively regulated by lysophosphatidic acid and cardiolipin in serum, which are ligands that can activate PPAR transcription factors.
C1 [Leslie, David S.; Cembrola, Katherine; Townes, Maria A.; Hava, David L.; Roura-Mir, Carme; Moody, D. Branch; Vincent, Michael S.; Brenner, Michael B.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Leslie, David S.; Cembrola, Katherine; Townes, Maria A.; Hava, David L.; Roura-Mir, Carme; Moody, D. Branch; Vincent, Michael S.; Brenner, Michael B.] Harvard Univ, Sch Med, Boston, MA USA.
[Dascher, Christopher C.] Mt Sinai Sch Med, Inst Immunol, New York, NY USA.
[Hugendubler, Lynne C.; Mueller, Elisabetta] NIDDK, GDDB, Bethesda, MD USA.
[Fox, Lisa; Gumperz, Jenny E.] Univ Wisconsin, Sch Med, Dept Med Microbiol & Immunol, Madison, WI 53706 USA.
[Illarionov, Petr A.; Besra, Gurdyal S.] Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England.
[Reynolds, Carol G.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA.
RP Dascher, CC (reprint author), 1 Gustave Levy Pl,Box 1630, New York, NY 10029 USA.
EM dascher@mssm.edu; mbrenner@rics.bwh.harvard.edu
RI Roura-Mir, Carme/D-4538-2013;
OI Roura-Mir, Carme/0000-0003-0514-337X; Besra, Gurdyal/0000-0002-5605-0395
FU Arthritis National Research Foundation; Pfizer, Inc.; National
Institutes of Health [K08AR02171]; Medical Research Council [G9901077,
G0400421]; Wellcome Trust [07221/Z/03/Z]
FX This research was supported by the Arthritis National Research
Foundation (D. S. L.), an ARA Award to D. S. L. sponsored by Pfizer,
Inc., the National Institutes of Health (K08AR02171 to D. S. L.), the
Medical Research Council (G9901077 and G0400421 to G. S. B.), and the
Wellcome Trust (07221/Z/03/Z to G. S. B.).
NR 40
TC 35
Z9 36
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD NOV
PY 2008
VL 125
IS 3
BP 289
EP 301
DI 10.1111/j.1365-2567.2008.02842.x
PG 13
WC Immunology
SC Immunology
GA 357RS
UT WOS:000259864500002
PM 18445008
ER
PT J
AU Narum, DL
Nguyen, V
Zhang, YL
Glen, J
Shimp, RL
Lambert, L
Ling, IT
Reiter, K
Ogun, SA
Long, C
Holder, AA
Herrera, R
AF Narum, David L.
Nguyen, Vu
Zhang, Yanling
Glen, Jacqueline
Shimp, Richard L.
Lambert, Lynn
Ling, Irene T.
Reiter, Karine
Ogun, Solabomi A.
Long, Carole
Holder, Anthony A.
Herrera, Raul
TI Identification and Characterization of the Plasmodium yoelii PyP140/RON4
Protein, an Orthologue of Toxoplasma gondii RON4, Whose Cysteine-Rich
Domain Does Not Protect against Lethal Parasite Challenge Infection
SO INFECTION AND IMMUNITY
LA English
DT Article
ID APICAL MEMBRANE ANTIGEN-1; MALARIA VACCINE CANDIDATE;
PASSIVE-IMMUNIZATION; MONOCLONAL-ANTIBODY; FALCIPARUM MALARIA;
PICHIA-PASTORIS; MOVING JUNCTION; CLINICAL-TRIAL; CELL INVASION;
EXPRESSION
AB Previously, we identified a Plasmodium yoelii YM 140-kDa merozoite protein, designated PyP140, which formed a complex with apical membrane antigen 1 (AMA1). Furthermore, we produced a nonprotective monoclonal antibody (MAb), 48F8, that immunoprecipitated metabolically labeled PyP140 and localized the protein to the merozoite's apical end and, less frequently, to the merozoite surface, as observed by immunofluorescence assay (IFA). Here, using MAb 48F8, we have identified the pyp140 gene by screening a P. yoelii lambda-Zap cDNA expression library. The pyp140 cDNA covers approximately 90% of the putative open reading frame (ORF) of PY02159 from the P. yoelii NL genome sequencing project. Analysis of the complete gene identified the presence of two introns. The ORF encodes a 102,407-Da protein with an amino-terminal signal sequence, a series of three unique types of repeats, and a cysteine-rich region. The binding site of MAb 48F8 was also identified. A BLAST search with the deduced amino acid sequence shows significant similarity with the Toxoplasma gondii RON4 protein and the Plasmodium falciparum RON4 protein, and the sequence is highly conserved in other Plasmodium species. We produced the cysteine-rich domain of PyP140/RON4 by using the Pichia pastoris expression system and characterized the recombinant protein biochemically and biophysically. BALB/c mice immunized with the protein formulated in oil-in-water adjuvants produced antibodies that recognize parasitized erythrocytes by IFA and native PyP140/RON4 by immunoblotting but failed to protect against a lethal P. yoelii YM infection. Our results show that PyP140/RON4 is located within the rhoptries or micronemes. It may associate in part with AMA1, but the conserved cysteine-rich domain does not appear to elicit inhibitory antibodies, a finding that is supported by the marked sequence conservation in this protein within Plasmodium spp., suggesting that it is not under immune pressure.
C1 [Narum, David L.; Nguyen, Vu; Zhang, Yanling; Glen, Jacqueline; Shimp, Richard L.; Lambert, Lynn; Reiter, Karine; Long, Carole; Herrera, Raul] NIH, Malaria Vaccine Dev Branch, Rockville, MD 20852 USA.
[Ling, Irene T.; Ogun, Solabomi A.; Holder, Anthony A.] Natl Inst Med Res, Div Parasitol, London NW7 1AA, England.
RP Narum, DL (reprint author), NIH, Malaria Vaccine Dev Branch, 5640 Fishers Lane, Rockville, MD 20852 USA.
EM dnarum@niaid.nih.gov
RI Holder, Anthony/A-7554-2013
OI Holder, Anthony/0000-0002-8490-6058
FU NIH; Medical Research Council (United Kingdom)
FX We express our gratitude to Louis Miller for insightful discussions
regarding PyP140, to Kim Lee Sim for support of this project while
D.L.N. was employed by EntreMed, Inc., and to Michael Fay for assistance
with the statistical analysis of parasitemias. We also thank Tin Luu
(EntreMed, Inc.) for performing the phage display assays, Kelly Magee
and Angela Lunger for assistance with the mouse immunization-challenge
study, and Ababacar Diouf for performing the ELISAs.; This work was
supported in part by the Intramural Research Program of the NIH and by
the Medical Research Council (United Kingdom).
NR 30
TC 27
Z9 28
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2008
VL 76
IS 11
BP 4876
EP 4882
DI 10.1128/IAI.01717-07
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 361YW
UT WOS:000260165500010
PM 18710865
ER
PT J
AU Battisti, JM
Bono, JL
Rosa, PA
Schrumpf, ME
Schwan, TG
Policastro, PF
AF Battisti, James M.
Bono, James L.
Rosa, Patricia A.
Schrumpf, Merry E.
Schwan, Tom G.
Policastro, Paul F.
TI Outer Surface Protein A Protects Lyme Disease Spirochetes from Acquired
Host Immunity in the Tick Vector
SO INFECTION AND IMMUNITY
LA English
DT Article
ID BORRELIA-BURGDORFERI INFECTION; WHITE-FOOTED MICE; IXODES-SCAPULARIS;
PEROMYSCUS-LEUCOPUS; ANTIBODY-RESPONSE; MEMBRANE-PROTEIN; FEEDING TICKS;
IXODIDAE; VACCINE; ACARI
AB The Lyme disease spirochete Borrelia burgdorferi alters the expression of outer surface protein (osp) genes as the bacterium cycles between ticks and mammals. OspA is produced as borreliae enter the tick vector and remains a major surface antigen during midgut colonization. To elucidate the role of OspA in the vector, we created an insertional deletion of ospA in strain B31-A3. The ospA mutant infects mice when it is injected intradermally and is acquired by larval ticks fed on these mice, where it persists through the molt to the nymph stage. Bacterial survival rates in artificially infected tick larvae fed on naive mice were compared with those in the vector fed on immune mice. The ospA mutant proliferates in larvae if it is exposed to blood from naive mice, but it declines in density after larval feeding if the blood is from immune mice. When uninfected larvae are fed on B-cell-deficient mice infected with the ospA mutant, larvae show borrelial densities and persistence that are significantly greater than those fed on infected, immunocompetent mice. We conclude that OspA serves a critical antibody-shielding role during vector blood meal uptake from immune hosts and is not required for persistence in the tick vector.
C1 [Battisti, James M.; Bono, James L.; Rosa, Patricia A.; Schrumpf, Merry E.; Schwan, Tom G.; Policastro, Paul F.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Policastro, PF (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM ppolicastro@niaid.nih.gov
FU NIAID; NIH
FX We thank Cyril Guyard and Kathy Wehrly for antibodies; Anita Mora and
Gary Hettrick for assistance with illustrations; and Kena Swanson, Chris
Bosio, and Phil Stewart for valuable comments on the manuscript.; We
acknowledge the construction of an initial series of ospAB mutants in
high-passage, noninfectious strain B31 by Aimee Geissler.; The
Intramural Research Program of the NIAID, NIH, supported this research.
NR 69
TC 43
Z9 45
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2008
VL 76
IS 11
BP 5228
EP 5237
DI 10.1128/IAI.00410-08
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 361YW
UT WOS:000260165500048
PM 18779341
ER
PT J
AU Hu, L
Tall, BD
Curtis, SK
Kopecko, DJ
AF Hu, Lan
Tall, Ben D.
Curtis, Sherill K.
Kopecko, Dennis J.
TI Enhanced Microscopic Definition of Campylobacter jejuni 81-176 Adherence
to, Invasion of, Translocation across, and Exocytosis from Polarized
Human Intestinal Caco-2 Cells
SO INFECTION AND IMMUNITY
LA English
DT Article
ID EPITHELIAL-CELLS; INT-407 CELLS; LINE CACO-2; SIGNAL-TRANSDUCTION;
EUKARYOTIC CELLS; TIGHT JUNCTIONS; SALMONELLA; TRANSPORT; VIRULENCE;
SURFACE
AB Campylobacter jejuni-mediated pathogenesis involves gut adherence and translocation across intestinal cells. The current study was undertaken to examine the C. jejuni interaction with and translocation across differentiated Caco-2 cells to better understand Campylobacter's pathogenesis. The efficiency of C. jejuni 81-176 invasion of Caco-2 cells was two- to threefold less than the efficiency of invasion of INT407 cells. Adherence-invasion analyses indicated that C. jejuni 81-176 adhered to most INT407 cells but invaded only about two- thirds of the host cells over 2 h (two bacteria/cell). In contrast, only 11 to 17% of differentiated Caco-2 cells were observed to bind and internalize either C. jejuni strain 81-176 or NCTC 11168, and a small percentage of infected Caco-2 cells contained 5 to 20 internalized bacteria per cell after 2 h. Electron microscopy revealed that individual C. jejuni cells adhered to the tips of host cell microvilli via intimate flagellar contacts and by lateral bacterial binding to the sides of microvilli. Next, bacteria were observed to bind at the apical host membrane surface via presumed interactions at one pole of the bacterium and with host membrane protrusions located near intercellular junctions. The latter contacts apparently resulted in coordinated, localized plasma membrane invagination, causing simultaneous internalization of bacteria into an endosome. Passage of this Campylobacter endosome intracellularly from the apical surface to the basolateral surface occurred over time, and bacterial release apparently resulted from endosome-basolateral membrane fusion (i.e., exocytosis). Bacteria were found intercellularly below tight junctions at 60 min postinfection, but not at earlier times. This study revealed unique host cell adherence contacts, early endocytosis-specific structures, and a presumptive exocytosis component of the transcellular transcytosis route.
C1 [Hu, Lan; Kopecko, Dennis J.] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Tall, Ben D.; Curtis, Sherill K.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA.
RP Kopecko, DJ (reprint author), US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, 29 Lincoln Dr,NIH Campus,Bldg 29-420, Bethesda, MD 20892 USA.
EM dennis.kopecko@fda.hhs.gov
OI Tall, Ben/0000-0003-0399-3629
NR 53
TC 26
Z9 26
U1 0
U2 4
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 NOV
PY 2008
VL 76
IS 11
BP 5294
EP 5304
DI 10.1128/IAI.01408-07
PG 11
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 361YW
UT WOS:000260165500055
PM 18765731
ER
PT J
AU Ambrose, CS
Luke, C
Coelingh, K
AF Ambrose, Christopher S.
Luke, Catherine
Coelingh, Kathleen
TI Current status of live attenuated influenza vaccine in the United States
for seasonal and pandemic influenza
SO INFLUENZA AND OTHER RESPIRATORY VIRUSES
LA English
DT Review
DE Influenza; live attenuated; vaccine
ID CULTURE-CONFIRMED INFLUENZA; RANDOMIZED CONTROLLED-TRIAL; B
VIRUS-VACCINES; YOUNG-CHILDREN; TEMPERATURE SENSITIVITY; B/ANN
ARBOR/1/66; WORKING ADULTS; A VIRUS; CAIV-T; TRIVALENT
AB A live attenuated influenza vaccine (LAIV) is currently approved in the United States for the prevention of influenza in individuals 2-49 years of age. This article summarizes the available data describing the safety and efficacy of LAIV for the prevention of influenza in both children and adults. LAIV is administered as an intranasal spray and has been shown to provide high levels of efficacy against influenza illness caused by both matched and mismatched strains in children and adults. In studies comparing LAIV and inactivated influenza vaccine in children, LAIV recipients experienced 35-53% fewer cases of culture-confirmed influenza illness caused by antigenically matched strains. Protection through a second influenza season against antigenically matched strains has also been seen in children. In adults, definitive comparative studies of LAIV and inactivated vaccine have not been conducted and no statistically significant differences in efficacy have been demonstrated. The most common adverse reactions with LAIV include runny nose/nasal congestion in all age groups, fever > 100 circle F in children, and sore throat in adults. Formulations of LAIV against pandemic influenza strains, including H5N1, H9N2, and H7N3, are currently being tested in preclinical and phase I clinical studies.
C1 [Ambrose, Christopher S.; Coelingh, Kathleen] Medimmune Inc, Gaithersburg, MD 20878 USA.
[Luke, Catherine] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Coelingh, K (reprint author), Medimmune Inc, 1 MedImmune Way, Gaithersburg, MD 20878 USA.
EM coelinghk@medimmune.com
RI Grigorieva, Elena/E-1744-2014; Rudenko, Larisa/B-5169-2015;
OI Grigorieva, Elena/0000-0002-0107-9959; Rudenko,
Larisa/0000-0002-0107-9959; Ambrose, Christopher/0000-0003-4175-7336
FU Intramural Research Program of the NIAID; NIH
FX This research was supported in part by the Intramural Research Program
of the NIAID, NIH. The authors thank Kanta Subbarao ( NIH), and Robert
Walker, Seth Toback, Robert Fuentes, and Gregory Susla ( MedImmune) for
helpful discussion and review of the manuscript.
NR 53
TC 54
Z9 59
U1 1
U2 9
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1750-2640
J9 INFLUENZA OTHER RESP
JI Influenza Other Respir. Viruses
PD NOV
PY 2008
VL 2
IS 6
BP 193
EP 202
DI 10.1111/j.1750-2659.2008.00056.x
PG 10
WC Infectious Diseases; Virology
SC Infectious Diseases; Virology
GA 467SD
UT WOS:000267761800002
PM 19453395
ER
PT J
AU Sweeney, DA
Danner, RL
Eichacker, PQ
Natanson, C
AF Sweeney, Daniel A.
Danner, Robert L.
Eichacker, Peter Q.
Natanson, Charles
TI Once is not enough: clinical trials in sepsis
SO INTENSIVE CARE MEDICINE
LA English
DT Editorial Material
ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; INTENSIVE INSULIN THERAPY;
GRAM-NEGATIVE BACTEREMIA; PLACEBO-CONTROLLED TRIAL; ACTIVATED PROTEIN-C;
HIGH-DOSE METHYLPREDNISOLONE; HUMAN MONOCLONAL-ANTIBODY; CRITICALLY-ILL
ADULTS; ESCHERICHIA-COLI J5; SEPTIC SHOCK
C1 [Sweeney, Daniel A.; Danner, Robert L.; Eichacker, Peter Q.; Natanson, Charles] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Sweeney, DA (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 2C145, Bethesda, MD 20892 USA.
EM sweeneyda@cc.nih.gov
NR 48
TC 29
Z9 31
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0342-4642
J9 INTENS CARE MED
JI Intensive Care Med.
PD NOV
PY 2008
VL 34
IS 11
BP 1955
EP 1960
DI 10.1007/s00134-008-1274-6
PG 6
WC Critical Care Medicine
SC General & Internal Medicine
GA 364AN
UT WOS:000260308700004
PM 18839140
ER
PT J
AU Lan, Q
He, XZ
Shen, M
Tian, LW
Liu, LZ
Lai, H
Chen, W
Berndt, SI
Hosgood, HD
Lee, KM
Zheng, TZ
Blair, A
Chapman, RS
AF Lan, Qing
He, Xingzhou
Shen, Min
Tian, Linwei
Liu, Larry Z.
Lai, Hong
Chen, Wei
Berndt, Sonja I.
Hosgood, Howard Dean
Lee, Kyoung-Mu
Zheng, Tongzhang
Blair, Aaron
Chapman, Robert S.
TI Variation in lung cancer risk by smoky coal subtype in Xuanwei, China
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE coal; lung cancer; indoor air pollution; Xuanwei; China
ID INDOOR AIR-POLLUTION; COMBUSTION EMISSIONS; DEVELOPING-COUNTRIES;
CURRENT PROGRESS; WEI; DISEASE; IMPROVEMENT; BURDEN; FUEL
AB Lung cancer rates in Xuanwei County have been among the highest in China for both males and females and have been causally associated with exposure to indoor smoky (bituminous) coal emissions that contain very high levels of polycyclic aromatic hydrocarbons. There are numerous coal mines across the County. Although lung cancer risk is strongly associated with the use of smoky coal as a whole, variation in risk by smoky coal subtype has not been characterized as yet. We conducted a population-based case-control study of 498 lung cancer cases and 498 controls, individually matched to case subjects on age ( 2 years) and sex to examine risk by coal subtype. Odds ratios (ORs) and 95% confidence intervals (CIs) for coal subtype were calculated by conditional logistic regression, adjusting for potential confounders. Overall, smoky coal use was positively and statistically significantly associated with lung cancer risk, when compared with the use of smokeless coal or wood (OR = 7.7, 95% CI = 4.5-13.3). Furthermore, there was a marked heterogeneity in risk estimates for specific subtypes of smoky coal (test for heterogeneity: p = 5.17 X 10(-10)). Estimates were highest for coal of the Laibin (OR = 24.8, 95 % CI = 12.4-49.6) and Longtan (OR = 11.6, 95 % CI = 5.0-27.2) coal types and lower for coal from other subtypes. These findings strongly suggest that in Xuanwei and elsewhere, the carcinogenic potential of coal combustion products can exhibit substantial local variation by specific coal source. Published 2008 Wiley-Liss, Inc.
C1 [Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[He, Xingzhou] Chinese Ctr Dis Control & Prevent, Inst Environm Hlth & Engn, Beijing, Peoples R China.
[Tian, Linwei] Chinese Univ Hong Kong, Sch Publ Hlth, Stanley Ho Ctr Emerging Infect Dis, Hong Kong, Hong Kong, Peoples R China.
[Liu, Larry Z.] Cornell Univ, Weill Med Coll, Dept Publ Hlth, New York, NY 10021 USA.
[Lai, Hong] Johns Hopkins Univ, Wilmer Eye Inst, Dept Radiol & Ophthalmol, Baltimore, MD 21218 USA.
[Chen, Wei] Forest Labs Inc, Harborside Financial Ctr, Jersey City, NJ USA.
[Zheng, Tongzhang] Yale Univ, Sch Med, Div Environm Sci, New Haven, CT USA.
[Chapman, Robert S.] Chulalongkorn Univ, Coll Publ Hlth Sci, Bangkok, Thailand.
RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, MSC 7240,6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA.
EM qingl@mail.nih.gov
RI Tian, Linwei/A-9736-2009
OI Tian, Linwei/0000-0002-4739-1534
FU Chinese Academy of Preventive Medicine, Beijing, China; Yunnan Province
Antiepidemic Station, Kunming, China; U.S. Environmental Protection
Agency; National Institutes of Health (Intramural Research Program)
FX Chinese Academy of Preventive Medicine, Beijing, China, Yunnan Province
Antiepidemic Station, Kunming, China, U.S. Environmental Protection
Agency, National Institutes of Health (Intramural Research Program).
NR 28
TC 33
Z9 42
U1 0
U2 16
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD NOV 1
PY 2008
VL 123
IS 9
BP 2164
EP 2169
DI 10.1002/ijc.23748
PG 6
WC Oncology
SC Oncology
GA 357HE
UT WOS:000259836100024
PM 18712724
ER
PT J
AU Chong, VZ
Webster, MJ
Rothmond, DA
Weickert, CS
AF Chong, Victor Z.
Webster, Maree J.
Rothmond, Debora A.
Weickert, Cynthia Shannon
TI Specific developmental reductions in subventricular zone ErbB1 and ErbB4
mRNA in the human brain
SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
LA English
DT Article
DE Subventricular zone; ErbB1; ErbB2; ErbB3; ErbB4; Postnatal; Development;
Human; In situ hybridization; mRNA; Immunohistochemistry
ID RECEPTOR TYROSINE KINASE; CENTRAL-NERVOUS-SYSTEM; ADULT MAMMALIAN
FOREBRAIN; MOUSE-BRAIN; SUBEPENDYMAL LAYER; PREFRONTAL CORTEX;
GENE-EXPRESSION; OLFACTORY-BULB; STEM-CELLS; RAT-BRAIN
AB The primate postnatal subventricular zone (SVZ) ties under the ventrolateral borders of the lateral ventricles as a discrete region of cells with gliogenic and neurogenic capacity regulated by ErbB receptors. However, the specific role of each ErbB subtype in SVZ cell development remains unclear, particularly in the human brain. The postnatal spatial and temporal expression profile of ErbB subtypes in the human brain may provide valuable insight into their distinct functions in the SVZ following birth. Hence, we examined the expression profile of ErbB1, ErbB2, ErbB3 and ErbB4 mRNA in the SVZ of human postmortem brains from neonates, infants, toddlers, school age subjects, adolescents, young adults and adults using in situ hybridization. SVZ transcript levels of ErbB1 and ErbB4 were highest in neonates and diminished with age. SVZ ErbB4 mRNA quantities significantly decreased by >85% to almost undetectable levels after the first year of life, while SVZ ErbB1 transcript levels displayed more gradual reductions, stabilizing to similar to 30-40% of neonate levels after the age of 5 years. In the neonate and infant SVZ, ErbB4 mRNA was localized to cell clusters resembling migratory neuroblast aggregates whereas ErbB1 mRNA was expressed in cells along but not within these clusters. ErbB2 mRNA appeared to be constantly expressed in the human SVZ at all postnatal ages as opposed to ErbB3 transcripts, which were not detected in the human SVZ at any age following birth. These findings suggest that ErbB1 and ErbB4 may play more salient roles than ErbB2 and ErbB3 in mediating early postnatal neurodevelopmental events. In addition, ErbB1- and ErbB4-immunoreactive cells and fibers were extensive throughout the human infant SVZ, but did not appear to overlap with PSA-NCAM-immunopositive clusters. The restriction of robust SVZ ErbB4 expression to neonate and infant age groups may indicate that SVZ-derived ErbB4-dependent postnatal neuronal development is most extensive within a narrow time frame early after birth. (C) 2008 ISDN. Published by Elsevier Ltd. All rights reserved.
C1 [Rothmond, Debora A.; Weickert, Cynthia Shannon] Univ New S Wales, Prince Wales Med Res Inst, Schizophrenia Res Inst, Sch Psychiat, Randwick, NSW 2031, Australia.
[Chong, Victor Z.; Rothmond, Debora A.; Weickert, Cynthia Shannon] NIMH, MiNDS Unit, CBDB, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Webster, Maree J.] USUHS, Dept Psychiat, Stanley Lab Brain Res, Bethesda, MD USA.
RP Weickert, CS (reprint author), Univ New S Wales, Prince Wales Med Res Inst, Schizophrenia Res Inst, Sch Psychiat, Corner Barker & Easy St, Randwick, NSW 2031, Australia.
EM c.weickert@powmri.edu.au
RI Shannon Weickert, Cynthia/G-3171-2011
FU NSERC Postdoctoral Fellowship; Stanley Medical Research Institute
FX Victor Z. Chong is a recipient of the NSERC Postdoctoral Fellowship.
This work was also supported by the Stanley Medical Research Institute.;
We are grateful for the help of Dr. H. Ronald Zielke and Robert Vigorito
of the University of Maryland Brain and Tissue Bank for Developmental
Disorders.
NR 59
TC 9
Z9 9
U1 1
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0736-5748
J9 INT J DEV NEUROSCI
JI Int. J. Dev. Neurosci.
PD NOV
PY 2008
VL 26
IS 7
BP 791
EP 803
DI 10.1016/j.ijdevneu.2008.06.004
PG 13
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA 373EH
UT WOS:000260953300017
PM 18662768
ER
PT J
AU Bhattacharjee, AK
Chang, L
Chen, M
White, L
Bell, JM
Bazinet, RP
Rapoport, SI
AF Bhattacharjee, Abesh K.
Chang, Lisa
Chen, Mei
White, Laura
Bell, Jane M.
Bazinet, Richard P.
Rapoport, Stanley I.
TI Chronic d-amphetamine depresses an imaging marker of arachidonic acid
metabolism in rat brain
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Arachidonic acid; d-amphetamine; dopamine; quinpirole; SKF-38393
ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL GLUCOSE-UTILIZATION; INDUCED
DOPAMINE RELEASE; UNANESTHETIZED RATS; SIGNAL-TRANSDUCTION;
PHOSPHOLIPASE A(2); TRANSCRIPTION FACTOR; NONHUMAN-PRIMATES; SENSITIZED
RATS; RECEPTOR
AB Acute d-amphetamine (d-Amph) administration to rats leads to the release of arachiclonic acid (AA, 20:4n-6) as a second messenger following indirect agonism at dopamine D-2-like receptors in the brain. We hypothesized that chronically administered d-Amph in rats also would alter brain AA metabolism and signalling. To test this, adult male rats were injected i.p. daily for 2 wk with saline or 2.5 mg/kg d-Amph. After a 1-d washout, the unanaesthetized rats were injected acutely with i.v. saline, 1 mg/kg quinpirole (a D-2-like receptor agonist) or 5.0 mg/kg SKF-38393 (a D-1-like receptor agonist), followed by i.v. [1-C-14]AA. The AA incorporation coefficient k* (brain radioactivity/integrated plasma radioactivity), a marker of AA signalling and metabolism, was quantified using autoractiography in each of 62 brain regions. Compared with chronic saline, chronic d-Amph widely decreased baseline values of k* in brain regions having D2-like receptors. On the other hand, chronic amphetamine did not alter the k* responses to quinpirole seen in chronic saline-treated rats. SKF-38393 had minimal effects on V in both chronic saline-treated and amphetamine-treated rats, consistent with D-1-like receptors not being coupled to AA signalling. The ability of chronic d-Amph after 1-d washout to down-regulate baseline values of k* probably reflects neuroplastic changes in brain AA signalling, and may correspond to depressive behaviours noted following withdrawal from chronic amphetamine in humans and in rats.
C1 [Bhattacharjee, Abesh K.; Chang, Lisa; Chen, Mei; White, Laura; Bell, Jane M.; Bazinet, Richard P.; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Bhattacharjee, AK (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126, Bethesda, MD 20892 USA.
EM abeshb@mail.nih.gov
FU Intramural Program of the National Institute on Aging
FX ``This work was entirely supported by the Intramural Program of the
National Institute on Aging.
NR 74
TC 5
Z9 5
U1 0
U2 3
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD NOV
PY 2008
VL 11
IS 7
BP 957
EP 969
DI 10.1017/S1461145708008833
PG 13
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 364BL
UT WOS:000260311100007
PM 18570702
ER
PT J
AU Rajagopal, R
Dattilo, LK
Kaartinen, V
Deng, CX
Umans, L
Zwijsen, A
Roberts, AB
Bottinger, EP
Beebe, DC
AF Rajagopal, Ramya
Dattilo, Lisa K.
Kaartinen, Vesa
Deng, Chu-Xia
Umans, Lieve
Zwijsen, An
Roberts, Anita B.
Bottinger, Erwin P.
Beebe, David C.
TI Functions of the Type 1 BMP Receptor Acvr1 (Alk2) in Lens Development:
Cell Proliferation, Terminal Differentiation, and Survival
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSFORMATION; NEURAL CREST CELLS; MOUSE EMBRYO;
CONDITIONAL KNOCKOUT; P53-DEPENDENT APOPTOSIS; TRANSCRIPTION FACTOR;
C-MAF; GROWTH; MICE; GENERATION
AB PURPOSE. Bone morphogenetic protein (BMP) signaling is essential for the induction and subsequent development of the lens. The purpose of this study was to analyze the function(s) of the type 1 BMP receptor, Acvr1, in lens development.
METHODS. Acvr1 was deleted from the surface ectoderm of mouse embryos on embryonic day 9 using the Cre-loxP method. Cell proliferation, cell cycle exit, and apoptosis were measured in tissue sections by immunohistochemistry, immunofluorescence, and TUNEL staining.
RESULTS. Lenses formed in the absence of Acvr1. However, Acvr1(CKO) (conditional knockout) lenses were small. Acvr1 signaling promoted proliferation at early stages of lens formation but inhibited proliferation at later stages. Inhibition of cell proliferation by Acvr1 was necessary for the proper regionalization of the lens epithelium and promoted the withdrawal of lens fiber cells from the cell cycle. In spite of the failure of all Acvr1CKO fiber cells to withdraw from the cell cycle, they expressed proteins characteristic of differentiated fiber cells. Although the stimulation of proliferation was Smad independent, the ability of Acvr1 to promote cell cycle exit later in development depended on classical R-Smad-Smad4 signaling. Loss of Acvr1 led to an increase in apoptosis of lens epithelial and fiber cells. Increased cell death, together with the initial decrease in proliferation, appeared to account for the smaller sizes of the Acvr1CKO lenses.
CONCLUSIONS. This study revealed a novel switch in the functions of Acvr1 in regulating lens cell proliferation. Previously unknown functions mediated by this receptor included regionalization of the lens epithelium and cell cycle exit during fiber cell differentiation. (Invest Ophthalmol Vis Sci. 2008;49: 4953-4960) DOI: 10.1167/iovs.08-2217
C1 [Rajagopal, Ramya; Dattilo, Lisa K.; Beebe, David C.] Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
[Beebe, David C.] Washington Univ, Dept Cell Biol & Physiol, St Louis, MO 63110 USA.
[Kaartinen, Vesa] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dev Biol Program,Dept Pathol, Los Angeles, CA 90033 USA.
[Kaartinen, Vesa] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dev Biol Program,Dept Surg, Los Angeles, CA 90033 USA.
[Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA.
[Umans, Lieve; Zwijsen, An] VIB, Dept Mol & Dev Genet, Lab Mol Biol Celgen, Louvain, Belgium.
[Umans, Lieve; Zwijsen, An] Katholieke Univ Leuven, Ctr Human Genet, Lab Mol Biol Celgen, Louvain, Belgium.
[Roberts, Anita B.] NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA.
[Bottinger, Erwin P.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
RP Rajagopal, R (reprint author), Washington Univ, Dept Ophthalmol & Visual Sci, Box 8096,660 S Euclid St, St Louis, MO 63110 USA.
EM rajagopal@vision.wustl.edu
RI deng, chuxia/N-6713-2016;
OI Kaartinen, Vesa/0000-0002-9432-510X
FU National Institutes of Health [EY02687, EY04853, 5R01HL074862,
5R01DE013085]
FX Supported by an unrestricted grant from Research to Prevent Blindness
and by National Institutes of Health Core Grant EY02687 (Department of
Ophthalmology and Visual Sciences) and Grants EY04853 (DCB),
5R01HL074862 (VK), and 5R01DE013085 (VK).
NR 45
TC 25
Z9 25
U1 0
U2 1
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 NOV
PY 2008
VL 49
IS 11
BP 4953
EP 4960
DI 10.1167/iovs.08-2217
PG 8
WC Ophthalmology
SC Ophthalmology
GA 366RX
UT WOS:000260502200037
PM 18566469
ER
PT J
AU Gangnon, RE
Davis, MD
Hubbard, LD
Aiello, LM
Chew, EY
Ferris, FL
Fisher, MR
AF Gangnon, Ronald E.
Davis, Matthew D.
Hubbard, Larry D.
Aiello, Lloyd M.
Chew, Emily Y.
Ferris, Frederick L., III
Fisher, Marian R.
CA Early Treatment Diabetic Retinopa
TI A Severity Scale for Diabetic Macular Edema Developed from ETDRS Data
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; RETINOPATHY
AB PURPOSE. To develop a severity scale for diabetic macular edema (DME) and to assess relationships between severity and duration of DME and visual acuity (VA).
METHODS. From the Early Treatment Diabetic Retinopathy Study (ETDRS), mean baseline VA scores were tabulated for 7422 eyes cross-classified by (1) location of retinal thickening (RT) and its area within 1 disc diameter of the macular center, and (2) degree of RT at the center. Adjacent (row, column, and off-diagonal) cells with the greatest similarity in baseline VA (mean and SD) based on a Gaussian (normal) likelihood were merged. An initial eight-step scale was chosen using the Schwarz criterion (Bayesian information criterion; BIC) and was revised based on clinical judgment to nine steps. Relationships between baseline VA and other photographic and fluorescein angiographic characteristics were examined singly and in combination with the scale.
RESULTS. Modeling baseline VA as a function of the nine-step scale yielded an R-2 of 38.0%, compared with 38.4% using the full cross-classification of these variables. Addition of each of the other baseline characteristics changed the adjusted R2 for the combination very little. Between scale levels 1A and 5B mean (SD) VA decreased from 86.8 (5.8) letters to 59.8 (13.6) letters. In a model of change in VA as a function of time spent at each DME severity level, VA loss increased progressively from 1 letter per year at level 2 to 17 letters per year at level 5B.
CONCLUSIONS. The scale facilitates documentation of the relationship of severity and duration of DME with VA. (Invest Ophthalmol Vis Sci. 2008;49:5041-5047) DOI:10.1167/iovs.08-2231
C1 [Davis, Matthew D.; Hubbard, Larry D.] Univ Wisconsin, FPRC, Dept Ophthalmol & Visual Sci, Madison, WI 53711 USA.
[Gangnon, Ronald E.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53711 USA.
[Gangnon, Ronald E.] Univ Wisconsin, Dept Stat, Madison, WI 53711 USA.
[Fisher, Marian R.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53711 USA.
[Aiello, Lloyd M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Chew, Emily Y.; Ferris, Frederick L., III] NEI, Bethesda, MD 20892 USA.
RP Hubbard, LD (reprint author), Univ Wisconsin, FPRC, Dept Ophthalmol & Visual Sci, Pk W 1, Madison, WI 53711 USA.
EM hubbard@rc.ophth.wisc.edu
FU National Eye Institute [R03 EY1029-01]
FX Supported by Grant R03 EY1029-01 from the National Eye Institute.
NR 13
TC 19
Z9 20
U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2008
VL 49
IS 11
BP 5041
EP 5047
DI 10.1167/iovs.08-2231
PG 7
WC Ophthalmology
SC Ophthalmology
GA 366RX
UT WOS:000260502200047
PM 18539929
ER
PT J
AU Bingham, RJ
AF Bingham, Raymond J.
TI Annotated Bibliography of NINR Findings on Women's Health Across the
Lifespan, 2008 Update
SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING
LA English
DT Article
C1 NINR, Off Sci Policy & Publ Lias, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Bingham, RJ (reprint author), NINR, Off Sci Policy & Publ Lias, Natl Inst Hlth, 31 Ctr Dr,MSC-2178 Bldg 31,Room 5B-10, Bethesda, MD 20892 USA.
EM info@ninr.nih.gov
FU Intramural NIH HHS [Z99 NR999999]
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0884-2175
J9 JOGNN-J OBST GYN NEO
JI JOGNN
PD NOV-DEC
PY 2008
VL 37
IS 6
BP 702
EP 704
DI 10.1111/j.1552-6909.2008.00294.x
PG 3
WC Nursing; Obstetrics & Gynecology
SC Nursing; Obstetrics & Gynecology
GA 370CK
UT WOS:000260740100011
PM 19012719
ER
PT J
AU Fitzgibbon, JE
Sagripanti, JL
AF Fitzgibbon, J. E.
Sagripanti, J. -L.
TI Analysis of the survival of Venezuelan equine encephalomyelitis virus
and possible viral simulants in liquid suspensions
SO JOURNAL OF APPLIED MICROBIOLOGY
LA English
DT Article
DE alphavirus; biodefense; disinfection; environmental water; Sindbis;
simulant; Venezuelan equine encephalitis; water
ID PLASMA-DERIVED PRODUCTS; FELINE CALICIVIRUS; ESCHERICHIA-COLI;
SOLAR-RADIATION; SINDBIS-VIRUS; PLAQUE-ASSAY; INACTIVATION; MS2;
COLIPHAGE; TEMPERATURE
AB Aims: To compare the inactivation rate of Venezuelan equine encephalomyelitis (VEE) virus in liquids to that of Sindbis virus (SV, another alphavirus) and to a bacteriophage (MS2) generally used as a viral simulant in the development of countermeasures in biodefense.
Methods and Results: Viruses were inoculated into liquids and viral titres were determined at various times postinoculation. The viruses were stable in distilled-deionized (dd) water at 4 degrees C during the 21 days of the study. The inactivation rates of VEE and SV in dd water at 21 and 30 degrees C were very similar (between 0.12 and 0.14 log(10) per day), while MS2 was three-fold slower. In tap water (chlorine content between 4 and 5 ppm) at 21 degrees C, VEE and SV were inactivated at twice the rate measured in dd water.
Conclusions: The inactivation rates of VEE and SV were similar to each other and faster than MS2 in all liquids tested.
Significance and Impact of the Study: VEE is likely to remain viable for many days after release into water, snow, or even chlorinated tap water. SV can be used to estimate the persistence of VEE in liquids, but using MS2 as a simulant would overestimate of the stability of VEE.
C1 [Sagripanti, J. -L.] USA, Edgewood Chem Biol Ctr, Res Engn & Dev Command, Aberdeen Proving Ground, MD 21010 USA.
[Fitzgibbon, J. E.] NIH, Div Aids, Therapeut Res Program, Drug Dev & Clin Sci Branch, Bethesda, MD 20892 USA.
RP Sagripanti, JL (reprint author), USA, Edgewood Chem Biol Ctr, Res Engn & Dev Command, AMSRD ECB RT 5183 Blackhawk Rd,Edgewood Area, Aberdeen Proving Ground, MD 21010 USA.
EM joseluis.sagripanti@us.army.mil
FU US Department of Defense Chemical and Biological Defense; Defense Threat
Reduction Agency; In-House Laboratory Independent Research (ILIR);
Research and Technology Directorate, Edgewood Chemical Biological
Center, Research Development and Engineering Command, US Army
FX We gratefully acknowledge Dr Mike Parker of USAMRIID for supplying the
VEE TC-83 virus. This work was supported by the US Department of Defense
Chemical and Biological Defense program administered by the Defense
Threat Reduction Agency and by In-House Laboratory Independent Research
(ILIR) funds from the Research and Technology Directorate, Edgewood
Chemical Biological Center, Research Development and Engineering
Command, US Army.
NR 24
TC 4
Z9 4
U1 2
U2 5
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1364-5072
J9 J APPL MICROBIOL
JI J. Appl. Microbiol.
PD NOV
PY 2008
VL 105
IS 5
BP 1477
EP 1483
DI 10.1111/j.1365-2672.2008.03919.x
PG 7
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 361FP
UT WOS:000260113200026
PM 19146486
ER
PT J
AU Walsh, S
Liu, DM
Metter, EJ
Ferrucci, L
Roth, SM
AF Walsh, Sean
Liu, Dongmei
Metter, E. Jeffrey
Ferrucci, Luigi
Roth, Stephen M.
TI ACTN3 genotype is associated with muscle phenotypes in women across the
adult age span
SO JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Article
DE genetics; muscle strength; sex differences; skeletal muscle
ID FAT-FREE MASS; ALPHA-ACTININ-3 DEFICIENCY; ATHLETIC PERFORMANCE; R577X
POLYMORPHISM; GENERAL-POPULATION; BODY-COMPOSITION; ALPHA-ACTININ;
HEALTHY-MEN; STRENGTH; EVOLUTION
AB Walsh S, Liu D, Metter EJ, Ferrucci L, Roth SM. ACTN3 genotype is associated with muscle phenotypes in women across the adult age span. J Appl Physiol 105: 1486-1491, 2008. First published August 28, 2008; doi:10.1152/japplphysiol.90856.2008.-The R577X polymorphism in the alpha-actinin-3 encoding gene (ACTN3) has been associated with elite athletic performance, and recently with differences in isometric and dynamic muscle strength and power in the general population. In this study we sought to determine the association of ACTN3 R577X genotype with muscle strength and mass phenotypes in men and women across the adult age span. Eight hundred forty-eight (n = 848) adult volunteers (454 men and 394 women) aged 22-90 yr were genotyped for ACTN3 R577X. Knee extensor (KE) shortening and lengthening peak torque values were determined using isokinetic dynamometry and fat-free mass (FFM) by dual-energy X-ray absorptiometry. Women deficient in alpha-actinin-3 (X/X; n = 53) displayed lower KE shortening peak torque (30 degrees/s: 89.5 +/- 3.5 vs. 99.3 +/- 1.4 N.m, P = 0.011; 180 degrees/s: 60.3 +/- 2.6 vs. 67.0 +/- 1.0 N.m, P = 0.019) and KE lengthening peak torque (30 degrees/s: 122.8 +/- 5.7 vs. 137.0 +/- 2.2 N.m, P = 0.022; 180 degrees/s: 121.8 +/- 5.8 vs. 138.5 +/- 2.2 N.m, P = 0.008) compared with R/X + R/R women (n = 341). Women X/X homozygotes also displayed lower levels of both total body FFM (38.9 +/- 0.5 vs. 40.1 +/- 0.2 kg, P = 0.040) and lower limb FFM (11.9 +/- 0.2 vs. 12.5 +/- 0.1 kg, P = 0.044) compared with R/X + R/R women. No genotype-related differences were observed in men. In conclusion, our results indicate that the absence of alpha-actinin-3 protein (i.e., ACTN3 X/X genotype) influences KE peak torque and FFM in women but not men.
C1 [Walsh, Sean; Liu, Dongmei; Roth, Stephen M.] Univ Maryland, Dept Kinesiol, Sch Publ Hlth, College Pk, MD 20742 USA.
Cent Connecticut State Univ, New Britain, CT 06050 USA.
[Metter, E. Jeffrey; Ferrucci, Luigi] Harbor Hosp, Clin Res Branch, NIA, Baltimore, MD USA.
RP Roth, SM (reprint author), Univ Maryland, Dept Kinesiol, Sch Publ Hlth, 2134 SPH Bldg, College Pk, MD 20742 USA.
EM sroth1@umd.edu
RI Liu, Dongmei/C-1525-2012;
OI Roth, Stephen/0000-0002-7841-3695
FU National Institutes of Health [AG-021500, AG-022791]
FX The BLSA research was conducted as a component of the Intramural
Research Program of the National Institute on Aging. This work was
further sponsored by National Institutes of Health Grants AG-021500 and
AG-022791.
NR 34
TC 67
Z9 68
U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 8750-7587
J9 J APPL PHYSIOL
JI J. Appl. Physiol.
PD NOV
PY 2008
VL 105
IS 5
BP 1486
EP 1491
DI 10.1152/japplphysiol.90856.2008
PG 6
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 368GO
UT WOS:000260609800014
PM 18756004
ER
PT J
AU Schirmbeck, F
Georgi, A
Strohmaier, J
Schmael, C
Boesshenz, KV
Muhleisen, TW
Herms, S
Hoffmann, P
Rami, RA
Schumacher, J
Maier, W
Propping, P
Nothen, MM
Cichon, S
Rietschel, M
Schulze, TG
AF Schirmbeck, Frederike
Georgi, Alexander
Strohmaier, Jana
Schmael, Christine
Boesshenz, Katja V.
Muehleisen, Thomas W.
Herms, Stefan
Hoffmann, Per
Jamra, Rami Abou
Schumacher, Johannes
Maier, Wolfgang
Propping, Peter
Noethen, Markus M.
Cichon, Sven
Rietschel, Marcella
Schulze, Thomas G.
TI Brief Report: No Association Between Premorbid Adjustment in Adult-Onset
Schizophrenia and Genetic Variation in Dysbindin
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Premorbid functioning; Susceptibility genes; Haplotypes; Phenotype
dissection; Complex genetics; Endophenotype
ID BIPOLAR DISORDER; FAMILIAL RISK; 6P22.3 GENE; DTNBP1; PHENOTYPE;
LINKAGE; INTELLIGENCE; PSYCHIATRY; PSYCHOSIS; RARE
AB Whereas Dysbindin is considered a schizophrenia vulnerability gene, there is no consistency of findings. Phenotype refinement approaches may help to increase the genetic homogeneity and thus reconcile conflicting results. Premorbid adjustment (PMA) has been suggested to aid the phenotypic dissection. Gornick et al. (J Autism Dev Disord 35:831-838, 2005) reported an association between Dysbindin and PMA in US-Caucasian individuals with childhood-onset psychosis. In a sample of 222 adult-onset schizophrenia inpatients from Germany, we could not detect an association between PMA and 36 SNPs in Dysbindin. Our results suggest that genetic variation in Dysbindin may not contribute to the schizophrenia phenotype with an onset beyond childhood. Further studies including even larger samples and more SNPs may be warranted to clarify the relationship between Dysbindin and PMA.
C1 [Schulze, Thomas G.] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA.
[Schirmbeck, Frederike; Georgi, Alexander; Strohmaier, Jana; Schmael, Christine; Boesshenz, Katja V.; Rietschel, Marcella; Schulze, Thomas G.] Univ Heidelberg, Dept Genet Epidemiol, Cent Inst Mental Hlth, D-6800 Mannheim, Germany.
[Muehleisen, Thomas W.; Herms, Stefan; Hoffmann, Per; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Dept Genom Life & Brain Ctr, D-5300 Bonn, Germany.
[Jamra, Rami Abou; Schumacher, Johannes; Propping, Peter; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany.
[Maier, Wolfgang] Univ Bonn, Dept Psychiat & Psychotherapy, D-5300 Bonn, Germany.
RP Schulze, TG (reprint author), NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, 35 Convent Dr,Bldg 35,Rm 1A202,MSC 3719, Bethesda, MD 20892 USA.
EM schulzet@mail.nih.gov
RI Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon,
Sven/B-9618-2014; Abou Jamra, Rami/I-4805-2015; Schirmbeck,
Frederike/G-8187-2016; Schumacher, Johannes/F-4970-2015; Herms,
Stefan/J-1949-2014;
OI Cichon, Sven/0000-0002-9475-086X; Nothen, Markus/0000-0002-8770-2464;
Cichon, Sven/0000-0002-9475-086X; Hoffmann, Per/0000-0002-6573-983X;
Abou Jamra, Rami/0000-0002-1542-1399; Schumacher,
Johannes/0000-0001-9217-6457; Georgi, Alexander/0000-0002-1499-8524;
Herms, Stefan/0000-0002-2786-8200; Schirmbeck,
Frederike/0000-0003-1700-0958
NR 34
TC 0
Z9 0
U1 2
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD NOV
PY 2008
VL 38
IS 10
BP 1977
EP 1981
DI 10.1007/s10803-008-0582-6
PG 5
WC Psychology, Developmental
SC Psychology
GA 373FJ
UT WOS:000260956100017
PM 18473158
ER
PT J
AU Gawel, D
Hamilton, MD
Schaaper, RM
AF Gawel, Damian
Hamilton, Michael D.
Schaaper, Roel M.
TI A Novel Mutator of Escherichia coli Carrying a Defect in the dgt Gene,
Encoding a dGTP Triphosphohydrolase
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID DEOXYGUANOSINE TRIPHOSPHATE TRIPHOSPHOHYDROLASE; DNA MISMATCH-REPAIR;
ADAPTIVE MUTATION; REPLICATION FIDELITY; INDUCED MUTAGENESIS; BASE
SUBSTITUTIONS; NUDIX HYDROLASES; POLYMERASE-IV; 1.2 PROTEIN; MUTT
AB A novel mutator locus in Escherichia coli was identified from a collection of random transposon insertion mutants. Several mutators in this collection were found to have an insertion in the dgt gene, encoding a previously characterized dGTP triphosphohydrolase. The mutator activity of the dgt mutants displays an unusual specificity. Among the six possible base pair substitutions in a lacZ reversion system, the G center dot C -> C center dot G transversion and A center dot T -> G center dot C transition are strongly enhanced (10- to 50-fold), while a modest effect (two- to threefold) is also observed for the G center dot C -> A center dot T transition. Interestingly, a two- to threefold reduction in mutant frequency (antimutator effect) is observed for the G center dot C -> T center dot A transversion. In the absence of DNA mismatch repair (mutL) some of these effects are reduced or abolished, while other effects remain unchanged. Analysis of these effects, combined with the DNA sequence contexts in which the reversions take place, suggests that alterations of the dGTP pools as well as alterations in the level of some modified dNTP derivatives could affect the fidelity of in vivo DNA replication and, hence, account for the overall mutator effects.
C1 [Gawel, Damian; Hamilton, Michael D.; Schaaper, Roel M.] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
RP Schaaper, RM (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
EM schaaper@niehs.nih.gov
FU NIH; National Institute of Environmental Health Sciences
FX This work was supported by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences. We thank S. Covo
and Z. Pursell of the NIEHS for their helpful review of the manuscript
for this paper and Sean Moore for his help in constructing the strains
containing the chromosomal lacZ alleles.
NR 54
TC 11
Z9 11
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
EI 1098-5530
J9 J BACTERIOL
JI J. Bacteriol.
PD NOV
PY 2008
VL 190
IS 21
BP 6931
EP 6939
DI 10.1128/JB.00935-08
PG 9
WC Microbiology
SC Microbiology
GA 361ZF
UT WOS:000260166900001
PM 18776019
ER
PT J
AU Thein, M
Bunikis, I
Denker, K
Larsson, C
Cutler, S
Drancourt, M
Schwan, TG
Mentele, R
Lottspeich, F
Bergstrom, S
Benz, R
AF Thein, Marcus
Bunikis, Ignas
Denker, Katrin
Larsson, Christer
Cutler, Sally
Drancourt, Michel
Schwan, Tom G.
Mentele, Reinhard
Lottspeich, Friedrich
Bergstroem, Sven
Benz, Roland
TI Oms38 Is the First Identified Pore-Forming Protein in the Outer Membrane
of Relapsing Fever Spirochetes
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID LIPID BILAYER-MEMBRANES; LYME-DISEASE SPIROCHETE; FRACTURE
ELECTRON-MICROSCOPY; BORRELIA-BURGDORFERI; ESCHERICHIA-COLI; ANTIGENIC
VARIATION; BINDING-SITE; MITOCHONDRIAL PORIN; TREPONEMA-PALLIDUM;
HERMSII
AB Relapsing fever is a worldwide, endemic disease caused by several spirochetal species belonging to the genus Borrelia. During the recurring fever peaks, borreliae proliferate remarkably quickly compared to the slow dissemination of Lyme disease Borrelia and therefore require efficient nutrient uptake from the blood of their hosts. This study describes the identification and characterization of the first relapsing fever porin, which is present in the outer membranes of B. duttonii, B. hermsii, B. recurrentis, and B. turicatae. The pore-forming protein was purified by hydroxyapatite chromatography and designated Oms38, for outer membrane-spanning protein of 38 kDa. Biophysical characterization of Oms38 was done by using the black lipid bilayer method, demonstrating that Oms38 forms small, water-filled channels of 80 pS in 1 M KCl that did not exhibit voltage-dependent closure. The Oms38 channel is slightly selective for anions and shows a ratio of permeability for cations over anions of 0.41 in KCl. Analysis of the deduced amino acid sequences demonstrated that Oms38 contains an N-terminal signal sequence which is processed under in vivo conditions. Oms38 is highly conserved within the four studied relapsing fever species, sharing an overall amino acid identity of 58% and with a strong indication for the presence of amphipathic beta-sheets.
C1 [Thein, Marcus; Benz, Roland] Univ Wurzburg, Dept Biotechnol, Bioctr, D-97074 Wurzburg, Germany.
[Bunikis, Ignas; Larsson, Christer; Bergstroem, Sven] Umea Univ, Dept Mol Biol, Umea, Sweden.
[Denker, Katrin] Univ Wurzburg, Rudolf Virchow Ctr, DFG Res Ctr Expt Biomed, Wurzburg, Germany.
[Cutler, Sally] Univ E London, Sch Hlth & Biosci, London E15 4LZ, England.
[Drancourt, Michel] Univ Aix Marseille 2, Unite Rickettsies, CNRS UMR 6020, IFR 48, Marseille, France.
[Schwan, Tom G.] NIAID, Rocky Mt Lab, Natl Inst Hlth, Hamilton, MT 59840 USA.
[Mentele, Reinhard; Lottspeich, Friedrich] Max Planck Inst Biochem, D-82152 Martinsried, Germany.
RP Benz, R (reprint author), Univ Wurzburg, Dept Biotechnol, Bioctr, D-97074 Wurzburg, Germany.
EM roland.benz@mail.uni-wuerzburg.de
OI Larsson, Christer/0000-0002-5714-924X; Benz, Roland/0000-0002-9510-9265
FU Fonds der Chemischen Industrie; Swedish Medical Research Council
FX We thank Christian Andersen for critical discussion of the results and
Stephen Porcella and Sandra Steward for the help with sequencing.; This
work was supported by grants from the joint project between Stint
(Sweden) and DAAD (Germany) to S. B. and R. B., from the Fonds der
Chemischen Industrie (to R. B.), and from the Swedish Medical Research
Council (to S. B.).
NR 75
TC 10
Z9 10
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
EI 1098-5530
J9 J BACTERIOL
JI J. Bacteriol.
PD NOV
PY 2008
VL 190
IS 21
BP 7035
EP 7042
DI 10.1128/JB.00818-08
PG 8
WC Microbiology
SC Microbiology
GA 361ZF
UT WOS:000260166900011
PM 18757545
ER
PT J
AU Ogura, K
Shiga, T
Yokochi, M
Yuzawa, S
Burke, TR
Inagaki, F
AF Ogura, Kenji
Shiga, Takanori
Yokochi, Masashi
Yuzawa, Satoru
Burke, Terrence R., Jr.
Inagaki, Fuyuhiko
TI Solution structure of the Grb2 SH2 domain complexed with a high-affinity
inhibitor
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE Perdeuterated Grb2 SH2; Solution structure; Inhibitor; Structure-based
drug design
ID RECEPTOR TYROSINE KINASES; STRUCTURE-BASED DESIGN; HUMAN BREAST-CANCER;
NUCLEOTIDE EXCHANGE; CRYSTAL-STRUCTURES; RAS PATHWAY; PROTEIN; PEPTIDE;
ACTIVATION; BINDING
AB The solution structure of the growth factor receptor-bound protein 2 (Grb2) SH2 domain complexed with a high-affinity inhibitor containing a non-phosphorus phosphate mimetic within a macrocyclic platform was determined by nuclear magnetic resonance (NMR) spectroscopy. Unambiguous assignments of the bound inhibitor and intermolecular NOEs between the Grb2 SH2 domain and the inhibitor was accomplished using perdeuterated Grb2 SH2 protein. The well-defined solution structure of the complex was obtained and compared to those by X-ray crystallography. Since the crystal structure of the Grb2 SH2 domain formed a domain-swapped dimer and several inhibitors were bound to a hinge region, there were appreciable differences between the solution and crystal structures. Based on the binding interactions between the inhibitor and the Grb2 SH2 domain in solution, we proposed a design of second-generation inhibitors that could be expected to have higher affinity.
C1 [Ogura, Kenji; Shiga, Takanori; Yokochi, Masashi; Yuzawa, Satoru; Inagaki, Fuyuhiko] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Biol Struct, Kita Ku, Sapporo, Hokkaido 0600812, Japan.
[Burke, Terrence R., Jr.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Inagaki, F (reprint author), Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Biol Struct, Kita Ku, N12 W6, Sapporo, Hokkaido 0600812, Japan.
EM finagaki@pharm.hokudai.ac.jp
RI Burke, Terrence/N-2601-2014
FU Ministry of Education, Science and Culture of Japan; International
Research Program of the NIH, Center for Cancer Research, National Cancer
Institute
FX This work was supported by Grant-in-Aid for Scientific Research and the
National Projects on Protein Structure and Functional Analysis from the
Ministry of Education, Science and Culture of Japan. This research was
also supported in part by the International Research Program of the NIH,
Center for Cancer Research, National Cancer Institute.
NR 39
TC 15
Z9 15
U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD NOV
PY 2008
VL 42
IS 3
BP 197
EP 207
DI 10.1007/s10858-008-9272-0
PG 11
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA 363QM
UT WOS:000260281800005
PM 18830565
ER
PT J
AU Nesti, LJ
Jackson, WM
Shanti, RM
Koehler, SM
Aragon, AB
Bailey, JR
Sracic, MK
Freedman, BA
Giuliani, JR
Tuan, RS
AF Nesti, Leon J.
Jackson, Wesley M.
Shanti, Rabie M.
Koehler, Steven M.
Aragon, Amber B.
Bailey, James R.
Sracic, Michael K.
Freedman, Brett A.
Giuliani, Jeffrey R.
Tuan, Rocky S.
TI Differentiation Potential of Multipotent Progenitor Cells Derived from
War-Traumatized Muscle Tissue
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; BONE-MARROW; STROMAL CELLS; CARTILAGE;
IDENTIFICATION; REGENERATION; FRACTURES; INJURY; MICE
AB Background: Recent military conflicts have resulted in numerous extremity injuries requiring complex orthopaedic reconstructive procedures, which begin with a thorough debridement of all contaminated and necrotic tissue in the zone of injury. The site of injury is also the site of healing, and we propose that debrided muscle tissue contains cells with robust reparative and regenerative potential.
Methods: Debrided muscle from soldiers who had sustained traumatic open extremity injuries was collected during surgical debridement procedures at Walter Reed Army Medical Center. With modifications to a previously described stem-cell-isolation protocol, mesenchymal progenitor cells were harvested from traumatized muscle, enriched, expanded in culture, and exposed to induction media for osteogenesis, adipogenesis, and chondrogenesis.
Results: The isolated mesenchymal progenitor cells stained positive for cell-surface markers (CD73, CD90, CD105), which are characteristic of adult human mesenchymal stem cells. Histological identification of lineage-specific markers demonstrated the potential of these cells to differentiate into multiple mesenchymal lineages. Reverse transcription-polymerase chain reaction analysis confirmed multilineage mesenchymal differentiation at the gene-expression level.
Conclusions: To our knowledge, the present report provides the first description of mesenchymal progenitor cell isolation from traumatized human muscle. These cells may play an integral role in tissue repair and regeneration and merit additional investigation as they could be useful in future cell-based tissue-engineering strategies.
Clinical Significance: Mesenchymal progenitor cells isolated from war-traumatized tissues have the potential for applications in cell-based tissue engineering. Elucidating the cellular mechanisms regulating their differentiation activities may lead to the development of novel treatments for musculoskeletal trauma and pathological healing responses, such as heterotopic ossification.
C1 [Jackson, Wesley M.; Shanti, Rabie M.; Koehler, Steven M.; Aragon, Amber B.; Giuliani, Jeffrey R.; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, US Dept HHS, NIH, Bethesda, MD 20892 USA.
[Bailey, James R.; Sracic, Michael K.] Uniformed Serv Univ Hlth Sci, Washington, DC USA.
[Freedman, Brett A.] Walter Reed Army Med Ctr, Integrated Dept Orthopaed & Rehabil, Washington, DC 20307 USA.
RP Nesti, LJ (reprint author), 6900 Georgia Ave NW,Bldg 2,Room 5B28, Washington, DC 20307 USA.
EM leonnesti@gmail.com
FU Military Amputee Research Program [P05-A011]; NIH; NIAMS [Z01 AR41131]
FX In support of their research for or preparation of this work, one or
more of the authors received, in any one year, outside funding or grants
in excess of $10,000 from the Military Amputee Research Program at
Walter Reed Army Medical Center (P05-A011) and by the Intramural
Research Program at the NIH, NIAMS (Z01 AR41131). Neither they nor a
member of their immediate families received payments or other benefits
ora commitment or agreement to provide such benefits from a commercial
entity. No commercial entity paid or directed, or agreed to pay or
direct, any benefits to any research fund, foundation, division, center,
clinical practice, or other charitable or nonprofit organization with
which the authors, or a member of their immediate families. are
affiliated or associated.
NR 28
TC 81
Z9 85
U1 0
U2 3
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD NOV
PY 2008
VL 90A
IS 11
BP 2390
EP 2398
DI 10.2106/JBJS.H.00049
PG 9
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 372NA
UT WOS:000260907100009
PM 18978407
ER
PT J
AU Kuznetsov, SA
Cherman, N
Riminucci, M
Collins, MT
Robey, PG
Bianco, P
AF Kuznetsov, Sergei A.
Cherman, Natasha
Riminucci, Mara
Collins, Michael T.
Robey, Pamela Gehron
Bianco, Paolo
TI Age-Dependent Demise of GNAS-Mutated Skeletal Stem Cells and
"Normalization" of Fibrous Dysplasia of Bone
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE fibrous dysplasia; Gs alpha; mutation; skeletal stem cells; bone marrow
stromal cells
ID MCCUNE-ALBRIGHT SYNDROME; ACTIVATING G(S)ALPHA MUTATION; MARROW STROMAL
FIBROBLASTS; STIMULATORY G-PROTEIN; IN-VIVO; GENE; ABNORMALITIES;
PIGMENTATION; OSTEOGENESIS; DYSFUNCTION
AB We Studied the role of somatic mosaicism in fibrous dysplasia of bone (FD) within the context of skeletal ("mesenchymal") stern cells by assessing the frequency of mutated colony forming unit-fibroblasts (CFU-Fs) from FD lesions. and in some cases, from unaffected sites, in a series of patients. There was a tight inverse correlation between the percentage mutant CFU-F versus age, suggesting demise of mutant stem cells caused by exuberant apoptosis noted in samples from young patients. In older patients. either partially or completely normal bone/marrow histology was observed. On in vivo transplantation. FD ossicles were generated only by cell strains in which mutant CFU-Fs were identified. strains that lacked mutant CFU-F (but were mutation positive) failed to regenerate an FD ossicle. These data indicate that GNAS Mutations are only Pathogenic when in clonogenic skeletal stern cells. From these data, we have evolved the novel concept of "normalization" of FD. As a lesion ages, mutant stern cells fail to self-renew, and their progeny are consumed by apoptosis. whereas residual normal stern cells survive, self-renew. and enable formation of a normal Structure. This suggests that activating GNAS Mutations disrupt a pathway that is required for skeletal stern cell self-renewal.
C1 [Kuznetsov, Sergei A.; Cherman, Natasha; Collins, Michael T.; Robey, Pamela Gehron] NIDCR, CSDB, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Riminucci, Mara] Univ Laquila, Dept Expt Med, Laquila, Italy.
[Bianco, Paolo] Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy.
[Riminucci, Mara; Bianco, Paolo] Biomed Sci Pk, Rome, Italy.
RP Robey, PG (reprint author), NIDCR, CSDB, NIH, US Dept HHS, 30 Convent Dr,MSC 4320,Bldg 30,Room 228, Bethesda, MD 20892 USA.
EM probey@dir.nidcr.nih.gov
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
FU Telethon [GGP0463]; MIUR; AIRL; DIR; NIDCR; NII; DHHS
FX This work Was Supported by Telethon Grant GGP0463 (to PB), MIUR (PB,
MR), AIRL (PB), and the DIR, NIDCR of the IRP, NII, DHHS (to SAK, NC,
MTC, and PGR).
NR 26
TC 44
Z9 44
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD NOV
PY 2008
VL 23
IS 11
BP 1731
EP 1740
DI 10.1359/JBMR.080609
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 362KF
UT WOS:000260195900004
PM 18597624
ER
PT J
AU Chen, A
Leikina, E
Melikov, K
Podbilewicz, B
Kozlov, MM
Chernomordik, LV
AF Chen, Andrew
Leikina, Eugenia
Melikov, Kamran
Podbilewicz, Benjamin
Kozlov, Michael M.
Chernomordik, Leonid V.
TI Fusion-pore expansion during syncytium formation is restricted by an
actin network
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Cell fusion; Syncytium formation; Fusion-pore expansion; Actin
cytoskeleton; Membrane-bending proteins; Baculovirus gp64
ID INDUCED POLYKARYOCYTE FORMATION; VIRUS MEMBRANE-FUSION; CELL-CELL
FUSION; MYOBLAST FUSION; CAENORHABDITIS-ELEGANS; BACULOVIRUS GP64;
INFLUENZA HEMAGGLUTININ; C-ELEGANS; PROTEIN; MORPHOGENESIS
AB Cell-cell fusion in animal development and in pathophysiology involves expansion of nascent fusion pores formed by protein fusogens to yield an open lumen of cell-size diameter. Here we explored the enlargement of micron-scale pores in syncytium formation, which was initiated by a well-characterized fusogen baculovirus gp64. Radial expansion of a single or, more often, of multiple fusion pores proceeds without loss of membrane material in the tight contact zone. Pore growth requires cell metabolism and is accompanied by a local disassembly of the actin cortex under the pores. Effects of actin-modifying agents indicate that the actin cortex slows down pore expansion. We propose that the growth of the strongly bent fusion-pore rim is restricted by a dynamic resistance of the actin network and driven by membrane-bending proteins that are involved in the generation of highly curved intracellular membrane compartments.
C1 [Chen, Andrew; Leikina, Eugenia; Melikov, Kamran; Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Lab Cellular & Mol Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Podbilewicz, Benjamin] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.
[Kozlov, Michael M.] Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel.
RP Chernomordik, LV (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Lab Cellular & Mol Biophys, Natl Inst Hlth, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM chernoml@mail.nih.gov
RI Melikov, Kamran/A-6604-2009; Podbilewicz, Benjamin/N-4825-2014;
OI Podbilewicz, Benjamin/0000-0002-0411-4182
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Institutes of
Health
FX We are indebted to Gary Blissard for the generous gift of
Sf9Op1D cells and Myoungsoon S. Hong for her kind help with
electron-microscopy experiments. We thank Alexander Bershadsky,
Jean-Philippe Richard and Joshua Zimmerberg for very helpful
discussions. This research was supported by the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health (L.V.C.).
NR 75
TC 28
Z9 28
U1 0
U2 0
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 NOV 1
PY 2008
VL 121
IS 21
BP 3619
EP 3628
DI 10.1242/jcs.032169
PG 10
WC Cell Biology
SC Cell Biology
GA 363KR
UT WOS:000260266700015
PM 18946025
ER
PT J
AU Jozwiak, K
Moaddel, R
Ravichandran, S
Plazinska, A
Kozak, J
Patel, S
Yamaguchi, R
Wainer, IW
AF Jozwiak, Krzysztof
Moaddel, Ruin
Ravichandran, Sarangan
Plazinska, Anita
Kozak, Joanna
Patel, Sharvil
Yamaguchi, Rika
Wainer, Irving W.
TI Exploring enantiospecific ligand-protein interactions using cellular
membrane affinity chromatography: Chiral recognition as a dynamic
process
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE Nicotinic acetylcholine receptors; Organic cation transporters;
Pharmacophore modeling; Non-linear chromatography; Molecular modeling
ID NICOTINIC ACETYLCHOLINE-RECEPTORS; CATION TRANSPORTER HOCT1;
STATIONARY-PHASE; NONCOMPETITIVE INHIBITORS; NONLINEAR CHROMATOGRAPHY;
MOLECULAR DOCKING; AMINO-ACIDS; SEPARATION; MODEL; ALPHA-3-BETA-4
AB The chiral recognition mechanisms responsible for the enantioselective binding on the alpha(3)beta(4) nicotinic acetylcholine receptor (alpha(3)beta(4) nAChR) and human organic cation transporter 1 (hOCT1) have been reviewed. The results indicate that chiral recognition on the CON nAChR is a process involving initial tethering of dextromethorphan and levomethorphan at hydrophobic pockets within the central lumen followed by hydrogen bonding interactions favoring dextromethorphan. The second step is the defining enantioselective step. Studies with the hOCT1 indentified four binding sites within the transporter that participated in chiral recognition. Each of the enantiomers of the compounds used in the study interacted with three of these sites, while (R)-verapamil interacted with all four. Chiral recognition arose from the conformational adjustments required to produce optimum interactions. With respect to the prevailing interaction-based models, the data suggest that chiral recognition is a dynamic process and that the static point-based models should be amended to reflect this. (c) 2008 Elsevier B.V. All rights reserved.
C1 [Moaddel, Ruin; Patel, Sharvil; Yamaguchi, Rika; Wainer, Irving W.] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
[Jozwiak, Krzysztof; Plazinska, Anita; Kozak, Joanna] Med Univ Lublin, Lab Drug Receptor Interact, PL-20081 Lublin, Poland.
[Ravichandran, Sarangan] NCI, SAIC, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
[Patel, Sharvil] Cadilia Healthcare Ltd, Ahmadabad 380015, Gujarat, India.
RP Wainer, IW (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM Wainerir@grc.nia.nih.gov
OI Plazinska, Anita/0000-0002-3698-2574
FU National Institute on Aging Intramural Research Program; Foundation for
Polish Science [FOCUS 4/2006]
FX This work was supported by funding from the National Institute on Aging
Intramural Research Program (IWW) and from the Foundation for Polish
Science (FOCUS 4/2006 programme) (K.J.).
NR 47
TC 9
Z9 9
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD NOV 1
PY 2008
VL 875
IS 1
BP 200
EP 207
DI 10.1016/j.jchromb.2008.07.048
PG 8
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 373BK
UT WOS:000260945800027
PM 18723411
ER
PT J
AU Batista, DL
Courcoutsakis, N
Riar, J
Keil, MF
Stratakis, CA
AF Batista, Dalia L.
Courcoutsakis, Nikos
Riar, Jehan
Keil, Margaret F.
Stratakis, Constantine A.
TI Severe Obesity Confounds the Interpretation of Low-Dose Dexamethasone
Test Combined with the Administration of Ovine Corticotrophin-Releasing
Hormone in Childhood Cushing Syndrome
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID SALIVARY CORTISOL MEASUREMENT; URINARY FREE CORTISOL; BODY-MASS INDEX;
SUPPRESSION TEST; STIMULATION TEST; DIFFERENTIAL-DIAGNOSIS; METABOLIC
SYNDROME; CHILDREN; ADOLESCENTS; STATES
AB Context: Suppression of cortisol secretion with a low-dose dexamethasone (Dex) followed by the administration of ovine CRH (Dex-oCRH) is used in the evaluation of adults with a pseudo-Cushing syndrome state (PCSS) vs. Cushing syndrome (CS).
Objective: The aim of the study was to determine the value of Dex-oCRH testing in the investigation of childhood CS.
Design: We conducted a retrospective analysis of data from children evaluated for CS vs. PCSS from 1998-2006; body mass index Z (BMIZ) and height-for-age Z (HAZ) scores were estimated. Setting: A clinical research center was the setting for the study.
Main Outcome Measures: The main outcomes were confirmation of the diagnosis of CS by histology and response to Dex-oCRH.
Results: Thirty-two children (ages 3-17 yr) were studied: 11 had CS and 21 had PCSS; of the latter, 11 had a BMIZ score greater than 2. Children with CS had a mean HAZ score of -1.3 +/- 0.51 vs. 0.31 +/- 0.38 in nonobese and 0.71 +/- 0.39 in obese children (P < 0.001). The previously established criterion of a cortisol of 1.4 mu g/dl (38 nmol/liter) after Dex-oCRH identified all 10 normal children who were not very obese and those with CS; 5 of 11 normal children with more severe obesity had cortisol values greater than 1.4 mu g/dl (38 nmol/liter) after Dex-oCRH, lowering the test specificity to 55%. Without consideration for obesity, an increase of the cutoff cortisol value after Dex-oCRH to 3.2 mu g/dl (88 nmol/liter) will have 91% sensitivity and 95% specificity; the corresponding values for a cutoff of 2.2 mu g/dl (61 nmol/liter) were 100 and 90.5%, respectively.
Conclusion: Our study showed that height gain is a simple way of distinguishing children with PCCS from those with CS; the interpretation of Dex-oCRH in children is confounded by severe obesity, which limits the utility of this test. (J Clin Endocrinol Metab 93: 4323-4330, 2008)
C1 [Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Batista, Dalia L.; Riar, Jehan; Stratakis, Constantine A.] NIH, Pediat Endocrinol Interinst Training Program, Bethesda, MD 20892 USA.
[Courcoutsakis, Nikos] Univ Hosp Alexandroupolis, Dept Radiol, Alexandroupolis 68100, Greece.
RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bldg 10,CRC E Labs,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU National Institutes of Health; National Institute of Child Health and
Human Development [Z01-HD-000642-04]
FX This work was supported by the National Institutes of Health, National
Institute of Child Health and Human Development intramural project
Z01-HD-000642-04 (Principal Investigator, C. A. Stratakis).
NR 33
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Z9 9
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2008
VL 93
IS 11
BP 4323
EP 4330
DI 10.1210/jc.2008-0985
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 368ZI
UT WOS:000260661900023
PM 18728165
ER
PT J
AU Nwachuku, CE
Bastien, A
Cutler, JA
Grob, GM
Margolis, KL
Roccella, EJ
Pressel, S
Davis, BR
Caso, M
Sheps, S
Weber, M
AF Nwachuku, Chuke E.
Bastien, Arnaud
Cutler, Jeffrey A.
Grob, Glenda M.
Margolis, Karen L.
Roccella, Edward J.
Pressel, Sara
Davis, Barry R.
Caso, Michael
Sheps, Sheldon
Weber, Michael
TI Management of High Blood Pressure in Clinical Practice: Perceptible
Qualitative Differences in Approaches Utilized by Clinicians
SO JOURNAL OF CLINICAL HYPERTENSION
LA English
DT Article
ID ISOLATED SYSTOLIC HYPERTENSION; LIPID-LOWERING TREATMENT; ATTACK TRIAL
ALLHAT; UNITED-STATES; ACTIVE TREATMENT; PLACEBO; PREVENTION;
PREVALENCE; COMMITTEE; AWARENESS
AB The authors recruited a group of physicians among the investigators participating in the Anti-bypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with a greater (more successful) or lesser (less successful) proportion of trial patients meeting blood pressure (BP) control goals. The authors utilized qualitative focus group methods to identify similarities and differences in practice behaviors. Successful and less successful physicians bad similarities in knowledge and practice behaviors regarding awareness of treatment guidelines, approaches to diagnosis, use of pharmacologic management, and the opinion that systolic BP guidelines should consider a patient's age. However, there were discernible differences between the two physician groups in their views on doctor-patient relationships: physicians from the less successful group were more paternalistic with their patients, while physicians from the more successful group were more likely to use a patient-centered clinical approach to BP awareness and management. J Clin Hypertens (Greenwich). 2008;10:822-829. (C) 2008 Le Jacq
C1 [Pressel, Sara; Davis, Barry R.] Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX 77030 USA.
[Bastien, Arnaud] Bristol Myers Squibb Co, Princeton, NJ USA.
[Bastien, Arnaud] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA.
[Grob, Glenda M.] Adelphi Res Design, Doylestown, PA USA.
[Margolis, Karen L.] Hlth Partners Res Fdn, Minneapolis, MN USA.
[Roccella, Edward J.] NHLBI, Ctr Applicat Res Discoveries, Bethesda, MD 20892 USA.
[Caso, Michael] Nexus Commun Inc, N Wales, PA USA.
[Sheps, Sheldon] Mayo Med Sch & Clin, Rochester, MN USA.
[Weber, Michael] SUNY Downstate Coll Med, Brooklyn, NY USA.
RP Pressel, S (reprint author), Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, 1200 Herman Pressler St,Suite E801, Houston, TX 77030 USA.
EM sara.l.pressel@uth.tmc.edu
FU Boehringer Ingelheim; National Heart, Lung, and Blood Institute
[N01-HC-3S130]; Pfizer Inc
FX The authors are fully responsible for the methodology, inclusion and
interpretation of data, and opinions and conclusions expressed in this
article, which are independent of and do not necessarily reflect the
study funders. The authors bad access to the data, reviewed each
manuscript draft, and approved the final manuscript. We would like to
thank Joe Riley (Editorial Director, Nexus Communications, Inc.), Carol
Greco (Managing Editor, Nexus Communications, Inc.), and Wendy Henson
(Editorial Associate, Nexus Communications, Inc.) for their editorial
support during preparation of the revised manuscript. This study was
funded by Boehringer Ingelheim and the National Heart, Lung, and Blood
Institute. ALLHAT was supported by contract N01-HC-3S130 from the
National Heart, Lung, and Blood Institute and by Pfizer Inc. The authors
of this paper disclose their affiliations below, and these relate to
personal or institutional-affiliated receipt of income in the areas of
research grants, consultant fees, or other compensation: KLM, King; BRD,
BioMarin, GlaxoSmithKline, Proctor & Gamble, and Takeda Pharmaceuticals;
MC, GlaxoSmithKline and Sanofi Aventis; SS, Kos Pharmaceuticals; and MW,
Novartis, Bristol-Myers Squibb, Pfizer, Merck, Sanofi Aventis,
DaiichiSankyo, Boehringer Ingelheim, ClaxoSmithKline, Forest
Laboratories, Gilead, and Takeda Pharmaceuticals. AB was associate
professor of medicine at Robert Wood Johnson School of Medicine's
Camden, NJ, campus at Cooper University Hospital, and GMG was account
manager at Migliara-Kaplan, Princeton, NJ, at the time of the study. The
other authors report no competing interests.
NR 28
TC 6
Z9 6
U1 2
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1524-6175
J9 J CLIN HYPERTENS
JI J. Clin. Hypertens.
PD NOV
PY 2008
VL 10
IS 11
BP 822
EP 829
DI 10.1111/j.1751-7176.2008.00035.x
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 377AJ
UT WOS:000261223800003
PM 19128270
ER
PT J
AU Milner, J
Paul, WE
AF Milner, Joshua
Paul, William E.
TI Limited T-Cell Receptor Diversity Predisposes to Th2 Immunopathology:
Involvement of Tregs and Conventional CD4 T Cells
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE TCR; receptor repertoire; eosinophil; immunopathology; TH2
ID MUTAGENESIS
AB Introduction A variety of immunodeficiencies characterized by limitations in the T-cell repertoire are also associated with Th2-like immunopathology.
Methods We established a model of this phenomenon by transferring limited numbers of mature CD4+ T-cells into lymphopenic mice.
Result This transfer resulted in eosinophilic pneumonia with alternatively activated macrophages, eosinophilic gastritis. and other organ infiltration, associated with elevated IgE levels and Th2 cytokine production by the transferred cells. Transfer of large numbers of T-cells did not result in any pathology. The disease Could be suppressed by CD25+ Foxp3+ regulatory T cells, but only when the T-cell receptor repertoire of the Tregs was diverse.
Conclusion Collectively, the data suggest that limited T-cell receptor repertoires derived from normal CD4+ T cells can cause severe Th2 immunopathology, and that failure of control by Tregs due to limitation of their repertoire is partially responsible for this phenotype.
C1 [Milner, Joshua; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike,NIH Bldg 10-11N311, Bethesda, MD 20892 USA.
EM wpaul@niaid.nih.gov
FU NIH [1 Z01 AI00926-06-LI]; NIAID
FX This research was Supported by Project 1 Z01 AI00926-06-LI of the
Intramural Research Program of the NIH, NIAID.
NR 10
TC 3
Z9 3
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD NOV
PY 2008
VL 28
IS 6
BP 631
EP 634
DI 10.1007/s10875-008-9245-9
PG 4
WC Immunology
SC Immunology
GA 399XW
UT WOS:000262833600004
PM 18792766
ER
PT J
AU Shevach, EM
Davidson, TS
Huter, EN
DiPaolo, RA
Andersson, J
AF Shevach, Ethan M.
Davidson, Todd S.
Huter, Eva N.
DiPaolo, Richard A.
Andersson, John
TI Role of TGF-beta in the Induction of Foxp3 Expression and T Regulatory
Cell Function
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE TGF-beta; gastritis; infectious tolerance; immune suppression;
latency-associated peptide
ID GROWTH-FACTOR-BETA; SUPPRESSOR FUNCTION; TGF-BETA-1; RECEPTOR; MICE;
AUTOIMMUNITY; INFLAMMATION
AB Introduction A number of studies have suggested that transforming growth factor beta (TGF-beta) plays a critical role In immune suppression mediated by Foxp3(+) regulatory T cells. TGF-beta in concert with interleukin 2 is a potent induction factor for the differentiation of Foxp3(+) Treg from naive precursors. Polyclonal TGF-beta-induced Treg (iTreg) are capable of preventing the autoimmune syndrome that develops in scurfy mice that lack Foxp3(+) Treg. Antigen-specific iTreg can be used to both prevent and treat autoimmune gastritis that is induced by transfer of naive or primed autoantigen-specific T cells. TGF-beta complexed with latency-associated peptide is expressed on the surface of activated thymus-derived Treg. Coculture of activated Treg with naive responder T cells results in the de novo generation of fully functional Foxp3(+) T cells in a contact-dependent and TGF-beta-dependent manner.
Conclusions and Speculations Generation of functional Foxp3(+) T cells via this pathway may represent a mechanism by which Treg maintain tolerance and expand their repertoire.
C1 [Shevach, Ethan M.; Davidson, Todd S.; Huter, Eva N.; DiPaolo, Richard A.; Andersson, John] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Blg 10,Room 11N315, Bethesda, MD 20892 USA.
EM eshevach@niaid.nih.gov
RI Andersson, John/A-4436-2009;
OI Andersson, John/0000-0003-2799-6349
NR 22
TC 63
Z9 67
U1 1
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD NOV
PY 2008
VL 28
IS 6
BP 640
EP 646
DI 10.1007/s10875-008-9240-1
PG 7
WC Immunology
SC Immunology
GA 399XW
UT WOS:000262833600006
PM 18810612
ER
PT J
AU Wohlfert, E
Belkaid, Y
AF Wohlfert, Elizabeth
Belkaid, Yasmine
TI Role of Endogenous and Induced Regulatory T Cells During Infections
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE Regulatory T cells; peripheral homeostasis; controlled immune response
ID TOLL-LIKE RECEPTORS; TRANSCRIPTION FACTOR FOXP3; DENDRITIC CELLS;
RETINOIC-ACID; IMMUNE-RESPONSES; IFN-GAMMA; LAMINA-PROPRIA; TGF-BETA;
TUBERCULOSIS PATIENTS; INTERFERON-GAMMA
AB Background Various populations of regulatory cells, including Foxp3+ T(Reg), have been shown to play a central role in the maintenance of peripheral homeostasis and establishment of controlled immune responses.
Objective In this review, we discuss current hypotheses and points of polemic associated with the origin, mode of action. and antigen specificity of both endogenous and induced regulatory T cells during infections.
C1 [Wohlfert, Elizabeth; Belkaid, Yasmine] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA.
EM ybelkaid@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health. We would like to thank David B. Chow for the confocal image. We
apologize to those authors whose work we were unable to cite because of
space limitations,
NR 93
TC 32
Z9 32
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD NOV
PY 2008
VL 28
IS 6
BP 707
EP 715
DI 10.1007/s10875-008-9248-6
PG 9
WC Immunology
SC Immunology
GA 399XW
UT WOS:000262833600013
PM 18810611
ER
PT J
AU Kasai, M
Harrington, SM
Francesconi, A
Petraitis, V
Petraitiene, R
Beveridge, MG
Knudsen, T
Milanovich, J
Cotton, MP
Hughes, J
Schaufele, RL
Sein, T
Bacher, J
Murray, PR
Kontoyiannis, DP
Walsh, TJ
AF Kasai, Miki
Harrington, Susan M.
Francesconi, Andrea
Petraitis, Vidmantas
Petraitiene, Ruta
Beveridge, Mara G.
Knudsen, Tena
Milanovich, Jeffery
Cotton, Margaret P.
Hughes, Johanna
Schaufele, Robert L.
Sein, Tin
Bacher, John
Murray, Patrick R.
Kontoyiannis, Dimitrios P.
Walsh, Thomas J.
TI Detection of a Molecular Biomarker for Zygomycetes by Quantitative PCR
Assays of Plasma, Bronchoalveolar Lavage, and Lung Tissue in a Rabbit
Model of Experimental Pulmonary Zygomycosis
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; ORGAN TRANSPLANT RECIPIENTS;
ASPERGILLUS-FUMIGATUS; PANFUNGAL PCR; MAGNA PURE; GENETIC
IDENTIFICATION; FUNGAL-INFECTIONS; FILAMENTOUS FUNGI; CANDIDA-ALBICANS
AB We developed two real-time quantitative PCR (qPCR) assays, targeting the 28S rRNA gene, for the diagnosis of zygomycosis caused by the most common, clinically significant Zygomycetes. The amplicons of the first qPCR assay (qPCR-1) from Rhizopus, Mucor, and Rhizomucor species were distinguished through melt curve analysis. The second qPCR assay (qPCR-2) detected Cunninghamella species using a different primer/probe set. For both assays, the analytic sensitivity for the detection of hyphal elements from germinating sporangiospores in bronchoalveolar lavage (BAL) fluid and lung tissue homogenates from rabbits was 1 to 10 sporangiospores/ml. Four unique and clinically applicable models of invasive pulmonary zygomycosis served as surrogates of human infections, facilitating the validation of these assays for potential diagnostic utility. For qPCR-1, 5 of 98 infarcted lung specimens were positive by qPCR and negative by quantitative culture (qCx). None were qCx positive only. Among 23 BAL fluid samples, all were positive by qPCR, while 22 were positive by qCx. qPCR-1 detected Rhizopus and Mucor DNA in 20 (39%) of 51 serial plasma samples as early as day 1 postinoculation. Similar properties were observed for qPCR-2, which showed greater sensitivity than qCx for BAL fluid (100% versus 67%; P = 0.04; n = 15). The assay detected Cunninghamella DNA in 18 (58%) of 31 serial plasma samples as early as day 1 postinoculation. These qPCR assays are sensitive and specific for the detection of Rhizopus, Mucor, Rhizomucor, and Cunninghamella species and can be used for the study and detection of infections caused by these life-threatening pathogens.
C1 [Kasai, Miki; Francesconi, Andrea; Petraitis, Vidmantas; Petraitiene, Ruta; Beveridge, Mara G.; Knudsen, Tena; Milanovich, Jeffery; Cotton, Margaret P.; Hughes, Johanna; Schaufele, Robert L.; Sein, Tin; Walsh, Thomas J.] NCI, NIH, Bethesda, MD 20892 USA.
[Harrington, Susan M.; Murray, Patrick R.] NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA.
[Petraitis, Vidmantas; Petraitiene, Ruta] SAIC Frederick Inc, LASP, Frederick, MD USA.
[Bacher, John] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD USA.
[Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Walsh, TJ (reprint author), Natl Canc Inst, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10-CRC,Room 1-5740, Bethesda, MD 20892 USA.
EM walsht@mail.nih.gov
NR 52
TC 51
Z9 54
U1 0
U2 1
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 NOV
PY 2008
VL 46
IS 11
BP 3690
EP 3702
DI 10.1128/JCM.00917-08
PG 13
WC Microbiology
SC Microbiology
GA 367DH
UT WOS:000260532200022
PM 18845827
ER
PT J
AU Herzlich, AA
Yeh, S
Shen, D
Ding, X
Uzel, G
Holland, SM
Chan, C
AF Herzlich, A. A.
Yeh, S.
Shen, D.
Ding, X.
Uzel, G.
Holland, S. M.
Chan, C.
TI Identification of Pseudomonas aeruginosa DNA in a chorioretinal lesion
associated with chronic granulomatous disease
SO JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Letter
C1 [Herzlich, A. A.; Yeh, S.; Shen, D.; Ding, X.; Chan, C.] NIAID, Immunol Lab, NEI, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Uzel, G.; Holland, S. M.] NIAID, Lab Clin Infect Dis, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Chan, C (reprint author), NEI, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
FU Intramural NIH HHS
NR 5
TC 4
Z9 4
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0021-9746
J9 J CLIN PATHOL
JI J. Clin. Pathol.
PD NOV
PY 2008
VL 61
IS 11
BP 1229
EP 1230
DI 10.1136/jcp.2008.059147
PG 4
WC Pathology
SC Pathology
GA 365RI
UT WOS:000260425100014
PM 18755713
ER
PT J
AU Bissmarck, F
Nakahara, H
Doya, K
Hikosaka, O
AF Bissmarck, Fredrik
Nakahara, Hiroyuki
Doya, Kenji
Hikosaka, Okihide
TI Combining Modalities with Different Latencies for Optimal Motor Control
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID OPTIMAL FEEDBACK-CONTROL; BASAL GANGLIA; VISUAL FEEDBACK; SENSORIMOTOR
CONTROL; FUNCTIONAL-ANATOMY; PRISM ADAPTATION; POPULATION CODES; MANUAL
TRACKING; TASK; ARCHITECTURE
AB Feedback signals may be of different modality, latency, and accuracy. To learn and control motor tasks, the feedback available may be redundant, and it would not be necessary to rely on every accessible feedback loop. Which feedback loops should then be utilized? In this article, we propose that the latency is a critical factor to determine which signals will be influential at different learning stages. We use a computational framework to study the role of feedback modules with different latencies in optimal motor control. Instead of explicit gating between modules, the reinforcement learning algorithm learns to rely on the more useful module. We tested our paradigm for two different implementations, which confirmed our hypothesis. In the first, we examined how feedback latency affects the competitiveness of two identical modules. In the second, we examined an example of visuomotor sequence learning, where a plastic, faster somatosensory module interacts with a preacquired, slower visual module. We found that the overall performance depended on the latency of the faster module alone, whereas the relative latency determines the independence of the faster from the slower. In the second implementation, the somatosensory module with shorter latency overtook the slower visual module, and realized better overall performance. The visual module played different roles in early and late learning. First, it worked as a guide for the exploration of the somatosensory module. Then, when learning had converged, it contributed to robustness against system noise and external perturbations. Overall, these results demonstrate that our framework successfully learns to utilize the most useful available feedback for optimal control.
C1 [Bissmarck, Fredrik; Doya, Kenji] ATR Int, Kyoto, Japan.
[Bissmarck, Fredrik] NICT, Kyoto, Japan.
[Nakahara, Hiroyuki] RIKEN, Brain Sci Inst, Saitama, Japan.
[Doya, Kenji] Okinawa Inst Sci & Technol, Okinawa, Japan.
[Hikosaka, Okihide] NIH, Bethesda, MD 20892 USA.
[Bissmarck, Fredrik] NAIST, Nara, Japan.
RP Bissmarck, F (reprint author), ATR, Computat Neurosci Labs, 2-2-2 Hikaridai Keihanna Sci City, Kyoto 6190288, Japan.
EM fredrik.bissmarck@gmail.com
RI Doya, Kenji/B-5841-2015; Nakahara, Hiroyuki/N-5411-2015
OI Doya, Kenji/0000-0002-2446-6820; Nakahara, Hiroyuki/0000-0001-6891-1175
FU Core Research for Evolutional Science and Technology (CREST); Japan
Science and Technology Agency
FX F. B. thanks Mitsuo Kawato, Erhan Oztop, and Jun Morimoto for comments
on an earlier draft. This research was funded by Core Research for
Evolutional Science and Technology (CREST), Japan Science and Technology
Agency.
NR 37
TC 4
Z9 4
U1 0
U2 2
PU M I T PRESS
PI CAMBRIDGE
PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA
SN 0898-929X
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD NOV
PY 2008
VL 20
IS 11
BP 1966
EP 1979
DI 10.1162/jocn.2008.20133
PG 14
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 360GM
UT WOS:000260046000004
PM 18416676
ER
PT J
AU Dolle, RE
Le Bourdonnec, B
Goodman, AJ
Morales, GA
Thomas, CJ
Zhang, W
AF Dolle, Roland E.
Le Bourdonnec, Bertrand
Goodman, Allan J.
Morales, Guillermo A.
Thomas, Craig J.
Zhang, Wei
TI Comprehensive Survey of Chemical Libraries for Drug Discovery and
Chemical Biology: 2007
SO JOURNAL OF COMBINATORIAL CHEMISTRY
LA English
DT Review
ID SOLID-PHASE SYNTHESIS; ONE-POT SYNTHESIS; DIVERSITY-ORIENTED SYNTHESIS;
ONE-STEP SYNTHESIS; APOPTOSIS-INDUCING PROPERTIES; MICROWAVE-ASSISTED
SYNTHESIS; CALCIUM-CHANNEL BLOCKERS; FLUOROUS BIPHASE SYSTEM;
SOLVENT-FREE CONDITIONS; PROMOTED 3-COMPONENT SYNTHESIS
C1 [Dolle, Roland E.; Le Bourdonnec, Bertrand; Goodman, Allan J.] Adolor Corp, Exton, PA 19341 USA.
[Morales, Guillermo A.] Semafore Pharmaceut Inc, Indianapolis, IN 46268 USA.
[Thomas, Craig J.] NHGRI, NIH, Chem Genom Ctr, Rockville, MD 20850 USA.
[Zhang, Wei] Univ Massachusetts, Dept Chem, Boston, MA 02125 USA.
RP Dolle, RE (reprint author), Adolor Corp, 700 Penn Dr, Exton, PA 19341 USA.
EM rdolle@adolor.com
NR 530
TC 74
Z9 74
U1 0
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-4766
J9 J COMB CHEM
JI J. Comb. Chem.
PD NOV-DEC
PY 2008
VL 10
IS 6
BP 753
EP 802
DI 10.1021/cc800119z
PG 50
WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary
SC Chemistry; Pharmacology & Pharmacy
GA 371SK
UT WOS:000260851400001
PM 18991466
ER
PT J
AU Cho, CH
Neuenswander, B
Lushington, GH
Larock, RC
AF Cho, Chul-Hee
Neuenswander, Benjamin
Lushington, Gerald H.
Larock, Richard C.
TI Parallel Synthesis of a Multi-Substituted Benzo[b]furan Library
SO JOURNAL OF COMBINATORIAL CHEMISTRY
LA English
DT Article
ID PALLADIUM-CATALYZED CYCLIZATION; HETEROAROMATIC RING-SYSTEMS;
CROSS-COUPLING REACTIONS; O-ALKYNYLPHENOLS; ELECTROPHILIC CYCLIZATION;
CARBONYLATIVE ANNULATION; DEVELOPMENT SETTINGS; ESTIMATE SOLUBILITY;
SELECTIVE LIGANDS; DRUG DISCOVERY
AB The solution-phase parallel synthesis of a 121-member library of multi-substituted benzo[b]furans is described. 2.3,5-Trisubstituted benzo[b]furans have been prepared by the palladium-catalyzed substitution of 3-iodobenzofurans by Suzuki-Miyaura, carbonylative Suzuki, Sonogashira, Heck, and carboalkoxylation chemistry. The 3-iodobenzofurans are readily prepared in good to excellent yields by the palladium/copper-catalyzed cross-coupling of various o-iodoanisoles and terminal alkynes, followed by electrophilic cyclization with ICI.
C1 [Cho, Chul-Hee; Larock, Richard C.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
[Neuenswander, Benjamin; Lushington, Gerald H.] Univ Kansas, NIH, Ctr Excellence Chem Methodol, Lawrence, KS 66047 USA.
[Neuenswander, Benjamin; Lushington, Gerald H.] Univ Kansas, NIH, Lib Dev, Lawrence, KS 66047 USA.
RP Larock, RC (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
EM larock@iastate.edu
FU National Institute of General Medical Sciences [GM070620, GM079593];
National Institutes of Health Kansas University Chemical Methodologies
and Library Development Center of Excellence [GM069663]; Johnson
Matthey, Inc; Kawaken Fine Chemicals Co., Ltd
FX We thank the National Institute of General Medical Sciences (GM070620
and GM079593) and the National Institutes of Health Kansas University
Chemical Methodologies and Library Development Center of Excellence
(GM069663) for support of this research, Johnson Matthey, Inc., and
Kawaken Fine Chemicals Co., Ltd., for donations of palladium catalysts,
and Frontier Scientific and Synthonix for donations of boronic acids.
NR 55
TC 53
Z9 54
U1 1
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-4766
J9 J COMB CHEM
JI J. Comb. Chem.
PD NOV-DEC
PY 2008
VL 10
IS 6
BP 941
EP 947
DI 10.1021/cc800120y
PG 7
WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary
SC Chemistry; Pharmacology & Pharmacy
GA 371SK
UT WOS:000260851400021
PM 18937516
ER
PT J
AU McCrae, RR
Terracciano, A
Realo, A
Allik, J
AF McCrae, Robert R.
Terracciano, Antonio
Realo, Anu
Allik, Jueri
TI Interpreting GLOBE Societal Practices Scales
SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY
LA English
DT Article
DE personality traits; national character; cultural identity; stereotypes;
GLOBE scales
ID NATIONAL CHARACTER; CULTURES; VALUES; MODEL
AB Some of the Global Leadership and Organizational Behavior Effectiveness (GLOBE) Societal Practices scales ask for descriptions of typical personality traits that might be interpreted as judgments of national character. Ratings of national character reflect cultural identities and social dynamics, but previous research suggests that they are unrelated to the mean personality traits of the culture's members. Analyses at the culture level comparing GLOBE scales with aggregate assessed personality traits (n = 34) and with measures of perceived national character (n = 33) showed that these GLOBE scales are better construed as unfounded stereotypes than as actual depictions of the society members' personality traits.
C1 [McCrae, Robert R.] NIA, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Terracciano, Antonio] NIA, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Allik, Jueri] Univ Tartu, Fac Social Sci, Tartu, Estonia.
RP McCrae, RR (reprint author), NIA, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100,Room 04B329, Baltimore, MD 21224 USA.
EM mccraej@grc.nia.nih.gov
RI terracciano, antonio/B-1884-2008; Allik, Juri/D-5609-2009; Realo,
Anu/M-9524-2016
OI Allik, Juri/0000-0002-8358-4747;
NR 19
TC 17
Z9 17
U1 0
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0221
J9 J CROSS CULT PSYCHOL
JI J. Cross-Cult. Psychol.
PD NOV
PY 2008
VL 39
IS 6
BP 805
EP 810
DI 10.1177/0022022108323806
PG 6
WC Psychology, Social
SC Psychology
GA 358ZM
UT WOS:000259956000010
ER
PT J
AU Masse, M
Falanga, V
Zhou, LH
AF Masse, Maureen
Falanga, Vincent
Zhou, Linda Hua
TI Use of topical povidone-iodine resulting in an iododerma-like eruption
SO JOURNAL OF DERMATOLOGY
LA English
DT Article
DE iododerma; povidone-iodine; leg pustules; leg abscesses; iodine
ID VEGETATING IODODERMA
AB Iododerma is a rare skin eruption that is usually induced by the systemic use of iodide-containing radiographic contrast medium or treatment with oral potassium iodide therapy. Iododerma has also rarely been reported to occur following topical application of iodine. We herein report the case of a 42-year-old male who developed multiple pinpoint pustules on both lower extremities. Three days after the eruption began, the patient started applying topical 10% povidone-iodine solution to the lesions. During this treatment, the lesions enlarged into multiple 2-9-cm pus-filled bullae, limited to the treated areas. Lesional bacterial culture swab and Gram stain were negative. Blood cultures were also negative and the patient's white blood cell count was normal. A punch biopsy specimen revealed pseudoepitheliomatous hyperplasia and dermal-epidermal separation with epidermal necrosis and underlying abscess formation. A superficial and deep perivascular, interstitial and perifollicular infiltrate containing numerous neutrophils, with abscess formation and eosinophils was also seen. This histology was consistent with iododerma and the patient's lesions involuted following cessation of topical iodine use, leaving only post-inflammatory hyperpigmentation. In summary, our patient likely had a folliculitis that was then treated with topical povidone-iodine that led to iododerma. Although it remains possible that the reaction was an unusual contact hypersensitivity response, the ulceration, pseudoepitheliomatous hyperplasia and abscess formation do support an iododerma-like eruption.
C1 [Zhou, Linda Hua] Roger Williams Med Ctr, Dept Dermatol & Skin Surg, Providence, RI 02908 USA.
Roger Williams Med Ctr, NIH, Ctr Biomed Res Excellence, Providence, RI 02908 USA.
RP Zhou, LH (reprint author), Roger Williams Med Ctr, Dept Dermatol & Skin Surg, Elmhurst Bldg,50 Maude St, Providence, RI 02908 USA.
EM lindahuazhou@yahoo.com
FU NIH [P20RR018757]
FX This work was supported in part by NIH grant P20RR018757 (Center of
Biomedical Research Excellence).
NR 13
TC 10
Z9 10
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0385-2407
J9 J DERMATOL
JI J. Dermatol.
PD NOV
PY 2008
VL 35
IS 11
BP 744
EP 747
DI 10.1111/j.1346-8138.2008.00554.x
PG 4
WC Dermatology
SC Dermatology
GA 377LB
UT WOS:000261251600009
PM 19120771
ER
PT J
AU Mohania, D
Nagpal, R
Kumar, M
Bhardwaj, A
Yadav, M
Jain, S
Marotta, F
Singh, V
Parkash, O
Yadav, H
AF Mohania, Dheeraj
Nagpal, Ravinder
Kumar, Manoj
Bhardwaj, Aarti
Yadav, Mukesh
Jain, Shalini
Marotta, Francesco
Singh, Vinod
Parkash, Om
Yadav, Hariom
TI Molecular approaches for identification and characterization of lactic
acid bacteria
SO JOURNAL OF DIGESTIVE DISEASES
LA English
DT Review
DE lactic acid bacteria; lactobacilli; molecular identification; polymerase
chain reaction; probiotics
ID GRADIENT GEL-ELECTROPHORESIS; AMPLIFIED POLYMORPHIC DNA; 16S
RIBOSOMAL-RNA; POTENTIALLY PROBIOTIC LACTOBACILLUS; POLYMERASE
CHAIN-REACTION; INTERGENIC SPACER REGION; HUMAN COLONIC BIOTA; REAL-TIME
PCR; GENETIC DIVERSITY; CASEI STRAINS
AB The last few years have produced a revolution in the development of very sensitive, rapid, automated, molecular detection methods for a variety of various species of lactic acid bacteria (LAB) associated with food and dairy products. Nowadays many such strains of LAB are considered probiotics. The genome-based methods are useful in identifying bacteria as a complementary or alternative tool to phenotypical methods. Over the years, identification methodologies using primers that target different sequences, such as the 16S ribosomal RNA (rRNA)-encoding gene, the 16S-23S rRNA intergenic spacer region, the 23S rRNA-encoding, recA and ldhD genes; randomly amplified polymorphic DNA, restriction fragment length polymorphism, denaturing gradient gel electrophoresis, temperature gradient gel electrophoresis, amplification rDNA restriction analysis, restriction enzyme analysis, rRNA, pulse field gel electrophoresis and amplification fragment length polymorphism have played a significant role in probiotic bacteriology. Hence, the aim of this review is to provide an overview of some rapid and reliable polymerase chain reaction-based molecular methods used for identifying and differentiating closely related species and strains of LAB associated with food and industry.
C1 [Yadav, Hariom] NIDDK, NIH, Bethesda, MD 20892 USA.
[Nagpal, Ravinder; Kumar, Manoj] Natl Dairy Res Inst, Dairy Microbiol Div, Karnal 132001, Haryana, India.
[Bhardwaj, Aarti] Meerut Inst Engn & Technol, Meerut, Uttar Pradesh, India.
[Yadav, Mukesh] Jiwaji Univ, Sch Studies Chem, Gwalior 474011, Madhya Pradesh, India.
[Jain, Shalini] Univ Illinois, Urbana, IL 61801 USA.
[Marotta, Francesco] GAIA Fdn, Nutraceut Nutragenom Unit, Milan, Italy.
[Singh, Vinod] Barkatullah Univ, Dept Microbiol, Bhopal 462026, Madhya Pradesh, India.
[Parkash, Om] Natl JALMA Inst Leprosy & Other Mycobacterial Dis, Agra, Uttar Pradesh, India.
RP Yadav, H (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM yadavh@mail.nih.gov
OI Yadav, Hariom/0000-0003-4504-1597
NR 78
TC 44
Z9 45
U1 2
U2 24
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1751-2972
J9 J DIGEST DIS
JI J. Dig. Dis.
PD NOV
PY 2008
VL 9
IS 4
BP 190
EP 198
DI 10.1111/j.1751-2980.2008.00345.x
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 364PZ
UT WOS:000260348900002
PM 18959589
ER
PT J
AU Szaszak, M
Chen, HD
Chen, HC
Baukal, A
Hunyady, L
Catt, KJ
AF Szaszak, Marta
Chen, Hung-Dar
Chen, Hao-Chia
Baukal, Albert
Hunyady, Laszlo
Catt, Kevin J.
TI Identification of the invariant chain (CD74) as an angiotensin
AGTR1-interacting protein
SO JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID ANTIGEN-PROCESSING COMPARTMENTS; II TYPE-1 RECEPTOR;
ENDOPLASMIC-RETICULUM; AT(1) RECEPTOR; CELL-SURFACE; COUPLED RECEPTORS;
CYTOPLASMIC TAIL; PLASMA-MEMBRANE; SORTING MOTIFS; KINASE-C
AB Little is known about the protein-protein interactions that regulate the trafficking of the angiotensin II type I receptor (AGTR1) through the biosynthetic pathway. The membrane-proximal region of the cytoplasmic tail of the AGTR1 has been identified by site-directed mutagenesis studies as an essential site for normal AGTR1 folding and surface expression. Based oil yeast two-hybrid screening of a human kidney cDNA library with the AGTR1 carboxyl-terminal tail as a bait, we identified the invariant chain (CD74) as a novel interacting protein. This association was confirmed by co-immunoprecipitation and co-localization Studies. The binding site for CD74 on the AGTR1 carboxyl-terminal tail was localized to a site previously identified as important For the exit of the AGTR1 front the endoplasmic reticulum (ER), and conserved in many G protein-coupled receptors. Transient co-expression of CD74 with the AGTR1 in CHO-K1 cells consistently reduced the AGTR1 density at the cell surface. Furthermore, the interaction of CD74 with the carboxyl-terminal tail of the AGTR1 caused its retention in the ER and promoted its proteasomal degradation. These observations indicate that CD74 and the AGTK1 become associated in the early biosynthetic pathway, and that CD74 is a negative regulator of AGTR1 expression.
C1 [Szaszak, Marta; Chen, Hung-Dar; Chen, Hao-Chia; Baukal, Albert; Catt, Kevin J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Dev Endocirnol & Genet, Sect Hormonal Regulat Endocrinol & Reprod Res Bra, Bethesda, MD 20892 USA.
[Hunyady, Laszlo] Semmelweis Univ, Dept Physiol, H-1444 Budapest, Hungary.
RP Catt, KJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Dev Endocirnol & Genet, Sect Hormonal Regulat Endocrinol & Reprod Res Bra, Bethesda, MD 20892 USA.
EM cattk@mail.nih.gov
RI Szaszak, Marta/G-7957-2011
FU Intramural NIH HHS
NR 51
TC 10
Z9 11
U1 0
U2 0
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 NOV
PY 2008
VL 199
IS 2
BP 165
EP 176
DI 10.1677/JOE-08-0190
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 370NJ
UT WOS:000260768600003
PM 18719072
ER
PT J
AU Chigurupati, S
Son, TG
Hyun, DH
Lathia, JD
Mughal, MR
Savell, J
Li, SC
Nagaraju, GPC
Chan, SL
Arumugam, TV
Mattson, MP
AF Chigurupati, Srinivasulu
Son, Tae Gen
Hyun, Dong-Hoon
Lathia, Justin D.
Mughal, Mohamed R.
Savell, Jason
Li, Shuan C.
Nagaraju, G. P. C.
Chan, Sic L.
Arumugam, Thiruma V.
Mattson, Mark P.
TI Lifelong running reduces oxidative stress and degenerative changes in
the testes of mice
SO JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID PHYSICAL-ACTIVITY; SERTOLI-CELLS; TESTOSTERONE LEVELS;
LIPID-PEROXIDATION; FUNCTIONAL-CHANGES; LEYDIG-CELLS; AGING MALE;
EXERCISE; MEN; CARDIOPROTECTION
AB Regular exercise can counteract the adverse effects of aging oil the musculoskeletal and cardiovascular systems. In males, the normal aging process is associated with reductions in testosterone production and impaired spermatogenesis, but the underlying mechanisms and their potential modification by exercise are unknown. Here, we report that lifelong regular exercise (running) protects the testes against the adverse effects of advancing age, and that this effect of running is associated with decreased amounts of oxidative damage to proteins, lipids, and DNA in spermatogenic and Leydig cells. Six-month-old male mice were divided into a sedentary group and a group that ran an average of 1.75 km/day, until the mice reached the age of 20 months. Seminiferous tubules of runners exhibited a full complement of cells at different stages of the spermatogenic process and a clear central lumen with large numbers of spermatozoa, in contrast to sedentary truce that exhibited disorganized spermatogenic cells and lacked spermatocytes in a central lumen. Levels of protein carbonyls, nitrotyrosine, lipid peroxidation products, and oxidatively modified DNA were significantly greater in spermatogenic and Leydig cells of sedentary mice compared with runners. These findings, suggest that lifelong regular exercise suppresses aging of testes by a mechanism that involves reduced oxidative damage to spermatogenic and Leydig cells.
C1 [Mattson, Mark P.] NIA, Biomed Res Ctr, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Savell, Jason; Li, Shuan C.] Orlando Reg Hlth Care, Dept Pathol, Orlando, FL 32806 USA.
[Chigurupati, Srinivasulu; Nagaraju, G. P. C.; Chan, Sic L.] Univ Cent Florida, Biomol Sci Ctr, Orlando, FL 32816 USA.
[Arumugam, Thiruma V.] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX 79106 USA.
[Hyun, Dong-Hoon] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul 120750, South Korea.
RP Mattson, MP (reprint author), NIA, Biomed Res Ctr, Neurosci Lab, Intramural Res Program, 5th Floor,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson,
Mark/F-6038-2012; Ganji, Purna chandra N/D-4193-2011
OI Ganji, Purna chandra N/0000-0002-4989-5234
FU Intramural Research Program of the National Institute on Aging
FX This work was supported by the Intramural Research Program of the
National Institute on Aging.
NR 48
TC 27
Z9 30
U1 0
U2 1
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND
SN 0022-0795
J9 J ENDOCRINOL
JI J. Endocrinol.
PD NOV
PY 2008
VL 199
IS 2
BP 333
EP 341
DI 10.1677/JOE-08-0306
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 370NJ
UT WOS:000260768600018
PM 18701639
ER
PT J
AU Rodes, CE
Pellizzari, ED
Dellarco, MJ
Erickson, MD
Vallero, DA
Reissman, DB
Lioy, PJ
Lippmann, M
Burke, TA
Goldstein, BD
AF Rodes, Charles E.
Pellizzari, Edo D.
Dellarco, Michael J.
Erickson, Mitchell D.
Vallero, Daniel A.
Reissman, Dori B.
Lioy, Paul J.
Lippmann, Morton
Burke, Thomas A.
Goldstein, Bernard D.
TI ISEA2007 panel: Integration of better exposure characterizations into
disaster preparedness for responders and the public
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Review
DE disaster; exposure assessment; personal exposure; risk
AB An expert panel was convened in October 2007 at the International Society for Exposure Analysis Annual Meeting in Durham, NC, entitled "The Path Forward in Disaster Preparedness Since WTC-Exposure Characterization and Mitigation: Substantial Unfinished Business!" The panel prospectively discussed the critical exposure issues being overlooked during disaster responses and highlighted the needs for an optimal blending of exposure characterizations and hazard controls within disaster settings. The cases were made that effective and timely exposure characterizations must be applied during responses to any disaster, whether terrorist, manmade, or natural in origin. The consistent application of exposure sciences across acute and chronic disaster timelines will assure that the most effective strategies are applied to collect the needed information to guide risk characterization and management approaches. Exposure sciences must be effectively applied across all phases of a disaster (defined as rescue, reentry, recovery, and rehabitation-the four Rs) to appropriately characterize risks and guide risk-mitigation approaches. Failure to adequately characterize and control hazardous exposures increases the likelihood of excess morbidity and mortality. Advancing the infrastructure and the technologies to collect the right exposure information before, during, and immediately after disasters would advance our ability to de. ne risks and protect responders and the public better. The panel provided conclusions, recommendations, and next steps toward effective and timely integration of better exposure science into disaster preparedness, including the need for a subsequent workshop to facilitate this integration. All panel presentations and a summary were uploaded to the ISES1 website (http://www.iseaweb.org/Disaster_Preparedness/index.php).
C1 [Rodes, Charles E.] RTI Int, CAT ATEEP, Res Triangle Pk, NC 27709 USA.
[Dellarco, Michael J.] NICHHD, Bethesda, MD 20892 USA.
[Erickson, Mitchell D.] Sci & Technol Directorate, Dept Homeland Secur, Washington, DC USA.
[Vallero, Daniel A.] US EPA, Natl Exposure Res Lab, Res Triangle Pk, NC 27711 USA.
[Reissman, Dori B.] NIOSH, CDC, Washington, DC USA.
[Lioy, Paul J.] RWJMS, Environm & Occupat Hlth Sci Inst, Piscataway, NJ USA.
[Lioy, Paul J.] Rutgers Univ UMDNJ, Piscataway, NJ USA.
[Lippmann, Morton] NYU Med Ctr, Tuxedo Pk, NY USA.
[Burke, Thomas A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Goldstein, Bernard D.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
RP Rodes, CE (reprint author), RTI Int, CAT ATEEP, 3040 Cornwallis Rd,Bldg 11 Room 409, Res Triangle Pk, NC 27709 USA.
EM charlesr@rti.org
RI Lioy, Paul/F-6148-2011
FU NIEHS NIH HHS [P30 ES005022]
NR 13
TC 5
Z9 5
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1559-0631
J9 J EXPO SCI ENV EPID
JI J. Expo. Sci. Environ. Epidemiol.
PD NOV
PY 2008
VL 18
IS 6
BP 541
EP 550
DI 10.1038/jes.2008.42
PG 10
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 364CJ
UT WOS:000260313500006
PM 18685563
ER
PT J
AU Meissner, HI
Tiro, JA
Haggstrom, D
Lu-Yao, G
Breen, N
AF Meissner, Helen I.
Tiro, Jasmin A.
Haggstrom, David
Lu-Yao, Grace
Breen, Nancy
TI Does Patient Health and Hysterectomy Status Influence Cervical Cancer
Screening in Older Women?
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE cervical screening; hysterectomy; older age; health status; comorbidity
ID CHARLSON COMORBIDITY INDEX; REGIONAL-VARIATIONS; INTERVIEW SURVEYS;
BEHAVIORAL-MODEL; UNITED-STATES; US WOMEN; CARE; MAMMOGRAPHY;
VALIDATION; BREAST
AB BACKGROUND: Decisions to screen older patients for cancer are complicated by the fact that aging populations are heterogeneous with respect to life expectancy.
OBJECTIVE: To examine national trends in the association between cervical cancer screening and age, health and hysterectomy status.
DESIGN AND PARTICIPANTS: Cross-sectional data from the 1993, 1998, 2000, and 2005 National Health Interview Surveys (NHIS) were used to examine trends in screening for women age 35-64 and 65+ years of age. We investigated whether health is associated with Pap testing among older women using the 2005 NHIS (N=3,073). We excluded women with a history of cervical cancer or who had their last Pap because of a problem.
MEASUREMENTS: The dependent variable was having a Pap test within the past 3 years. Independent variables included three measures of respondent health (the Charlson comorbidity index (CCI), general health status and having a chronic disability), hysterectomy status and sociodemographic factors.
MAIN RESULTS: NHIS data showed a consistent pattern of lower Pap use among older women (65+) compared to younger women regardless of hysterectomy status. Screening also was lower among older women who reported being in fair/poor health, having a chronic disability, or a higher CCI score (4+). Multivariate models showed that over 50% of older women reporting poor health status or a chronic disability and 47% with a hysterectomy still had a recent Pap.
CONCLUSIONS: Though age, health and hysterectomy status appear to influence Pap test use, current national data suggest that there still may be overutilization and inappropriate screening of older women.
C1 [Meissner, Helen I.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Tiro, Jasmin A.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
[Haggstrom, David] Indiana Univ, Regenstrief Inst Inc, Ctr Hlth Serv & Outcomes Res,Roudenbush Vet Affai, VA Hlth Serv Res & Dev Ctr Excellence Implementin, Indianapolis, IN 46204 USA.
[Haggstrom, David] Indiana Univ, Sch Med, Dept Med, Div Gen Internal Med & Geriatr, Indianapolis, IN USA.
[Lu-Yao, Grace] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Canc Inst New Jersey, New Brunswick, NJ 08903 USA.
[Breen, Nancy] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Meissner, HI (reprint author), NIH, Off Behav & Social Sci Res, 31 Ctr Dr,Bldg 31 Room B1C19, Bethesda, MD 20892 USA.
EM meissneh@od.nih.gov
OI Tiro, Jasmin/0000-0001-8300-0441
NR 48
TC 12
Z9 12
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2008
VL 23
IS 11
BP 1822
EP 1828
DI 10.1007/s11606-008-0775-x
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 379VI
UT WOS:000261423900015
PM 18784967
ER
PT J
AU Yan, ZH
Li, S
Liang, ZD
Tomic, M
Stojilkovic, SS
AF Yan, Zonghe
Li, Shuo
Liang, Zhaodong
Tomic, Melanija
Stojilkovic, Stanko S.
TI The P2X(7) Receptor Channel Pore Dilates under Physiological Ion
Conditions
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID FUNCTIONAL EVIDENCE; AGONIST BINDING; XENOPUS OOCYTES; CELLS;
PURINOCEPTOR; PERMEABILITY; PANNEXIN-1; EXPRESSION; DYNAMICS; CURRENTS
AB Activation of the purinergic P2X(7) receptor leads to the rapid opening of an integral ion channel that is permeable to small cations. This is followed by a gradual increase in permeability to fluorescent dyes by integrating the actions of the pannexin-1 channel. Here, we show that during the prolonged agonist application a rapid current that peaked within 200 ms was accompanied with a slower current that required tens of seconds to reach its peak. The secondary rise in current was observed under different ionic conditions and temporally coincided with the development of conductivity to larger organic cations. The biphasic response was also observed in cells with blocked pannexin channels and in cells not expressing these channels endogenously. The biphasic current was preserved in N-terminal T15A, T15S, and T15V mutants that have low or no permeability to organic cations, reflecting enhanced permeability to inorganic cations. In contrast, the T15E, T15K, and T15W mutants, and the Delta 18 mutant with deleted P2X(7) receptor-specific 18-amino acid C-terminal segment, were instantaneously permeable to organic cations and generated high amplitude monophasic currents. These results indicate that the P2X(7) receptor channel dilates under physiological ion conditions, leading to generation of biphasic current, and that this process is controlled by residues near the intracellular side of the channel pore.
C1 [Yan, Zonghe; Li, Shuo; Liang, Zhaodong; Tomic, Melanija; Stojilkovic, Stanko S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Stojilkovic, SS (reprint author), NICHHD, Sect Cellular Signaling, Program Dev Neurosci, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM stankos@helix.nih.gov
RI Tomic, Melanija/C-3371-2016
FU Intramural Research Program of the National National Institutes of
HealthInstitute of Child Health and Human Development,
FX We are thankful to Tomas Obsil for helpful discussion.; This work is
supported by the Intramural Research Program of the National Institute
of Child Health and Human Development, National Institutes of Health.
NR 32
TC 83
Z9 85
U1 0
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD NOV
PY 2008
VL 132
IS 5
BP 563
EP 573
DI 10.1085/jgp.200810059
PG 11
WC Physiology
SC Physiology
GA 454HK
UT WOS:000266672800008
PM 18852304
ER
PT J
AU Bourhy, H
Reynes, JM
Dunham, EJ
Dacheux, L
Larrous, F
Huong, VTO
Xu, GL
Yan, JX
Miranda, MEG
Holmes, EC
AF Bourhy, Herve
Reynes, Jean-Marc
Dunham, Eleca J.
Dacheux, Laurent
Larrous, Florence
Huong, Vu Thi Oue
Xu, Gelin
Yan, Jiaxin
Miranda, Mary Elizabeth G.
Holmes, Edward C.
TI The origin and phylogeography of dog rabies virus
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID MOLECULAR EPIDEMIOLOGY; NUCLEOPROTEIN GENE; EVOLUTIONARY DYNAMICS;
INFECTIOUS-DISEASES; LYSSAVIRUS GENUS; SRI-LANKA; HISTORY; AFRICA; HOST;
EAST
AB Rabies is a progressively fatal and incurable viral encephalitis caused by a lyssavirus infection. Almost all of the 55 000 annual rabies deaths in humans result from infection with dog rabies viruses (RABV). Despite the importance of rabies for human health, little is known about the spread of RABV in dog populations, and patterns of biodiversity have only been studied in limited geographical space. To address these questions on a global scale, we sequenced 62 new isolates and performed an extensive comparative analysis of RABV gene sequence data, representing 192 isolates sampled from 55 countries. From this, we identified six clades of RABV in non-flying mammals, each of which has a distinct geographical distribution, most likely reflecting major physical barriers to gene flow. Indeed, a detailed analysis of phylogeographic structure revealed only limited viral movement among geographical localities. Using Bayesian coalescent methods we also reveal that the sampled lineages of canid RABV derive from a common ancestor that originated within the past 1500 years. Additionally, we found no evidence for either positive selection or widespread population bottlenecks during the global expansion of canid RABV. Overall, our study reveals that the stochastic processes of genetic drift and population subdivision are the most important factors shaping the global phylogeography of canid RABV.
C1 [Bourhy, Herve; Dacheux, Laurent; Larrous, Florence] Inst Pasteur, WHO, Collaborating Ctr Reference & Res Rabies, UPRE Lyssavirus Dynam & Host Adaptat, F-75724 Paris 15, France.
[Reynes, Jean-Marc] Inst Pasteur Cambodia, Phnom Penh, Cambodia.
[Dunham, Eleca J.; Holmes, Edward C.] Penn State Univ, Mueller Lab, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Huong, Vu Thi Oue] Inst Pasteur Ho Chi Minh City, Ho Chi Minh City, Vietnam.
[Miranda, Mary Elizabeth G.] Res Inst Trop Med, Vet Res Dept, Manila, Philippines.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Bourhy, H (reprint author), Inst Pasteur, WHO, Collaborating Ctr Reference & Res Rabies, UPRE Lyssavirus Dynam & Host Adaptat, F-75724 Paris 15, France.
EM hbourhy@pasteur.fr
RI Bourhy, Herve/F-5272-2010; Reynes, Jean-Marc/M-6108-2014;
OI Holmes, Edward/0000-0001-9596-3552
FU 'Programme de Recherches Avancees de Cooperations Franco-Chinoises' [PRA
B01-06]; European Union [FP6/VIZIER]; NIH [GM080533-01]
FX This work was supported by the 'Programme de Recherches Avancees de
Cooperations Franco-Chinoises' (PRA B01-06): 'Epidemiologie moleculaire
de la rage en Chine et standardisation des techniques de detection du
virus rabique', by the European Union through the FP6/VIZIER program,
and by NIH grant GM080533-01. We are also grateful to the genomic
platform of Institut Pasteur, Paris, France and particularly to M.
Tichit and C. Bouchier for their help with sequencing. We also thank
Andres Paez Fernandez for providing RABV isolates from Colombia and Alan
Calaor from the Research Institute for Tropical Medicine, Metro Manila,
Philippines, for his help.
NR 52
TC 96
Z9 106
U1 3
U2 26
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD NOV
PY 2008
VL 89
BP 2673
EP 2681
DI 10.1099/vir.0.2008/003913-0
PN 11
PG 9
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 372ES
UT WOS:000260885500003
PM 18931062
ER
PT J
AU Han, JY
Shaw, BR
Hawkins, RP
Pingree, S
Mctavish, F
Gustafson, DH
AF Han, Jeong Yeob
Shaw, Bret R.
Hawkins, Robert P.
Pingree, Suzanne
Mctavish, Fiona
Gustafson, David H.
TI Expressing Positive Emotions within Online Support Groups by Women with
Breast Cancer
SO JOURNAL OF HEALTH PSYCHOLOGY
LA English
DT Article
DE breast cancer; emotional expression; online support groups; positive
emotions
ID NEGATIVE EMOTIONS
AB Based upon Fredrickson's Broaden-and-Build Theory of Positive Emotions, this study examined the role of expressing positive emotions in online support groups for women with breast cancer. Underserved women with breast cancer in rural Wisconsin and Detroit, Michigan were recruited from 2001 to 2003, and they were given access to online support groups. Both pretest and four-month posttest surveys were conducted with a sample of 231 women. Messages from 96 active participants were analyzed using a computerized text analysis program. Psychological benefits that occurred following the expression of positive emotions were greater among those who expressed more negative emotions.
C1 [Han, Jeong Yeob] Univ Georgia, Grady Coll Journalism & Mass Commun, Dept Telecommun, Athens, GA 30602 USA.
[Shaw, Bret R.; Hawkins, Robert P.; Pingree, Suzanne] Univ Wisconsin, Natl Canc Inst, Ctr Excellence Canc Commun Res, Madison, WI 53706 USA.
[Mctavish, Fiona] Univ Wisconsin, Ctr Hlth Enhancement Syst Studies, Madison, WI 53706 USA.
[Gustafson, David H.] Univ Wisconsin, Natl Canc Inst, Ctr Excellence Canc Commun, Madison, WI 53706 USA.
RP Han, JY (reprint author), Univ Georgia, Grady Coll Journalism & Mass Commun, Dept Telecommun, Athens, GA 30602 USA.
EM jeonghan@uga.edu
FU NCI NIH HHS [P50 CA095817]
NR 19
TC 35
Z9 37
U1 1
U2 10
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1359-1053
J9 J HEALTH PSYCHOL
JI J. Health Psychol.
PD NOV
PY 2008
VL 13
IS 8
BP 1002
EP 1007
DI 10.1177/1359105308097963
PG 6
WC Psychology, Clinical
SC Psychology
GA 370CD
UT WOS:000260739400005
PM 18987072
ER
PT J
AU Chung, JY
Braunschweig, T
Williams, R
Guerrero, N
Hoffmann, KM
Kwon, M
Song, YK
Libutti, SK
Hewitt, SM
AF Chung, Joon-Yong
Braunschweig, Till
Williams, Reginald
Guerrero, Natalie
Hoffmann, Karl M.
Kwon, Mijung
Song, Young K.
Libutti, Steven K.
Hewitt, Stephen M.
TI Factors in Tissue Handling and Obtained From Formalin-fixed, Processing
That Impact RNA Paraffin-embedded Tissue
SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
LA English
DT Article
DE paraffin embedded; gene expression; RNA integrity; real-time; RT-PCR;
tissue fixation and processing
ID POLYMERASE CHAIN-REACTION; EXPRESSION ANALYSIS; GENE-EXPRESSION; DNA;
OPTIMIZATION; AMPLIFICATION; PURIFICATION; EXPERIENCE; FIXATION; QUALITY
AB Formalin-fixed, paraffin-embedded (FFPE) tissue is the most common specimen available for molecular assays on tissue after diagnostic histopathological examination. RNA from FFPE tissue suffers from strand breakage and cross-linking. Despite excellent extraction methods, RNA quality from FFPE material remains variable. To address the RNA quality factors within FFPE tissues, we studied RNA quality, isolating individual elements of the tissue fixation and processing including length of fixation in formalin and the type of buffer incorporated in the fixative. We examined the impact of the length of the tissue processing cycle as well. The optimal fixation period of 12-24 hr in phosphate-buffered formalin resulted in better-quality RNA. Longer tissue processing times were associated with higher quality RNA. We determined that the middle region of gene suffers less damage by these processes as shown by real-time quantitative RT-PCR. These data provide key information for the development of methods of analysis of gene expression in archival FFPE tissues and contribute to the establishment of objective standards for the processing and handling of tissue in surgical pathology. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 56:1033-1042, 2008)
C1 [Chung, Joon-Yong; Braunschweig, Till; Williams, Reginald; Guerrero, Natalie; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Bethesda, MD 20892 USA.
[Kwon, Mijung; Libutti, Steven K.] NCI, Surg Branch, Bethesda, MD 20892 USA.
[Song, Young K.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Song, Young K.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Hoffmann, Karl M.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA.
RP Hewitt, SM (reprint author), TARP Lab, Adv Technol Ctr, MSC 4605, Bethesda, MD 20892 USA.
EM genejock@helix.nih.gov
OI Chung, Joon-Yong/0000-0001-5041-5982
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 22
TC 54
Z9 56
U1 0
U2 9
PU HISTOCHEMICAL SOC INC
PI SEATTLE
PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA
SN 0022-1554
J9 J HISTOCHEM CYTOCHEM
JI J. Histochem. Cytochem.
PD NOV
PY 2008
VL 56
IS 11
BP 1033
EP 1042
DI 10.1369/jhc.2008.951863
PG 10
WC Cell Biology
SC Cell Biology
GA 361UI
UT WOS:000260152200008
PM 18711211
ER
PT J
AU Noguchi, M
Yi, HF
Rosenblatt, HM
Filipovich, AH
Adelstein, S
Modl, WS
McBride, OW
Leonard, WJ
AF Noguchi, Masayuki
Yi, Huefang
Rosenblatt, Howard M.
Filipovich, Alexandra H.
Adelstein, Stephen
Modl, William S.
McBride, O. Wesley
Leonard, Warren J.
TI Interleukin-2 Receptor gamma Chain Mutation Results in X-Linked Severe
Combined Immunodeficiency in Humans
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID RECEPTOR BETA-CHAIN; GENETIC-LINKAGE MAP; IL-2 RECEPTOR; B-CELLS;
MOLECULAR-CLONING; ALPHA-CHAIN; CHROMOSOME INACTIVATION; IMMATURE
THYMOCYTES; SIGNAL TRANSDUCER; HUMAN GENOME
AB The Interleukin-2 (IL-2) receptor gamma chain (IL-2R gamma) Is a component of high and Intermediate affinity IL-2 receptors that Is required to achieve full ligand binding affinity and Internalization. We have localized the IL-2R gamma gone to human chromosome Xq13. Genetic linkage analysis Indicates that the IL-2R gamma gene and the locus for X-linked severe combined immunodeficiency (XSCID) appear to be at the same position. Moreover, we demonstrate that each of three unrelated patients with XSCID has a different mutation In his IL-2R gamma gone resulting In a different premature stop codon and predicted C-terminal truncation. These data establish that XSCID Is associated with mutations of the IL-2R gamma gene product. Since XSCID Is characterized by absent or markedly reduced numbers of T cells, our findings Imply that IL-2R gamma plays a vital role In thymic maturation of T cells. These results also have Important Implications for prenatal and postnatal diagnosis, carrier female detection, and gene therapy for XSCID.
C1 [Noguchi, Masayuki; Adelstein, Stephen; Leonard, Warren J.] NHLBI, Sect Pulm & Mol Immunol, Off Director Intramural Res Program, Bethesda, MD 20892 USA.
[Yi, Huefang; McBride, O. Wesley] NCI, Biochem Lab, Div Canc Biol & Diag, Bethesda, MD 20892 USA.
[Rosenblatt, Howard M.] Baylor Coll Med, Dept Pediat, Div Allergy & Immunol, Houston, TX 77030 USA.
[Filipovich, Alexandra H.] Univ Minnesota, Univ Hosp & Clin, Dept Pediat, Div Immunol, Minneapolis, MN 55455 USA.
[Modl, William S.] NCI, Biol Carcinogenesis & Dev Program, Program Resources Inc Dyncorp, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA.
RP Noguchi, M (reprint author), NHLBI, Sect Pulm & Mol Immunol, Off Director Intramural Res Program, Bldg 10, Bethesda, MD 20892 USA.
FU NIH GCRC [M01 RR00188]; David Research Fund
FX We thank G. Tosato (FDA) for establishing cell lines from patients 1 and
2, J. Ott for LINKAGE v, 5.1, H. Cann for CEPH database v. 5 and
database management system v. 5.2, J. P. Siegel (FDA), A. Weissman
(NCL), and K.-I. Jeang (NIAID) for critical comments, and the XSCID
patients whose cells were studied. H. M. R. was supported by NIH GCRC
grant M01 RR00188 and the David Research Fund. We thank W. T. Shearer
for support and work through the David Center and R. Shapiro, H.
Jyonouchi, and B. Loechelt (V. of Minnesota) and C. Roifman (Toronto)
for their work with patients 1 and 2.
NR 64
TC 9
Z9 9
U1 3
U2 20
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD NOV 1
PY 2008
VL 181
IS 9
BP 5817
EP 5827
PG 11
WC Immunology
SC Immunology
GA 368YI
UT WOS:000260659000004
PM 18941169
ER
PT J
AU Sahu, N
Venegas, AM
Jankovic, D
Mitzner, W
Gomez-Rodriguez, J
Cannons, JL
Sommers, C
Love, P
Sher, A
Schwartzberg, PL
August, A
AF Sahu, Nisebita
Venegas, Ana M.
Jankovic, Dragana
Mitzner, Wayne
Gomez-Rodriguez, Julio
Cannons, Jennifer L.
Sommers, Connie
Love, Paul
Sher, Alan
Schwartzberg, Pamela L.
August, Avery
TI Selective Expression Rather than Specific Function of Txk and Itk
Regulate Th1 and Th2 Responses
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD4(+) T-CELLS; TYROSINE KINASE ITK; TEC FAMILY KINASES;
ALLERGIC-ASTHMA; MICE LACKING; AIRWAY HYPERRESPONSIVENESS; CYTOKINE
PRODUCTION; ACTIVE ITK; DEFICIENT; ABSENCE
AB Itk and Txk/Rlk are Tee family kinases expressed in T cells. Itk is expressed in both Th1 and Th2 cells. By contrast, Txk is preferentially expressed in Th1 cells. Although Itk is required for Th2 responses in vivo and Txk is suggested to regulate IFN-gamma expression and Th1 responses, it remains unclear whether these kinases have distinct roles in Th cell differentiation/function. We demonstrate here that Txk-null CD4(+) T cells are capable of producing both Th1 and Th2 cytokines similar to those produced by wild-type CD4(+) T cells. To further examine whether Itk and Txk play distinct roles in Th cell differentiation and function, we examined Itk-null mice carrying a transgene that expresses Txk at levels similar to the expression of Itk in Th2 cells. Using two Th2 model systems, allergic asthma and schistosome egg-induced lung granulomas, we found that the Txk transgene rescued Th2 cytokine production and all Th2 symptoms without notable enhancement of IFN-gamma expression. These results suggest that Txk is not a specific regulator of Th1 responses. Importantly, they suggest that Itk and Txk exert their effects on Th cell differentiation/function at the level of expression. The Journal of Immunology, 2008, 181: 6125-6131.
C1 [Sahu, Nisebita; August, Avery] Penn State Univ, Ctr Mol Immunol & Infect Dis, University Pk, PA 16802 USA.
[Sahu, Nisebita; August, Avery] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Sahu, Nisebita] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Jankovic, Dragana; Sher, Alan] NIAID, Bethesda, MD 20892 USA.
[Sommers, Connie; Love, Paul] NICHHD, NIH, Bethesda, MD 20892 USA.
[Mitzner, Wayne] Johns Hopkins Univ, Dept Environm Hlth Sci, Baltimore, MD 21205 USA.
[Venegas, Ana M.; Gomez-Rodriguez, Julio; Cannons, Jennifer L.] NHGRI, Bethesda, MD 20892 USA.
RP August, A (reprint author), Penn State Univ, Ctr Mol Immunol & Infect Dis, 115 Henning Bldg, University Pk, PA 16802 USA.
EM pams@imail.nih.gov; avery@psu.cdu
FU Intramural NIH HHS [Z01 HG000123-10]; NIAID NIH HHS [R01 AI051626,
AI051626, AI065566, R01 AI051626-04, R01 AI051626-05, R01 AI065566, R01
AI065566-02A2, R01 AI065566-03, R56 AI065566]
NR 33
TC 22
Z9 23
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 NOV 1
PY 2008
VL 181
IS 9
BP 6125
EP 6131
PG 7
WC Immunology
SC Immunology
GA 368YI
UT WOS:000260659000037
PM 18941202
ER
PT J
AU Yang, S
Rosenberg, SA
Morgan, RA
AF Yang, Shicheng
Rosenberg, Steven A.
Morgan, Richard A.
TI Clinical-scale Lentiviral Vector Transduction of PBL for TCR Gene
Therapy and Potential for Expression in Less-differentiated Cells
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE lentivirus; T-cell receptor; adoptive immunotherapy; gene therapy
ID EMBRYONIC STEM-CELLS; CD8(+) T-CELLS; CENTRAL-MEMORY; IN-VIVO;
LYMPHOCYTES; TUMOR; ANTIGEN; RECOGNITION; IMPAIRS; MODEL
AB In human gene therapy applications, lentiviral vectors may have advantages over gamma-retroviral vectors because of their ability to transduce nondividing cells, their resistance to gene silencing, and a lack of integration site preference. In this study, we used VSV-G pseudotype third generation lentiviral vectors harboring specific antitumor T-cell receptor (TCR) to establish clinical-scale lentiviral transduction of peripheral blood lymphocyte (PBL). Spinoculation (1000g, 32 degrees C for 2h) in the presence of protamine sulfate represents the most efficient and economical approach to transduce a large number of PBLs compared with RetroNectin-based methods. Up to 20 million cells per well of a 6-well plate were efficiently transduced and underwent an average 50-fold expansion in 2 weeks. TCR transduced PBL-mediated specific antitumor activities including interferon-7 release and cell lysis. Compared with gammaretroviral vectors, the TCR transgene could be preferentially expressed on a less-differentiated cell population.
C1 [Yang, Shicheng; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Morgan, RA (reprint author), 10 Ctr Dr,Bldg 10,CRC 3W-3864, Bethesda, MD 20892 USA.
EM rmorgan@mail.nih.gov
FU Intramural NIH HHS [Z01 SC003811-33]
NR 39
TC 22
Z9 22
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 830
EP 839
DI 10.1097/CJI.0b013e31818817c5
PG 10
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800005
PM 18833004
ER
PT J
AU Restifo, NP
AF Restifo, Nicholas P.
TI Three Ways to Enhance the Destructive Power of Tumor-specific T Cells
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
ID ADOPTIVE IMMUNOTHERAPY; AUTOIMMUNITY; ANTIGEN
C1 [Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA.
RI Restifo, Nicholas/A-5713-2008
NR 7
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 925
EP 925
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800027
ER
PT J
AU Shafer-Weaver, KA
Watkins, SK
Malyguine, A
Hurwitz, AA
AF Shafer-Weaver, Kimberly A.
Watkins, Stephanie K.
Malyguine, Anatoli
Hurwitz, Arthur A.
TI Provision of CD4+T Cell Help Prevents Tolerization of Tumorspecific CTLs
and Enhances Tumor Immunity in a Murine Model of Prostate Cancer
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
C1 [Shafer-Weaver, Kimberly A.; Malyguine, Anatoli] SAIC Frederick Inc, Clin Serv Program, Lab Cell Mediated Immun, Frederick, MD USA.
[Shafer-Weaver, Kimberly A.; Watkins, Stephanie K.; Hurwitz, Arthur A.] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 925
EP 925
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800028
ER
PT J
AU Pos, Z
Selleri, S
Spivey, TL
Liu, H
Worschech, A
Sabatino, M
Monaco, A
Falus, A
Wang, E
Marincola, FM
AF Pos, Zoltan
Selleri, Silvia
Spivey, Tara L.
Liu, Hui
Worschech, Andrea
Sabatino, Marianna
Monaco, Alessandro
Falus, Andras
Wang, Ena
Marincola, Francesco M.
TI The Genetic Background of IFN-alpha Responsiveness: A Genome-wide Study
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
C1 [Pos, Zoltan; Spivey, Tara L.; Liu, Hui; Worschech, Andrea; Sabatino, Marianna; Monaco, Alessandro; Wang, Ena; Marincola, Francesco M.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
[Selleri, Silvia] San Raffaele Telethon Inst, Milan, Italy.
[Falus, Andras] Semmelweis Univ, HAS, Immunogenom Res Grp, H-1085 Budapest, Hungary.
RI Worschech, Andrea/I-3919-2012; Monaco, Alessandro/O-5338-2015
OI Worschech, Andrea/0000-0002-4303-8653; Monaco,
Alessandro/0000-0002-9941-7003
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 930
EP 931
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800045
ER
PT J
AU Weiss, JM
Bouchlaka, M
Subleski, J
Back, T
Wilkins, D
Alderson, K
Welniak, L
Redelman, D
Murphy, WJ
Wiltrout, RH
AF Weiss, Jonathan M.
Bouchlaka, Myriam
Subleski, Jeff
Back, Tim
Wilkins, Danice
Alderson, Kory
Welniak, Lisbeth
Redelman, Doug
Murphy, William J.
Wiltrout, Robert H.
TI Impairment of Secondary Antitumor Responses After IL-2/Anti-CD40
Immunotherapy: A Putative Role for Natural Killer Cells and Perforin
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
C1 [Weiss, Jonathan M.; Subleski, Jeff; Back, Tim; Wiltrout, Robert H.] NCI Frederick, Canc & Inflammat Program, Frederick, MD USA.
[Bouchlaka, Myriam; Wilkins, Danice; Alderson, Kory; Welniak, Lisbeth; Redelman, Doug; Murphy, William J.] Univ Nevada, Sch Med, Dept Microbiol & Immunol, Reno, NV 89557 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 934
EP 934
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800055
ER
PT J
AU Wilkins, DE
Alderson, KL
Weiss, JM
Bouchlaka, M
Redelman, D
Welniak, LA
Murphy, WJ
AF Wilkins, Danice E.
Alderson, Kory L.
Weiss, Jonathan M.
Bouchlaka, Myriam
Redelman, Doug
Welniak, Lisbeth A.
Murphy, William J.
TI Immunotherapy With Anti-CD40 and IL-2 Results in Antigen Independent
CD8+T Cell Activation In Vivo
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
C1 [Wilkins, Danice E.; Alderson, Kory L.; Bouchlaka, Myriam; Welniak, Lisbeth A.; Murphy, William J.] Univ Nevada, Sch Med, Reno, NV 89557 USA.
[Weiss, Jonathan M.] NCI, Canc Inflammat Program, Frederick, MD 21701 USA.
[Redelman, Doug] Univ Nevada, Sch Med, Dept Physiol, Reno, NV 89557 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 934
EP 934
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800056
ER
PT J
AU Fiammenghi, L
Ancarani, V
Petrini, M
Riccobon, A
Granato, AM
Pancisi, E
Ridolfi, L
Ridolfi, R
Knutson, JR
Rosales, T
Neyroz, P
AF Fiammenghi, Laura
Ancarani, Valentina
Petrini, Massimiliano
Riccobon, Angela
Granato, Anna Maria
Pancisi, Elena
Ridolfi, Laura
Ridolfi, Ruggero
Knutson, Jay R.
Rosales, Tilman
Neyroz, Paolo
TI Tumor Lysate Capture and Processing by Dendritic Cells: A Kinetic and an
Immunofluorescence Study by Flow Cytometry and Confocal Microscopy
Imaging
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
C1 [Ancarani, Valentina; Neyroz, Paolo] Univ Bologna, Dept Biochem, I-40126 Bologna, Italy.
[Knutson, Jay R.; Rosales, Tilman] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 935
EP 935
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800059
ER
PT J
AU Han, TH
Jin, P
Ren, JQ
Slezak, S
Marincola, FM
Stroncek, DF
AF Han, Tae Hee
Jin, Ping
Ren, Jiaqiang
Slezak, Stefanie
Marincola, Francesco M.
Stroncek, David F.
TI The Evaluation of Monocyte Derived Mature Dendritic Cells With Gene and
Microrna Expression Microarrays
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
C1 [Han, Tae Hee; Jin, Ping; Ren, Jiaqiang; Slezak, Stefanie; Marincola, Francesco M.; Stroncek, David F.] NIH, DTM, Bethesda, MD 20892 USA.
[Han, Tae Hee] Inje Univ, Sanggye Paik Hosp, Seoul, South Korea.
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 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 935
EP 936
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800060
ER
PT J
AU Steel, JC
Ramlogan, CA
Yu, P
Waldmann, TA
Morris, JC
AF Steel, Jason C.
Ramlogan, Charmaine A.
Yu, Ping
Waldmann, Thomas A.
Morris, John C.
TI Interleukin-15 and Its Receptor Enhance Antitumor Activity Following a
Genetically Modified Dendritic Cell Vaccine
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
C1 [Steel, Jason C.; Ramlogan, Charmaine A.; Yu, Ping; Waldmann, Thomas A.; Morris, John C.] NCI, Metab Branch, Bethesda, MD 20892 USA.
RI Steel, Jason/D-1805-2013
OI Steel, Jason/0000-0003-3608-7542
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 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 949
EP 949
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800104
ER
PT J
AU Monaco, A
Marincola, FM
Sabatino, M
Pos, Z
Tornesello, ML
Stroncek, DF
Wang, E
Gallo, RC
Lewis, GK
Buonaguro, FM
Buonaguro, L
AF Monaco, Alessandro
Marincola, F. M.
Sabatino, M.
Pos, Zoltan
Tornesello, Maria Lina
Stroncek, David F.
Wang, Ena
Gallo, Robert C.
Lewis, George K.
Buonaguro, Franco M.
Buonaguro, Luigi
TI Gauging Innate Immunity in HIV Infection
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
C1 [Monaco, Alessandro; Marincola, F. M.; Sabatino, M.; Pos, Zoltan; Stroncek, David F.; Wang, Ena] NIH, DTM, Bethesda, MD 20892 USA.
[Monaco, Alessandro] IRCCS Giovanni Paolo II, CEO Lab, Bari, Italy.
[Tornesello, Maria Lina; Buonaguro, Franco M.; Buonaguro, Luigi] Ist Naz Tumori, Lab Mol Biol Viral Oncogen, Naples, Italy.
[Gallo, Robert C.; Lewis, George K.; Buonaguro, Luigi] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA.
RI Tornesello, Maria Lina/A-1564-2009; Monaco, Alessandro/O-5338-2015
OI Tornesello, Maria Lina/0000-0002-3523-3264; Monaco,
Alessandro/0000-0002-9941-7003
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 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 953
EP 953
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800118
ER
PT J
AU Worschech, A
Chen, NH
Yu, Y
Zhang, Q
Sabatino, M
Monaco, A
Pos, Z
Lui, H
Buller, MR
Wang, E
Szalay, AA
Marincola, FM
AF Worschech, Andrea
Chen, Nanhai
Yu, Yong
Zhang, Qian
Sabatino, Marianna
Monaco, Alessandro
Pos, Zoltan
Lui, Hui
Buller, Mark R.
Wang, Ena
Szalay, Aladar A.
Marincola, Francesco M.
TI Predicting the Immunologic Constant of Rejection
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
C1 [Worschech, Andrea; Chen, Nanhai; Yu, Yong; Zhang, Qian; Szalay, Aladar A.] Genelux Corp, San Diego, CA USA.
[Worschech, Andrea; Szalay, Aladar A.] Univ Wurzburg, Virchow Ctr Expt Biomed, Wurzburg, Germany.
[Worschech, Andrea; Szalay, Aladar A.] Univ Wurzburg, Dept Biochem, Wurzburg, Germany.
[Worschech, Andrea; Sabatino, Marianna; Monaco, Alessandro; Pos, Zoltan; Lui, Hui; Wang, Ena; Marincola, Francesco M.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Buller, Mark R.] St Louis Univ, Sch Med, Dept Mol Biol & Immunol, St Louis, MO USA.
RI Worschech, Andrea/I-3919-2012; Monaco, Alessandro/O-5338-2015
OI Worschech, Andrea/0000-0002-4303-8653; Monaco,
Alessandro/0000-0002-9941-7003
NR 2
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 954
EP 955
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800122
ER
PT J
AU Sabatino, M
Kim-Schulze, S
Kim, DW
Panelli, MC
Stroncek, D
Wang, E
Marincola, FM
Kaufman, HL
AF Sabatino, Marianna
Kim-Schulze, Seunghee
Kim, Dae Won
Panelli, Monica C.
Stroncek, David
Wang, Ena
Marincola, Francesco M.
Kaufman, Howard L.
TI Serum Vascular Endothelial Growth Factor (VEGF) and Fibronectin as a
Potential Predictor of Responsiveness to High-dose Interleukin (IL)-2
Therapy
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
C1 [Sabatino, Marianna; Stroncek, David; Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Bethesda, MD USA.
[Kim-Schulze, Seunghee; Kim, Dae Won; Kaufman, Howard L.] Columbia Univ, Dept Surg, New York, NY USA.
[Panelli, Monica C.] Univ Pittsburgh, Pittsburgh Canc Inst, Dept Med, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 960
EP 960
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800140
ER
PT J
AU Watkins, SK
Shafer-Weaver, KA
Hurwitz, AA
AF Watkins, Stephanie K.
Shafer-Weaver, Kimberly A.
Hurwitz, Arthur A.
TI Increasing Immunostimulatory Ability of Tolerogenic APCs Enhances
Anti-tumor Immunity
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
C1 [Watkins, Stephanie K.; Hurwitz, Arthur A.] NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA.
[Shafer-Weaver, Kimberly A.] SAIC Frederick, Clin Serv Program, Lab Cell Mediated Immun, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 968
EP 968
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800167
ER
PT J
AU Baskar, S
Yang, JH
Rader, C
AF Baskar, Sivasubramanian
Yang, Jiahui
Rader, Christoph
TI Targeting Human B Cell Chronic Lymphocytic Leukemia With a Monoclonal
Antibody Specific for the Receptor Tyrosine Kinase ROR1
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 23rd Annual Scientific Meeting of the
International-Society-for-Biological-Therapy-of-Cancer
CY OCT 31-NOV 02, 2008
CL San Diego, CA
SP Int Soc Biol Therapy Canc
C1 [Baskar, Sivasubramanian; Yang, Jiahui; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2008
VL 31
IS 9
BP 969
EP 969
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 364TS
UT WOS:000260358800170
ER
PT J
AU Crompton, PD
Traore, B
Kayentao, K
Doumbo, S
Ongoiba, A
Diakite, SAS
Krause, MA
Doumtabe, D
Kone, Y
Weiss, G
Huang, CY
Doumbia, S
Guindo, A
Fairhurst, RM
Miller, LH
Pierce, SK
Doumbo, OK
AF Crompton, Peter D.
Traore, Boubacar
Kayentao, Kassoum
Doumbo, Safiatou
Ongoiba, Aissata
Diakite, Seidina A. S.
Krause, Michael A.
Doumtabe, Didier
Kone, Younoussou
Weiss, Greta
Huang, Chiung-Yu
Doumbia, Seydou
Guindo, Aldiouma
Fairhurst, Rick M.
Miller, Louis H.
Pierce, Susan K.
Doumbo, Ogobara K.
TI Sickle cell trait is associated with a delayed onset of malaria:
Implications for time-to-event analysis in clinical studies of malaria
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 56th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene
CY NOV 04-08, 2007
CL Philadelphia, PA
SP Amer Soc Trop Med & Hyg
ID PLASMODIUM-FALCIPARUM MALARIA; EXTENDED FOLLOW-UP; UGANDAN CHILDREN;
PARASITE DENSITY; PROTECTION; MECHANISM; HEMOGLOBIN; ANTIGENS; MALI;
ERYTHROCYTES
AB Background. The World Health Organization (WHO) recently recommended that the time to first malaria episode serve as the primary end point in phase III malaria vaccine trials-the first of which will be held in Africa. Although common red blood cell (RBC) polymorphisms such as sickle hemoglobin (HbS) are known to protect against malaria in Africa, their impact on this end point has not been investigated.
Methods. A longitudinal study of 225 individuals aged 2-25 years was conducted in Mali. The association between common RBC polymorphisms and the time to first malaria episode was evaluated.
Results. Among children aged 2-10 years, sickle cell trait (HbAS) was associated with a 34-day delay in the median time to first malaria episode (P = .017). Cox regression analysis showed that greater age (hazard ratio [HR], 0.87 [95% CI, 0.80-0.94]; P = .001), HbAS (HR, 0.48 [95% CI, 0.26-0.91]; P = .024), and asymptomatic parasitemia at enrollment (HR, 0.35 [95% CI, 0.14-0.85]; P = .021) were associated with decreased malaria risk.
Conclusion. Given the delay in the time to first malaria episode associated with HbAS, it would be advisable for clinical trials and observational studies that use this end point to include Hb typing in the design of studies conducted in areas where HbAS is prevalent.
C1 [Crompton, Peter D.; Weiss, Greta] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
[Huang, Chiung-Yu] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Krause, Michael A.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA.
[Traore, Boubacar; Kayentao, Kassoum; Doumbo, Safiatou; Ongoiba, Aissata; Diakite, Seidina A. S.; Doumtabe, Didier; Kone, Younoussou; Doumbia, Seydou; Guindo, Aldiouma; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Dept Epidemiol Parasit Dis, Fac Med Pharm & Odonto Stomatol, Bamako, Mali.
RP Crompton, PD (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2 Bldg,Rm 213,12441 Parklawn Dr, Rockville, MD 20852 USA.
EM pcrompton@niaid.nih.gov
RI Crompton, Peter/N-1130-2016
FU Intramural NIH HHS [Z01 AI000949-04]
NR 41
TC 54
Z9 55
U1 1
U2 6
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 NOV 1
PY 2008
VL 198
IS 9
BP 1265
EP 1275
DI 10.1086/592224
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 360AU
UT WOS:000260030200004
PM 18752444
ER
PT J
AU Pandey, JP
Namboodiri, AM
Luo, YQ
Wu, YP
Elston, RC
Thomas, DL
Rosen, HR
Goedert, JJ
AF Pandey, Janardan P.
Namboodiri, Aryan M.
Luo, Yuqun
Wu, Yuping
Elston, Robert C.
Thomas, David L.
Rosen, Hugo R.
Goedert, James J.
TI Genetic markers of IgG influence the outcome of infection with hepatitis
C virus
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID CORE PROTEIN; IMMUNOGLOBULIN ALLOTYPES; GAMMA; CLEARANCE; GENOTYPES; GM
AB We examined the role that immunoglobulin GM and KM allotypes-genetic markers of gamma and kappa chains, respectively-play in the outcome of hepatitis C virus (HCV) infection in white Americans. A total of 119 persons who had cleared HCV and 111 with persistent HCV infection were genotyped for the presence of several GM and KM determinants. Persistent HCV infection was more than three times as likely (odds ratio, 3.50; P = .01) in subjects who were carriers of the GM3 allele than in those who were noncarriers. These results show that particular GM alleles may be important determinants of the outcome of HCV infection.
C1 [Pandey, Janardan P.; Namboodiri, Aryan M.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
[Luo, Yuqun; Elston, Robert C.] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Wu, Yuping] Cleveland State Univ, Dept Math, Cleveland, OH 44115 USA.
[Thomas, David L.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Goedert, James J.] Natl Canc Inst, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, Rockville, MD USA.
[Rosen, Hugo R.] Univ Colorado, Div Gastroenterol & Hepatol, Denver, CO 80202 USA.
RP Pandey, JP (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
EM pandeyj@musc.edu
FU National Institutes of Health [DK070877, DA13224, HG003054]
FX Financial support: National Institutes of Health (grants DK070877 to
J.P.P., DA13224 to D.L.T., and HG003054 to Y.L.).
NR 15
TC 8
Z9 8
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 NOV 1
PY 2008
VL 198
IS 9
BP 1334
EP 1336
DI 10.1086/592282
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 360AU
UT WOS:000260030200012
PM 18855559
ER
PT J
AU Fang, L
Lonsdorf, AS
Hwang, ST
AF Fang, Lei
Lonsdorf, Anke S.
Hwang, Sam T.
TI Immunotherapy for Advanced Melanoma
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; CD8(+) T-CELLS; ACTIVE SPECIFIC
IMMUNOTHERAPY; TUMOR-INFILTRATING LYMPHOCYTES; DOSE RECOMBINANT
INTERLEUKIN-2; COLONY-STIMULATING FACTOR; PULSED DENDRITIC CELLS;
HIGH-RISK MELANOMA; STAGE-IV MELANOMA; PHASE-III TRIAL
AB Immunotherapy for melanoma has undergone significant change since the first attempts to treat patients with high dose IL-2. Herein, strategies to boost patient antitumor immunity through vaccination, treatment with agents that augment host immunity, and adoptive cell transfer will be discussed. The first two strategies have yielded only limited clinical success, but adoptive cell transfer therapy, particularly following a lymphodepleting, preconditioning regimen has resulted in objective response rates approaching 50%. For a number of reasons, lymphodepletion appears to be critical for maintenance of circulating antitumor T cells following adoptive cell transfer. Balancing antitumor efficacy, autoimmunity, and reconstitution of a functioning immune system remain challenging and potentially life-threatening issues.
C1 [Fang, Lei; Lonsdorf, Anke S.; Hwang, Sam T.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hwang, ST (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1908 NIH,Bldg 10,Rm 12N238, Bethesda, MD 20892 USA.
EM hwangs@mail.nih.gov
FU German Research Foundation (DFG); NIH
FX We thank Drs Mark C. Udey (Dermatology Branch, NCI) and Steven A.
Rosenberg (Surgery Branch, NCI) for helpful comments and suggestions.
ASL is a recipient of a German Research Foundation (DFG)-NIH Career
Transition Award. This work was supported by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 99
TC 52
Z9 54
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD NOV
PY 2008
VL 128
IS 11
BP 2596
EP 2605
DI 10.1038/jid.2008.101
PG 10
WC Dermatology
SC Dermatology
GA 364XL
UT WOS:000260368800006
PM 18927541
ER
PT J
AU Rosenberg, HF
AF Rosenberg, Helene F.
TI HMGB1, a novel biomarker of inflammatory demyelinating disease: an
interview with Dr. Robert A. Harris
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Editorial Material
ID PROTEIN
C1 NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA.
RP Rosenberg, HF (reprint author), NIAID, NIH, Lab Allerg Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD NOV 1
PY 2008
VL 84
IS 5
BP 1256
EP 1258
DI 10.1189/jlb.1307844
PG 3
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 359VN
UT WOS:000260016300004
PM 18780873
ER
PT J
AU Millum, J
AF Millum, J.
TI Are pharmaceutical patents protected by human rights?
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
ID MEDICINES; HEALTH
AB The International Bill of Rights enshrines a right to health, which includes a right to access essential medicines. This right frequently appears to conflict with the intellectual property regime that governs pharmaceutical patents. However, there is also a human right that protects creative works, including scientific productions. Does this right support intellectual property protections, even when they may negatively affect health? This article examines the recent attempt by the Committee on Economic, Social and Cultural Rights to resolve this issue and argues that it fails. This is problematic because it means defenders of the present patent regime can continue using human rights documents to support their position. I offer a new framework for resolving the problem by examining the values that underlie human rights.
C1 NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Millum, J (reprint author), NIH, Dept Bioeth, Bldg 10,1C118,10 Ctr Dr, Bethesda, MD 20892 USA.
EM millumj@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 19
TC 2
Z9 2
U1 0
U2 4
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
J9 J MED ETHICS
JI J. Med. Ethics
PD NOV
PY 2008
VL 34
IS 11
AR e25
DI 10.1136/jme.2007.022483
PG 5
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 367EZ
UT WOS:000260536600018
PM 18974405
ER
PT J
AU Liem, DA
Zhao, P
Angelis, E
Chan, SS
Zhang, J
Wang, G
Berthet, C
Kaldis, P
Ping, P
MacLellan, WR
AF Liem, David A.
Zhao, Peng
Angelis, Ekaterini
Chan, Shing S.
Zhang, Jun
Wang, Guangwu
Berthet, Cyril
Kaldis, Philipp
Ping, Peipei
MacLellan, W. Robb
TI Cyclin-dependent kinase 2 signaling regulates myocardial
ischemia/reperfusion injury
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Article
DE Myocardial ischemia; Cardioprotection; Apoptosis; Cyclin-dependent
kinase 2; Retinoblastoma gene
ID HYPOXIA-INDUCED APOPTOSIS; DEATH IN-VITRO; CELL-DEATH; RETINOBLASTOMA
PROTEIN; NERVOUS-SYSTEM; ISCHEMIA-REPERFUSION; DEFICIENT MICE; CDK2
ACTIVITY; RB; ACTIVATION
AB Ischemia/reperfusion (I/R) injury to the heart is accompanied by the upregulation and posttranslational modification of a number of proteins normally involved in regulating cell cycle progression. Two proteins, cyclin-dependent kinase-2 (Cdk2) and its downstream target, the retinoblastoma gene product (Rb), also play a critical role in the control of apoptosis. Myocardial ischemia activates Cdk2, resulting in the phosphorylation and inactivation of Rb. Blocking Cdk2 activity reduces apoptosis in cultured cardiac myocytes. Genetic or pharmacological inhibition of Cdk2 activity in vivo during I/R injury led to a 36% reduction in infarct size (IFS), when compared to control mice, associated with a reduction in apoptotic myocytes. To confirm that Rb was the critical target in Cdk2-mediated I/R injury, we determined the consequences of I/R injury in cardiac-specific Rb-deficient mice (CRbL/L). IFS was increased 140% in CRbL/L mice compared to CRb+/+ controls. TUNEL positive nuclei and caspase-3 activity were augmented by 92% and 36%, respectively, following injury in the CRbL/L mice demonstrating that loss of Rb in the heart significantly exacerbates I/R injury. These data suggest that Cdk2 signaling pathways are critical regulators of cardiac I/R injury in vivo and support a cardioprotective role for Rb. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Liem, David A.; Zhao, Peng; Angelis, Ekaterini; Chan, Shing S.; Ping, Peipei; MacLellan, W. Robb] Univ Calif Los Angeles, David Geffen Sch Med, Cardiovasc Res Lab, Los Angeles, CA 90095 USA.
[Liem, David A.; Zhang, Jun; Wang, Guangwu; Ping, Peipei; MacLellan, W. Robb] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
[Berthet, Cyril; Kaldis, Philipp] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Liem, DA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Cardiovasc Res Lab, 675 CE Young Dr,MRL 3-645, Los Angeles, CA 90095 USA.
EM rmaclellan@mednet.ucla.edu
RI Kaldis, Philipp/G-2714-2010;
OI Kaldis, Philipp/0000-0002-7247-7591; Ping, Peipei/0000-0003-3583-3881
FU NHLBI NIH HHS [P01 HL080111, P01 HL080111-040004, R01 HL065431, R01
HL070748, R01 HL070748-04, R01 HL65431, R01 HL70748]
NR 56
TC 9
Z9 9
U1 0
U2 6
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 NOV
PY 2008
VL 45
IS 5
BP 610
EP 616
DI 10.1016/j.yjmcc.2008.07.003
PG 7
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 373PD
UT WOS:000260983300003
PM 18692063
ER
PT J
AU Igbokwe, A
Lacbawani, F
Pineda, D
Muenke, M
AF Igbokwe, A.
Lacbawani, F.
Pineda, D.
Muenke, M.
TI Molecular Characterization and Postmortem Review of Holoprosencephaly
(HPE) Cases
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the Association-for-Molecular-Pathology
CY OCT 29-NOV 02, 2008
CL Grapevine, TX
SP Assoc Mol Pathol
C1 [Igbokwe, A.; Lacbawani, F.] Suny Downstate, Brooklyn, NY USA.
[Lacbawani, F.] NHGRI, MGB, NIH, Brooklyn, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2008
VL 10
IS 6
BP 574
EP 574
PG 1
WC Pathology
SC Pathology
GA 367DV
UT WOS:000260533600052
ER
PT J
AU Wragg, A
Mellad, JA
Beltran, LE
Konoplyannikov, M
San, H
Boozer, S
Deans, RJ
Mathur, A
Lederman, RJ
Kovacic, JC
Boehm, M
AF Wragg, Andrew
Mellad, Jason A.
Beltran, Leilani E.
Konoplyannikov, Mikhail
San, Hong
Boozer, Sherry
Deans, Robert J.
Mathur, Anthony
Lederman, Robert J.
Kovacic, Jason C.
Boehm, Manfred
TI VEGFR1/CXCR4-positive progenitor cells modulate local inflammation and
augment tissue perfusion by a SDF-1-dependent mechanism
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE Vascular biology; Cell therapy; Stem cell; Inflammation
ID MESENCHYMAL STEM-CELLS; MARROW-DERIVED CELLS; ACUTE
MYOCARDIAL-INFARCTION; ENDOTHELIAL GROWTH-FACTOR; BONE-MARROW;
MONONUCLEAR-CELLS; ISCHEMIC LIMBS; STROMAL CELLS; RAT MODEL; FACTOR-I
AB Recruitment and retention of circulating progenitor cells at the site of injured or ischemic tissues facilitates adult neo-vascularization. We hypothesized that cell therapy could modulate local neo-vascularization through the vascular endothelial growth factor (VEGF)/stromal cell-derived factor-1 (SDF-1) axis and by paracrine effects on local endothelial cells. We isolated from rat bone marrow a subset of multipotent adult progenitor cell-derived progenitor cells (MDPC). In vitro, MDPCs secreted multiple cytokines related to inflammation and angiogenesis, including monocyte chemotactic protein-1, SDF-1, basic fibroblast growth factor, and VEGF, and expressed the chemokine receptors CXCR4 and VEGFR1. To investigate in vivo properties, we transplanted MDPCs into the ischemic hind limbs of rats. Elevated levels of the chemokine SDF-1 and colocalization of CD11b(+) cells marked the initial phase of tissue remodeling after cell transplantation. Prolonged engraftment was observed in the adventitial-medial border region of arterioles of ischemic muscles. However, engrafted cells did not differentiate into endothelial or smooth muscle cells. Limb perfusion normalized 4 weeks after cell injection. Inhibition of SDF-1 reduced the engraftment of transplanted cells and decreased endothelial cell proliferation. These findings suggest a two-stage model whereby transplanted MDPCs modulate wound repair through recruitment of inflammatory cells to ischemic tissue. This is an important potential mechanism for cell transplantation, in addition to the direct modulation of local vascular cells through paracrine mechanisms.
C1 [Wragg, Andrew; Mellad, Jason A.; Beltran, Leilani E.; Konoplyannikov, Mikhail; San, Hong; Lederman, Robert J.; Kovacic, Jason C.; Boehm, Manfred] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20817 USA.
[Boozer, Sherry; Deans, Robert J.] Athersys, Cleveland, OH 44115 USA.
[Wragg, Andrew; Mathur, Anthony] William Harvey Res Inst, London EC1M 6BQ, England.
RP Boehm, M (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10-CRC,Room 5-3132, Bethesda, MD 20817 USA.
EM boehmm@nhlbi.nih.gov
OI lederman, robert/0000-0003-1202-6673
FU Intramural NIH HHS [Z99 HL999999, Z01 HL005066-04]
NR 37
TC 26
Z9 26
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
J9 J MOL MED
JI J. Mol. Med.
PD NOV
PY 2008
VL 86
IS 11
BP 1221
EP 1232
DI 10.1007/s00109-008-0390-7
PG 12
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 362TL
UT WOS:000260219900003
PM 18690419
ER
PT J
AU Park, J
Kim, TY
Jung, Y
Song, SH
Kim, SH
Oh, DY
Im, SA
Bang, YJ
AF Park, Jinah
Kim, Tae-You
Jung, Yeonjoo
Song, Sang-Hyun
Kim, Sung-Hak
Oh, Do-Youn
Im, Seock-Ah
Bang, Yung-Jue
TI DNA methyltransferase 3B mutant in ICF syndrome interacts non-covalently
with SUMO-1
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE DNMT3B; ICF syndrome; SUMOylation; S270P mutation
ID NF-KAPPA-B; IMMUNODEFICIENCY SYNDROME; SACCHAROMYCES-CEREVISIAE; DNMT3B
MUTATIONS; PWWP DOMAIN; METHYLATION; GENE; TRANSCRIPTION; SUMOYLATION;
PROTEINS
AB Mutations of the DNA methyltransferase 3B (DNMT3B) gene have been detected in patients with immunodeficiency, centromere instability, and facial anomalies (ICF) syndrome. Most of these mutations are clustered in its catalytic domain and thus lead to defective DNA methylation. Nevertheless, the S270P mutation in the N-terminal PWWP (Pro-Trp-Trp-Pro) domain of the DNMT3B gene has prompted questions as to how this mutation contributes to the development of ICF syndrome. In this study, we found that wild-type DNMT3B is SUMOylated through covalent modification, whereas the S270P mutant interacts with SUMO-1 via non-covalent interaction. The S270P mutation results in diffuse nucleus localization. Moreover, the S270P mutant fails to interact with PIAS1, a small ubiquitin-related modifier (SUMO) E3 ligase, and causes the constitutive activation of nuclear factor-kappa B, which induces the expression of interleukin 8. Collectively, our data demonstrate that the S270P mutation affects DNMT3B functions via specific, non-covalent interaction with SUMO-1.
C1 [Kim, Tae-You; Oh, Do-Youn; Im, Seock-Ah; Bang, Yung-Jue] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110744, South Korea.
[Park, Jinah; Kim, Tae-You; Jung, Yeonjoo; Kim, Sung-Hak; Oh, Do-Youn; Im, Seock-Ah; Bang, Yung-Jue] Canc Res Inst, Natl Res Lab Canc Epigenet, Seoul, South Korea.
[Song, Sang-Hyun] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Bang, YJ (reprint author), Seoul Natl Univ, Coll Med, Dept Internal Med, 28 Yongon Dong, Seoul 110744, South Korea.
EM bangyj@plaza.snu.ac.kr
RI Kim, Tae-You/J-2750-2012; Im, Seock-Ah/J-5620-2012; Bang, Yung
Jue/J-2759-2012
FU Korea Science and Engineering Foundation (KOSEF); Ministry of Science
and Technology [M10400000336-06J0000-33610, BK21]
FX We thank Dr. Jong-Soo Lee (Ajou University, Korea) for discussions and
providing the SUMO-1 constructs. We also thank all members of Bang's
laboratory. This work was supported by the Korea Science and Engineering
Foundation (KOSEF) through the National Research Lab. Program funded by
the Ministry of Science and Technology (No. M10400000336-06J0000-33610)
and the BK21 Project for Medicine, Dentistry and Pharmacy.
NR 32
TC 7
Z9 7
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
J9 J MOL MED
JI J. Mol. Med.
PD NOV
PY 2008
VL 86
IS 11
BP 1269
EP 1277
DI 10.1007/s00109-008-0392-5
PG 9
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 362TL
UT WOS:000260219900007
PM 18762900
ER
PT J
AU Wu, MX
Yu, KF
AF Wu, Mi-Xia
Yu, Kai-Fun
TI Remarks on between estimator in the intraclass correlation model with
missing data
SO JOURNAL OF MULTIVARIATE ANALYSIS
LA English
DT Article
DE Between estimator; Intraclass correlation model; Contrast; Missing data;
Exact test; Confidence interval
ID SIMULTANEOUS CONFIDENCE-INTERVALS; MULTIVARIATE NORMAL-DISTRIBUTION;
NORMAL-MEAN VECTOR; INCOMPLETE DATA
AB In this paper, we consider the between estimator under the intraclass correlation model with missing data. We give a necessary and sufficient condition for existing exact simultaneous confidence intervals for all contrasts in the means under the between transformed model, which indicates the F-test statistic and simultaneous confidence intervals, constructed by Seo et al. [T. Seo, J. Kikuchi, K. Koizumi, On simultaneous confidence intervals for all contracts in the means of the intraclass correlation model with missing data, J. Multivariate Anal. 97 (2006) 1976-1983] based on the between estimator, is invalid. Furthermore, using the distribution of the between estimator, we present the exact test statistics and confidence intervals for partial contrasts. Published by Elsevier Inc.
C1 [Wu, Mi-Xia; Yu, Kai-Fun] NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Rockville, MD 20852 USA.
[Wu, Mi-Xia] Beijing Univ Technol, Coll Appl Sci, Beijing 100022, Peoples R China.
RP Wu, MX (reprint author), NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, 6100 Execut Blvd,Rm 7B05A, Rockville, MD 20852 USA.
EM wumixia@mail.nih.gov
FU National Institute of Child Health and Human Development, National
Institutes of Health; Academic Human Resources Development in
Institutions of Higher Learning; National Natural Science Foundation of
China (NSFC) [10771010]
FX The work was supported by the Intramural Research Program of the
National Institute of Child Health and Human Development, National
Institutes of Health. Wu's research was also partially supported by
Funding Project for Academic Human Resources Development in Institutions
of Higher Learning Under the Jurisdiction of Beijing Municipality
PHR(IHLB) and National Natural Science Foundation of China (NSFC)
(10771010). We are grateful to the two referees for their detailed
suggestions which considerably improved the quality of the paper.
NR 10
TC 0
Z9 0
U1 1
U2 5
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0047-259X
J9 J MULTIVARIATE ANAL
JI J. Multivar. Anal.
PD NOV
PY 2008
VL 99
IS 10
BP 2444
EP 2452
DI 10.1016/j.jmva.2008.02.030
PG 9
WC Statistics & Probability
SC Mathematics
GA 369MD
UT WOS:000260697700017
ER
PT J
AU Summy-Long, JY
Hu, S
Long, A
Phillips, TM
AF Summy-Long, J. Y.
Hu, S.
Long, A.
Phillips, T. M.
TI Interleukin-1 beta Release in the Supraoptic Nucleus Area During Osmotic
Stimulation Requires Neural Function
SO JOURNAL OF NEUROENDOCRINOLOGY
LA English
DT Article
DE magnocellular system; microdialysis; oxytocin; vasopressin; microglia
ID RAT HYPOTHALAMUS; MAGNOCELLULAR NEURONS; MONOCLONAL-ANTIBODIES;
VASOPRESSIN RELEASE; RECEPTOR ANTAGONIST; SPINAL-CORD; IN-VITRO;
CHANNELS; BRAIN; CALCIUM
AB Interleukin (IL)-1 beta is present throughout the magnocellular neuroendocrine system and co-depletes with oxytocin and vasopressin from the neural lobe during salt-loading. To examine whether IL-1 beta is released from the dendrites/soma of magnocellular neurones during osmotic stimulation, microdialysis adjacent to the supraoptic nucleus (SON) in conscious rats was combined with immunocapillary electrophoresis and laser-induced fluorescence detection to quantify cytokine in 5-min dialysates collected before (0-180 min; basal), and after (180-240 min), hypertonic saline injected s.c. (1.5 M NaCl). Osmotic release of IL-1 beta was compared after inhibiting local voltage-gated channels for Na+ (tetrodotoxin) and Ca2+ (cadmium and nickel) or by reducing intracellular Ca2+ stores (thapsigargin). Immunohistochemistry combined with microdialysis was used to localise cytokine sources (IL-1 beta(+)) and microglia (OX-42(+)). Under conditions of microdialysis, the basal release of IL-1 beta(+) in the SON area was measurable and stable (pg/ml; mean +/- SEM) from 0-60 min (2.2 +/- 0.06), 60-120 min (2.32 +/- 0.05) and 120-180 min (2.33 +/- 0.06), likely originating locally from activated microglia (OX42(+); IL-1 beta(+); ameboid, hypertrophied) and magnocellular neurones expressing IL-1 beta. In response to osmotic stimulation, IL-1 beta increased progressively in dialysates of the SON area by a mechanism dependent on intracellular Ca2+ stores sensitive to thapsigargin and, similar to dendritic secretion of oxytocin and vasopressin, required local voltage-gated Na+ and Ca2+ channels for activation by osmoregulatory pathways from the forebrain. During osmotic stimulation, neurally dependent release of IL-1 beta in the SON area likely upregulates osmosensitive cation currents on magnocellular neurones (observed in vitro by others), to facilitate dendritic release of neurohypophysial hormones.
C1 [Summy-Long, J. Y.; Hu, S.; Long, A.] Penn State Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA.
[Phillips, T. M.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA.
RP Summy-Long, JY (reprint author), Penn State Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA.
EM jsl2@psu.edu
FU NIMH [R01-MH65271]
FX This research was supported by the NIMH (R01-MH65271 to J.S-L). The
authors appreciate technical support from Mindy Lull, Xiaofen Chen, Ann
Pruss, David Widitz and X. Wang. A portion of this research was
published previously as an abstract: Long, A., T. M. Phillips, X. Wang,
X. Chen, A. Pruss, K. Seaton and J. Y. Summy-Long. Basal and
osmotic-stimulated release of interleukin-1 beta from the supraoptic
nucleus: dependence on Na+ and Ca++ channels.
Programme No. 422.14. 2004 Abstract Viewer/Itinerary Planner;
Washington, DC: Society for Neuroscience.
NR 60
TC 6
Z9 6
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-8194
EI 1365-2826
J9 J NEUROENDOCRINOL
JI J. Neuroendocrinol.
PD NOV
PY 2008
VL 20
IS 11
BP 1224
EP 1232
DI 10.1111/j.1365-2826.2008.01783.x
PG 9
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 359VQ
UT WOS:000260016600002
PM 18752652
ER
PT J
AU Miura, K
Sugita, Y
Matsuura, K
Inaba, N
Kawano, K
Miles, FA
AF Miura, K.
Sugita, Y.
Matsuura, K.
Inaba, N.
Kawano, K.
Miles, F. A.
TI The Initial Disparity Vergence Elicited With Single and Dual Grating
Stimuli in Monkeys: Evidence for Disparity Energy Sensing and Nonlinear
Interactions
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID OCULAR-FOLLOWING RESPONSES; PURSUIT EYE-MOVEMENTS; RADIAL OPTIC FLOW;
OPPOSITE-CONTRAST STIMULI; VISUAL-CORTEX NEURONS; TAKE-ALL MECHANISM;
BINOCULAR DISPARITY; MACAQUE MONKEY; DEPTH-PERCEPTION; STRIATE CORTEX
AB Miura K, Sugita Y, Matsuura K, Inaba N, Kawano K, Miles FA. The initial disparity vergence elicited with single and dual grating stimuli in monkeys: evidence for disparity energy sensing and non-linear interactions. J Neurophysiol 100: 2907-2918, 2008. First published September 3, 2008; doi: 10.1152/jn.90535.2008. We recorded the initial vertical vergence eye movements elicited in monkeys at short latency (similar to 70 ms) when the two eyes see one-dimensional (1D) horizontal grating patterns that are identical except for a phase difference (disparity) of one-quarter wavelength. With gratings composed of single sine waves, responses were always compensatory, showing Gaussian dependence on log spatial frequency (on average: peak = 0.75 cycles/deg; SD = 0.74; r(2) = 0.980) and monotonic dependence on log contrast with a gradual saturation well described by the Naka-Rushton equation (on average: n = 0.89; C-50 = 4.1%; r(2) = 0.978). With gratings composed of two sine waves whose spatial frequencies were in the ratio 3: 5 and whose disparities were of opposite sign (the 3f5f stimulus), responses were determined by the disparities and contrasts of the two sine-wave components rather than the disparity of the features, consistent with early spatial filtering of the monocular inputs before their binocular combination and mediation by detectors sensitive to disparity energy. In addition, responses to the 3f5f stimulus showed a nonlinear dependence on the relative contrasts of the two sine waves. Thus on average, when the contrast of one sine wave was 2.3 times greater than that of the other, the one with the lower contrast was largely ineffective as though suppressed, and responses were determined almost entirely by the sine wave of higher contrast: Winner-Take-All. These findings are very similar to those published previously on the vertical vergence responses of humans, indicating that the monkey provides a good animal model for studying these disparity vergence responses.
C1 [Miura, K.; Sugita, Y.; Matsuura, K.; Inaba, N.; Kawano, K.] Kyoto Univ, Grad Sch Med, Dept Integrat Brain Sci, Kyoto 6068501, Japan.
[Sugita, Y.; Kawano, K.] Kyoto Univ, Nanomed Merger Educ Unit, Kyoto 6068501, Japan.
[Miles, F. A.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Miura, K (reprint author), Kyoto Univ, Grad Sch Med, Dept Integrat Brain Sci, Konoe Cho, Kyoto 6068501, Japan.
EM kmiura@brain.med.kyoto-u.ac.jp
OI Inaba, Naoko/0000-0002-0073-275X
FU Japan Society for the Promotion of Science [16GS0312]; Japan-U.S. Brain
Research Cooperative Program; Intramural Program of the National Eye
Institute at the National Institutes of Health
FX This work was supported by Grant-in-Aid for Scientific Research 16GS0312
from the Japan Society for the Promotion of Science, the Japan-U.S.
Brain Research Cooperative Program, and the Intramural Program of the
National Eye Institute at the National Institutes of Health.
NR 82
TC 6
Z9 6
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD NOV
PY 2008
VL 100
IS 5
BP 2907
EP 2918
DI 10.1152/jn.90535.2008
PG 12
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 370XE
UT WOS:000260795600041
PM 18768642
ER
PT J
AU Joiner, WM
Smith, MA
AF Joiner, Wilsaan M.
Smith, Maurice A.
TI Long-Term Retention Explained by a Model of Short-Term Learning in the
Adaptive Control of Reaching
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID SACCADIC EYE-MOVEMENTS; GROSS MOTOR SKILL; MEMORY; ADAPTATION; DYNAMICS;
CONSOLIDATION; CORTEX; MONKEY; PET
AB Joiner WM, Smith MA. Long-term retention explained by a model of short-term learning in the adaptive control of reaching. J Neurophysiol 100: 2948-2955, 2008. First published September 10, 2008; doi: 10.1152/jn.90706.2008. Extensive theoretical, psychophysical, and neurobiological work has focused on the mechanisms by which short-term learning develops into long-term memory. Better understanding of these mechanisms may lead to the ability to improve the efficiency of training procedures. A key phenomenon in the formation of long-term memory is the effect of over learning on retention discovered by Ebbinghaus in 1885: when the initial training period in a task is prolonged even beyond what is necessary for good immediate recall, long-term retention improves. Although this over learning effect has received considerable attention as a phenomenon in psychology research, the mechanisms governing this process are not well understood, and the ability to predict the benefit conveyed by varying degrees of over learning does not yet exist. Here we studied the relationship between the duration of an initial training period and the amount of retention 24 h later for the adaptation of human reaching arm movements to a novel force environment. We show that in this motor adaptation task, the amount of long-term retention is predicted not by the overall performance level achieved during the training period but rather by the level of a specific component process in a multi-rate model of short-term memory formation. These findings indicate that while multiple learning processes determine the ability to learn a motor adaptation, only one provides a gateway to long-term memory formation. Understanding the dynamics of this key learning process may allow for the rational design of training and rehabilitation paradigms that maximize the long-term benefit of each session.
C1 [Smith, Maurice A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Joiner, Wilsaan M.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Smith, MA (reprint author), Harvard Univ, Sch Engn & Appl Sci, 29 Oxford St,325 Pierce Hall, Cambridge, MA 02138 USA.
EM mas@seas.harvard.edu
FU Alfred P. Sloan Foundation; McKnight Endowment
FX This work was supported by Sloan Research Fellowship from the Alfred P.
Sloan Foundation and a Scholar Award from the McKnight Endowment for
Neuroscience to M. A. Smith.
NR 41
TC 65
Z9 65
U1 0
U2 8
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD NOV
PY 2008
VL 100
IS 5
BP 2948
EP 2955
DI 10.1152/jn.90706.2008
PG 8
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 370XE
UT WOS:000260795600045
PM 18784273
ER
PT J
AU Kontos, MC
Haney, A
Ornato, JP
Jesse, RL
Tatum, JL
AF Kontos, Michael C.
Haney, Anthony
Ornato, Joseph P.
Jesse, Robert L.
Tatum, James L.
TI Value of simultaneous functional assessment in association with acute
rest perfusion imaging for predicting short- and long-term outcomes in
emergency department patients with chest pain
SO JOURNAL OF NUCLEAR CARDIOLOGY
LA English
DT Article
DE Myocardial perfusion imaging; emergency department; chest pain
ID ACUTE MYOCARDIAL-INFARCTION; VENTRICULAR EJECTION FRACTION; ST-SEGMENT
ELEVATION; RISK STRATIFICATION; UNSTABLE ANGINA; HEART-FAILURE;
THROMBOLYTIC THERAPY; PROGNOSTIC VALUE; NORMAL LIMITS; WALL MOTION
AB Background. Rest tomographic myocardial perfusion imaging (MPI) has significant utility for clinical decision making in emergency department chest pain patients. The role of functional data, commonly acquired with perfusion, has not been systematically evaluated.
Methods and Results. Low- to moderate-risk patients undergoing rest MPI for risk stratification were included. The patients' MPI findings were classified as normal (normal perfusion or function), abnormal (perfusion defect with abnormal regional function), or discordant (perfusion defect with normal regional function). Ejection fraction was determined from the gated MPI studies. Events based on perfusion classifications and ejection fraction were evaluated. A total of 2,826 consecutive patients (abnormal MPI results in 40%, normal in 32%, and discordant in 27%) were studied. Outcomes were similar for those with normal MPI results versus those with discordant MPI results (myocardial infarction [MI] based on troponin I [TnI], 3.5% vs 4.0%; MI based on creatine kinase-MB, 1.5% vs 1.7%; revascularization, 5.2% vs 5.5%; and MI/revascularization based on TnI, 7.9% vs 8.1%) (P = not significant for all). Both groups had significantly fewer events (P <.001 for all) when compared with patients with abnormal MPI studies (MI based on TnI, 15%; MI based on creatine kinase-MB, 10%; revascularization, 17%; MI based on TnI or revascularization, 24%). The mortality rate was not different among the 3 groups. Multivariate analysis showed that mild/moderate and severe systolic dysfunction were independent predictors of 30-day and 1-year mortality rates (P.001).
Conclusions. The concurrent evaluation of perfusion and function (regional and global) with MPI provides significant risk/outcome predictive power. (J Nucl Cardiol 2008;15:774-82.)
C1 [Kontos, Michael C.; Haney, Anthony; Jesse, Robert L.] Virginia Commonwealth Univ, Dept Internal Med, Div Cardiol, Richmond, VA USA.
[Kontos, Michael C.; Ornato, Joseph P.] Virginia Commonwealth Univ, Dept Emergency Med, Richmond, VA USA.
[Kontos, Michael C.] Virginia Commonwealth Univ, Dept Radiol, Richmond, VA USA.
[Tatum, James L.] NCI, NIH, Bethesda, MD 20892 USA.
RP Kontos, MC (reprint author), Room 285 Gateway Bldg,2nd Floor,POB 980051,1200 E, Richmond, VA 23298 USA.
EM mkontos@mcvh-vcu.edu
NR 34
TC 11
Z9 11
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1071-3581
J9 J NUCL CARDIOL
JI J. Nucl. Cardiol.
PD NOV-DEC
PY 2008
VL 15
IS 6
BP 774
EP 782
DI 10.1016/j.nuclcard.2008.06.004
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 368TG
UT WOS:000260644800007
PM 18984452
ER
PT J
AU Radican, L
Blair, A
Stewart, P
Wartenberg, D
AF Radican, Larry
Blair, Aaron
Stewart, Patricia
Wartenberg, Daniel
TI Mortality of Aircraft Maintenance Workers Exposed to Trichloroethylene
and Other Hydrocarbons and Chemicals: Extended Follow-Up
SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID RETROSPECTIVE COHORT MORTALITY; OBSTRUCTIVE PULMONARY-DISEASE; CANCER
INCIDENCE; RESPIRATORY SYMPTOMS; AEROSPACE WORKERS; ORGANIC-SOLVENTS;
EPIDEMIOLOGY; FACILITY; SMOKING; RISK
AB Objective: To extend follow-up of 14,455 workers from 1990 to 2000, and evaluate mortality risk from exposure to trichloroethylene (TCE) and other chemicals. Methods: Multivariable Cox models were used to estimate relative risk (RR) for exposed versus unexposed workers based on previously developed exposure surrogates. Results: Among TCE-exposed workers, there was no statistically significant increased risk of all-cause mortality (RR = 1.04) or death from all cancers (RR = 1.03). Exposure-response gradients for TCE, were relatively flat and did not materially change since 1990. Statistically significant excesses were found for several chemical exposure subgroups and causes and were generally consistent with the previous follow-up. Conclusions: Patterns of mortality have not changed substantially since 1990. Although positive associations with several cancers were observed, and are consistent with the published literature, interpretation is limited due to the small numbers of events for specific exposures. (J Occup Environ Med. 2008;50:1306-1319)
C1 [Radican, Larry] Merck & Co Inc, Global Outcomes Res Dept, Whitehouse Stn, NJ 08889 USA.
[Blair, Aaron; Stewart, Patricia] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wartenberg, Daniel] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Environm & Occupat Med, Div Environm Epidemiol, Newark, NJ 07103 USA.
RP Radican, L (reprint author), Merck & Co Inc, Global Outcomes Res Dept, 1 Merck Dr, Whitehouse Stn, NJ 08889 USA.
EM larry_radican@merck.com
FU Intramural Research Program of the National Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (National Cancer Institute.
Division of Cancer Epidemiology and Genetics) and by an unrestricted
educational grant from Merck and Co.
NR 34
TC 19
Z9 19
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1076-2752
J9 J OCCUP ENVIRON MED
JI J. Occup. Environ. Med.
PD NOV
PY 2008
VL 50
IS 11
BP 1306
EP 1319
DI 10.1097/JOM.0b013e3181845f7f
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 372DC
UT WOS:000260880800012
PM 19001957
ER
PT J
AU Milner, J
Jensen, GL
AF Milner, John
Jensen, Gordon L.
TI The Best Is Yet to Come: The Future of Nutrition and Inflammation
Research
SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION
LA English
DT Article; Proceedings Paper
CT Intersociety Research Workshop on Nutrition and Inflammation
CY FEB 08-09, 2008
CL Chicago, IL
SP Amer Dietet Assoc, Amer Soc Nutr, Amer Soc Parenteral & Enteral Nutr, Obes Soc
C1 [Jensen, Gordon L.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Milner, John] NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Jensen, GL (reprint author), Penn State Univ, Dept Nutr Sci, 126 Henderson S, University Pk, PA 16802 USA.
NR 0
TC 2
Z9 2
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0148-6071
J9 JPEN-PARENTER ENTER
JI J. Parenter. Enter. Nutr.
PD NOV-DEC
PY 2008
VL 32
IS 6
BP 667
EP 668
DI 10.1177/0148607108325250
PG 2
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 365YU
UT WOS:000260446800015
PM 18974250
ER
PT J
AU De Ravin, SS
Shum, E
Zarember, KA
Rezvani, G
Rosenfeld, RG
Stratakis, CA
Malech, HL
AF De Ravin, Suk See
Shum, Elaine
Zarember, Kol A.
Rezvani, Geoffrey
Rosenfeld, Ron G.
Stratakis, Constantine A.
Malech, Harry L.
TI Short Stature in Partially Corrected X-linked Severe Combined
Imniunodeficiency - Suboptimal Response to Growth Hormone
SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
LA English
DT Article
DE X-linked severe combined immunodeficiency; growth hormone; IGF-I; gamma
c; short stature
ID SEVERE COMBINED IMMUNODEFICIENCY; BONE-MARROW-TRANSPLANTATION; IMMUNE
RECONSTITUTION; GENE-THERAPY; GAMMA-CHAIN; GH; PHENOTYPE; PATIENT
AB Background: X-linked severe combined immunodeficiency (XSCID) results from defects in the common cytokine receptor gamma chain (gamma c) required for signaling by receptors for interleukin (IL)-2, -4, -7, -9, -15, and -21(1). Following haploidentical bone marrow transplant without myelo-conditioning for XSCID, most patients achieve partial reconstitution 2 often limited to T lymphocytes. Many partially corrected patients manifest extreme short stature (< 5(th) percentile). Previous reports have implicated gamma c in growth hormone (GH) receptor signaling, thus severe growth failure in XSCID may be related to the underlying ye defect.
Aim: To evaluate the GH/insulin-like growth factor-I (IGF-I) axis in three children with XSCID and partial immune reconstitution with profound growth failure.
Methods: The IGF-I generation test was performed by administering recombinant GH subcutaneously for 5 days, and measuring serum levels for IGF-I before GH injection, and on days 5 and 8.
Results: Study of the somatotropic axis revealed profoundly diminished IGF-I production following rGH challenge in all three patients.
Conclusion: The data indicate that the GH/IGF-I axis in these partially corrected XSCID patients with severe short stature is profoundly impaired, and supports previous studies suggesting that the underlying gamma c defect may contribute to the severe growth failure in XSCID. This supports a role for defective gamma c in the extreme short stature of XSCID, and raises the possibility of recombinant IGF-I treatment to bypass this defect.
C1 [De Ravin, Suk See] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Rezvani, Geoffrey; Stratakis, Constantine A.] NICHD, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD 20892 USA.
[Rosenfeld, Ron G.] NICHD, Lucile Packard Fdn Childrens Hlth, NIH, Bethesda, MD 20892 USA.
[Stratakis, Constantine A.] NICHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
RP De Ravin, SS (reprint author), NIAID, Host Def Lab, NIH, Bldg 10-CRC,Room 5-3816,10 Ctr Dr, Bethesda, MD 20892 USA.
EM sderavin@niaid.nih.gov
FU NIH [Z01-HD-00064204]; National Institute of Allergy and Infectious
Diseases; NICHD
FX This project was supported by the Intramural Research Program of the
NIH, National Institute of Allergy and Infectious Diseases, and, in
part, by NICHD, NIH intramural project Z01-HD-00064204 to Dr. C.A.
Stratakis. We have no other financial relationships to disclose.
NR 23
TC 2
Z9 2
U1 0
U2 0
PU FREUND PUBLISHING HOUSE LTD
PI TEL AVIV
PA PO BOX 35010, TEL AVIV 61350, ISRAEL
SN 0334-018X
J9 J PEDIATR ENDOCR MET
JI J. Pediatr. Endocrinol. Metab.
PD NOV
PY 2008
VL 21
IS 11
BP 1057
EP 1063
PG 7
WC Endocrinology & Metabolism; Pediatrics
SC Endocrinology & Metabolism; Pediatrics
GA 388KN
UT WOS:000262018800006
PM 19189700
ER
PT J
AU Hamilton, FA
AF Hamilton, Frank A.
TI NIH Funding Opportunities for Functional Bowel Disorders in the
Pediatric Age Group
SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
LA English
DT Article; Proceedings Paper
CT Symposium on New Insights into Children Functional Abdominal Pain and
Irritable Bowel Syndrome
CY OCT 24, 2007
CL Salt Lake City, UT
SP NASPGHAN
ID GASTROINTESTINAL DISORDERS; ABDOMINAL-PAIN; CHILDREN
C1 NIDDK, Digest Dis Program, NIH, Div Digest Dis & Nutr, Bethesda, MD 20892 USA.
RP Hamilton, FA (reprint author), NIDDK, Digest Dis Program, NIH, Div Digest Dis & Nutr, 6707 Democracy Blvd,Room 669, Bethesda, MD 20892 USA.
EM fh14c@nih.gov
NR 8
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2008
VL 47
IS 5
BP 709
EP 711
PG 3
WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
GA 366YL
UT WOS:000260519400040
PM 18955887
ER
PT J
AU Varma, S
Jenkins, T
Wendler, D
AF Varma, Sumeeta
Jenkins, Tammara
Wendler, David
TI How do Children and Parents Make Decisions About Pediatric Clinical
Research?
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Article
DE assent; research; permission
ID ASSENT; PARTICIPATION; PROTECTION; UNDERSTAND; PERMISSION; TRIALS
AB Little is known about how children and parents make decisions regarding pediatric research. To provide data, we surveyed children aged 7 to 14 years who were enrolled in clinical research or receiving clinical care for cancer or asthma at one of 7 sites. and a parent or guardian. The present manuscript reports data on the respondents' attitudes and experiences regarding the child's involvement in making clinical care and research decisions. Of 117 parent-child pairs invited to participate. 81 completed the survey (response rate = 69.2%). Pediatric respondents reported that their decisions regarding research enrollment were influenced primarily by I desire to benefit themselves. and to help others. In the research group, 90.5% of pediatric respondents believed they should be involved in making research enrollment decisions. whereas only 61.5% of the adult respondents believed children Should be involved in making these decisions. These findings highlight the potential for disagreement within families regarding children's involvement in making decisions about research enrollment. Investigators should be aware of and find ways to address these disagreements when soliciting assent from children.
C1 [Varma, Sumeeta; Wendler, David] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
[Jenkins, Tammara] NICHHD, Pediat Crit Care & Rehabil Res Program, Bethesda, MD 20892 USA.
RP Wendler, D (reprint author), NIH, Ctr Clin, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM dwendler@nih.gov
NR 21
TC 15
Z9 15
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1077-4114
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD NOV
PY 2008
VL 30
IS 11
BP 823
EP 828
DI 10.1097/MPH.0b013e318180bc0d
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 369XK
UT WOS:000260727000007
PM 18989159
ER
PT J
AU Wallis, D
Russell, HF
Muenke, M
AF Wallis, Deeann
Russell, Heather F.
Muenke, Maximilian
TI Review: Genetics of Attention Deficit/Hyperactivity Disorder
SO JOURNAL OF PEDIATRIC PSYCHOLOGY
LA English
DT Review
DE ADHD; association studies; DAT1; DRD4; genetics; linkage analysis
ID DEFICIT HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENE;
CATECHOL-O-METHYLTRANSFERASE; ADOLESCENT FEMALE TWINS; LATENT CLASS
ANALYSIS; CONDUCT DISORDER; RECEPTOR GENE; ADHD SYMPTOMS; PREFERENTIAL
TRANSMISSION; ENVIRONMENT INTERACTIONS
AB Objective The intent of this review is to provide an overview for the practicing psychologist/psychiatrist regarding the complexities of and the most recent advances made in the study of the genetic basis of attention-deficit/hyperactivity disorder (ADHD).
Methods We review a variety of concepts including: (a) complexities involved in studying the genetics of ADHD, (b) evidence for a primarily genetic component of ADHD, (c) evidence suggesting that there are only a few genes with major effects contributing to ADHD, (d) identification of the best candidate genes, (e) linkage analysis for the identification of novel candidate genes, and (f) data on geneenvironment interactions.
Results It is now generally accepted that ADHD has a biological and even primarily genetic basis. However, despite the identification of several candidate genes, none of them seems to have a substantial effect and the exact etiology underlying ADHD has remained elusive. Genome-wide linkage analysis can help in the identification of novel candidate genes. While several independent groups have initiated these studies, we await further details and specific genes from fine-mapping studies. Most recently, researchers have been trying to identify gene by environment interactions to help understand ADHD. Replication of positive findings will be essential in teasing out these combinatorial influences.
Conclusions Ideally, one day specific genes with major effects and specific risk factors with which they interact will be identified and we will be able to implement personalized medicine. Knowledge of such genes will allow us to identify specific diagnostic biological markers. In addition, defining the target genes is the first step in developing novel drug therapies to treat the ADHD symptoms that lead to impairment. Furthermore, such markers could also identify at risk individuals at a younger age in order to implement treatments sooner to decrease the severity of ADHD symptoms or even to prevent future ADHD symptomatology.
C1 [Wallis, Deeann] Texas Inst Genom Med, Houston, TX 77030 USA.
[Wallis, Deeann; Muenke, Maximilian] NIH, Med Genet Branch, NHGRI, Bethesda, MD 20892 USA.
[Russell, Heather F.] Shriners Hosp Children Philadelphia, Philadelphia, PA USA.
RP Wallis, D (reprint author), Texas Inst Genom Med, 2121W Holcombe Blvd, Houston, TX 77030 USA.
EM dwallis@tigm.org
NR 112
TC 48
Z9 48
U1 9
U2 16
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0146-8693
J9 J PEDIATR PSYCHOL
JI J. Pediatr. Psychol.
PD NOV-DEC
PY 2008
VL 33
IS 10
BP 1085
EP 1099
DI 10.1093/jpepsy/jsn049
PG 15
WC Psychology, Developmental
SC Psychology
GA 367NB
UT WOS:000260557600003
PM 18522996
ER
PT J
AU Haerynck, F
Holland, SM
Rosenzweig, SD
Casanova, JL
Schelstraete, P
De Baets, F
AF Haerynck, Filomeen
Holland, Steve M.
Rosenzweig, Sergio D.
Casanova, Jean-Laurent
Schelstraete, Petra
De Baets, Frans
TI Disseminated Mycobacterium avium Infection in a Patient with a Novel
Mutation in the Interleukin-12 Receptor-beta 1 Chain
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID MENDELIAN SUSCEPTIBILITY; DEFICIENCY
AB A girl with relapsing cervical lymphadenopathy due to Mycobacterium avium subsequently developed abdominal endenopathy and intestinal inflammation. 1 known (c.1623_1624delGCinsTT) and 1 novel mutation (c.65_68delCTGC of exons2) of the Interleukin-12 Receptor-beta 1 (IL-12R beta 1) gene was detected. Unlike reports of a more favorable outcome in these patients, our patient died of severe intestinal involvement. (J Pediatr 2008;153:721-2)
C1 [Haerynck, Filomeen; Schelstraete, Petra; De Baets, Frans] Ghent Univ Hosp, Dept Pediat Pulmonol & Immunol, B-9000 Ghent, Belgium.
[Holland, Steve M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Rosenzweig, Sergio D.] Hosp Nacl Pediat, Serv Immunol, Buenos Aires, DF, Argentina.
[Casanova, Jean-Laurent] Univ Paris 05, Lab Human Genet Infect Dis, INSERM, U550, Paris, France.
Univ Paris 05, Hop Necker Enfants Malad, Unite Clin Immunol & Hematol Pediat, Paris, France.
RP Haerynck, F (reprint author), Ghent Univ Hosp, Dept Pediat Pulmonol & Immunol, Pintelaan 185, B-9000 Ghent, Belgium.
EM filomeen.haerynck@Ugent.be
NR 9
TC 12
Z9 12
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR
JI J. Pediatr.
PD NOV
PY 2008
VL 153
IS 5
BP 721
EP 722
DI 10.1016/j.jpeds.2008.05.050
PG 2
WC Pediatrics
SC Pediatrics
GA 372EC
UT WOS:000260883600035
PM 18940359
ER
PT J
AU Mazaki-Tovi, S
Romero, R
Kusanovic, JP
Erez, O
Gotsch, F
Mittal, P
Than, NG
Nhan-Chang, CL
Hamill, N
Vaisbuch, E
Chaiworapongsa, T
Edwin, SS
Nien, JK
Gomez, R
Espinoza, J
Kendal-Wright, C
Hassan, SS
Bryant-Greenwood, G
AF Mazaki-Tovi, Shali
Romero, Roberto
Kusanovic, Juan Pedro
Erez, Offer
Gotsch, Francesca
Mittal, Pooja
Than, Nandor Gabor
Nhan-Chang, Chia-Lang
Hamill, Neil
Vaisbuch, Edi
Chaiworapongsa, Tinnakorn
Edwin, Samuel S.
Nien, Jyh Kae
Gomez, Ricardo
Espinoza, Jimmy
Kendal-Wright, Claire
Hassan, Sonia S.
Bryant-Greenwood, Gillian
TI Visfatin/Pre-B cell colony-enhancing factor in amniotic fluid in normal
pregnancy, spontaneous labor at term, preterm labor and prelabor rupture
of membranes: an association with subclinical intrauterine infection in
preterm parturition
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Review
DE Microbial invasion of the amniotic cavity (MIAC); pre-B cell
colony-enhancing factor (PBEF); preterm labor; preterm prelabor rupture
of membranes (preterm PROM); visfatin
ID TUMOR-NECROSIS-FACTOR; DIFFERENTIALLY EXPRESSED GENES; GESTATIONAL
DIABETES-MELLITUS; HUMAN FETAL MEMBRANES; NF-KAPPA-B; VASCULAR
ENDOTHELIAL-CELLS; MESSENGER-RNA EXPRESSION; SMOOTH-MUSCLE-CELLS;
PREMATURE RUPTURE; INTRAAMNIOTIC INFECTION
AB Objective: Visfatin, a novel adipokine originally discovered as a pre-B-cell colony enhancing factor, is expressed by amniotic epithelium, cytotrophoblast, and decidua and is over-expressed when fetal membranes are exposed to mechanical stress and/or pro-inflammatory stimuli. Visfatin expression by fetal membranes is dramatically up-regulated after normal spontaneous labor. The aims of this study were to determine if visfatin is detectable in amniotic fluid (AF) and whether its concentration changes with gestational age, spontaneous labor, preterm prelabor rupture of membranes (preterm PROM) and in the presence of microbial invasion of the amniotic cavity (MIAC).
Methods: In this cross-sectional study, visfatin concentration in AF was determined in patients in the following groups: 1) mid-trimester (n=75); 2) term not in labor (n=27); 3) term in spontaneous labor (n=51); 4) patients with preterm labor with intact membranes (PTL) without MIAC who delivered at term (n=35); 5) patients with PTL without MIAC who delivered preterm (n=52); 6) patients with PTL with MIAC (n=25); 7) women with preterm PROM without MIAC (n=26); and 8) women with preterm PROM with MIAC (n=26). Non-parametric statistics were used for analysis.
Results: 1) The median AF concentration of visfatin was significantly higher in patients at term than in mid-trimester; 2) Among women with PTL who delivered preterm, the median visfatin concentration was significantly higher in patients with MIAC than those without MIAC; 3) Similarly, patients with PTL and MIAC had a higher median AF visfatin concentration than those with PTL who delivered at term; 4) Among women with preterm PROM, the median AF visfatin concentration was significantly higher in patients with MIAC than those without MIAC.
Conclusions: 1) Visfatin is a physiologic constituent of AF; 2) The concentration of AF visfatin increases with advancing gestational age; 3) AF visfatin concentration is elevated in patients with MIAC, regardless of the membrane status, suggesting that visfatin participates in the host response against infection.
C1 [Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Mittal, Pooja; Than, Nandor Gabor; Nhan-Chang, Chia-Lang; Hamill, Neil; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Edwin, Samuel S.; Espinoza, Jimmy; Hassan, Sonia S.] NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS,Hutzel Womens Hospital, Detroit, MI 48201 USA.
[Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Mittal, Pooja; Than, Nandor Gabor; Nhan-Chang, Chia-Lang; Hamill, Neil; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Edwin, Samuel S.; Espinoza, Jimmy; Hassan, Sonia S.] NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS,Hutzel Womens Hospital, Bethesda, MD USA.
[Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Erez, Offer; Mittal, Pooja; Nhan-Chang, Chia-Lang; Hamill, Neil; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Espinoza, Jimmy; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Nien, Jyh Kae; Gomez, Ricardo] Pontificia Univ Catolica Chile, Hosp Sotero Rio, Ctr Perinatal Diag & Res CEDIP, Puente Alto, Chile.
[Kendal-Wright, Claire; Bryant-Greenwood, Gillian] Univ Hawaii, John A Burns Sch Med, Dept Obstet Gynecol & Womens Hlth, Honolulu, HI 96822 USA.
RP Romero, R (reprint author), NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS,Hutzel Womens Hospital, Box 4,3990 John R, Detroit, MI 48201 USA.
EM nichdprbchiefstaff@mail.nih.gov
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; NIH; DHHS
FX This research was supported in part by the Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, NIH, DHHS.
NR 136
TC 55
Z9 55
U1 0
U2 5
PU WALTER DE GRUYTER & CO
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
J9 J PERINAT MED
JI J. Perinat. Med.
PD NOV
PY 2008
VL 36
IS 6
BP 485
EP 496
DI 10.1515/JPM.2008.084
PG 12
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 381CK
UT WOS:000261512500003
PM 18598235
ER
PT J
AU Park, CW
Lee, SM
Park, JS
Jun, JK
Romero, R
Yoon, BH
AF Park, Chan-Wook
Lee, Seung Mi
Park, Joong Shin
Jun, Jong Kwan
Romero, Roberto
Yoon, Bo Hyun
TI The antenatal identification of funisitis with a rapid MMP-8 bedside
test
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article
DE bedside test; chorioamnionitis; funisitis; MMP-8; preterm gestation
ID FLUID MATRIX METALLOPROTEINASE-8; INFLAMMATORY RESPONSE SYNDROME;
PRETERM PREMATURE RUPTURE; INTRAAMNIOTIC INFLAMMATION; POLYMORPHONUCLEAR
LEUKOCYTES; CLINICAL-SIGNIFICANCE; INTACT MEMBRANES; COLLAGENASE;
INFECTION; LABOR
AB Aims: The purpose of this study was to determine if a bedside test, the MMP-8 PTD Check (TM), can be of value in the antenatal identification of funisitis. This test can be performed in 15 min without any laboratory equipment.
Methods: The relationship between the presence or absence of funisitis and the results of an MMP-8 PTD Check (TM) was examined in 139 patients who delivered preterm singleton neonates (gestational age <35 weeks) within 72 h of amniocentesis. Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and for genital mycoplasmas. AF was analyzed for white blood cell (WBC) count, interleukin-6 (IL-6) and an MMP-8 PTD Check (TM). The IL-6 concentration was also determined in umbilical cord plasma collected at birth. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton's jelly.
Results: 1) Funisitis was present in 27% (38/139) of cases; 2) A positive MMP-8 PTD Check (TM) had a sensitivity of 97% (37/38), a specificity of 63% (64/101), a positive predictive value of 50% (37/74) and a negative predictive value of 99% (64/65) in the identification of funisitis; 3) Among cases without funisitis, patients with a positive MMP-8 PTD Check (TM) had a significantly higher median AF IL-6 concentration, AF WBC count, and umbilical cord plasma IL-6 concentration at birth than those with a negative MMP-8 PTD Check (TM) (P<0.05 for each).
Conclusions: The MMP-8 PTD Check (TM) is a rapid, simple and sensitive bedside test which allows assessment of the risk of funisitis.
C1 [Park, Chan-Wook; Lee, Seung Mi; Park, Joong Shin; Jun, Jong Kwan; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.
[Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.
[Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.
EM Yoonbh@snu.ac.kr
RI Jun, Jong Kwan/D-5776-2012; Yoon, Bo Hyun/H-6344-2011; Park,
Chan-Wook/J-5498-2012;
OI Jun, Jong Kwan/0000-0002-0242-1736; Park, Joong Shin/0000-0002-5246-0477
FU Intramural NIH HHS [Z01 HD002400-16]
NR 24
TC 31
Z9 31
U1 0
U2 1
PU WALTER DE GRUYTER & CO
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
J9 J PERINAT MED
JI J. Perinat. Med.
PD NOV
PY 2008
VL 36
IS 6
BP 497
EP 502
DI 10.1515/JPM.2008.079
PG 6
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 381CK
UT WOS:000261512500004
PM 19127606
ER
PT J
AU Cheung, C
Gonzalez, FJ
AF Cheung, Connie
Gonzalez, Frank J.
TI Humanized Mouse Lines and Their Application for Prediction of Human Drug
Metabolism and Toxicological Risk Assessment
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID PROLIFERATOR-ACTIVATED RECEPTOR; PREGNANE-X-RECEPTOR; HEPATIC
CYTOCHROME-P450 3A4; TRANSGENIC MICE; PPAR-ALPHA; SPECIES-DIFFERENCES;
GENE-EXPRESSION; HUMAN LIVER; PEROXISOME PROLIFERATORS; HETEROCYCLIC
AMINES
AB Cytochrome P450s (P450s) are important enzymes involved in the metabolism of xenobiotics, particularly clinically used drugs, and are also responsible for metabolic activation of chemical carcinogens and toxins. Many xenobiotics can activate nuclear receptors that in turn induce the expression of genes encoding xenobiotic metabolizing enzymes and drug transporters. Marked species differences in the expression and regulation of cytochromes P450 and xenobiotic nuclear receptors exist. Thus, obtaining reliable rodent models to accurately reflect human drug and carcinogen metabolism is severely limited. Humanized transgenic mice were developed in an effort to create more reliable in vivo systems to study and predict human responses to xenobiotics. Human P450s or human xenobiotic-activated nuclear receptors were introduced directly or replaced the corresponding mouse gene, thus creating "humanized" transgenic mice. Mice expressing human CYP1A1/CYP1A2, CYP2E1, CYP2D6, CYP3A4, CY3A7, pregnane X receptor, and peroxisome proliferator-activated receptor alpha were generated and characterized. These humanized mouse models offer a broad utility in the evaluation and prediction of toxicological risk that may aid in the development of safer drugs.
C1 [Cheung, Connie; Gonzalez, Frank J.] Natl Canc Inst, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gonzalez, FJ (reprint author), Natl Canc Inst, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 3106,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
FU Intramural NIH HHS [Z01 BC005562-20]
NR 70
TC 73
Z9 74
U1 0
U2 6
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD NOV
PY 2008
VL 327
IS 2
BP 288
EP 299
DI 10.1124/jpet.108.141242
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 361YZ
UT WOS:000260166000001
PM 18682571
ER
PT J
AU Scherma, M
Panlilio, LV
Fadda, P
Fattore, L
Gamaleddin, I
Le Foll, B
Justinova, Z
Mikics, E
Haller, J
Medalie, J
Stroik, J
Barnes, C
Yasar, S
Tanda, G
Piomelli, D
Fratta, W
Goldberg, SR
AF Scherma, Maria
Panlilio, Leigh V.
Fadda, Paola
Fattore, Liana
Gamaleddin, Islam
Le Foll, Bernard
Justinova, Zuzana
Mikics, Eva
Haller, Jozsef
Medalie, Julie
Stroik, Jessica
Barnes, Chanel
Yasar, Sevil
Tanda, Gianluigi
Piomelli, Daniele
Fratta, Walter
Goldberg, Steven R.
TI Inhibition of Anandamide Hydrolysis by Cyclohexyl Carbamic Acid 3
'-Carbamoyl-3-yl Ester (URB597) Reverses Abuse-Related Behavioral and
Neurochemical Effects of Nicotine in Rats
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article; Proceedings Paper
CT 37th Annual Meeting of the Society-for-Neuroscience
CY NOV 03-07, 2007
CL San Diego, CA
SP Soc Neurosci
ID ENDOGENOUS CANNABINOID ANANDAMIDE; VENTRAL TEGMENTAL AREA; CONDITIONED
PLACE PREFERENCES; ANTIDEPRESSANT-LIKE ACTIVITY;
ACETYLCHOLINE-RECEPTORS; NUCLEUS-ACCUMBENS; OLEOYLETHANOLAMIDE;
ENDOCANNABINOIDS; ANTAGONIST; ACTIVATION
AB Emerging evidence suggests that the rewarding, abuse-related effects of nicotine are modulated by the endocannabinoid system of the brain. For example, pharmacological blockade or genetic deletion of cannabinoid CB1 receptors can reduce or eliminate many abuse-related behavioral and neurochemical effects of nicotine. Furthermore, doses of Delta(9)-tetrahydrocannabinol and nicotine that are ineffective when given alone can induce conditioned place preference when given together. These previous studies have used systemically administered CB1 receptor agonists and antagonists and gene deletion techniques, which affect cannabinoid CB1 receptors throughout the brain. A more functionally selective way to alter endocannabinoid activity is to inhibit fatty acid amide hydrolase (FAAH), thereby magnifying and prolonging the effects of the endocannabinoid anandamide only when and where it is synthesized and released on demand. Here, we combined behavioral and neurochemical approaches to evaluate whether the FAAH inhibitor URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester) could alter the abuse-related effects of nicotine in rats. We found that URB597, at a dose (0.3 mg/kg) that had no behavioral effects by itself, prevented development of nicotine-induced conditioned place preference (CPP) and acquisition of nicotine self-administration. URB597 also reduced nicotine-induced reinstatement in both CPP and self-administration models of relapse. Furthermore, in vivo microdialysis showed that URB597 reduced nicotine-induced dopamine elevations in the nucleus accumbens shell, the terminal area of the brain's mesolimbic reward system. These findings suggest that FAAH inhibition can counteract the addictive properties of nicotine and that FAAH may serve as a new target for development of medications for treatment of tobacco dependence.
C1 [Scherma, Maria; Fadda, Paola; Fratta, Walter] Univ Cagliari, Bb Brodie Dept Neurosci, I-09124 Cagliari, Italy.
[Fattore, Liana] Inst Neurosci, CNR, Cagliari, Italy.
[Gamaleddin, Islam; Le Foll, Bernard] Univ Toronto, Translat Addict Res Lab, Toronto, ON, Canada.
[Le Foll, Bernard] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
[Mikics, Eva; Haller, Jozsef] Hungarian Acad Sci, Inst Expt Med, Budapest, Hungary.
[Yasar, Sevil] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA.
[Piomelli, Daniele] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92717 USA.
[Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch,Biomed Res Ctr 05A711, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Tanda, Gianluigi] Natl Inst Drug Abuse, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
RP Goldberg, SR (reprint author), Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch,Biomed Res Ctr 05A711, Intramural Res Program,NIH,Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sgoldber@mail.nih.gov
RI Tanda, Gianluigi/B-3318-2009; Justinova, Zuzana/A-9109-2011; Le Foll,
Bernard/K-2952-2014;
OI Tanda, Gianluigi/0000-0001-9526-9878; Justinova,
Zuzana/0000-0001-5793-7484; Le Foll, Bernard/0000-0002-6406-4973; FADDA,
PAOLA/0000-0002-0642-6710; Haller, Jozsef/0000-0002-1953-3726
FU Intramural NIH HHS [Z01 DA000003-22, Z99 DA999999]; NIDA NIH HHS [N01
DA059909]
NR 45
TC 74
Z9 75
U1 1
U2 5
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD NOV
PY 2008
VL 327
IS 2
BP 482
EP 490
DI 10.1124/jpet.108.142224
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 361YZ
UT WOS:000260166000021
PM 18725543
ER
PT J
AU Jia, L
Noker, PE
Piazza, GA
Leuschner, C
Hansel, W
Gorman, GS
Coward, LU
Tomaszewski, J
AF Jia, Lee
Noker, Patricia E.
Piazza, Gary A.
Leuschner, Carola
Hansel, William
Gorman, Gregory S.
Coward, Lori U.
Tomaszewski, Joseph
TI Pharmacokinetics and pharmacodynamics of Phor21-beta CG(ala), a lytic
peptide conjugate
SO JOURNAL OF PHARMACY AND PHARMACOLOGY
LA English
DT Article
ID LUTEINIZING-HORMONE RECEPTORS; PROSTATE-CANCER CELLS; CG-BETA CONJUGATE;
IN-VITRO; TARGETED DESTRUCTION; DRUG-METABOLISM; LUCIFERASE GENE;
BREAST; VIVO; XENOGRAFTS
AB Phor21-beta CG(ala), a 36-amino acid peptide comprised of a lytic peptide (Phor21) conjugated to a modified 15-amino acid segment of the beta-chain of chorionic gonadotropin (beta CG(ala)), selectively kills cancer cells that over-express luteinizing hormone/chorionic gonadotropin (LH/CG) receptors by disrupting cellular membrane structure. These studies were designed to further characterize its in-vitro inhibition and in-vivo destruction of prostate cancer cells, biostability and pharmacokinetics to determine its pharmacokinetic and pharmacodynamic profile. Inhibitory effects of Phor21-beta CG(ala) were tested in PC-3 and Caco-2 cells as well as in nude mice bearing PC-3 cells transfected with the luciferase gene (PC-3.luc). Plasma stability, protease hydrolysis and pharmacokinetics of Phor21-beta CG(ala) were measured by using liquid chromatography mass spectrometry (LC/MS/MS). Phor21-beta CG(ala) selectively inhibited proliferation in-vitro and in-vivo metastases of PC-3 cells. Phor21-beta CG(ala) was relatively stable in mouse, rat, dog and human plasma. Its degradation was partially due to protease hydrolysis and thermodynamic catalysis. Intravenous administration of Phor21-beta CG(ala) showed its blood C-max and AUC(0 ->infinity) around the in-vitro effective levels. In the tested rodents, Phor21-beta CG(ala) displayed a moderate volume of distribution at steady state (Vd(ss)) and slow clearance (Cl) in the rodents. In conclusion, Phor21-beta CG(ala) displayed promising in-vitro and in-vivo anti-cancer activity with favourable pharmacokinetics, and may offer a novel approach to metastatic cancer chemotherapy.
C1 [Jia, Lee] NCI, NIH, Rockville, MD 20852 USA.
[Noker, Patricia E.; Piazza, Gary A.; Gorman, Gregory S.; Coward, Lori U.] So Res Inst, Birmingham, AL 35255 USA.
[Leuschner, Carola; Hansel, William] Pennington Biomed Res Ctr, Baton Rouge, LA USA.
RP Jia, L (reprint author), NCI, NIH, 6130 Execut Blvd,Rm 8042, Rockville, MD 20852 USA.
EM jiale@mail.nih.gov
FU Gordon and Mary Cain Foundation; Department of Defense
[DAMD-17-03-1-0150]; National Cancer Institute. [N01-CM-07110]
FX Funding: The studies were supported by Gordon and Mary Cain Foundation,
Grant #DAMD-17-03-1-0150 from the Department of Defense, and Contract
No. N01-CM-07110 from the National Cancer Institute.
NR 26
TC 7
Z9 7
U1 0
U2 3
PU PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN
PI LONDON
PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND
SN 0022-3573
J9 J PHARM PHARMACOL
JI J. Pharm. Pharmacol.
PD NOV
PY 2008
VL 60
IS 11
BP 1441
EP 1448
DI 10.1211/jpp.60.11.0004
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 372SG
UT WOS:000260921500004
PM 18957164
ER
PT J
AU Crespo, CJ
Garcia-Palmieri, MR
Smit, E
Lee, IM
McGee, D
Muti, P
Valle, NRF
Ramirez-Marrero, FA
Freudenheim, JL
Sorlie, P
AF Crespo, Carlos J.
Garcia-Palmieri, Mario R.
Smit, Ellen
Lee, I-Min
McGee, Daniel
Muti, Paola
Valle, Nayda R. Figueroa
Ramirez-Marrero, Farah A.
Freudenheim, Jo L.
Sorlie, Paul
TI Physical Activity and Prostate Cancer Mortality in Puerto Rican Men
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE cancer; epidemiology; physical activity; mortality; chronic disease
AB Studies on the association between physical activity and fatal prostate cancer have produced inconclusive results. The Puerto Rico Heart Health Program was a cohort study of a randomly selected sample of 9824 men age 35 to 79 years at baseline who were followed for mortality until 2002. Multiple examinations collected information on lifestyle, diet, body composition, exercise, urban-rural residence, and smoking habits. Physical activity status was measured using the Framingham Physical Activity Index, an assessment of occupational, leisure-time, and other physical activities measured as usual activity over the course of a 24-hour day. Physical activity was stratified into quartiles. Multivariate logistic regression analysis was used to assess the association of physical activity with prostate cancer mortality. Other covariates included age, education, urban-rural residence, smoking, and body mass index. Compared with the lowest level of physical activity (Q1), the risk of prostate cancer mortality was OR = 0.99 (95% CI = 0.64-1.55) for Q2, OR = 1.34 (95% CI = 0.88-2.05) for Q3, and OR = 1.19 (95% CI = 0.75-1.90) for Q4. Further analyses by age group, overweight status, or vigorous physical activity also did not show a significant association between physical activity and prostate cancer mortality. Physical activity did not predict prostate cancer mortality in this group of Puerto Rican men.
C1 [Crespo, Carlos J.; Smit, Ellen] Portland State Univ, Sch Community Hlth, Portland, OR 97207 USA.
[Garcia-Palmieri, Mario R.; Valle, Nayda R. Figueroa; Ramirez-Marrero, Farah A.] Univ Puerto Rico, San Juan, PR 00936 USA.
[Lee, I-Min; Muti, Paola] Harvard Univ, Sch Med, Boston, MA 02446 USA.
[McGee, Daniel] Florida State Univ, Dept Stat, Tallahassee, FL 32306 USA.
[Muti, Paola] Italian Natl Canc Inst, Rome, Italy.
[Freudenheim, Jo L.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Sorlie, Paul] NHLBI, Bethesda, MD 20892 USA.
RP Crespo, CJ (reprint author), Portland State Univ, Sch Community Hlth, Portland, OR 97207 USA.
FU NCI NIH HHS [1P20CA96256-01A1, 1R03 CA103475-01]
NR 64
TC 2
Z9 3
U1 0
U2 3
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 NOV
PY 2008
VL 5
IS 6
BP 918
EP 929
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA V18PB
UT WOS:000208015600012
PM 19164825
ER
PT J
AU Oermann, MH
Nordstrom, CK
Ineson, V
Wilmes, NA
AF Oermann, Marilyn H.
Nordstrom, Cheryl K.
Ineson, Vicki
Wilmes, Nancy A.
TI WEB CITATIONS IN THE NURSING LITERATURE: HOW ACCURATE ARE THEY?
SO JOURNAL OF PROFESSIONAL NURSING
LA English
DT Article
DE Web citation; References; Nursing literature; Citation analysis
ID EPISTEMIC ORIGINS; COMMUNICATION; INTERNET; JOURNALS
AB One problem with using Web citations is whether those documents will be available over time. We examined 573 Web citations in articles published in nursing journals and checked their availability (either by direct link or by searching the main site). There was a mean of 3.1 Web citations per article. Most Web citations were to documents that related to clinical practice, for example, clinical guidelines and explanations of clinical conditions and treatments. Of the 573 Web citations, 414 (72.3%) were still available; of those, 229 (55.3%) were able to be accessed by direct link and the other 185 (44.7%) by searching the main Web site. However, 159 (27.7%) of the references were not available, not even by searching the Internet using key terms from the citation. Considering that more than a fourth of the Web citations in this study were no longer available, authors need to be cautious about using the Web as a primary source of information for their publications.
C1 [Oermann, Marilyn H.] Univ N Carolina, Sch Nursing, Chapel Hill, NC 27515 USA.
[Nordstrom, Cheryl K.] Wayne State Univ, Coll Nursing, Detroit, MI 48202 USA.
[Ineson, Vicki] Wayne State Univ, Serv Support Perinatol Res Branch, NICHD, NIH,DHHS, Detroit, MI USA.
[Wilmes, Nancy A.] Wayne State Univ, Univ Lib, Sci & Engn Lib, Detroit, MI USA.
RP Oermann, MH (reprint author), Univ N Carolina, Sch Nursing, Chapel Hill, NC 27515 USA.
EM moermann@email.unc.edu
NR 19
TC 5
Z9 5
U1 1
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 8755-7223
J9 J PROF NURS
JI J. Prof. Nurs.
PD NOV-DEC
PY 2008
VL 24
IS 6
BP 347
EP 351
DI 10.1016/j.profnurs.2007.12.004
PG 5
WC Nursing
SC Nursing
GA 381JQ
UT WOS:000261532600004
PM 19022207
ER
PT J
AU Rodriguez, H
AF Rodriguez, Henry
TI International Summit on Proteomics Data Release and Sharing Policy
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Editorial Material
C1 NCI, Clin Proteom Technol Canc, NIH, Bethesda, MD 20892 USA.
RP Rodriguez, H (reprint author), NCI, Clin Proteom Technol Canc, NIH, Bethesda, MD 20892 USA.
NR 0
TC 3
Z9 3
U1 0
U2 0
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 NOV
PY 2008
VL 7
IS 11
BP 4609
EP 4609
DI 10.1021/pr800779q
PG 1
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 370VU
UT WOS:000260792000001
PM 18837532
ER
PT J
AU Albe, E
Chang, JH
Azar, NF
Ivanov, AR
Azar, DT
AF Albe, Elena
Chang, Jin-Hong
Azar, Nathalie F.
Ivanov, Alexander R.
Azar, Dimitri T.
TI Proteomic Analysis of the Hyaloid Vascular System Regression during
Ocular Development
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE hyaloid vascular system; vasa hyaloidea propria; tunica vasculosa
lentis; proteomic analysis; kininogen; angiogenic factors;
antiangiogenic factors; vessel regression
ID ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; CELL-GROWTH; APOPTOSIS;
NEOVASCULARIZATION; MACROPHAGES; INHIBITION; KININOGEN; MICE; EYE
AB We describe a proteomic approach to investigate the differential protein expression patterns and identify the physiologically relevant angiogenic and antiangiogenic factors involved in the hyaloid vascular system regression. Differentially expressed proteins were identified using two-dimensional gel electrophoresis followed by nanoflow chromatography coupled with tandem mass spectrometry. These proteins are expected to provide insight as to their function in the early maintenance and eventual regression of the hyaloid vascular system.
C1 [Chang, Jin-Hong; Azar, Nathalie F.; Azar, Dimitri T.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA.
[Albe, Elena; Chang, Jin-Hong; Azar, Nathalie F.; Azar, Dimitri T.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Ivanov, Alexander R.] Harvard Univ, Sch Publ Hlth, Harvard NIEHS Ctr Environm Hlth Proteom Facil, Boston, MA 02115 USA.
RP Azar, DT (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA.
EM dazar@uic.edu
FU S. Elizabeth O'Brien Trust; NIH [EY10101, P30-001792, EY14048]; Research
to Prevent Blindness (New York, NY)
FX The authors wish to thank Drs. Faisal Tobaigy and Ramon Ghanem for
immunoconfocal microscopy. Supported by S. Elizabeth O'Brien Trust
(D.TA.), NIH EY10101 (D.TA.), P30-001792 (D.TA.), EY14048 (J.H.C.), and
an unrestricted departmental support from Research to Prevent Blindness
(New York, NY).
NR 46
TC 5
Z9 5
U1 0
U2 0
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 NOV
PY 2008
VL 7
IS 11
BP 4904
EP 4913
DI 10.1021/pr800551m
PG 10
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 370VU
UT WOS:000260792000030
PM 18841878
ER
PT J
AU Mamasakhlisov, Y
Naji, A
Podgornik, R
AF Mamasakhlisov, Yevgeni S.
Naji, Ali
Podgornik, Rudolf
TI Partially Annealed Disorder and Collapse of Like-Charged Macroions
SO JOURNAL OF STATISTICAL PHYSICS
LA English
DT Article
DE Classical charged systems; Like-charge attraction; Charge disorder;
Partial annealing
ID DENSITY-FUNCTIONAL THEORY; ELECTRICAL DOUBLE-LAYER; POISSON-BOLTZMANN;
COUPLED DYNAMICS; FAST SPINS; AMPHOTERIC SURFACES; SLOW INTERACTIONS;
NEURAL-NETWORKS; COULOMB FLUID; SOFT MATTER
AB Charged systems with partially annealed charge disorder are investigated using field-theoretic and replica methods. Charge disorder is assumed to be confined to macroion surfaces surrounded by a cloud of mobile neutralizing counterions in an aqueous solvent. A general formalism is developed by assuming that the disorder is partially annealed (with purely annealed and purely quenched disorder included as special cases), i.e., we assume in general that the disorder undergoes a slow dynamics relative to fast-relaxing counterions making it possible thus to study the stationary-state properties of the system using methods similar to those available in equilibrium statistical mechanics. By focusing on the specific case of two planar surfaces of equal mean surface charge and disorder variance, it is shown that partial annealing of the quenched disorder leads to renormalization of the mean surface charge density and thus a reduction of the inter-plate repulsion on the mean-field or weak-coupling level. In the strong-coupling limit, charge disorder induces a long-range attraction resulting in a continuous disorder-driven collapse transition for the two surfaces as the disorder variance exceeds a threshold value. Disorder annealing further enhances the attraction and, in the limit of low screening, leads to a global attractive instability in the system.
C1 [Naji, Ali] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA.
[Mamasakhlisov, Yevgeni S.] Yerevan State Univ, Dept Mol Phys, Yerevan 375025, Armenia.
[Naji, Ali] Univ Calif Santa Barbara, Mat Res Lab, Santa Barbara, CA 93106 USA.
[Naji, Ali; Podgornik, Rudolf] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
[Podgornik, Rudolf] Univ Ljubljana, Dept Phys, Fac Math & Phys, Ljubljana 1000, Slovenia.
[Podgornik, Rudolf] Jozef Stefan Inst, Dept Theoret Phys, Ljubljana 1000, Slovenia.
[Podgornik, Rudolf] Natl Inst Hlth, Lab Phys & Struct Biol, Bethesda, MD 20892 USA.
RP Naji, A (reprint author), Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA.
EM anaji@chem.ucsb.edu
RI Naji, Ali/F-6352-2010; Podgornik, Rudolf/C-6209-2008
OI Naji, Ali/0000-0003-3436-1499; Podgornik, Rudolf/0000-0002-3855-4637
NR 69
TC 20
Z9 20
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0022-4715
J9 J STAT PHYS
JI J. Stat. Phys.
PD NOV
PY 2008
VL 133
IS 4
BP 659
EP 681
DI 10.1007/s10955-008-9635-7
PG 23
WC Physics, Mathematical
SC Physics
GA 373GF
UT WOS:000260958300004
ER
PT J
AU Dawson, DA
Stinson, FS
Chou, SP
Grant, BF
AF Dawson, Deborah A.
Stinson, Frederick S.
Chou, S. Patricia
Grant, Bridget F.
TI Three-Year Changes in Adult Risk Drinking Behavior in Relation to the
Course of Alcohol-Use Disorders
SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS
LA English
DT Article
ID NATIONAL EPIDEMIOLOGIC SURVEY; DSM-IV ALCOHOL; HEAVY DRINKING; YOUNG
ADULTHOOD; BINGE DRINKING; UNITED-STATES; DRUG-USE; LONGITUDINAL
PROJECT; EMERGING ADULTHOOD; ANXIETY DISORDERS
AB Objective: This study examines the associations between the course of alcohol-use disorder (AUD) and changes in average daily volume of ethanol intake, frequency of risk drinking, and maximum quantity of drinks consumed per day over a 3-year follow-up interval in a sample of U.S. adults. Method: Data were taken from a longitudinal of a nationally representative sample of U.S. adults, who were 18 years of age and older (mean age = 46.4) when initially interviewed in 2001-2002 and successfully reinterviewed approximately 3 years later (n = 22,245 baseline drinkers). The time reference period for the drinking measures was the 12 months preceding the interviews Changes in consumption reflect differences between Wave I and Wave 2 measures for individuals with nonmissing values at both Waves (n = 22,003 for volume of intake, 22,132 for frequency of risk drinking and 2 1,942 for maximum quantity of drinks). Results: There were positive changes in all consumption measures associated with developing an AUD and negative changes associated with remission of ail AUD, even among individuals who continued to drink. Increases and decreases associated with onset and offset of dependence exceeded those associated with onset/offset of abuse only. and the decreases associated with full remission from dependence exceeded those associated with partial remission. There were few changes in consumption among individuals whose AUD status did not change. Interactions of AUD transitions with other factors indicate that development of an AUD is associated with a greater increase in consumption among men, possibly reflecting their greater total body water and lower blood alcohol concentration in response to a given dose of ethanol, and among individuals with high baseline levels of consumption. Conclusions: Changes in consumption associated with onset and offset of AUD are substantial enough to have important implications for the risk of associated physical and psychological harm. (J. Stud. Alcohol Drugs 69: 866-877, 2008)
C1 [Dawson, Deborah A.; Stinson, Frederick S.; Chou, S. Patricia; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
RP Dawson, DA (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Lane,Room 3071,MSC 9304, Bethesda, MD 20892 USA.
EM ddawson@mail.nih.gov
FU National Institutes of Health; National Institute on Alcohol Abuse and
Alcoholism; U.S. Department of Health and Human Services; National
Institute on Drug Abuse
FX This research was supported, in part, by the Intramural Program of the
National Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism, The study on which this article is based. the National
Epidemiologic Survey on Alcohol and Related Conditions, is sponsored by
the National Institute on Alcohol Abuse and Alcoholism, National
Institutes of Health, U.S. Department of Health and Human Services, with
supplemental support from the National Institute on Drug Abuse. The
views and opinions expressed in this article are those of the authors
and should not be construed to represent the views of any of the
sponsoring organizations, agencies. or the U.S. government.
NR 66
TC 26
Z9 27
U1 2
U2 5
PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV
PI PISCATAWAY
PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA
SN 1937-1888
J9 J STUD ALCOHOL DRUGS
JI J. Stud. Alcohol Drugs
PD NOV
PY 2008
VL 69
IS 6
BP 866
EP 877
PG 12
WC Substance Abuse; Psychology
SC Substance Abuse; Psychology
GA 373BS
UT WOS:000260946600010
PM 18925345
ER
PT J
AU Leibenluft, E
AF Leibenluft, Ellen
TI Skating to Where the Puck Will Be: The Importance of Neuroimaging
Literacy in Child Psychiatry
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Editorial Material
ID YOUNG-CHILDREN; MATURATION; DISORDER; AUTISM
C1 NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Leibenluft, E (reprint author), NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, NIH,Dept Hlth & Human Serv, Bldg 15K,Room 203,15K N Dr,MSC 2670, Bethesda, MD 20892 USA.
EM leibs@mail.nih.gov
FU Intramural NIH HHS [Z99 MH999999]
NR 21
TC 2
Z9 2
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD NOV
PY 2008
VL 47
IS 11
BP 1213
EP 1216
DI 10.1097/CHI.0b013e318185dab8
PG 4
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 365YC
UT WOS:000260444800001
PM 18931607
ER
PT J
AU Pine, DS
Guyer, AE
Leibenluft, E
AF Pine, Daniel S.
Guyer, Amanda E.
Leibenluft, Ellen
TI Functional Magnetic Resonance Imaging and Pediatric Anxiety
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Editorial Material
ID PREFRONTAL CORTEX ACTIVATION; ATTENTIONAL BIAS; ANGRY FACES; DISORDER;
THREAT; ADOLESCENTS; PLASTICITY; VIGILANCE; AMYGDALA; CHILDREN
C1 [Pine, Daniel S.; Guyer, Amanda E.; Leibenluft, Ellen] NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Pine, DS (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bldg 15K,Room 203,15K N Dr,MSC 2670, Bethesda, MD 20892 USA.
EM pined@mail.nih.gov
FU Intramural NIH HHS [Z01 MH002782-06]
NR 14
TC 17
Z9 17
U1 7
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD NOV
PY 2008
VL 47
IS 11
BP 1217
EP 1221
DI 10.1097/CHI.0b013e318185dad0
PG 5
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 365YC
UT WOS:000260444800002
PM 18931608
ER
PT J
AU Mahindra, P
DiGiovanna, JJ
Tamura, D
Brahim, JS
Hornyak, TJ
Stern, JB
Lee, CCR
Khan, SG
Brooks, BP
Smith, JA
Driscoll, BP
Montemarano, AD
Sugarman, K
Kraemer, KH
AF Mahindra, Priya
DiGiovanna, John J.
Tamura, Deborah
Brahim, Jaime S.
Hornyak, Thomas J.
Stern, Jere B.
Lee, Chyi-Chia Richard
Khan, Sikandar G.
Brooks, Brian P.
Smith, Janine A.
Driscoll, Brian P.
Montemarano, Andrew D.
Sugarman, Kate
Kraemer, Kenneth H.
TI Skin cancers, blindness, and anterior tongue mass in African brothers
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
ID DNA-REPAIR DISORDERS; XERODERMA-PIGMENTOSUM; COCKAYNE-SYNDROME; XPC
GENE; TRICHOTHIODYSTROPHY; MANIFESTATIONS; MUTATION; PROTECTS; DAMAGE;
CELL
C1 [Mahindra, Priya; DiGiovanna, John J.; Tamura, Deborah; Khan, Sikandar G.; Kraemer, Kenneth H.] NCI, Basic Res Lab, DNA Repair Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Mahindra, Priya] NIH, Clin Res Training Program, Bethesda, MD 20892 USA.
[DiGiovanna, John J.] Brown Univ, Warren Alpert Sch Med, Dept Dermatol, Div Dermatopharmacol, Providence, RI 02912 USA.
[Hornyak, Thomas J.] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Stern, Jere B.; Lee, Chyi-Chia Richard] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Driscoll, Brian P.] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA.
[Montemarano, Andrew D.] Skin Canc Surg Ctr, Bethesda, MD USA.
[Sugarman, Kate] Community Hope Hlth Serv, Washington, DC USA.
RP Kraemer, KH (reprint author), NCI, Basic Res Lab, DNA Repair Sect, Ctr Canc Res, Bldg 37,Room 4002,MSC 4258, Bethesda, MD 20892 USA.
FU Center for Cancer Research; National Cancer Institute; National
Institute of Dental and Craniofacial Research; National Eye Institute;
National Institute of Deafness; National Institutes of Health (NIH);
Pfizer Inc
FX Supported by the Intramural Research Programs of the Center for Cancer
Research, National Cancer Institute, of the National Institute of Dental
and Craniofacial Research, of the National Eye Institute, and of the
National Institute of Deafness and other Communication Disorders of the
National Institutes of Health (NIH). Support for author Mahindra was
made possible through the Clinical Research Training Program, a
public-private partnership supported jointly by the NIH and Pfizer Inc
(via a grant to the Foundation for NIH from Pfizer Inc).
NR 25
TC 16
Z9 16
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD NOV
PY 2008
VL 59
IS 5
BP 881
EP 886
DI 10.1016/j.jaad.2008.06.030
PG 6
WC Dermatology
SC Dermatology
GA 365CT
UT WOS:000260384200018
PM 19119101
ER
PT J
AU Dang, V
Bao, S
Ault, A
Murray, C
McFarlane-Mills, J
Chiedi, C
Dillon, M
Todd, JP
DeTolla, L
Rao, S
AF Dang, Vi
Bao, Saran
Ault, Alida
Murray, Catherine
McFarlane-Mills, Joy
Chiedi, Carmelo
Dillon, Marlon
Todd, John-Paul
DeTolla, Louis
Rao, Srinivas
TI Efficacy and Safety of Five Injectable Anesthetic Regimens for Chronic
Blood Collection from the Anterior Vena Cava of Guinea Pigs
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Article
ID LABORATORY-ANIMALS; KETAMINE; XYLAZINE
AB Despite several published methods of inducing surgical anesthesia in guinea pigs, viable methods of anesthesia for blood collection from the vena cava are inadequate. We compared 5 anesthesia regimens and their efficacy in inducing anesthesia for blood sampling in guinea pigs: ketamine-xylazine (30 and 2.5 mg/kg) administered subcutaneously, intramuscularly, or intraperitoneally; pentobarbital (37 mg/kg) administered intraperitoneally; and medetomidine (0.5 mg/kg) administered intramuscularly. Parameters measured included time to onset of anesthesia, time to recovery from anesthesia, and complete blood count (CBC) and serum chemistry values. CBC values did not differ among the 5 regimens, but serum glucose, BUN, phosphorous, and creatine phosphokinase levels varied among groups. Based on our data, intraperitoneal ketamine-xylazine appears to emerge as a preferable injectable anesthetic regimen in guinea pigs for blood collection from the anterior vena cava.
C1 [Dang, Vi; Bao, Saran; Ault, Alida; Murray, Catherine; McFarlane-Mills, Joy; Chiedi, Carmelo; Dillon, Marlon; Todd, John-Paul; Rao, Srinivas] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[DeTolla, Louis] Univ Maryland, Sch Med, Program Comparat Med, Baltimore, MD 21201 USA.
[DeTolla, Louis] Univ Maryland, Sch Med, Dept Pathol Epidemiol & Prevent Med & Med, Div Infect Dis, Baltimore, MD 21201 USA.
RP Rao, S (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM srao1@mail.nih.gov
NR 27
TC 7
Z9 7
U1 0
U2 2
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD NOV
PY 2008
VL 47
IS 6
BP 56
EP 60
PG 5
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 380AR
UT WOS:000261438400012
PM 19049255
ER
PT J
AU Ayres, EJ
Hoggle, LB
AF Ayres, Elaine J.
Hoggle, Lindsey B.
TI ADA Nutrition Informatics Member Survey: Results and Future Steps
SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION
LA English
DT Editorial Material
C1 [Ayres, Elaine J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA.
RP Ayres, EJ (reprint author), NIH, Lab Informat Dev, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM eayres@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 6
TC 8
Z9 9
U1 0
U2 0
PU AMER DIETETIC ASSOC
PI CHICAGO
PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA
SN 0002-8223
J9 J AM DIET ASSOC
JI J. Am. Diet. Assoc.
PD NOV
PY 2008
VL 108
IS 11
BP 1822
EP +
DI 10.1016/j.jada.2008.09.016
PG 4
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 368LK
UT WOS:000260622400003
PM 18954567
ER
PT J
AU Guenther, PM
Reedy, J
Krebs-Smith, SM
Reeve, BB
AF Guenther, Patricia M.
Reedy, Jill
Krebs-Smith, Susan M.
Reeve, Bryce B.
TI Evaluation of the Healthy Eating Index-2005
SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION
LA English
DT Article
ID DIET QUALITY INDEX; NUTRIENT INTAKE; PATTERNS; NONSMOKERS; ADHERENCE;
GUIDANCE; SMOKING; SMOKERS; WOMEN; RISK
AB Background The Healthy Eating Index (HEI), a measure of diet quality as specified by federal dietary guidance, was revised to conform to the Dietary Guidelines for Americans 2005. The HEI has several components, the scores of which are totaled.
Objective The validity and reliability of the HEI-2005 were evaluated.
Design Validity was assessed by answering four questions: Does the HEI-2005 1) give maximum scores to menus developed by experts; 2) distinguish between groups wit known differences in diet quality-smokers and nonsmokers; 3) measure diet quality independently of energy intake, a proxy for diet quantity; and 4) have more than one underlying dimension? The relevant type of reliability, internal consistency, was also assessed.
Subjects Twenty-four-hour recalls from 8,650 participants, aged 2 years and older, in the National Health and Nutrition Examination Survey, 2001-2002 were analyzed to answer questions 2 to 4. Results were weighted to consider sample design and nonresponse. Statistical analyses T tests determined differences in scores between smokers and nonsmokers. Pearson correlation coefficients determined the relationship between energy intake and scores. Principal components analysis determined the number of factors that comprise the HEI-2005. Cronbach's coefficient a tested internal consistency.
Results HEI-2005 scores are at or very near the maximum levels for all sets of exemplary menus with one exception; the Harvard menus scored low on the milk component because these menus intentionally include only small amounts of milk products. Nine of 12 component scores were lower for smokers than nonsmokers. The correlations of component scores were virtually independent of energy intake (< 1.221). Multiple factors underlie the HEI-2005. Coefficient a was .43. The a value for all tests was .01,
Conclusions The HEI-2005 is a valid measure of diet quality. Potential uses include population monitoring, evaluation of interventions, and research. The individual component scores provide essential information in addition to that provided by the total score.
C1 [Guenther, Patricia M.] Ctr Nutr Policy & Promot, USDA, Alexandria, VA 22302 USA.
[Reedy, Jill; Krebs-Smith, Susan M.] Natl Canc Inst, Div Canc Control & Populat Sci, Risk Factor Monitoring & Methods Branch, Appl Res Program, Bethesda, MD USA.
[Reeve, Bryce B.] Natl Canc Inst, Div Canc Control & Populat Sci, Outcomes Res Branch, Appl Res Program, Bethesda, MD USA.
RP Guenther, PM (reprint author), Ctr Nutr Policy & Promot, USDA, 3101 Pk Ctr Dr,Suite 1034, Alexandria, VA 22302 USA.
EM Patricia.Guenther@cnpp.usda.gov
NR 32
TC 125
Z9 128
U1 0
U2 20
PU AMER DIETETIC ASSOC
PI CHICAGO
PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA
SN 0002-8223
J9 J AM DIET ASSOC
JI J. Am. Diet. Assoc.
PD NOV
PY 2008
VL 108
IS 11
BP 1854
EP 1864
DI 10.1016/j.jada.2008.08.011
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 368LK
UT WOS:000260622400011
PM 18954575
ER
PT J
AU Guenther, PM
Reedy, J
Krebs-Smith, SM
AF Guenther, Patricia M.
Reedy, Jill
Krebs-Smith, Susan M.
TI Development of the Healthy Eating Index-2005
SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION
LA English
DT Article
AB The Healthy Eating Index (HEI) is a measure of diet quality as specified by Federal dietary guidance, and publication of the Dietary Guidelines for Americans 2005 necessitated its revision. An interagency working group based the HEI-2005 on the food patterns found in My-Pyramid. Diets that meet the least restrictive of the food-group recommendations, expressed on a per 1,000 calorie basis, receive maximum scores for the nine adequacy components of the index: total fruit (5 points), whole fruit (5 points), total vegetables (5 points), dark green and orange vegetables and legumes (5 points), total grains (5 points), whole grains (5 points), milk (10 points), meat and beans (10 points), and oils (10 points). Lesser amounts are prorated linearly. Population probability densities were examined when setting the standards for minimum and maximum scores for the three moderation components: saturated fat (10 points), sodium (10 points), and calories from solid fats, alcoholic beverages (ie, beer, wine, and distilled spirits), and added sugars (20 points). Calories from solid fats, alcoholic beverages, and added sugars is a proxy for the discretionary calorie allowance. The 2005 Dietary Guideline for saturated fat and the Adequate Intake and Tolerable Upper Intake Level for sodium, expressed per 1,000 calories, were used when setting the standards for those components. Intakes between the maximum and minimum standards are prorated. The HEI-2005 is a measure of diet quality as described by the key diet-related recommendations of the 2005 Dietary Guidelines. It has a variety of potential uses, including monitoring the diet quality of the US population and subpopulations, evaluation of interventions, and research.
C1 [Guenther, Patricia M.] Ctr Nutr Policy & Promot, USDA, Alexandria, VA 22302 USA.
[Reedy, Jill; Krebs-Smith, Susan M.] Natl Canc Inst, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control, Bethesda, MD USA.
RP Guenther, PM (reprint author), Ctr Nutr Policy & Promot, USDA, 3101 Pk Ctr Dr,Suite 1034, Alexandria, VA 22302 USA.
EM Patricia.Guenther@cnpp.usda.gov
NR 20
TC 261
Z9 269
U1 3
U2 31
PU AMER DIETETIC ASSOC
PI CHICAGO
PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA
SN 0002-8223
J9 J AM DIET ASSOC
JI J. Am. Diet. Assoc.
PD NOV
PY 2008
VL 108
IS 11
BP 1896
EP 1901
DI 10.1016/j.jada.2008.08.016
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 368LK
UT WOS:000260622400016
PM 18954580
ER
PT J
AU Houston, DK
Schwartz, AV
Cauley, JA
Tylavsky, FA
Simonsick, EM
Harris, TB
de Rekeneire, N
Schwartz, GG
Kritchevsky, SB
AF Houston, Denise K.
Schwartz, Ann V.
Cauley, Jane A.
Tylavsky, Frances A.
Simonsick, Eleanor M.
Harris, Tamara B.
de Rekeneire, Nathalie
Schwartz, Gary G.
Kritchevsky, Stephen B.
CA Health Aging & Body Composition
TI Serum Parathyroid Hormone Levels Predict Falls in Older Adults with
Diabetes Mellitus
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE PTH; falls; physical performance
ID VITAMIN-D STATUS; COMMUNITY-DWELLING WOMEN; MUSCLE STRENGTH;
NURSING-HOME; CYSTATIN-C; SECONDARY HYPERPARATHYROIDISM;
AFRICAN-AMERICAN; BLACK-WOMEN; RISK; INJURIES
AB To examine the association between serum parathyroid hormone (PTH) levels and incident falls in older adults with diabetes mellitus.
Longitudinal analysis of incident falls over 1 year in a substudy of participants with diabetes mellitus in the Health, Aging and Body Composition Study.
Pittsburgh, Pennsylvania, and Memphis, Tennessee.
Well-functioning, community-dwelling black and white adults aged 70 to 79 with diabetes mellitus (N=472).
Measured baseline serum PTH. Self-report of falls over the subsequent 12 months. Baseline physical performance and self-reported demographic, behavioral, and health status measures including kidney function, chronic conditions, and medication use.
One-third (30.3%) of participants reported falling over 1 year of follow-up. Mean baseline serum PTH was 53.5 +/- 30.0 pg/mL in nonfallers and 62.6 +/- 46.2 pg/mL in fallers (P=.01). For every 1 standard deviation (36 pg/mL) increment in baseline serum PTH, there was approximately a 30% greater likelihood of reporting a fall in the subsequent year, after adjusting for age, sex, race, field center, alcohol consumption, body mass index, physical activity, and winter or spring season (adjusted odds ratio (aOR)=1.30, 95% confidence interval (CI)=1.06-1.59). Further adjustment for kidney function, chronic conditions, medication and supplement use, and physical performance attenuated the association slightly (aOR=1.26, 95% CI=1.01-1.58). A trend remained after additional adjustment for reported falls in the previous year.
Higher serum PTH was associated with incident falls in older, well-functioning men and women with diabetes mellitus. Further investigation aimed at understanding the underlying mechanism for the association between serum PTH and falls is needed.
C1 [Houston, Denise K.; Schwartz, Gary G.; Kritchevsky, Stephen B.] Wake Forest Univ, Med Ctr, Sch Med, Dept Internal Med,Sect Gerontol & Geriatr Med, Winston Salem, NC 27157 USA.
[Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostatist, San Francisco, CA USA.
[Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA.
Univ Tennessee Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
[Harris, Tamara B.] Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD USA.
Natl Inst Aging, Clin Res Branch, Baltimore, MD USA.
[de Rekeneire, Nathalie] Div Diabet Translat, Centers Dis Control & Prevent, Atlanta, GA USA.
[Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27157 USA.
[Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Schwartz, Gary G.] Wake Forest Univ, Dept Canc Biol, Winston Salem, NC 27157 USA.
[Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Tylavsky, Frances A.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[de Rekeneire, Nathalie] Ctr Dis Control & Prevent, Div Diabet, Atlanta, GA USA.
RP Houston, DK (reprint author), Wake Forest Univ, Med Ctr, Sch Med, Dept Internal Med,Sect Gerontol & Geriatr Med, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM dhouston@wfubmc.edu
RI Cauley, Jane/N-4836-2015;
OI Cauley, Jane/0000-0003-0752-4408; Kritchevsky,
Stephen/0000-0003-3336-6781
FU Merck Company; Eli Lilly Company; Pfizer Pharmaceuticals; Novartis
Pharmaceuticals
FX Jane A. Cauley has received research support from Merck & Company, Eli
Lilly & Company, Pfizer Pharmaceuticals, and Novartis Pharmaceuticals.
She has also received consulting fees from Eli Lilly & Company and
Novartis Pharmaceuticals.
NR 41
TC 7
Z9 7
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD NOV
PY 2008
VL 56
IS 11
BP 2027
EP 2032
DI 10.1111/j.1532-5415.2008.01966.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 374SS
UT WOS:000261064600006
PM 19016936
ER
PT J
AU Semba, RD
Patel, KV
Sun, K
Guralnik, JM
Ershler, WB
Longo, DL
Ferrucci, L
AF Semba, Richard D.
Patel, Kushang V.
Sun, Kai
Guralnik, Jack M.
Ershler, William B.
Longo, Dan L.
Ferrucci, Luigi
TI ASSOCIATION BETWEEN SERUM CARBOXYMETHYL-LYSINE, A DOMINANT ADVANCED
GLYCATION END PRODUCT, AND ANEMIA IN ADULTS: THE BALTIMORE LONGITUDINAL
STUDY OF AGING
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Letter
ID N-EPSILON-(CARBOXYMETHYL)LYSINE; ERYTHROCYTES; PROTEINS; BLOOD; AGES
C1 [Semba, Richard D.; Sun, Kai] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21218 USA.
[Patel, Kushang V.; Guralnik, Jack M.] NIA, Lab Epidemiol Biometry & Dermog, NIH, Bethesda, MD 20892 USA.
[Ershler, William B.; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Longo, Dan L.] NIA, Lymphocyte Cell Biol Unit, Immunol Lab, NIH, Baltimore, MD 21224 USA.
RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21218 USA.
FU NIA NIH HHS [R01 AG027012, R01 AG027012-03, R01 AG029148, R01
AG029148-02]
NR 10
TC 1
Z9 1
U1 0
U2 2
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD NOV
PY 2008
VL 56
IS 11
BP 2145
EP 2147
DI 10.1111/j.1532-5415.2008.01968.x
PG 3
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 374SS
UT WOS:000261064600027
PM 19016950
ER
PT J
AU Kanapuru, B
Posani, K
Muller, D
Ershler, WB
AF Kanapuru, Bindu
Posani, Karuna
Muller, Denis
Ershler, William B.
TI DECREASED CANCER PREVALENCE IN THE NURSING HOME
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Letter
ID FRAILTY; INTERLEUKIN-6; DISEASES
C1 [Kanapuru, Bindu; Posani, Karuna; Muller, Denis; Ershler, William B.] NIA, Clin Res Branch, Intramural Res Program, Baltimore, MD 21224 USA.
RP Kanapuru, B (reprint author), NIA, Clin Res Branch, Intramural Res Program, Baltimore, MD 21224 USA.
NR 10
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD NOV
PY 2008
VL 56
IS 11
DI 10.1111/j.1532-5415.2008.01864.x
PG 2
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 374SS
UT WOS:000261064600040
ER
PT J
AU Feero, WG
Bigley, MB
Brinner, KM
AF Feero, W. Gregory
Bigley, Mary Beth
Brinner, Kristin M.
CA Amer Hlth Information Community
TI New Standards and Enhanced Utility for Family Health History Information
in the Electronic Health Record: An Update from the American Health
Information Community's Family Health History Multi-Stakeholder
Workgroup
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID PRIMARY-CARE
AB Family health history is a complex, Multifaceted tool for assessing disease risk that can offer insight into the interplay between inherited and social factors relevant to patient care. Family health history tools in electronic health records can enable the user to collect, represent, and interpret structured data that properly supports clinical decisions. If these data can be made interoperable, important health information can be shared with minimal duplication of effort among entities involved in the Continuum of patient care. This paper reviews the efforts by the American Health Information Community's Family Health History Multi-Stakeholder Workgroup to create a core data set for family health history information and to determine requirements to promote incorporation of such information in electronic health records. The Workgroup is a component of the U.S. Department of Health and Human Services' Personalized Health Care Initiative.
C1 [Feero, W. Gregory] NHGRI, Genom Healthcare Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Bigley, Mary Beth] US Dept HHS, Off US Srug Gen, Washington, DC 20201 USA.
[Brinner, Kristin M.] US Dept HHS, Personalized Hlth Care Initiat, Amer Assoc Adv Sci, Washington, DC 20201 USA.
RP Feero, WG (reprint author), NHGRI, Genom Healthcare Branch, NIH, Dept Hlth & Human Serv, Bldg 31,Room 4B09,31 Ctr Dr, Bethesda, MD 20892 USA.
EM feerow@mail.nih.gov
NR 16
TC 57
Z9 57
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD NOV-DEC
PY 2008
VL 15
IS 6
BP 723
EP 728
DI 10.1197/jamia.M2793
PG 6
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Information Science & Library Science;
Medical Informatics
SC Computer Science; Information Science & Library Science; Medical
Informatics
GA 372MK
UT WOS:000260905500003
PM 18755994
ER
PT J
AU Del Fiol, G
Haug, PJ
Cimino, JJ
Narus, SP
Norlin, C
Mitchell, JA
AF Del Fiol, Guilherme
Haug, Peter J.
Cimino, James J.
Narus, Scott P.
Norlin, Chuck
Mitchell, Joyce A.
TI Effectiveness of Topic-specific Infobuttons: A randomized Controlled
Trial
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID INFORMATION-RETRIEVAL TECHNOLOGY; CLINICAL QUESTIONS; ONLINE EVIDENCE;
MIXED METHODS; PHYSICIANS; IMPACT; NEEDS; CARE; KNOWLEDGE; SYSTEMS
AB Objective: Infobuttons are decision support tools that provide links within electronic medical record systems to relevant content in online information resources. The aim of infobuttons is to help clinicians promptly meet their information needs. The objective of this Study was to determine whether infobutton links that direct to specific content topics ("topic links") are more effective than links that point to general overview content ("nonspecific links").
Design: Randomized controlled trial with a control and an intervention group. Clinicians in the control group had access to nonspecific links, while those in the intervention group had access to topic links.
Measurements: Infobutton session duration, number of infobutton sessions, session success rate, and the self-reported impact that the infobutton session produced on decision making.
Results: The analysis was performed On 90 Subjects and 3,729 infobutton sessions. Subjects in the intervention group spent 17.4% less time seeking for information (35.5 seconds vs. 43 seconds, p = 0.008) than those in the control group. Subjects in the intervention group used infobuttons 20.5% (22 sessions vs. 17.5 sessions, p = 0.21) more often than in the control group, but the difference was not significant. The information seeking success rate was equally high in both groups (89.4%, control vs. 87.2% intervention, p = 0.99). Subjects reported a high positive clinical impact (i.e., decision enhancement or knowledge update) in 62% of the sessions.
Limitations: The exclusion Of users with a low frequency of infobutton use and the focus on medication-related information needs may limit the generalization of the results, The session outcomes measurement was based on clinicians' setf-assessment and therefore prone to bias.
Conclusion: The results support the hypothesis that topic links are more efficient than nonspecific links regarding the time seeking for information. It is unclear whether the statistical difference demonstrated will result in a clinically significant impact. However, the overall results confirm previous evidence that infobuttons are effective at helping clinicians to answer questions at the point of care and demonstrate a modest incremental change in the efficiency of information delivery for routine users of this tool.
C1 [Del Fiol, Guilherme; Haug, Peter J.; Narus, Scott P.; Mitchell, Joyce A.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA.
[Del Fiol, Guilherme; Haug, Peter J.] Intermt Healthcare, Salt Lake City, UT USA.
[Cimino, James J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA.
[Norlin, Chuck] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
RP Del Fiol, G (reprint author), Intermt Healthcare, 4646 Lake Pk Blvd, Salt Lake City, UT USA.
EM guilheme.delfiol@utah.edu
OI Del Fiol, Guilherme/0000-0001-9954-6799; Cimino,
James/0000-0003-4101-1622
FU NLM NIH HHS [1T15LM007124-10, R01 LM007593, R01-LM07593, T15 LM007124]
NR 35
TC 31
Z9 31
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD NOV-DEC
PY 2008
VL 15
IS 6
BP 752
EP 759
DI 10.1197/jamia.M2725
PG 8
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Information Science & Library Science;
Medical Informatics
SC Computer Science; Information Science & Library Science; Medical
Informatics
GA 372MK
UT WOS:000260905500007
PM 18755999
ER
PT J
AU Jackson, SN
Ugarov, M
Post, JD
Egan, T
Langlais, D
Schultz, JA
Woods, AS
AF Jackson, Shelley N.
Ugarov, Michael
Post, Jeremy D.
Egan, Thomas
Langlais, Denis
Schultz, J. Albert
Woods, Amina S.
TI A Study of Phospholipids by Ion Mobility TOFMS
SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
LA English
DT Article
ID FLIGHT MASS-SPECTROMETRY; BRAIN-TISSUE; MALDI; LIPIDOMICS; DEFICIENCY;
SYSTEMS; MS
AB Combining matrix-assisted laser desorption/ionization (MALDI) mass spectrometry with ion mobility (IM) results in the fast sorting of biomolecules in complex mixtures along trend lines. In this two-dimensional (2D) analysis of biological families, lipids, peptides, and nucleotides are separated from each other by differences in their ion mobility drift times in a timescale of hundreds of microseconds. Molecular ions of similar chemical type fall along trend lines when plotted in 2D plots of ion mobility drift time as a function of m/z. In this study, MALDI-IM MS is used to analyze species from all of the major phospholipid classes. Complex samples, including tissue extracts and sections, were probed to demonstrate the effects that radyl chain length, degree of unsaturation, and class/head group have upon an ion's cross section in the gas phase. We illustrate how these changes can be used to identify individual lipid species in complex Mixtures, as well as the effects of cationization on ion cross section and ionization efficiency. (J Am Soc Mass Spectrom 2008, 19, 1655-1662) (C) 2008 American Society for Mass Spectrometry
C1 [Jackson, Shelley N.; Post, Jeremy D.; Woods, Amina S.] NIDA, IRP, NIH, Baltimore, MD 21224 USA.
[Ugarov, Michael; Egan, Thomas; Langlais, Denis; Schultz, J. Albert] Ionwerks Inc, Houston, TX USA.
RP Woods, AS (reprint author), NIDA, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM awoods@intra.nida.nih.gov
FU Intramural NIH HHS [Z99 DA999999]; NIDA NIH HHS [N44DA-3-7727]; PHS HHS
[HHSN271200677593C, HHSN271200677563C]
NR 31
TC 52
Z9 52
U1 2
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1044-0305
J9 J AM SOC MASS SPECTR
JI J. Am. Soc. Mass Spectrom.
PD NOV
PY 2008
VL 19
IS 11
BP 1655
EP 1662
DI 10.1016/j.jasms.2008.07.005
PG 8
WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy
SC Chemistry; Spectroscopy
GA 378TD
UT WOS:000261345900009
PM 18703352
ER
PT J
AU Cohen, SD
Kimmel, PL
Neff, R
Agodoa, L
Abbottt, KC
AF Cohen, Scott D.
Kimmel, Paul L.
Neff, Robert
Agodoa, Lawrence
Abbottt, Kevin C.
TI Association of Incident Gout and Mortality in Dialysis Patients
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article; Proceedings Paper
CT 40th Annual Meeting of the American-Society-of-Nephrology/Annual Renal
Week
CY OCT 31-NOV 05, 2007
CL San Francisco, CA
SP Amer Soc Nephrol
ID SERUM URIC-ACID; STAGE RENAL-DISEASE; CORONARY-HEART-DISEASE; ALL-CAUSE
MORTALITY; MIDDLE-AGED MEN; HEMODIALYSIS-PATIENTS; CARDIOVASCULAR
MORTALITY; RISK-FACTOR; FOLLOW-UP; METABOLIC SYNDROME
AB Previous studies have shown that gout is associated with an increased risk for cardiovascular mortality in the general population, but this has not been well studied in patients with ESRD. In this study, the incidence of gout and its association with mortality was evaluated in 259,209 patients in the United States Renal Data System. Overall, the incidence of gout in the first year of dialysis was 5% and in the first 5 yr was 15.4%. Independent risk factors for gout in adjusted analyses included black race, older age, female gender, hypertension, ischemic heart disease, congestive heart failure, and alcohol use. Factors associated with a lower risk for gout included a history of diabetes, smoking, and peripheral vascular disease. Time-dependent Cox regression analysis suggested that an episode of gout was independently associated with a 1.5-fold increase in mortality risk (adjusted hazard ratio 1.49; 95% confidence interval 1.43 to 1.55). The mechanisms underlying this association require further study.
C1 [Neff, Robert; Abbottt, Kevin C.] Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA.
[Cohen, Scott D.; Kimmel, Paul L.] George Washington Univ, Med Ctr, Dept Med, Div Renal Dis, Washington, DC 20052 USA.
[Agodoa, Lawrence] NIDDK, NIH, Bethesda, MD USA.
[Neff, Robert; Abbottt, Kevin C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
RP Abbottt, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA.
EM kevin.abbott@amedd.army.mil
OI Abbott, Kevin/0000-0003-2111-7112
NR 57
TC 39
Z9 42
U1 0
U2 0
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2008
VL 19
IS 11
BP 2204
EP 2210
DI 10.1681/ASN.2007111256
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 367YI
UT WOS:000260588100021
PM 18508965
ER
PT J
AU Arlen, PM
Bander, NH
Hall, SJ
AF Arlen, Philip M.
Bander, Neil H.
Hall, Simon J.
TI Treatment of Biochemical Recurrence of Prostate Cancer With
Granulocyte-Macrophage Colony-Stimulating Factor Secreting, Allogeneic,
Cellular Immunotherapy COMMENTS
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
ID VACCINE
C1 [Arlen, Philip M.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bander, Neil H.] Cornell Univ, Weill Med Coll, Dept Urol, New York, NY 10021 USA.
[Hall, Simon J.] Mt Sinai Sch Med, Dept Urol, New York, NY USA.
RP Arlen, PM (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD NOV
PY 2008
VL 180
IS 5
BP 2017
EP 2018
DI 10.1016/j.juro.2008.07.127
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 361BH
UT WOS:000260102000042
ER
PT J
AU McDermott, MM
Ades, PA
Dyer, A
Guralnik, JM
Kibbe, M
Criqui, MH
AF McDermott, Mary M.
Ades, Philip A.
Dyer, Alan
Guralnik, Jack M.
Kibbe, Melina
Criqui, Michael H.
TI Corridor-based functional performance measures correlate better with
physical activity during daily life than treadmill measures in persons
with peripheral arterial disease
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID LOWER-EXTREMITY FUNCTION; CHRONIC HEART-FAILURE; 6-MINUTE WALK;
INTERMITTENT CLAUDICATION; SUBSEQUENT DISABILITY; LEG SYMPTOMS;
ASSOCIATION; DECLINE; UTILITY; INDEX
AB Objective: To compare associations of physical activity during daily life with treadmill walking performance and corridor-based functional performance measures in persons with lower extremity peripheral arterial disease (PAD).
Study Design: Cross-sectional.
Subjects: One hundred fifty-six men and women with PAD who completed baseline measurements and were randomized into the study to improve leg circulation (SILC) exercise clinical trial.
Main Outcome Measures. Participants completed a Gardner-Skinner treadmill protocol. Corridor-based functional performance measures were the 6-minute walk, walking velocity over four meters at usual and fastest pace, and the short physical performance battery (SPPB) (0-12 scale, 12 = best). Physical activity during daily life was measured continuously over 7 days with a Caltrac (Muscle Dynamics Fitness Network, Inc, Torrence, Calif) accelerometer.
Results. Adjusting for age, gender, and race, higher levels of physical activity during daily life were associated with greater distance achieved in the 6-minute walk (P trend = .001), faster fast-paced four-meter walking velocity (P trend < .001 faster usual-paced four-meter walking speed (P trend = .027) and a higher SPPB (P trend = .005). The association of physical activity level with maximum treadmill walking distance did not reach statistical significance (P trend = .083). There were no associations of physical activity with treadmill distance to onset of leg symptoms (P trend = .795).
Conclusion: Functional performance measures arc more strongly associated with physical activity levels during daily life than treadmill walking measures. (J Vasc Surg 2008;48:1231-7.)
C1 [McDermott, Mary M.; Dyer, Alan; Kibbe, Melina] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
[McDermott, Mary M.; Dyer, Alan; Kibbe, Melina] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Ades, Philip A.] Vermont Sch Med, Dept Med, Burlington, VT USA.
[Guralnik, Jack M.] NIA, Demog & Biochem & Clin Res Branch, Lab Epidemiol, Bethesda, MD 20892 USA.
[Criqui, Michael H.] Univ Calif San Diego, Dept Prevent Med, San Diego, CA 92103 USA.
[Criqui, Michael H.] Univ Calif San Diego, Dept Family Med, San Diego, CA 92103 USA.
RP McDermott, MM (reprint author), 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
FU National Heart Lung and Blood Institute [R01-HL073551]; National Center
for Research Resources [RR-00048]; National Institutes of Health (NIH);
Intramural Research Program; National Institutes on Aging;
ClinicalTrials.gov Identifier [NCT00106327]
FX Supported by R01-HL073551 from the National Heart Lung and Blood
Institute and by grant #RR-00048 from the National Center for Research
Resources, National Institutes of Health (NIH). Supported in part by the
Intramural Research Program, National Institutes on Aging, NIH May 16,
2008. ClinicalTrials.gov Identifier: NCT00106327.
NR 24
TC 51
Z9 51
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD NOV
PY 2008
VL 48
IS 5
BP 1231
EP 1237
DI 10.1016/j.jvs.2008.06.050
PG 7
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 369WT
UT WOS:000260725300023
PM 18829215
ER
PT J
AU Aitichou, M
Saleh, S
Kyusung, P
Huggins, J
O'Guinn, M
Jahrling, P
Ibrahim, S
AF Aitichou, Mohamed
Saleh, Sharron
Kyusung, Park
Huggins, John
O'Guinn, Monica
Jahrling, Peter
Ibrahim, Sofi
TI Dual-probe real-time PCR assay for detection of variola or other
orthopoxviruses with dried reagents
SO JOURNAL OF VIROLOGICAL METHODS
LA English
DT Article
DE Orthopox virus; Smallpox; Variola; Monkeypox; Cowpox; Vaccinia; Taqman;
PCR; Real-time PCR; Multiplex PCR; Dried PCR reagents
ID SMALLPOX-VIRUS; ROCHE LIGHTCYCLER; MONKEYPOX; IDENTIFICATION; DNA;
COWPOX
AB A real-time, multiplexed polymerase chain reaction (PCR) assay based on dried PCR reagents was developed. Only variola virus could be specifically detected by a FAM (6-carboxyfluorescein)-labeled probe while camelpox, cowpox, monkeypox and vaccinia viruses could be detected by a TET (6-carboxytetramethylrhodamine)-labeled probe in a single PCR reaction. Approximately 25 copies of cloned variola virus DNA and 50 copies of genomic orthopoxviruses DNA could be detected with high reproducibility. The assay exhibited a dynamic range of seven orders of magnitude with a correlation coefficient value greater than 0.97. The sensitivity and specificity of the assay, as determined from 100 samples that contained nucleic acids from a multitude of bacterial and viral species were 96% and 98%, respectively. The limit of detection, sensitivity and specificity of the assay were comparable to standard real-time PCR assays with wet reagents. Employing a multiplexed format in this assay allows simultaneous discrimination of the variola virus from other closely related orthopoxviruses. Furthermore, the implementation of dried reagents in real-time PCR assays is an important step towards simplifying such assays and allowing their use in areas where cold storage is not easily accessible. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Aitichou, Mohamed; Saleh, Sharron; Huggins, John; O'Guinn, Monica; Ibrahim, Sofi] USA, Med Res Inst Infect Dis, Div Virol, Frederick, MD 21702 USA.
[Jahrling, Peter] NIAID, NIH, Bethesda, MD 20892 USA.
[Kyusung, Park] Invitrogen Corp, Carlsbad, CA USA.
RP Aitichou, M (reprint author), USA, Med Res Inst Infect Dis, Div Virol, 1425 Porter St,Ft Frederick, Frederick, MD 21702 USA.
EM mohamed.aitichou@amedd.army.mil
FU Defense Threat Reduction Agency [02-4-41-091]
FX This work was supported by research program funds managed by the Defense
Threat Reduction Agency grant #02-4-41-091. We thank Katheryn Kenyon for
reviewing the manuscript. The mention of materials or products in this
article does not constitute endorsement by the Department of Defense or
the United States government.
NR 28
TC 8
Z9 10
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-0934
J9 J VIROL METHODS
JI J. Virol. Methods
PD NOV
PY 2008
VL 153
IS 2
BP 190
EP 195
DI 10.1016/j.jviromet.2008.07.018
PG 6
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Virology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Virology
GA 367PV
UT WOS:000260565200017
PM 18725245
ER
PT J
AU Gillim-Ross, L
Santos, C
Chen, ZY
Aspelund, A
Yang, CF
Ye, D
Jin, H
Kemble, G
Subbarao, K
AF Gillim-Ross, Laura
Santos, Celia
Chen, Zhongying
Aspelund, Amy
Yang, Chin-Fen
Ye, Dan
Jin, Hong
Kemble, George
Subbarao, Kanta
TI Avian Influenza H6 Viruses Productively Infect and Cause Illness in Mice
and Ferrets
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID A H5N1 VIRUSES; HONG-KONG; MOUSE MODEL; INTERSPECIES TRANSMISSION;
SOUTHERN CHINA; POULTRY; HUMANS; PATHOGENESIS; CHICKENS; GENE
AB Influenza pandemic preparedness has focused on influenza virus H5 and H7 subtypes. However, it is not possible to predict with certainty which subtype of avian influenza virus will cause the next pandemic, and it is prudent to include other avian influenza virus subtypes in pandemic preparedness efforts. An H6 influenza virus was identified as a potential progenitor of the H5N1 viruses that emerged in Hong Kong in 1997. This virus continues to circulate in the bird population in Asia, and other H6 viruses are prevalent in birds in North America and Asia. The high rate of reassortment observed in influenza viruses and the prevalence of H6 viruses in birds suggest that this subtype may pose a pandemic risk. Very little is known about the replicative capacity, immunogenicity, and correlates of protective immunity for low-pathogenicity H6 influenza viruses in mammals. We evaluated the antigenic and genetic relatedness of 14 H6 influenza viruses and their abilities to replicate and induce a cross-reactive immune response in two animal models: mice and ferrets. The different H6 viruses replicated to different levels in the respiratory tracts of mice and ferrets, causing varied degrees of morbidity and mortality in these two models. H6 virus infection induced similar patterns of neutralizing antibody responses in mice and ferrets; however, species-specific differences in the cross-reactivity of the antibody responses were observed. Overall, cross-reactivity of neutralizing antibodies in H6 virus-infected mice did not correlate well with protection against heterologous wild-type H6 viruses. However, we have identified an H6 virus that induces protective immunity against viruses in the North American and Eurasian lineages.
C1 [Gillim-Ross, Laura; Santos, Celia; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Zhongying; Aspelund, Amy; Yang, Chin-Fen; Ye, Dan; Jin, Hong; Kemble, George] MedImmune, Mountain View, CA 94043 USA.
RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 33,Room 3E13C-1,33 N Dr,MSC 3203, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
FU NIAID, NIH; Laboratory of Infectious Diseases, NIAID; MedImmune, Inc
FX This research was supported by the Intramural Research Program of the
NIAID, NIH. This research was performed under a Cooperative Research and
Development Agreement (CRADA no. AI-0155) between the Laboratory of
Infectious Diseases, NIAID, and MedImmune, Inc.; We thank Jadon Jackson,
the staff of SoBran Inc., and the Comparative Medicine Branch, NIAID,
for excellent technical support for animal work. We also thank Robert G.
Webster for providing the virus isolates used in this study.
NR 48
TC 53
Z9 61
U1 1
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 NOV
PY 2008
VL 82
IS 21
BP 10854
EP 10863
DI 10.1128/JVI.01206-08
PG 10
WC Virology
SC Virology
GA 361EF
UT WOS:000260109600051
PM 18715930
ER
PT J
AU Demberg, T
Boyer, JD
Malkevich, N
Patterson, LJ
Venzon, D
Summers, EL
Kalisz, I
Kalyanaraman, VS
Lee, EM
Weiner, DB
Robert-Guroff, M
AF Demberg, Thorsten
Boyer, Jean D.
Malkevich, Nina
Patterson, L. Jean
Venzon, David
Summers, Ebonita L.
Kalisz, Irene
Kalyanaraman, V. S.
Lee, Eun Mi
Weiner, David B.
Robert-Guroff, Marjorie
TI Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA
Vaccines, with or without Encoded Cytokines, and a Replicating
Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control
a Pathogenic SIVmac251 Mucosal Challenge
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CELLULAR IMMUNE-RESPONSES; HOST-RANGE MUTANT; REGIMEN INDUCES BROAD;
MEMORY T-CELLS; RHESUS MACAQUES; DISEASE PROGRESSION; SHIV89.6P
CHALLENGE; NEUTRALIZING ANTIBODIES; PROTECTIVE EFFICACY; VIRAL
REPLICATION
AB Previously, combination DNA/nonreplicating adenovirus (Ad)-or poxvirus-vectored vaccines have strongly protected against SHIV89.6P, DNAs expressing cytokines have modulated immunity elicited by DNA vaccines, and replication-competent Ad-recombinant priming and protein boosting has strongly protected against simian immunodeficiency virus (SIV) challenge. Here we evaluated a vaccine strategy composed of these promising components. Seven rhesus macaques per group were primed twice with multigenic SIV plasmid DNA with or without interleukin-12 (IL-12) DNA or IL-15 DNA. After a multigenic replicating Ad-SIV immunization, all groups received two booster immunizations with SIV gp140 and SIV Nef protein. Four control macaques received control DNA plasmids, empty Ad vector, and adjuvant. All vaccine components were immunogenic, but the cytokine DNAs had little effect. Macaques that received IL-15-DNA exhibited higher peak anti-Nef titers, a more rapid anti-Nef anamnestic response postchallenge, and expanded CD8(CM) T cells 2 weeks postchallenge compared to the DNA-only group. Other immune responses were indistinguishable between groups. Overall, no protection against intrarectal challenge with SIVmac251 was observed, although immunized non-Mamu-A*01 macaques as a group exhibited a statistically significant 1-log decline in acute viremia compared to non-Mamu-A*01 controls. Possible factors contributing to the poor outcome include administration of cytokine DNAs to sites different from the Ad recombinants (intramuscular and intratracheal, respectively), too few DNA priming immunizations, a suboptimal DNA delivery method, failure to ensure delivery of SIV and cytokine plasmids to the same cell, and instability and short half-life of the IL-15 component. Future experiments should address these issues to determine if this combination approach is able to control a virulent SIV challenge.
C1 [Robert-Guroff, Marjorie] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
[Boyer, Jean D.; Weiner, David B.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Kalisz, Irene; Kalyanaraman, V. S.; Lee, Eun Mi] Adv BioSci Labs Inc, Kensington, MD 20895 USA.
RP Robert-Guroff, M (reprint author), NCI, Vaccine Branch, NIH, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA.
EM guroffm@mail.nih.gov
RI Weiner, David/H-8579-2014
FU National Institutes of Health National Cancer Institute
FX We thank Ronald C. Desrosiers, New England National Primate Research
Center, and Nancy Miller, Division of AIDS, NIAID, for the
SIVmac251 challenge virus, Barbara Felber and George Pavlakis
for the DNA plasmids originally provided to the Weiner laboratory, and
Ersell Richardson and Kris Aldrich for their technical assistance. We
also acknowledge the contributions of Sanjeev Kumar, who sadly passed
away during the course of this study. Complete sets of
SIVmac239 Gag and SIVmac239 Env peptides were
provided by the AIDS Research and Reference Reagent Program, NIAID,
NIH.; This work was supported by the Intramural Research Program of the
National Institutes of Health National Cancer Institute.
NR 66
TC 18
Z9 18
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 NOV
PY 2008
VL 82
IS 21
BP 10911
EP 10921
DI 10.1128/JVI.01129-08
PG 11
WC Virology
SC Virology
GA 361EF
UT WOS:000260109600057
PM 18753198
ER
PT J
AU Willcox, BJ
Willcox, DC
Ferrucci, L
AF Willcox, Bradley J.
Willcox, D. Craig
Ferrucci, Luigi
TI Secrets of Healthy Aging and Longevity From Exceptional Survivors Around
the Globe: Lessons From Octogenarians to Supercentenarians
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Editorial Material
ID OKINAWAN CENTENARIANS; GENETIC-DETERMINANTS; FUNCTIONAL STATUS; OLD-AGE;
POPULATIONS; LIFE; PREVALENCE; DISABILITY; PHENOTYPES; MORBIDITY
C1 [Willcox, Bradley J.; Willcox, D. Craig] Pacific Hlth Res Inst, Honolulu, HI 96813 USA.
[Willcox, Bradley J.] Queens Med Ctr, Dept Res Planning & Dev, Honolulu, HI USA.
[Willcox, Bradley J.] Univ Hawaii Manoa, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA.
[Willcox, Bradley J.; Willcox, D. Craig] Okinawa Res Ctr Longev Sci, Okinawa, Japan.
[Willcox, D. Craig] Okinawa Int Univ, Dept Human Welf, Okinawa, Japan.
[Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
RP Willcox, BJ (reprint author), Pacific Hlth Res Inst, 846 S Hotel St,Suite 201, Honolulu, HI 96813 USA.
EM bjwillcox@phrihawaii.org
FU Intramural NIH HHS [Z01 AG000015-49]; NIA NIH HHS [R01 AG027060,
R01AG027060-01]
NR 61
TC 22
Z9 22
U1 2
U2 7
PU GERONTOLOGICAL SOC AMER
PI WASHINGTON
PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD NOV
PY 2008
VL 63
IS 11
BP 1181
EP 1185
PG 5
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 379KR
UT WOS:000261395600006
PM 19038832
ER
PT J
AU Delmonico, MJ
Zmuda, JM
Taylor, BC
Cauley, JA
Harris, TB
Martini, TM
Schwartz, A
Li, R
Roth, SM
Hurley, BF
Bauer, DC
Ferrell, RE
Newman, AB
AF Delmonico, Matthew J.
Zmuda, Joseph M.
Taylor, Brent C.
Cauley, Jane A.
Harris, Tamara B.
Martini, Todd M.
Schwartz, Ann
Li, Rongling
Roth, Stephen M.
Hurley, Ben F.
Bauer, Douglas C.
Ferrell, Robert E.
Newman, Anne B.
CA Health ABC & MrOs Res Grp
TI Association of the ACTN3 Genotype and Physical Functioning With Age in
Older Adults
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Genetics; Elderly; Sarcopenia; Skeletal muscle
ID LOWER-EXTREMITY FUNCTION; BODY-COMPOSITION; MUSCLE MASS; ALPHA-ACTININ-3
DEFICIENCY; OSTEOPOROTIC FRACTURES; ATHLETIC PERFORMANCE; STRENGTH;
WOMEN; MEN; DISABILITY
AB Objective. The purpose of this study was to examine the association of the alpha-actinin-3 (ACTN3) R577X polymorphism on muscle function and physical performance in older adults.
Methods. We measured knee extensor torque, midthigh muscle cross-sectional area, muscle quality, short physical performance battery score, and 400-meter walk time at baseline and after 5 years in white older adults aged 70-79 years in the Health, Aging and Body Composition Study cohort (n = 1367). Incident persistent lower extremity limitation (PLL) over 5 years was additionally assessed. We also examined white men in the Osteoporotic Fractures in Men Study, a longitudinal, observational cohort (n = 1152) of men 65 years old or older as a validation cohort for certain phenotypes.
Results. There were no significant differences between genotype groups in men or women for adjusted baseline phenotypes. Male X-homozygotes had a significantly greater adjusted 5-year increase in their 400-meter walk time compared to R-homozygotes and heterozygotes (p = .03). In women, X-homozygotes had a similar to 35% greater risk of incident PILL compared to R-homozygotes (hazard ratio = 0.65, 95% confidence interval = 0.44-0.94). There were no other significant associations between any of the phenotypes and ACTN3 genotype with aging in either cohort.
Conclusions. The ACTN3 polymorphism may influence declines in certain measures of physical performance with aging in older white adults, based on longitudinal assessments. However, the influence of the ACTN3 R577X polymorphism does not appear to have a strong effect on skeletal muscle-related phenotypes based on the strength and consistency of the associations and lack of replication with regard to specific phenotypes.
C1 [Delmonico, Matthew J.] Univ Rhode Isl, Dept Kinesiol, Kingston, RI 02881 USA.
[Delmonico, Matthew J.; Zmuda, Joseph M.; Cauley, Jane A.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Zmuda, Joseph M.; Ferrell, Robert E.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15260 USA.
[Taylor, Brent C.] Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Martini, Todd M.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA.
[Schwartz, Ann] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Li, Rongling] Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
[Roth, Stephen M.; Hurley, Ben F.] Univ Maryland, Sch Publ Hlth, Dept Kinesiol, College Pk, MD 20742 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
RP Delmonico, MJ (reprint author), Univ Rhode Isl, Dept Kinesiol, 210 Flag Rd,Room 120, Kingston, RI 02881 USA.
EM delmonico@uri.edu
RI Taylor, Brent/A-8069-2009; Newman, Anne/C-6408-2013; Cauley,
Jane/N-4836-2015;
OI Taylor, Brent/0000-0002-2140-8377; Newman, Anne/0000-0002-0106-1150;
Cauley, Jane/0000-0003-0752-4408; Roth, Stephen/0000-0002-7841-3695
FU National Institutes of Health (NIH), NIA [1-AG-6-2101, 1-AG-6-2103,
1-AG-6-2106, U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01
AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]; National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
[U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01
AR45583, U01 AG18197, U01-AG027810, UL1 RR024140, R01-AR051124,
R01-AG021024, AG-022791]; National Center for Research Resources (NCRR)
[U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01
AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]; Department of
Epidemiology, University of Pittsburgh
FX The Health ABC study was supported by research contracts #1-AG-6-2101,
#1-AG-6-2103, and #1-AG-6-2106 from the National Institute on Aging
(NIA). This study was supported in part by the Intramural Research
Program of the National Institutes of Health (NIH), NIA. The MrOS Study
is supported by NIH funding. The following institutes provide support:
the National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS), the NIA, the National Center for Research Resources
(NCRR), 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.
Additional Support was also provided by NIAMS grants R01-AR051124,
R01-AG021024, AG-022791, the NIA Aging Training Grant, and a grant from
the Department of Epidemiology, University of Pittsburgh.
NR 33
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PU GERONTOLOGICAL SOC AMER
PI WASHINGTON
PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD NOV
PY 2008
VL 63
IS 11
BP 1227
EP 1234
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 379KR
UT WOS:000261395600012
PM 19038838
ER
PT J
AU Alley, DE
Ferrucci, L
Barbagallo, M
Studenski, SA
Harris, TB
AF Alley, Dawn E.
Ferrucci, Luigi
Barbagallo, Mario
Studenski, Stephanie A.
Harris, Tarnara B.
TI A Research Agenda: The Changing Relationship Between Body Weight and
Health in Aging
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
ID OLDER OBESE ADULTS; MASS INDEX; LONGITUDINAL CHANGES; KNEE
OSTEOARTHRITIS; PHYSICAL-DISABILITY; MUSCLE STRENGTH; SKELETAL-MUSCLE;
ELDERLY-MEN; MORTALITY; WOMEN
C1 [Ferrucci, Luigi] Harbor Hosp, NIA, Longitudinal Studies Sect, Clin Res Branch,NIA ASTRA Unit, Baltimore, MD 21225 USA.
[Alley, Dawn E.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
[Barbagallo, Mario] Univ Palermo, I-90133 Palermo, Italy.
[Studenski, Stephanie A.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15260 USA.
[Studenski, Stephanie A.] Pittsburgh Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Pittsburgh, PA USA.
[Harris, Tarnara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Ferrucci, L (reprint author), Harbor Hosp, NIA, Longitudinal Studies Sect, Clin Res Branch,NIA ASTRA Unit, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA.
EM ferruccilu@grc.nia.nih.gov
OI BARBAGALLO, MARIO/0000-0002-1349-6530
FU Intramural NIH HHS [Z01 AG000015-49]
NR 40
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U2 1
PU GERONTOLOGICAL SOC AMER
PI WASHINGTON
PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD NOV
PY 2008
VL 63
IS 11
BP 1257
EP 1259
PG 3
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 379KR
UT WOS:000261395600016
PM 19038842
ER
PT J
AU Mottl, AK
Vupputuri, S
Cole, SA
Almasy, L
Goring, HHH
Diego, VP
Laston, S
Franceschini, N
Shara, NM
Lee, ET
Best, LG
Fabsitz, RR
MacCluer, JW
Umans, JG
North, KE
AF Mottl, Amy K.
Vupputuri, Suma
Cole, Shelley A.
Almasy, Laura
Goering, Harald H. H.
Diego, Vincent P.
Laston, Sandra
Franceschini, Nora
Shara, Nawar M.
Lee, Elisa T.
Best, Lyle G.
Fabsitz, Richard R.
MacCluer, Jean W.
Umans, Jason G.
North, Kari E.
TI Linkage analysis of glomerular filtration rate in American Indians
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE glomerular filtration rate; genetic epidemiology; linkage analysis
ID STAGE RENAL-DISEASE; CHRONIC KIDNEY-DISEASE; GENES-CONTROLLING
VARIATION; URINARY ALBUMIN EXCRETION; STRONG HEART FAMILY;
DIABETIC-NEPHROPATHY; CARDIOVASCULAR-DISEASE; AFRICAN-AMERICANS;
BLOOD-PRESSURE; COLLABORATIVE APPROACH
AB American Indians have a disproportionately high rate of kidney disease likely due to a combination of environmental and genetic factors. We performed a genome wide scan of estimated glomerular filtration rate in 3665 participants of the Strong Heart Family Study to localize genes influencing kidney disease risk factors. The participants were men and women from 13 American Indian tribes recruited from 3 centers located in Arizona, the Dakotas and Oklahoma. Multipoint variance component linkage analysis was performed for each center and on the entire cohort after controlling for center effects. Modeling strategies that incorporated age, gender and interaction terms ( model 1) and another that also controlled for diabetes mellitus, systolic and diastolic blood pressure, body mass index, low density and high density lipoproteins, triglycerides and smoking status ( model 2) were used. Significant evidence for linkage in the Arizona group was found on chromosome 12p12.2 at 39cM ( nearest marker D12S310) using model 1. Additional loci with very suggestive evidence for linkage were detected at 1p36.31 for all groups using both models and at 2q33.3 and 9q34.2 for the Dakotas group each using model 1. No significant evidence for additive interaction with diabetes, hypertension or obesity was noted. This evidence for linkage of a quantitative trait locus influencing estimated glomerular filtration rate to a region of chromosome 12p in a large cohort of American Indians will be worth studying in more detail in the future.
C1 [Mottl, Amy K.; Vupputuri, Suma] Univ N Carolina, Kidney Ctr, Sch Med, Chapel Hill, NC 27599 USA.
[Vupputuri, Suma; Franceschini, Nora; North, Kari E.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Cole, Shelley A.; Almasy, Laura; Goering, Harald H. H.; Diego, Vincent P.; Laston, Sandra; MacCluer, Jean W.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA.
[Shara, Nawar M.; Umans, Jason G.] NHLBI, MedStar Res Inst, Bethesda, MD 20892 USA.
[Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA.
[Best, Lyle G.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA.
[Fabsitz, Richard R.] NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA.
[Umans, Jason G.] Georgetown Univ, Gen Clin Res Ctr, Dept Med, Div Obstet & Gynecol, Washington, DC USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
RP Mottl, AK (reprint author), Univ N Carolina, Kidney Ctr, Sch Med, CB 7155,6008 Burnett Womack Bldg, Chapel Hill, NC 27599 USA.
EM amy_mottl@med.unc.edu
OI Mottl, Amy/0000-0002-4258-1726; Diego, Vincent/0000-0002-0007-2085
FU National Heart, Lung and Blood Institute [U01 HL65520, U01 HL41642, U01
HL41652, U01 HL41654, U01 HL65521]; National Institutes of Health
[MH059490]
FX We thank the Strong Heart Family Study participants. Without their
participation, this project would not have been possible. In addition,
the cooperation of the Indian Health Service hospitals and clinics, and
the directors of the SHS clinics, and the many collaborators and staff
of the Strong Heart Study have made this project possible. This research
was funded by a cooperative agreement that includes grants U01 HL65520,
U01 HL41642, U01 HL41652, U01 HL41654, and U01 HL65521 from the National
Heart, Lung and Blood Institute. Development of SOLAR and the methods
implemented in it are supported by US Public Health Service grant
MH059490 from the National Institutes of Health. The views expressed in
this paper are those of the authors and do not necessarily reflect those
of the Indian Health Service.
NR 58
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U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD NOV
PY 2008
VL 74
IS 9
BP 1185
EP 1191
DI 10.1038/ki.2008.410
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 360MJ
UT WOS:000260061300013
PM 18854848
ER
PT J
AU Jacob, VA
Harbaugh, CM
Dietz, JR
Fenton, RA
Kim, SM
Castrop, H
Schnermann, J
Knepper, MA
Chou, CL
Anderson, SA
AF Jacob, Vinitha A.
Harbaugh, Calista M.
Dietz, John R.
Fenton, Robert A.
Kim, Soo M.
Castrop, Hayo
Schnermann, Jurgen
Knepper, Mark A.
Chou, Chung-Lin
Anderson, Stasia A.
TI Magnetic resonance imaging of urea transporter knockout mice shows renal
pelvic abnormalities
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE hydronephrosis; renal pelvic reflux; blood pressure
ID SALT-SENSITIVE HYPERTENSION; POLYCYSTIC KIDNEY-DISEASE; CONCENTRATING
ABILITY; LACKING AQUAPORIN-1; HYDRONEPHROSIS; URINE; MODEL; RATS; MRI
AB Many transgenic and knockout mice with increased urine flow have structural abnormalities of the renal pelvis and inner medulla. Here, we used high resolution contrast enhanced T1-weighted magnetic resonance imaging of mice whose urea transporters UT-A1 and UT-A3 were deleted (UT-A1/3(-/-) mice) as a model for the in vivo study of such abnormalities. Three distinct variations in the appearance of the renal pelvis were found. These included normal kidneys with no accumulation of contrast agent in the renal pelvis; infrequent frank right-sided unilateral hydronephrosis with marked atrophy of the renal medulla; and a renal pelvic reflux pattern characterized by the presence of contrast agent in the renal pelvis surrounding the renal inner medulla but no substantial atrophy of the medulla. This last pattern was found in most of the advanced age UT-A1/3(-/-) mice and in aquaporin-1 knockout mice. The UT-A1/3(-/-) mice also had increased mean arterial blood pressures. Feeding the mice a low protein diet did not prevent development of their renal pelvic abnormalities. Our studies show that real time imaging of renal pelvic structure in genetically manipulated mice provides a tool for the non-destructive, temporal evaluation of kidney structure.
C1 [Jacob, Vinitha A.; Harbaugh, Calista M.; Knepper, Mark A.; Chou, Chung-Lin] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA.
[Dietz, John R.] Univ S Florida, Dept Physiol & Biophys, Tampa, FL USA.
[Fenton, Robert A.] Univ Aarhus, Inst Anat, Water & Salt Res Ctr, Aarhus, Denmark.
[Kim, Soo M.; Castrop, Hayo; Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD 20892 USA.
[Anderson, Stasia A.] NHLBI, Anim MRI Imaging Core, NIH, Bethesda, MD 20892 USA.
RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,Bldg 10,Room 6N260, Bethesda, MD 20892 USA.
EM knepperm@nhlbi.nih.gov
FU NHLBI [Z01-HL00185]; NIDDK [Z01-DK043408]
FX We thank Aneeka Chaudhry for her excellent technical assistance with MRI
imaging. The work described in this paper was supported by the
Intramural budgets of NHLBI (Z01-HL00185) and NIDDK (Z01-DK043408).
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD NOV
PY 2008
VL 74
IS 9
BP 1202
EP 1208
DI 10.1038/ki.2008.392
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 360MJ
UT WOS:000260061300016
PM 18854850
ER
PT J
AU Motoyoshi, Y
Matsusaka, T
Saito, A
Pastan, I
Willnow, TE
Mizutani, S
Ichikawa, I
AF Motoyoshi, Yaeko
Matsusaka, Taiji
Saito, Akihiko
Pastan, Ira
Willnow, Thomas E.
Mizutani, Shuki
Ichikawa, Iekuni
TI Megalin contributes to the early injury of proximal tubule cells during
nonselective proteinuria
SO KIDNEY INTERNATIONAL
LA English
DT Article; Proceedings Paper
CT 40th Annual Meeting of the American-Society-of-Nephrology/Annual Renal
Week
CY OCT 31-NOV 05, 2007
CL San Francisco, CA
SP Amer Soc Nephrol
DE chronic kidney disease; endocytosis; focal segmental glomerulosclerosis;
nephrotic syndrome
ID SEGMENTAL GLOMERULOSCLEROSIS; RENAL AQUAPORINS; TRANSGENIC MICE;
KAPPA-B; EXPRESSION; ALBUMIN; GENE; APOPTOSIS; OVERLOAD; DISEASE
AB Megalin, a member of the LDL receptor family, is expressed on the apical membrane of proximal tubules and serves as an endocytic scavenger of filtered proteins and hence might contribute to the tubule injury as a consequence of glomerular disease. To study its role, we crossed megalin knockout mosaic mice (lacking megalin expression in 60% of proximal tubule cells) with NEP25 mice (a transgenic line expressing human CD25 in the podocyte). Treatment of this transgenic mouse with the immunotoxin causes nephrotic syndrome, focal segmental glomerulosclerosis and tubule-interstitial injury. Following this treatment, the double transgenic mice had massive non-selective proteinuria and mild glomerular and tubular injury. Comparison of megalin-containing to megalin-deficient proximal tubule cells within each kidney showed that albumin, immunoglobulin light chain, IgA and IgG were preferentially accumulated in proximal tubule cells expressing megalin. Tubule injury markers such as heme-oxygenase-1, monocyte chemoattractant protein-1 and cellular apoptosis were also preferentially found in these megalin-expressing cells. These results show that megalin plays a pivotal role in the reabsorption of small to large molecular size proteins and provides direct in vivo evidence that reabsorption of filtered proteins triggers events leading to tubule injury.
C1 [Motoyoshi, Yaeko; Ichikawa, Iekuni] Tokai Univ, Sch Med, Dept Bioeth, Isehara, Kanagawa 2591193, Japan.
[Motoyoshi, Yaeko; Mizutani, Shuki] Tokyo Med & Dent Univ, Grad Sch Med, Dept Pediat & Dev Biol, Bunkyo Ku, Tokyo, Japan.
[Matsusaka, Taiji; Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37212 USA.
[Matsusaka, Taiji] Tokai Univ, Sch Med, Dept Internal Med, Isehara, Kanagawa 25911, Japan.
[Saito, Akihiko] Niigata Univ, Grad Sch Med & Dent Sci, Dept Appl Mol Med, Niigata, Japan.
[Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Willnow, Thomas E.] Max Delbruck Ctr Mol Med, Berlin, Germany.
RP Ichikawa, I (reprint author), Tokai Univ, Sch Med, Dept Bioeth, 143 Shimo Kasuya, Isehara, Kanagawa 2591193, Japan.
EM ichikawaMD@aol.com
FU Intramural NIH HHS [Z01 BC008753-25]
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U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD NOV
PY 2008
VL 74
IS 10
BP 1262
EP 1269
DI 10.1038/ki.2008.405
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 367DI
UT WOS:000260532300008
PM 18769366
ER
PT J
AU O'Meara, WP
Bejon, P
Mwangi, TW
Okiro, EA
Peshu, N
Snow, RW
Newton, CRJC
Marsh, K
AF O'Meara, Wendy P.
Bejon, Phillip
Mwangi, Tabitha W.
Okiro, Emelda A.
Peshu, Norbert
Snow, Robert W.
Newton, Charles R. J. C.
Marsh, Kevin
TI Effect of a fall in malaria transmission on morbidity and mortality in
Kilifi, Kenya
SO LANCET
LA English
DT Article
ID PLASMODIUM-FALCIPARUM TRANSMISSION; INSECTICIDE-TREATED BEDNETS; AFRICAN
CHILDREN; REDUCING TRANSMISSION; PROGNOSTIC INDICATORS; CLINICAL
PRESENTATION; CHILDHOOD MALARIA; SEVERE DISEASE; DRUG POLICY; COAST
AB Background As efforts to control malaria are expanded across the world, understanding the role of transmission intensity in determining the burden of clinical malaria is crucial to the prediction and measurement of the effectiveness of interventions to reduce transmission. Furthermore, studies comparing several endemic sites led to speculation that as transmission decreases morbidity and mortality caused by severe malaria might increase. We aimed to assess the epidemiological characteristics of malaria in Kilifi, Kenya, during a period of decreasing transmission intensity.
Methods We analyse 18 years (1990-2007) of surveillance data from a paediatric ward in a malaria-endemic region of Kenya. The hospital has a catchment area of 250000 people. Clinical data and blood-film results for more than 61000 admissions are reported.
Findings Hospital admissions for malaria decreased from 18-43 per 1000 children in 2003 to 3.42 in 2007. Over 18 years of surveillance, the incidence of cerebral malaria initially increased; however, malaria mortality decreased overall because of a decrease in incidence of severe malarial anaemia since 1997 (4.75 to 0.37 per 1000 children) and improved survival among children admitted with non-severe malaria. Parasite prevalence, the mean age of children admitted with malaria, and the proportion of children with cerebral malaria began to change 10 years before hospitalisation for malaria started to fall.
Interpretation Sustained reduction in exposure to infection leads to changes in mean age and presentation of disease similar to those described in multisite studies. Changes in transmission might not lead to immediate reductions incidence of clinical disease. However, longitudinal data do not indicate that reductions in transmission intensity lead to transient increases in morbidity and mortality.
Funding Wellcome Trust, Kenya Medical Research Institute.
C1 [O'Meara, Wendy P.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Okiro, Emelda A.; Snow, Robert W.] Kenya Govt Med Res Ctr, Wellcome Trust Collaborat Program, Nairobi, Kenya.
[Bejon, Phillip; Snow, Robert W.; Marsh, Kevin] Univ Oxford, John Radcliffe Hosp, Ctr Trop Med, Nuffield Dept Clin Med, Oxford OX3 9DU, England.
[Newton, Charles R. J. C.] UCL, Inst Child Hlth, London, England.
[O'Meara, Wendy P.; Bejon, Phillip; Mwangi, Tabitha W.; Peshu, Norbert; Newton, Charles R. J. C.; Marsh, Kevin] Kenya Govt Med Res Ctr, Ctr Geog Med Res, Wellcome Trust Collaborat Program, Kilifi, Kenya.
RP O'Meara, WP (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA.
EM prudhomw@mail.nih.gov
OI Newton, Charles/0000-0002-6999-5507
FU Fogarty International Center; Wellcome Trust
FX This work is published with the permission of the Director of Kenya
Medical Research Institute. We wish to thank all the clinical, field,
and laboratory staff at the Kenya Medical Research Institute-Wellcome
Must Programme who made this study possible. WPO is funded by the
Fogarty International Center. CRJCN is funded by the Wellcome Trust. RWS
is a Wellcome Trust Principal Research Fellow (#079080).
NR 38
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U1 1
U2 14
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 NOV 1
PY 2008
VL 372
IS 9649
BP 1555
EP 1562
DI 10.1016/S0140-6736(08)61655-4
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 367ZG
UT WOS:000260590500027
PM 18984188
ER
PT J
AU Morens, DM
Folkers, GK
Fauci, AS
AF Morens, David M.
Folkers, Gregory K.
Fauci, Anthony S.
TI Emerging infections: a perpetual challenge
SO LANCET INFECTIOUS DISEASES
LA English
DT Review
ID PANDEMIC INFLUENZA; BIOLOGICAL WARFARE; EPIDEMIC ANTHRAX; DISEASES;
ORIGIN; PERSPECTIVE; EMERGENCE; MORTALITY; OUTBREAK; PLAGUES
AB Emerging and re-emerging infectious diseases, and their determinants, have recently attracted substantial scientific and popular attention. HIV/AIDS, severe acute respiratory syndrome, H5N1 avian influenza, and many other emerging diseases have either proved fatal or caused international alarm. Common and interactive co-determinants of disease emergence, including population growth, travel, and environmental disruption, have been increasingly documented and studied. Are emerging infections a new phenomenon related to modern life, or do more basic determinants, transcending time, place, and human progress, govern disease generation? By examining a number of historically notable epidemics, we suggest that emerging diseases, similar in their novelty, impact, and elicitation of control responses, have occurred throughout recorded history. Fundamental determinants, typically acting in concert, seem to underlie their emergence, and infections such as these are likely to continue to remain challenges to human survival.
C1 [Morens, David M.; Folkers, Gregory K.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, NIH, Bldg 31,Room 7A10,31 Ctr Dr, Bethesda, MD 20892 USA.
EM dm270q@nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 87
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U1 1
U2 34
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 NOV
PY 2008
VL 8
IS 11
BP 710
EP 719
DI 10.1016/S1473-3099(08)70256-1
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA 365EK
UT WOS:000260388500020
PM 18992407
ER
PT J
AU Simon-Sanchez, J
Singleton, A
AF Simon-Sanchez, Javier
Singleton, Andrew
TI Genome-wide association studies in neurological disorders
SO LANCET NEUROLOGY
LA English
DT Review
ID AMYOTROPHIC-LATERAL-SCLEROSIS; PERIODIC LIMB MOVEMENTS; GENETIC
RISK-FACTOR; PARKINSON-DISEASE; SUSCEPTIBILITY GENE; MULTIPLE-SCLEROSIS;
ISCHEMIC-STROKE; REVEALS; VARIANTS; RELEASE
AB Background During the past decade, the genetic causes of monogenic forms of disease have been successfully defined; this work has helped the progression of basic scientific investigation into many disorders, and has helped to characterise several molecular biological processes. An important goal of genetic research is to extend this work and define genetic risk factor loci for complex disorders. The aim is for these data not only to offer further basic understanding of the disease process, but also to provide the opportunity to obtain genetic risk assessments that could be generalised to the public.
Recent developments The development of resources such as the Human Genome Project and the international Human Haplotype Map Project, coupled with technological advances in ultra-high-throughput genotyping, have provided the basis for genome-wide association studies (GWAS). This approach has been successful for several complex disorders in a short time. Although GWAS are still a new method, these studies have been used for a small number of neurological disorders and, despite varied results for these conditions, GWAS can usefully show the power and limitations of this approach.
Where next? GWAS have the potential to show and emphasise common genetic variability associated with disease. However, a challenge of this approach is that large sample series and considerable resources are required. One important consideration will be the interpretation of the results of GWAS in a clinically meaningful way and to discern the implications for all therapy areas, including neurological disorders; this challenge will require specialised skills and resources from both the medical and the scientific communities.
C1 [Simon-Sanchez, Javier; Singleton, Andrew] NIA, Mol Genet Sect, Neurogenet Lab, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Simon-Sanchez, Javier] CSIC, Inst Biomed, Dept Genom & Prote, Unidad Genet Mol, Valencia, Spain.
[Singleton, Andrew] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
RP Singleton, A (reprint author), NIA, Mol Genet Sect, Neurogenet Lab, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Singleton, Andrew/C-3010-2009
FU National Institute on Aging; National Institutes of Health; Department
of Health and Human Services; Intramural project [Z01 AG000949-02]
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, the National Institutes of Health, and the
Department of Health and Human Services, and relates to concepts
developed under Intramural project Z01 AG000949-02.
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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 NOV
PY 2008
VL 7
IS 11
BP 1067
EP 1072
DI 10.1016/S1474-4422(08)70241-2
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 370EP
UT WOS:000260745800018
PM 18940696
ER
PT J
AU Klier, M
Anastasov, N
Hermann, A
Meindl, T
Angermeier, D
Raffeld, M
Fend, F
Quintanilla-Martinez, L
AF Klier, M.
Anastasov, N.
Hermann, A.
Meindl, T.
Angermeier, D.
Raffeld, M.
Fend, F.
Quintanilla-Martinez, L.
TI Specific lentiviral shRNA-mediated knockdown of cyclin D1 in mantle cell
lymphoma has minimal effects on cell survival and reveals a regulatory
circuit with cyclin D2
SO LEUKEMIA
LA English
DT Article
DE cyclin D1; cyclin D1 knockdown; MCL; lentiviral infection
ID MESSENGER-RNA LEVELS; MOLECULAR PATHOGENESIS; MULTIPLE-MYELOMA;
EXPRESSION; APOPTOSIS; GENES; OVEREXPRESSION; PROLIFERATION; INDUCTION;
PERSPECTIVES
AB Cyclin D1 overexpression is the hallmark of mantle cell lymphoma (MCL). However, the importance of cyclin D1 in the maintenance and progression of the disease remains to be defined. The aim of this study was to elucidate the role of cyclin D1 overexpression using an efficient cyclin D1-shRNA and a lentiviral system in well-characterized MCL cell lines. Surprisingly, the knockdown of cyclin D1 led to a moderate retardation in growth, without induction of apoptosis. The cyclin D1-shRNA-transduced MCL cells showed a 15% shift from S phase to G(1) phase of the cell cycle, a weak induction of p27(Kip1), decreased Rb (Ser807/811) phosphorylation, and a consistent upregulation of cyclin D2 mRNA and protein expression. However, double knockdown of cyclins D1 and D2 did not intensify the effects observed with cyclin D1 knockdown alone. These data suggest that the moderate effects of cyclin D1 downregulation on survival and proliferation are likely the result of compensatory cyclin-independent mechanisms governing proliferation or alternatively, secondary genetic events that make cyclin D1 dispensable. These findings have important implications for MCL therapy, as strategies targeting only cyclin D1 function might be hampered by compensatory regulatory mechanisms, resulting in a low probability of treatment response.
C1 [Klier, M.; Anastasov, N.; Angermeier, D.; Quintanilla-Martinez, L.] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Pathol, D-85764 Neuherberg, Germany.
[Hermann, A.] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Stem Cell Res, D-85764 Neuherberg, Germany.
[Meindl, T.] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Toxicol, D-85764 Neuherberg, Germany.
[Raffeld, M.] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Fend, F.] Univ Tubingen, Inst Pathol, Tubingen, Germany.
RP Quintanilla-Martinez, L (reprint author), German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Pathol, Bldg 35,Room 2055,Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.
EM quintanilla-fend@helmholtz-muenchen.de
RI Anastasov, Natasa/M-9848-2014
OI Anastasov, Natasa/0000-0002-4088-1119
FU Mantle cell lymphoma Consortium; Lymphoma Research foundation
FX We are grateful to Dr Dolors Colomer (University of Barcelona) for
donating some of the MCL cell lines used in this study. We thank Dr
Ludger Hengst (University of Innsbruck) for donating pSuper vector and
Ulrike Reich for her excellent technical assistance. This study was
supported in part by-grant from the Mantle cell lymphoma Consortium,
Lymphoma Research foundation (to LQ-M). LQ-M, FF and MR designed the
research; MK, NA, TM, AH and DA performed the research; and LQ-M, MK, FF
and MR drafted the paper.
NR 36
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Z9 49
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD NOV
PY 2008
VL 22
IS 11
BP 2097
EP 2105
DI 10.1038/leu.2008.213
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA 371LM
UT WOS:000260832800014
PM 18685613
ER
PT J
AU Lu, HB
Yang, SL
Zuo, YT
Demny, S
Stein, EA
Yang, YH
AF Lu, Hanbing
Yang, Shaolin
Zuo, Yantao
Demny, Steven
Stein, Elliot A.
Yang, Yihong
TI Real-time animal functional magnetic resonance imaging and its
application to neurophamacological studies
SO MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE Real-time MRI; Manganese-enhanced MRI; Functional MRI; phMR; Cocaine
ID HUMAN BRAIN; RAT-BRAIN; MRI; FMRI; COCAINE; ACTIVATION; RESPONSES; BOLD;
MEMRI; PHYSIOLOGY
AB In pharmacological magnetic resonance imaging (phMRI) with anesthetized animals, there is usually only a single time window to observe the dynamic signal change to an acute drug administration since subsequent drug injections are likely to result in altered response properties (e.g., tolerance). Unlike the block-design experiments in which fMRI signal can be elicited with multiple repetitions of a task, these single-event experiments require stable baseline in order to reliably identify drug-induced signal changes. Such factors as subject motion, scanner instability and/or alterations in physiological conditions of the anesthetized animal could confound the baseline signal. The unique feature of such functional MRI (fMRI) studies necessitates a technique that is able to monitor MRI signal in a real-time fashion and to interactively control certain experimental procedures. In the present Study, an approach for real-time MRI on a Bruker scanner is presented. The custom software runs on the console computer in parallel with the scanner imaging software, and no additional hardware is required. The utility of this technique is demonstrated in manganese-enhanced MRI (MEMRI) with acute cocaine challenge, in which temporary disruption of the blood-brain barrier (BBB) is a critical step for MEMRI experiments. With the aid of real-time MRI, we were able to assess the outcome of BBB disruption following bolus injection of hyperosmolar mannitol in a near real-time fashion prior to drug administration, improving experimental success rate. It is also shown that this technique can be applied to monitor baseline physiological conditions in conventional fMRI experiments using blood oxygenation level-dependent (BOLD) contrast, further demonstrating the versatility of this technique. (c) Published by Elsevier Inc.
C1 [Lu, Hanbing; Yang, Shaolin; Zuo, Yantao; Demny, Steven; Stein, Elliot A.; Yang, Yihong] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Lu, HB (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM luha@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse,;
National Institutes of Health
FX The authors thank T.J. Ross at the National Institute on Drug Abuse and
M. Mattingly of Bruker Biospin MRI, Inc., for valuable discussions. This
work was supported by the Intramural Research Program of the National
Institute on Drug Abuse, National Institutes of Health.
NR 34
TC 6
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 0730-725X
J9 MAGN RESON IMAGING
JI Magn. Reson. Imaging
PD NOV
PY 2008
VL 26
IS 9
BP 1266
EP 1272
DI 10.1016/j.mri.2008.02.020
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 375AS
UT WOS:000261085500010
PM 18448300
ER
PT J
AU Fried, LP
Varadhan, R
Bohr, VA
AF Fried, Linda P.
Varadhan, Ravi
Bohr, Vilhelm A.
TI Opinion section on frailty Preface
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Editorial Material
C1 [Bohr, Vilhelm A.] NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA.
[Fried, Linda P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Varadhan, Ravi] Johns Hopkins Univ, Baltimore, MD USA.
RP Bohr, VA (reprint author), NIA, NIH, Lab Mol Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
FU Intramural NIH HHS [Z01 AG000726-15]; NIA NIH HHS [R37 AG019905]
NR 0
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD NOV
PY 2008
VL 129
IS 11
BP 665
EP 665
DI 10.1016/j.mad.2008.10.001
PG 1
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 397KJ
UT WOS:000262661300007
PM 18951913
ER
PT J
AU Ferrucci, L
Giallauria, F
Schlessinger, D
AF Ferrucci, Luigi
Giallauria, Francesco
Schlessinger, David
TI Mapping the road to resilience: Novel math for the study of frailty
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Editorial Material
DE frailty; aging; resilience; biological homeostasis; biology of aging
ID SPECTROSCOPY; DISORDERS
AB Frailty stands at the nexus of geriatrics and gerontology, and requires both basic biology and clinical knowledge for its analysis. Understanding frailty difficulties much more than simply adding another outcome measure in epidemiological studies. The major challenge is the identification of multiple feed-forward and feed-back signaling pathways involved in the maintenance of biological homeostasis in complex organisms that may fail with aging. The cause of frailty and loss of resilience is probably a progressive loss of redundancy in these response patterns and connections.
Advances toward the development of a theoretical model that can potentially embrace the complexity of frailty should be highly encouraged, especially models designed to explain the biology of aging which can promote a better integration and communication between scientists who study this problem from different perspectives. Published by Elsevier Ireland Ltd.
C1 [Ferrucci, Luigi; Giallauria, Francesco; Schlessinger, David] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
RP Ferrucci, L (reprint author), Harbor Hosp, NIA, NIH, Longitudinal Studies Sect,Clin Res Branch, 3001 S Hanover St, Baltimore, MD 21225 USA.
EM ferruccilu@grc.nia.nih.gov
RI Giallauria, Francesco/B-5681-2013
OI Giallauria, Francesco/0000-0003-4119-9397
FU NIA NIH HHS [Z01 AG000971-01]
NR 10
TC 13
Z9 13
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD NOV
PY 2008
VL 129
IS 11
BP 677
EP 679
DI 10.1016/j.mad.2008.09.007
PG 3
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 397KJ
UT WOS:000262661300012
PM 18929593
ER
PT J
AU Romagnoli, R
Baraldi, PG
Sarkar, T
Cara, CL
Lopez, OC
Carrion, MD
Preti, D
Tolomeo, M
Balzarini, J
Hamel, E
AF Romagnoli, Romeo
Baraldi, Pier Giovanni
Sarkar, Taradas
Cara, Carlota Lopez
Lopez, Olga Cruz
Carrion, Maria Dora
Preti, Delia
Tolomeo, Manlio
Balzarini, Jan
Hamel, Ernest
TI Synthesis and Biological Evaluation of
2-aroyl-4-phenyl-5-hydroxybenzofurans as a New Class of Antitubulin
Agents
SO MEDICINAL CHEMISTRY
LA English
DT Article
DE Microtubule; benzofuran; antiproliferative activity
ID POTENT ANTITUMOR AGENTS; ETHYL-ESTER DERIVATIVES; ANTIMITOTIC AGENTS;
TUBULIN; CANCER; POLYMERIZATION; DISCOVERY; GROWTH
AB Microtubules are among the most successful targets for development of compounds useful for anticancer therapy. Continuing our project to develop new small molecule antitumor agents, two new series of derivatives based on the 2-aroyl-4-phenylbenzofuran molecular skeleton were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. SAR were elucidated with various substitutions on the benzoyl moiety at the 2-position of the benzofuran ring. The most promising compound in this series, the (5-hydroxy-4-phenylbenzofuran-2yl)( 4-methoxyphenyl) methanone derivative (3d), has significant growth inhibitory activity in the submicromolar range against the Molt4, CEM and HeLa cancer cell lines and interacts with tubulin by binding to the colchicine site. Exposure to 3d led to the arrest of K562 cells in the G2-M phase of the cell cycle and to the induction of apoptosis.
C1 [Romagnoli, Romeo; Baraldi, Pier Giovanni; Cara, Carlota Lopez; Lopez, Olga Cruz; Carrion, Maria Dora; Preti, Delia] Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy.
[Sarkar, Taradas; Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[Tolomeo, Manlio] Univ Palermo, Div Ematol, Palermo, Italy.
[Tolomeo, Manlio] Univ Palermo, Policlin P Giaccone, Dipartimento Oncol, AIDS Serv, Palermo, Italy.
[Balzarini, Jan] Rega Inst, Lab Virol & Chemotherapy, B-3000 Louvain, Belgium.
RP Romagnoli, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, Via Fossato di Mortara 17-19, I-44100 Ferrara, Italy.
EM rmr@unife.it
RI LOPEZ-CARA, LUISA CARLOTA/F-9686-2014; Carrion, M. Dora/G-8638-2015;
preti, delia/G-9916-2015; Romagnoli, Romeo/G-9887-2015; Baraldi, Pier
Giovanni/B-7933-2017
OI LOPEZ-CARA, LUISA CARLOTA/0000-0003-1142-6448; Carrion, M.
Dora/0000-0002-6794-3949; preti, delia/0000-0002-1075-3781;
FU Ramon Areces Foundation
FX OC- L thanks the Ramon Areces Foundation for financial support.
NR 17
TC 6
Z9 8
U1 0
U2 2
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1573-4064
J9 MED CHEM
JI Med. Chem.
PD NOV
PY 2008
VL 4
IS 6
BP 558
EP 564
DI 10.2174/157340608786242007
PG 7
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 387BK
UT WOS:000261926500008
PM 18991740
ER
PT J
AU van der Hilst, JCH
Bodar, EJ
Barron, KS
Frenkel, J
Drenth, JPH
van der Meer, JWM
Simon, A
AF van der Hilst, Jeroen C. H.
Bodar, Evelien J.
Barron, Karyl S.
Frenkel, Joost
Drenth, Joost P. H.
van der Meer, Jos W. M.
Simon, Anna
CA Int HIDS Study Grp
TI Long-Term Follow-Up, Clinical Features, and Quality of Life in a Series
of 103 Patients With Hyperimmunoglobulinemia D Syndrome
SO MEDICINE
LA English
DT Article
ID PERIODIC FEVER SYNDROME; FAMILIAL MEDITERRANEAN FEVER; HYPER-IGD
SYNDROME; MEVALONATE KINASE-DEFICIENCY; INTERLEUKIN-1-BETA SECRETION;
DIAGNOSTIC-VALUE; SYNDROME HIDS; HEALTH-STATUS; MUTATIONS; SPECTRUM
AB The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). one of the autoinflammatory syndromes, is caused by Mutations in the gene coding for mevalonate kinase (MVK). We conducted the current study to assess the genetic, laboratory, and clinical features as well as the complications and course of disease in patients with genetically confirmed HIDS. fit addition. we studied the quality of lite Mid Course of life in a selection of patients. Follow-up data were obtained by a questionnaire sent to all physicians of patients in the international HIDS Database. In addition. we assessed the course of life and quality of life in Dutch patients aged >16 years using validated quality of life instruments.
Data were obtained from 103 patients from 18 different countries. The median age of first attack was 6 months (rang-c. 0-120 mo). with a median period of 9.9 years from onset of disease to diagnosis. The most frequent symptoms that accompanied attacks of fever were lymphadenopathy, abdominal pain, arthralgia, diarrhea. vomiting, skin lesions, and aphthous ulcers. Amyloidosis was a severe but infrequent complication (2.9%). The median serum IgD level was 400 U/mL. IgD levels were normal in 22%, of patients. The 4 most prevalent Mutations (V3771, 1268T, H20P/N, P167L) accounted for 71.5% of mutations found. The frequency Of attacks decreased with the patient's increasing age, although 50% of patients over the age of 20 years still had 6 or more attacks per year. Many drugs have been tried in HIDS. Some patients responded to high-close prednisone (24.4% response). Anakinra and etanercept can also be effective (33.3% response). Quality of life was determined in a Subgroup of patients (n = 28). Social functioning, general health perception, and vitality were significantly lower in patients with HIDS than in controls, as were autonomy and social development. In addition, HIDS had all adverse impact oil educational achievements and employment status. In conclusion, HIDS is ail early-onset disease that is accompanied by in array of inflammatory symptoms. Although the frequently of attacks decreases during the patient's life, many patients continue to have frequent attacks. HIDS impairs several aspects of quality of life.
C1 [van der Hilst, Jeroen C. H.; Bodar, Evelien J.; van der Meer, Jos W. M.; Simon, Anna] Radboud Univ Nijmegen, Med Ctr, Dept Gen Internal Med, NL-6500 HB Nijmegen, Netherlands.
[Drenth, Joost P. H.] Radboud Univ Nijmegen, Med Ctr, Dept Gastroenterol & Hepatol, NL-6500 HB Nijmegen, Netherlands.
[Frenkel, Joost] Univ Med Ctr, Div Pediat, Dept Gen Pediat, Utrecht, Netherlands.
[Frenkel, Joost] Univ Med Ctr, Div Pediat, Dept Pediat Immunol, Utrecht, Netherlands.
[Barron, Karyl S.] NIAID, NIH, Bethesda, MD 20892 USA.
RP van der Hilst, JCH (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Gen Internal Med 463, St Radboud,Geert Grrotepl 8,POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM j.vanderhilst@aig.umcn.nl
RI Simon, Anna/D-3757-2009; Gardner-Medwin, Janet/J-2512-2012; Drenth,
J.P.H./H-8025-2014; van der Meer, Jos/C-8521-2013
OI Simon, Anna/0000-0002-6141-7921; van der Meer, Jos/0000-0001-5120-3690
FU Intramural Research Divisions of the National Institute of Allergy and
Infectious Diseases; National Institute of Arthritis and Musculosketal
and Skin Diseases; National Institutes of Health, Bethesda, Maryland
FX This work was partially supported by the Intramural Research Divisions
of the National Institute of Allergy and Infectious Diseases and the
National Institute of Arthritis and Musculosketal and Skin Diseases,
National Institutes of Health, Bethesda, Maryland.
NR 40
TC 127
Z9 128
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7974
J9 MEDICINE
JI Medicine (Baltimore)
PD NOV
PY 2008
VL 87
IS 6
BP 301
EP 310
DI 10.1097/MD.0b013e318190cfb7
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 373NG
UT WOS:000260978100001
PM 19011501
ER
PT J
AU Cooper, R
Mishra, G
Clennell, S
Guralnik, J
Kuh, D
AF Cooper, Rachel
Mishra, Gita
Clennell, Suzie
Guralnik, Jack
Kuh, Diana
TI Menopausal status and physical performance in midlife: findings from a
British birth cohort study
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Menopause; Hysterectomy; Grip strength; Chair rises; Standing balance;
Physical performance
ID HORMONE REPLACEMENT THERAPY; MUSCLE STRENGTH; GRIP STRENGTH;
DEVELOPMENTAL ORIGINS; POSTMENOPAUSAL WOMEN; NATIONAL-SURVEY;
ELDERLY-WOMEN; RISK-FACTORS; LIFE-COURSE; AGE
AB Objective: To test the associations of menopausal status, timing of menopause, and hysterectomy with physical performance at age 53 years.
Design: Using data on women participating in the Medical Research Council National Survey of Health and Development who have been followed up since birth in March 1946 (N = 1,386), associations of interest were examined. Menopausal status, grip strength, chair rises, and standing balance time were assessed at age 53, and covariates were measured across life.
Results: Women who were postmenopausal and not using hormone therapy at age 53 had lower mean grip strength than women who were still pre- or perimenopausal at this age. However, this trend of decreasing grip strength across the three natural menopausal categories (from pre- to postmenopausal) was explained by current body size. Those women who had undergone hysterectomy before age 40 had significantly weaker grip strength than women who had undergone hysterectomy at later ages; in fully adjusted analyses, those women who had a hysterectomy before age 40 had a mean grip strength 5.21 kg (95% CI: 2.18-8.25) lower than women who had a hysterectomy between ages 50 and 53. There were no significant associations between menopausal status or age at hysterectomy and chair rise or standing balance time and also no significant associations between timing of menopause and any of the performance measures.
Conclusions: Women who have hysterectomies at young ages represent a group who may require more support than other women to achieve and maintain good physical performance, especially muscle strength, in midlife.
C1 [Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Cooper, Rachel; Mishra, Gita; Clennell, Suzie; Kuh, Diana] UCL, MRC Unit Lifelong Hlth & Ageing, Dept Epidemiol & Publ Hlth, London, England.
RP Cooper, R (reprint author), Royal Free & Univ Coll Med Sch, Dept Epidemiol & Publ Hlth, MRC Unit Lifelong Hlth & Ageing, MRC Natl Survery Hlth & Dev, 1-19 Torrington Pl, London WC1E 6BT, England.
EM r.cooper@nshd.mrc.ac.uk
RI Mishra, Gita/F-8052-2011;
OI Mishra, Gita/0000-0001-9610-5904; Cooper, Rachel/0000-0003-3370-5720
FU Medical Research Council, United Kingdom; Intramural Research Program;
National Institute oil Aging; National Institutes of Health
FX This Study was supported by the Medical Research Council, United Kingdom
and in part by the Intramural Research Program, National Institute oil
Aging, National Institutes of Health.
NR 33
TC 19
Z9 22
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD NOV-DEC
PY 2008
VL 15
IS 6
BP 1079
EP 1085
DI 10.1097/gme.0b013e31816f63a3
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 371VA
UT WOS:000260858500013
PM 18520694
ER
PT J
AU Varnai, P
Balla, T
AF Varnai, Peter
Balla, Tamas
TI Live cell imaging of phosphoinositides with expressed inositide binding
protein domains
SO METHODS
LA English
DT Article
DE Calcium signaling; Pleckstrin homology domain; Phosphoinositide; Green
fluorescent protein; Confocal microscopy
ID PLECKSTRIN-HOMOLOGY-DOMAIN; RESONANCE ENERGY-TRANSFER; BRUTONS TYROSINE
KINASE; SINGLE LIVING CELLS; PLASMA-MEMBRANE; PH DOMAIN;
PHOSPHATIDYLINOSITOL 3,5-BISPHOSPHATE; STIMULATED TRANSLOCATION;
PHOSPHOLIPASE-C; LIPID PRODUCTS
AB Inositol lipids and calcium signaling has been inseparable twins during the 1980s when the molecular details of phospholipase C-mediated generation of inositol 1,4,5-trisphosphate (InsP(3)) and its Ca2+ mobilizing action were discovered. Since then, both the Ca2+ and inositol lipid signaling fields have hugely expanded and the tools allowing dissection of the finest details of their molecular organization also followed closely. Although phosphoinositides regulate many cell functions unrelated to Ca2+ signaling there are still many open questions even in the Ca2+ field that would benefit from single cell monitoring of PtdIns(4,5)P-2. or InSP3 changes during agonist stimulation. This chapter is designed to provide practical guidance as well as some theoretical background on measurements of phosphoinositides in live cells using protein domain-GFP chimeras that could be also useful for people working on calcium signaling. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Varnai, Peter] Semmelweis Univ, Fac Med, Dept Physiol, H-1088 Budapest, Hungary.
[Balla, Tamas] NICHD, Program Dev Neurosc, Sect Mol Signal Transduct, Bethesda, MD 20892 USA.
RP Varnai, P (reprint author), Semmelweis Univ, Fac Med, Dept Physiol, Puskin Utca 9, H-1088 Budapest, Hungary.
EM varnai@puskin.sote.hu
OI Balla, Tamas/0000-0002-9077-3335
FU Intramural Research Program of the National Institute of Child Health
and Human Development of the National Institutes of Health; Hungarian
Scientific Research fund [OTKA NF-68563]; Medical Research Council [ETT
440/2006]
FX The authors wish to thank Dr. Kees Jalink (The Netherlands Cancer
Institute) for his collaboration, critical comments and fruitful
discussions over the years. This research was supported in part by the
Intramural Research Program of the National Institute of Child Health
and Human Development of the National Institutes of Health. P.V. is a
Bolyai Fellow of the Hungarian Academy of Science and was also supported
by the Hungarian Scientific Research fund (OTKA NF-68563) and the
Medical Research Council (ETT 440/2006).
NR 74
TC 32
Z9 32
U1 0
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
J9 METHODS
JI Methods
PD NOV
PY 2008
VL 46
IS 3
BP 167
EP 176
DI 10.1016/j.ymeth.2008.09.019
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 381NW
UT WOS:000261544200005
PM 18930153
ER
PT J
AU Bird, GS
DeHaven, WI
Smyth, JT
Putney, JW
AF Bird, Gary S.
DeHaven, Wayne I.
Smyth, Jeremy T.
Putney, James W., Jr.
TI Methods for studying store-operated calcium entry
SO METHODS
LA English
DT Article
DE Calcium signaling; Inositol trisphosphate; Store-operated calcium entry;
Icrac; Fluorescence; Electrophysiology
ID CAPACITATIVE CA2+ ENTRY; PAROTID ACINAR-CELLS; 2-AMINOETHOXYDIPHENYL
BORATE 2-APB; VASCULAR ENDOTHELIAL-CELLS; EMBRYONIC KIDNEY-CELLS;
CURRENT I-CRAC; PLASMA-MEMBRANE; INOSITOL TRISPHOSPHATE; 2ND MESSENGER;
T-LYMPHOCYTES
AB Activation of surface membrane receptors coupled to phospholipase C results in the generation of cytoplasmic Ca(2+), signals comprised of both intracellular Ca(2+) release, and enhanced entry of Ca(2+) across the plasma membrane. A primary mechanism for this Ca(2+) entry process is attributed to store-operated Ca(2+) entry, a process that is activated by depletion of Ca(2+) ions from an intracellular store by inositol 1,4,5-trisphosphate. Our understanding of the mechanisms underlying both Ca(2+) release and store-operated Ca(2+) entry have evolved from experimental approaches that include the use of fluorescent Ca(2+) indicators and electrophysiological techniques. Pharmacological manipulation of this Ca(2+) signaling process has been somewhat limited; but recent identification of key molecular players, STIM and Orai family proteins, has provided new approaches. Here we describe practical methods involving fluorescent Ca(2+) indicators and electrophysiological approaches for dissecting the observed intracellular Ca(2+) signal to reveal characteristics of store-operated Ca(2+) entry. highlighting the advantages, and limitations, of these approaches. Published by Elsevier Inc.
C1 [Bird, Gary S.; DeHaven, Wayne I.; Smyth, Jeremy T.; Putney, James W., Jr.] NIEHS, Lab Signal Transduct, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Bird, GS (reprint author), NIEHS, Lab Signal Transduct, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM bird@niehs.nih.gov
FU Intramural NIH HHS [Z99 ES999999]
NR 87
TC 99
Z9 100
U1 1
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
J9 METHODS
JI Methods
PD NOV
PY 2008
VL 46
IS 3
BP 204
EP 212
DI 10.1016/j.ymeth.2008.09.009
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 381NW
UT WOS:000261544200009
PM 18929662
ER
PT J
AU Ionin, B
Hammamieh, R
Shupp, JW
Das, R
Pontzer, CH
Jett, M
AF Ionin, Boris
Hammamieh, Rasha
Shupp, Jeffrey W.
Das, Rina
Pontzer, Carol H.
Jett, Marti
TI Staphylococcal enterotoxin B causes differential expression of Rnd3 and
RhoA in renal proximal tubule epithelial cells while inducing actin
stress fiber assembly and apoptosis
SO MICROBIAL PATHOGENESIS
LA English
DT Article
DE Renal proximal tubule epithelium; SEB; Toxic shock syndrome; RhoE; Rnd3;
RhoA
ID IN-VIVO; PROTEIN; SHOCK; RECEPTOR; TOXINS
AB Staphylococcal enterotoxin B (SEB) is a toxic shock-inducing agent produced by Staphylococcus aureus. The hallmark of SEB-induced lethal shock is acute vasodilation leading to severe hypotension. Animal studies reveal that approximate to 70% of intravenously administered toxin localizes to renal proximal tubule epithelial cells (RPTEC). This evidence, together with the well-documented role of the kidney in regulation of vascular tone, suggests that molecular events induced in RPTEC by SEB may contribute to the blood pressure dysregulation seen in enterotoxic shock. In an attempt to elucidate these molecular mechanisms, differential display was performed on SEB-treated and untreated RPTEC, and 32 differentially expressed transcripts (DETs) were identified. One of the down-regulated DETs matched the sequence for Rnd3, which normally inhibits Rho protein function. Consistent with Rnd3 down-regulation, message for RhoA was shown to increase upon SEB exposure, and actin stress fiber formation was dramatically increased. Further, SEB-exposed cells showed both increased enzymatic activity of caspase-3 and an increase in the percentage of apoptotic cells. Taken together, these results support the hypothesis that RPTEC undergo apoptosis upon exposure to SEB. Furthermore, these data implicate the involvement of the Rho family proteins in the molecular signaling pathway induced by SEB in RPTEC. (C) 2008 Published by Elsevier Ltd.
C1 [Ionin, Boris; Hammamieh, Rasha; Shupp, Jeffrey W.; Das, Rina; Jett, Marti] Walter Reed Army Inst Res, Div Pathol, Dept Mol Pathol, Silver Spring, MD 20910 USA.
[Pontzer, Carol H.] NIH, NCCAM, Bethesda, MD 20892 USA.
RP Jett, M (reprint author), Walter Reed Army Inst Res, Div Pathol, Dept Mol Pathol, 503 Robert Grant Ave, Silver Spring, MD 20910 USA.
EM martijett@us.army.mil
NR 29
TC 9
Z9 10
U1 0
U2 3
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0882-4010
J9 MICROB PATHOGENESIS
JI Microb. Pathog.
PD NOV-DEC
PY 2008
VL 45
IS 5-6
BP 303
EP 309
DI 10.1016/j.micpath.2008.07.002
PG 7
WC Immunology; Microbiology
SC Immunology; Microbiology
GA 397SG
UT WOS:000262681800001
PM 18721871
ER
PT J
AU Jamison, WP
Hackstadt, T
AF Jamison, Wendy P.
Hackstadt, Ted
TI Induction of type III secretion by cell-free Chlamydia trachomatis
elementary bodies
SO MICROBIAL PATHOGENESIS
LA English
DT Article
DE Chlamydia trachomatis; Type III secretion; Actin; Endocytosis
ID SMALL-MOLECULE INHIBITOR; OUTER-MEMBRANE PROTEIN; EPITHELIAL-CELLS;
HOST-CELLS; PSEUDOMONAS-AERUGINOSA; TRANSLOCATED PROTEIN; BACTERIAL
EFFECTORS; ACTIN CYTOSKELETON; IPA INVASINS; ENTRY
AB Chlamydiae secrete type III effector proteins at two distinct stages of their developmental cycle. Elementary bodies (EBs) secrete at least one pre-formed effector protein, Tarp, across the host plasma membrane from an extracellular location. Once internalized, a set of newly transcribed proteins are secreted to modify the inclusion membrane. In an effort to better understand the triggers for chlamydial type III secretion and develop means to identify new effectors, we investigated various inducers of T3SS in other Gram-negative bacterial systems to determine if they were able to activate chlamydial type III secretion from EBs using Tarp secretion as an indicator of activation. Chlamydial EBs are induced to secrete Tarp by exposure to FBS, BSA, or sphingolipid and cholesterol-rich liposomes (SCRLs). The induction by FBS and BSA, but not SCRL, is enhanced in the presence of the calcium-chelator, EGTA. This secretion was temperature dependent and inhibited by paraformaldehyde fixation of the EBs. Published by Elsevier Ltd.
C1 [Jamison, Wendy P.; Hackstadt, Ted] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM ted_hackstadt@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX We thank Janet Sager for excellent technical assistance, the RML
Microscopy Unit for confirmation of liposome morphology, Drs. T. Jewett,
B. Kleba, and E. Moore for critical reading of the manuscript, and
members of the Hackstadt lab for helpful comments and suggestions. This
work was supported by the Intramural Research program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 46
TC 23
Z9 23
U1 1
U2 2
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0882-4010
J9 MICROB PATHOGENESIS
JI Microb. Pathog.
PD NOV-DEC
PY 2008
VL 45
IS 5-6
BP 435
EP 440
DI 10.1016/j.micpath.2008.10.002
PG 6
WC Immunology; Microbiology
SC Immunology; Microbiology
GA 397SG
UT WOS:000262681800018
PM 18984037
ER
PT J
AU Seo, DW
Kim, SH
Eom, SH
Yoon, HJ
Cho, YR
Kim, PH
Kim, YK
Han, JW
Diaz, T
Wei, BY
Stetler-Stevenson, WG
AF Seo, Dong-Wan
Kim, Soo Hyeon
Eom, Seok-Hyun
Yoon, Hyun Jae
Cho, Young-Rak
Kim, Pyeung-Hyeun
Kim, Yong Kee
Han, Jeung-Whan
Diaz, Tere
Wei, Bei-yang
Stetler-Stevenson, William G.
TI TIMP-2 disrupts FGF-2-induced downstream signaling pathways
SO MICROVASCULAR RESEARCH
LA English
DT Article
DE TIMP-2; Angiogenesis; Integrin alpha 3 beta 1; Shp-1; FGF-2
ID TISSUE INHIBITOR; METALLOPROTEINASE INHIBITORS; MATRIX
METALLOPROTEINASES; ANGIOGENESIS; MECHANISM; PROTEIN; CANCER; INTEGRINS;
TARGET; CELLS
AB We have previously reported that tissue inhibitor of metalloproteinases-2 (TIMP-2), an endogenous inhibitor of matrix metalloproteinase, modulates angiogenic responses through the MMP inhibition-independent activity. In this study, we investigate the molecular mechanisms of TIMP-2-mediated growth inhibition in response to fibroblast growth factor-2 (FGF-2). Pre-treatment with a protein tyrosine phosphatase inhibitor orthovanadate or expression of a dominant negative Shp-1 mutant fails to induce TIMP-2 inactivation of FGF-2 signaling pathways in human microvascular endothelial cells. We also show that TIMP-2 inhibition of FGF-2-induced p42/44(MAPK) activation and cell proliferation is associated with TIMP-2 binding to integrin alpha 3 beta 1 on endothelial cell surfaces, as demonstrated by use of anti-integrin alpha 3 or beta 1 blocking antibodies, or disruption of integrin alpha 3 expression by siRNA. Collectively, our results indicate that TIMP-2 inhibits FGF-2 signaling pathways through association with integrin alpha 3 beta 1 and Shp-1-dependent inhibition of p42/44(MAPK) signaling, which in turn, results in suppression of FGF-2-stimulated endothelial cell mitogenesis. (C) 2008 Elsevier Inc. All rights reserved
C1 [Seo, Dong-Wan; Kim, Soo Hyeon; Eom, Seok-Hyun; Yoon, Hyun Jae; Cho, Young-Rak; Kim, Pyeung-Hyeun] Kangwon Natl Univ, Sch Biosci & Biotechnol, Dept Mol Biosci, Inst Biosci & Biotechnol, Chunchon 200701, South Korea.
[Diaz, Tere; Wei, Bei-yang; Stetler-Stevenson, William G.] Natl Canc Inst, Natl Inst Hlth, Ctr Canc Res, Cell & Canc Biol Branch, Gaithersburg, MD 20877 USA.
[Kim, Yong Kee] Kwandong Univ, Coll Med, Dept Pharmacol, Kangnung 210701, South Korea.
[Han, Jeung-Whan] Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea.
RP Seo, DW (reprint author), Kangwon Natl Univ, Sch Biosci & Biotechnol, Dept Mol Biosci, Inst Biosci & Biotechnol, Nat Sci Bldg 4-113, Chunchon 200701, South Korea.
EM dwseomb@kangwon.ac.kr; sstevenw@mail.nih.gov
RI Stetler-Stevenson, William/H-6956-2012;
OI Stetler-Stevenson, William/0000-0002-5500-5808; cho,
young-rak/0000-0002-1077-796X; Seo, Dong-Wan/0000-0003-4971-834X
FU NCI; Center for Cancer Research [Z01SC 009179]; Korean Government
(MOEHRD) [KRF-2006-311-C00547]; Korea Food & Drug Administration
[07102Biotechnology398]; Korea Science and Engineering Foundation;
Kangwon National University
FX This work was supported by intramural research funds from the NCI,
Center for Cancer Research Project Z01SC 009179, the Korea Research
Foundation Grant from the Korean Government (MOEHRD)
(KRF-2006-311-C00547), the Research Grant from the Korea Food & Drug
Administration (07102Biotechnology398), the Vascular System Research
Center Grant from the Korea Science and Engineering Foundation, and 2006
Research Grant from Kangwon National University.
NR 31
TC 26
Z9 26
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 0026-2862
J9 MICROVASC RES
JI Microvasc. Res.
PD NOV
PY 2008
VL 76
IS 3
BP 145
EP 151
DI 10.1016/j.mvr.2008.07.003
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 368FT
UT WOS:000260607700002
PM 18721821
ER
PT J
AU Hurt, EM
Saykally, JN
Anose, BM
Kalli, KR
Sanders, MM
AF Hurt, Elaine M.
Saykally, Jessica N.
Anose, Bynthia M.
Kalli, Kimberly R.
Sanders, Michel M.
TI Expression of the ZEB1 (delta EF1) transcription factor in human:
additional insights
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE ZEB1; delta EF1; Estrogen; Gynecologic carcinomas; TCF8
ID BREAST-CANCER CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; E-CADHERIN
EXPRESSION; QUANTITATIVE RT-PCR; ZINC-FINGER; GENE-REGULATION;
ENDOMETRIAL CARCINOMA; LUNG-CANCER; TGF-BETA; REPRESSOR
AB The zinc finger E-box binding transcription factor ZEB1 (delta EF1/Nil-2-a/AREB6/zfhx1a/TCF8/zfhep/BZP) is emerging as an important regulator of the epithelial to mesenchymal transitions (EMT) required for development and cancer metastasis. ZEB1 promotes EMT by repressing genes contributing to the epithelial phenotype while activating those associated with the mesenchymal phenotype. TCF8 (zfhx1a), the gene encoding ZEB1, is induced by several potentially oncogenic ligands including TGF-beta, estrogen, and progesterone. TGF-beta appears to activate EMT, at least in part, by inducing ZEB1. However, our understanding of how ZEB1 contributes to signaling pathways elicited by estrogen and progesterone is quite limited, as is our understanding of its functional roles in normal adult tissues. To begin to address these questions, a human tissue mRNA array analysis was done. In adults, the highest ZEB1 mRNA expression is in bladder and uterus, whereas in the fetus highest expression is in lung, thymus, and heart. To further investigate the regulation of TCF8 by estrogen, ZEB1 mRNA was measured in ten estrogen-responsive cell lines, but it is only induced in the OV266 ovarian carcinoma line. Although high expression of ZEB1 mRNA is estrogen-dependent in normal human ovarian and endometrial biopsies, high expression is estrogen-independent in late stage ovarian and endometrial carcinomas, raising the possibility that deregulated expression promotes cancer progression. In contrast, TCF8 is at least partially deleted in 4 of 5 well-differentiated, grade I endometrial carcinomas, which may contribute to their non-aggressive phenotype. These data support the contention that high ZEB1 encourages gynecologic carcinoma progression.
C1 [Saykally, Jessica N.; Sanders, Michel M.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
[Hurt, Elaine M.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Anose, Bynthia M.] Bethel Univ, Dept Chem, St Paul, MN 55112 USA.
[Kalli, Kimberly R.] Mayo Clin, Coll Med, Dept Oncol, Rochester, MN 55905 USA.
RP Sanders, MM (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, 6-155 Jackson Hall,321 Church St SE, Minneapolis, MN 55455 USA.
EM sande001@umn.edu
FU NIH [R01 DK40082, DK061913]
FX This research was supported by NIH grants R01 DK40082 and DK061913 to
MMS. The technical assistance of Michelle Hon is gratefully
acknowledged.
NR 54
TC 35
Z9 37
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0300-8177
J9 MOL CELL BIOCHEM
JI Mol. Cell. Biochem.
PD NOV
PY 2008
VL 318
IS 1-2
BP 89
EP 99
DI 10.1007/s11010-008-9860-z
PG 11
WC Cell Biology
SC Cell Biology
GA 363UO
UT WOS:000260292600011
PM 18622689
ER
PT J
AU Monge, C
Beraud, N
Kuznetsov, AV
Rostovtseva, T
Sackett, D
Schlattner, U
Vendelin, M
Saks, VA
AF Monge, Claire
Beraud, Nathalie
Kuznetsov, Andrey V.
Rostovtseva, Tatiana
Sackett, Dan
Schlattner, Uwe
Vendelin, Marko
Saks, Valdur A.
TI Regulation of respiration in brain mitochondria and synaptosomes:
restrictions of ADP diffusion in situ, roles of tubulin, and
mitochondrial creatine kinase
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE Brain; Creatine kinase; Functional coupling; Mitochondria; Synaptosomes;
Tubulin
ID ENZYME-CATALYZED REACTIONS; RAT-HEART MITOCHONDRIA;
OXIDATIVE-PHOSPHORYLATION; KINETIC-PROPERTIES; ENERGY-METABOLISM;
OUTER-MEMBRANE; INTACT SYNAPTOSOMES; ELECTRON-TRANSPORT; MUSCLE-CELLS;
GIANT AXONS
AB The role of ubiquitous mitochondrial creatine kinase (uMtCK) reaction in regulation of mitochondrial respiration was studied in purified preparations of rat brain synaptosomes and mitochondria. In permeabilized synaptosomes, apparent Km for exogenous ADP, Km (ADP), in regulation of respiration in situ was rather high (110 +/- 11 mu M) in comparison with isolated brain mitochondria (9 +/- 1 mu M). This apparent Km for ADP observed in isolated mitochondria in vitro dramatically increased to 169 +/- 52 mu M after their incubation with 1 mu M of dimeric tubulin showing that in rat brain, particularly in synaptosomes, mitochondrial outer membrane permeability for ADP, and ATP may be restricted by tubulin binding to voltage dependent anion channel (VDAC). On the other hand, in synaptosomes apparent Km (ADP) decreased to 25 +/- 1 mu M in the presence of 20 mM creatine. To fully understand this effect of creatine on kinetics of respiration regulation, complete kinetic analysis of uMtCK reaction in isolated brain mitochondria was carried out. This showed that oxidative phosphorylation specifically altered only the dissociation constants for MgATP, by decreasing that from ternary complex MtCK.Cr.MgATP (Ka) from 0.13 +/- 0.02 to 0.018 +/- 0.007 mM and that from binary complex MtCK. MgATP (Kia) from 1.1 +/- 0.29 mM to 0.17 +/- 0.07 mM. Apparent decrease of dissociation constants for MgATP reflects effective cycling of ATP and ADP between uMtCK and adenine nucleotide translocase (ANT). These results emphasize important role and various pathophysiological implications of the phosphocreatine-creatine kinase systemin energy transfer in brain cells, including synaptosomes.
C1 [Monge, Claire; Beraud, Nathalie; Schlattner, Uwe; Saks, Valdur A.] Univ Grenoble 1, Lab Fundamental & Appl Bioenerget, Grenoble, France.
[Kuznetsov, Andrey V.] D Swarovski Res Lab, Dept Transplant Surg, Innsbruck, Austria.
[Rostovtseva, Tatiana] NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA.
[Sackett, Dan] NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA.
[Vendelin, Marko] Tallinn Univ Technol, Inst Cybernet Tallin, Lab Syst Biol, EE-200108 Tallinn, Estonia.
[Saks, Valdur A.] NICPB, Lab Bioenerget, Tallinn, Estonia.
RP Saks, VA (reprint author), 2280 Rue Piscine,BP53X, F-38041 Grenoble 9, France.
EM Valdur.Saks@ujf-grenoble.fr
RI Schlattner, Uwe/D-1267-2009; Monge, Claire/E-2933-2012
OI Schlattner, Uwe/0000-0003-1159-5911;
FU INSERM, France; Agence National de la Recherche [BLAN07-2_188128];
Estonian Science Foundation [6142, 7117]
FX This work was supported by INSERM, France; Agence National de la
Recherche (project no BLAN07-2_188128), France, to C. M. and
V. S.; grants of Estonian Science Foundation (No 6142 and
7117 to V. S.).
NR 82
TC 45
Z9 46
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0300-8177
J9 MOL CELL BIOCHEM
JI Mol. Cell. Biochem.
PD NOV
PY 2008
VL 318
IS 1-2
BP 147
EP 165
DI 10.1007/s11010-008-9865-7
PG 19
WC Cell Biology
SC Cell Biology
GA 363UO
UT WOS:000260292600016
PM 18629616
ER
PT J
AU Nguyen, P
Bar-Sela, G
Sun, LC
Bisht, KS
Cui, HM
Kohn, E
Feinberg, AP
Gius, D
AF Nguyen, Phuongmai
Bar-Sela, Gil
Sun, Lunching
Bisht, Kheem S.
Cui, Hengmi
Kohn, Elise
Feinberg, Andrew P.
Gius, David
TI BAT3 and SET1A Form a Complex with CTCFL/BORIS To Modulate H3K4 Histone
Dimethylation and Gene Expression
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID ENHANCER-BLOCKING ACTIVITY; THIOREDOXIN REDUCTASE; BINDING PROTEIN;
CTCF-BINDING; METHYLATION; H19; CANCER; CHROMATIN; IGF2; PROMOTER
AB Chromatin status is characterized in part by covalent posttranslational modifications of histones that regulate chromatin dynamics and direct gene expression. BORIS (brother of the regulator of imprinted sites) is an insulator DNA-binding protein that is thought to play a role in chromatin organization and gene expression. BORIS is a cancer-germ line gene; these are genes normally present in male germ cells (testis) that are also expressed in cancer cell lines as well as primary tumors. This work identifies SET1A, an H3K4 methyltransferase, and BAT3, a cochaperone recruiter, as binding partners for BORIS, and these proteins bind to the upstream promoter regions of two well-characterized procarcinogenic genes, Myc and BRCA1. RNA interference (RNAi) knockdown of BAT3, as well as SET1A, decreased Myc and BRCA1 gene expression but did not affect the binding properties of BORIS, but RNAi knockdown of BORIS prevented the assembly of BAT3 and SET1A at the Myc and BRCA1 promoters. Finally, chromatin analysis suggested that BORIS and BAT3 exert their effects on gene expression by recruiting proteins such as SET1A that are linked to changes in H3K4 dimethylation. Thus, we propose that BORIS acts as a platform upon which BAT3 and SET1A assemble and exert effects upon chromatin structure and gene expression.
C1 [Nguyen, Phuongmai; Bar-Sela, Gil; Sun, Lunching; Bisht, Kheem S.; Gius, David] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Cui, Hengmi; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Mol Biol, Dept Med,Inst Genet Med, Baltimore, MD 21205 USA.
[Cui, Hengmi; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Genet, Dept Med,Inst Genet Med, Baltimore, MD 21205 USA.
[Cui, Hengmi; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA.
[Kohn, Elise] NCI, Pathol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gius, D (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM afeinberg@jhu.edu; giusd@mail.nih.gov
FU NCI [CA65145]; NIH; CCR
FX This work was supported by grant CA65145 (to A.P.F.) from the NCI and
also (in part) by the Intramural Research Program of the NIH, the NCI,
and the CCR.
NR 46
TC 43
Z9 46
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 NOV
PY 2008
VL 28
IS 21
BP 6720
EP 6729
DI 10.1128/MCB.00568-08
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 359ZS
UT WOS:000260027400015
PM 18765639
ER
PT J
AU Anglesio, MS
Arnold, JM
George, J
Tinker, AV
Tothill, R
Waddell, N
Simms, L
Locandro, B
Fereday, S
Traficante, N
Russell, P
Sharma, R
Birrer, MJ
Defazio, A
Chenevix-Trench, G
Bowtelll, DDL
AF Anglesio, Michael S.
Arnold, Jeremy M.
George, Joshy
Tinker, Anna V.
Tothill, Richard
Waddell, Nic
Simms, Lisa
Locandro, Bianca
Fereday, Sian
Traficante, Nadia
Russell, Peter
Sharma, Raghwa
Birrer, Michael J.
deFazio, Anna
Chenevix-Trench, Georgia
Bowtelll, David D. L.
CA AOCS Study Grp
TI Mutation of ERBB2 Provides a Novel Alternative Mechanism for the
Ubiquitous Activation of RAS-MAPK in Ovarian Serous Low Malignant
Potential Tumors
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; GENE-EXPRESSION PATTERNS; HER2 KINASE DOMAIN;
BORDERLINE TUMORS; PROTEIN-KINASE; EPITHELIAL-CELLS; LOW-GRADE;
DIFFERENTIAL REGULATION; SOMATIC MUTATIONS; TYROSINE KINASES
AB Approximately, 10% to 15% of serous ovarian tumors fall into the category designated as tumors of low malignant potential (LMP). Like their invasive counterparts, LMP tumors may be associated with extraovarian disease, for example, in the peritoneal cavity and regional lymph nodes. However, unlike typical invasive carcinomas, patients generally have a favorable prognosis. The mutational profile also differs markedly from that seen in most serous carcinomas. Typically, LMP tumors are associated with KRAS and BRAF mutations. Interrogation of expression profiles in serous LMP tumors suggested overall redundancy of RAS-MAPK pathway mutations and a distinct mechanism of oncogenesis compared with high-grade ovarian carcinomas. Our findings indicate that activating mutation of the RAS-MAPK pathway in serous LMP may be present in >70% of cases compared with similar to 12.5% in serous ovarian carcinomas. In addition to mutations of KRAS (18%) and BRAF (48%) mutations, ERBB2 mutations (6%), but not EGFR, are prevalent among serous LMP tumors. Based on the expression profile signature observed throughout our serous LMP cohort, we propose that RAS-MAPK pathway activation is a requirement of serous LMP tumor development and that other activators of this pathway are yet to be defined. Importantly, as few nonsurgical options exist for treatment of recurrent LMP tumors, therapeutic targeting of this pathway may prove beneficial, especially in younger patients where maintaining fertility is important. (Mol Cancer Res 2008;6(11):1678-90)
C1 [Anglesio, Michael S.; George, Joshy; Tothill, Richard; Locandro, Bianca; Fereday, Sian; Traficante, Nadia; Bowtelll, David D. L.; AOCS Study Grp] Peter MacCallum Canc Ctr, Melbourne, Vic 8006, Australia.
[AOCS Study Grp] Univ Melbourne, Melbourne, Vic, Australia.
[Arnold, Jeremy M.; Waddell, Nic; Simms, Lisa; Chenevix-Trench, Georgia; AOCS Study Grp] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Tinker, Anna V.] British Columbia Canc Agcy, Vancouver Ctr, Dept Oncol, Vancouver, BC V5Z 4E6, Canada.
[Russell, Peter] Univ Sydney, Dept Pathol, Royal Prince Alfred Hosp, Dept Anat Pathol, Sydney, NSW 2006, Australia.
[Sharma, Raghwa] Westmead Hosp, Dept Anat Pathol, Sydney, NSW, Australia.
[deFazio, Anna; AOCS Study Grp] Univ Sydney, Westmead Millennium Inst, Westmead Hosp, Westmead Inst Canc Res, Sydney, NSW 2006, Australia.
[deFazio, Anna] Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia.
[Birrer, Michael J.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Bowtelll, DDL (reprint author), Peter MacCallum Canc Ctr, Locked Bag 1,ABeckett St, Melbourne, Vic 8006, Australia.
EM d.bowtell@petermac.org
RI deFazio, Anna/D-3939-2013; Bowtell, David/H-1007-2016; Waddell,
Nic/H-4929-2015;
OI deFazio, Anna/0000-0003-0057-4744; Bowtell, David/0000-0001-9089-7525;
Anglesio, Michael/0000-0003-1639-5003; Tothill,
Richard/0000-0003-4522-1184
NR 93
TC 52
Z9 54
U1 0
U2 2
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 NOV
PY 2008
VL 6
IS 11
BP 1678
EP 1690
DI 10.1158/1541-7786.MCR-08-0193
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 375SV
UT WOS:000261134500003
PM 19010816
ER
PT J
AU Kinyamu, HK
Collins, JB
Grissom, SF
Hebbar, PB
Archer, TK
AF Kinyamu, H. Karimi
Collins, Jennifer B.
Grissom, Sherry F.
Hebbar, Pratibha B.
Archer, Trevor K.
TI Genome Wide Transcriptional Profiling in Breast Cancer Cells Reveals
Distinct Changes in Hormone Receptor Target Genes and Chromatin
Modifying Enzymes After Proteasome inhibition
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE proteasome inhibitor; receptors; glucocorticoid; estrogen; gene
expression profiling; microarray analysis
ID GLUCOCORTICOID-RECEPTOR; ESTROGEN-RECEPTOR; REGULATED TRANSCRIPTION;
PROSTATE-CANCER; PROTEIN-DEGRADATION; NUCLEAR RECEPTORS;
CERVICAL-CANCER; HUMAN-DISEASES; EXPRESSION; UBIQUITIN
AB Steroid hormone receptors, like glucocorticoid (GR) and estrogen receptors (ER), are master regulators of genes that control many biological processes implicated in health and disease. Gene expression is dependent on receptor levels which are tightly regulated by the ubiquitin-proteasome system. Previous studies have shown that proteasome inhibition increases GR, but decreases ER-mediated gene expression. At the gene expression level this divergent role of the proteasome in receptor-dependent transcriptional regulation is not well understood. We have used a genomic approach to examine the impact of proteasome activity on GR- and ER-mediated gene expression in MCF-7 breast cancer cells treated with dexamethasone (DEX) or 17 beta-estradiol (E2), the proteasome inhibitor MG132 (MG) or MG132 and either hormone (MID or ME2) for 24 h. Transcript profiling reveals that inhibiting proteasome activity modulates gene expression by GR and ER in a similar manner in that several GR and ER target genes are upregulated and downregulated after proteasome inhibition. In addition, proteasome inhibition modulates receptor-dependent genes involved in the etiology of a number of human pathological states, including multiple myeloma, leukemia, breast/prostate cancer, HIV/AIDS, and neurodegenerative disorders. Importantly, our analysis reveals that a number of transcripts encoding histone and DNA modifying enzymes, prominently histone/DNA methyltransf erases and demethylases, are altered after proteasome inhibition. As proteasome inhibitors are currently in clinical trials as therapy for multiple myeloma, HIV/AIDS and leukemia, the possibility that some of the target molecules are hormone regulated and chromatin modifying enzymes is intriguing in this era of epigenetic therapy. Published 2008 Wiley-Liss, Inc.
C1 [Kinyamu, H. Karimi; Hebbar, Pratibha B.; Archer, Trevor K.] Natl Inst Environm Hlth Sci, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Collins, Jennifer B.; Grissom, Sherry F.] Natl Inst Environm Hlth Sci, Microarray Grp, NIH, Res Triangle Pk, NC 27709 USA.
RP Kinyamu, HK (reprint author), Natl Inst Environm Hlth Sci, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, 111 Alexander Dr,POB 12233,MD C4-06, Res Triangle Pk, NC 27709 USA.
FU NIH; NIEHS
FX We are deeply grateful to Dr. Pierre Bushel (Biostatistics Branch,
NIEHS) for providing help with the statistical analysis and rewriting
the methods section to answer the reviewers concerns. We thank Wendy
Jefferson and Sylvia Hewitt for helpful comments in organizing the
paper. This research was supported by the Intramural Research Program of
NIH and NIEHS.
NR 83
TC 18
Z9 18
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0899-1987
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD NOV
PY 2008
VL 47
IS 11
BP 845
EP 885
DI 10.1002/mc.20440
PG 41
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 371BZ
UT WOS:000260808100004
PM 18381591
ER
PT J
AU McFarland, MA
Ellis, CE
Markey, SP
Nussbaum, RL
AF McFarland, Melinda A.
Ellis, Christopher E.
Markey, Sanford P.
Nussbaum, Robert L.
TI Proteomics Analysis Identifies Phosphorylation-dependent alpha-Synuclein
Protein Interactions
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID SPECTRAL ABUNDANCE FACTORS; MITOCHONDRIAL COMPLEX-I; CORTICAL LEWY
BODIES; PARKINSONS-DISEASE; SHOTGUN PROTEOMICS; BRAIN; MICE; SER-129;
RELEASE; SYSTEM
AB Mutations and copy number variation in the SNCA gene encoding the neuronal protein alpha-synuclein have been linked to familial Parkinson disease ( Thomas, B., and Beal, M. F. ( 2007) Parkinson's disease. Hum. Mol. Genet. 16, R183-R194). The carboxyl terminus of alpha-synuclein can be phosphorylated at tyrosine 125 and serine 129, although only a small fraction of the protein is phosphorylated under normal conditions (Okochi, M., Walter, J., Koyama, A., Nakajo, S., Baba, M., Iwatsubo, T., Meijer, L., Kahle, P. J., and Haass, C. ( 2000) Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein. J. Biol. Chem. 275, 390-397). Under pathological conditions, such as in Parkinson disease, alpha-synuclein is a major component of Lewy bodies, a pathological hallmark of Parkinson disease, and is mostly phosphorylated at Ser-129 ( Anderson, J. P., Walker, D. E., Goldstein, J. M., de Laat, R., Banducci, K., Caccavello, R. J., Barbour, R., Huang, J. P., Kling, K., Lee, M., Diep, L., Keim, P. S., Shen, X. F., Chataway, T., Schlossmacher, M. G., Seubert, P., Schenk, D., Sinha, S., Gai, W. P., and Chilcote, T. J. ( 2006) Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J. Biol. Chem. 281, 29739 29752). Controversy exists over the extent to which phosphorylation of alpha-synuclein and/or the visible protein aggregation in Lewy bodies are steps in disease pathogenesis, are protective, or are neutral markers for the disease process. Here we used the combination of peptide pulldown assays and mass spectrometry to identify and compare protein-protein interactions of phosphorylated and non-phosphorylated alpha-synuclein. We showed that non-phosphorylated alpha-synuclein carboxyl terminus pulled down protein complexes that were highly enriched for mitochondrial electron transport proteins, whereas alpha-synuclein carboxyl terminus phosphorylated on either Ser-129 or Tyr-125 did not. Instead the set of proteins pulled down by phosphorylated alpha-synuclein was highly enriched in certain cytoskeletal proteins, in vesicular trafficking proteins, and in a small number of enzymes involved in protein serine phosphorylation. This targeted comparative proteomics approach for unbiased identification of protein-protein interactions suggests that there are functional consequences when alpha-synuclein is phosphorylated. Molecular & Cellular Proteomics 7: 2123-2137, 2008.
C1 [Nussbaum, Robert L.] Univ Calif San Francisco, Div Med Genet, Dept Med, San Francisco, CA 94143 USA.
[McFarland, Melinda A.; Markey, Sanford P.] NHGRI, NIMH, Bethesda, MD 20891 USA.
[Ellis, Christopher E.] NHGRI, NIH, Bethesda, MD 20891 USA.
RP Nussbaum, RL (reprint author), Univ Calif San Francisco, Div Med Genet, Dept Med, Box 0794,513 Parnassus Ave,Rm HSE901E, San Francisco, CA 94143 USA.
EM nussbaumr@humgen.ucsf.edu
RI McFarland, Melinda/A-1866-2013
FU National Institutes of Health [Z01 MH000279]; Sandler Family Foundation
FX We thank Douglas Slotta, Sara Yang, and Anthony J. Makusky for help with
data processing; Jeffrey Kowalak and Joanne Connolly for preliminary
observations on this project; and Dr. Yien- Ming Kuo and Dr. Valerie
Drews for help in preparing and critically reading the manuscript. We
thank Nelson Cole for providing some recombinant synucleins and helping
us to make others.; This work was supported, in whole or in part, by
National Institutes of Health Grant Z01 MH000279 from the intramural
programs of the National Institute of Mental Health and by the NHGRI.
This work was also supported by the Sandler Family Foundation. The costs
of publication of this article were defrayed in part by the payment of
page charges. This article must therefore be hereby marked
"advertisement" in accordance with 18 U. S. C. Section 1734 solely to
indicate this fact.
NR 58
TC 72
Z9 73
U1 4
U2 10
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD NOV
PY 2008
VL 7
IS 11
BP 2123
EP 2137
DI 10.1074/mcp.M800116-MCP200
PG 15
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 372HV
UT WOS:000260893600005
PM 18614564
ER
PT J
AU Anderson, SJ
Stone, CL
Posada-Buitrago, ML
Boore, JL
Neelam, BA
Stephens, RM
Luster, DG
Frederick, RD
Pedley, KF
AF Anderson, Sharon J.
Stone, Christine L.
Posada-Buitrago, Martha Lucia
Boore, Jeffrey L.
Neelam, Beena A.
Stephens, Robert M.
Luster, Douglas G.
Frederick, Reid D.
Pedley, Kerry F.
TI Development of simple sequence repeat markers for the soybean rust
fungus, Phakopsora pachyrhizi
SO MOLECULAR ECOLOGY RESOURCES
LA English
DT Article
DE basidiomycetes; microsatellites; Phakopsora pachyrhizi; soybean rust;
SSR
AB Twenty-four simple sequence repeat markers were developed for Phakopsora pachyrhizi, a fungal pathogen of soybean (Glycine max) and other legumes. All 24 of the loci were evaluated on 28 isolates of P. pachyrhizi. Twenty-one loci were polymorphic, with allelic diversity ranging from two to eight alleles, and null alleles were observed for eight of the 24 loci. A preliminary screen with the closely related species, P. meibomiae, indicated that these primer pairs are specific to P. pachyrhizi.
C1 [Anderson, Sharon J.; Stone, Christine L.; Luster, Douglas G.; Frederick, Reid D.; Pedley, Kerry F.] USDA ARS, Foreign Dis Weed Sci Res Unit, Ft Detrick, MD 21702 USA.
[Posada-Buitrago, Martha Lucia; Boore, Jeffrey L.] Joint Genome Inst, Walnut Creek, CA 94598 USA.
[Posada-Buitrago, Martha Lucia; Boore, Jeffrey L.] Lawrence Berkeley Natl Lab, US Dept Energy, Walnut Creek, CA USA.
[Neelam, Beena A.; Stephens, Robert M.] NCI Frederick, SAIC Frederick Inc, Adv Biomed Comp Ctr, Adv Technol Program, Ft Detrick, MD 21702 USA.
RP Pedley, KF (reprint author), USDA ARS, Foreign Dis Weed Sci Res Unit, Ft Detrick, MD 21702 USA.
EM kerry.pedley@ars.usda.gov
RI Moreira, Eder/B-2309-2010; POSADA, MARTHA/G-7927-2012
NR 8
TC 8
Z9 9
U1 1
U2 2
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1755-098X
J9 MOL ECOL RESOUR
JI Mol. Ecol. Resour.
PD NOV
PY 2008
VL 8
IS 6
BP 1310
EP 1312
DI 10.1111/j.1755-0998.2008.02272.x
PG 3
WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology
SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology;
Evolutionary Biology
GA 367BY
UT WOS:000260528700027
PM 21586030
ER
PT J
AU Shen, JS
Meng, XL
Moore, DF
Quirk, JM
Shayman, JA
Schiffmann, R
Kaneski, CR
AF Shen, Jin-Song
Meng, Xing-Li
Moore, David F.
Quirk, Jane M.
Shayman, James A.
Schiffmann, Raphael
Kaneski, Christine R.
TI Globotriaosylceramide induces oxidative stress and up-regulates cell
adhesion molecule expression in Fabry disease endothelial cells
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Fabry disease; alpha-Galactosidase A deficiency; Globotriaosylceramide;
Endothelial cells; Reactive oxygen species; Cell adhesion molecule
ID ENZYME-REPLACEMENT THERAPY; NITRIC-OXIDE SYNTHASE; CEREBRAL
HYPERPERFUSION; SUPEROXIDE GENERATION; AGALSIDASE-ALPHA;
ATHEROSCLEROSIS; MICE; GLYCOSPHINGOLIPIDS; DEFICIENCY; CHILDREN
AB Fabry disease, an X-linked systemic vasculopathy, is caused by a deficiency of alpha-galactosidase A resulting in globotriaosylceramide (Gb(3)) storage in cells. The pathogenic role of Gb(3) in the disease is not known. Based on previous work, we tested the hypothesis that accumulation of Gb(3) in the vascular endothelium of Fabry disease is associated with increased production of reactive oxygen species (ROS) and increased expression of cell adhesion molecules. Gb(3)-loading resulted in increased intracellular ROS production in cultured vascular endothelial cells in a dose-dependent manner. Increased Gb(3) also induced expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Reduction of endogenous Gb(3) by treatment of the cells with an inhibitor of glycosphingolipid synthase or alpha-galactosidase A led to decreased expression of adhesion molecules. Plasma from Fabry patients significantly increased ROS generation in endothelial cells when compared with plasma from non-Fabry controls. This effect was not influenced by reduction of intracellular Gb(3). This study provided direct evidence that excess intracellular Gb(3) induces oxidative stress and up-regulates the expression of cellular adhesion molecules in vascular endothelial cells. In addition. other factors in patient's plasma may also contribute to oxidative stress in Fabry vascular endothelial cells. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Shen, Jin-Song; Quirk, Jane M.; Schiffmann, Raphael; Kaneski, Christine R.] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA.
[Meng, Xing-Li] NICHHD, Lab Clin Genome, NIH, Bethesda, MD 20892 USA.
[Shayman, James A.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Shen, Jin-Song; Meng, Xing-Li] Jikei Univ, Sch Med, Inst DNA Med, Dept Gene Therapy, Tokyo, Japan.
[Moore, David F.] Walter Reed Army Med Ctr, Def & Vet Brain Injury Ctr, Washington, DC 20307 USA.
RP Schiffmann, R (reprint author), Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA.
EM Raphael.schiffmann@baylorhealth.edu
OI Kaneski, Christine/0000-0003-1453-2502
FU National Institute of Neurological Disorders and Stroke; NIH
FX We thank Drs. R.O. Brady and G.J. Murray for discussions. This work was
funded by the Intramural Program of the National Institute of
Neurological Disorders and Stroke, NIH.
NR 36
TC 77
Z9 81
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD NOV
PY 2008
VL 95
IS 3
BP 163
EP 168
DI 10.1016/j.ymgme.2008.06.016
PG 6
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 368DQ
UT WOS:000260601900006
PM 18707907
ER
PT J
AU Tang, JR
Donsante, A
Desai, V
Patronas, N
Kaler, SG
AF Tang, Jingrong
Donsante, Anthony
Desai, Vishal
Patronas, Nicholas
Kaler, Stephen G.
TI Clinical outcomes in Menkes disease patients with a copper-responsive
ATP7A mutation, G727R
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Copper transport; Neurodevelopment; Gene expression; Menkes disease;
Newborn screening
ID OCCIPITAL-HORN-SYNDROME; UNFOLDED PROTEIN RESPONSE; TANDEM
MASS-SPECTROMETRY; CANDIDATE GENE; NMDA RECEPTOR; TRANSPORTING ATPASE;
TRAFFICKING; EXPRESSION; LOCALIZATION; HOMEOSTASIS
AB Menkes disease is a fatal neurodegenerative disorder of infancy caused by defects in an X-linked copper transport gene, ATHA. Evidence from a recent clinical trial indicates that favorable response to early treatment of this disorder with copper injections involves mutations that retain some copper transport capacity. In three unrelated infants, we identified the same mutation, G727R, in the second transmembrane segment of ATP7A that complemented a Saccharomyces cerevisiae copper transport mutant. consistent with partial copper transport activity. Quantitative reverse transcription-polymerase chain reaction studies showed approximately normal levels of ATP7A(G727R) transcript in two patients' fibroblasts compared to wild-type controls, but Western blot analyses showed markedly reduced quantities of ATP7A, suggesting post-translational degradation. We confirmed the latter by comparing degradation rates of mutant and wild-type ATP7A via cyclohexamide treatment of cultured fibroblasts; half-life of the G727R mutant was 2.9 h and for the wild-type, 11.4 h. We also documented a X-box binding protein 1 splice variant in G727R cells-known to be associated with the cellular misfolded protein response. Patient A, diagnosed 6 months of age, began treatment at 228 days (7.6 months) of age. At his current age (2.5 years), his overall neurodevelopment remains at a 2- to 4-month level. In contrast, patient B and patient C were diagnosed in the neonatal period, began treatment within 25 days of age, and show near normal neurodevelopment at their current ages, 3 years (patient B), and 7 months (patient C). The poor clinical outcome in patient A with the same missense mutation as patient A and patient B with near normal oucomes, confirms the importance of early medical intervention in Menkes disease and highlights the critical potential benefit of newborn screening for this disorder. Published by Elsevier Inc.
C1 [Tang, Jingrong; Donsante, Anthony; Desai, Vishal; Kaler, Stephen G.] NICHHD, Unit Pediat Genet, Program Mol Med, Bethesda, MD 20892 USA.
[Patronas, Nicholas] NIH, Imaging Sci Program, Mark O Hatfield Clin Ctr, Bethesda, MD 20892 USA.
RP Kaler, SG (reprint author), NICHHD, Unit Pediat Genet, Program Mol Med, Bldg 10,Room 10N-313,10 Ctr Dr,MSC 1832, Bethesda, MD 20892 USA.
EM kalers@mail.nih.gov
FU NICHD Intramural Research Program
FX We are grateful to Sarah Godwin for help in mutation screening, Courtney
Holmes and David Goldstein for catecholamine analysis, Christine Kaneski
for cell culture, and Olga Protchenko and Caroline Philpott for advice
on yeast Western blotting. This work was supported by the NICHD
Intramural Research Program.
NR 37
TC 20
Z9 20
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD NOV
PY 2008
VL 95
IS 3
BP 174
EP 181
DI 10.1016/j.ymgme.2008.06.015
PG 8
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 368DQ
UT WOS:000260601900008
PM 18752978
ER
PT J
AU Porras, A
Kozar, S
Russanova, V
Salpea, P
Hirai, T
Sammons, N
Mittal, P
Kim, JY
Ozato, K
Romero, R
Howard, BH
AF Porras, Analia
Kozar, Sarah
Russanova, Valya
Salpea, Paraskevi
Hirai, Tazuko
Sammons, Nicholas
Mittal, Pooja
Kim, Ji Young
Ozato, Keiko
Romero, Roberto
Howard, Bruce H.
TI Developmental and epigenetic regulation of the human TLR3 gene
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Innate immunity; Toll-like receptors; Development; Epigenetics;
Chromatin
ID TOLL-LIKE RECEPTORS; INNATE IMMUNITY; X-INACTIVATION;
CHROMATIN-STRUCTURE; DENDRITIC CELLS; EXPRESSION; MECHANISMS; DISEASE;
GAMMA; AGE
AB The receptor encoded by the human TLR3 gene recognizes double-strand RNAs (dsRNAs) associated with Viral infection. TLR3 expression is strongly activated upon differentiation of monocytes to dendritic cells, and can be further stimulated by the dsRNA analog polyinosine:polycytosine (PI:C). We report evidence for developmental regulation of the TLR3 gene. In dendritic cells derived from cord blood, both differentiation and PI:C-associated TLR3 transcriptional activation are impaired as compared to cells from adults. Consistent with relative expression patterns, chromatin states and remodeling differ between newborn and adult samples. TLR3 expression in newborn dendritic cells exhibits heterocellularity and allelic imbalance (skewing), features characteristic of cis-acting epigenetic control. These findings reveal a new source for variability in innate immune system function and provide a model for further study of perinatal epigenetic transitions during development. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Porras, Analia; Kozar, Sarah; Russanova, Valya; Salpea, Paraskevi; Hirai, Tazuko; Sammons, Nicholas; Kim, Ji Young; Ozato, Keiko; Howard, Bruce H.] NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA.
[Mittal, Pooja; Romero, Roberto] NICHHD, Perinatal Res Branch, NIH, Bethesda, MD 20892 USA.
RP Howard, BH (reprint author), NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA.
EM howard@helix.nih.gov
RI Salpea, Paraskevi/A-8027-2010
FU NICHD; National Institutes of Health
FX We are very grateful to Sandy Field and Nancy Hauff (Perinatology
Research Branch), and to Cindy Matthews (Dept. of Transfusion Medicine,
National Institutes of Health) for the collection of blood and apheresis
specimens. We thank to Vincent Schram in the National Institute of Child
Health and Human Development (NICHD) Imaging Facility for assistance
with fluorescence imaging experiments. We also thank Michael Doctor and
Jonathan Epstein for contributions to graphics and bioinformatics used
in this study. This research was supported by the Intramural Research
Program of the NICHD, National Institutes of Health.
NR 42
TC 7
Z9 7
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD NOV
PY 2008
VL 46
IS 1
BP 27
EP 36
DI 10.1016/j.molimm.2008.06.030
PG 10
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 371BV
UT WOS:000260807700004
PM 18715647
ER
PT J
AU Sung, MH
Bagain, L
Chen, Z
Karpova, T
Yang, X
Silvin, C
Voss, TC
McNally, JG
Van Waes, C
Gordon, L
AF Sung, Myong-Hee
Bagain, Lorena
Chen, Zhong
Karpova, Tatiana
Yang, Xinping
Silvin, Christopher
Voss, Ty C.
McNally, James G.
Van Waes, Carter
Hager, Gordon L.
TI Dynamic Effect of Bortezomib on Nuclear Factor-kappa B Activity and Gene
Expression in Tumor Cells
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID INFLAMMATION-ASSOCIATED CANCER; HUMAN HEAD; TRANSCRIPTION FACTORS;
FEEDBACK LOOP; TARGET GENES; NECK-CANCER; LIVE CELLS; CARCINOMA;
ACTIVATION; OSCILLATIONS
AB Nuclear factor-kappa B (NF-kappa B) influences the initiation, progression, and maintenance of diverse cancer types. Despite current therapeutic efforts to block hyperactive NF-kappa B in cancer cells, the in vivo effects of a drug upon this complex pathway are unclear. We monitored NF-kappa B activity and a fast-expressing reporter level simultaneously in head and neck squamous carcinoma cells by quantitative live microscopy. The real-time single cell assay revealed the tumor necrosis factor-alpha-induced oscillation of NF-kappa B was echoed by equally dynamic reporter expression rate. Bortezomib is a proteasome inhibitor whose anticancer action is partly mediated through inhibition of NF-kappa B. When administered to preactivated cells, the drug gave rise to distinct inhibition dynamics, with discrete pulses of reporter induction remaining for hours. These findings suggest that, contrary to a simplistic presumption for a pathway "blockade," the network dynamics and the intracellular pharmacokinetics of the inhibitor must be critically evaluated in developing strategies for optimal intervention of oncogenic pathways.
C1 [Sung, Myong-Hee; Karpova, Tatiana; Voss, Ty C.; McNally, James G.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Bagain, Lorena; Chen, Zhong; Yang, Xinping; Van Waes, Carter] Natl Inst Deafness & Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
[Silvin, Christopher] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Sung, MH (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Room B602,Bldg 41,41 Lib Dr, Bethesda, MD 20892 USA.
EM sungm@mail.nih.gov
FU National Institute on Deafness and Other Communication Disorders
[Z01-DC-00016]; National Institutes of Health Intramural Research
Program for Center for Cancer Research; National Cancer Institute;
National Institutes of Health-approved Cooperative Research and
Development Agreement with Millennium Pharmaceuticals
FX This work was supported by National Institute on Deafness and Other
Communication Disorders intramural project Z01-DC-00016 and by the
National Institutes of Health Intramural Research Program for Center for
Cancer Research, National Cancer Institute. C. V. W. has received
bortezomib and clinical trial support under a National Institutes of
Health-approved Cooperative Research and Development Agreement with
Millennium Pharmaceuticals.
NR 39
TC 11
Z9 11
U1 0
U2 0
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 NOV
PY 2008
VL 74
IS 5
BP 1215
EP 1222
DI 10.1124/mol.108.049114
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 362KT
UT WOS:000260197300006
PM 18684839
ER
PT J
AU Yin, X
Li, B
Chen, H
Catt, KJ
AF Yin, Xing
Li, Bo
Chen, Hungdar
Catt, Kevin J.
TI Differential Signaling Pathways in Angiotensin II- and Epidermal Growth
Factor-stimulated Hepatic C9 Cells
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID SMOOTH-MUSCLE-CELLS; FACTOR RECEPTOR TRANSACTIVATION; PROTEIN-KINASE-C;
PHOSPHOINOSITIDE 3-KINASE; TYPE-1 RECEPTOR; INDEPENDENT ACTIVATION;
REGULATED KINASE-1/2; CAVEOLAE MEMBRANE; EPITHELIAL-CELLS; TYROSINE
KINASE
AB Caveolin1 (Cav1) is an important component of the plasma-membrane microdomains, such as caveolae/lipid rafts, that are associated with angiotensin II type 1 (AT(1)) and epidermal growth factor (EGF) receptors in certain cell types. The interactions of Cav1 with other signaling molecules that mediate AT(1) receptor function were analyzed in angiotensin II (Ang II)and EGF-stimulated hepatic C9 cells. This study demonstrated that cholesterol-rich domains mediate the actions of early upstream signaling molecules such as Src and intracellular Ca2+ in cells stimulated by Ang II, but not by EGF, and that Cav1 has a scaffolding role in the process of mitogen-activated protein kinase activation. Furthermore, Cav1 phosphorylation by Ang II and EGF was regulated by intracellular Ca2+ and Src, further indicating reciprocal interactions among Cav1, Src, and intracellular Ca2+ through the AT(1) receptor. Phosphorylation of Cav1 and the EGF receptor by Ang II, but not of extracellular signal-regulated kinase 1/2, was dependent on intracellular Ca2+. The phosphatidylinositol 3-kinase inhibitors, 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) and wortmannin, differentially modulated both Cav1 and EGF receptor activation by Ang II through intracellular Ca2+. These findings further demonstrate the importance of Cav1 in conjunction with the receptor-mediated signaling pathways involved in cell proliferation and survival. It is clear that differential signaling pathways are operative in Ang II- and EGF-stimulated C9 cells and that cholesterol-enriched microdomains are essential components in cellular signaling processes that are dependent on specific agonists and/or cell types.
C1 [Yin, Xing; Chen, Hungdar; Catt, Kevin J.] NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA.
[Li, Bo] NIDDK, Mol Signalling Lab Bioorgan Chem, NIH, Bethesda, MD USA.
RP Catt, KJ (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA.
EM cattk@mail.nih.gov
NR 40
TC 5
Z9 5
U1 0
U2 2
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 NOV
PY 2008
VL 74
IS 5
BP 1223
EP 1233
DI 10.1124/mol.108.048504
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 362KT
UT WOS:000260197300007
PM 18687808
ER
PT J
AU Roy, A
Ganguly, A
BoseDasgupta, S
Das, BB
Pal, C
Jaisankar, P
Majumder, HK
AF Roy, Amit
Ganguly, Agneyo
BoseDasgupta, Somdeb
Das, Benu Brata
Pal, Churala
Jaisankar, Parasuraman
Majumder, Hemanta K.
TI Mitochondria-Dependent Reactive Oxygen Species-Mediated Programmed Cell
Death Induced by 3,3 '-Diindolylmethane through Inhibition of F0F1-ATP
Synthase in Unicellular Protozoan Parasite Leishmania donovani
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID APOPTOSIS-LIKE DEATH; BREAST-CANCER CELLS; TOPOISOMERASE-I; TRYPANOSOME
MITOCHONDRIA; DYSKINETOPLASTID CELLS; OXIDATIVE STRESS; ATP SYNTHASE;
CYTOCHROME-C; CAMPTOTHECIN; PROMASTIGOTES
AB Mitochondria are the principal site for the generation of cellular ATP by oxidative phosphorylation. F0F1-ATP synthase, a complex V of the electron transport chain, is an important constituent of mitochondria-dependent signaling pathways involved in apoptosis. In the present study, we have shown for the first time that 3,3'-diindolylmethane (DIM), a DNA topoisomerase I poison, inhibits mitochondrial F0F1-ATP synthase of Leishmania donovani and induces programmed cell death (PCD), which is a novel insight into the mechanism in protozoan parasites. DIM-induced inhibition of F0F1-ATP synthase activity causes depletion of mitochondrial ATP levels and significant stimulation of mitochondrial reactive oxygen species (ROS) production, followed by depolarization of mitochondrial membrane potential (Delta Psi m). Because Delta Psi m is the driving force for mitochondrial ATP synthesis, loss of Delta Psi m results in depletion of cellular ATP level. The loss of Delta Psi m causes the cellular ROS generation and in turn leads to the oxidative DNA lesions followed by DNA fragmentation. In contrast, loss of Delta Psi m leads to release of cytochrome c into the cytosol and subsequently activates the caspase-like proteases, which lead to oligonucleosomal DNA cleavage. We have also shown that mitochondrial DNA-depleted cells are insensitive to DIM to induce PCD. Therefore, mitochondria are necessary for cytotoxicity of DIM in kinetoplastid parasites. Taken together, our study indicates for the first time that DIM-induced mitochondrial dysfunction by inhibition of F0F1-ATP synthase activity leads to PCD in Leishmania spp. parasites, which could be exploited to develop newer potential therapeutic targets.
C1 [Roy, Amit; Ganguly, Agneyo; BoseDasgupta, Somdeb; Majumder, Hemanta K.] Indian Inst Chem Biol, Mol Parasitol Lab, Kolkata 700032, India.
[Pal, Churala; Jaisankar, Parasuraman] Indian Inst Chem Biol, Dept Med Chem, Kolkata 700032, India.
[Das, Benu Brata] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
RP Majumder, HK (reprint author), Indian Inst Chem Biol, Mol Parasitol Lab, 4 Raja SC Mullick Rd, Kolkata 700032, India.
EM hkmajumder@iicb.res.in
FU Network Project NWP-38 of Council of Scientific and Industrial Research,
Government of India
FX This work was supported by the grants from Network Project NWP-38 of
Council of Scientific and Industrial Research, Government of India.
NR 39
TC 80
Z9 82
U1 3
U2 9
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD NOV
PY 2008
VL 74
IS 5
BP 1292
EP 1307
DI 10.1124/mol.108.050161
PG 16
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 362KT
UT WOS:000260197300013
PM 18703668
ER
PT J
AU Borland, MG
Foreman, JE
Girroir, EE
Zolfaghari, R
Sharma, AK
Amin, S
Gonzalez, FJ
Ross, AC
Peters, JM
AF Borland, Michael G.
Foreman, Jennifer E.
Girroir, Elizabeth E.
Zolfaghari, Reza
Sharma, Arun K.
Amin, Shantu
Gonzalez, Frank J.
Ross, A. Catharine
Peters, Jeffrey M.
TI Ligand Activation of Peroxisome Proliferator-Activated
Receptor-beta/delta Inhibits Cell Proliferation in Human HaCaT
Keratinocytes
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID DIETARY RETINOIC ACID; SKIN TUMOR PROMOTION; FEMALE SENCAR MICE;
PPAR-BETA/DELTA; MOUSE SKIN; CARCINOGENESIS PROTOCOL; MALIGNANT
CONVERSION; 9-CIS-RETINOIC ACID; HIGH-RISK; GROWTH
AB Although there is strong evidence that ligand activation of peroxisome proliferator-activated receptor (PPAR)-beta/delta induces terminal differentiation and attenuates cell growth, some studies suggest that PPAR beta/delta actually enhances cell proliferation. For example, it was suggested recently that retinoic acid (RA) is a ligand for PPAR beta/delta and potentiates cell proliferation by activating PPAR beta/delta. The present study examined the effect of ligand activation of PPAR beta/delta on cell proliferation, cell cycle kinetics, and target gene expression in human HaCaT keratinocytes using two highly specific PPAR beta/delta ligands [4-[[[2-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-5-thiazolyl] methyl]thio]-2-methylphenoxy acetic acid (GW0742) and 2-methyl-4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-thiazol-5- yl)-methylsulfanyl)phenoxy-acetic acid (GW501516)] and RA. Both PPAR beta/delta ligands and RA inhibited cell proliferation of HaCaT keratinocytes. GW0742 and GW501516 increased expression of known PPAR beta/delta target genes, whereas RA did not; RA increased the expression of known retinoic acid receptor/retinoid X receptor target genes, whereas GW0742 did not affect these genes. GW0742, GW501516, and RA did not modulate the expression of 3-phosphoinositide-dependent protein kinase or alter protein kinase B phosphorylation. GW0742 and RA increased annexin V staining as quantitatively determined by flow cytometry. The effects of GW0742 and RA were also examined in wild-type and PPAR beta/delta-null primary mouse keratinocytes to determine the specific role of PPAR beta/delta in modulating cell growth. Although inhibition of keratinocyte proliferation by GW0742 was PPAR beta/delta-dependent, inhibition of cell proliferation by RA occurred in both genotypes. Results from these studies demonstrate that ligand activation of PPAR beta/delta inhibits keratinocyte proliferation through PPAR beta/delta-dependent mechanisms. In contrast, the observed inhibition of cell proliferation in mouse and human keratinocytes by RA is mediated by PPAR beta/delta-independent mechanisms and is inconsistent with the notion that RA potentiates cell proliferation by activating PPAR beta/delta.
C1 [Borland, Michael G.; Foreman, Jennifer E.; Girroir, Elizabeth E.; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Borland, Michael G.; Foreman, Jennifer E.; Girroir, Elizabeth E.; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Borland, Michael G.; Peters, Jeffrey M.] Penn State Univ, Grad Program Biochem Microbiol & Mol Biol, University Pk, PA 16802 USA.
[Zolfaghari, Reza; Ross, A. Catharine] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Sharma, Arun K.; Amin, Shantu] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Penn State Canc Inst, Hershey, PA 17033 USA.
[Gonzalez, Frank J.] Natl Canc Inst, Lab Metab, Bethesda, MD USA.
RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA.
EM jmp21@psu.edu
RI Peters, Jeffrey/D-8847-2011
FU National Science Foundation Graduate Research Fellowship; National
Institutes of Health [CA124533, CA90214]
FX This work was supported by a National Science Foundation Graduate
Research Fellowship and by National Institutes of Health grants CA124533
(to J. M. P.) and CA90214 (to A. C. R.).
NR 53
TC 32
Z9 33
U1 1
U2 2
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 NOV
PY 2008
VL 74
IS 5
BP 1429
EP 1442
DI 10.1124/mol.108.050609
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 362KT
UT WOS:000260197300026
PM 18687807
ER
PT J
AU Volkow, N
Rutter, J
Pollock, JD
Shurtleff, D
Baler, R
AF Volkow, N.
Rutter, J.
Pollock, J. D.
Shurtleff, D.
Baler, R.
TI One SNP linked to two diseases-addiction and cancer: A Double Whammy?
Nicotine addiction and lung cancer susceptibility
SO MOLECULAR PSYCHIATRY
LA English
DT Editorial Material
ID IN-VIVO; ALPHA-3; ASSOCIATION; DEPENDENCE; RECEPTORS; GENES; LOCUS; RNA
C1 [Volkow, N.] Natl Inst Drug Abuse, NIH, Off Director, Bethesda, MD 20892 USA.
[Rutter, J.; Pollock, J. D.; Shurtleff, D.] Natl Inst Drug Abuse, NIH, Div Basic Neurosci & Behav Res, Bethesda, MD USA.
[Baler, R.] Natl Inst Drug Abuse, NIH, Off Sci Policy & Commun, Bethesda, MD USA.
RP Volkow, N (reprint author), Natl Inst Drug Abuse, NIH, Off Director, Bethesda, MD 20892 USA.
EM balerr@mail.nih.gov
RI Pollock, Jonathan/B-1554-2009;
OI Rutter, Joni/0000-0002-6502-2361
FU Intramural NIH HHS [Z99 DA999999]
NR 17
TC 10
Z9 11
U1 0
U2 1
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 NOV
PY 2008
VL 13
IS 11
BP 990
EP 992
DI 10.1038/mp.2008.71
PG 3
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 368OS
UT WOS:000260632200001
PM 18936755
ER
PT J
AU Brosh, R
Shalgi, R
Liran, A
Landan, G
Korotayev, K
Nguyen, GH
Enerly, E
Johnsen, H
Buganim, Y
Solomon, H
Goldstein, I
Madar, S
Goldfinger, N
Brresen-Dale, AL
Ginsberg, D
Harris, CC
Pilpel, Y
Oren, M
Rotter, V
AF Brosh, Ran
Shalgi, Reut
Liran, Atar
Landan, Gilad
Korotayev, Katya
Nguyen, Giang Huong
Enerly, Espen
Johnsen, Hilde
Buganim, Yosef
Solomon, Hilla
Goldstein, Ido
Madar, Shalom
Goldfinger, Naomi
Brresen-Dale, Anne-Lise
Ginsberg, Doron
Harris, Curtis C.
Pilpel, Yitzhak
Oren, Moshe
Rotter, Varda
TI p53-repressed miRNAs are involved with E2F in a feed-forward loop
promoting proliferation
SO MOLECULAR SYSTEMS BIOLOGY
LA English
DT Article
DE breast cancer; microarray; miR-106; mir-155; senescence
ID CELL-CYCLE PROGRESSION; P53 TUMOR-SUPPRESSOR; GENE-EXPRESSION;
MESSENGER-RNA; BREAST-CANCER; COLON-CANCER; MUTANT P53; S-PHASE;
MICRORNAS; APOPTOSIS
AB Normal cell growth is governed by a complicated biological system, featuring multiple levels of control, often deregulated in cancers. The role of microRNAs (miRNAs) in the control of gene expression is now increasingly appreciated, yet their involvement in controlling cell proliferation is still not well understood. Here we investigated the mammalian cell proliferation control network consisting of transcriptional regulators, E2F and p53, their targets and a family of 15 miRNAs. Indicative of their significance, expression of these miRNAs is downregulated in senescent cells and in breast cancers harboring wild-type p53. These miRNAs are repressed by p53 in an E2F1-mediated manner. Furthermore, we show that these miRNAs silence antiproliferative genes, which themselves are E2F1 targets. Thus, miRNAs and transcriptional regulators appear to cooperate in the framework of a multi-gene transcriptional and post-transcriptional feed-forward loop. Finally, we show that, similarly to p53 inactivation, overexpression of representative miRNAs promotes proliferation and delays senescence, manifesting the detrimental phenotypic consequence of perturbations in this circuit. Taken together, these findings position miRNAs as novel key players in the mammalian cellular proliferation network.
C1 [Brosh, Ran; Shalgi, Reut; Liran, Atar; Landan, Gilad; Buganim, Yosef; Solomon, Hilla; Goldstein, Ido; Madar, Shalom; Goldfinger, Naomi; Oren, Moshe; Rotter, Varda] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
[Shalgi, Reut; Pilpel, Yitzhak] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
[Korotayev, Katya; Ginsberg, Doron] Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel.
[Nguyen, Giang Huong; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Nguyen, Giang Huong] Howard Hughes Med Inst, Natl Inst Hlth Res Scholar, Chevy Chase, MD USA.
[Enerly, Espen; Brresen-Dale, Anne-Lise] Univ Oslo, Norwegian Radium Hosp, Fac Div, Dept Genet, Oslo, Norway.
RP Rotter, V (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
EM varda.rotter@weizmann.ac.il
OI Shalgi, Reut/0000-0002-7589-1798; Brosh, Ran/0000-0001-9714-8623;
Goldstein, Ido/0000-0003-0139-1499
FU Flight Attendant Medical Research Institute; EC [502983]; FP7 funding
(ONCOMIRS) [201102]; Ben May Charitable Trust; Israel Science
Foundation; Yad Abraham Center for Cancer Diagnosis and Therapy;
Intramural Research Program; NIH; NCI; CCR; Howard Hughes Medical
Institute Grant for Graduate Medical Education
FX This study was supported by a Center of Excellence grant from the Flight
Attendant Medical Research Institute; EC FP6 funding (contract no.
502983); FP7 funding (ONCOMIRS, agreement 201102); the Ben May
Charitable Trust; the Israel Science Foundation and the Yad Abraham
Center for Cancer Diagnosis and Therapy. This research was supported in
part by the Intramural Research Program, NIH, NCI and CCR. VR is the
incumbent of the Norman and Helen Asher Professorial Chair Cancer
Research at the Weizmann institute. YP is an incumbent of the Rothstein
Career Development Chair in Genetic Diseases. RS is a fellow of the
Horowitz Foundation for Complexity Sciences. GHN was supported by the
Howard Hughes Medical Institute Grant for Graduate Medical Education.
This publication reflects only authors' views. The European Commission
is not liable for any use that may be made of the information herein. We
thank Agilent Technologies for access to the early version of their
miRNA arrays and for their support.
NR 66
TC 103
Z9 110
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1744-4292
J9 MOL SYST BIOL
JI Mol. Syst. Biol.
PD NOV
PY 2008
VL 4
AR 229
DI 10.1038/msb.2008.65
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 379KG
UT WOS:000261394500004
PM 19034270
ER
PT J
AU Dobrikova, EY
Broadt, T
Poiley-Nelson, J
Yang, XY
Soman, G
Giardina, S
Harris, R
Gromeier, M
AF Dobrikova, Elena Y.
Broadt, Trevor
Poiley-Nelson, Judith
Yang, Xiaoyi
Soman, Gopalan
Giardina, Steve
Harris, Ray
Gromeier, Matthias
TI Recombinant Oncolytic Poliovirus Eliminates Glioma In Vivo Without
Genetic Adaptation to a Pathogenic Phenotype
SO MOLECULAR THERAPY
LA English
DT Article
ID RIBOSOMAL ENTRY SITE; ATTENUATED POLIOVIRUS; TRANSGENIC MICE; ATHYMIC
MICE; NEUROBLASTOMA; THERAPY; GROWTH; REGION; TUMORS; NEUROVIRULENCE
AB Many viruses, either naturally occurring or as a result of genetic manipulation, exhibit conditional replication in transformed cells. This principle is the basis for experimental therapeutic approaches exploiting the oncolytic potential of such agents without the danger of collateral damage to resistant normal tissues. One of the potential obstacles to these approaches is the possibility of genetic adaptation of oncolytic viruses upon replication in susceptible tumor tissues. Genetic variation can reverse genetic manipulations of parental viral genomes that determine attenuation of virulence, selective tumor cell tropism or other desirable traits. Alternatively, it may convey new properties not originally associated with parental strains, e. g., adaptation to a human host range. We examined genetic stability of an oncolytic nonpathogenic poliovirus recombinant considered for therapy of recurrent glioblastoma multiforme (GBM). This was done by serial passage experiments in glioma xenografts in vivo and investigation of phenotypic and genotypic markers of attenuation. Intratumoral inoculation of oncolytic poliovirus produced efficient tumor regress and elimination without altering temperature-sensitive growth, selective cytotoxicity, or genetic markers of attenuation of virus recovered from inoculated animals. Our studies demonstrate that active viral oncolysis of malignant glioma does not alter the conditional replication properties of oncolytic nonpathogenic poliovirus recombinants.
C1 [Dobrikova, Elena Y.; Gromeier, Matthias] Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA.
[Broadt, Trevor; Poiley-Nelson, Judith; Yang, Xiaoyi; Soman, Gopalan; Giardina, Steve; Harris, Ray] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Gromeier, M (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA.
EM grome001@mc.duke.edu
FU PHS [NS20023, CA124756]; Alex's Lemonade Stand Foundation; Developmental
Therapeutics Program; Division of Cancer Treatment and Diagnosis;
National Cancer Institute; National Institutes of Health
FX We gratefully acknowledge A. Nomoto (University of Tokyo, Japan) for
providing the genomic complementary DNA clone of poliovirus type 1
(Sabin) used to generate PVS-RIPO. This work was supported by the PHS
grants NS20023 (to M. G.), CA124756 (to M. G.), and Alex's Lemonade
Stand Foundation. This project has been supported in whole or in part
through the NCI-RAID Program of the Developmental Therapeutics Program,
Division of Cancer Treatment and Diagnosis, National Cancer Institute,
National Institutes of Health. 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 any organization imply endorsement by the US Government.
NR 33
TC 28
Z9 28
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD NOV
PY 2008
VL 16
IS 11
BP 1865
EP 1872
DI 10.1038/mt.2008.184
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 366HY
UT WOS:000260472600017
PM 18766173
ER
PT J
AU Kelsall, B
AF Kelsall, B.
TI Recent progress in understanding the phenotype and function of
intestinal dendritic cells and macrophages
SO MUCOSAL IMMUNOLOGY
LA English
DT Review
ID REGULATORY T-CELLS; FOLLICLE-ASSOCIATED EPITHELIUM;
INFLAMMATORY-BOWEL-DISEASE; MURINE PEYERS PATCH; ORAL SALMONELLA
INFECTION; TOLL-LIKE RECEPTOR-5; TRANS-RETINOIC ACID; LAMINA-PROPRIA;
TGF-BETA; IMMUNE-RESPONSES
AB Mucosal immune responses must be tightly controlled, particularly in the intestine. As members of the mononuclear phagocyte family, dendritic cells (DCs) and macrophages are well represented in intestinal tissues and have developed unique functional niches. This review will focus on recent findings on antigen uptake and processing in the intestine and the role of DCs in the imprinting of homing receptors on T and B cells, the induction of immunoglobulin A B-cell responses, and the differentiation of regulatory T cells. It will also address the unique phenotype of intestinal macrophages and briefly what is known regarding the relationships between these cell types.
C1 NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Kelsall, B (reprint author), NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Kelsall@nih.gov
FU Intramural NIH HHS [Z01 AI000833-10]
NR 123
TC 76
Z9 79
U1 2
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD NOV
PY 2008
VL 1
IS 6
BP 460
EP 469
DI 10.1038/mi.2008.61
PG 10
WC Immunology
SC Immunology
GA 366HL
UT WOS:000260471300007
PM 19079213
ER
PT J
AU Udey, MC
Nagao, K
AF Udey, M. C.
Nagao, K.
TI Characteristics and functions of murine cutaneous dendritic cells: a
synopsis of recent developments
SO MUCOSAL IMMUNOLOGY
LA English
DT Review
ID EPIDERMAL LANGERHANS CELLS; STEADY-STATE; CONTACT HYPERSENSITIVITY;
BONE-MARROW; NULL MICE; T-CELLS; IN-VIVO; SKIN; LANGERIN/CD207;
IDENTIFICATION
AB Cutaneous accessory cells include dendritic cells (DCs) and macrophages. Heterogeneity, plasticity, and responsiveness to local environmental cues are hallmarks of both types of cells. Until recently, results of studies of cells that had been extracted from tissues or propagated in vitro provided the foundation for most conceptual frameworks. The availability of a variety of spontaneously occurring and genetically engineered mice has facilitated in vivo studies that have provided new insights into the developmental and functional aspects of DCs in skin and other tissues. In several instances, results of these in vivo studies have been very surprising. Existing paradigms have been modified or debunked, and new hypotheses have been generated. We can anticipate that detailed understanding of the biology of individual cutaneous accessory cells and their relationships with each other will continue to accumulate as these types of studies are actively pursued.
C1 [Udey, M. C.; Nagao, K.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Udey, MC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM udey@helix.nih.gov
RI Nagao, Keisuke/J-5116-2013
OI Nagao, Keisuke/0000-0002-7005-3138
FU Intramural Program of the NIH; Center for Cancer Research; NCI
FX We thank Miriam Merad for helpful discussions and for allowing us to
review and cite materials that were in press when this paper was
prepared. This study was supported by the Intramural Program of the NIH,
Center for Cancer Research, NCI.
NR 32
TC 6
Z9 6
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD NOV
PY 2008
VL 1
IS 6
BP 470
EP 474
DI 10.1038/mi.2008.37
PG 5
WC Immunology
SC Immunology
GA 366HL
UT WOS:000260471300008
PM 19079214
ER
PT J
AU Macal, M
Sankaran, S
Chun, TW
Reay, E
Flamm, J
Prindiville, TJ
Dandekar, S
AF Macal, M.
Sankaran, S.
Chun, T-W
Reay, E.
Flamm, J.
Prindiville, T. J.
Dandekar, S.
TI Effective CD4+T-cell restoration in gut-associated lymphoid tissue of
HIV-infected patients is associated with enhanced Th17 cells and
polyfunctional HIV-specific T-cell responses
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; TYPE-1
INFECTION; HIV-1-INFECTED SUBJECTS; ANTIVIRAL THERAPY; CCR5 EXPRESSION;
MUCOSAL REPAIR; MEMORY; REPLICATION; PERSISTENCE
AB Human immunodeficiency virus (HIV) infection leads to severe CD4+ T-cell depletion in gut-associated lymphoid tissue (GALT) that persists despite the initiation of highly active antiretroviral therapy (HAART). It is not known whether restoration of gut mucosal CD4+ T cells and their functions is feasible during therapy and how that relates to immune correlates and viral reservoirs. Intestinal biopsies and peripheral blood samples from HIV-infected patients who were either HAART naive or on long-term HAART were evaluated. Our data demonstrated that gut CD4+ T-cell restoration ranged from modest (<50%) to high (>50%), compared with uninfected controls. Despite persistent CD4+ T-cell proviral burden and residual immune activation in GALT during HAART, effective CD4+ T-cell restoration (>50%) was achieved, which was associated with enhanced Th17 CD4+ T-cell accumulation and polyfunctional anti-HIV cellular responses. Our findings suggest that a threshold of >50% CD4+ T-cell restoration may be sufficient for polyfunctional HIV-specific T cells with implications in the evaluation of vaccines and therapeutics.
C1 [Macal, M.; Sankaran, S.; Reay, E.; Dandekar, S.] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA.
[Chun, T-W] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Flamm, J.] Kaiser Permanente Med Grp, Sacramento, CA USA.
[Prindiville, T. J.] Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA.
RP Dandekar, S (reprint author), Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA.
EM sdandekar@ucdavis.edu
FU National Institute of Health (NIH) [R01 DK61297, AIO43274, T32 AI-60555]
FX We thank UCDMC GI and J St Clinic staff, California HIV AIDS Research
Program CH5-D-606, Dr Jerome Braun for statistical advice, Dr Michael
George for paper review, and patients for their participation. Study
support was provided by the National Institute of Health (NIH) R01
DK61297 and by NIH supplemental award AIO43274 and T32 AI-60555 for
primary author.
NR 45
TC 111
Z9 116
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD NOV
PY 2008
VL 1
IS 6
BP 475
EP 488
DI 10.1038/mi.2008.35
PG 14
WC Immunology
SC Immunology
GA 366HL
UT WOS:000260471300009
PM 19079215
ER
PT J
AU Vaccari, M
Boasso, A
Ma, ZM
Cecchinato, V
Venzon, D
Doster, MN
Tsai, WP
Shearer, GM
Fuchs, D
Felber, BK
Pavlakis, GN
Miller, CJ
Franchini, G
AF Vaccari, M.
Boasso, A.
Ma, Z-M
Cecchinato, V.
Venzon, D.
Doster, M. N.
Tsai, W. P.
Shearer, G. M.
Fuchs, D.
Felber, B. K.
Pavlakis, G. N.
Miller, C. J.
Franchini, G.
TI CD4(+) T-cell loss and delayed expression of modulators of immune
responses at mucosal sites of vaccinated macaques following SIVmac251
infection
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID SIMIAN-IMMUNODEFICIENCY-VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX;
LYMPHOID-TISSUE; RHESUS-MONKEYS; SIV INFECTION; ANTIRETROVIRAL THERAPY;
SYSTEMIC VACCINATION; TYPE-1 INFECTION; TGF-BETA; MEMORY
AB Systemic immunization of macaques with a combination of DNA-poxvirus-based vaccines confers protection from high level of both systemic and mucosal viral replication following rectal exposure to the pathogenic SIVmac251. Here we investigated early post-infection events in rectal and vaginal tissues, and found that the loss of CCR5(+) CD4(+) T cells was equivalent in vaccinated and control macaques, despite a three logs reduction at mucosal sites of simian immunodeficiency virus (SIV) RNA in the vaccinated group. Even though a normal CD4(+) T cell number is not reconstituted at mucosal sites in either group, vaccination appeared to confer a better preservation of the CD4(+) CCR5(+) T cells that replenish these sites. Analysis of rectal tissues RNA following challenge exposure demonstrated a decreased expression in vaccinated macaques of transforming growth factor-beta, cytotoxic T lymphocyte antigen-4, FoxP3, and indoleamine 2,3-dioxygenase, an immune suppressive enzyme expressed by dendritic cells that converts tryptophan to kynurenine and limits T-cell responses. Accordingly, the ratio of kynurenine and tryptophan in the plasma was significantly reduced in the vaccinated animals respect to the controls. Thus, preexisting adaptive immune responses induced by these vaccine modalities, although they do not protect from CD4(+) T-cell depletion, nevertheless, they contain SIVmac251 replication and delay expression of markers of T-cell activation and/or suppression at mucosal sites.
C1 [Vaccari, M.; Cecchinato, V.; Doster, M. N.; Tsai, W. P.; Franchini, G.] NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA.
[Boasso, A.; Shearer, G. M.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Ma, Z-M] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA.
[Venzon, D.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
[Fuchs, D.] Innsbruck Med Univ, Div Biol Chem, Bioctr, Innsbruck, Austria.
[Felber, B. K.] NCI, Human Retrovirus Pathogenesis Sect, NIH, Frederick, MD 21701 USA.
[Pavlakis, G. N.] NCI, Human Retrovirus Sect, NIH, Frederick, MD 21701 USA.
RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA.
EM franchig@mail.nih.gov
OI Boasso, Adriano/0000-0001-9673-6319
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research
FX We thank P. D. Markham, S. Orndorff, D. Weiss, and J. Treece of Advanced
BioScience Laboratories, Kensington, MD. We thank D. Panicali from
Therion for constructing and providing us the recombinant poxviruses. We
also thank Steven Snodgrass, Ryan Kelly, and Teresa Habina for the
editorial assistance. This research was supported by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 43
TC 21
Z9 21
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD NOV
PY 2008
VL 1
IS 6
BP 497
EP 507
DI 10.1038/mi.2008.60
PG 11
WC Immunology
SC Immunology
GA 366HL
UT WOS:000260471300011
PM 19079217
ER
PT J
AU Fichtner-Feigl, S
Strober, W
Geissler, EK
Schlitt, HJ
AF Fichtner-Feigl, S.
Strober, W.
Geissler, E. K.
Schlitt, H-J
TI Cytokines mediating the induction of chronic colitis and
colitis-associated fibrosis
SO MUCOSAL IMMUNOLOGY
LA English
DT Article; Proceedings Paper
CT Workshop on Mechanisms of Intestinal Inflammation
CY OCT, 2007
CL Dresden, GERMANY
SP Falk Fdn
ID INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; IL-13; RECEPTOR
AB To investigate the immunopathogenesis of inflammation-associated fibrosis we analyzed the chronic colitis and late-developing fibrosis occurring in BALB/c mice administered weekly doses of intrarectal trinitrobenzene sulfonic acid (TNBS). We showed first in this model that an initial T helper type 1 response involving interleukin (IL)-12p70 and interferon-gamma subsides after 3 weeks to be supplanted by an IL-23/IL-25 response beginning after 4-5 weeks. This evolution is followed by gradually increasing production of IL-17 and cytokines ordinarily seen in a T helper type 2 response, particularly IL-13, which reaches a plateau at 8-9 weeks. We then show that IL-13 production results in the induction of an IL-13 receptor formerly thought to function only as a decoy receptor, IL-13R alpha(2), and this receptor is critical to the production of tumor growth factor (TGF)-beta(1) and the onset of fibrosis. Thus, if IL-13 signaling through this receptor is blocked by administration of soluble IL-13R alpha(2)-Fc, or by administration of IL-13R alpha(2)-specific siRNA, TGF-beta(1) is not produced and fibrosis does not occur. These studies show that in chronic TNBS colitis, fibrosis is dependent on the development of an IL-13 response that acts through a novel cell-surface-expressed IL-13 receptor to induce TGF-beta(1).
C1 [Fichtner-Feigl, S.; Strober, W.] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Fichtner-Feigl, S.; Geissler, E. K.; Schlitt, H-J] Univ Regensburg, Dept Surg, Regensburg, Germany.
RP Fichtner-Feigl, S (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
EM stefan.fichtner@klinik.uni-regensburg.de
RI Geissler, Edward/R-4131-2016
FU Intramural NIH HHS [ZIA AI000432-25]
NR 12
TC 29
Z9 30
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD NOV
PY 2008
VL 1
SU 1
BP S24
EP S27
DI 10.1038/mi.2008.41
PG 4
WC Immunology
SC Immunology
GA 366HN
UT WOS:000260471500006
PM 19079223
ER
PT J
AU Fuss, IJ
Strober, W
AF Fuss, I. J.
Strober, W.
TI The role of IL-13 and NK T cells in experimental and human ulcerative
colitis
SO MUCOSAL IMMUNOLOGY
LA English
DT Article; Proceedings Paper
CT Workshop on Mechanisms of Intestinal Inflammation
CY OCT, 2007
CL Dresden, GERMANY
SP Falk Fdn
ID ANTIGEN PRESENTATION; OXAZOLONE COLITIS; MODEL
AB Recent studies that have evaluated the immunologic factors that mediate the development of the two forms of inflammatory bowel disease, namely Crohn's disease and ulcerative colitis (UC), have suggested that these diseases are because of disparate immune responses. Although Crohn's disease has been characterized as a dysregulation of the T helper (Th)1/Th17 pathways more recent evidence has emerged that UC pathogenesis is associated with a nonclassical NK (natural killer) T cell producing an atypical Th2 (interleukin (IL)-13) response. In the following review the insights gained from both animal models and human studies as to the function that IL-13 and NK T cells have in the pathogenesis of UC will be discussed.
C1 [Fuss, I. J.; Strober, W.] NIH, Mucosal Immun Sect, Host Def Lab, Bethesda, MD 20892 USA.
RP Fuss, IJ (reprint author), NIH, Mucosal Immun Sect, Host Def Lab, Bldg 10, Bethesda, MD 20892 USA.
EM ifuss@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000354-25]
NR 12
TC 46
Z9 47
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD NOV
PY 2008
VL 1
SU 1
BP S31
EP S33
DI 10.1038/mi.2008.40
PG 3
WC Immunology
SC Immunology
GA 366HN
UT WOS:000260471500008
PM 19079225
ER
PT J
AU Kitani, A
Xu, L
AF Kitani, A.
Xu, L.
TI Regulatory T cells and the induction of IL-17
SO MUCOSAL IMMUNOLOGY
LA English
DT Article; Proceedings Paper
CT Workshop on Mechanisms of Intestinal Inflammation
CY OCT, 2007
CL Dresden, GERMANY
SP Falk Fdn
ID GROWTH-FACTOR-BETA; TGF-BETA; CUTTING EDGE; HELPER-CELLS;
DIFFERENTIATION; INTERLEUKIN-17; COLITIS; LINEAGE; CURE
AB T helper (Th)17 cells have been shown to play a role in the pathogenesis of inflammatory and autoimmune diseases including inflammatory bowel diseases (IBD). It is now well established that although transforming growth factor (TGF)-beta alone induces FoxP3(+) regulatory T (Treg) cells, TGF-beta and interleukin (IL)-6, acting in concert, induce differentiation of mouse naive T cells into Th17. As we previously showed that CD4(+)CD25(+)Foxp3(+) "natural" Treg cells express cell surface or secrete TGF-beta, we examined whether Treg cells serve to induce Th17 differentiation. We found that upon activation, Treg cells induce CD4(+)CD25(-) naive T cells or Treg cells themselves to differentiate into Th17 in the presence of IL-6 alone without exogenous addition of TGF-beta. We also found that TGF-beta is also produced by dendritic cells that are in contact with Treg cells. Although Treg cells are effectively recruited at inflamed mucosa in patients with IBD, it is possible that Treg cells may have undesirable effects through their ability to differentiate into pathogenic Th17 in the presence of IL-6 and/or IL-23 at sites of inflammation. Further study of the relationship between Treg cells and Th17 cells in the inflamed tissue in IBD is important for possible Treg cell-mediated therapeutic applications.
C1 [Kitani, A.; Xu, L.] NIAID, Mucosal Immun Sect, Host Def Lab, Bethesda, MD 20892 USA.
RP Kitani, A (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, Bethesda, MD 20892 USA.
EM akitani@niaid.nih.gov
NR 18
TC 30
Z9 36
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD NOV
PY 2008
VL 1
SU 1
BP S43
EP S46
DI 10.1038/mi.2008.51
PG 4
WC Immunology
SC Immunology
GA 366HN
UT WOS:000260471500011
PM 19079228
ER
PT J
AU Strober, W
Kitani, A
Fuss, I
Asano, N
Watanabe, T
AF Strober, W.
Kitani, A.
Fuss, I.
Asano, N.
Watanabe, T.
TI The molecular basis of NOD2 susceptibility mutations in Crohn's disease
SO MUCOSAL IMMUNOLOGY
LA English
DT Article; Proceedings Paper
CT Workshop on Mechanisms of Intestinal Inflammation
CY OCT, 2007
CL Dresden, GERMANY
SP Falk Fdn
ID COLITIS; INDUCTION; RESPONSES; MICE
AB Nucleotide oligomerization domain (NOD) 2 is a member of the NOD-like receptor family of proteins that initiate inflammatory responses when exposed to ligands derived from bacterial components that gain access to the intracellular milieu. It is thus somewhat paradoxical that polymorphisms in the gene that encode NOD2 (CARD15) that lead to impaired NOD2 function, are susceptibility factors in Crohn's disease, a condition marked by excessive inflammatory responses to normal bacterial flora. In an initial series of studies conducted in our laboratory to better define NOD2 function and to resolve this paradox we showed that NOD2 activation by its ligand, muramyl dipeptide (MDP) ordinarily downregulates responses to Toll-like receptor (TLR) stimulation, and thus cells lacking NOD2 mount increased responses to such stimulation. This fits with the fact that mice bearing an NOD2 transgene, and thus having cells with increased NOD2 function display decreased responses to TLR stimulation and are resistant to experimental colitis induction. In further studies, we showed that prestimulation of cells with NOD2 ligand renders them unresponsive to TLR stimulation, because such prestimulation results in the elaboration of inhibitory factor (IRF4), an inhibitor of TLR-induced inflammatory pathways. Furthermore, administration of MDP to normal mice induces IRF4 and prevents experimental colitis. These studies strongly suggest that NOD2 polymorphisms are associated with Crohn's disease because they lead to a decrease in the negative regulation of TLR responses occurring in the normal gut, and thus a pathologic increase in responses to the normal flora. The finding that MDP administration prevents experimental colitis opens the door to the possibility that such treatment might quell Crohn's disease relapses in patients without NOD2 abnormalities.
C1 [Strober, W.; Kitani, A.; Fuss, I.; Asano, N.; Watanabe, T.] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Watanabe, T.] Kyoto Univ, Dept Gastroenterol & Hepatol, Grad Sch Med, Kyoto, Japan.
RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
EM wstrober@niaid.nih.gov
OI Asano, Naoki/0000-0003-4452-8459
FU Intramural NIH HHS [Z01 AI000354-25]
NR 8
TC 53
Z9 54
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD NOV
PY 2008
VL 1
SU 1
BP S5
EP S9
DI 10.1038/mi.2008.42
PG 5
WC Immunology
SC Immunology
GA 366HN
UT WOS:000260471500002
PM 19079230
ER
PT J
AU Strober, W
Zeitz, M
Blumberg, RS
AF Strober, W.
Zeitz, M.
Blumberg, R. S.
TI Preface
SO MUCOSAL IMMUNOLOGY
LA English
DT Editorial Material
C1 [Strober, W.] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Zeitz, M.] Charite Univ Med Berlin, Med Klin 1, Berlin, Germany.
[Blumberg, R. S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Gastroenterol Div, Boston, MA 02115 USA.
RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD NOV
PY 2008
VL 1
SU 1
BP S1
EP S4
DI 10.1038/mi.2008.58
PG 4
WC Immunology
SC Immunology
GA 366HN
UT WOS:000260471500001
PM 19079219
ER
PT J
AU Miller, DH
Weinshenker, BG
Filippi, M
Banwell, BL
Cohen, JA
Freedman, MS
Galetta, SL
Hutchinson, M
Johnson, RT
Kappos, L
Kira, J
Lublin, FD
McFarland, HF
Montalban, X
Panitch, H
Richert, JR
Reingold, SC
Polman, CH
AF Miller, D. H.
Weinshenker, B. G.
Filippi, M.
Banwell, B. L.
Cohen, J. A.
Freedman, M. S.
Galetta, S. L.
Hutchinson, M.
Johnson, R. T.
Kappos, L.
Kira, J.
Lublin, F. D.
McFarland, H. F.
Montalban, X.
Panitch, H.
Richert, J. R.
Reingold, S. C.
Polman, C. H.
TI Differential diagnosis of suspected multiple sclerosis: a consensus
approach
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Review
DE diagnosis; differential diagnosis; multiple sclerosis
ID DEVICS-NEUROMYELITIS-OPTICA; CLINICALLY ISOLATED SYNDROMES; ACUTE
DISSEMINATED ENCEPHALOMYELITIS; MAGNETIZATION-TRANSFER; IMAGING CHANGES;
IGG PREDICTS; MRI FINDINGS; FOLLOW-UP; NMO-IGG; CRITERIA
AB Background and objectives Diagnosis of multiple sclerosis ( MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis.
Methods Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases.
Results We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of "clinically isolated syndromes" (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. Conclusions Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision. Multiple Sclerosis 2008; 14: 1157 1174. http://msj.sagepub. com
C1 [Miller, D. H.] UCL, NMR Res Unit, Inst Neurol, Dept Inflammat, London WC1E 6BT, England.
[Weinshenker, B. G.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA.
[Filippi, M.] Osped San Rafaele, Dept Neurol, Neuroimaging Res Unit, Milan, Italy.
[Banwell, B. L.] Hosp Sick Children, Dept Paediat, Div Neurol, Toronto, CA USA.
[Cohen, J. A.] Cleveland Clin, Mellen Ctr, Cleveland, OH 44106 USA.
[Freedman, M. S.] Univ Ottawa, Ottawa Hosp, Dept Med Neurol, MS Res Unit, Ottawa, CA USA.
[Galetta, S. L.] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Hutchinson, M.] St Vincents Univ Hosp, Dept Neurol, Dublin 4, Ireland.
[Johnson, R. T.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA.
[Kappos, L.] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland.
[Kira, J.] Kyushu Univ, Dept Neurol, Kyushu, Japan.
[Lublin, F. D.] Mt Sinai Sch Med, Corrine Goldsmith Dickinson Ctr Multiple Sclerosi, New York, NY USA.
[McFarland, H. F.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Montalban, X.] Hosp Univ Hebron, Unitat Neuroimmunol Clin, Barcelona, Spain.
[Panitch, H.] Univ Vermont, Coll Med, Neurol Serv, Burlington, VT USA.
[Richert, J. R.; Reingold, S. C.] Natl Multiple Sclerosis Soc, Res & Clin Programs Dept, New York, NY USA.
[Reingold, S. C.] Sci & Clin Review Associates LLC, New York, NY USA.
[Polman, C. H.] UCL, Inst Neurol, Dept Neuroinflammat, London WC1E 6BT, England.
RP Polman, CH (reprint author), Free Univ Amsterdam, Med Ctr, Dept Neurol, NL-1007 MB Amsterdam, Netherlands.
EM ch.polman@vumc.nl
OI hutchinson, michael/0000-0002-8675-1723
FU National Multiple Sclerosis Society (US)
FX The authors gratefully acknowledge constructive criticism provided in
review of an earlier version of the manuscript by Drs Sten Fredrikson
(Copenhagen), Andrew Goodman (Rochester, NY), Catherine Lubetzki
(Paris), John Newsom-Davis (Oxford, deceased), Paul O'Connor (Toronto),
Richard Rudick (Cleveland), and Jack Simon (Portland, OR). The work of
the Task Force was supported by the National Multiple Sclerosis Society
(US).
NR 62
TC 260
Z9 275
U1 1
U2 19
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
J9 MULT SCLER J
JI Mult. Scler. J.
PD NOV
PY 2008
VL 14
IS 9
BP 1157
EP 1174
DI 10.1177/1352458508096878
PG 18
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 364MR
UT WOS:000260340300003
PM 18805839
ER
PT J
AU O'Brien, EP
Stan, G
Thirumalai, D
Brooks, BR
AF O'Brien, Edward P.
Stan, George
Thirumalai, D.
Brooks, Bernard R.
TI Factors Governing Helix Formation in Peptides Confined to Carbon
Nanotubes
SO NANO LETTERS
LA English
DT Article
ID 4-HELIX BUNDLE PROTEIN; GLOBULAR-PROTEINS; EXIT TUNNEL; SECONDARY
STRUCTURE; ALPHA-HELICES; NATIVE-STATE; RIBOSOME; STABILITY;
ENHANCEMENT; SIMULATIONS
AB The effect of confinement on the stability and dynamics of peptides and proteins is relevant in the context of a number of problems in biology and biotechnology. We have examined the stability of different helix-forming sequences upon confinement to a carbon nanotube using Langevin dynamics simulations of a coarse-grained representation of the polypeptide chain. We show that the interplay of several factors that include sequence, solvent conditions, strength (lambda) of nanotube-peptide interactions, and the nanotube diameter (D) determines confinement-induced stability of helicies. In agreement with predictions based on polymer theory, the helical state is entropically stabilized for all sequences when the interaction between the peptide and the nanotube is weakly hydrophobic and D is small. However, there is a strong sequence dependence as the strength of the lambda increases. For an amphiphilic sequence, the helical stability increases with lambda, whereas for polyalanine the diagram of states is a complex function of lambda and D. In addition, decreasing the size of the "hydrophobic patch" lining the nanotube, which mimics the chemical heterogeneity of the ribosome tunnel, increases the helical stability of the polyalanine sequence. Our results provide a framework for interpreting a number of experiments involving the structure formation of peptides in the ribosome tunnel as well as transport of biopolymers through nanotubes.
C1 [O'Brien, Edward P.; Thirumalai, D.] Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA.
[O'Brien, Edward P.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Stan, George] Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA.
[Thirumalai, D.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
RP Thirumalai, D (reprint author), Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA.
EM thirum@glue.umd.edu
RI O'Brien, Edward/C-3587-2015
FU NSF [05-14056]; American Heart Association; NIH, National Heart Lung and
Blood Institute; NIH GPP Biophysics
FX The authors thank Vincent Crespi for a computer program to generate
atomic coordinates of carbon nanotubes. This work was supported in part
by grants from the NSF (05-14056) to D.T., Scientific Development Grant
from the American Heart Association to G.S., the Intramural Research
Program of the NIH, National Heart Lung and Blood Institute, to B.R.B.,
and a NIH GPP Biophysics Fellowship to E.P.O.
NR 36
TC 28
Z9 28
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1530-6984
J9 NANO LETT
JI Nano Lett.
PD NOV
PY 2008
VL 8
IS 11
BP 3702
EP 3708
DI 10.1021/nl8019328
PG 7
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 372FX
UT WOS:000260888600027
PM 18817452
ER
PT J
AU Naetar, N
Korbei, B
Kozlov, S
Kerenyi, MA
Dorner, D
Kral, R
Gotic, I
Fuchs, P
Cohen, TV
Bittner, R
Stewart, CL
Foisner, R
AF Naetar, Nana
Korbei, Barbara
Kozlov, Serguei
Kerenyi, Marc A.
Dorner, Daniela
Kral, Rosana
Gotic, Ivana
Fuchs, Peter
Cohen, Tatiana V.
Bittner, Reginald
Stewart, Colin L.
Foisner, Roland
TI Loss of nucleoplasmic LAP2 alpha-lamin A complexes causes erythroid and
epidermal progenitor hyperproliferation
SO NATURE CELL BIOLOGY
LA English
DT Article
ID STEM-CELL DIFFERENTIATION; LAMIN-A; ERYTHROPOIESIS; RB; PROTEINS; MOUSE;
GENE; PROLIFERATION; ASSOCIATION; EXPRESSION
AB Lamina-associated polypeptide (LAP) 2 alpha is a chromatin-associated protein that binds A-type lamins(1,2). Mutations in both LAP2 alpha and A-type lamins are linked to human diseases called laminopathies(3), but the molecular mechanisms are poorly understood. The A-type lamin-LAP2a complex interacts with and regulates retinoblastoma protein (pRb)(4,5), but the significance of this interaction in vivo is unknown. Here we address the function of the A-type lamin-LAP2a complex with the use of LAP2 alpha-deficient mice. We show that LAP2a loss causes relocalization of nucleoplasmic A-type lamins to the nuclear envelope and impairs pRb function. This causes inefficient cell-cycle arrest in dense fibroblast cultures and hyperproliferation of epidermal and erythroid progenitor cells in vivo, leading to tissue hyperplasia. Our results support a disease-relevant model(6) in which LAP2a defines A-type lamin localization in the nucleoplasm, which in turn affects pRb-mediated regulation of progenitor cell proliferation and differentiation in highly regenerative tissues.
C1 [Naetar, Nana; Korbei, Barbara; Kerenyi, Marc A.; Dorner, Daniela; Kral, Rosana; Gotic, Ivana; Fuchs, Peter; Foisner, Roland] Med Univ Vienna, Max F Perutz Labs, A-1030 Vienna, Austria.
[Naetar, Nana; Korbei, Barbara; Kerenyi, Marc A.; Dorner, Daniela; Kral, Rosana; Gotic, Ivana; Fuchs, Peter; Foisner, Roland] Univ Vienna, A-1030 Vienna, Austria.
[Kozlov, Serguei; Cohen, Tatiana V.; Stewart, Colin L.] NCI, Adv BioSci Labs, Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA.
[Kerenyi, Marc A.] Vienna Bioctr, Inst Mol Pathol, A-1030 Vienna, Austria.
[Bittner, Reginald] Med Univ Vienna, Neuromuscular Res Ctr, Ctr Anat & Cell Biol, A-1090 Vienna, Austria.
RP Foisner, R (reprint author), Med Univ Vienna, Max F Perutz Labs, Dr Bohr Gasse 9, A-1030 Vienna, Austria.
EM roland.foisner@meduniwien.ac.at
OI Korbei, Barbara/0000-0002-0439-0435; Fuchs, Peter/0000-0003-3933-7674
FU Austrian Science Research Fund [FWF P17871]; European Commission
[LSHM-CT-2005-018690]; L'Oreal/UNESCO/OADW/BMWF
FX We thank W. Muller for the Cre-deleter mouse strain, Larry Gerace for
the genomic BAC clone, T. Jacks for triple knockout mouse embryonic
fibroblasts, P. Luvalle for providing paws from lamin A/C-deficient
mice, K. Biadasiewicz for expert technical assistance, and H. Beug and
E. W. Mullner for helpful discussions. This study was supported by
grants from the Austrian Science Research Fund (FWF P17871) and the
EURO-Laminopathies research project of the European Commission (contract
LSHM-CT-2005-018690) to R. F. and a postdoctoral fellowship from
L'Oreal/UNESCO/OADW/BMWF to N. N.
NR 33
TC 69
Z9 70
U1 0
U2 5
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 NOV
PY 2008
VL 10
IS 11
BP 1341
EP U213
DI 10.1038/ncb1793
PG 32
WC Cell Biology
SC Cell Biology
GA 367XU
UT WOS:000260586700017
PM 18849980
ER
PT J
AU Merino, JG
Latour, LL
AF Merino, Jose G.
Latour, Lawrence L.
TI The Boston Acute Stroke Imaging Scale: ready for use in clinical
practice?
SO NATURE CLINICAL PRACTICE NEUROLOGY
LA English
DT Editorial Material
DE acute stroke; imaging; MRI; prognosis
ID ACUTE ISCHEMIC-STROKE
AB This Practice Point commentary discusses a report by Torres-Mozqueda et al. on newly developed classification instrument for predicting outcome after stroke, the Boston Acute Stroke Imaging Scale (BASIS). This tool incorporates imaging data on the patency of the vasculature and the parenchyma and classifies ischemic strokes as major (if large vessels are occluded or parenchymal changes are present) or minor (all others). When testing the scale, the authors looked at short-term outcome at the time of hospital discharge; patients classified with major stroke by BASIS had a higher mortality and longer hospital stay and were more likely to be discharged to a rehabilitation facility than patients with minor stroke. The authors concluded that BASIS can predict outcome after stroke. We point to several shortcomings in the study methodology and argue that, although BASIS has potential as a prognostic tool, further studies are needed before it can be widely used.
C1 [Merino, Jose G.] Suburban Hosp, Stroke Program, Bethesda, MD 20814 USA.
[Latour, Lawrence L.] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA.
RP Merino, JG (reprint author), Suburban Hosp, Stroke Program, 8600 Old Georgetown Rd, Bethesda, MD 20814 USA.
EM merinoj@ninds.nih.gov
OI Merino, Jose/0000-0002-6676-0008
NR 7
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1745-834X
J9 NAT CLIN PRACT NEURO
JI Nat. Clin. Pract. Neurol.
PD NOV
PY 2008
VL 4
IS 11
BP 592
EP 593
DI 10.1038/ncpneuro0919
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 367ZS
UT WOS:000260591700005
PM 18825146
ER
PT J
AU Ahmed, ZM
Masmoudi, S
Kalay, E
Belyantseva, IA
Mosrati, MA
Collin, RWJ
Riazuddin, S
Hmani-Aifa, M
Venselaar, H
Kawar, MN
Tlili, A
van der Zwaag, B
Khan, SY
Ayadi, L
Riazuddin, SA
Morell, RJ
Griffith, AJ
Charfedine, I
Caylan, R
Oostrik, J
Karaguzel, A
Ghorbel, A
Riazuddin, S
Friedman, TB
Ayadi, H
Kremer, H
AF Ahmed, Zubair M.
Masmoudi, Saber
Kalay, Ersan
Belyantseva, Inna A.
Mosrati, Mohamed Ali
Collin, Rob W. J.
Riazuddin, Saima
Hmani-Aifa, Mounira
Venselaar, Hanka
Kawar, Mayya N.
Tlili, Abdelaziz
van der Zwaag, Bert
Khan, Shahid Y.
Ayadi, Leila
Riazuddin, S. Amer
Morell, Robert J.
Griffith, Andrew J.
Charfedine, Ilhem
Caylan, Refik
Oostrik, Jaap
Karaguzel, Ahmet
Ghorbel, Abdelmonem
Riazuddin, Sheikh
Friedman, Thomas B.
Ayadi, Hammadi
Kremer, Hannie
TI Mutations of LRTOMT, a fusion gene with alternative reading frames,
cause nonsyndromic deafness in humans
SO NATURE GENETICS
LA English
DT Article
ID CATECHOL-O-METHYLTRANSFERASE; OUTER HAIR-CELLS; HEARING IMPAIRMENT;
CORTICAL LATTICE; LOCUS DFNB63; GENOME-WIDE; EAR; TRANSCRIPTION;
LOCALIZATION; METHYLATION
AB Many proteins necessary for sound transduction have been identified through positional cloning of genes that cause deafness(1-3). We report here that mutations of LRTOMT are associated with profound nonsyndromic hearing loss at the DFNB63 locus on human chromosome 11q13.3-q13.4. LRTOMT has two alternative reading frames and encodes two different proteins, LRTOMT1 and LRTOMT2, detected by protein blot analyses. LRTOMT2 is a putative methyltransferase. During evolution, new transcripts can arise through partial or complete coalescence of genes(4). We provide evidence that in the primate lineage LRTOMT evolved from the fusion of two neighboring ancestral genes, which exist as separate genes (Lrrc51 and Tomt) in rodents.
C1 [Kalay, Ersan; Collin, Rob W. J.; Oostrik, Jaap; Kremer, Hannie] Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, NL-6500 HB Nijmegen, Netherlands.
[Kalay, Ersan; Collin, Rob W. J.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands.
[Ahmed, Zubair M.; Belyantseva, Inna A.; Riazuddin, Saima; Kawar, Mayya N.; Morell, Robert J.; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, Rockville, MD 20850 USA.
[Masmoudi, Saber; Mosrati, Mohamed Ali; Hmani-Aifa, Mounira; Tlili, Abdelaziz; Ayadi, Leila; Ayadi, Hammadi] Ctr Biotechnol, Unite Cibles Diagnost & Therapie, Sfax 3018, Tunisia.
[Kalay, Ersan; Karaguzel, Ahmet] Karadeniz Tech Univ, Fac Med, Dept Med Biol, TR-61080 Trabzon, Turkey.
[Venselaar, Hanka] Radboud Univ Nijmegen, Ctr Mol & Biomol Informat, NL-6500 HB Nijmegen, Netherlands.
[van der Zwaag, Bert] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurosci & Pharmacol, NL-3584 CG Utrecht, Netherlands.
[Khan, Shahid Y.; Riazuddin, S. Amer; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan.
[Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, Rockville, MD 20850 USA.
[Charfedine, Ilhem; Ghorbel, Abdelmonem] CHU Habib Bourguiba Sfax, Serv ORL, Sfax 3029, Tunisia.
[Caylan, Refik] Karadeniz Tech Univ, Fac Med, Dept Otorhinolaryngol, TR-61080 Trabzon, Turkey.
[Kremer, Hannie] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, NL-6525 ED Nijmegen, Netherlands.
[Kremer, Hannie] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands.
RP Kremer, H (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, NL-6500 HB Nijmegen, Netherlands.
EM friedman@nidcd.nih.gov; directeur.general@cbs.rnrt.tn;
H.Kremer@antrg.umcn.nl
RI Kremer, Hannie/F-5126-2010; Collin, Rob/N-3575-2014; Oostrik,
Jaap/A-1703-2016; SHEIKH, RIAZUDDIN/L-2406-2015; Venselaar,
Hanka/D-2009-2016;
OI Kremer, Hannie/0000-0002-0841-8693; Morell, Robert/0000-0003-1537-7356
FU NIDCD/NIH [ZO1DC00035-06, ZO1DC000060, ZO1DC000064]; European Commission
FP6 Integrated Project EUROHEAR [LSHG-CT-20054-512063:2]; Heinsius
Houbolt Foundation; Karadeniz Technical University Research Fund
[2002.114.001.3, 2006.114.001.1]; Le Ministere de l'Enseignement
Superieur; de la Recherche Scientifique et de la Technologie, Tunisia;
Higher Education Commission and the Ministry of Science and Technology
in Islamabad, Pakistan
FX We thank the families for their participation in this study, which was
supported by NIDCD/NIH (intramural research fund ZO1DC00035-06 and
ZO1DC00035-06 to T.B.F., ZO1DC000060 and ZO1DC000064 to A.J.G.), funds
from the European Commission FP6 Integrated Project EUROHEAR (contract
number LSHG-CT-20054-512063:2), the Heinsius Houbolt Foundation and the
Karadeniz Technical University Research Fund (contract numbers
2002.114.001.3 and 2006.114.001.1). In Tunisia work was also funded by
Le Ministere de l'Enseignement Superieur, de la Recherche Scientifique
et de la Technologie, Tunisia. In Pakistan the Higher Education
Commission and the Ministry of Science and Technology in Islamabad,
Pakistan supported this project. We thank B. Ploplis, M. Ansari, A.
Lagziel, E. Boger, S. Kitajiri, E. van Wijk, T. Peters and H.
Spierenburg for their technical help and G. Vriend, F. Cremers, H.
Brunner and C. Cremers for discussion. We also thank J. Bird, D. Drayna,
M. Meisler and S. Sullivan for advice and comments in preparing the
manuscript. We thank the Southwest National Primate Research Center, San
Antonio, Texas for providing brain tissue samples from chimpanzee and
baboon, and the Duke Lemur Center, Durham, North Carolina for brain
tissue samples from a lemur.
NR 30
TC 28
Z9 39
U1 6
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD NOV
PY 2008
VL 40
IS 11
BP 1335
EP 1340
DI 10.1038/ng.245
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 366RQ
UT WOS:000260501500027
PM 18953341
ER
PT J
AU Rahimov, F
Marazita, ML
Visel, A
Cooper, ME
Hitchler, MJ
Rubini, M
Domann, FE
Govil, M
Christensen, K
Bille, C
Melbye, M
Jugessur, A
Lie, RT
Wilcox, AJ
Fitzpatrick, DR
Green, ED
Mossey, PA
Little, J
Steegers-Theunissen, RP
Pennacchio, LA
Schutte, BC
Murray, JC
AF Rahimov, Fedik
Marazita, Mary L.
Visel, Axel
Cooper, Margaret E.
Hitchler, Michael J.
Rubini, Michele
Domann, Frederick E.
Govil, Manika
Christensen, Kaare
Bille, Camille
Melbye, Mads
Jugessur, Astanand
Lie, Rolv T.
Wilcox, Allen J.
Fitzpatrick, David R.
Green, Eric D.
Mossey, Peter A.
Little, Julian
Steegers-Theunissen, Regine P.
Pennacchio, Len A.
Schutte, Brian C.
Murray, Jeffrey C.
CA NISC Comparative Sequencing Pr
TI Disruption of an AP-2 alpha binding site in an IRF6 enhancer is
associated with cleft lip
SO NATURE GENETICS
LA English
DT Article
ID OROFACIAL CLEFTS; ORAL CLEFTS; PALATE; GENE; POPULATION; SEQUENCES;
POLYMORPHISMS; CONTRIBUTES; EXPRESSION; MUTATIONS
AB Previously we have shown that nonsyndromic cleft lip with or without cleft palate (NSCL/P)(1) is strongly associated with SNPs in IRF6 (interferon regulatory factor 6)(2). Here, we use multispecies sequence comparisons to identify a common SNP (rs642961, G>A) in a newly identified IRF6 enhancer. The A allele is significantly overtransmitted (P = 1 x 10(-11)) in families with NSCL/P, in particular those with cleft lip but not cleft palate. Further, there is a dosage effect of the A allele, with a relative risk for cleft lip of 1.68 for the AG genotype and 2.40 for the AA genotype. EMSA and ChIP assays demonstrate that the risk allele disrupts the binding site of transcription factor AP-2a and expression analysis in the mouse localizes the enhancer activity to craniofacial and limb structures. Our findings place IRF6 and AP-2a in the same developmental pathway and identify a high-frequency variant in a regulatory element contributing substantially to a common, complex disorder.
C1 [Rahimov, Fedik; Schutte, Brian C.; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Marazita, Mary L.; Cooper, Margaret E.; Govil, Manika] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Ctr Craniofacial & Dent Genet, Pittsburgh, PA 15219 USA.
[Visel, Axel; Pennacchio, Len A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genome Div, Berkeley, CA 94720 USA.
[Hitchler, Michael J.; Domann, Frederick E.] Univ Iowa, Dept Radiat Oncol, Iowa City, IA 52242 USA.
[Rubini, Michele] Univ Ferrara, Med Genet Unit, Dept Expt Diagnost Med, I-44100 Ferrara, Italy.
[Christensen, Kaare; Bille, Camille] Univ So Denmark, Inst Publ Hlth, Ctr Prevent Congenital Malinformat, DK-5000 Odense C, Denmark.
[Melbye, Mads] Danish Epidemiol Sci Ctr, State Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.
[Jugessur, Astanand; Lie, Rolv T.] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Sect Epidemiol & Med Stat, N-5018 Bergen, Norway.
[Wilcox, Allen J.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Fitzpatrick, David R.] Western Gen Hosp, Med Res Council Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
[Green, Eric D.; NISC Comparative Sequencing Pr] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Green, Eric D.; NISC Comparative Sequencing Pr] NHGRI, US Natl Inst Hlth Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Mossey, Peter A.] Univ Dundee, Dent Hosp & Sch, Dundee DD1 4HR, Scotland.
[Little, Julian] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON K1H 8M5, Canada.
[Steegers-Theunissen, Regine P.] Univ Med Ctr, NL-3015 GD Rotterdam, Netherlands.
RP Murray, JC (reprint author), Univ Iowa, Dept Pediat, 2182 ML,S Grand Ave, Iowa City, IA 52242 USA.
EM jeff-murray@uiowa.edu
RI Visel, Axel/A-9398-2009; Christensen, Kaare/C-2360-2009; FitzPatrick,
David/C-7301-2013; Rahimov, Fedik/H-2685-2013;
OI Visel, Axel/0000-0002-4130-7784; Christensen, Kaare/0000-0002-5429-5292;
Mossey, Peter/0000-0002-9914-6901; Wilcox, Allen/0000-0002-3376-1311
FU National Institutes of Health (NIH) [P50 DE16215, P30 ES05605, R37
DE08559, R01-DE13513, 1 UL1 RR024979-01, R01-CA73612, R01-HG003988];
Intramural Research Program of the National Human Genome Research
Institute; Intramural Research Program of the NIH; National Institute of
Environmental Health Sciences; European Commission FP5; EUROCRAN
[QLG1-CT-2000-01019]; American Heart Association; [DE-AC02-05CH11231];
[T32 CA078586]
FX We would like to thank A. Kinoshita, K. Frees, A. Mansilla, J.
L'Heureux, M. Johnson, H. Morrison, G. Wehby, N. Rorick, K. Bedell and
L. Powers for technical assistance and S. McConnell, D. Benton and M.
DeVore for their administrative assistance. We would also like to thank
A. Klingelhutz (University of Iowa) for kindly providing us with HFK
cell line. This work was supported by grants from the National
Institutes of Health (NIH): P50 DE16215 (J.C.M., M.L.M., B.C.S.), P30
ES05605 (J.C.M.), R37 DE08559 (J.C.M., M.L.M.), R01-DE13513 (B.C.S.), 1
UL1 RR024979-01 (J.C.M., B.C.S.), R01-CA73612 (F.E.D.), R01-HG003988
administered under Department of Energy Contract DE-AC02-05CH11231
(L.A.P.) as well as by the Intramural Research Program of the National
Human Genome Research Institute (E.D.G.), in part by the Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences (A.J.W.), and European Commission FP5: EUROCRAN Project
(contract no. QLG1-CT-2000-01019) (M.R., P.A.M., J.L., R.P.S.-T.). A.V.
was supported by the American Heart Association. M.J.H. received salary
support from T32 CA078586.
NR 30
TC 222
Z9 235
U1 2
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD NOV
PY 2008
VL 40
IS 11
BP 1341
EP 1347
DI 10.1038/ng.242
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 366RQ
UT WOS:000260501500028
PM 18836445
ER
PT J
AU Jeong, Y
Leskow, FC
El-Jaick, K
Roessler, E
Muenke, M
Yocum, A
Dubourg, C
Li, X
Geng, X
Oliver, G
Epstein, DJ
AF Jeong, Yongsu
Leskow, Federico Coluccio
El-Jaick, Kenia
Roessler, Erich
Muenke, Maximilian
Yocum, Anastasia
Dubourg, Christele
Li, Xue
Geng, Xin
Oliver, Guillermo
Epstein, Douglas J.
TI Regulation of a remote Shh forebrain enhancer by the Six3 homeoprotein
SO NATURE GENETICS
LA English
DT Article
ID VENTRAL FOREBRAIN; EYE DEVELOPMENT; GENE; EXPRESSION; MUTATIONS;
REPRESSION; MEMBERS; FAMILY; RISK; FACE
AB In humans, SHH haploinsufficiency results in holoprosencephaly (HPE), a defect in anterior midline formation(1,2). Despite the importance of maintaining SHH transcript levels above a critical threshold, we know little about the upstream regulators of SHH expression in the forebrain. Here we describe a rare nucleotide variant located 460 kb upstream of SHH in an individual with HPE that resulted in the loss of Shh brain enhancer-2 (SBE2) activity in the hypothalamus of transgenic mouse embryos. Using a DNA affinity-capture assay, we screened the SBE2 sequence for DNA-binding proteins and identified members of the Six3 and Six6 homeodomain family as candidate regulators of Shh transcription. Six3 showed reduced binding affinity for the mutant compared to the wild-type SBE2 sequence. Moreover, Six3 with HPE-causing alterations failed to bind and activate SBE2. These data suggest a direct link between Six3 and Shh regulation during normal forebrain development and in the pathogenesis of HPE.
C1 [Jeong, Yongsu; Leskow, Federico Coluccio; Epstein, Douglas J.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[El-Jaick, Kenia; Roessler, Erich; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Yocum, Anastasia] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
[Dubourg, Christele] Univ Rennes 1, CNRS, UMR 6061, F-35043 Rennes, France.
[Li, Xue] Harvard Univ, Sch Med, Childrens Hosp, Dept Urol Surg, Boston, MA 02115 USA.
[Geng, Xin; Oliver, Guillermo] St Jude Childrens Res Hosp, Dept Genet, Memphis, TN 38105 USA.
RP Epstein, DJ (reprint author), Univ Penn, Sch Med, Dept Genet, 415 Curie Blvd, Philadelphia, PA 19104 USA.
EM epsteind@mail.med.upenn.edu
OI Jeong, Yongsu/0000-0002-0008-9928
FU NINDS [R01 NS39421, R01 NS052386]; March of Dimes [1-FY05-112]; Pew
Scholar Award in the Biomedical Sciences; Cancer Center [CA-21765];
American Lebanese Syrian Associated Charities (ALSAC); Division of
Intramural Research; National Human Genome Research Institute; National
Institutes of Health
FX We thank the families for their participation in these studies. We also
thank J. Richa and his staff at the University of Pennsylvania
Transgenic and Mouse Chimeric Facility for their assistance in
transgenic mouse production. We are grateful to V. Cheung, D. Kessler
and T. Kadesch for their helpful comments on the manuscript. We are also
grateful to K. Ewens and W. Ankener (R. Spielman laboratory) for the
control human genotyping data and P. Bovolenta (Instituto Cajal, CSIC,
Madrid, Spain) for kindly providing the human Six3 and Six6 expression
constructs. This work was supported by NIH grants R01 NS39421 from NINDS
(D.J.E.), R01 NS052386 (G.O.), March of Dimes grant # 1-FY05-112
(D.J.E.), a Pew Scholar Award in the Biomedical Sciences (D.J.E.),
Cancer Center Support CA-21765 (G.O.), the American Lebanese Syrian
Associated Charities (ALSAC) (G.O.) and the Division of Intramural
Research, National Human Genome Research Institute, National Institutes
of Health (M.M.).
NR 30
TC 82
Z9 85
U1 0
U2 4
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 NOV
PY 2008
VL 40
IS 11
BP 1348
EP 1353
DI 10.1038/ng.230
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 366RQ
UT WOS:000260501500029
PM 18836447
ER
PT J
AU Feng, CG
Zheng, LX
Jankovic, D
Bafica, A
Cannons, JL
Watford, WT
Chaussabel, D
Hieny, S
Caspar, P
Schwartzberg, PL
Lenardo, MJ
Sher, A
AF Feng, Carl G.
Zheng, Lixin
Jankovic, Dragana
Bafica, Andre
Cannons, Jennifer L.
Watford, Wendy T.
Chaussabel, Damien
Hieny, Sara
Caspar, Patricia
Schwartzberg, Pamela L.
Lenardo, Michael J.
Sher, Alan
TI The immunity-related GTPase Irgm1 promotes the expansion of activated
CD4(+) T cell populations by preventing interferon-gamma-induced cell
death
SO NATURE IMMUNOLOGY
LA English
DT Article
ID MYCOBACTERIUM-AVIUM INFECTION; RECEPTOR-BETA CHAIN; IFN-GAMMA; CYTOKINE
SIGNALING-1; MICE DEFICIENT; T(H)1 CELLS; IN-VIVO; AUTOPHAGY; LRG-47;
TUBERCULOSIS
AB Mice deficient in the interferon-gamma (IFN-gamma)-inducible, immunity-related GTPase Irgm1 have defective host resistance to a variety of intracellular pathogens. This greater susceptibility to infection is associated with impaired IFN-gamma-dependent macrophage microbicidal activity in vitro. Here we show that Irgm1 also regulated the survival of mature effector CD4(+) T lymphocytes by protecting them from IFN-gamma-induced autophagic cell death. Mice deficient in both IFN-gamma and Irgm1 were 'rescued' from the lymphocyte depletion and greater mortality that occurs in mice singly deficient in Irgm1 after mycobacterial infection. Our studies identify a feedback mechanism in the T helper type 1 response that limits the detrimental effects of IFN-gamma on effector T lymphocyte survival while promoting the antimicrobial functions of IFN-gamma.
C1 [Feng, Carl G.; Jankovic, Dragana; Bafica, Andre; Hieny, Sara; Caspar, Patricia; Sher, Alan] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Zheng, Lixin; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Cannons, Jennifer L.; Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Watford, Wendy T.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Chaussabel, Damien] Baylor Inst Immunol Res, Dallas, TX 75204 USA.
RP Feng, CG (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
EM cfeng@niaid.nih.gov
RI Vacinas, Inct/J-9431-2013
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases; National Institutes of Health, Department of Health
and Human Services
FX We thank G. Taylor ( Duke University) for Irgm1-/- mice
backcrossed more than 12 times to C57BL/6 mice; S. White, C. Henry and
C. Eigsti for technical assistance; J. Zhu and L. Yu for advice and
discussions; K. Nagashima ( Electron Microscope Facility, Image Analysis
Laboratory, Science Applications International Corporation-National
Cancer Institute, Frederick) for the electron microscopy studies; A.
Cheever ( Biomedical Research Institute) for assessing tissue fibrosis
and pathology in S. mansoni infection experiments; R. Donnelly ( Center
for Biologics Evaluation and Research, Food and Drug Administration) for
initial help in measuring STAT1 phosphorylation; and H. Young and D. L.
Barber for critical reading of the manuscript. Supported by the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Department of Health
and Human Services.
NR 49
TC 75
Z9 75
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD NOV
PY 2008
VL 9
IS 11
BP 1279
EP 1287
DI 10.1038/ni.1653
PG 9
WC Immunology
SC Immunology
GA 363EA
UT WOS:000260248600015
PM 18806793
ER
PT J
AU Liao, W
Schones, DE
Oh, J
Cui, YZ
Cui, KR
Roh, TY
Zhao, K
Leonard, WJ
AF Liao, Wei
Schones, Dustin E.
Oh, Jangsuk
Cui, Yongzhi
Cui, Kairong
Roh, Tae-Young
Zhao, Keji
Leonard, Warren J.
TI Priming for T helper type 2 differentiation by interleukin 2-mediated
induction of interleukin 4 receptor alpha-chain expression
SO NATURE IMMUNOLOGY
LA English
DT Article
ID TH2 DIFFERENTIATION; IL-4 RECEPTOR; CELL-PROLIFERATION; UP-REGULATION;
STAT5; RESPONSES; MECHANISMS; GENE; MICE; SUFFICIENT
AB T helper type 2 (T(H)2) cells are essential for humoral immunity and host defense. Interleukin 4 (IL-4) drives T(H)2 differentiation and IL-2 augments the accessibility of Il4 chromatin. Here we demonstrate that IL-2, by inducing binding of STAT5 to the Il4ra locus, which encodes IL-4 receptor alpha-chain (IL-4R alpha), was essential for inducing and maintaining IL-4R alpha expression. Although IL-4 induced IL-4R alpha expression, T cell receptor-induced IL-4R alpha expression was normal in Il4(-/-) cells but was much lower in Il2(-/-) cells. Notably, forced IL-4R alpha expression restored the T(H)2 differentiation of Il2(-/-) cells. Moreover, genome-wide mapping by chromatin immunoprecipitation coupled with sequencing showed broad interaction of the transcription factors STAT5A and STAT5B with genes associated with T(H)2 differentiation. Our results identify a previously unappreciated function for IL-2 in 'priming' T cells for T(H)2 differentiation and in maintaining the expression of Il4ra and other genes in T(H)2-committed cells.
C1 [Liao, Wei; Schones, Dustin E.; Oh, Jangsuk; Cui, Kairong; Roh, Tae-Young; Zhao, Keji; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Cui, Yongzhi] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
EM wjl@helix.nih.gov
FU Division of Intramural Research of the National Heart, Lung, and Blood
Institute, National Institutes of Health
FX We thank P. Ryan (National Heart, Lung and Blood Institute, National
Institutes of Health) for Il4-/- mice; J. X. Lin (National
Heart, Lung and Blood Institute, National Institutes of Health) for
discussions and real-time PCR primers; J. F. Zhu, H. H. Xue, H. P. Kim
and R. Spolski for discussions and technical assistance; L. Hennighausen
for support and discussions; and X. Shirley Liu for the 'model-based
analysis of ChiP-seq' algorithm. Supported by the Division of Intramural
Research of the National Heart, Lung, and Blood Institute, National
Institutes of Health.
NR 41
TC 120
Z9 121
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD NOV
PY 2008
VL 9
IS 11
BP 1288
EP 1296
DI 10.1038/ni.1656
PG 9
WC Immunology
SC Immunology
GA 363EA
UT WOS:000260248600016
PM 18820682
ER
PT J
AU Zhang, FP
Meng, GX
Strober, W
AF Zhang, Fuping
Meng, Guangxun
Strober, Warren
TI Interactions among the transcription factors Runx1, ROR gamma t and
Foxp3 regulate the differentiation of interleukin 17-producing T cells
SO NATURE IMMUNOLOGY
LA English
DT Article
ID GROWTH-FACTOR-BETA; TGF-BETA; GENE-EXPRESSION; IFN-GAMMA; BINDING-SITE;
RECEPTOR; IL-21; SUSCEPTIBILITY; INDUCTION; ARTHRITIS
AB The molecular mechanisms underlying the differentiation of interleukin 17-producing T helper cells (T-H-17 cells) are still poorly understood. Here we show that optimal transcription of the gene encoding interleukin 17 (Il17) required a 2-kilobase promoter and at least one conserved noncoding (enhancer) sequence, CNS-5. Both cis-regulatory elements contained regions that bound the transcription factors ROR gamma t and Runx1. Runx1 influenced T-H-17 differentiation by inducing ROR gamma t expression and by binding to and acting together with ROR gamma t during Il17 transcription. However, Runx1 also interacts with the transcription factor Foxp3, and this interaction was necessary for the negative effect of Foxp3 on T-H-17 differentiation. Thus, our data support a model in which the differential association of Runx1 with Foxp3 and with ROR gamma t regulates T-H-17 differentiation.
C1 [Zhang, Fuping; Meng, Guangxun; Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
EM wstrober@niaid.nih.gov
OI 孟, 广勋/0000-0002-4253-9675
FU Intramural NIH HHS [Z01 AI000354-25, Z01 AI000432-23]
NR 37
TC 273
Z9 287
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD NOV
PY 2008
VL 9
IS 11
BP 1297
EP 1306
DI 10.1038/ni.1663
PG 10
WC Immunology
SC Immunology
GA 363EA
UT WOS:000260248600017
PM 18849990
ER
PT J
AU Strauss, JF
De Paolo, LV
AF Strauss, Jerome F., III
De Paolo, Louis V.
TI Funding for the reproductive sciences in the US
SO NATURE MEDICINE
LA English
DT Editorial Material
ID ANIMAL REPRODUCTION; AGRICULTURE; TECHNOLOGY; PRIORITIES; BIOLOGY
C1 [Strauss, Jerome F., III] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23298 USA.
[De Paolo, Louis V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Strauss, JF (reprint author), Virginia Commonwealth Univ, Sch Med, 1101 E Marshall St, Richmond, VA 23298 USA.
EM jfstrauss@vcu.edu
NR 15
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 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD NOV
PY 2008
VL 14
IS 11
SU S
BP 1214
EP 1217
DI 10.1038/nm1108-1214
PG 4
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 397FU
UT WOS:000262649100032
PM 18989308
ER
PT J
AU Strauss, JF
De Paolo, LV
AF Strauss, Jerome F., III
De Paolo, Louis V.
TI Funding for the reproductive sciences in the US
SO NATURE MEDICINE
LA English
DT Editorial Material
ID ANIMAL REPRODUCTION; AGRICULTURE; TECHNOLOGY; PRIORITIES; BIOLOGY
C1 [Strauss, Jerome F., III] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23298 USA.
[De Paolo, Louis V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Strauss, JF (reprint author), Virginia Commonwealth Univ, Sch Med, 1101 E Marshall St, Richmond, VA 23298 USA.
EM jfstrauss@vcu.edu
NR 15
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 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD NOV
PY 2008
VL 14
IS 11
BP 1214
EP 1217
DI 10.1038/nm1108-1214
PG 4
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 370GR
UT WOS:000260751200039
PM 18989308
ER
PT J
AU Ozato, K
Shin, DM
Chang, TH
Morse, HC
AF Ozato, Keiko
Shin, Dong-Mi
Chang, Tsung-Hsien
Morse, Herbert C., III
TI TRIM family proteins and their emerging roles in innate immunity
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID INTERFERON REGULATORY FACTOR-8; RET FINGER PROTEIN; PROMYELOCYTIC
LEUKEMIA PROTEIN; RESTRICTION FACTOR TRIM5-ALPHA; TRIPARTITE MOTIF
PROTEINS; NUCLEAR-BODY FORMATION; E3 UBIQUITIN LIGASE; RING-FINGER;
RETROVIRAL RESTRICTION; ANTIVIRAL DEFENSE
AB The superfamily of tripartite motif-containing ( TRIM) proteins is conserved throughout the metazoan kingdom and has expanded rapidly during vertebrate evolution; there are now more than 60 TRIM proteins known in humans and mice. Many TRIM proteins are induced by type I and type II interferons, which are crucial for many aspects of resistance to pathogens, and several are known to be required for the restriction of infection by lentiviruses. In this Review, we describe recent data that reveal broader antiviral and antimicrobial activities of TRIM proteins and discuss their involvement in the regulation of pathogen-recognition and transcriptional pathways in host defence.
C1 [Ozato, Keiko; Chang, Tsung-Hsien] NICHHD, Program Genom & Differentiat, NIH, Bethesda, MD 20892 USA.
[Shin, Dong-Mi; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA.
RP Ozato, K (reprint author), NICHHD, Program Genom & Differentiat, NIH, Bethesda, MD 20892 USA.
EM ozatok@nih.gov; hmorse@mail.nih.gov
RI Liu, FL/D-1795-2009;
OI Morse, Herbert/0000-0002-9331-3705
FU National Institutes of Health; National Institute of Child Health and
Human Development; National Institute of Allergy and Infectious Diseases
FX We thank J. Weddle for his assistance in the preparation of this
manuscript. This work was supported by the Intramural Research Program
of the National Institutes of Health, National Institute of Child Health
and Human Development, and National Institute of Allergy and Infectious
Diseases.
NR 127
TC 299
Z9 316
U1 6
U2 30
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 NOV
PY 2008
VL 8
IS 11
BP 849
EP 860
DI 10.1038/nri2413
PG 12
WC Immunology
SC Immunology
GA 364CE
UT WOS:000260313000010
PM 18836477
ER
PT J
AU Redd, AD
Quinn, TC
AF Redd, Andrew D.
Quinn, Thomas C.
TI CD4 immunodiagnostics for HIV in the developing world FOREWORD
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Editorial Material
ID TOTAL LYMPHOCYTE COUNT; ANTIRETROVIRAL THERAPY
AB This supplement on evaluating CD4 diagnostics for HIV is the fourth in a series of user-friendly operational guides explaining how to conduct evaluations of diagnostic tests for infectious diseases that are of public health importance in the developing world. Here, Andrew Redd and Thomas Quinn introduce the supplement.
C1 [Redd, Andrew D.; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Redd, AD (reprint author), NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tquinn@jhmi.edu
RI Redd, Andrew/D-1802-2010
NR 7
TC 1
Z9 1
U1 0
U2 0
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 NOV
PY 2008
VL 6
IS 11
SU S
BP S1
EP S1
DI 10.1038/nrmicro1996
PG 1
WC Microbiology
SC Microbiology
GA 372EE
UT WOS:000260883800001
PM 22745948
ER
PT J
AU Wang, WD
AF Wang, Weidong
TI A major switch for the Fanconi anemia DNA damage-response pathway
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Editorial Material
ID REPLICATION FORKS; PROTEIN; REPAIR; COMPLEX; FANCD2
AB The Fanconi anemia pathway is part of the DNA-damage network including breast cancer-susceptibility proteins BRCA1 and BRCA2. This pathway is activated by the ataxia telangiectasia and Rad3-related (ATR) kinase, but the underlying mechanism remains unclear. A new study demonstrates that a major switch activating the pathway is the ATR-dependent phosphorylation of FANCI.
C1 NIA, Genet Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Wang, WD (reprint author), NIA, Genet Lab, NIH, Biomed Res Ctr, Room 10B113,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM wangw@grc.nia.nih.gov
FU Intramural NIH HHS
NR 15
TC 13
Z9 13
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD NOV
PY 2008
VL 15
IS 11
BP 1128
EP 1130
DI 10.1038/nsmb1108-1128
PG 3
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 368QV
UT WOS:000260638500002
PM 18985065
ER
PT J
AU Yang, W
AF Yang, Wei
TI An equivalent metal ion in one- and two-metal-ion catalysis
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID SINGLE-STRANDED-DNA; T4 ENDONUCLEASE VII; ACTIVE-SITE; ESCHERICHIA-COLI;
CRYSTAL-STRUCTURE; POLYMERASE-I; SUBSTRATE-SPECIFICITY; CONJUGATIVE
RELAXASE; ANGSTROM RESOLUTION; 3'-5' EXONUCLEASE
AB Nucleotidyl-transfer enzymes, which synthesize, degrade and rearrange DNA and RNA, often depend on metal ions for catalysis. All DNA and RNA polymerases, MutH-like or RNase H-like nucleases and recombinases, and group I introns seem to require two divalent cations to form a complete active site. The two-metal-ion mechanism has been proposed to orient the substrate, facilitate acid-base catalysis and allow catalytic specificity to exceed substrate binding specificity attributable to the stringent metal-ion (Mg2+ in particular) coordination. Not all nucleotidyl-transfer enzymes use two metal ions for catalysis, however. The beta beta alpha-Me and HUH nucleases depend on a single metal ion in the active site for the catalysis. All of these one- and two metal ion-dependent enzymes generate 5'- phosphate and 3'-OH products. Structural and mechanistic comparisons show that these seemingly unrelated nucleotidyl-transferases share a functionally equivalent metal ion.
C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Yang, W (reprint author), NIDDK, Mol Biol Lab, NIH, 9000 Rockville Pike,Bldg 5,Room B1-03, Bethesda, MD 20892 USA.
EM Wei.Yang@nih.gov
RI Yang, Wei/D-4926-2011
OI Yang, Wei/0000-0002-3591-2195
FU US National Institute of Diabetes and Digestive and Kidney Diseases;
National Institutes of Health
FX I thank C. Biertumpfel, C. Larkin and M. Nowotny for stimulating
discussion, and B. Craigie, F. Dyda, D. Leahy and H. Yuan for critical
reading of the manuscript. This research was supported by the Intramural
Research Program of the US National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health.
NR 50
TC 47
Z9 48
U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD NOV
PY 2008
VL 15
IS 11
BP 1228
EP 1231
DI 10.1038/nsmb.1502
PG 4
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 368QV
UT WOS:000260638500023
PM 18953336
ER
PT J
AU Roschke, A
Glebov, OK
Lababidi, S
Gehlhaus, KS
Weinstein, JN
Kirsch, IR
AF Roschke, Anna
Glebov, Oleg K.
Lababidi, Samir
Gehlhaus, Kristen S.
Weinstein, John N.
Kirsch, Ilan R.
TI Chromosomal Instability Is Associated with Higher Expression of Genes
Implicated in Epithelial-Mesenchymal Transition, Cancer Invasiveness,
and Metastasis and with Lower Expression of Genes Involved in Cell Cycle
Checkpoints, DNA Repair, and Chromatin Maintenance
SO NEOPLASIA
LA English
DT Article
ID MITOTIC CHECKPOINT; BREAST-CANCER; NEOPLASTIC TRANSFORMATION; KARYOTYPIC
COMPLEXITY; LUNG-CANCER; HBUB1; PROGRESSION; MICROARRAY; INACTIVATION;
PHENOTYPES
AB Chromosomal instability-a hallmark of epithelial cancers-is an ongoing process that results in aneuploidy and karyotypic heterogeneity of a cancer cell population. Previously, we stratified cancer cell lines in the NCI-60 drug discovery panel based on their karyotypic complexity and heterogeneity. Using this stratification in conjunction with drug response data for the cell lines allowed us to identify classes of chemical compounds whose growth-inhibitory activity correlates with karyotypic complexity and chromosomal instability. In this article, we asked the question: What are the biological processes, pathways, or genes associated with chromosomal instability of cancer cells? We found that increased instability of the chromosomal content in a cancer cell population, particularly, persistent gains and losses of chromosomes, is associated with elevated expression of genes involved with aggressive cellular behavior, including invasion-and metastasis-associated changes in cell communication, adhesion, motility, and migration. These same karyotypic features are negatively correlated with the expression of genes involved in cell cycle checkpoints, DNA repair, and chromatin maintenance.
C1 [Roschke, Anna] NCI, Ctr Canc Res, NNMC, Bethesda, MD 20889 USA.
RP Roschke, A (reprint author), NCI, Ctr Canc Res, NNMC, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA.
EM roschkea@mail.nih.gov
NR 43
TC 16
Z9 17
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1522-8002
EI 1476-5586
J9 NEOPLASIA
JI Neoplasia
PD NOV
PY 2008
VL 10
IS 11
BP 1222
EP U72
DI 10.1593/neo.08682
PG 26
WC Oncology
SC Oncology
GA 358AX
UT WOS:000259889800007
PM 18953431
ER
PT J
AU Duffy, KB
Spangler, EL
Devan, BD
Guo, ZH
Bowker, JL
Janas, AM
Hagepanos, A
Minor, RK
DeCabo, R
Mouton, PR
Shukitt-Hale, B
Joseph, JA
Ingram, DK
AF Duffy, Kara B.
Spangler, Edward L.
Devan, Bryan D.
Guo, Zhihong
Bowker, Jonna L.
Janas, Anne M.
Hagepanos, Adrienne
Minor, Robin K.
DeCabo, Rafael
Mouton, Peter R.
Shukitt-Hale, Barbara
Joseph, James A.
Ingram, Donald K.
TI A blueberry-enriched diet provides cellular protection against oxidative
stress and reduces a kainate-induced learning impairment in rats
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE flavanoid; neurotoxicity; nutrition; memory; glutamate; hippocampus;
Alzheimer's disease
ID RADICAL ABSORBENCY CAPACITY; ACTIVATED PROTEIN-KINASE; LONG-TERM
POTENTIATION; ALZHEIMERS-DISEASE; AGED RATS; MEMORY CONSOLIDATION;
ANTIOXIDANT CAPACITY; BEHAVIORAL DEFICITS; LIPID-PEROXIDATION; KAINIC
ACID
AB Young male Fischer-344 rats were fed a diet containing 2% blueberry (BB) extract or control diet for at least 8 weeks and then received bilateral hippocampal injections of kainic acid (KA 200 ng/0.5 mu l) or phosphate buffered saline (PBS). One week later rats were trained in one-way active footshock avoidance in a straight runway followed the next day by training in a footshock motivated 14-unit T-maze with documented sensitivity to hippocampal glutamatergic manipulations. Based on analyses of several performance variables, KA-treated rats exhibited clearly impaired learning performance; however. the BB diet significantly reduced this impairment. Supporting the behavioral findings. stereological assessment of CA1 pyramidal neurons documented greater neuronal loss in KA-treated controls compared to KA-treated rats on the BB diet. In an in vitrio experiment, FaO cells grown in medium supplemented with serum from BB-fed rats had enhanced viability after exposure to hydrogen peroxide. These findings suggest that BB supplementation may protect against neurodegeneration and cognitive impairment mediated by excitotoxicity and oxidative stress. Published by Elsevier Inc.
C1 [Ingram, Donald K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA.
[Duffy, Kara B.; Spangler, Edward L.; Devan, Bryan D.; Bowker, Jonna L.; Janas, Anne M.; Minor, Robin K.; DeCabo, Rafael; Mouton, Peter R.; Ingram, Donald K.] NIA, Lab Expt Geront, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Guo, Zhihong; Hagepanos, Adrienne] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Shukitt-Hale, Barbara; Joseph, James A.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
RP Ingram, DK (reprint author), Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
EM Donald.Ingram@pbrc.edu
RI de Cabo, Rafael/E-7996-2010; de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU National Institute on Aging; National Institutes of Health; United
States Department of Agriculture; NASA [NAG9-1529]; U.S. Highbush
Blueberry Council (USHBC); Wild Blueberry Association of North America
(WBANA)
FX This research was supported in part by funds from the Intramural
Research Program of the National Institute on Aging, National Institutes
of Health, and also in part by the United States Department of
Agriculture and NASA Grant NAG9-1529 to J.A. Joseph. The laboratory of
J.A. Joseph also receives research support from the U.S. Highbush
Blueberry Council (USHBC) and the Wild Blueberry Association of North
America (WBANA).
NR 72
TC 52
Z9 59
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD NOV
PY 2008
VL 29
IS 11
BP 1680
EP 1689
DI 10.1016/j.neurobiolaging.2007.04.002
PG 10
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 356JP
UT WOS:000259774800007
PM 17524525
ER
PT J
AU Basselin, M
Chang, L
Chen, M
Bell, JM
Rapoport, SI
AF Basselin, Mireille
Chang, Lisa
Chen, Mei
Bell, Jane M.
Rapoport, Stanley I.
TI Chronic administration of valproic acid reduces brain NMDA signaling via
arachidonic acid in unanesthetized rats
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE valproic acid; NMDA; arachidonic acid; bipolar disorder; phospholipase
A(2); prostaglandin E2
ID EXCITATORY AMINO-ACIDS; D-ASPARTATE RECEPTORS; DNA-BINDING ACTIVITY;
BIPOLAR DISORDER; SODIUM-VALPROATE; CHRONIC LITHIUM; IN-VIVO; MOOD
STABILIZERS; ANTIEPILEPTIC DRUGS; PHOSPHOLIPASE A(2)
AB Evidence that brain glutamatergic activity is pathologically elevated in bipolar disorder suggests that mood stabilizers are therapeutic in the disease in part by downregulating glutamatergic activity. Such activity can involve the second messenger, arachidonic acid (AA, 20:4n-6). We tested this hypothesis with regard to valproic acid (VPA), when stimulating glutamatergic N-methyl-D-aspartate (NMDA) receptors in rat brain and measuring AA and related responses. An acute subconvulsant dose of NMDA (25 mg/kg i.p.) or saline was administered to unanesthetized rats that had been treated i.p. daily with VPA (200 mg/kg) or vehicle for 30 days. Quantitative autoradiography following intravenous [1-(14)C] AA infusion was used to image regional brain AA incorporation coefficients k*, markers of AA signaling. In chronic vehicle-pretreated rats, NMDA compared with saline significantly increased k* in 41 of 82 examined brain regions, many of which have high NMDA receptor densities, and also increased brain concentrations of the AA metabolites, prostaglandin E(2) (PGE(2)) and thromboxane B(2) (TXB(2)). VPA pretreatment reduced baseline concentrations of PGE2 and TXB2, and blocked the NMDA induced increases in k* and in eicosanoid concentrations. These results, taken with evidence that carbamazepine and lithium also block k* responses to NMDA in rat brain, suggest that mood stabilizers act in bipolar disorder in part by downregulating glutamatergic signaling involving AA.
C1 [Basselin, Mireille; Chang, Lisa; Chen, Mei; Bell, Jane M.; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Basselin, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126,MSC 0947,9 Mem Dr, Bethesda, MD 20892 USA.
EM mirvasln@mail.nih.gov
FU Intramural Research Program of the National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institute on Aging. None of the authors has a financial or
other conflict of interest related to this work.
NR 96
TC 22
Z9 22
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD NOV
PY 2008
VL 33
IS 11
BP 2229
EP 2240
DI 10.1007/s11064-008-9700-2
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 352GG
UT WOS:000259483300008
PM 18461450
ER
PT J
AU Chang, YC
Kim, HW
Rapoport, SI
Rao, JS
AF Chang, Yunyoung C.
Kim, Hyung-Wook
Rapoport, Stanley I.
Rao, Jagadeesh S.
TI Chronic NMDA administration increases neuroinflammatory markers in rat
frontal cortex: Cross-talk between excitotoxicity and neuroinflammation
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE excitotoxicity; neuroinflammation; interleukin-1beta; tumor necrosis
factor alpha; interleukin-10; glial fibrillary acidic protein; inducible
nitric oxide synthase; brain
ID D-ASPARTATE RECEPTOR; ARACHIDONIC-ACID METABOLISM; MESSENGER-RNA
EXPRESSION; NITRIC-OXIDE SYNTHASE; DNA-BINDING ACTIVITY;
PROTEIN-KINASE-II; PHOSPHOLIPASE A(2); TRANSCRIPTION FACTOR;
PARKINSONS-DISEASE; ALZHEIMERS-DISEASE
AB Chronic N-Methyl-D-aspartate (NMDA) administration, a model of excitotoxicity, and chronic intracerebroventricular lipopolysaccharide infusion, a model of neuroinflammation, are reported to upregulate arachidonic acid incorporation and turnover in rat brain phospholipids as well as enzymes involved in arachidonic acid metabolism. This suggests cross-talk between signaling pathways of excitotoxicity and of neuroinflammation, involving arachidonic acid. To test whether chronic NMDA administrations to rats can upregulate brain markers of neuroinflammation, NMDA (25 mg/kg i. p.) or vehicle (1 ml saline/kg i. p.) was administered daily to adult male rats for 21 days. Protein and mRNA levels of cytokines and other inflammatory markers were measured in the frontal cortex using immunoblot and realtime PCR. Compared with chronic vehicle, chronic NMDA significantly increased protein and mRNA levels of interleukin-1beta, tumor necrosis factor alpha, glial fibrillary acidic protein and inducible nitric oxide synthase. Chronic NMDA receptor overactivation results in increased levels of neuro-inflammatory markers in the rat frontal cortex, consistent with cross-talk between excitotoxicity and neuroinflammation. As both processes have been reported in a number of human brain diseases, NMDA receptor inhibitors might be of use in treating neuroinflammation in these diseases.
C1 [Chang, Yunyoung C.; Kim, Hyung-Wook; Rapoport, Stanley I.; Rao, Jagadeesh S.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,1S-126, Bethesda, MD 20892 USA.
EM jrao@mail.nih.gov
RI Kim, Hyung-Wook/B-6308-2009; Rao, Jagadeesh/C-1250-2009
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX This work was entirely supported by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health.
NR 48
TC 38
Z9 39
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD NOV
PY 2008
VL 33
IS 11
BP 2318
EP 2323
DI 10.1007/s11064-008-9731-8
PG 6
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 352GG
UT WOS:000259483300019
PM 18500552
ER
PT J
AU Taniura, S
Kamitani, H
Watanabe, T
Eling, TE
AF Taniura, Seijiro
Kamitani, Hideki
Watanabe, Takashi
Eling, Thomas E.
TI Induction of Cyclooxygenase-2 Expression by Interleukin-1 beta in Human
Glioma Cell Line, U87MG
SO NEUROLOGIA MEDICO-CHIRURGICA
LA English
DT Article
DE cyclooxygenase-2; interleukin-1 beta; glioma
ID HUMAN GLIOBLASTOMA CELLS; SQUAMOUS CARCINOMA-CELLS;
PROGNOSTIC-SIGNIFICANCE; GENE-EXPRESSION; P53; APOPTOSIS; PROTEIN;
INHIBITION; ASTROCYTES; CANCER
AB Cyclooxygenase-2 (COX-2) is up-regulated in most high-grade gliomas, and high COX-2 expression is associated with aggressive character and poor prognosis. However, the effect of COX-2 in human glioma cell lines is not well known. This study examined the effect of several stimuli, including interleukin-1 beta (IL-1 beta) and carcinogens, on COX-2 induction in normal astrocyte cells and human glioma cell lines U87MG, A172, and T98G. IL-1 beta-induced COX-2 expression strongly at both protein and messenger ribonucleic acid levels in only the U87MG cells of the glioma cell lines. Furthermore, carcinogen induced COX-2 expression. Similar findings were also observed in normal human astrocyte cells. The U87MG glioma cell line is a good model for COX-2 induction in glioma cell lines.
C1 [Taniura, Seijiro; Kamitani, Hideki; Watanabe, Takashi] Tottori Univ, Fac Med, Inst Neurol Sci, Dept Neurosurg, Yonago, Tottori 683, Japan.
[Eling, Thomas E.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA.
RP Taniura, S (reprint author), Takashima Hosp, Dept Neurosurg, 6 Nishi Cho, Tottori 6830826, Japan.
EM taniura@sanmedia.or.jp
FU Intramural NIH HHS [Z01 ES010016-09]
NR 34
TC 3
Z9 3
U1 0
U2 0
PU JAPAN NEUROSURGICAL SOC
PI TOKYO
PA C/O AKAMON-MAE IWATA BLDG, 5-27-8 HONGO, BUNKYO-KU, TOKYO, 113-0033,
JAPAN
SN 0470-8105
J9 NEUROL MED-CHIR
JI Neurol. Med.-Chir.
PD NOV
PY 2008
VL 48
IS 11
BP 500
EP 505
DI 10.2176/nmc.48.500
PG 6
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 372UZ
UT WOS:000260928800011
PM 19029777
ER
PT J
AU Murphy, DL
Fox, MA
Timpano, KR
Moya, PR
Ren-Patterson, R
Andrews, AM
Holmes, A
Lesch, KP
Wendland, JR
AF Murphy, Dennis L.
Fox, Meredith A.
Timpano, Kiara R.
Moya, Pablo R.
Ren-Patterson, Renee
Andrews, Anne M.
Holmes, Andrew
Lesch, Klaus-Peter
Wendland, Jens R.
TI How the serotonin story is being rewritten by new gene-based discoveries
principally related to SLC6A4, the serotonin transporter gene, which
functions to influence all cellular serotonin systems
SO NEUROPHARMACOLOGY
LA English
DT Review
DE Homeostasis; Serotonin transporter; Anxiety; Obsessive-compulsive
disorder; Depression; Epistasis
ID OBSESSIVE-COMPULSIVE DISORDER; KNOCK-OUT MICE;
POSITRON-EMISSION-TOMOGRAPHY; IRRITABLE-BOWEL-SYNDROME; PRIMARY
PULMONARY-HYPERTENSION; DEFICIT HYPERACTIVITY DISORDER; 5-HT2A PROMOTER
POLYMORPHISM; CATECHOL O-METHYLTRANSFERASE; ANTIDEPRESSANT-INDUCED
MANIA; BIOGENIC-AMINE TRANSPORTERS
AB Discovered and crystallized over sixty years ago, serotonin's important functions in the brain and body were identified over the ensuing years by neurochemical, physiological and pharmacological investigations. This 2008 M. Rapport Memorial Serotonin Review focuses on some of the most recent discoveries involving serotonin that are based on genetic methodologies. These include examples of the consequences that result from direct serotonergic gene manipulation (gene deletion or overexpression) in mice and other species: an evaluation of some phenotypes related to functional human serotonergic gene variants, particularly in SLC6A4, the serotonin transporter gene: and finally, a consideration of the pharmacogenomics of serotonergic drugs with respect to both their therapeutic actions and side effects. The serotonin transporter (SERT) has been the most comprehensively studied of the serotonin system molecular components, and will be the primary focus of this review. We provide in-depth examples of gene-based discoveries primarily related to SLC6A4 that have clarified serotonin's many important homeostatic functions in humans, non-human primates, mice and other species. Published by Elsevier Ltd.
C1 [Murphy, Dennis L.; Fox, Meredith A.; Timpano, Kiara R.; Moya, Pablo R.; Wendland, Jens R.] NIMH, Clin Sci Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Timpano, Kiara R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Ren-Patterson, Renee] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Andrews, Anne M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Andrews, Anne M.] Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA.
[Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA.
[Lesch, Klaus-Peter] Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany.
[Wendland, Jens R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Murphy, DL (reprint author), NIMH, Clin Sci Lab, Intramural Res Program, NIH, Bldg 10,Room 3D41,10 Ctr Dr,MSC 1264, Bethesda, MD 20892 USA.
EM dennismurphy@mail.nih.gov
RI Andrews, Anne/B-4442-2011; Wendland, Jens/A-1809-2012; Timpano,
Kiara/C-8760-2012; Lesch, Klaus-Peter/J-4906-2013;
OI Andrews, Anne/0000-0002-1961-4833; Lesch,
Klaus-Peter/0000-0001-8348-153X; Timpano, Kiara/0000-0002-0665-8722
FU NIMH, NIH; NARSAD 2007 Young Investigator Award; NIMH Division of
Intramural Research Programs Julius Axelrod Memorial Fellowship Training
Award
FX This research was supported by the Intramural Research Program of the
NIMH, NIH. Jens R. Wendland, M.D. was also supported by a NARSAD 2007
Young Investigator Award and an NIMH Division of Intramural Research
Programs Julius Axelrod Memorial Fellowship Training Award. The authors
are also grateful to Theresa B. DeGuzman, Teresa Tolliver, Su-Jan Huang
and Justin LaPorte for their assistance in these studies.
NR 290
TC 124
Z9 128
U1 7
U2 18
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD NOV
PY 2008
VL 55
IS 6
BP 932
EP 960
DI 10.1016/j.neuropharm.2008.08.034
PG 29
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 373OX
UT WOS:000260982700003
PM 18824000
ER
PT J
AU Childs, E
Hohoff, C
Deckert, J
Xu, K
Badner, J
de Wit, H
AF Childs, Emma
Hohoff, Christa
Deckert, Juergen
Xu, Ke
Badner, Judith
de Wit, Harriet
TI Association between ADORA2A and DRD2 polymorphisms and caffeine-induced
anxiety
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE caffeine; adenosine; dopamine; polymorphism; single nucleotide; anxiety
ID ADENOSINE A(2A) RECEPTOR; PROMOTER REGION; GENE; DOPAMINE; WITHDRAWAL;
DISCRIMINATION; DISEQUILIBRIUM; IDENTIFICATION; SCHIZOPHRENIA;
AMPHETAMINE
AB Caffeine produces mild psychostimulant and sometimes anxiogenic effects by antagonizing adenosine at A(1) and A(2A) receptors, and perhaps through interactions with other transmitter systems. Adenosine receptors are colocalized and functionally interact with dopamine receptors in the brain. Thus, functional polymorphisms in the genes for either adenosine or dopamine receptors may affect responses to caffeine. In this study, we examined associations between self-reported anxiogenic effects of caffeine and variation in the genes for A(2A) (ADORA2A) and DRD(2) (DRD(2)) receptors. Healthy male and female individuals (n = 102), who consumed less than 300 mg caffeine per week, ingested capsules containing 0, 50, 150, and 450 mg caffeine under double-blind conditions in four separate experimental sessions. Subjective anxiety was measured before and at repeated times after capsules were consumed. At the 150 mg dose of caffeine, we found a significant association between caffeine-induced anxiety ( Visual Analog Scales, VAS) and ADORA2A rs5751876 (1976C/T), rs2298383 (intron 1a) and rs4822492 (3'-flank), and DRD2 rs1110976 (intron 6). Caffeine-induced anxiety (VAS) was also associated with two-loci interactions of selected ADORA2A and DRD2 polymorphisms. The lowest dose of caffeine did not increase ratings of anxiety while the highest dose increased anxiety in the majority of subjects. These findings provide support for an association between an ADORA2A polymorphism and self-reported anxiety after a moderate dose of caffeine. It is likely that other ADORA2A and DRD2 polymorphisms also contribute to responses to caffeine.
C1 [Childs, Emma; Badner, Judith; de Wit, Harriet] Univ Chicago, Dept Psychiat, Chicago, IL 60657 USA.
[Hohoff, Christa; Deckert, Juergen] Univ Munster, Dept Psychiat, Munster, Germany.
[Deckert, Juergen] Univ Wurzburg, Dept Psychiat, D-8700 Wurzburg, Germany.
[Xu, Ke] NIAAA, Sect Human Neurogenet, Neurogenet Lab, NIH, Bethesda, MD USA.
RP Childs, E (reprint author), Univ Chicago, Dept Psychiat, 5841 S Maryland Ave MC3077, Chicago, IL 60657 USA.
EM echilds@yoda.bsd.uchicago.edu
RI Childs, Emma/K-6775-2014;
OI Childs, Emma/0000-0003-1747-5208; de Wit, Harriet/0000-0002-7211-8994
FU NIDA [DA02812]; General Clinical Research Center [USPHS MO1RR000555]
FX This research was supported by NIDA (DA02812) and the General Clinical
Research Center (USPHS MO1RR000555). We thank Michelle Dassinger, Liz
Young, Lisa Vicini, Maliha Darugar, and Kathrin Schwarte for their
technical assistance.
NR 44
TC 80
Z9 82
U1 2
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD NOV
PY 2008
VL 33
IS 12
BP 2791
EP 2800
DI 10.1038/npp.2008.17
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 359SB
UT WOS:000260007300001
PM 18305461
ER
PT J
AU Justinova, Z
Munzar, P
Panlilio, LV
Yasar, S
Redhi, GH
Tanda, G
Goldberg, SR
AF Justinova, Zuzana
Munzar, Patrik
Panlilio, Leigh V.
Yasar, Sevil
Redhi, Godfrey H.
Tanda, Gianluigi
Goldberg, Steven R.
TI Blockade of THC-Seeking Behavior and relapse in monkeys by the
cannabinoid CB(1)-Receptor antagonist rimonabant
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE cannabinoids; drug seeking; reinstatement; rimonabant; second-order
schedule; self-administration
ID CB1 RECEPTOR ANTAGONIST; SQUIRREL-MONKEYS; 2ND-ORDER SCHEDULES;
DRUG-SEEKING; DELTA(9)-TETRAHYDROCANNABINOL THC; FIXED-RATIO; COCAINE;
HEROIN; REINFORCEMENT; INJECTION
AB Accumulating evidence suggests the endocannabinoid system modulates environmental cues' ability to induce seeking of drugs, including nicotine and alcohol. However, little attention has been directed toward extending these advances to the growing problem of cannabis use disorders. Therefore, we studied intravenous self-administration of Delta(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, using a second-order schedule of drug seeking. Squirrel monkeys' lever responses produced only a brief cue light until the end of the session, when the final response delivered THC along with the cue. When a reinstatement procedure was used to model relapse following a period of abstinence, THC-seeking behavior was robustly reinstated by the cue or by pre-session administration of THC, other cannabinoid agonists, or morphine, but not cocaine. The cannabinoid antagonist rimonabant blocked cue-induced drug seeking, THC-induced drug seeking, and the direct reinforcing effects of THC. Thus, rimonabant and related medications might be effective as treatments for cannabinoid dependence.
C1 [Justinova, Zuzana; Munzar, Patrik; Panlilio, Leigh V.; Redhi, Godfrey H.; Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch,Dept Hlth & Human Serv, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
[Munzar, Patrik] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Yasar, Sevil] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA.
[Tanda, Gianluigi] Natl Inst Drug Abuse, Psychobiol Sect, Medicat Discovery Res Branch,Dept Hlth & Human Se, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Goldberg, SR (reprint author), Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch,Dept Hlth & Human Serv, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM sgoldber@intra.nida.nih.gov
RI Tanda, Gianluigi/B-3318-2009; Justinova, Zuzana/A-9109-2011
OI Tanda, Gianluigi/0000-0001-9526-9878; Justinova,
Zuzana/0000-0001-5793-7484
FU Intramural Research Program of the National Institute on Drug Abuse;
NIH; DHHS
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse, NIH, DHHS. We thank Eric Thorndike for
programming assistance and Kathleen Stillwell and Dr Ira Baum for
excellent surgical assistance with catheter implantation and
maintenance.
NR 36
TC 44
Z9 44
U1 3
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD NOV
PY 2008
VL 33
IS 12
BP 2870
EP 2877
DI 10.1038/npp.2008.21
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 359SB
UT WOS:000260007300008
PM 18305459
ER
PT J
AU Rex, EB
Rankin, ML
Ariano, MA
Sibley, DR
AF Rex, Elizabeth B.
Rankin, Michele L.
Ariano, Marjorie A.
Sibley, David R.
TI Ethanol regulation of D-1 dopamine receptor signaling is mediated by
protein kinase c in an isozyme-specific manner
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE ethanol; dopamine; PKC; D-1 receptor; DARPP-32; phosphorylation
ID VENTRAL TEGMENTAL AREA; AGONIST-INDUCED DESENSITIZATION;
CENTRAL-NERVOUS-SYSTEM; NULL MUTANT MICE; IN-VIVO; NUCLEUS-ACCUMBENS;
ADENYLYL-CYCLASE; DORSAL STRIATUM; NMDA RECEPTORS; RAT-BRAIN
AB Ethanol consumption potentiates dopaminergic signaling that is partially mediated by the D-1 dopamine receptor; however, the mechanism(s) underlying ethanol-dependent modulation of D-1 signaling is unclear. We now show that ethanol treatment of D-1 receptor-expressing cells decreases D-1 receptor phosphorylation and concurrently potentiates dopamine-stimulated cAMP accumulation. Protein kinase C (PKC) inhibitors mimic the effects of ethanol on D-1 receptor phosphorylation and dopamine-stimulated cAMP levels in a manner that is non-additive with ethanol treatment. Ethanol was also found to modulate specific PKC activities as demonstrated using in vitro kinase assays where ethanol treatment attenuated the activities of lipid-stimulated PKC gamma and PKC delta in membrane fractions, but did not affect the activities of PKC alpha, PKC beta(1), or PKC epsilon. Importantly, ethanol treatment potentiated D-1 receptor-mediated DARPP-32 phosphorylation in rat striatal slices, supporting the notion that ethanol enhances D-1 receptor signaling in vivo. These findings suggest that ethanol inhibits the activities of specific PKC isozymes, resulting in decreased D-1 receptor phosphorylation and enhanced dopaminergic signaling.
C1 [Rex, Elizabeth B.; Rankin, Michele L.; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA.
[Rex, Elizabeth B.] NIAAA, NIH, Rockville, MD 20852 USA.
[Ariano, Marjorie A.] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Neurosci, N Chicago, IL USA.
RP Sibley, DR (reprint author), NINDS, Mol Neuropharmacol Sect, NIH, 5625 Fishers Lane,Room 4S-04, Bethesda, MD 20892 USA.
EM sibley@helix.nih.gov
FU NINDS
FX We thank David Cabrera for technical support and Dr David Lovinger for
reading the manuscript. MLR was supported by a NINDS Competitive
Fellowship.
NR 53
TC 15
Z9 16
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD NOV
PY 2008
VL 33
IS 12
BP 2900
EP 2911
DI 10.1038/npp.2008.16
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 359SB
UT WOS:000260007300011
PM 18288091
ER
PT J
AU Liu, ZH
Shin, R
Ikemoto, S
AF Liu, Zhong-Hua
Shin, Rick
Ikemoto, Satoshi
TI Dual role of medial A10 dopamine neurons in affective encoding
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE ventral tegmental area; substantia nigra; nucleus accumbens; incentive
motivation; conditioned place preference; avoidance
ID VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS SHELL; CONDITIONED PLACE
PREFERENCE; OLFACTORY TUBERCLE; EXTRACELLULAR DOPAMINE; RECEPTOR
ANTAGONISTS; WITHDRAWAL SYNDROME; AVERSIVE STIMULI; TASTE-AVERSION;
BASAL GANGLIA
AB Increasing evidence suggests that the activation of medial A10 neurons mediates positive affective encoding. However, little is known about the functions of the inhibition of midbrain dopamine neurons. Here we show evidence suggesting that the inhibition of medial A10 neurons mediates a negative affective state, leading to negative affective encoding, whereas blunting the activation of medial A10 neurons disrupts positive affective encoding involving food reward. We used a microinjection procedure, in which the D(2) dopamine receptor agonist quinpirole was administered into the cell body region of the dopamine neurons, a procedure that reduces dopamine cell firing. Microinjections of quinpirole into the posteromedial ventral tegmental area, but not its more lateral counterparts, led to conditioned place aversion. Quinpirole administration to this site also decreased food intake and basal dopamine concentration in the ventromedial striatum, a major projection area of medial A10 neurons. In addition, moderate quinpirole doses that did not lead to conditioned place aversion or disrupt food intake abolished food-conditioned place preference, suggesting that blunting dopamine impulse activity in response to food reward disrupts positive affective encoding in associated external stimuli. Our data support the hypothesis that activation of medial A10 dopamine neurons mediates a positive affective state, leading to positive affective encoding, while their inhibition mediates a negative affective state, leading to negative affective encoding. Together with previous findings, we propose that medial A10 neurons are an important component of the mechanism via which animals learn to avoid negative incentive stimuli.
C1 [Liu, Zhong-Hua; Shin, Rick; Ikemoto, Satoshi] Natl Inst Drug Abuse, Behav Neurosci Res Branch, NIH, US Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
RP Ikemoto, S (reprint author), Natl Inst Drug Abuse, Behav Neurosci Res Branch, NIH, US Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM sikemoto@mail.nih.gov
OI Ikemoto, Satoshi/0000-0002-0732-7386
FU Intramural Research Program of National Institute on Drug Abuse;
National Institutes of Health
FX The present research was supported by the Intramural Research Program of
National Institute on Drug Abuse, National Institutes of Health. We
thank Drs Bin Wang, Roy Wise, and Zhi-Bing You for their help with
microdialysis and Mary Pfeiffer and Emily Wentzell for editorial
assistance.
NR 76
TC 33
Z9 33
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD NOV
PY 2008
VL 33
IS 12
BP 3010
EP 3020
DI 10.1038/npp.2008.4
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 359SB
UT WOS:000260007300020
PM 18256592
ER
PT J
AU Toscano, CD
Kingsley, PJ
Marnett, LJ
Bosetti, F
AF Toscano, Christopher D.
Kingsley, Philip J.
Marnett, Lawrence J.
Bosetti, Francesca
TI NMDA-induced seizure intensity is enhanced in COX-2 deficient mice
SO NEUROTOXICOLOGY
LA English
DT Article
DE N-Methyl-D-aspartate; Prostaglandin; Excitotoxicity; Lindane; Kainate;
Fluoro Jade B
ID ACID-INDUCED SEIZURE; NEURONAL CELL-DEATH; KAINIC ACID; CYCLOOXYGENASE-2
EXPRESSION; SELECTIVE INHIBITORS; RAT HIPPOCAMPUS; BRAIN-INJURY;
RECEPTORS; LINDANE; LIPOPOLYSACCHARIDE
AB Pharmacological inhibition or genetic deletion of cyclooxygenase (COX)-2, but not COX-1, has been shown to increase susceptibility to kainic acid (KA)-induced excitotoxicity. However, it is unclear if susceptibility to excitotoxins that act through other neurotransmitter receptors is altered by COX-2 inhibition. To further understand the involvement of COX-2 in regulating susceptibility to excitotoxicity, we investigated the effect of COX-2 deletion on excitotoxicity induced by peripheral injection of Nmethyl-D-aspartate (NMDA, a specific agonist of the NMDA receptors) or lindane (a GABA(A) receptor antagonist). COX-2(-/-) mice injected intraperitoneally with NMDA (50-100 mg/kg) exhibited significantly increased median seizure intensity when compared to COX-2(+/+) mice. Further, COX-2(-/-) mice exposed to NMDA showed neuronal damage, detected by Fluoro Jade B (FJB) staining, in the CA3 region of the hippocampus. There was no FJB staining nor any significant difference in median or maximal seizure intensity in COX-2(+/+) and COX-2(-/-) mice exposed to lindane. LC-MS/MS analysis of brain prostaglandin profile in COX-2(-/-) mice demonstrated a significant increase in PGF(2 alpha), TXB(2), PGE(2) and PGD(2) expression 1 h after administration of an excitotoxic dose of KA, but not of NMDA. Our findings demonstrate that COX-2 regulates susceptibility to KA and NMDA excitotoxicity, which directly activate glutamatergic neurotransmission, but not to lindane, which indirectly alters glutamatergic neurotransmission. Furthermore, increased levels of prostaglandins after seizures are associated with consistent manifestation of neuronal damage. Published by Elsevier B.V.
C1 [Toscano, Christopher D.; Bosetti, Francesca] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Kingsley, Philip J.; Marnett, Lawrence J.] Vanderbilt Univ, Sch Med, Ctr Mol Toxicol, Nashville, TN 37232 USA.
RP Bosetti, F (reprint author), NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, 9 Mem Dr,Bldg 9,Room 1S126,MSC 0947, Bethesda, MD 20892 USA.
EM frances@mail.nih.gov
FU NIH [GM15431]; National Institute on Aging [Z01AG000423-04]
FX The authors would like to thank Dr. Robert Langenbach for supplying the
cyclooxygenase-2 knockout mice and Drs. Saba Aid and Sang-Ho Choi for
their helpful discussions and technical advice. This research was
supported by the Intramural Research Program of the NIH, National
Institute on Aging (Z01AG000423-04; CDT, FB) and by NIH grant # GM15431
(LJM).
NR 33
TC 25
Z9 25
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0161-813X
J9 NEUROTOXICOLOGY
JI Neurotoxicology
PD NOV
PY 2008
VL 29
IS 6
BP 1114
EP 1120
DI 10.1016/j.neuro.2008.08.008
PG 7
WC Neurosciences; Pharmacology & Pharmacy; Toxicology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
GA 381QU
UT WOS:000261551800025
PM 18834901
ER
PT J
AU Li, SK
Lizak, MJ
Jeong, EK
AF Li, S. Kevin
Lizak, Martin J.
Jeong, Eun-Kee
TI MRI in ocular drug delivery
SO NMR IN BIOMEDICINE
LA English
DT Review
DE MRI; eye; ocular; drug delivery; contrast agent
ID BLOOD-RETINAL BARRIER; CONTRAST-ENHANCED MRI;
NUCLEAR-MAGNETIC-RESONANCE; POSTERIOR SEGMENT; HUMAN EYE;
HIGH-RESOLUTION; AQUEOUS-HUMOR; RABBIT EYE; TRANSTYMPANIC IONTOPHORESIS;
PHARMACEUTICAL RESEARCH
AB Conventional pharmacokinetic method for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology present some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. Copyright (C) 2008 John Wiley & Sons. Ltd.
C1 [Li, S. Kevin] Univ Cincinnati, Coll Pharm, Div Pharmaceut Sci, Cincinnati, OH 45267 USA.
[Lizak, Martin J.] NINDS, NIH, Bethesda, MD 20892 USA.
[Jeong, Eun-Kee] Univ Utah, Dept Radiol, Salt Lake City, UT 84108 USA.
[Jeong, Eun-Kee] Univ Utah, Utah Ctr Adv Imaging Res, Salt Lake City, UT 84108 USA.
RP Li, SK (reprint author), Univ Cincinnati, Coll Pharm, Div Pharmaceut Sci, Cincinnati, OH 45267 USA.
EM kevin.li@uc.edu
OI Li, Kevin/0000-0001-8626-9630
FU NIH [EN 015181]
FX We thank Sarah A. Molokhia and Stephanie H. Kim for providing the MR
data in this review, and Drs Hyuncheol Kim. Jinsong Hao, and Yanhui
Zhano for their help. Some Unpublished MR data were obtained from
Studies supported by NIH Grant EN 015181.
NR 113
TC 16
Z9 17
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD NOV
PY 2008
VL 21
IS 9
SI SI
BP 941
EP 956
DI 10.1002/nbm.1230
PG 16
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 375TM
UT WOS:000261136200003
PM 18186077
ER
PT J
AU Shakes, LA
Malcolm, TL
Allen, KL
De, S
Harewood, KR
Chatterjee, PK
AF Shakes, Leighcraft A.
Malcolm, Tennison L.
Allen, Kevin L.
De, Supriyo
Harewood, Ken R.
Chatterjee, Pradeep K.
TI Context dependent function of APPb enhancer identified using enhancer
trap-containing BACs as transgenes in zebrafish
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID BACTERIAL ARTIFICIAL CHROMOSOMES; AMYLOID PRECURSOR PROTEIN; CONSERVED
NONCODING ELEMENTS; ALZHEIMERS-DISEASE; IN-VIVO; ESCHERICHIA-COLI;
GENE-EXPRESSION; BETA-GLOBIN; HOMOLOGOUS RECOMBINATION; NESTED DELETIONS
AB An enhancer within intron 1 of the amyloid precursor protein gene (APPb) of zebrafish is identified functionally using a novel approach. Bacterial artificial chromosomes (BACs) were retrofitted with enhancer traps, and expressed as transgenes in zebrafish. Expression from both transient assays and stable lines were used for analysis. Although the enhancer was active in specific nonneural cells of the notochord when placed with APPb gene promoter proximal elements its function was restricted to, and absolutely required for, specific expression in neurons when juxtaposed with additional far-upstream promoter elements of the gene. We demonstrate that expression of green fluorescent protein fluorescence resembling the tissue distribution of APPb mRNA requires both the intron 1 enhancer and 28 kb of DNA upstream of the gene. The results indicate that tissue-specificity of an isolated enhancer may be quite different from that in the context of its own gene. Using this enhancer and upstream sequence, polymorphic variants of APPb can now more closely recapitulate the endogenous pattern and regulation of APPb expression in animal models for Alzheimers disease. The methodology should help functionally map multiple noncontiguous regulatory elements in BACs with or without gene-coding sequences.
C1 [Shakes, Leighcraft A.; Malcolm, Tennison L.; Allen, Kevin L.; Harewood, Ken R.; Chatterjee, Pradeep K.] N Carolina Cent Univ, Julius L Chambers Biomed Biotechnol Res Inst, Durham, NC 27707 USA.
[Malcolm, Tennison L.; Chatterjee, Pradeep K.] N Carolina Cent Univ, Dept Chem, Durham, NC 27707 USA.
[Allen, Kevin L.; Harewood, Ken R.] N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA.
[De, Supriyo] NIA, Gene Express & Genom Unit, NIH, Triad Technol Ctr, Baltimore, MD 21224 USA.
RP Chatterjee, PK (reprint author), N Carolina Cent Univ, Julius L Chambers Biomed Biotechnol Res Inst, Durham, NC 27707 USA.
EM pchatterjee@nccu.edu
OI De, Supriyo/0000-0002-2075-7655
FU MBRS-SCORE [608049]; NIGMS and EXPORT [1P20 MD00175-01]; National
Institute of Health; North Carolina Biotechnology Center; National
Institutes of Health-NCMH HD
FX MBRS-SCORE (# SO 608049); NIGMS and EXPORT (#1P20 MD00175-01); National
Institute of Health; North Carolina Biotechnology Center. Funding for
open access charge: National Institutes of Health-NCMH& HD.
NR 74
TC 8
Z9 8
U1 0
U2 2
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 NOV
PY 2008
VL 36
IS 19
BP 6237
EP 6248
DI 10.1093/nar/gkn628
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 373PA
UT WOS:000260983000028
PM 18832376
ER
PT J
AU Abes, R
Moulton, HM
Clair, P
Yang, ST
Abes, S
Melikov, K
Prevot, P
Youngblood, DS
Iversen, PL
Chernomordik, LV
Lebleu, B
AF Abes, Rachida
Moulton, Hong M.
Clair, Philippe
Yang, Sung-Tae
Abes, Said
Melikov, Kamran
Prevot, Paul
Youngblood, Derek S.
Iversen, Patrick L.
Chernomordik, Leonid V.
Lebleu, Bernard
TI Delivery of steric block morpholino oligomers by (R-X-R)(4) peptides:
structure-activity studies
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID EFFICIENT SPLICING CORRECTION; CELL-PENETRATING PEPTIDES; DYSTROPHIN
EXPRESSION; VIRUS-INFECTIONS; MDX MOUSE; IN-VITRO; OLIGONUCLEOTIDES;
TRANSPORTERS; INHIBITION; STABILITY
AB Redirecting the splicing machinery through the hybridization of high affinity, RNase H-incompetent oligonucleotide analogs such as phosphoramidate morpholino oligonucleotides (PMO) might lead to important clinical applications. Chemical conjugation of PMO to arginine-rich cell penetrating peptides (CPP) such as (R-Ahx-R)(4) (with Ahx standing for 6-aminohexanoic acid) leads to sequence-specific splicing correction in the absence of endosomolytic agents in cell culture at variance with most conventional CPPs. Importantly, (R-Ahx-R)(4) PMO conjugates are effective in mouse models of various viral infections and Duchenne muscular dystrophy. Unfortunately, active doses in some applications might be close to cytotoxic ones thus presenting challenge for systemic administration of the conjugates in those clinical settings. Structure activity relationship studies have thus been undertaken to unravel CPP structural features important for the efficient nuclear delivery of the conjugated PMO and limiting steps in their internalization pathway. Affinity for heparin (taken as a model heparan sulfate), hydrophobicity, cellular uptake, intracellular distribution and splicing correction have been monitored. Spacing between the charges, hydrophobicity of the linker between the Arg-groups and Arg-stereochemistry influence splicing correction efficiency. A significant correlation between splicing correction efficiency, affinity for heparin and ability to destabilize model synthetic vesicles has been observed but no correlation with cellular uptake has been found. Efforts will have to focus on endosomal escape since it appears to remain the limiting factor for the delivery of these splice-redirecting ON analogs.
C1 [Abes, Rachida; Clair, Philippe; Abes, Said; Prevot, Paul; Lebleu, Bernard] Univ Montpellier 2, CNRS, UMR 5235, F-34095 Montpellier 5, France.
[Moulton, Hong M.; Youngblood, Derek S.; Iversen, Patrick L.] AVI BioPharma, Corvallis, OR 97333 USA.
[Yang, Sung-Tae; Melikov, Kamran; Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Lebleu, B (reprint author), Univ Montpellier 2, CNRS, UMR 5235, Pl Eugene Bataillon, F-34095 Montpellier 5, France.
EM bernard.lebleu@univ-montp2.fr
RI Melikov, Kamran/A-6604-2009
FU AFM and ARC; Ligue Regionale de Lutte contre le Cancer; EEC
post-doctoral fellowship; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institutes of Health
[HD001501-17]; Centre National de la Recherche Scientifique
FX AFM and ARC (B. L.); Ligue Regionale de Lutte contre le Cancer, PhD
fellowships (S. A. and R. A.); EEC post-doctoral fellowship (P. C.);
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (S.-T.Y., K. M. and L.
V. C.); National Institutes of Health (HD001501-17 L. V. C.). Funding
for open access charge: Centre National de la Recherche Scientifique.
NR 27
TC 52
Z9 58
U1 1
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 NOV
PY 2008
VL 36
IS 20
BP 6343
EP 6354
DI 10.1093/nar/gkn541
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 373NA
UT WOS:000260977500009
PM 18796528
ER
EF